Acta Neuropsychiatrica

BackgroundLithium is one of the key medications for the treatment of bipolar disorder, but it requires therapeutic drug monitoring because of its narrow therapeutic window. In routine clinical practice, blood sampling is often performed outside the recommended 10-14 hour interval after the last evening dose, which distorts interpretation of the measured concentration (overestimation with early sampling and underestimation with late sampling) and may lead to inappropriate dose adjustment. ObjectiveTo develop and validate, using synthetic data, a multiplicative model (SimpLi) that standardizes a measured lithium concentration to the 12-hour level while accounting for sampling time and daily dose. Materials and MethodsA simulation study was conducted in accordance with ADEMP recommendations. A synthetic cross-sectional dataset (n = 1000) was generated with distributions of time since the last lithium dose, serum concentrations, and doses derived from the Bipolar CHOICE study, with a median sampling time of 12 hours (IQR 11-14) and a time-concentration correlation of r {approx} -0.30. The dataset was split 70/30 with stratification by time intervals, and 5-fold cross-validation was performed. Model performance was evaluated using RMSE, MAE, and R2. ResultsThe simulation closely reproduced the prespecified time distribution, achieved the target time-concentration correlation (r {approx} -0.30), and yielded a clinically plausible dose structure. A model using time as the only predictor showed limited accuracy (RMSE = 0.316; R2 = 0.108), while adding dose provided a moderate improvement (RMSE = 0.303; R2 = 0.177). When sampling occurred exactly at 12 hours, direct prediction was biased (-0.150; RMSE = 0.357), supporting the need for an individual correction factor. In a proof-of-concept analysis of five clinical cases, SimpLi produced a lower MAE than the eLi12 formula (0.042 vs 0.056 mEq/L). ConclusionsSimpLi is a practical tool (psyandneuro.ru/bekhterev-ai/simpli/) for standardizing lithium levels to 12 hours when sampling times vary. External validation on real-world data and robustness testing across clinical scenarios are needed.

IntroductionSepsis is a life-threatening ailment caused by an exaggerated immune response to infection that poses a major health problem, with increasing prevalence, high costs, and poor outcomes. Improved outcomes are seen in patients when providers follow the Surviving Sepsis Campaign recommended clinical practice guidelines for identifying and treating sepsis using a 3-hour and 6-hour bundle after sepsis is suspected. Previous research has shown patients with mental health issues receive worse quality of diabetes and cardiac care and have poorer outcomes compared with those without mental health issues. Similarly, patients with mental health issues may receive worse sepsis care due to inability to explain symptoms, agitation, etc. This study explores sepsis quality of care among patients with vs. without an acute mental health crisis, and whether patients with certain mental health issues were more likely to receive sepsis bundle care than others. MethodsUsing data extracted from 2018-2019 at the Long Island Jewish Medical Center Emergency Department (ED), patients who met sepsis inclusion criteria were grouped into either having, or not having, a severe mental illness crisis on the basis of whether physical or chemical restraints were used in the ED. Patients with a history of a severe mental illness, but who were not in a severe mental health crisis, were grouped with the patients without mental health illness, as, in the absence of an acute psychiatric problem, their mental health issue unlikely affected sepsis care. We describe demographic characteristics of both groups and performed a univariate analysis using Students T-test to compare the percent of those with vs. without acute mental health crisis who received full 3- and 6-hour sepsis bundle care. Patients with an acute mental health crisis were grouped according to "cognitive" (eg, dementia) vs. "non-cognitive" (eg, schizophrenia) disorders. ResultsComparing those with vs. without acute mental health crisis, there was no difference in the percent of patients who received 3-hour sepsis bundle care (80.7% vs 74.9%, p = 0.1456). However, among patients who received the 3-hour bundle, a significantly-greater percent of those with an acute mental health crisis received the 6-hour sepsis bundle (51.0% vs. 30.7%, p <0.0001). There was no difference between different groups of patients with mental health issues (eg, "cognitive" vs. "non-cognitive") with respect to receiving 3- or 6-hour sepsis bundle care. DiscussionSurprisingly, although there was no significant difference in likelihood to receive a 3-hour sepsis bundle among patients with vs. without an acute mental health crisis, those with an acute mental health crisis were more-likely to receive 6-hour care. We suspect this difference might be due to increased attention paid to patients with an acute mental health crisis, including more-frequent room visits by hospital staff or more concerns among family members. No particular set of mental health conditions was associated with receiving or not receiving appropriate care. Future research could address possible confounding factors, go into more detail about the specific component of the sepsis protocol that patients failed to receive, and specify what aspects of a mental health crisis affected treatment plans. Future studies are needed to assess possible associations between severe mental illness crisis, bundle care, and mortality in relation to ED, Intensive Care Unit (ICU), or hospital length-of-stay (LOS).

