Journal of psychiatric research最新文献

{"title":"Comparison of the effects of aerobic exercise and computer-based cognitive stimulation in patients with schizophrenia - A randomized controlled trial","authors":"İsmail Koç ,&nbsp;Ebru Akbuğa Koç ,&nbsp;Nilgün Çınar ,&nbsp;Türker Şahiner","doi":"10.1016/j.jpsychires.2026.01.039","DOIUrl":"10.1016/j.jpsychires.2026.01.039","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to compare of the effects of aerobic exercise (AE) and computer-based cognitive stimulation (CS) in terms of cognition, clinical symptoms, depression, and quality of life (QOL) in patients with schizophrenia.</div></div><div><h3>Methods</h3><div>A total of 58 individuals diagnosed with schizophrenia completed to the study (aerobic exercise group (AEG): n = 18, cognitive stimulation group (CSG): n = 20, control group (CG): n = 20). The AEG participated in a 12-week AE program, whereas the CSG engaged in computer-based CS over the same period. Also, the CG did not receive any intervention. Cognition with Montreal Cognitive Assessment scale and Frontal Assessment Battery, clinical symptoms with Positive and Negative Syndrome Scale, depression with Calgary Depression Scale for Schizophrenia, and QOL with Quality of Life Scale for Schizophrenia Patients scale were assessed at baseline and post-intervention.</div></div><div><h3>Results</h3><div>Within-group improvements were observed in general cognitive function, clinical symptoms, and selected QOL domains in the AEG, whereas the CSG showed significant improvements across cognitive functions, clinical symptoms, depressive symptoms, and multiple QOL domains. In contrast, the CG exhibited significant deterioration in cognitive functions, selected clinical symptoms, depressive symptoms, and certain QOL domains over the 12-week period. Between-group comparisons revealed no statistically significant differences in general cognitive function, executive function, and depression at week 12. However, significant differences were observed in specific PANSS and QOL subscales.</div></div><div><h3>Conclusions</h3><div>These findings suggested that computer-based CS and AE may offer domain-specific and complementary effects in cognitive and clinical domains in PwS.</div></div>","PeriodicalId":16868,"journal":{"name":"Journal of psychiatric research","volume":"195 ","pages":"Pages 123-132"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146080476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retrospective chart review on psychiatric manifestations of GLP-1 agonist usage","authors":"Brianna Sa ,&nbsp;Anthony Maristany ,&nbsp;Ashwin Subramaniam ,&nbsp;Nayha Kumbkarni ,&nbsp;Rachel Lange ,&nbsp;Sean Oldak ,&nbsp;Adela-Georgiana Buciuc ,&nbsp;Vanessa Padilla","doi":"10.1016/j.jpsychires.2026.01.042","DOIUrl":"10.1016/j.jpsychires.2026.01.042","url":null,"abstract":"<div><h3>Background</h3><div>Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly prescribed for type 2 diabetes mellitus and obesity. Beyond metabolic effects, GLP-1 signaling influences central pathways involved in mood, reward, and stress regulation, raising interest in possible psychiatric implications.</div></div><div><h3>Methods</h3><div>We conducted a retrospective chart review of adults (≥18 years) prescribed GLP-1 RAs at a private university hospital between January 2021 and April 2024. Demographic, medication, and psychiatric data were extracted from electronic health records. Primary outcomes included stability, improvement, worsening, or new onset of psychiatric disorders during treatment.</div></div><div><h3>Results</h3><div>Among 226 patients (mean age 53.5 years; 66.8 % female; mean BMI 33.6 kg/m²), semaglutide was most frequently prescribed (73 %). The mean treatment duration was 20.2 months, with an average 6.7 % weight loss. Major depressive disorder (MDD) and generalized anxiety disorder (GAD) were most prevalent (68.6 % and 65.9 % of patients, respectively). Most remained stable (MDD: 73.6 %; GAD: 78.5 %). New-onset MDD occurred in 9.0 % and GAD in 8.7 % of affected patients, with mean latencies of 15.8 and 16.8 months, respectively. Adjustment disorder, ADHD, and insomnia also emerged in a subset, with ADHD showing the shortest latency to onset (7.8 months). Rare new-onset alcohol use disorder, trichotillomania, and opioid use disorder were observed.</div></div><div><h3>Conclusions</h3><div>GLP-1 RAs appear psychiatrically well-tolerated for most patients, though new-onset or worsening symptoms occur in a minority, underscoring the need for monitoring, particularly in high-risk populations. Prospective studies are warranted to clarify causality, mechanisms, and potential therapeutic roles in psychiatric care.