BACKGROUND/OBJECTIVE:Once-daily INGREZZA® (valbenazine), a selective vesicular monoamine transporter 2 (VMAT2) inhibitor, is approved for tardive dyskinesia (TD) and Huntington's chorea. KINECT-PRO™ (NCT05859698) is currently the only study to assess the effects of a VMAT2 inhibitor (valbenazine) on quality of life (QoL) and functionality in patients with TD using multiple validated patient-reported outcomes (PROs). METHODS:Adults with mild-to-severe TD movement severity (per Abnormal Involuntary Movement Scale [AIMS] item 8) and awareness of TD with mild-to-severe associated distress (per AIMS item 10) received open-label valbenazine (40, 60, or 80 mg) for 24 weeks. Primary endpoints included changes from baseline (CFBs) at Week 24 in 3 validated QoL/functionality PROs: Tardive Dyskinesia Impact Scale (TDIS), the only psychometrically validated PRO developed specifically for TD; Sheehan Disability Scale (SDS); and EuroQoL Group's EQ-Visual Analogue Scale (EQ-VAS). Secondary endpoints included CFB in AIMS total score. RESULTS:Substantial and clinically meaningful improvements in patient-reported QoL/functionality and clinician-reported TD severity were observed throughout treatment with valbenazine in the overall study population and regardless of psychiatric diagnosis (mood disorders, psychotic disorders) or TD severity at baseline (mild, moderate/severe). At Week 24 (N = 45), mean CFBs were: TDIS (-8.0); SDS Social/Leisure (-2.3); SDS Family/Home (-1.6); EQ-VAS (+13.1); AIMS (-6.8). Previously established minimal clinically important difference (MCID) thresholds for TD were exceeded for TDIS and AIMS. Safety and tolerability were consistent with valbenazine's known profile. CONCLUSIONS:KINECT-PRO is the first study of its kind, and valbenazine is the only VMAT2 inhibitor to demonstrate QoL/functional improvements in patients with TD across multiple validated PROs.
Abstract Metabolic dysfunction-associated steatotic liver disease (MASLD) (formerly known as nonalcoholic fatty liver disease) is the most prevalent liver disease globally. Emerging evidence suggests MASLD-related metabolic and inflammatory processes may disrupt frontostriatal–limbic circuits, contributing to alterations in cognitive and reward-related brain function. This systematic review aimed to examine whether MASLD is associated with changes in cognitive functioning and reward-related processes, and whether these changes correspond to structural and functional brain alterations. A systematic search of PubMed, Web of Science, and Google Scholar was conducted from inception to November 11, 2025, using terms related to MASLD, cognition, and reward. Eligible studies included adult MASLD populations and observational designs assessing cognitive and/or reward outcomes. Studies involving neuropsychiatric or neurological disorders or medications known to affect cognition were excluded. Fourteen studies (eight cross-sectional, four cohort or case–control, and two Mendelian randomization) found MASLD significantly associated with poorer attention, executive function and memory, often proportional to disease severity. Neuroimaging studies reported significant reductions in cortical thickness, hippocampal and white matter volume, increased white matter hyperintensities, and cerebrovascular dysfunction ( p < 0.05), most pronounced in executive and visuospatial regions. Limited evidence suggested alterations in small-to-moderate circuits, including nucleus accumbens dysfunction and reduced hippocampal–orbitofrontal connectivity. MASLD is associated with cognitive impairment, reward-related neural systems, and structural and cerebrovascular brain alterations. These findings reinforce its characterization as a multisystem condition affecting brain health and neuropsychiatric risk. Longitudinal studies with standardized criteria and confounder adjustment are needed to clarify causal mechanisms.