ObjectivePosttraumatic stress disorder (PTSD) after a traumatic birth is a serious but overlooked maternal morbidity, affecting [~]20% of women following medically complicated deliveries. PTSD can undermine maternal caregiving. Rapid screening tools suited to busy obstetric settings are lacking. We developed and evaluated a brief screener, derived from the 20-item PTSD Checklist for DSM-5 (PCL-5), to identify PTSD related to childbirth. Study DesignWe enrolled 107 women with traumatic childbirth. Participants completed the PCL-5 and the gold-standard clinician diagnostic interview for PTSD (CAPS-5); depression was measured with the Edinburgh Postnatal Depression Scale (EPDS). Bootstrap resampling with LASSO regression identified PCL-5 items most associated with PTSD. Firth logistic regression models estimated diagnostic accuracy. Sensitivity, specificity, area under the ROC curve (AUC), and Youdens J statistic determined performance and optimal cut-off. ResultsA six-item version of the PCL-5 (PCL-5 R6), statistically derived from the full scale, showed excellent discrimination for PTSD compared with clinician evaluation (AUC = 0.95; 95% CI, 0.89-1.00). A cut-off score of 7 yielded high sensitivity (0.96) and good specificity (0.83), with an overall diagnostic efficiency of 0.86, detecting most PTSD cases while minimizing false positives. The PCL-5 R6 correlated moderately with the EPDS (rho = 0.53), showing that a depression screen alone cannot reliably detect PTSD. ConclusionsA short, 6-item PCL-5 provides a valid, efficient tool for detecting childbirth PTSD. Its brevity and accuracy make it practical for integration into routine postpartum care, enabling timely mental health screening.

Esketamine is a fast-acting antidepressant drug which induces acute psychoactive effects. The most frequent is a dissociative state which seems unrelated to therapeutic efficacy. Other esketamine-induced effects, including psychedelic-like mystical experiences, have been poorly studied in terms of phenomenology and frequency, and may carry specific therapeutic relevance. In this study, we characterised esketamine-induced mystical experiences in relation with clinical outcomes. We conducted a longitudinal observational study and systematically measured acute subjective effects in patients receiving esketamine for treatment-resistant depression after each administration across the induction phase. A total of 45 patients were included, from two independent centres, totalling 352 esketamine administrations. Principal Component Analysis (PCA) supported the validity of the Mystical Experience Questionnaire (MEQ-30) for assessing esketamine-induced subjective effects, with components recovering dimensions previously validated with classic psychedelics. Mystical experiences (MEQ-30 score above 60) occurred in 58% of patients, with high inter- and intra-individual variability in frequency, intensity, and phenomenology across sessions. Higher mean and peak MEQ scores were associated with greater improvement in Montgomery-Asberg Depression Rating Scale scores from pre- to post-treatment, whereas the intensity of dissociative or other non-mystical effects was not. Positive mood and mystical MEQ dimensions in particular predicted therapeutic outcomes. Baseline spirituality also significantly predicted treatment outcomes and peak MEQ scores in the first week of treatment. These findings add to the growing body of evidence suggesting that psychedelic-like mystical experiences may be associated to therapeutic efficacy, not only in classic psychedelic-assisted therapy, but also in esketamine treatment.

ObjectiveGiven the episodic nature of bipolar disorder (BD) and the variability in mood episode recurrence across individuals, accurate recurrence prediction is critical. The original COBY recurrence risk calculator (RC) was developed in a longitudinal youth cohort to estimate threshold recurrence risk. However, its accuracy for predicting subthreshold recurrences had not been fully evaluated. The objective of this study was to extend the previously developed COBY mood recurrence RC to predict both threshold and subthreshold mood recurrences and evaluate its performance in an independent sample. MethodAdolescents and young adults with BD-I/II (N= 51; BD-I: 38, BD-II: 13; 14-24 years old) were interviewed with standard instruments at intake and during the follow-up on average every 6 months for a median of 54 weeks. We assessed the degree to which the COBY RC predicted mood recurrence (threshold or subthreshold) in this independent sample. Discrimination was measured using the area under the receiver operating characteristic curves (AUC); calibration and variable importance were also assessed. ResultsThe model demonstrated good prediction of any recurrence within the next six months (any threshold recurrence AUC = 0.72, any subthreshold or worse recurrence AUC = 0.77). Calibration analysis demonstrated the model tended to overestimate risk in the external sample, plausibly attributable to differences in recurrence ascertainment strategy (prospective vs retrospective) or the significant difference in prior remission length, a key predictor. Recalibration greatly improved calibration without loss of discrimination. ConclusionThe mood recurrence RC demonstrated good discrimination for both threshold and subthreshold mood recurrences in an independent young adult cohort, consistent with prior youth and adult validations. Validation now spans across developmental stages and different degrees of severity of mood symptoms opening the opportunity for clinical implementation to provide personalized monitoring and early intervention for people with BD.