</div></div>","PeriodicalId":16868,"journal":{"name":"Journal of psychiatric research","volume":"195 ","pages":"Pages 92-96"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146080479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lithium treatment and risk of neurocognitive disorders in older patients with bipolar disorder: A systematic review","authors":"Eleni Parlapani ,&nbsp;Anna Kirka ,&nbsp;Vasiliki Holeva ,&nbsp;Stergios Kaprinis","doi":"10.1016/j.jpsychires.2026.01.022","DOIUrl":"10.1016/j.jpsychires.2026.01.022","url":null,"abstract":"<div><h3>Objective</h3><div>Bipolar disorder is a chronic mental illness that requires long-term treatment. Reports from patients of cognitive dulling have prompted research into the impact of long-term Lithium treatment on cognition. The present systematic review aimed to investigate the effects of Lithium on neurocognitive disorder outcomes in older patients with bipolar disorder.</div></div><div><h3>Method</h3><div>A systematic literature search was conducted in four databases: PubMed, Scopus, ScienceDirect and EBSCO. Study inclusion was based on concrete inclusion/exclusion criteria. The literature search and the final study selection were conducted in four stages. Included studies were assessed for quality using the Newcastle-Ottawa Quality Assessment Scale for cohort studies, and the Modifications to the Newcastle-Ottawa Scale for cross-sectional studies.</div></div><div><h3>Results</h3><div>The original search yielded a total of 8285 records. Among these, nine studies were included in the systematic review. Eight out of nine studies did not support an association between Lithium treatment and increased risk of neurocognitive disorders. One study found that the association between bipolar disorder and neurocognitive disorder may be mediated by Lithium treatment.</div></div><div><h3>Conclusion</h3><div>There is no conclusive evidence that long-term Lithium treatment is harmful with respect to neurocognitive outcomes in older patients with bipolar disorder. Beyond its efficacy as a mood-stabilizer, accumulating evidence supports Lithium's neurotrophic effects. To date, there is enough evidence to support Lithium maintenance as a first-line treatment for older patients with bipolar disorder.</div></div>","PeriodicalId":16868,"journal":{"name":"Journal of psychiatric research","volume":"195 ","pages":"Pages 13-20"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146018997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"“When is it late”? Optimal threshold for duration of untreated illness (DUI) to predict SSRI-treatment resistance in individuals with obsessive-compulsive disorder (OCD)","authors":"Luca Pellegrini ,&nbsp;Gabriele Di Salvo ,&nbsp;Nicola Rizzo Pesci ,&nbsp;Gianluca Rosso ,&nbsp;Giuseppe Maina ,&nbsp;Umberto Albert","doi":"10.1016/j.jpsychires.2026.01.056","DOIUrl":"10.1016/j.jpsychires.2026.01.056","url":null,"abstract":"<div><h3>Background</h3><div>Obsessive-compulsive disorder (OCD) is a chronic psychiatric condition in which delays to appropriate treatment—known as duration of untreated illness (DUI)—are common and clinically consequential. Although prolonged DUI has been associated with poor response, the specific time point beyond which treatment resistance becomes likely remains unclear.</div></div><div><h3>Methods</h3><div>We analysed 220 adults with DSM-5 OCD consecutively recruited at the University of Turin OCD clinic (2015–2023). DUI was defined as the interval between onset of clinically significant symptoms and the initiation of an adequate selective serotonin reuptake inhibitor (SSRI) trial (moderate-to-high dose for ≥12 weeks). Response was defined as a ≥35 % reduction in Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score and a Clinical Global Impression–Improvement (CGI-I) rating ≤2. Receiver-operating-characteristic (ROC) analysis identified the DUI cut-off predicting SSRI non-response.</div></div><div><h3>Results</h3><div>Mean age was equal to 34.5 ± 12.4 years; mean DUI was 107.2 ± 116.7 months. Half of the sample (50.4 %) responded to first-line SSRIs. ROC analysis yielded area under the curve = 0.634 (p &lt; 0.001). The optimal cut-off was 42 months, corresponding to a sensitivity of 70.1 % and a specificity of 53.9 %.</div></div><div><h3>Conclusions</h3><div>A DUI exceeding about 3.5 years is associated with a substantially lower probability of SSRI response. These data suggest that a duration of untreated illness beyond forty-two months may predict reduced responsiveness to first-line SSRI therapy in OCD, though replication in larger, multicentric samples is warranted.