Background Nonalcoholic fatty liver disease (NAFLD) is frequently associated with depression, anxiety, and chronic fatigue syndrome (CFS). Major depression and NAFLD are accompanied by low-grade inflammation, increased atherogenicity, and insulin resistance. There is a paucity of data on serum tryptophan and tryptophan catabolites (TRYCATs) in relation to these symptoms in patients with NAFLD. This study aims to determine the relationships between the severity of NAFLD, the severity of the above neuropsychiatric symptoms and neuro-immune, metabolic, and TRYCAT pathway biomarkers.Methods This case-control study included 56 patients with Grade 1 NAFLD, 52 with Grade 2 NAFLD, and 60 healthy controls. We assessed serum insulin, tryptophan, kynurenine, 3-hydroxykynurenine, kynurenic acid, indoleamine 2,3-dioxygenase 1 (IDO1), interleukin (IL)-6, IL-10, HOMA2 insulin resistance index (HOMA2IR), and atherogenic indices.Results The severity of depression, anxiety, and fibro-fatigue symptoms was significantly higher in NAFLD than in controls and in grade 2 as compared with grade 1 NAFLD. The atherogenic and HOMA2IR indices increased significantly from controls to grade 1 and then to grade 2. Serum tryptophan, kynurenine, kynurenic acid, and 3-OH-kynurenine were significantly lower in NAFLD and especially in grade 2 than in controls, while IL-6 and IL-10 were higher in grade 2 NAFLD than in controls. The rating scale scores were significantly and positively correlated with liver tests, atherogenicity, and HOMA2 indices, and inversely with tryptophan and TRYCATs.Conclusions Affective and fibro-fatigue symptoms due to NAFLD might be mediated by the cumulative neurotoxic effects of lipids, IR, and lowered anti-inflammatory and antioxidant effects of the TRYCAT pathway.
OBJECTIVE:A mutual influence between mood disorders and obesity has been reported. Maladapting eating behaviors associated with mood spectrum swings may play a pivotal role in the development and maintenance of obesity. Considering that, the aim of the present study is to investigate the relationship between problematic eating behaviors, namely emotional eating, grazing and night eating, with impulsivity and lifetime mood spectrum (mood, energy, cognition, rhythmicity and vegetative functions) in severe obese patients seeking bariatric surgery. METHODS:304 obese outpatients were recruited at the Psychiatric Unit of the University Hospital of Pisa. Participants completed psychometric tools including the Emotional Eating Scale (EES), the Italian-Night Eating Questionnaire (I-NEQ), the Grazing Questionnaire (GRAZ), the Barratt Impulsiveness Scale (BIS-11), and the Mood Spectrum Self-Report - lifetime version (MOODS-SR). Descriptive analyses and linear correlation were performed. RESULTS:The sample was predominantly female (71.4%), with a mean age of 47.5 ± 10.9 years and a mean BMI of 43.3 ± 6.3 kg/m2. Impulsivity was positively correlated with depressive and manic mood, energy, and cognitive MOODS-SR domains. Emotional eating, night eating, and grazing were significantly associated with the MOODS-SR total score (r=0.422, p=0.000; r=0.321, p=0.001; r=0.321, p=0.000, respectively) and with specific depressive and manic subdomains of the MOODS-SR. CONCLUSION:Loss-of-control eating behaviors were positively associated with lifetime depressive and manic mood spectrum features in bariatric patients, highlighting the importance of assessing these dimensions to promote a tailored and integrated treatment.
OBJECTIVE:To characterize qualitative Clock Drawing Test (CDT) error profiles across dementia etiologies and mild cognitive impairment (MCI), and to propose a clinically interpretable six-class framework. METHODS:In a hospital-based study in Kolkata, India, consecutive adults with cognitive impairment completed a free-drawn "ten past ten" CDT. Errors were coded using classical qualitative categories and clock components (face, numbers, hands), then collapsed into six classes: conceptual, stimulus-bound/perseveration, spatial, planning, number-related, and graphic-conceptual. For nonexclusive domains, omnibus Pearson χ² tests summarized error distributions across diagnoses; Cramér's V quantified effect size. RESULTS:Participants included Alzheimer's disease (AD; n = 36), vascular dementia (VaD; n = 16), behavioral variant frontotemporal dementia (bvFTD; n = 9), MCI (n = 19), and other conditions (n = 22). Although 50.0% drew a normal clock face, only 11.8% achieved perfect numbering and 12.7% set the hands correctly. Conceptual errors were most frequent (70.6%), followed by spatial errors (47.1%); neglect and counterclockwise numbering were rare (3.9% each). Error distributions differed by diagnosis for face, numbers, and hands (all p < 0.001; V = 0.4-0.5). The six-class scheme retained a significant distributional association with diagnosis (χ² = 43.365, p = 0.002; V = 0.3): bvFTD showed prominent conceptual and graphic-conceptual failures, AD combined conceptual and spatial errors, MCI emphasized spatial and number-related errors, and VaD was heterogeneous. CONCLUSIONS:Qualitative CDT profiles vary meaningfully across cognitive disorders. This concise six-class framework captures clinically salient patterns, especially in severely degraded drawings, and may complement brief memory screening and digital CDT metrics.
