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	<title>Innovations in Clinical Neuroscience</title>
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	<link>https://innovationscns.com</link>
	<description>A peer-reviewed journal providing evidence-based information</description>
	<lastBuildDate>Mon, 08 Jun 2026 14:29:35 +0000</lastBuildDate>
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		<title>The Association of Alzheimer’s Disease and Related Dementias Blood-Based Biomarkers With Depressive Symptoms</title>
		<link>https://innovationscns.com/the-association-of-alzheimers-disease-and-related-dementias-blood-based-biomarkers-with-depressive-symptoms/</link>
		
		<dc:creator><![CDATA[ICNS Online Editor]]></dc:creator>
		<pubDate>Mon, 01 Jun 2026 16:00:54 +0000</pubDate>
				<category><![CDATA[Alzheimer’s disease]]></category>
		<guid isPermaLink="false">https://innovationscns.com/?p=77232</guid>

					<description><![CDATA[Research Summary: Depressive symptoms are common in older adults and have been associated with risk of Alzheimer’s disease and Alzheimer’s disease and related dementias (AD/ADRD), but the mechanisms and biomarkers underlying this relationship remain unclear. Prior studies have reported associations between depressive symptoms and AD/ADRD pathologies, sometimes before cognitive symptoms emerge, suggesting that late-life depressive symptoms might reflect early underlying disease processes. Blood-based biomarkers (BBMs) provide in vivo measures of AD/ADRD-related pathology, including amyloid beta (Aβ) 42/40 ratio, phosphorylated tau181 (p-tau181), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP). Studies examining associations between amyloid or tau biomarkers and depressive symptoms have produced mixed findings, and neurodegeneration and neuroinflammation might represent shared biological pathways between depression and AD/ADRD. GFAP, an intermediate filament expressed by astrocytes, might reflect astrocytic damage, astrogliosis, or neuroinflammation, and plasma GFAP has previously been associated with clinical depression. This study by Bacci et al1 examined cross-sectional associations between AD/ADRD BBMs and depressive symptoms in a large, community-based cohort of older adults enrolled in the Aspirin in Reducing Events in the Elderly (ASPREE) clinical trial and evaluated whether these associations differed by sex or apolipoprotein E (APOE) ε4 carrier status. Baseline data were analyzed from participants in ASPREE, a double-blind, randomized primary prevention trial that enrolled older adults from 2010 to 2014 to evaluate daily low-dose aspirin effects on dementia, persistent physical disability, and death. ASPREE excluded individuals with a history of cardiovascular disease events, diagnosed dementia or Modified Mini-Mental State Examination score &#60;78, disability affecting activities of daily living, or conditions likely to cause death within 5 years. Of 19,114 participants enrolled at ASPREE baseline, 7,167 were excluded because of missing or incomplete data, leaving 11,947 participants with baseline AD/ADRD BBM and depressive symptom data for the current analysis. Baseline blood samples were collected within the first 12 months of the trial. Depressive symptoms were measured with the 10-item Center for Epidemiological Studies Depression Scale (CESD-10), with scores ranging from 0 to 30, with higher scores indicating greater depressive symptoms. Associations between BBMs and depressive symptoms were assessed using linear regression models. Model 1 was unadjusted; Model 2 adjusted for demographic, lifestyle, chronic condition, laboratory, and cognition variables; and Model 3 additionally adjusted for antidepressant use and history of depression. Sex- and APOE ε4-stratified analyses and interaction terms were used to evaluate effect modification, with P&#60;0.05 as the significance threshold. The 11,947 included participants had a median age of 73.87 years, 53.5% were women, and 98.6% were White. The median education duration was 12.00 years, 22.2% reported parental history of dementia, and 24.9% were APOE ε4 carriers. Median CESD-10 score was 2.00. Median BBM values were 0.06 for Aβ42/40 ratio, 31.46 pg/mL for p-tau181, 19.84 pg/mL for NfL, and 120.58 pg/mL for GFAP. In the unadjusted Model 1, lower p-tau181, higher NfL, and higher GFAP were associated with higher depressive symptoms, with beta values of −0.096 (standard error [SE]: 0.045; P=0.033), 0.183 (SE: 0.050; P&#60;0.001), and 0.221 (SE: 0.044; P&#60;0.001), respectively. Aβ42/40 ratio was not associated with depressive symptoms (beta: −0.034; SE: 0.086; P=0.690). In Model 2, after adjustment for demographic, lifestyle, clinical, laboratory, and cognition variables, higher NfL and higher GFAP remained associated with higher depressive symptoms, with beta values of 0.142 (SE: 0.060; P=0.018) and 0.123 (SE: 0.051; P=0.015), respectively; Aβ42/40 ratio and p-tau181 were not associated with depressive symptoms. In Model 3, after additional adjustment for antidepressant use and history of depression, only higher GFAP remained associated with higher depressive symptoms (beta: 0.270; SE: 0.088; P=0.002), while Aβ42/40 ratio, p-tau181, and NfL were not associated. Results were largely unchanged after correction for multiple comparisons. In sex-stratified analyses, higher GFAP was associated with higher depressive symptoms only among men, but formal interaction testing showed that no BBM-by-sex interaction term was statistically significant; the GFAP-sex interaction was shown to be trending, but not significant (P=0.075). In APOE ε4-stratified analyses, higher GFAP was associated with higher depressive symptoms only among APOE ε4 noncarriers, but this association did not remain significant after multiple-comparison correction, and no BBM-APOE ε4 interaction term was significant. This study found that plasma GFAP, but not Aβ42/40 ratio, p-tau181, or NfL, was independently associated with depressive symptoms. Plasma Aβ42/40 ratio, p-tau181, and NfL were not independently associated with depressive symptoms in the fully adjusted model. These findings suggest that neuroinflammation, reflected by plasma GFAP, might be linked to depressive symptoms in older adults, but longitudinal studies in more diverse cohorts are needed to determine directionality and clarify whether this association differs across subgroups. Reference: Bacci JR, Ryan J, Murray AM, et al. The association of Alzheimer’s disease and related dementias blood-based biomarkers with depressive symptoms. Alzheimers Dement. 2026;22(1):e71007.The post <a href="https://innovationscns.com/the-association-of-alzheimers-disease-and-related-dementias-blood-based-biomarkers-with-depressive-symptoms/">The Association of Alzheimer’s Disease and Related Dementias Blood-Based Biomarkers With Depressive Symptoms</a> appeared first on <a href="https://innovationscns.com">Innovations in Clinical Neuroscience</a>.]]></description>
		
		
		
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		<title>2026 AAN Annual Meeting Highlights</title>
		<link>https://innovationscns.com/2026-aan-annual-meeting-highlights/</link>
		
		<dc:creator><![CDATA[ICNS Online Editor]]></dc:creator>
		<pubDate>Mon, 01 Jun 2026 15:59:17 +0000</pubDate>
				<category><![CDATA[Alzheimer’s disease]]></category>
		<guid isPermaLink="false">https://innovationscns.com/?p=77234</guid>

					<description><![CDATA[Rising mortality related to early-onset Alzheimer’s disease in the United States: trends and disparities, 2003–2023. This retrospective population-based study used Centers for Disease Control (CDC) and Prevention WONDER data to examine early-onset Alzheimer’s disease-related mortality (EOAD-RM) in the United States (US) from 2003 to 2023. Among 5,167 EOAD-related deaths, 62.4% occurred in female patients, and the age-adjusted mortality rate (AAMR) increased from 0.08 to 2.06 per 1 million population. From 2015 to 2023, the annualized percentage change was 19.9% (95% confidence interval [CI]: 17.98–21.82), with increases observed across sex, race/ethnicity, and region. Women had a faster increase in AAMR than men, Black individuals had the greatest relative increase from 2018 to 2023 (206%), and the West and Midwest had the largest regional increases. Overall, EOAD-RM rose substantially over 2 decades, supporting further investigation into factors driving these mortality trends and disparities. Access abstract here: https://index.mirasmart.com/AAN2026/PDFfiles/AAN2026-000942.html Lifestyle interventions vs monoclonal antibodies in mild cognitive impairment and early Alzheimer’s disease: a comparative review of randomized controlled trials. This comparative review evaluated randomized controlled trials of multimodal lifestyle interventions (MMLIs) and monoclonal antibody (MAB) therapies in patients with mild cognitive impairment (MCI) or early Alzheimer’s disease (AD) using Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog) outcomes. Five MMLI trials reported ADAS-Cog improvements of 1.3 to 2.6 points, with benefits also reported for executive function, mood, gait speed, quality of life, and biomarkers. Three phase 3 MAB trials showed 1.4 to 1.5 points of ADAS-Cog preservation vs placebo, with robust amyloid clearance but modest clinical benefit. Relative benefit analysis showed 27% to 32% preservation with MABs compared to greater than 200% benefit with MMLIs. Overall, the review suggests that lifestyle interventions might provide broader cognitive and health benefits than MABs alone and supports future studies looking at lifestyle and pharmacologic approaches. Access abstract here: https://index.mirasmart.com/AAN2026/PDFfiles/AAN2026-002745.html Investigating the association between episodic and persistent depression in early to middle life with Alzheimer’s disease and related dementias in later life: a retrospective cohort analysis. This retrospective cohort study used TriNetX electronic medical records from 108 healthcare organizations to assess whether depression diagnoses from ages 18 to 44 years were associated with later Alzheimer’s disease and related dementias (ADRDs). A single episode of major depressive disorder (MDD) was most strongly associated with vascular dementia (odds ratio [OR]: 15.069; 95% CI: 13.159–17.255), while recurrent MDD was associated with increased risk across all dementia outcomes and showed the strongest association with AD (OR: 417.82; 95% CI: 373.785–460.879). Dysthymia showed intermediate associations between single-episode and recurrent MDD, with the greatest risk observed for vascular dementia (OR: 16.178; 95% CI: 12.277–21.317). Overall, chronic episodic depression showed the strongest association with later ADRD diagnoses, while dysthymia also appeared to contribute to ADRD risk. Access abstract here: https://index.mirasmart.com/AAN2026/PDFfiles/AAN2026-004441.html Diverging trends in Alzheimer’s disease mortality linked to psychoactive substance in White adult population in US, 1999–2023. This mortality analysis used CDC and Prevention WONDER data to examine deaths involving AD and psychoactive substance use (PASU) among White US adults aged ≥25 years from 1999 to 2023. Across 62,894 deaths, the age-adjusted mortality rate increased from 0.15 in 1999 to 1.98 in 2023, with the steepest rise from 1999 to 2005 and a nonsignificant decline from 2020 to 2023. Mortality was higher in men compared to women (1.70 vs 1.13), higher in nonmetropolitan compared to metropolitan areas (1.67 vs 1.14), and highest in the Midwest US (1.67). Overall, deaths involving AD and PASU increased substantially over time, with persistent demographic and geographic disparities. Access abstract here: https://index.mirasmart.com/AAN2026/PDFfiles/AAN2026-004451.html Associations between continuing medical education participation and real-world readiness for amyloid-targeting therapies in Alzheimer’s disease. This matched real-world analysis evaluated whether participation in a multi-activity continuing medical education (CME) curriculum improved clinician readiness to integrate amyloid-targeting therapies (ATTs) for AD. Clinician learners were matched 1:1 with nonparticipating controls (n=311 matched pairs) using baseline characteristics, and ATT initiation was tracked from May 2024 through January 2025. CME participants initiated 1,079 ATT treatments vs 548 in controls, corresponding to 531 incremental treatments with a 96.2% confidence level in statistical significance. Clinicians who completed multiple activities had greater increases than those completing a single activity, supporting the value of longitudinal, curriculum-based education. Overall, CME participation was associated with higher ATT initiation and greater real-world readiness to incorporate emerging AD therapies. Access abstract here: https://index.mirasmart.com/AAN2026/PDFfiles/AAN2026-003131.html Demographic variances and regional trends in Alzheimer’s and cardiac arrest-related mortality among older adults in the United States: a 20-year nationwide analysis. This nationwide mortality analysis used CDC and Prevention WONDER data to examine AD and cardiac arrest (CA)–related deaths among US adults aged 65 years and older from 1999 to 2020. A total of 254,007 deaths were identified, with mortality declining significantly from 2005 to 2013 (annual percent change [APC]: −2.93%; P&#60;0.001) before mildly increasing, resulting in a slight overall rise from 1999 to 2020 (average APC: 0.32). AAMRs were higher in women compared to men (29.4 vs 23.5), highest among Hispanic individuals (39), and highest geographically in the West US (56.1), with California showing the highest state-level rate (93.6). Overall, AD and CA-related mortality showed modest long-term growth with notable sex, racial, geographic, and urban-rural disparities. Access abstract here: https://index.mirasmart.com/AAN2026/PDFfiles/AAN2026-004405.html Data-driven subtypes of subjective cognitive decline: neuropsychological profiles, Alzheimer’s disease biomarkers, and clinical trajectories. This study used Alzheimer’s Disease Neuroimaging Initiative data to identify data-driven subtypes of subjective cognitive decline (SCD) among 353 individuals with SCD, alongside 542 cognitively normal controls and 1,113 patients with MCI). Three SCD clusters were identified: a dysexecutive subtype with poorer executive functioning, fludeoxyglucose positron emission tomography hypometabolism, and phosphorylated tau and amyloid-beta 42 biomarker levels resembling MCI; a “worried-well” subtype with subjective memory and attentional complaints but no objective impairment; and an amnesic subtype with primarily memory deficits. Longitudinal analyses showed the greatest clinical decline in the dysexecutive cluster, suggesting higher risk for progression to neurodegenerative disease. Overall, the findings highlight the heterogeneity of SCD and suggest that some subtypes might reflect early neurodegeneration, while others might remain stable and potentially relate to psychological or affective factors. Access abstract here:The post <a href="https://innovationscns.com/2026-aan-annual-meeting-highlights/">2026 AAN Annual Meeting Highlights</a> appeared first on <a href="https://innovationscns.com">Innovations in Clinical Neuroscience</a>.]]></description>
		
