It is unclear whether patients with obsessive-compulsive disorder (OCD) and expert clinicians agree on the symptoms’ qualities that are essential for a diagnosis of OCD. This study examined whether OCD patients and expert clinicians agree on the essential characteristics for an OCD diagnosis. It compared the endorsement rates of various descriptive terms and assessed whether response profiles could predict group membership (patients versus expert clinicians).

Sixty-four OCD patients and 36 OCD expert clinicians answered a questionnaire on their views regarding the defining characteristics of OCD symptoms. It included a compilation of adjectives extracted from DSM-5 to describe disorders in the compulsive–impulsive spectrum. Chi-square tests compared response prevalence between groups and binary regression identified distinguishing features. The significance level was set at 0.05.

All descriptors differed significantly between OCD patients and expert clinicians (p < 0.01), with clinicians consistently endorsing more items as applicable or essential. Although the logistic regression model significantly distinguished the 2 groups and showed high explanatory power (R2 = 0.7) with 99% classification accuracy, no individual descriptors were significant predictors.

There is a mismatch between clinician-defined diagnostic language and patients’ subjective experience of OCD, including core symptom descriptors. This gap suggests that current OCD diagnostic construct may not fully capture how patients perceive their condition, potentially limiting its validity and clinical utility. Adopting more patient-centered language could improve assessment, psychoeducation, and treatment engagement.

To characterize the treatment burden of generalized anxiety disorder (GAD) using real-world data on pharmacotherapy use, treatment changes, and treatment progression.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

These findings support further mechanistic and prospective studies of GLP-1 RAs as a renoprotective strategy for patients receiving lithium treatment.

To evaluate the validity and correlates of inaccurate clinically diagnosed moderate/severe ICD-10 major depressive disorder (MDD) and psychiatric comorbidities in adult inpatients.

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.

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).

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.

To report prevalence, severity and clinical and inflammatory correlates of Post-Traumatic Stress Disorder (PTSD) in patients with schizophrenia.

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.

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).

PTSD is common and clinically relevant in people with schizophrenia, underscoring the need for routine screening and targeted interventions in this population.

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).

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.

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.

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.

Gambling disorder frequently co-occurs with other psychiatric conditions, yet its relationship with obsessive-compulsive disorder (OCD) remains unclear. Emerging evidence suggests impulsivity and compulsivity may be inter-related rather than diametrically opposed constructs, warranting investigation of their clinical overlap. The aim of this study is to examine the rate of gambling disorder in adults with OCD and to explore associated clinical, behavioral, and treatment-related characteristics.

Adults with probable OCD were recruited via online Reddit groups for OCD, OCD clinics, and support groups and completed a cross-sectional survey. OCD symptom types were assessed using the Obsessive-Compulsive Inventory-Revised, and gambling disorder was identified using the Minnesota Impulsive Disorders Interview. Additional measures included gambling severity, impulsivity, and problematic internet use. Group comparisons were conducted between participants with and without gambling disorder.

Among 186 adults with OCD, 34 (18.8%) met criteria for gambling disorder. Individuals with comorbid gambling disorder demonstrated significantly greater OCD severity, particularly in ordering, checking, and neutralizing symptoms, and reported later onset of OCD. The comorbid group showed higher impulsivity, greater problematic internet use, and distinct gambling behaviors, including higher rates of online gambling, esports betting, and use of artificial intelligence tools for gambling. They were also less likely to have received pharmacological treatment for OCD.

Gambling disorder in adults with OCD is associated with distinct clinical characteristics, greater impulsivity, problematic internet use, and concerning treatment gaps. These findings highlight the importance of screening for gambling in OCD, and vice versa, and suggest a need for integrated treatment approaches.

Impairments in spatial working memory (SWM) have been observed in several disparate psychiatric conditions. The present study investigated how SWM varied across a range of psychiatric disorders in a large sample of young adults using the SWM test from the Cambridge Neuropsychological Test Automated Battery.

A sample of 575 participants aged 18–29 years was enrolled from the general community and evaluated for psychiatric disorders using several screening evaluations. Performance on the SWM test was assessed, with outcome measures of strategy and total errors. Using Z-scores and Cohen’s d effect sizes, SWM was compared between each psychiatric disorder and healthy controls.