OBJECTIVE:To characterize the treatment burden of generalized anxiety disorder (GAD) using real-world data on pharmacotherapy use, treatment changes, and treatment progression. METHODS:This retrospective analysis used closed claims from the Komodo Healthcare Map (2021-2024) to identify U.S. adults (≥18 years) with newly diagnosed or established GAD. Treatment patterns were assessed at the drug level. RESULTS:Among the 259 158 newly diagnosed and 1 018 288 established GAD patients, GAD-related pharmacotherapy use during the 12 months post-index was 76% and 98%, respectively. Treatment patterns were further analyzed in 59 275 newly diagnosed and 86 920 established GAD patients with ≥1 pharmacy claim. Among newly diagnosed patients, 55% discontinued and 28% added or switched treatments; among established patients, 16% discontinued and 55% added or switched treatments. The median time to first treatment event varied by cohort and event type: discontinuation occurred at a median of 84 days in newly diagnosed and 119 days in established patients, combination therapy at 49 and 32 days, and switching at 31 and 42 days, respectively. Of those who discontinued, 57% of newly diagnosed and 26% of established GAD patients did not resume treatment; among those who restarted, the median treatment gap was 146 and 96 days, respectively. Overall, 75% of newly diagnosed and 94% of established GAD patients who underwent treatment modification experienced at least one additional therapy change during the study. CONCLUSION:This study underscores the significant unmet needs in the current treatment of GAD, evidenced by high rates of pharmacotherapy switching, discontinuation, and prolonged gaps in care.
OBJECTIVES:To report prevalence, severity and clinical and inflammatory correlates of Post-Traumatic Stress Disorder (PTSD) in patients with schizophrenia. METHODS:This cross-sectional, observational study included adult outpatients with schizophrenia/schizophreniform disorder. Assessments included the Mini-International Neuropsychiatric Interview (MINI), Post-traumatic Stress Disorder Symptom Severity Scale-Revised, Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale for Schizophrenia (CDSS), Global Assessment of Functioning Scale (GAF), and inflammatory markers (neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio, systemic immune-inflammation index: platelets × neutrophils)/lymphocytes). Analyses compared patients with (SCZ + PTSD) versus without PTSD (SCZ-PTSD) across demographic, clinical, and biological variables. RESULTS:SCZ + PTSD had higher PANSS-total scores (80.7 ± 19.5 vs. 71.6 ± 17.1; p = 0.003), more comorbid depression (73.8% vs. 23.3%; p < .001), higher CDSS scores (9.5 ± 4.9 vs. 3.2 ± 4.1; p < .001), more frequent suicide attempts (40.5% vs. 23.0%; p = 0.05), lower GAF scores (39.8 ± 12.3 vs. 49.6 ± 12.3; p < .001) and more medical comorbidities (51.1% vs. 42.8%; p = .014). Inflammatory markers did not differ significantly between groups. Logistic regression analyses identified higher CDSS scores (OR = 1.25, 95% CI [1.15, 1.36], p < .001) and lower GAF scores (OR = 0.96, 95% CI [0.93, 0.99], p = .007) as significant correlates of PTSD (r2 = 0.22). CONCLUSIONS:PTSD is common and clinically relevant in people with schizophrenia, underscoring the need for routine screening and targeted interventions in this population.
BACKGROUND:Use of GLP-1 receptor agonists (GLP-1 RAs) is an established therapy that delays progression of chronic kidney disease in type 2 diabetes mellitus (T2DM), but their impact on lithium-associated nephrotoxicity is unclear. We evaluated whether GLP-1 RA use is associated with reduced renal risk in adults receiving long-term lithium therapy. METHODS:We conducted a retrospective, propensity score-matched cohort study using TriNetX electronic health records (>127 million patients across 109 healthcare organizations). Adults (≥18 years) with T2DM and lithium exposure within 2 years prior to index were included. The primary outcome was renal nephrotoxicity, defined as a composite of ICD-10 and CPT-coded renal disease. Incidence and time-to-event outcomes were assessed using Kaplan-Meier curves and Cox proportional hazards models. RESULTS:In a 24-month analysis of 452 matched patient pairs, GLP-1 RA initiation during lithium therapy was associated with a marked reduction in renal events versus lithium alone (23.5% vs 44.7%), corresponding to a risk difference of -21.2% (95% CI -36.9 to -5.5) and a risk ratio of 0.53 (95% CI 0.30-0.91; p = 0.013). Event-free survival was higher (62.5% vs 43.4%; log-rank p = 0.0115), with a hazard ratio of 0.45 (95% CI 0.23-0.85; p = 0.0089). This represents a 47% relative risk reduction and a number needed to treat (NNT) of 5 over 24 months. CONCLUSION:These findings support further mechanistic and prospective studies of GLP-1 RAs as a renoprotective strategy for patients receiving lithium treatment.