		
		
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		<title>Journal Watch: Alzheimer’s disease</title>
		<link>https://innovationscns.com/journal-watch-alzheimers-disease/</link>
		
		<dc:creator><![CDATA[ICNS Online Editor]]></dc:creator>
		<pubDate>Mon, 01 Jun 2026 15:58:19 +0000</pubDate>
				<category><![CDATA[Alzheimer’s disease]]></category>
		<guid isPermaLink="false">https://innovationscns.com/?p=77238</guid>

					<description><![CDATA[Neuroplasticity and Alzheimer&#8217;s disease Gashtrodkhani AA, Shirkouhi SG, Khatami SS, et al. J Integr Neurosci. 2026;25(1):48051.  Summary. In a narrative review of literature investigating neuroplasticity related to Alzheimer’s disease, researchers found that pharmacological interventions might have therapeutic potential. Evidence showed that brain-derived neurotrophic factor and nerve growth factor mimetics, exercise, light therapy, diet therapy, and neuromodulation approaches might have the potential to promote neuroplasticity, offer complementary prevention and treatment benefits for Alzheimer’s disease, and improve cognitive function. *PMID: 42060649, PMCID: PMC13132236 &#160; Visual memory correlates with Alzheimer&#8217;s disease biomarkers in cognitively unimpaired individuals James TA, Zhao L, Xu H, et al. Alzheimers Dement. 2026;22:e71417. Summary. In an exploratory factor analysis utilizing neuropsychological testing of 1,697 healthy adults, researchers identified 5 latent cognitive domain factors. Two of the factors, verbal memory and visual memory, were correlated with hippocampal volume. In addition, visual memory correlated with cerebrospinal fluid tau levels and resting state functional magnetic resonance imaging (MRI) connectivity, suggesting a significant relationship with Alzheimer&#8217;s disease biomarkers. Verbal memory did not correlate with cerebrospinal fluid biomarkers or network connectivity. *PMID: 42029420, PMCID: PMC13108244 &#160; Early Alzheimer&#8217;s diagnosis: U.S. primary care physicians and use of blood biomarkers Burns JM, Alford S, Coppinger J, et al. Alzheimers Dement. 2026; 22(1):e70986. Summary. In an exploratory study, researchers performed 20 in-depth (60-minute) interviews with primary care physicians from May 12 to May 26, 2023. The interviews addressed early Alzheimer’s disease diagnosis, primary care physician’s role, and blood biomarker test implementation. The results of the interviews showed that primary care physicians value examining cognitive decline and have confidence in their ability to diagnose Alzheimer’s disease. The main barriers to early diagnosis were complexity and inefficiency of current diagnostic workflows, lack of effective treatments, and stigma. In terms of blood biomarkers, primary care physicians considered the tests accurate and cost-effective but continue to have reimbursement and diagnostic pathway placement concerns. *PMID: 41549413, PMCID: PMC12812852&#8242; &#160; From traumatic brain injury to Alzheimer&#8217;s disease: multilevel biomechanical, neurovascular, and molecular mechanisms with emerging therapeutic directions Katramadou A, Bender ES, Kanakis D. Int J Mol Sci. 2026;27(3):1570. Summary. In a synthesizing review of data linking biomechanical injury to molecular and neurovascular pathways of neurodegeneration, researchers found that traumatic brain injury is associated with long-term cognitive decline, psychiatric comorbidities, and pathological hallmarks. However, researchers determined that a multimodal framework combining traumatic brain injury models, standardized biomarkers, stratification by demographic factors like age, sex, and genotype, and temporally adapted therapeutic approaches is necessary to determine if traumatic brain injury is a potential initiator of chronic neurodegenerative processes. *PMID: 41683989, PMCID: PMC12898350 &#160; Digital therapeutics for Alzheimer&#8217;s and Parkinson&#8217;s diseases: current trends and future perspectives Jeong YJ, Lee HJ, Kim JS, et al. Med Res Rev. 2025;46(1):316–327. Summary. In a review of digital therapeutic development for Alzheimer’s disease and Parkinson’s disease, researchers found that there are personalized, evidence-based digital therapeutics that have been developed to monitor and modulate cognitive, motor, and psychological functions in individuals with either Alzheimer’s or Parkinson’s disease. Findings in the review showed improvements associated with digital therapeutics, including improved global cognition, executive function, attention, verbal memory, and working memory. However, there were limitations associated with the application of digital therapeutics to neurodegenerative diseases, including unclear long-term safety profiles and a lack of systematic longitudinal studies on negative outcomes. *PMID: 40745950, PMCID: PMC12673471 &#160; Alzheimer’s disease and related dementias in rural Medicare populations: a scoping review Kianfar N, Alsharayri S, Mollalo S. BMC Geriatr. 2026;26:237. Summary. In a systematic scoping review of 33 studies analyzing Alzheimer’s disease and related dementias in rural Medicare populations from January 1, 2000, to March 5, 2025, researchers found that this population remains underrepresented in research despite their disproportionate disease burden. The available literature focused primarily on care delivery (30.3%) and hospitalization outcomes (21.2%), while Alzheimer’s disease and related dementias incidence, prevalence, mortality, medication use, dementia subtypes, environmental exposures, and policy interventions were rarely explored or evaluated. *PMID: 41593510, PMCID: PMC12918024 &#160; Nanomaterials for Alzheimer&#8217;s disease: emerging strategies in diagnosis and therapy Na Y, Bai J, Zhang N, et al. J Nanobiotechnology. 2026;24:398. Summary. In an analysis of emerging therapeutic targets in Alzheimer’s disease and nanomaterial-based approaches for targeted treatment, researchers found that nanomedicine offers distinct advantages compared to conventional Alzheimer’s disease treatment methods. Advantages include enhanced diagnostic sensitivity and accuracy, superior therapeutic efficacy and reduced side effects, and flexible administration and improved pharmokinetics. Researchers also suggested that the future of nanomedicine will involve personalized treatment strategies and a convergence with advanced technologies like artificial intelligence. *PMID: 41864895; PMCID: PMC13126975 &#160; Predicting onset of symptomatic Alzheimer&#8217;s disease with plasma p-tau217 clocks Petersen KK, Milà-Alomà M, Li Y, et al. Nat Med. 2026;32(3):1085–1094. Summary. Using longitudinal plasma ratio of phosphorylated to non-phosphorylated tau at position 217 (%p-tau217) from 2 independent cohorts (n=258 and n=345), researchers utilized clock models to estimate the age at plasma %p-tau217 positivity. In the study, researchers found that the estimated age at plasma %p-tau217 positivity was associated with the age at onset of Alzheimer’s disease symptoms. Time from %p-tau217 positivity to onset of Alzheimer’s disease symptoms was shorter in older individuals. These findings suggest that time until onset of Alzheimer’s disease symptoms might be predictable using a single blood test. *PMID: 41714746; PMCID: PMC13004683 &#160; Postmenopausal sarcopenia and Alzheimer&#8217;s disease: The interplay of mitochondria, insulin resistance, and myokines Farhana F, Sultana MA, Hia RA, Hegde V. Neurosci Biobehav Rev. 2026;180:106501. Summary. In a review, researchers analyzed pathophysiological causes and identified treatment options to slow cognitive deterioration in postmenopausal women. Researchers found nonpharmacological approaches, such as dietary intake and physical activity were associated with improvement in sarcopenia and cognitive health. However, researchers found that that there were currently no pharmocological treatments available for older postmenopausal women with Alzheimer&#8217;s disease or sarcopenia. *PMID: 41325816The post <a href="https://innovationscns.com/journal-watch-alzheimers-disease/">Journal Watch: Alzheimer’s disease</a> appeared first on <a href="https://innovationscns.com">Innovations in Clinical Neuroscience</a>.]]></description>
		
		
		
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		<title>Enhancing Alzheimer Disease Detection Using Neuropsychiatric Symptoms: The Role of Mild Behavioral Impairment in the Revised NIA-AA Research Framework</title>
		<link>https://innovationscns.com/enhancing-alzheimer-disease-detection-using-neuropsychiatric-symptoms-the-role-of-mild-behavioral-impairment-in-the-revised-nia-aa-research-framework/</link>
		
		<dc:creator><![CDATA[ICNS Online Editor]]></dc:creator>
		<pubDate>Mon, 01 Jun 2026 15:57:28 +0000</pubDate>
				<category><![CDATA[Alzheimer’s disease]]></category>
		<guid isPermaLink="false">https://innovationscns.com/?p=77243</guid>

					<description><![CDATA[Reprinted with permission. J Geriatr Psychiatry Neurol. 2026;39(3):277–287.* by Rebeca Leon, MSc; Maryam Ghahremani, PhD; Dylan X. Guan, BSc; Eric E. Smith, MD; Henrik Zetterberg, MD; and Zahinoor Ismail, MD Drs. Leon, Ghahremani, Guan, Smith, and Ismail are with Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada. Drs. Ghahremani and Ismail are additionally with Department of Psychiatry, University of Calgary, Calgary, AB, Canada. Drs. Smith and Ismail are additionally with Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada; and Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada. Dr. Zetterberg is additionally with Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Molndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Molndal, Sweden; Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK; UK Dementia Research Institute at UCL, London, UK; Hong Kong Center for Neurodegenerative Diseases, InnoHK, Hong Kong, China; Wisconsin Alzheimer’s Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA. Dr. Ismail is additionally with O’Brien Institute for Public Health, University of Calgary, Calgary, AB, Canada; Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, Canada; Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK *Copyright: © 2026, the authors. This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). The article may have been modified to adhere to journal style. FUNDING: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Z. Ismail is supported by the Canadian Institutes of Health Research (BCA527734), Gordie Howe CARES, and the NIHR Exeter Biomedical Research Centre. H. Zetterberg is a Wallenberg Scholar and a Distinguished Professor at the Swedish Research Council supported by grants from the Swedish Research Council (#2023-00356, #2022-01018 and #2019-02397), the European Union’s Horizon Europe research and innovation programme under grant agreement No 101053962, Swedish State Support for Clinical Research (#ALFGBG-71320), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862), the AD Strategic Fund and the Alzheimer’s Association (#ADSF-21-831376-C, #ADSF-21-831381-C, #ADSF-21-831377-C, and #ADSF-24-1284328-C), the European Partnership on Metrology, co-financed from the European Union’s Horizon Europe Research and Innovation Programme and by the Participating States (NEu-roBioStand, #22HLT07), the Bluefield Project, Cure Alzheimer’s Fund, the Olav Thon Foundation, the Erling-Persson Family Foundation, Familjen Ronstroms Stiftelse, Stiftelsen for Gamla Tjanarinnor, Hjarnfonden, Sweden (#FO2022-0270), the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 860197 (MIRIADE), the European Union Joint Programme– Neurodegenerative Disease Research (JPND2021-00694), the National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre, the UK Dementia Research Institute at UCL (UKDRI-1003), and an anonymous donor. DISCLOSURES: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: ZI has served as an advisor/consultant to CADTH, Eisai, Lilly, Lundbeck/Otsuka, Novo Nordisk, and Roche. E.S. has provided consulting (unpaid) to Alnylam, Eisai, and Lilly. HZ has served at scientific advisory boards and/or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZpath, Amylyx, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, Enigma, LabCorp, Merry Life, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Quanterix, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, has given lectures sponsored by Alzecure, BioArctic, Biogen, Cellectricon, Fujirebio, Lilly, Novo Nordisk, Roche, and WebMD, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). RL, MG, and DXG report no conflicts of interest relevant to this manuscript. Abstract: Background: As the prevalence of Alzheimer disease (AD) rises, early identification of at-risk individuals is essential for effective intervention. Mild behavioral impairment (MBI), which captures emergent and persistent neuropsychiatric symptoms (NPS) in later life, may enhance early detection of AD; however, its associations with 2024 NIA-AA Core 1 biomarkers remain unexplored. We investigated associations between MBI and cerebrospinal fluid (CSF) amyloid β-42 (Aβ42) and phosphorylated tau-181 (p-tau181). Methods: Baseline data from 1327 dementia-free Alzheimer’s Disease Neuroimaging Initiative (ADNI) participants were analyzed. Participants were classified as MBI, non-MBI NPS, or no NPS. Gaussian mixture modeling defined biomarker positivity. Logistic and multinomial logistic regressions modeled associations between NPS status and biomarker positivity or biomarker profiles, adjusting for age, sex, education, and cognition. Results: MBI was associated with Aβ42+ (aOR=2.26, 95% confidence interval [CI]=1.71–2.99), p-tau181+ (aOR=1.72, 95% CI=1.30–2.28), and AD continuum profile (aOR=2.33, 95% CI=1.73–3.14), but not with non-AD pathology. Non-MBI NPS showed no association. Conclusion: MBI may serve as a behavioral marker of AD pathology. Keywords: Alzheimer disease, core 1 biomarkers, biomarker profiles, neuropsychiatric symptoms, mild behavioral impairment Introduction In 2018, the National Institute on Aging–Alzheimer’s Association (NIA-AA) introduced a research framework to define Alzheimer disease (AD) biologically through a biomarker continuum and to operationalize clinical progression across several stages from cognitively unimpaired (CU) through dementia.1 This framework has since been updated, refining the criteria for diagnosing and staging AD.2 The 2024 revised guidelines introduce Core 1 biomarkers as the most important for early detection of AD neuropathologic changes (ADNPC). Core 1 biomarkers include amyloid positron emission tomography (Aβ-PET) and validated cerebrospinal fluid (CSF) and plasma biomarkers (amyloid beta-42 (Aβ42), phosphorylated tau-217 (p-tau217), p-tau181, p-tau231). These biomarkers become abnormal around the same time as Aβ-PET and can detect AD in both symptomatic and asymptomatic individuals.2 Notwithstanding some controversy regarding the diagnosis of AD in the absence of cognitive symptoms,3 these biomarkers are recognized in the revised guidelines as sufficient for AD diagnosis and clinical decision-making. Despite advances in the biological definition of AD and the role of biomarkers, understanding the clinical manifestations is essential for appreciating AD across the clinical continuum. Cognitive decline in AD is well documented, progressing from CU to subjective cognitive decline (SCD) and mild cognitive impairment (MCI).4,5 Neuropsychiatric symptoms (NPS), nearly ubiquitous in AD dementia, often emergeThe post <a href="https://innovationscns.com/enhancing-alzheimer-disease-detection-using-neuropsychiatric-symptoms-the-role-of-mild-behavioral-impairment-in-the-revised-nia-aa-research-framework/">Enhancing Alzheimer Disease Detection Using Neuropsychiatric Symptoms: The Role of Mild Behavioral Impairment in the Revised NIA-AA Research Framework</a> appeared first on <a href="https://innovationscns.com">Innovations in Clinical Neuroscience</a>.]]></description>
		