</div></div>","PeriodicalId":16868,"journal":{"name":"Journal of psychiatric research","volume":"195 ","pages":"Pages 181-184"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146113003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transitioning into and out of economic hardship and their effects on depressive symptoms: Moderating roles of housing tenure and educational attainment","authors":"Gum-Ryeong Park ,&nbsp;Jinho Kim","doi":"10.1016/j.jpsychires.2026.01.057","DOIUrl":"10.1016/j.jpsychires.2026.01.057","url":null,"abstract":"<div><div>This study examines the asymmetric effects of economic hardship on depressive symptoms among Korean women. It focuses on whether transitions into and out of hardship have differing impacts on depressive symptoms and how these effects vary by socioeconomic status. This study used data from the Korean Longitudinal Survey of Women &amp; Families (2007–2022). An asymmetric fixed effects model was employed to separately estimate the effects of transitioning into and out of perceived economic hardship on depressive symptoms. We also included interaction terms for housing tenure and years of education in separate models. Transitioning into economic hardship significantly increases depressive symptoms, with a stronger effect than transitioning out. Individuals with homeownership and higher education experience a smaller increase in depressive symptoms when transitioning into hardship compared to others. However, housing tenure and educational attainment do not moderate the effects of transitioning out of hardship on depressive symptoms. These findings highlight the need for targeted interventions to improve the psychological health of women experiencing economic hardship.</div></div>","PeriodicalId":16868,"journal":{"name":"Journal of psychiatric research","volume":"195 ","pages":"Pages 193-198"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146113077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trends in anticholinergic drug exposure and associated risk factors in older Australian patients with dementia","authors":"Woldesellassie M. Bezabhe ,&nbsp;Jan Radford ,&nbsp;Mohammed S. Salahudeen ,&nbsp;Ivan Bindoff ,&nbsp;Tristan Ling ,&nbsp;Peter Gee ,&nbsp;Gregory M. Peterson","doi":"10.1016/j.jpsychires.2026.01.048","DOIUrl":"10.1016/j.jpsychires.2026.01.048","url":null,"abstract":"<div><h3>Background</h3><div>Awareness of anticholinergic drug exposure and its harm in people with dementia has been increasing. We investigated whether this had transpired into reduced use and determined factors associated with high anticholinergic burdens.</div></div><div><h3>Methods</h3><div>We used the anticholinergic cognitive burden (ACB) scale to measure the mean daily ACB score from 135 medicines in patients with dementia using data from 400 general practices across Australia from 2013 to 2020. We determined factors associated with exposure to high anticholinergic burden.</div></div><div><h3>Results</h3><div>Included patients with dementia (1:1 matched controls) ranged from 3989 in 2013 to 6278 in 2020. The proportion of patients with a mean total daily ACB score ≥3 declined from 26.1% (95% CI 24.7–27.5%) in 2013 to 19.2% (95% CI 18.3–20.2%) in 2020 in the dementia groups (p &lt;0.001). Schizophrenia (adjusted odds ratio [aOR], 3.51; 95% CI, 2.62–4.78), depression (aOR, 2.31; 95% CI, 2.11–2.54) and anxiety (aOR, 1.41; 95% CI, 1.26–1.57) were associated with a high daily mean ACB score in patients with dementia. Living in outer regional, remote and very remote areas (compared with major cities) (aOR, 1.43; 95% CI, 1.22–1.68) and living in disadvantaged areas, compared with most advantaged areas (aOR 1.25; 95% CI, 1.07–1.46), were also associated with a higher ACB score.</div></div><div><h3>Conclusions</h3><div>While the use of anticholinergic medicines had significantly reduced, nearly one-fifth of the patients with dementia had high anticholinergic exposure at the end of the study period. The findings support the rationale for efforts to deprescribe antidepressants, antipsychotics, and opioids, especially in relatively disadvantaged areas.</div></div>","PeriodicalId":16868,"journal":{"name":"Journal of psychiatric research","volume":"195 ","pages":"Pages 212-218"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the relationship between ADHD symptoms and suicide risk through the lens of the Integrated Motivational-Volitional Model of suicidal behaviour","authors":"Seonaid Cleare,&nbsp;Rory C. O'Connor","doi":"10.1016/j.jpsychires.2026.01.036","DOIUrl":"10.1016/j.jpsychires.2026.01.036","url":null,"abstract":"<div><h3>Introduction</h3><div>Attention Deficit-Hyperactivity Disorder (ADHD) is associated with increased vulnerability to suicide. However, understanding of the psychological factors associated with increased risk is limited. Therefore, we investigated the extent to which psychological factors from the Integrated Motivational–Volitional (IMV) model of suicidal behaviour were associated with suicide risk.