The majority of psychiatric diagnoses examined demonstrated SWM deficits in both strategy and total errors. Large effect sizes in strategy were observed for bulimia, post-traumatic stress disorder, major depressive disorder, social phobia, and agoraphobia. Large effect sizes in total errors were observed for agoraphobia, major depressive disorder, social phobia, intermittent explosive disorder, obsessive-compulsive disorder, bulimia, post-traumatic stress disorder, and gambling disorder.

Our findings suggest that SWM impairment is a transdiagnostic element of psychiatric illness rather than serving as a specific feature of any one diagnosis. Future directions include the exploration of how SWM deficits may be utilized in prognostic and therapeutic interventions.

The care of patients with borderline personality disorder (BPD) places a significant burden on emergency inpatient mental health services. The aim of this study was to investigate predisposing risk factors for early rehospitalization over 12 months.

A total of 117 inpatients with BPD were included. The Beck Hopelessness Scale, Adolescent/Adult Sensory Profile, Coping Orientation to Problems Experienced (COPE), and Toronto Alexithymia Scale (TAS-20) were administered.

Forty-seven percent of the sample was rehospitalized. Divorced marital status, current substance abuse, a higher score on the TAS-20 externally oriented thinking score and on the COPE Alcohol and drug disengagement subscales, and a lower score on the COPE. Use of social–emotional support subscale were significantly associated with rehospitalization. Therefore, alcohol and substance misuse, impaired social support, and alexithymia were the most relevant predictors for rehospitalization.

Maladaptive coping, depressive symptoms, and history of high service utilization and multiple high-lethality suicide attempts were also found to be more common in readmitted subjects. Further research could help to better define potential different therapeutic interventions.

Cognitive dysfunction is a core feature of major depressive disorder. During transcranial magnetic stimulation (TMS) for treatment-resistant depression (TRD), the temporal relationship between symptom changes and cognitive performance remains unclear. We examined depressive symptoms and cognitive trajectories during TMS and tested whether time-varying cognitive change was associated with symptom trajectories.

This retrospective naturalistic study included 89 patients with TRD who completed 20 sessions of left dorsolateral prefrontal cortex TMS (high-frequency repetitive TMS or intermittent theta-burst stimulation). Depression severity (Hamilton Depression Rating Scale [HAMD-17]) and computerized attentional control measures from the Test of Attentional Performance were assessed at baseline, day 10, and day 20. Generalized estimating equations examined time effects and time-adjusted symptom-cognition associations. Exploratory analyses evaluated whether early cognitive change was associated with subsequent symptom improvement. Multiple comparisons were controlled.

Depressive symptoms decreased significantly (p < 0.001), with response and remission rates of 65.2% and 51.7%. Several attentional indices showed significant time effects; however, after false discovery rate correction, only visual divided-attention commission errors were independently associated with depressive severity beyond time effects. Person-mean centering indicated that this association was driven by within-person change (B = 0.209, p < 0.001), not between-person differences. Greater early reduction in visual divided-attention commission errors was associated with larger overall symptom improvement (B = 0.172, p = 0.016).

Within-person changes in divided attention tracked depressive symptom trajectories during TMS. Attentional control measures may therefore help track symptom-cognition dynamics during TMS in real-world clinical settings.

To determine whether pharmacologic exposure is associated with differences in fibromyalgia neurobehavioral phenotypes and whether medication burden explains symptom variability within phenotypes.

We analyzed a multisite cohort of 695 adults meeting fibromyalgia criteria, stratified into low- and high-impact phenotypes using a disability-based classification. Medication burden was quantified as total, centrally acting, and noncentrally acting medication counts. Between-phenotype differences and within-phenotype associations between medication burden and symptom severity were evaluated using nonparametric tests, Spearman correlation analyses, and multivariable linear regression models. Phenotypes were interpreted within the framework of centrally mediated neurobehavioral dysfunction.