		
		
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		<title>Digital Resource Center</title>
		<link>https://innovationscns.com/digital-resource-center/</link>
		
		<dc:creator><![CDATA[ICNS Online Editor]]></dc:creator>
		<pubDate>Mon, 01 Jun 2026 15:56:38 +0000</pubDate>
				<category><![CDATA[Alzheimer’s disease]]></category>
		<guid isPermaLink="false">https://innovationscns.com/?p=77248</guid>

					<description><![CDATA[Upcoming educational events and digital resources related to Alzheimer’s disease Alzheimer’s Association International Conference 2026 July 12–15, 2026 London, United Kingdom * https://aaic.alz.org/ &#160; Autoimmune Neurology Conference August 7–8, 2026 Houston, Texas *https://www.aan.com/events/autoimmune-neurology-conference &#160; American Neurological Association 2026 October 17–20, 2026 San Diego, California *https://myana.org/meetings/annual-meeting/ &#160; 2026 Fall ADRC meeting October 25–27, 2026 Seattle, Washington *https://www.naccdata.org/adrc-meetings/upcoming-adrc-meeting/ &#160; Neuroscience 2026 November 14–18, 2026 Washington DC *https://www.sfn.org/meetings/neuroscience-2026 &#160; Clinical Trials on Alzheimer’s Disease 2026 November 16–19, 2026 Boston, Massachussets *https://www.ctad-alzheimer.com/The post <a href="https://innovationscns.com/digital-resource-center/">Digital Resource Center</a> appeared first on <a href="https://innovationscns.com">Innovations in Clinical Neuroscience</a>.]]></description>
		
		
		
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		<title>Irene Malaty, MD: Identifying the Appropriate Patients for Subcutaneous Parkinson&#8217;s Disease Therapy</title>
		<link>https://innovationscns.com/irene-malaty-md-identifying-the-appropriate-patients-for-subcutaneous-parkinsons-disease-therapy/</link>
		
		<dc:creator><![CDATA[ICNS Online Editor]]></dc:creator>
		<pubDate>Mon, 01 Jun 2026 05:00:46 +0000</pubDate>
				<category><![CDATA[Expert Perspectives in Parkinson's Disease]]></category>
		<guid isPermaLink="false">https://innovationscns.com/?p=77169</guid>

					<description><![CDATA[Dr. Irene Malaty, from the University of Florida, discusses how to identify patients who may benefit from Vyalev (foscarbidopa/foslevodopa), highlighting key indicators that a patient is ready to transition beyond oral levodopa therapy. She reviews the impact of motor fluctuations, medication burden, and absorption challenges, and explains how continuous subcutaneous levodopa delivery may help address both daytime and overnight symptom control in patients with advanced Parkinson&#8217;s disease.The post <a href="https://innovationscns.com/irene-malaty-md-identifying-the-appropriate-patients-for-subcutaneous-parkinsons-disease-therapy/">Irene Malaty, MD: Identifying the Appropriate Patients for Subcutaneous Parkinson&#8217;s Disease Therapy</a> appeared first on <a href="https://innovationscns.com">Innovations in Clinical Neuroscience</a>.]]></description>
		
		
		
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		<title>Lessons Learned from Drug Development Programs in Autism: Implications for Future Programs</title>
		<link>https://innovationscns.com/lessons-learned-from-drug-development-programs-in-autism-implications-for-future-programs/</link>
		
		<dc:creator><![CDATA[ICNS Online Editor]]></dc:creator>
		<pubDate>Tue, 19 May 2026 15:27:59 +0000</pubDate>
				<category><![CDATA[Current Issue]]></category>
		<category><![CDATA[Drug Development]]></category>
		<category><![CDATA[Review]]></category>
		<category><![CDATA[autism spectrum disorder]]></category>
		<category><![CDATA[pharmacotherapy]]></category>
		<guid isPermaLink="false">https://innovationscns.com/?p=73794</guid>

					<description><![CDATA[Innov Clin Neurosci. 2026;23(4–6):9–16. Epub ahead of print. by Gahan Pandina, PhD; William J. Martin, PhD; Christopher Chatham, PhD; Declan Murphy, MD; Jane Myles, MSc; Robert H. Ring, PhD; and Amir Kalali, MD Dr. Pandina is with Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey. Dr. Martin was SVP/Global Therapeutic Head of Neuroscience R&#38;D, Johnson and Johnson, San Francisco, California, at the time of writing. Dr. Chatham is with Medical Biomarker Research, Shionogi, Inc., Florham Park, New Jersey. Dr. Murphy is with Institute of Psychiatry Psychology and Neuroscience, King’s College, London, United Kingdom. Ms. Myles is VP, Programs and Initiatives, Decentralized Trials and Research Alliance, Pacifica, California. Dr. Ring is with Kaerus Bioscience Ltd., London, United Kingdom. Dr. Kalali is with the International Society for CNS Drug Development (ISCDD), San Diego, California. FUNDING: Supported by the Sergey Brin Family Foundation. DISCLOSURES: GP is an employee of Johnson &#38; Johnson Innovative Medicine and is a stockholder of Johnson &#38; Johnson. CC is a full-time employee of Shionogi, Inc. All other authors have no conflicts of interest relevant to the contents of this article. ABSTRACT: There are no approved drugs for autism core features; the heterogeneous biology, symptom presentation, and clinical outcomes complicate drug trials design, and have hampered therapeutic drug development. We synthesized expert viewpoints from industry and academia on recent diagnostics and biomarker advances as well as pharmacotherapy evidence, aligned to patient-focused drug development outcomes and key concepts. Key learnings include: (i) measure what matters to patients and caregivers; (ii) enrich populations where they can be rationally matched to mechanism; (iii) do not use diagnostic tools as efficacy endpoints; (iv) align biomarker science with a potential qualification pathway associated with relevant behavior and biology; (v) design trials that reduce placebo response, burden, and attrition; (vi) assess co-occurring conditions and treatments explicitly. Observations and recommendations serve as a practical roadmap for sponsors and clinicians to increase trial informativeness and chance of success. Keywords: Autism spectrum disorder, treatment outcomes, biomarkers, enrichment, clinical trial methodology, caregiver burden, pharmacotherapy, regulatory science Introduction There is a significant unmet medical need for therapeutic options for the treatment of autism spectrum disorder (ASD). Although risperidone and aripiprazole are approved by the United States Food and Drug Administration (FDA) for the treatment of irritability, a cluster of associated symptoms in ASD, no treatments exist for the core symptoms of ASD. Autism is a spectrum condition, with a wide heterogeneity of clinical symptom presentations and cognitive and functional abilities. This heterogeneity represents a fundamental challenge facing outcome measurement and is a foundational thread passing through all aspects of drug development discussed in this article. Heterogeneity spans biology, behavior, developmental trajectories, language abilities, intellectual functioning, support needs, and co-occurring conditions. Other methodologic issues hamper therapeutic development, including high reliance on self- or caregiver-reported outcomes, oftentimes leading to large placebo effects, as with other central nervous system (CNS) conditions. Lastly, drug development has historically underemphasized the diverse voices and at times heterogeneous priorities of patients and caregivers. An FDA patient-focused drug development (PFDD) for autism meeting report highlighted priorities including better treatments for aggression, sleep, and co-occurring anxiety and mood symptoms, which for some individuals even outweighed the desire for treatments targeting or pathologizing “core” social communication or repetitive behaviors in daily life. This article aims to identify challenges and pitfalls faced in novel drug development for ASD to date and identify potential paths forward for clinicians and sponsors planning ASD therapeutics for pediatric and adult populations. Methods Comprehensive information was gathered and synthesized from diverse sources, including the following: the FDA’s PFDD Voice of the Patient report for Autism;1 literature reviews of diagnostics and biomarkers; updated ASD pharmacotherapy guidelines and meta-analyses; internal expert interviews, including information from expert consortia and novel biomarker development collaborations such as the Autism Biomarker for Clinical trials (sponsored by the Foundation for the National Institutes of Health)2,3 and the Autism Innovative Medicine Studies-2-Trials (AIMS-2-TRIALS)4 consortium (sponsored by the European Innovative Medicines Initiative); and detailed interviews on lessons learned from industry leaders with direct drug development experience. Framing the Therapeutic Problem: Targets, Populations, and Indications Before discussing endpoints and trial mechanics, we first frame the goals of autism drug development, focusing on the symptom domains of interest, the populations being studied, and the real-world priorities that matter most. Treat the person, not “the spectrum.” A critical success factor for developing effective therapies for autism is adherence to a set of core treatment principles. Treatment should focus on the individual rather than “the spectrum,” with decisions guided by the specific symptom profile, severity, development stage, and co-occurring condition(s). The field should avoid one-size-fits-all “autism drug” programs that are unlikely to succeed given the considerations above. Core symptoms vs. co-occurring conditions: clinical and development priorities. Co-occurring conditions should not be deprioritized. For many individuals, anxiety, attention deficit hyperactivity disorder (ADHD), depression, epilepsy, and sleep disturbances drive distress and functional impairment more than core traits. Researchers should align clinical trial targets and real-world care as much as possible. Historical concerns regarding potential “pseudospecificity” of treatment effect are no longer a dominant concern in psychiatric drug development, given an evolution in regulatory perspective.5 However, symptoms outside current Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)/International Classification of Diseases (ICD) diagnostic criteria, such as anxiety, hyperactivity and/or ADHD, sensory sensitivity, and sleep disturbances, among others, in individuals with ASD are nonetheless considered important clinical targets by many families and patient organizations.6 Moreover, there is increasing evidence that pharmacologic treatments developed in neurotypical populations for common co-occurring conditions (such as depression and anxiety) are less effective in autistic individuals, likely due to differences in brain responsivity.7 Pursuit of potential treatment indications requires thoughtful, early regulatory engagement to assure that development pathways are clearly defined. This will help to head off concerns about nonspecific effects and might also help sponsors navigate the landscape of frequently inadequate trial endpoints. With target domains defined, the next step is aligning ethical and regulatory choices to those targets and populations. A recent systematicThe post <a href="https://innovationscns.com/lessons-learned-from-drug-development-programs-in-autism-implications-for-future-programs/">Lessons Learned from Drug Development Programs in Autism: Implications for Future Programs</a> appeared first on <a href="https://innovationscns.com">Innovations in Clinical Neuroscience</a>.]]></description>
		
		
		
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		<title>Part 2—Jason Aldred, MD: Understanding Possible Side Effects When Treating Patients with Parkinson’s Disease</title>
		<link>https://innovationscns.com/part-2-jason-aldred-md-understanding-possible-side-effects-when-treating-patients-with-parkinsons-disease/</link>
		