Cognitive impairment is a major determinant of disability in bipolar disorder (BD) and a defining feature of both mild cognitive impairment (MCI) and Alzheimer's disease (AD). Lithium, a first-line maintenance treatment for BD, is implicated in neuroprotective mechanisms including glycogen synthase kinase-3β inhibition, amyloid and tau modulation, and neurogenesis promotion. The overarching aim of this systematic review is to evaluate the long-term effects of lithium on cognition across BD, MCI, and early-to-moderate AD using randomized controlled trial (RCT) evidence. Online databases were searched from inception through May 2025 for RCTs reporting lithium's effect on cognitive outcomes in BD, MCI, or early-to-moderate AD with ≥8 weeks of follow-up. Risk of bias was assessed using the Cochrane RoB 2 tool. Eight RCTs met the inclusion criteria, ranging from 10 weeks to 3 years in duration. Across four BD trials, lithium did not exhibit consistent improvement or worsening on composite cognitive scores. Three of four MCI/AD trials reported attenuated global cognitive deterioration with low-dose lithium, especially when exposure was ≥12 months. Methodological limitations included small sample sizes, exploratory endpoints, and variable measures for cognitive function as well as lithium strategies. Lithium demonstrates preliminary signals of slower cognitive decline in MCI/AD. Available evidence suggests lithium has neutral effects on cognitive impairment in BD. Future adequately powered RCTs with cognition as a primary endpoint, functional measures, and biomarker outcomes are warranted to clarify lithium's role as a maintenance treatment in psychiatric disorders and its potential neuroprotective effects in neurodegenerative diseases.
Abstract Objective To evaluate the validity and correlates of inaccurate clinically diagnosed moderate/severe ICD-10 major depressive disorder (MDD) and psychiatric comorbidities in adult inpatients. Methods The multicenter Patient Characteristics, Validity of Clinical Diagnoses and Outcomes Associated with Suicidality in Inpatients with Symptoms of Depression (OASIS-D) study enrolled 18- to 75-year-old inpatients with MDD who underwent assessments for clinical, illness, and treatment characteristics, including the Mini-International-Neuropsychiatric-Interview (MINI). False-positive clinically MDD diagnoses were characterized via MINI. Diagnostic agreement between clinical and MINI-based psychiatric comorbidities was assessed with kappa-statistic. Results Among 401 patients (median age = 33.0 years; female = 57.1%), 42 (10.5%) were false positive for MDD (i.e., different primary diagnosis). Reasons for misdiagnosing MDD exclusive to false-positive cases included bipolar disorder (45.2%), subsyndromal depression (16.7%), and physical illness-related/substance use disorder (SUD)-related depression (4.8%), whereas missed diagnoses that could also occur in true-positive, MINI-based MDD patients included primary SUDs (23.8%) and primary anxiety disorders (9.5%). Among comorbidities, greatest disagreement between clinical and MINI-based research diagnoses existed for antisocial personality disorder (0% vs. 5.2%, κ =0), followed by anxiety disorders (7.5% vs. 45.1%, κ =0.17), obsessive-compulsive disorder (3.0% vs. 8.7%, κ =0.27), SUDs (11.0% vs. 28.4%, κ =0.29), eating disorders (3.5% vs. 7.2%, κ =0.39), and posttraumatic stress disorder (10.7% vs. 23.7%, κ =0.40). Conclusions Bipolar depression and SUDs contributed to two thirds of misdiagnosed MDD. Missed comorbidities included mostly anxiety disorders, SUDs, and PTSD. Accurate diagnostic assessment, including longitudinal history, is essential to reduce misdiagnosis and ensure guideline-based treatment for psychiatric disorders in MDD inpatients.