</div></div><div><h3>Methods</h3><div>696 adults who were recruited to a study on ADHD, mental health and suicide risk completed validated measures that assessed components of the IMV model, ADHD symptoms and mental health history.</div></div><div><h3>Results</h3><div>642 (92.2 %) participants scored 4 or more on the Adult ADHD Self-Report screener (ASRS; Kessler et al., 2005), indicating recent ADHD symptoms. Analyses of IMV model factors were conducted in this subgroup. More than nine out of ten (93 %) participants reported lifetime suicidal thoughts (n = 597), and 41.7 % (n = 268) reported a history of suicide attempts. Multivariable analyses showed higher defeat, internal entrapment and perceived burdensomeness were associated with recent suicidal thoughts, while mental imagery distinguished those with suicide attempt from suicidal thought histories. Perceived burdensomeness moderated the entrapment-to-suicidal thoughts relationship. Exploratory mediation analysis indicated entrapment may mediate the defeat-to-suicidal thoughts relationship.</div></div><div><h3>Conclusions</h3><div>This is the first study to apply the IMV model to understanding the ADHD-suicide risk relationship. Psychological factors from the IMV model warrant investigation longitudinally as potentially targets for suicide prevention in people with ADHD.</div></div>","PeriodicalId":16868,"journal":{"name":"Journal of psychiatric research","volume":"195 ","pages":"Pages 142-152"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146105727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurobiological, molecular, and systemic mechanisms of exercise in the treatment of mental health disorders","authors":"Tony R. Montgomery Jr.,&nbsp;DeMond M. Grant","doi":"10.1016/j.jpsychires.2026.01.043","DOIUrl":"10.1016/j.jpsychires.2026.01.043","url":null,"abstract":"<div><div>Exercise is a potent modulator of mental health, with accumulating evidence highlighting its ability to produce structural and functional changes in the brain. This review synthesizes findings across neurobiological, molecular, and systemic domains to explain how exercise improves outcomes in mood, anxiety, and stress-related disorders. We examine how exercise stimulates brain-derived neurotrophic factor (BDNF), regulates monoaminergic systems (serotonin, dopamine, norepinephrine), modulates inflammatory and oxidative stress pathways, and promotes neurogenesis and synaptic plasticity. The review also explores systemic mechanisms including the gut–brain axis, myokine signaling (e.g., irisin, cathepsin B), and the regulation of the hypothalamic–pituitary–adrenal (HPA) axis. Furthermore, we discuss how exercise influences key psychological mechanisms, including emotion regulation, self-efficacy, and cognitive reappraisal, offering a translational bridge between physiology and psychotherapy. Understanding these overlapping mechanisms can guide clinicians in prescribing exercise as an evidence-based adjunct or standalone therapy for mental health disorders. This model of exercise as medicine has the potential to enhance both accessibility and efficacy of mental health care. Implications for clinical integration, mechanistic research, and policy development are discussed.</div></div>","PeriodicalId":16868,"journal":{"name":"Journal of psychiatric research","volume":"195 ","pages":"Pages 113-122"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146080478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Opioid use disorder of any severity is associated with increased suicidality","authors":"William H. Craft ,&nbsp;Keith Humphreys ,&nbsp;Michael J. Ostacher ,&nbsp;Claudia B. Padula","doi":"10.1016/j.jpsychires.2026.01.049","DOIUrl":"10.1016/j.jpsychires.2026.01.049","url":null,"abstract":"<div><h3>Background</h3><div>Suicide represents an underappreciated contributor to drug-related mortality, with 20%–30% of opioid overdoses estimated to be intentional. However, suicide risk relative to opioid use disorder (OUD) severity has not been well characterized. Understanding suicidality risk across the OUD severity spectrum will inform which healthcare providers should be screening and treating self-harm.