		<dc:creator><![CDATA[ICNS Online Editor]]></dc:creator>
		<pubDate>Thu, 02 Apr 2026 18:56:07 +0000</pubDate>
				<category><![CDATA[Expert Perspectives in Parkinson's Disease]]></category>
		<guid isPermaLink="false">https://innovationscns.com/?p=53692</guid>

					<description><![CDATA[Dr. Jason Aldred, owner of Selkirk Neurology in Spokane, WA, discusses the neuropsychiatric effects and dyskinesia that patients may experience when taking Vyalev (foscarbidopa/foslevodopa).The post <a href="https://innovationscns.com/part-2-jason-aldred-md-understanding-possible-side-effects-when-treating-patients-with-parkinsons-disease/">Part 2—Jason Aldred, MD: Understanding Possible Side Effects When Treating Patients with Parkinson’s Disease</a> appeared first on <a href="https://innovationscns.com">Innovations in Clinical Neuroscience</a>.]]></description>
		
		
		
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		<title>Part 1—Jason Aldred, MD: Understanding Possible Side Effects When Treating Patients with Parkinson’s Disease</title>
		<link>https://innovationscns.com/jason-aldred-md-part-1-understanding-possible-side-effects-when-treating-patients-with-parkinsons-disease/</link>
		
		<dc:creator><![CDATA[ICNS Online Editor]]></dc:creator>
		<pubDate>Thu, 02 Apr 2026 18:37:52 +0000</pubDate>
				<category><![CDATA[Expert Perspectives in Parkinson's Disease]]></category>
		<guid isPermaLink="false">https://innovationscns.com/?p=53670</guid>

					<description><![CDATA[Dr. Jason Aldred, owner of Selkirk Neurology in Spokane, WA, discusses the safety profile of Vyalev (foscarbidopa/foslevodopa), notably injection site reactions and skin considerations.The post <a href="https://innovationscns.com/jason-aldred-md-part-1-understanding-possible-side-effects-when-treating-patients-with-parkinsons-disease/">Part 1—Jason Aldred, MD: Understanding Possible Side Effects When Treating Patients with Parkinson’s Disease</a> appeared first on <a href="https://innovationscns.com">Innovations in Clinical Neuroscience</a>.]]></description>
		
		
		
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		<title>January-March 2026 Digital Edition</title>
		<link>https://innovationscns.com/january-march-2026-digital-edition/</link>
		
		<dc:creator><![CDATA[ICNS Online Editor]]></dc:creator>
		<pubDate>Sun, 01 Mar 2026 13:00:23 +0000</pubDate>
				<category><![CDATA[Digital Editions]]></category>
		<guid isPermaLink="false">https://innovationscns.com/?p=41712</guid>

					<description><![CDATA[Click the cover below to access the January-March 2026 Digital EditionThe post <a href="https://innovationscns.com/january-march-2026-digital-edition/">January-March 2026 Digital Edition</a> appeared first on <a href="https://innovationscns.com">Innovations in Clinical Neuroscience</a>.]]></description>
		
		
		
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		<title>Letters to the Editor: Post-SSRI Sexual Dysfunction: Challenges and Treatment Approaches</title>
		<link>https://innovationscns.com/letters-to-the-editor-post-ssri-sexual-dysfunction-challenges-and-treatment-approaches/</link>
		
		<dc:creator><![CDATA[ICNS Online Editor]]></dc:creator>
		<pubDate>Sun, 01 Mar 2026 12:59:25 +0000</pubDate>
				<category><![CDATA[Current Issue]]></category>
		<category><![CDATA[Letters to the Editor]]></category>
		<guid isPermaLink="false">https://innovationscns.com/?p=41717</guid>

					<description><![CDATA[Innov Clin Neurosci. 2026;23(1–3):5–9. Dear Editor: Selective serotonin reuptake inhibitors (SSRIs) have long been a cornerstone in the treatment of mood disorders, particularly depression and anxiety. Since their introduction in the late 1980s, SSRIs have revolutionized psychiatric care by offering a safer alternative to older classes of antidepressants with fewer adverse effects. However, despite their widespread use and proven efficacy, SSRIs are not without their drawbacks, one of which is sexual dysfunction, both during treatment and after discontinuation.1 This persistent sexual dysfunction, which can continue long after stopping the medication, is becoming increasingly recognized as a significant and distressing component of post-SSRI sexual dysfunction (PSSD). PSSD refers to a collection of symptoms that some individuals experience following the discontinuation or reduction in dosage of SSRI medications. The syndrome typically includes a range of physical, emotional, and cognitive disturbances, such as brain fog, fatigue, insomnia, dizziness, anxiety, and sensory and cognitive disturbance. While these symptoms are well-documented, sexual dysfunction remains one of the most challenging and persistent aspects of PSSD.1,2 Even after stopping SSRI treatment, many individuals report enduring sexual difficulties, such as diminished libido, erectile dysfunction, and difficulty achieving orgasm. For these individuals, the lasting sexual side effects represent a severe impairment of quality of life, and they can cause significant emotional distress, relationship issues, and reluctance to seek further treatment. Sexual dysfunction during SSRI treatment is a well-known adverse effect, affecting a substantial proportion of patients. These issues typically manifest as decreased libido, anorgasmia, delayed ejaculation, or erectile dysfunction. Although these adverse effects are expected to resolve upon discontinuation of the medication, patients with PSSD often report continued sexual difficulties long after stopping their SSRI regimen. This lingering dysfunction may include reduced sexual desire, persistent erectile issues, or difficulties achieving orgasm, all of which can have profound impacts on personal relationships and emotional wellbeing.3 The mechanisms behind PSSD remain unclear, but researchers speculate that they are linked to long-term changes in the brain’s serotonin system. SSRIs work by increasing serotonin levels in the brain, which is thought to enhance mood and alleviate symptoms of depression and anxiety. However, serotonin plays a critical role in regulating sexual behavior, and prolonged exposure to high levels of serotonin can interfere with sexual function. As the brain adjusts to the heightened serotonin levels during SSRI treatment, it may decrease the sensitivity or number of serotonin receptors. When the medication is stopped, the brain may struggle to return to its pretreatment state, leading to ongoing sexual dysfunction.3 This disruption in the serotonin system, particularly the alteration of serotonin receptor sensitivity, could be a major factor in the persistence of sexual dysfunction in this enduring and disabling syndrome. While serotonin is essential for regulating sexual arousal and satisfaction, the imbalance in the brain dopamine/serotonin ratio caused by SSRI discontinuation could result in a continued sexual deficit.1–3 Additionally, this dysfunction can be exacerbated by the psychological effects of PSSD, as patients may experience anxiety, depression, and frustration, all of which further impact sexual desire and performance. Currently, there is no standard treatment protocol specifically for PSSD, and patients often face a lack of understanding from healthcare providers. Since PSSD is not universally recognized as a formal medical diagnosis, many physicians are unsure of how to approach treatment.4,5 Furthermore, sexual dysfunction is often an overlooked and underreported side effect of SSRI discontinuation, leaving many patients feeling isolated and unsure where to turn for help. The treatment of PSSD presents significant challenges due to the condition’s heterogeneous nature. The severity and duration of sexual side effects vary widely between individuals, and there is no universally effective solution.3–5 Some patients may find that their sexual function gradually improves with time, while others report persistent issues that do not resolve after months or even years. In the absence of well-established treatment guidelines, management strategies often involve a combination of approaches, including pharmacological treatments, therapy, and lifestyle changes.6 For some individuals, switching to a different class of antidepressant (eg, vortioxetine, bupropion, or desvenlafaxine) or using adjunct medications, such as bupropion and mirtazapine, which have a lower incidence of sexual side effects, may help alleviate sexual dysfunction. Other patients may benefit from medications specifically designed to address sexual dysfunction, such as sildenafil or tadalafil, which may help with erectile issues. However, these treatments are not always effective for all patients, and the adverse effects may not fully resolve the sexual difficulties.5,6 Notably, much of the existing literature on pharmacological management of iatrogenic sexual dysfunction has predominantly focused on male patients, particularly in relation to erectile dysfunction. Psychotherapy, particularly cognitive-behavioral therapy, can also play a vital role in managing PSSD. Therapy can help individuals address the emotional and psychological aspects of sexual dysfunction, including the anxiety or depression that may exacerbate the issue. In addition, couples therapy may be helpful for partners who are experiencing relationship strain due to sexual difficulties, providing a supportive environment to discuss and address the issue. Looking toward the future, the treatment of PSSD is likely to improve as research into the condition continues. While much remains unknown, several promising areas of investigation could lead to more effective therapies. One potential avenue for future treatment is the development of medications that target specific serotonin receptors or pathways to rebalance serotonin signaling. These therapies may offer a more tailored approach to treatment, potentially reducing the sexual side effects associated with SSRIs and improving outcomes for those with PSSD. Moreover, emerging research on neuroplasticity suggests that techniques such as transcranial magnetic stimulation and focal muscle vibration6 could offer novel ways to stimulate changes in brain function and restore neurotransmitter balance. These therapies, which are already being explored for other neuropsychiatric conditions, could hold promise for alleviating the lingering sexual dysfunction seen in PSSD. Personalized medicine, guided by genetic and biomarker data, may also provide a more targeted approach to treating sexual dysfunction in individuals with PSSD. By understanding how a patient’s unique genetic makeup influences their response to SSRIs and other medications, healthcare providers may be able to developThe post <a href="https://innovationscns.com/letters-to-the-editor-post-ssri-sexual-dysfunction-challenges-and-treatment-approaches/">Letters to the Editor: Post-SSRI Sexual Dysfunction: Challenges and Treatment Approaches</a> appeared first on <a href="https://innovationscns.com">Innovations in Clinical Neuroscience</a>.]]></description>
		
		
		
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		<title>Letters to the Editor: Response to “Burnout and Ethical Awareness in Mental Health Professionals: A Correlational Study”</title>
		<link>https://innovationscns.com/letters-to-the-editor-response-to-burnout-and-ethical-awareness-in-mental-health-professionals-a-correlational-study/</link>
		
		<dc:creator><![CDATA[ICNS Online Editor]]></dc:creator>
		<pubDate>Sun, 01 Mar 2026 12:58:42 +0000</pubDate>
				<category><![CDATA[Current Issue]]></category>
		<category><![CDATA[Letters to the Editor]]></category>
		<guid isPermaLink="false">https://innovationscns.com/?p=41722</guid>

					<description><![CDATA[Innov Clin Neurosci. 2026;23(1–3):5–9. Dear Editor: We read with great interest the study by Fatima and Ilyas,1 which explores the relationship between ethical awareness and burnout among mental health professionals in Pakistan. The integration of the Santa Clara Ethics Scale and Counselor Burnout Inventory, both psychometrically sound instruments, lends credibility to the study’s measurement approach. Moreover, the study’s attention to sector-based differences and its inclusion of a predominantly female sample reflects the composition of Pakistan’s mental health workforce, offering contextually meaningful insights into burnout dynamics. However, certain analytical and interpretive aspects warrant closer scrutiny. The decision to use purposive nonprobability sampling restricts the generalizability of the findings. Yet more crucially, it may introduce unmeasured sectoral or institutional clustering effects. Given that burnout is influenced by organizational culture and administrative load,2 future studies may benefit from incorporating multilevel modeling to account for institution-level variance. Clinically, this distinction matters because uniform policy interventions may overlook localized drivers of emotional exhaustion and professional dissatisfaction. The reported inverse association between ethical awareness and multiple burnout domains is interpreted as suggesting a protective role. While plausible, this inference may be confounded by professional seniority or role autonomy, factors often correlated with both age and ethical reasoning.3 Without stratified analysis or adjustment for professional role (eg, counselor vs psychiatrist), the strength of the association may be overestimated. In practical terms, this could affect how interventions are designed, as prioritizing ethics training alone may not suffice unless embedded within a broader framework addressing job role constraints and decision latitude. The significant difference in exhaustion between public and private sector professionals, with a small effect size (Cohen’s d=0.27), invites a cautious interpretation. Though statistically significant, the modest magnitude emphasizes the need for deeper investigation into structural inequities, caseload variability, and supervisory availability within each sector. Clinically, this finding should not prompt binary policy responses but rather tailored support mechanisms responsive to sector-specific constraints. We commend the authors for addressing a critical gap in the Pakistani mental health literature and for anchoring their analysis within validated psychometric tools. Future research may be strengthened by longitudinal designs, stratified role-based analyses, and the integration of qualitative inquiry to uncover latent factors that shape both ethical sensitivity and burnout risk. Advancing such research is essential for informing targeted policy reform and sustaining a resilient mental health workforce in low-resource settings. With regards, Shyam S. Sah, MD, and Abhishek Kumbhalwar, PhD Dr. Sah is with the Dr. D. Y. Patil Medical College Hospital and Research Centre at Dr. D. Y. Patil Vidyapeeth (Deemed-to-be-University), Pune, India. Dr. Kumbhalwar is with the Dr. D. Y. Patil Dental College and Hospital, Dr. D. Y. Patil Vidyapeeth (Deemed-to-be-University), Pune, India. Funding/financial disclosures. The authors have no relevant conflicts of interest. No funding was received for the preparation of this letter. Correspondence. Shyam S. Sah, MD; References Fatima M, Ilyas U. Burnout and ethical awareness in mental health professionals: a correlational study. Innov Clin Neurosci. 2025;22(7–9):24–27. Kinetova NK, Kospakov AM. The impact of the organizational culture of universities on the psychological wellbeing of students and staff. Bulletin Zhubanov Aktobe Regional University. 2024;78(4):85–91. Franklin-Hall A. On becoming an adult: autonomy and the moral relevance of life’s stages. Philos Q. 2013;63(251):223–247.The post <a href="https://innovationscns.com/letters-to-the-editor-response-to-burnout-and-ethical-awareness-in-mental-health-professionals-a-correlational-study/">Letters to the Editor: Response to “Burnout and Ethical Awareness in Mental Health Professionals: A Correlational Study”</a> appeared first on <a href="https://innovationscns.com">Innovations in Clinical Neuroscience</a>.]]></description>
		