OBJECTIVE:Longitudinal investigation of brain alterations in children putatively at risk of developing schizophrenia may identify early markers of pathophysiology associated with vulnerability for the disorder. METHODS:Children aged 9-12 years with multiple antecedents of schizophrenia (psychotic-like experiences; speech and/or motor delays; and social, emotional, and/or behavioral difficulties; ASz, n = 31), with a family history of schizophrenia/schizoaffective disorder (FHx, n = 21), and typically developing children (TD, n = 35) were recruited through community screening using questionnaires. T1-weighted structural MRI scans were obtained at baseline and after approximately 2 and 4 years of follow-up, and processed using the FreeSurfer longitudinal pipeline. Across these 3 assessment waves, total gray matter (GM) and white matter (WM) volume, and regional GM volumes in 12 regions of interest, were compared among the groups using linear mixed models. RESULTS:Children were aged 11.21 (±1.61) years at baseline and the average lapse-of-time between each assessment was 1.76 (±0.36) years. The ASz group exhibited consistently higher total WM volume (b = 29.45) compared to the TD group, with no statistically significant time-related volumetric WM or GM differences in any region. The FHx group also demonstrated higher total WM volume (b = 36.49), and time-related total and regional GM volume changes were observed; however, these effects were attenuated after correction. CONCLUSION:Global and regionally specific brain abnormalities distinguished children with different risk profiles for schizophrenia relative to their typically developing peers. Follow-up is required to determine how these changes may relate to later schizophrenia.
OBJECTIVE:Autistic traits (ATs) are associated with difficulties in social functioning, but their impact on the quantity and the quality of daily-life social interactions is not yet fully understood. Hereby, we examined the relationship between AT and daily-life social interactions in adolescents and young adults. METHODS:Data were derived from the TwinssCan cohort (N = 593). ATs were assessed using the Autism Spectrum Quotient (AQ), while the quantity and the quality of daily-life social interactions were evaluated using the Experience Sampling Methodology. Multilevel regressions were performed, with the AQ as the independent variable and each social/solitary quantity/quality variable as the dependent variable. Models were adjusted for age, sex, and general psychopathology, measured with the Symptom Checklist-90. RESULTS:No significant association was found between AQ total scores and quantity of social interactions. However, AQ total scores were significantly associated with quality of social interactions. Higher ATs were associated with an increased preference to be alone (B = 0.04, 95% CI 0.01-0.07), less pleasure while in-company (B = -0.02, 95% CI -0.04 to -0.01), less feeling of safety while in-company (B = -0.02, 95% CI -0.04 to -0.002), and less feeling of belongingness (B = -0.02, 95% CI -0.03 to -0.001). ATs were differently associated with the quality of social interactions depending on the familiarity. No significant associations were found between ATs and solitary qualities. CONCLUSIONS:Our findings highlight the importance of evaluating ATs during clinical assessments, especially in adolescents and young adults, to evaluate the impact on social interactions and the potential psychopathological consequences.
OBJECTIVE:Resting-state networks (RSNs) consist of coherent spontaneous activity patterns that support a wide range of sensorimotor and higher-order cognitive functions. In schizophrenia (SZ), RSN alterations reflect disruptions in the brain's functional architecture. Given the heterogeneity of SZ, accurate spatial mapping of RSNs at the individual level is crucial for characterizing altered brain connectivity in a more personalized manner. To achieve this, we used single-subject independent component analysis (ICA) to extract RSNs at the individual level, preserving unique functional patterns and accounting for variability among SZ patients. METHODS:We analyzed a resting-state functional magnetic resonance imaging dataset from 74 SZ patients and 74 matched healthy controls (HCs) obtained from the publicly available COINS database. Using single-subject ICA, we extracted 14 distinct RSNs associated with sensory, motor, and higher-order cognitive functions. Voxel-wise statistical comparisons were performed to identify spatial differences between the groups. RESULTS:The SZ group exhibited widespread RSN alterations in regions associated with visual, motor, and cognitive processing. Significant spatial differences were observed within each network, with the most extensive changes occurring in the somatomotor network and three cognitive networks: the cingulo-insular, medial prefrontal, and left frontoparietal networks. Within the default mode network, differences between SZ patients and HC were observed exclusively in visual areas. CONCLUSIONS:Single-subject ICA provides a valuable approach for investigating RSN alterations in SZ and enables a detailed, individualized characterization of functional connectivity disruptions. The extensive connectivity alterations in visual, motor, and cognitive networks highlight the complex interplay among these systems in SZ.