</div></div><div><h3>Methods</h3><div>We estimated the odds of past-year suicidal thoughts, plans, and attempts relative to OUD severity using data from the National Survey on Drug Use and Health (NSDUH), a cross-sectional, nationally representative, population-based survey study of noninstitutionalized individuals. Data were analyzed for adults (18+) from 2021 to 2023 (N = 139,524). Past-year DSM-5 OUD, OUD severity, and past-year suicidal thoughts, plans, and attempts were estimated, and logistic regression was utilized to assess the association of OUD severity with suicidality measures.</div></div><div><h3>Results</h3><div>Among individuals with OUD, 62.9% (95% CI, 60.1%–65.6%) had mild, 15.9% (95% CI, 13.5%–18.6%) had moderate, and 21.2% (95% CI, 19.1%–23.6%) had severe OUD. Individuals with OUD were at increased odds of reporting suicidal thoughts compared to individuals without OUD: mild OUD was associated with 2.18-fold greater odds (95% CI, 1.61–2.95), moderate OUD was associated with 1.88-fold greater odds (95% CI, 1.08–3.28), and severe OUD was associated with 4.17-fold greater odds (95% CI, 2.99–5.82). Individuals with OUD were also at increased odds of reporting a suicide plan relative to no OUD: mild OUD was associated with 3.35-fold greater odds (95% CI, 2.07–5.41), moderate OUD was associated with 4.66-fold greater odds (95% CI, 2.66–8.17), and severe OUD was associated with 6.70-fold greater odds (95% CI, 4.59–9.75). Lastly, across OUD severities, there was an increased odds of reporting a suicide attempt relative no OUD: mild OUD was associated with 2.80-fold greater odds (95% CI, 1.53–5.13), moderate OUD was associated with 8.45-fold greater odds (95% CI, 3.28–21.8), and severe OUD was associated with 9.96-fold greater odds (95% CI, 5.52–18.0).</div></div><div><h3>Conclusions</h3><div>These findings suggest OUD of any severity is associated with markedly increased risk of suicidal thoughts, plans, and suicide attempts. This highlights a continued need to integrate suicide screening and prevention into OUD treatment and clinical settings where opioids are frequently prescribed, such as primary care.</div></div>","PeriodicalId":16868,"journal":{"name":"Journal of psychiatric research","volume":"195 ","pages":"Pages 177-180"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146113070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic shifts, a consequence of hyperosmolarity, are a hallmark of mental disorders","authors":"Laurent Schwartz ,&nbsp;Ashraf Bakkar ,&nbsp;Frederic Bouillaud ,&nbsp;Romain Attal ,&nbsp;Marion Leboyer","doi":"10.1016/j.jpsychires.2026.01.047","DOIUrl":"10.1016/j.jpsychires.2026.01.047","url":null,"abstract":"<div><div>Mental and neurodevelopmental disorders are heterogeneous, complex, and overlapping entities. Despite progress, their neurobiological underpinnings are not well understood, and current treatments have limited efficacy. However, a growing number of studies have shown impaired brain and systemic energy metabolism evidenced by low-grade inflammation, metabolic syndrome, mitochondrial dysfunction, and abnormal glucose utilization, although their underlying mechanisms remain poorly understood.</div><div>This paper reviews metabolic shifts in mental disorders, examines the underlying mechanisms driving these metabolic abnormalities in patient subgroups, and explores targeted therapeutic strategies. We argue here that this inflammation results in hyperosmolarity because of increased protein concentration in the extracellular fluid, resulting from vascular leakages. Hyperosmolarity exerts pressure on the capillaries resulting in altered blood flow (hypoperfusion and/or hyper perfusion). Another consequence of hyperosmolarity is metabolic shifts such as aerobic glycolysis. Hyperosmolarity is also responsible for releasing neurotransmitters such as serotonin, dopamine, glutamate, or gamma-aminobutyric acid (GABA). Drugs known to interfere with metabolism such as methylene blue and lipoic acid have been found to have antidepressant, anxiolytic, and neuroprotective effects (both in animals and in humans) in a large array of mental disorders.</div><div>We suggest that metabolic shifts are a hallmark of mental disorders and that treatments aiming to alleviate these metabolic shifts may improve patients' prognoses. Mechanisms-based treatments should be tested in future clinical trials, where subgroups of patients characterized as having the most profoundly impaired metabolism should be included, following the rules of precision psychiatry.</div></div>","PeriodicalId":16868,"journal":{"name":"Journal of psychiatric research","volume":"195 ","pages":"Pages 160-168"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146105656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}