		
		
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		<title>Letters to the Editor: Responding to Correspondence on “Burnout and Ethical Awareness in Mental Health Professionals: A Correlational Study”</title>
		<link>https://innovationscns.com/letters-to-the-editor-responding-to-correspondence-on-burnout-and-ethical-awareness-in-mental-health-professionals-a-correlational-study/</link>
		
		<dc:creator><![CDATA[ICNS Online Editor]]></dc:creator>
		<pubDate>Sun, 01 Mar 2026 12:57:03 +0000</pubDate>
				<category><![CDATA[Current Issue]]></category>
		<category><![CDATA[Letters to the Editor]]></category>
		<guid isPermaLink="false">https://innovationscns.com/?p=41726</guid>

					<description><![CDATA[Innov Clin Neurosci. 2026;23(1–3):5–9. Dear Editor: We thank Sah and Kumbhalwar for their careful reading of our article, “Burnout and Ethical Awareness in Mental Health Professionals: A Correlational Study,”1 and for their constructive engagement with its findings. Their letter raises important methodological and interpretive points that extend scholarly discussion on burnout and ethical awareness within low-resource mental health contexts such as Pakistan. Regarding sampling, we acknowledge the limitations inherent in purposive nonprobability methods, particularly with respect to generalizability. This approach was intentionally adopted to recruit mental health professionals with a minimum of 2 years of clinical experience in Lahore, Pakistan, where probability-based sampling is often constrained by fragmented service delivery systems and limited institutional access.2 Within these contextual constraints, this approach allowed for focused examination of an under-researched professional group. We agree that future studies incorporating multilevel or hierarchical analytic techniques would be well-positioned to account for institution-level effects and enhance generalizability across broader and nonurban clinical settings. The authors also appropriately highlighted the potential influence of professional seniority and role autonomy when interpreting the inverse association between ethical awareness and burnout. Our sample included professionals from multiple disciplines, including psychiatrists, psychologists, couples and family therapists, and counselors. Age was examined as a correlational variable and demonstrated a consistent protective association with overall burnout and its dimensions (r=−0.22 to –0.19; P&#60;0.001), consistent with prior evidence linking greater professional experience with reduced burnout risk.3 While ANOVA post-hoc analyses did not indicate statistically significant differences across professional roles, we concur that future research using larger, multisite samples and role-stratified multivariate analyses would more precisely clarify the contribution of professional position, autonomy, and decision-making latitude. With respect to sector-based differences, we agree with the authors’ cautious interpretation of the small effect size observed between public and private sector professionals. Although exhaustion levels were significantly higher among those working in the public sector, the modest magnitude of this difference underscores the importance of nuanced interpretation. Rather than supporting binary policy interpretations, this finding highlights the need for context-sensitive interventions that address systemic stressors such as high caseloads, limited resources, and infrastructural constraints, which are particularly salient within public healthcare settings in Pakistan. In this context, ethics-informed training initiatives and complementary assessment tools, for example, instruments designed to capture ethical dilemma–related distress,4 may represent one potential component of broader organizational strategies aimed at mitigating professional burnout. We appreciate the authors’ thoughtful critique and their recommendations for future research directions. Longitudinal designs, role-stratified analyses, and multilevel modeling would substantially advance understanding of the dynamic interplay between ethical awareness, professional context, and burnout. Importantly, within its stated methodological limits, the present study contributes initial empirical evidence linking ethical awareness with lower burnout across multiple domains among mental health professionals in Pakistan, an area in which systematic data remain limited. We thank the authors for their valuable contribution to this scholarly exchange and welcome continued dialogue on strategies to promote the wellbeing and sustainability of the mental health workforce. With regards, Muqadas Fatima, MS, and Uzma Ilyas, PhD Ms. Fatima is Lecturer at the National University of Modern Languages, Lahore, Pakistan. Dr. Ilyas is Senior Lecturer at Forman Christian College University, Lahore, Pakistan. Funding/financial disclosures. The authors have no relevant conflicts of interest. No funding was received for the preparation of this letter. Correspondence. Muqadas Fatima, MS References Fatima M, Ilyas U. Burnout and ethical awareness in mental health professionals: a correlational study. Innov Clin Neurosci. 2025;22(7–9):24–27. Dayani K, Zia M, Qureshi O, et al. Evaluating Pakistan’s mental healthcare system using World Health Organization’s Assessment Instrument for Mental Health Systems (WHO-AIMS). Int J Ment Health Syst. 2024;18(1):32. Sofology M, Efstratopoulou M, Dunn T. Predicting burnout syndrome in Greek mental health professionals. J Soc Serv Res. 2019;45(1):142–149. Fatima M, Ilyas U. Development of Ethical Dilemma Distress Scale for Mental Health Practitioners (EDDS-MHP). Pak J Psychol Res. 2024;39(3):613–637.The post <a href="https://innovationscns.com/letters-to-the-editor-responding-to-correspondence-on-burnout-and-ethical-awareness-in-mental-health-professionals-a-correlational-study/">Letters to the Editor: Responding to Correspondence on “Burnout and Ethical Awareness in Mental Health Professionals: A Correlational Study”</a> appeared first on <a href="https://innovationscns.com">Innovations in Clinical Neuroscience</a>.]]></description>
		
		
		
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		<title>Letters to the Editor: “AI Literacy” is a Deflection of Responsibility</title>
		<link>https://innovationscns.com/letters-to-the-editor-ai-literacy-is-a-deflection-of-responsibility/</link>
		
		<dc:creator><![CDATA[ICNS Online Editor]]></dc:creator>
		<pubDate>Sun, 01 Mar 2026 12:56:27 +0000</pubDate>
				<category><![CDATA[Current Issue]]></category>
		<category><![CDATA[Letters to the Editor]]></category>
		<guid isPermaLink="false">https://innovationscns.com/?p=41730</guid>

					<description><![CDATA[Innov Clin Neurosci. 2026;23(1–3):5–9. Dear Editor: Pierre et al1 carefully document a case of a phenomenon that has received widespread media attention in recent months. The authors correctly note that certain fundamental characteristics of large language model (LLM) “chatbot” products could encourage or exacerbate delusional thinking—because they have a textual interface, humans are prone to anthropomorphize them; because they are optimized for engagement, they tend to be flattering toward the user regardless of what the user is saying; and because they are predictive text generators, they produce output that aligns closely with the content and style of the user’s input but is not necessarily accurate. However, by suggesting that “regarding artificial intelligence (AI) chatbots as a kind of superhuman intelligence or god-like entity” might be a risk factor for AI-associated psychosis and that preventive strategies might include “enhanced AI literacy,” the authors stop just short of making an important ethical point. The textual interface of LLM chatbot products is knowingly implemented despite decades of human-computer interaction research going back to Joseph Weizenbaum’s ELIZA that this interface is extraordinarily persuasive in its implicit suggestion of an anthropomorphic “intelligence” on the other side.2,3 This interface is persuasive even if one knows “better.” Notably, the authors describe the woman in their case report as having “extensive experience” with LLM technologies, with “a firm understanding” of how they work. Although LLM products are text prediction engines, they are aggressively promoted by well-capitalized corporations as a form of “AI,” a term with specific pop-cultural resonance: Data (Star Trek), Jarvis (Iron Man), Samantha (Her). They are marketed with a specific quasimystical visual language: ChatGPT has a mandala-like logo; Claude and Gemini have stylized stars. The chief executives of the companies developing them make hyperbolic claims about their capabilities: that talking to ChatGPT is like talking to “a legitimate PhD-level expert in anything, in any area you need” (OpenAI’s Sam Altman)4 and that in the imminent future LLMs will be “smarter than a Nobel Prize winner across most relevant fields—biology, programming, math, engineering, writing, etc.” (Anthropic’s Dario Amodei).5 In this context, it is not at all surprising that many users might regard these products as superhuman or god-like. Implicitly and explicitly, the developers of these products are encouraging consumers to regard them as such—and have an obvious incentive to do so. A user who trusts a chatbot as an oracle-like source of advice or information will stay engaged with the product and purchase a subscription. What Pierre et al1 call “deification” is not a misunderstanding. It is the predictable outcome of decisions made in the design and marketing of these products with textual interfaces. Education alone cannot overcome this intentional persuasiveness. I worry that in discussing “AI literacy” without emphasizing this dynamic, we are deflecting responsibility away from the developers of chatbot products and toward their users. Commercial gambling serves as an illustrative analogy: the industry successfully guided policy and research away from interrogation of its own practices and toward individuals engaging in problematic gambling behavior, even though the industry’s practices encourage that very behavior.6 Pierre et al1 do reasonably note that “governmental regulation and the development of safer products” is important, but here, too, the problem is less with the safety of individual products and more with the safety of the “AI” paradigm in which they are positioned. An important component of what we might call “AI literacy” is the acknowledgement that “AI” is itself a constructed category. With regards, Amandeep Jutla, MD Dr. Jutla is with Columbia University and the New York State Psychiatric Institute, New York, New York. Funding/financial disclosures. The author has no relevant conflicts of interest. No funding was received for the preparation of this letter. Correspondence. Amandeep Jutla, MD References Pierre JM, Gaeta B, Raghavan G, Sarma KV. “You’re not crazy”: a case of new-onset AI-associated psychosis. Innov Clin Neurosci. 2025;22(10–12):11–13. Weizenbaum, J. Contextual understanding by computers. Commun ACM. 1967;10(8):474–480. Hofstadter DR. The ineradicable Eliza effect and its dangers. Fluid Concepts and Creative Analogies: Computer Models of the Fundamental Mechanisms of Thought. Harvester Wheatsheaf; 1995:155–169. Kan M. With GPT-5, OpenAI promises access to &#8220;PhD-level&#8221; AI expertise. PC Magazine. 7 Aug 2025. Accessed 13 Jan 2026. https://www.pcmag.com/news/with-gpt-5-openai-promises-access-to-phd-level-ai-expertise Amodei D. Machines of loving grace. 11 Oct 2024. Accessed 13 Jan 2026. https://www.darioamodei.com/essay/machines-of-loving-grace Wardle H, Degenhardt L, Marionneau V, et al. The Lancet Public Health Commission on gambling. Lancet Public Health. 2024:S2468–2667(24)00167–1.The post <a href="https://innovationscns.com/letters-to-the-editor-ai-literacy-is-a-deflection-of-responsibility/">Letters to the Editor: “AI Literacy” is a Deflection of Responsibility</a> appeared first on <a href="https://innovationscns.com">Innovations in Clinical Neuroscience</a>.]]></description>
		
		
		
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		<title>Letters to the Editor: Response to “‘AI Literacy’ is a Deflection of Responsibility”</title>
		<link>https://innovationscns.com/letters-to-the-editor-response-to-ai-literacy-is-a-deflection-of-responsibility/</link>
		
		<dc:creator><![CDATA[ICNS Online Editor]]></dc:creator>
		<pubDate>Sun, 01 Mar 2026 12:55:45 +0000</pubDate>
				<category><![CDATA[Current Issue]]></category>
		<category><![CDATA[Letters to the Editor]]></category>
		<guid isPermaLink="false">https://innovationscns.com/?p=41734</guid>