Objective The present study investigated the management of predominant negative symptoms in hospitalized patients and assess the impact of targeted pharmacological and psychological interventions.Methods This longitudinal, prospective, multicenter cohort study was conducted across multiple hospitals in Slovakia, focusing on inpatients, with assessments at admission and discharge. Eligible participants were hospitalized adults (18-65) diagnosed with schizophrenia and predominant negative symptoms. Treatment effectiveness was measured using the modified Short Assessment of Negative Domain, Self-evaluation of Negative Symptoms, Personal and Social Performance, and Clinical Global Impression scales. Means changes and effect sizes were calculated from baseline to final assessment. Differences in the perception of negative symptoms between patients and doctors were examined.Results At discharge, patients showed significant improvements in symptom severity and functioning on all scales. Primary and secondary negative symptoms significantly decreased, especially those linked to positive and affective symptoms. Functioning improved, with fewer severe impairments in daily life. Most patients were on antipsychotic polytherapy throughout hospitalization, with around 85% receiving multiple antipsychotics at admission and at discharge. Non-pharmacological interventions were also widely used, with nearly nine out of ten patients receiving at least one such therapy during hospitalization.Conclusions Negative symptoms in schizophrenia pose a major treatment challenge, leading to functional impairment and poor quality of life. While positive symptoms often trigger hospitalizations, negative symptoms have a lasting impact on prognosis. Results suggest both D3-receptor-targeted pharmacotherapy, particularly cariprazine, and integrated non-pharmacological interventions may contribute to meaningful improvements in negative symptoms during hospital care.
BACKGROUND:Schizophrenia frequently coexists with various physical and psychiatric comorbidities, but the influence of these comorbidities on mortality outcomes, particularly suicide mortality, among young patients with schizophrenia remains inadequately understood. METHODS:We followed 109 900 young patients with schizophrenia aged 10-44 years for up to 10 years. We assessed 12 physical diseases, including diabetes, myocardial infarction, chronic liver disease, and malignancies, and two psychiatric disorders, namely alcohol use disorder and substance use disorder (SUD). Time-dependent Cox regression models were used to analyze the associations of these comorbidities with all-cause and suicide mortality. RESULTS:SUD was strongly associated with increased all-cause mortality (hazard ratio [HR]: 1.80) and suicide mortality (HR: 3.76). Malignancies (HR: 14.39) and chronic kidney disease (HR: 6.46) were also strongly linked to all-cause mortality. The risk of all-cause mortality increased with the number of comorbidities (HR: ≥2: 2.02 versus 1: 1.45). No significant association was found between physical comorbidities and suicide risk. CONCLUSIONS:SUD is a significant risk factor for suicide mortality among young patients with schizophrenia. Physical comorbidities such as malignancies and chronic kidney disease are primarily associated with increased all-cause mortality in this population.
Bipolar disorder (BD) is associated with increased cardiometabolic risk, contributing to elevated morbidity and premature mortality. Childhood trauma (CT) is a common environmental risk factor in BD and may exacerbate metabolic dysfunction, but no prior systematic synthesis has focused on their intersection. The objective of this review was to systematically review and synthesize evidence on the association between childhood trauma exposure and metabolic biomarkers in adults with bipolar disorder. This review adhered to PRISMA 2020 guidelines and was registered in PROSPERO (ID CRD420251045565). A comprehensive search of PubMed/MEDLINE, Web of Science, Scopus, and Embase (from inception to September 2025) was conducted. Eligible studies were peer-reviewed observational studies assessing associations between CT and metabolic markers (eg, BMI, lipids, HbA1c, hs-CRP) in adult BD populations. Data extraction and NIH quality assessments were performed independently by multiple reviewers. Sixteen studies were included (total n ≈ 6,200 across study samples). CT was significantly associated with higher body mass index and elevated hs-CRP. Two third of studies reported adverse associations with lipid profiles, and one study showed increased HbA1c among CT-exposed BD patients. Most findings emerged from cross-sectional designs, though one longitudinal study revealed large effect sizes across multiple metabolic markers. CT is consistently associated with adverse metabolic outcomes in individuals with BD, particularly elevated BMI, inflammation, and dyslipidemia. These findings support the need for trauma-informed metabolic screening and personalized interventions in this subgroup BD population. Further prospective studies are warranted to elucidate causal pathways and inform personalized care.