Participants classified within the high-impact neurobehavioral phenotype (n = 175) demonstrated substantially greater symptom burden across fibromyalgia impact, central sensitization, depressive symptoms, pain severity, and vitality compared with low-impact participants (n = 520). Centrally acting medication burden increased stepwise with phenotype severity, whereas noncentrally acting medication use did not differ between phenotypes. Within phenotypes, centrally acting medication burden showed weak and nonsignificant associations with symptom severity after adjustment for demographic covariates, explaining minimal variance in fibromyalgia impact (R2 < 0.05).

Fibromyalgia symptom phenotypes remained distinct across varying levels of pharmacologic exposure, and medication burden explained little within-phenotype symptom variability. Medication burden primarily reflects downstream clinical response to symptom severity rather than a determinant of phenotype organization. These findings support the use of stable multidimensional phenotypes for mechanistic, neurobiological, and stratified intervention studies in chronic pain and related central nervous system disorders.

Major depressive disorder (MDD) and bipolar disorder (BD) exhibit overlapping depressive presentations, making early differentiation difficult and misdiagnosis clinically consequential. Entropy-based resting-state electroencephalography (EEG) markers were evaluated for differentiating drug-naïve patients with stable MDD, converted BD, and diagnosed BD.

Resting-state EEG was acquired from 92 drug-naïve patients: 50 with stable MDD, 16 who converted to bipolar II disorder over 3 years, and 26 with diagnosed BD. Band-scale entropy and cross-sample entropy (CSE) were analyzed. Group differences were tested by analysis of covariance adjusted for depressive severity; classification was evaluated by nested cross-validation with permutation testing.

Relative to stable MDD, diagnosed BD showed higher theta- and alpha-band entropy in frontal and central regions and lower values for selected intra- and inter-regional CSE measures. Two CSE measures correlated positively with non-planning impulsiveness in diagnosed BD. Converted BD showed intermediate values without significant pairwise differences. Prospective discrimination of stable MDD versus converted BD was modest (balanced accuracy, 65.4%; area under the receiver operating characteristic curve [ROC-AUC], 0.661). Classification was strongest for stable MDD versus diagnosed BD, yielding 78.9% pooled accuracy, 76.6% balanced accuracy, and an ROC-AUC of 0.832 when entropy features were combined with depressive severity; combined entropy outperformed either single-family configuration.

Entropy-derived EEG measures differentiated stable MDD from diagnosed BD and suggested a weaker, intermediate profile in converted BD. They may serve as candidate adjunctive biomarkers for mood disorder differentiation, although larger prospective cohorts are required to clarify their value in predicting conversion to bipolar II disorder.

Adult ADHD assessments have increased sharply in recent years, yet the diagnostic yield and predictors of confirmed ADHD among assessment-seeking individuals remain insufficiently understood. This study aimed to examine the sociodemographic and clinical characteristics of adults self-referred or referred by clinicians for suspected ADHD, to determine confirmation rates, factors associated with confirmation, and alternative diagnoses.

A cross-sectional study was conducted on 232 adults evaluated at a regional ADHD referral center. Assessments included semi-structured clinical interviews and standardized instruments (DIVA, SCID-5, ADHD-RS). Logistic regression was used to examine factors associated with the final clinical ADHD diagnosis.

Overall, 64.2% of individuals received an ADHD diagnosis. Compared with non-ADHD participants, those diagnosed with ADHD were more frequently referred by other healthcare professionals and displayed greater academic impairment. They also showed higher rates of mood swings and delayed sleep onset. Childhood inattention emerged as the only DIVA interview score significantly associated with an ADHD diagnosis. Among individuals without ADHD, the most frequent alternative diagnoses were anxiety disorders and depressive disorders, followed by personality disorders, substance use disorders, and bipolar disorders.

Adult ADHD emerges as a multifactorial condition shaped by clinical and functional factors. The final clinical diagnosis was most strongly associated with structured clinical tools, functional impairments (in the academic domain), emotional-regulation difficulties, and childhood inattention, whereas self-reported and more general factors were less informative. These findings underscore the importance of a developmentally informed and comprehensive assessment approach, given the high prevalence of psychiatric conditions that may mimic ADHD.