					<description><![CDATA[Dear Editor: I thank Dr. Jutla for his comments on our case report1 of artificial intelligence (AI)–associated psychosis. As we predicted, other cases have followed in the academic literature, along with first-person accounts and continued reports in the media.2–4 Dr. Jutla voices concern about our emphasis on user-end risk factors for AI-associated psychosis, such as immersion and deification, at the expense of calling out chatbot developers for hyping their products and encouraging such unhealthy consumer behavior through product design. I agree that the risk of AI-associated psychosis is best mitigated through not only user-end interventions (eg, avoiding immersion and deification, AI literacy), but product-end safety enhancements (eg, making chatbots less sycophantic, training them to detect signs of mental health issues, strengthening warnings and “guardrails,” and generating therapeutic responses when needed). While Dr. Jutla compares the AI chatbot industry to the gambling industry, I also see relevant parallels with the tobacco and gun industries where the responsibility for preventing potential harm from products is optimally shared by both consumers and manufacturers. However, such industries have been historically averse to safety refinements that negatively impact profits, with corporate decisions to implement them often coming only in response to government regulation and class action lawsuits. In the case of AI chatbots, consumer backlash when OpenAI released the less-sycophantic ChatGPT5.0 suggests that what makes some people vulnerable to AI-associated psychosis is the very same thing that gives it mass appeal.5 If that is the case—and in an environment where the current presidential administration in the United States has strongly advocated against regulation of the industry,6 along with the fact that AI chatbot companies are already struggling to generate profits7—then I am not particularly sanguine about chatbot makers taking responsibility to walk back the marketing hype of AI and committing themselves to making safer but less lucrative products. As a psychiatrist, I find such prognostication especially discouraging for the wellbeing of my patients, but only the tip of the iceberg in terms of the potential harm of AI chatbots. Elsewhere, I have called AI-associated psychosis a “canary in the coal mine,” based on the potential for AI chatbots to encourage not only delusional thinking, but “more mundane false beliefs related to conspiracy theories, science denialism, political propaganda, and so-called alternative facts.”8 Researchers have likewise identified AI-associated psychosis and “widely shared unfounded beliefs” fueled by AI as a potential national security threat.9 Indeed, AI chatbots and other forms of generative AI, such as deepfake videos, are already being exploited on an increasingly alarming scale to disseminate propaganda aimed at manipulating human belief and behavior.10,11 Going forward, such weaponization in the service of information warfare will likely pose a much greater risk than AI-associated psychosis and lie well beyond the control of either consumers or chatbot makers. With regards, Joseph M. Pierre, MD Dr. Pierre is with the University of California, San Francisco, San Francisco, California. Funding/financial disclosures. The author has no relevant conflicts of interest. No funding was received for the preparation of this letter. Correspondence. Joseph M. Pierre, MD; References Pierre JM, Gaeta B, Raghavan G, Sarma KV. “You’re not crazy”: a case of new-onset AI-associated psychosis. Innov Clin Neurosci. 2025;22(10–12):11–13. Caldwell MR, Ho PA. A case of artificial intelligence psychosis co-occurring with substance-induced psychosis. Prim Care Companion CNS Disord. 2025;27(6):25cr04059 Ner C. I couldn’t stop creating AI images of myself—until I had a breakdown. Newsweek. 23 Dec 2025. Accessed 2 Feb 2026. https://www.newsweek.com/ai-psychosis-couldnt-stop-creating-images-bipolar-episode-11255008 Dupre MH. A man bought Meta’s AI glasses, and ended up wandering the desert in search of aliens. Futurism. 15 Jan 2026. Accessed 2 Feb 2026. https://futurism.com/artificial-intelligence/meta-ai-glasses-desert-aliens Hill K, Valentino-Davies J. What OpenAI did when ChatGPT users lost touch with reality. The New York Times. 23 Nov 2025. Accessed 2 Feb 2026. https://www.nytimes.com/2025/11/23/technology/openai-chatgpt-users-risks.html The White House. Winning the race: America’s AI action plan. Jul 2025. Accessed 2 Feb 2026. https://www.whitehouse.gov/wp-content/uploads/2025/07/Americas-AI-Action-Plan.pdf Wilkins J. AI industry nervous about small detail: they’re not making any real money. Futurism. 8 Aug 2025. Accessed 2 Feb 2026. https://futurism.com/ai-industry-nervous-money Pierre JM. Can AI chatbots validate delusional thinking? BMJ. 2025;391:r2229. Treyger E, Matveyenko J, Ayer L. Manipulating minds: security implications of AI-induced psychosis. RAND Corporation. 8 Dec 2025. Accessed 2 Feb 2026. https://www.rand.org/pubs/research_reports/RRA4435-1.html Frances A, Pierre JM. Chatbot-generated propaganda threatens democracy. Psychiatric Times. 27 Jan 2026. Accessed 2 Feb 2026.https://www.psychiatrictimes.com/view/chatbot-generated-propaganda-threatens-democracy Schroeder DT, Cha M, Baronchelli A, et al. How malicious AI swarms can threaten democracy. Science. 2026;391(6783):354–357.The post <a href="https://innovationscns.com/letters-to-the-editor-response-to-ai-literacy-is-a-deflection-of-responsibility/">Letters to the Editor: Response to “‘AI Literacy’ is a Deflection of Responsibility”</a> appeared first on <a href="https://innovationscns.com">Innovations in Clinical Neuroscience</a>.]]></description>
		
		
		
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		<title>Social Media Use and Technology Use in Patients with Intellectual and Developmental Disabilities</title>
		<link>https://innovationscns.com/social-media-use-and-technology-use-in-patients-with-intellectual-and-developmental-disabilities/</link>
		
		<dc:creator><![CDATA[ICNS Online Editor]]></dc:creator>
		<pubDate>Sun, 01 Mar 2026 12:54:47 +0000</pubDate>
				<category><![CDATA[Current Issue]]></category>
		<category><![CDATA[Psychotherapy Rounds]]></category>
		<guid isPermaLink="false">https://innovationscns.com/?p=41741</guid>

					<description><![CDATA[Innov Clin Neurosci. 2026;23(1–3):10–16. by Larrilyn Grant, MD, MS; Lexi Singh, BS; and Anisha Mandava, MS All authors are with the Wright State, University Boonshoft School of Medicine Department of Psychiatry and Wright State University Boonshoft School of Medicine, Dayton, Ohio. FUNDING: No funding was provided for this article. DISCLOSURES: The authors have no relevant conflicts of interest. Department Editor: Julie P. Gentile, MD, is Professor and Chair of the Department of Psychiatry at Wright State University in Dayton, Ohio. Editor’s Note: The patient scenarios presented in this article are composite cases written to illustrate certain diagnostic characteristics and to instruct on treatment techniques. The composite cases are not real patients in treatment. Any resemblance to real patients is purely coincidental. Abstract: As internet and social media use become increasingly central to youth development, it is critical to address the unique opportunities and challenges these technologies pose for individuals with intellectual and developmental disabilities (IDD). This column explores how digital tools can enhance social connection, identity formation, adaptive skill-building, and access to therapeutic resources in youth with IDD, while also acknowledging the heightened risks of cyberbullying, overstimulation, exploitation, and digital exclusion. Through a review of current literature, clinical vignettes, and practical guidance, we offer a nuanced framework for clinicians to promote safe, inclusive, and developmentally appropriate internet use. We highlight the importance of caregiver support, tailored digital tools, and mental health–informed approaches to digital literacy. Clinicians are encouraged to integrate technology discussions into care planning, advocate for accessible digital environments, and empower youth with IDD to participate meaningfully in the digital world. Keywords: intellectual and developmental disabilities (IDD); social media; internet use; digital inclusion; online safety; cyberbullying; social connectedness; caregiver support Introduction The internet is used globally, has become an integral part of everyday life, and supports daily functioning, education, health, and the economy.1 In the United States, 96% of youth report using the internet daily and 95% report using social media.2 With the rapid rise of internet usage and diversity of social media applications, it is important that practitioners review internet usage with youths and take the opportunity to maximize benefits and minimize risks. Intellectual disability (ID) is characterized by substantial impairments in cognitive functioning and adaptive behavior, affecting a wide range of everyday social and practical skills.3 Some evidence has suggested that individuals with ID are more likely to experience social isolation and loneliness and have smaller social networks.4,5 The use of the internet and social media could increase the quality and frequency of social interactions in this population.6 Despite this potential benefit, there is a digital divide between individuals without disability and individuals with a disability.7,8 Research indicates that more youths with ID do not have access to a smartphone, computer, or tablet compared to neurotypical youths.9 While prevalence rates of internet use are understudied in individuals with ID, some studies suggest that between 80% to 85% of individuals with ID use the internet, with use being on the rise in the last decade.10,11 Despite emerging research, there remains a lack of tailored guidance for clinicians, caregivers, and educators on how to support safe and beneficial digital engagement for youths with ID. This column aims to highlight both the promising opportunities and the pressing challenges of internet and social media use in youths with intellectual and developmental disabilities (IDD). Drawing from the growing body of literature and clinical insights, we explore how digital tools can enhance social connectedness, support skill-building, and expand therapeutic access—while also addressing safety risks, cognitive vulnerabilities, and systemic barriers to inclusion. Practitioners are encouraged to consider these nuanced factors when discussing internet and social media use with patients and families and to promote digital inclusion as an important aspect of holistic care. Benefits of Social Media and Internet Use for Individuals with IDD Enhancing social interaction and reducing isolation. Strengthening relationships with family and friends. Individuals with IDD often rely on caregivers for social contact, which can limit the development and maintenance of relationships in their lives and, ultimately, their sense of independence.12,13 However, social media can act as a bridge, empowering them to connect, express themselves, and participate in social life more freely.12 Virtual spaces offer an alternative to face-to-face interaction, allowing individuals to communicate at their own pace and comfort level. Whether gaming, posting videos, or texting, these platforms provide control and independence, boosting their confidence and self-esteem.14 Within a supportive environment, social media use can increase social confidence and improve peer relationships.15 Individuals with IDD enjoy the privacy and autonomy of online spaces, allowing them to interact beyond caregiver oversight.16 While there are specialized websites for individuals with IDD, the majority of people with IDD use mainstream social media sites to interact with a broader and more diverse audience.6 Finding community through shared interest. Online platforms facilitate the development of friendships and provide a sense of community for individuals with IDD. Whether it&#8217;s through online communities, Discord servers, or Facebook groups, these platforms offer forums to discuss shared passions, entertainment, and advocacy.12 Many online discussions spill over into real-world interactions, validating their social skills and contributing to the development of their self-identity.13,15 Expressing identity. Social media allows individuals with IDD to control their online presence, choosing how they present themselves to the world. Some openly disclose their disability as part of their advocacy efforts, while others choose to engage without revealing this aspect of themselves.15 Online forums allow individuals with IDD to be recognized based on their interests and passions rather than being defined solely by their disability status.6 Digital advocacy and self-representation. People with IDD use social media as a tool for advocacy to raise awareness about discrimination and promote inclusion. By sharing their experiences, providing resources, and amplifying their voices, they use their platforms to advocate for disability rights.15 Digital platforms as tools for skill development. Strengthening cognitive and adaptive skills. Navigating social media requires decision-making. One must decide what to post, how to respond, and how to manage online interactions. This process fosters adaptive skills andThe post <a href="https://innovationscns.com/social-media-use-and-technology-use-in-patients-with-intellectual-and-developmental-disabilities/">Social Media Use and Technology Use in Patients with Intellectual and Developmental Disabilities</a> appeared first on <a href="https://innovationscns.com">Innovations in Clinical Neuroscience</a>.]]></description>
		
		
		
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		<title>Exploring Anticholinergic Burden in a Psychiatric Inpatient Population</title>
		<link>https://innovationscns.com/exploring-anticholinergic-burden-in-a-psychiatric-inpatient-population/</link>
		
		<dc:creator><![CDATA[ICNS Online Editor]]></dc:creator>
		<pubDate>Sun, 01 Mar 2026 12:53:26 +0000</pubDate>
				<category><![CDATA[Current Issue]]></category>
		<category><![CDATA[Original Research]]></category>
		<guid isPermaLink="false">https://innovationscns.com/?p=41746</guid>

					<description><![CDATA[Innov Clin Neurosci. 2026;23(1–3):17–22. by Kenny Nguyen, PharmD; Tammie Lee Demler, PharmD, MBA, BCGP, BCPP; and Eileen Trigoboff, PMHCNS-BC, DNS, DABFN Drs. Nguyen and Demler are with The New York State Office of Mental Health at Buffalo Psychiatric Center, Buffalo, New York. Drs. Demler and Trigoboff are with State University of New York at Buffalo School of Pharmacy and Pharmaceutical Sciences, Department of Pharmacy Practice, Buffalo, New York. Dr. Demler is additionally with State University of New York at Buffalo School of Medicine, Department of Psychiatry, Buffalo, New York. FUNDING: No funding was provided for this article. DISCLOSURES: The authors have no relevant conflicts of interest. ABSTRACT: Purpose: Many psychiatric inpatients are prescribed complex medication regimens that include both psychiatric and medical drugs with high anticholinergic (ACH) activity. The cumulative ACH burden (ACB), arising from the pharmacodynamic additive effects of concomitant medication use, has been linked to a range of adverse effects. These include both short-term effects and long-term consequences. Our study aims to determine the degree of ACB in a psychiatric inpatient hospital using current measurement assessment tools. Methods: This retrospective, observational study collected medication regimens and demographic data from the electronic health records of psychiatric inpatients. We included 250 adults aged 18 years or older who were institutionalized in a psychiatric hospital. The ACB was assessed using the ACH toxicity score (ATS), with data collected at two distinct time points, one in the spring and another in the winter, from different calendar years. The total ACB for both psychiatric and medical medications was compared across the patient population, analyzing the potential seasonal variation in the cumulative burden. Results: The degree of total ACB was not statistically significantly different (P=0.526) between the seasonal cohorts and remained consistent with an average total ATS of 8. An ATS score of 5 or higher is assumed to be clinically significant, with 75% of patients (93/124) and 78.6% (99/126) having shown significant burden in the winter and spring cohorts, respectively. Conclusion: The prescribing of ACH medication did not significantly vary seasonally, however, most patients observed showed significant and consistent levels of ACB. It is recommended that clinicians should consider monitoring ACB in their prescribed regimens and consider pharmacologic strategies to reduce ACB. Risk reduction strategies include discontinuation of nonessential ACH medications or consideration of therapeutic interchange with an alternative agent with a lesser ACH profile. The deprescribing of long-term ACH medications for individuals who are otherwise clinically stable may improve both clinical outcomes and quality of life. Keywords: Anticholinergic burden, Beers criteria, anticholinergic adverse effects Introduction Anticholinergic (ACH) burden (ACB) represents a critical, yet often overlooked, pharmacological consideration. The risk of ACB is magnified by prescribing trends that utilize polypharmacy, which is a well-recognized, increasingly common trend seen in the aging population and is associated with multimorbidity.1–3 The surge in medication use may reflect beneficial advances in chronic disease management and drug research but also results in detrimental consequences that include a greater likelihood of drug interactions, adverse effects, and a state of being overmedicated. The proportion of older adults prescribed ACH medications increased from 20.7% in 1995 to 23.7% in 2010, with high ACH exposure rising from 7.3% to 9.9% during the same time period.4,5 Antidepressants, some of which are highly ACH, have nearly doubled in prescribing in developed countries between 2000 and 2017.6 ACH medications have a broad range of indications and are likely to continue to be widely utilized. There is extensive research on the impact of prescribing and the resulting impact of high ACB in at-risk populations. Peripheral and central adverse effects have been noted in the general population; however, they are not as frequent or severe as those observed in older adults and patients with psychiatric disorders, and thus less researched. Up to 50% of older adults are prescribed at least one ACH medication, with up to roughly 12% exposed to clinically significant burden.7,8 Peripheral effects of ACB include constipation, dry mouth, tachycardia, and urinary retention, and central side effects include agitation, confusion, delirium, and cognitive impairment. Elderly patients are more vulnerable to significant ACB due to age-related changes in pharmacokinetic and pharmacodynamic parameters, in addition to cognitive and physical decline. In individuals with psychotic disorders, polypharmacy often includes the use of medications having highly ACH properties, and the total number of medications only increases with illness duration. Since psychotic disorders may be chronic and lifelong, many patients on psychotropic medications are at risk of experiencing iatrogenic, central cholinergic dysfunction.9–11 A study evaluating the degree of ACB in geriatric inpatients revealed that most patients with psychiatric illnesses had a higher likelihood of receiving ACH medications and were overall exposed to significant burden.12 Given the heightened susceptibility of geriatric patients to ACB and the significant exposure often observed in psychiatric patient populations, these two groups should be prioritized when addressing and mitigating the risks associated with ACB. According to the Beers criteria established by the American Geriatrics Society, ACH medications are recognized as potentially inappropriate for older adults as they have a higher risk of adverse effects.13 Although numerous studies have established associations between certain drug classes and ACH-like adverse effects, many fail to explicitly attribute these relationships to ACH  pathophysiology, leaving a gap in knowledge of the precise mechanism behind observed clinical outcomes.14,15 Despite this, these side effects should not be underestimated, as prolonged exposure may lead to worsening symptoms and potentially contribute to significant mortality. Graves-Morris et al16 conducted a comprehensive systematic review and meta-analysis and assessed the prognostic utility of specific ACB-focused measures on mortality in older individuals and found that ACB was associated with an increased risk of death, with an odds ratio (OR) of about 1.4, in those aged 65 years or older. This increased mortality rate emphasizes the importance of early identification and intervention to ultimately reduce these adverse outcomes in vulnerable populations. Due to the severity of long-term exposure to ACB, numerous complications can arise, and substantial research has been conducted to investigate these outcomes. A multitude of morbidities may resultThe post <a href="https://innovationscns.com/exploring-anticholinergic-burden-in-a-psychiatric-inpatient-population/">Exploring Anticholinergic Burden in a Psychiatric Inpatient Population</a> appeared first on <a href="https://innovationscns.com">Innovations in Clinical Neuroscience</a>.]]></description>
		
		
		
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		<title>Gut Microbiota as a Therapeutic Target for Chronic Pain Disorders</title>
		<link>https://innovationscns.com/gut-microbiota-as-a-therapeutic-target-for-chronic-pain-disorders/</link>
		
		<dc:creator><![CDATA[ICNS Online Editor]]></dc:creator>
		<pubDate>Sun, 01 Mar 2026 12:52:24 +0000</pubDate>
				<category><![CDATA[Commentary]]></category>
		<category><![CDATA[Current Issue]]></category>
		<guid isPermaLink="false">https://innovationscns.com/?p=41754</guid>

					<description><![CDATA[Innov Clin Neurosci. 2026;23(1–3):23–26. by Takahiko Nagamine, MD, PhD Dr. Nagamine is with the Department of Psychiatric Internal Medicine, Sunlight Brain Research Center, Hofu, Japan. FUNDING: No funding was provided for this article. DISCLOSURES: The author has no relevant conflicts of interest. ABSTRACT: Chronic pain disorders of unknown etiology, including burning mouth syndrome, chronic pelvic pain, fibromyalgia, irritable bowel syndrome, myofascial pain syndrome, and temporomandibular joint disorders, have been demonstrated to result in a substantial reduction in quality of life. These diseases exhibit a discernible gender bias, manifesting with greater frequency in women. The neurobiological underpinnings of these conditions are characterized by a decline in the volume of white matter in the medial prefrontal cortex and alterations in the connectivity of the default mode network. These conditions are frequently linked to impaired function of the central dopaminergic nervous system. The potential mechanisms connecting the gut microbiota to chronic pain disorders may be the decrease in butyrate-producing bacteria in dopamine signaling and the change in estrobolome in estrogen signaling. Consequently, an approach targeting the gut microbiota using probiotics has emerged as a potential treatment for chronic pain disorders. Keywords: Butyrate-producing bacteria, chronic pain disorders, dopamine, dysbiosis, microbiota-gut-brain axis, neuroinflammation, probiotics Introduction Chronic pain disorders, including burning mouth syndrome, chronic pelvic pain, fibromyalgia, irritable bowel syndrome, myofascial pain syndrome, and temporomandibular joint disorders, have been demonstrated to result in a substantial reduction in quality of life. The prevalence of chronic pain disorders is higher in women, and the etiology of these conditions is not fully elucidated.1 These conditions are characterized by intractable pain that persists for months or years and include a range of symptoms, including fatigue, sleep disturbances, and mood disorders. Conventional pharmacological interventions, including analgesics, antidepressants, clonazepam, and gabapentin, are employed; however, the efficacy of these therapeutic agents is inherently constrained.1 Since chronic pain disorders are often accompanied by disruptions to the gut microbiota, an approach based on the brain-gut axis may be considered.2 This article aims to delineate the pathophysiology of chronic pain disorders and propose the possibility of approaching the gut microbiota as a novel treatment method. Central Mechanisms of Chronic Pain Disorders The unknown etiology of chronic pain disorders highlights the complexity of these conditions. The pathogenesis of these conditions is multifaceted, involving a complex interplay of genetic, environmental, and psychological factors. Noteworthy pathological mechanisms encompass central sensitization and neuroinflammation.3 Central sensitization is defined as an amplification of neural signaling within the central nervous system (CNS) that lowers the threshold for pain perception and increases the response to painful and nonpainful stimuli.3 The underlying mechanism involves the wind-up phenomenon, which occurs when nociceptive input is repeated or intense, leading to changes in the excitability of neurons in the spinal cord and brain. This phenomenon is characterized by an augmented release of excitatory neurotransmitters such as glutamate, activation of N-methyl-D-aspartate receptors, and alterations in their gene expression. Consequently, typically innocuous stimuli (eg, light touch) may be perceived as painful (allodynia), and painful stimuli are experienced with greater intensity (hyperalgesia).4 Neuroinflammation, defined as the activation of glial cells (ie, microglia and astrocytes) and the subsequent release of pro-inflammatory mediators within the spinal cord and brain, has been identified as a significant contributor to central sensitization. Neuroinflammation plays a critical role in the wind-up phenomenon by enhancing neuronal excitability and synaptic transmission in the CNS.5 This process of central sensitization, driven by neuroinflammation, is a key mechanism in the development and maintenance of chronic pain. Abnormal firing of the nervous system during pain transmission, particularly in the context of chronic pain, leads to significant alterations in neuronal communication and the connectivity of large-scale brain circuits. The association between chronic pain and structural changes, such as alterations in gray matter volume, along with widespread alterations in functional connectivity within the brain, has been well documented.6 These alterations extend beyond the conventional pain-processing regions. The involvement of brain regions in the experience of chronic pain has been welldocumented. These regions, which include the amygdala, prefrontal cortex, nucleus accumbens, hippocampus, and other areas, play a crucial role in emotional processing, reward systems, memory, and stress response. A growing body of research has demonstrated that resting-state functional magnetic resonance imaging studies can reveal altered functional connectivity within large-scale brain networks, such as the default mode network (DMN), salience network, and sensorimotor network, in individuals with chronic pain.7 It has been demonstrated that these alterations have the potential to contribute to the cognitive, emotional, and behavioral comorbidities that are frequently observed in cases of chronic pain. A substantial body of research has demonstrated that individuals with chronic pain disorders exhibit notable alterations in brain circuitry, particularly within the DMN and its connections to regions involved in emotional and sensory processing, including the anterior cingulate cortex, anterior insula cortex, hippocampus, and amygdala.8 The phenomenon of maladaptive neuroplasticity, in which the brain undergoes reorganization to reinforce pain perception, has been observed in individuals afflicted with chronic pain conditions. A notable finding is the observation of reduced gray matter volume in the medial prefrontal cortex (mPFC) in individuals with chronic pain disorders, resulting in altered functional connectivity to the brain‘s pain matrix.9 These results consistently indicate structural and functional changes in the mPFC and its connectivity due to impaired functioning of the basal ganglia dopaminergic system.10 This finding suggests that therapeutic interventions targeting the central dopaminergic nervous system may offer a promising avenue for addressing chronic pain disorders. Gut Mechanisms of Chronic Pain Disorders Recent studies have highlighted the pivotal role of the microbiota-gut-brain axis in the context of chronic pain disorders.11 Individuals with chronic pain disorders frequently have dysbiosis, an imbalance in the gut microbiota.12 This condition is typified by a decline in the diversity and stability of beneficial bacteria within the gastrointestinal microbiota. Gut dysbiosis has been demonstrated to result in increased intestinal permeability, otherwise referred to as “leaky gut.” This condition allows bacterial byproducts, such as lipopolysaccharide, to penetrate the bloodstream, thereby inducing systemic inflammation. This inflammation has the potential to affect the nervousThe post <a href="https://innovationscns.com/gut-microbiota-as-a-therapeutic-target-for-chronic-pain-disorders/">Gut Microbiota as a Therapeutic Target for Chronic Pain Disorders</a> appeared first on <a href="https://innovationscns.com">Innovations in Clinical Neuroscience</a>.]]></description>
		
		
		
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		<title>Multifactorial Approach for Depression in Multiple Endocrine Neoplasia 2A (MEN2A): A Case Report</title>
		<link>https://innovationscns.com/multifactorial-approach-for-depression-in-multiple-endocrine-neoplasia-2a-men2a-a-case-report/</link>
		
		<dc:creator><![CDATA[ICNS Online Editor]]></dc:creator>
		<pubDate>Sun, 01 Mar 2026 12:51:29 +0000</pubDate>
				<category><![CDATA[Case Report]]></category>
		<category><![CDATA[Current Issue]]></category>
		<guid isPermaLink="false">https://innovationscns.com/?p=41759</guid>

					<description><![CDATA[Innov Clin Neurosci. 2026;23(1–3):27–31. by Vatsala Sharma, MD; Vimala Sim, MD, MBA; and Maria Chona P. San Gabriel, MD, DFAPA All authors are with Department of Psychiatry, Icahn School of Medicine at Mount Sinai-NYC Health+Hospitals/Elmhurst, Queens, New York. Dr. Sharma is additionally with Department of Child and Adolescent Psychiatry, SUNY Downstate-NYC Health+Hospitals/Kings County, Brooklyn, New York. Dr. Sim is additionally with Department of Medicine, Maimonides Medical Center, Brooklyn, New York. Dr. San Gabriel is additionally with Department of Psychiatry, NYC Health+Hospitals/Woodhull, Brooklyn, New York. FUNDING: No funding was provided for this article. DISCLOSURES: The authors have no relevant conflicts of interest. ABSTRACT: Background: Multiple endocrine neoplasia 2A (MEN2A) is an uncommon autosomal dominant disorder characterized by medullary thyroid cancer (MTC), parathyroid adenoma or hyperplasia, and pheochromocytoma with associated hypothyroidism, hyperparathyroidism, hypercalcemia, and catecholamine excess. Existing literature elucidates the correlation of depression with each endocrine condition. To our knowledge, this is the first case report emphasizing the multifaceted association of MEN2A and depression with contributory intergenerational psychosocial factors. case presentation: We present a 21-year-old male patient with past medical history of MEN2A and family history of coexisting MEN2A and depression, who presented with depression, psychosis, and suicidality. After exclusion of plausible MEN2A-associated endocrine causes, depression was identified to be psychiatric in etiology, subsequently responsive to sertraline and risperidone with adjunctive psychotherapy. discussion: Prophylactic thyroidectomy for MTC in MEN2A may result in thyroid derangement due to inappropriate replacement. Parathyroid adenoma can cause hyperparathyroidism with hypercalcemia. Pheochromocytoma is a benign adrenal tumor secreting excess catecholamines. These endocrine conditions in MEN2A can potentially contribute to depression. This report discusses attributing endocrine, genetic, and social factors for depression and suicidal ideation in MEN2A. Highlighted is the holistic treatment approach, including hormonal imbalance correction and psychopharmacological and psychosocial interventions necessary for symptom abatement. Conclusion: The importance of a multidisciplinary investigation of plausible etiologic factors of depression in MEN2A before committing to psychiatric interventions is emphasized. This perspective optimally addresses diagnosis, differential diagnoses, and treatment options. Awareness of familial depression in MEN2A is reinforced with potential for future research regarding genetic anticipation and holistic management strategies. Keywords: MEN2A, hypothyroidism, hyperparathyroidism, pheochromocytoma, depression Introduction Multiple endocrine neoplasia type 2A (MEN2A) is a rare autosomal dominant genetic disease secondary to the missense mutation in RET proto-oncogene at chromosome 10 amounting to exaggerated cell growth, resulting in medullary thyroid cancer (MTC), parathyroid adenoma, and pheochromocytoma.1 Patients with MEN2A do not necessarily develop all 3 carcinomas. According to Guerrieri et al,2 MTC is present in 100%, primary hyperparathyroidism (PHPT) in nearly 30%, and pheochromocytoma in 50% of MEN2A cases. Due to its autosomal dominance, MEN2A can affect several generations with a prevalence of 1:40,000 individuals in the United States and 1:30,000 globally.3–5 Aside from cancer-associated medical complications, patients with MEN2A may develop significant psychiatric comorbidities, such as depression, psychosis, suicidal ideation with attempts, anxiety, panic disorder, and delirium.2,3,6 MTC, a cancer of the parafollicular C cells, is the most common cause of MEN2A morbidity, thus warranting early diagnosis and timely management.7 Total thyroidectomy is performed prophylactically after detecting childhood RET mutation.7,8 Life-long thyroid hormone supplementation is required post-thyroidectomy, as improper hormonal replacement potentially leads to psychiatric symptoms.9–13 PHPT in MEN2A develops due to parathyroid adenoma or hyperplasia, indicated by an unsuppressed parathyroid hormone (PTH) level with hypercalcemia.14 Calcium affects central nervous system metabolism of monoamines, potentially modifying neurotransmission and consequently altering mood and cognition.15 Surgical resection of the parathyroid glands remains the treatment of choice.16 Pheochromocytoma, &#8220;the great mimic&#8221; in MEN2A, is a rare catecholamine-producing tumor.17 Depression in pheochromocytoma is hypothesized to be secondary to brain changes due to blood pressure variations.2 Aside from depression secondary to endocrine issues, the heritable pattern of MEN2A can chronically impact quality of life across successive generations, resulting in depression and suicidality.6 The etiology of psychiatric conditions in MEN2A and their management is complex and inadequately studied, requiring further research to delineate the management guidelines of psychiatric conditions in MEN2A. This case report describes the diagnostic and management challenges of a unique case of MEN2A presenting with suicidal ideation and psychotic depression. Psychiatric comorbidities commonly develop secondary to thyroid abnormalities post-thyroidectomy, but interestingly, patients with MEN2A who undergo prophylactic thyroidectomy in childhood can develop psychiatric manifestations many years later in life. To our knowledge, this case report is the first to discuss the impact of thyroid abnormalities on depression and suicidality post-prophylactic thyroidectomy in MEN2A. Along with the underlying psychosocial factors, the holistic endocrine and psychiatric etiology, along with cumulative etiology-focused depression management, has not been discussed to date. By sequentially examining depression in a patient with MEN2A, this report aims to facilitate the understanding of etiology-oriented management and familial depression that could potentially inform further research for holistic therapeutic strategies. Case Presentation A 21-year-old male patient presented at the emergency room with depression, psychosis, and suicidal ideation after a verbal altercation with his mother. The patient penned a suicide note stating, &#8220;God told me to jump, and that I will. Till [sic] then, may God give you the strength to jump as well.&#8221; He exhibited past medical history of MEN2A and depression with no suicide attempt or self-harm behavior. On evaluation, he displayed significant psychomotor retardation, depressed affect, ongoing auditory hallucinations, paranoia, and intermittent suicidal thoughts with no plan. The patient was domiciled with family and recently stopped attending college due to academic difficulties. At 5 years of age, given his family history, genetic testing was done which revealed RET proto-oncogene mutations, and he was subsequently diagnosed with MEN2A. Thereafter, genotype-led prophylactic thyroidectomy was performed, and thyroid replacement therapy was initiated (levothyroxine 200–250 mcg daily). The patient had been a social drinker with no significant substance use. He acknowledged sexually assaulting his 6-year-old sister &#8220;out of curiosity&#8221; at 11 years of age and endorsed ongoing guilt. He had a history of depression with ongoing therapy sessions for the past 3 months with no pharmacologic intervention. Family history was significant for MEN2A in his maternal grandmother, mother, and sister. His maternal grandmother developed depressionThe post <a href="https://innovationscns.com/multifactorial-approach-for-depression-in-multiple-endocrine-neoplasia-2a-men2a-a-case-report/">Multifactorial Approach for Depression in Multiple Endocrine Neoplasia 2A (MEN2A): A Case Report</a> appeared first on <a href="https://innovationscns.com">Innovations in Clinical Neuroscience</a>.]]></description>
		
		
		
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		<title>Development of a Probiotic-Infused Carbamazepine Dosage Form</title>
		<link>https://innovationscns.com/development-of-a-probiotic-infused-carbamazepine-dosage-form/</link>
		
		<dc:creator><![CDATA[ICNS Online Editor]]></dc:creator>
		<pubDate>Sun, 01 Mar 2026 12:50:03 +0000</pubDate>
				<category><![CDATA[Current Issue]]></category>
		<category><![CDATA[Original Research]]></category>
		<guid isPermaLink="false">https://innovationscns.com/?p=41763</guid>

					<description><![CDATA[Innov Clin Neurosci. 2026;23(1–3):32–38. by Humphrey Masimba Makumbirofa, MSc; Tariro Tsitsidzashe Hluyo, BPharm; Jonathan Chaweza, BTech; Simbarashe Wandayi, MVPG, BVSc; and Nyarai Desiree Soko, PhD, MSc Messrs. Makumbirofa, Hluyo, Chaweza, and Dr. Soko are with Department of Pharmaceutical technology, School of Allied Health Sciences, Harare Institute of Technology, Harare, Zimbabwe. Mr. Wandayi is with Department of Pathobiology, Faculty of Veterinary Science, University of Zimbabwe, Harare, Zimbabwe. FUNDING: This research was funded by the Harare Institute of Technology. DISCLOSURES: The authors have no relevant conflicts of interest. ABSTRACT: Objective: We describe the development of a probiotic-infused carbamazepine dosage form. This dosage form combines carbamazepine with probiotics, proposing the potential use of both active pharmaceutical ingredients in a single dosage form. Design: Evaluation of Bifidobacterium bifidum and Lactobacillus acidophilus susceptibility to carbamazepine using agar disk diffusion revealed the B. bifidum was resistant to carbamazepine, prompting its selection for development of the dosage form. A suspension was formulated using the precipitation method with stability testing assessing organoleptic properties, pH, and viability of the bacteria in the dosage form. Toxicity assessment was done using 20 male albino Wistar rats, measuring weight, urination, and anxiety changes postadministration of carbamazepine and probiotics, following ethical approval from the University of Zimbabwe’s animal house laboratory and board. Results: Rats receiving only B. bifidum exhibited heightened anxiety and reduced weight, while those receiving carbamazepine alone increased weight and urination but lowered anxiety. Combining carbamazepine with B. bifidum significantly decreased anxiety (P=0.0312) and increased urination, with significant weight reduction (P=0.03186). The dosage form maintained stability, preserving B. bifidum viability over a period of 28 days. Conclusion: Integrating probiotics into carbamazepine formulations offers a promising strategy, with potential applications to other antiepileptic drugs. Keywords: Carbamazepine, probiotics, Bifidiobacterium bifidum, dosage form, infused Introduction Carbamazepine is indicated for use as an anticonvulsant drug. Evidence supporting its efficacy as an antiepileptic drug (AED) was derived from studies that enrolled patients with partial seizures with complex symptomatology (psychomotor, temporal lobe), generalized tonic–clonic seizures (grand mal), and mixed-seizure patterns, including the latter 2 types or other partial or generalized seizures.1,2 Absence (petit mal) seizures do not appear to be controlled by carbamazepine. The mechanism of action of carbamazepine remains unknown, but its anticonvulsant activity may result from use-dependent blockade of voltage-sensitive sodium channels.1,2 Carbamazepine has demonstrated anticonvulsant properties in animals with electrically and chemically induced seizures, and it reduces or abolishes pain induced by stimulation of the infraorbital nerve in animals.1,2 Recent studies have shown a link between the gut microbiome and neurological diseases, including epilepsy. Although there have been only a few studies to date that have reported alterations in the gut microbiome in human epilepsy,3,4 the associations between epilepsy and infection, inflammation, and antibiotic treatment raise the question of whether alterations in microbial communities under those conditions may be involved in its pathophysiology.5 A study by Wang et al6 provided evidence that the addition of probiotics in the treatment of patients with temporal lobe epilepsy can effectively enhance the antiseizure effects and alleviate cognitive impairment, neuropsychiatric symptoms, and overall quality of life to a certain degree. The functional activities of the brain depend on the signal transmission between different types of neurons and glial cells, which depends on neurotransmitters; for example, an imbalance of excitatory and inhibitory neurotransmitters may lead to epileptic seizures.7 The intestinal microbiota has a profound influence on several neurotransmitters and neuromodulators, such as monoamines, serotonin, gamma-aminobutyric acid (GABA), and brain-derived neurotrophic factors.8 Different bacterial strains may synthesize different neurotransmitters. GABA is secreted by certain strains of Lactobacillus and Bifidobacterium. Conversely, norepinephrine is produced by certain strains of Saccharomyces, Bacillus, and Escherichia.9 Serotonin comes from Enterococcus, Streptococcus, Escherichia, and Candida,10,11 dopamine from Bacillus and Serratia,7 acetylcholine from Bacillus and certain lactic acid bacteria strains,7 and glutamate from various coryneforms and lactic acid bacterial strains.10,11 Some studies have demonstrated that mice or rats fed with probiotics showed altered neurotransmitter composition and changes in their target receptor throughout different brain regions.12 Interestingly, certain bacterial taxa in the gut produce certain enzymes that can facilitate the synthesis of short-chain fatty acids (SCFAs) by fermentation. SCFAs exert their functions on the central nervous system by binding to the G receptors on entero-endocrine cells.13 This induces the secretion of diverse hormones and neurotransmitters, indirectly influencing brain neurochemistry. One example is acetate, which alters the levels of glutamate, glutamine, and GABA in the hypothalamus. These neurotransmitters play a crucial role in the development of neurological disorders.14 Probiotics are generally regarded as safe; however, due to their increasing consumption and their potential to influence metabolism, the efficacy and safety of orally administered probiotics deserve a closer look.15 These organisms act by affecting absorption, composition, or metabolic activity of the gut microbiota, potentially altering the bioavailability of the drug.16 Probiotics can influence bioavailability of drugs by several possible mechanisms, including alterations of gastrointestinal properties like pH, increasing intestinal transit time,17 or thickening adherent mucus and altered expression of intestinal transporters across the intestinal wall. In addition, they work by inducing or inhibiting microbial enzymes, thus modulating their activity on drugs and by using drugs as surrogate substrates for their growth.15 Effective amounts of a probiotic when combined with an effective amount of drug tend to result in enhanced therapeutic outcomes.18 Developing a single product that combines carbamazepine with probiotics as a unified dosage form has the potential to reduce the burden of polypharmacy by improving patient adherence to medication since it is easy to administer. Thus, this study aimed to develop a probiotic-infused carbamazepine dosage form for the potential use in the management of epilepsy. Materials and Methods Viability testing of microbial strains in carbamazepine. The susceptibility of the potential probiotic cultures to carbamazepine was determined using the disk diffusion method as per recommendations from the National Committee for Clinical Laboratory Standards.19 Isolates of Lactobacillus acidophilus and Bifidobacterium bifidum were obtained from the Department of Biotechnology at the Harare Institute of Technology. A range of carbamazepine (Datlabs) concentrations were prepared—4 mg/mL, 5 mg/mL, 8 mg/mL, 10 mg/mL, andThe post <a href="https://innovationscns.com/development-of-a-probiotic-infused-carbamazepine-dosage-form/">Development of a Probiotic-Infused Carbamazepine Dosage Form</a> appeared first on <a href="https://innovationscns.com">Innovations in Clinical Neuroscience</a>.]]></description>
		
		
		
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