BackgroundWorldwide, common mental disorders such as anxiety and depression are major contributors to disability. However, the role of diet as a risk factor for anxiety and depression remains underexplored. Therefore, we investigated the associations between food groups and major depressive disorder (MDD) and anxiety disorders, following a harmonized protocol to enable integration of studies. MethodsWe analysed data from 1,634 participants in the Netherlands Study of Depression and Anxiety to examine cross-sectional associations between 14 dietary exposures--derived from a 238-item Food Frequency Questionnaire (fruit, vegetables, legumes, whole grains, nuts and seeds, milk, red meat, processed meat, sweet drinks, fibre, calcium, omega-3 fatty acids, polyunsaturated fatty acids, and trans fats)--and anxiety and depressive disorders in the past month (assessed with the Composite International Diagnostic Interview). Secondary outcomes were depressive symptoms (Quick Inventory of Depressive Symptomatology score [&ge;]13 vs. <13) and anxiety symptoms (Beck Anxiety Index score [&ge;]16 vs. <16). Logistic regression analyses were conducted for each dietary exposure, with depression and anxiety measures as outcomes. Results8.7% had MDD and 14.4% had an anxiety disorder in the past month. Higher vegetable intake was associated with lower odds of depression and anxiety disorders. Additionally, higher intakes of omega-3 fatty acids, red meat, whole grains, and fibre were associated with lower odds of depression and anxiety, whereas higher intake of trans fats was associated with increased odds of these disorders. Other dietary exposures were not significantly related to depression or anxiety. DiscussionCertain dietary exposures, particularly vegetables, as well as omega-3 fatty acids, red meat, whole grains, and fibre, were associated with depression and anxiety outcomes. These findings may contribute to integration of results in Global Burden of Diseases initiatives on exploring dietary risk factors of depression and anxiety.

BackgroundOptical coherence tomography (OCT) is increasingly used to investigate retinal structural changes across neurological and neuropsychiatric conditions. This systematic review and meta-analysis synthesises evidence examining retinal thickness in anxiety, depression, and substance use disorders (SUD) compared with healthy controls. MethodsA pre-registered systematic search (PROSPERO: CRD42024559542) of major databases following PRISMA guidelines was conducted. Case-control studies measuring retinal layer thickness via OCT in adults with DSM or ICD diagnosed anxiety, depression, or SUD were included. Multilevel random-effects models were used to calculate pooled standardised mean differences (SMD) and account for dependencies. ResultsThirty-three studies were included for narrative review, and 25 studies with 145 effect sizes were included for meta-analysis. The primary analysis, which pooled all disorders and effect sizes from available retinal thickness measures, found no significant differences between cases and controls (SMD = -0.20; 95% CI [-0.53, 0.14]; p = .244). Subgroup analyses for anxiety, depression, and SUD also yielded non-significant results (all p > .05). No specific retinal layer was consistently affected, and there was no evidence of an age x diagnosis interaction. Significant heterogeneity (Q = 756.57, p < .001) was present across analyses. ConclusionThis meta-analysis found no significant associations between retinal structural differences and anxiety, depression, or SUD. The field is characterised by high heterogeneity and publication bias, limiting the strength of evidence for the utility of OCT as a reliable biomarker for these conditions. Standardised, large-scale studies are needed with strict controls for confounding factors, including medication, disease stage and ocular parameters, alongside standardised OCT segmentation protocols. Article HighlightsO_LIFirst meta-analysis of OCT retinal thickness in anxiety, depression and SUD. C_LIO_LINo significant retinal thickness differences found between cases and healthy controls. C_LIO_LIAge and sex did not moderate the association between diagnosis and retinal thickness. C_LIO_LIHigh heterogeneity and publication bias limit utility of OCT as a neuropsychiatric biomarker. C_LIO_LIStandardised protocols are needed to clarify retinal changes in psychiatric research. C_LI

BackgroundEarly detection of individuals at risk for clinical deterioration in first-episode psychosis (FEP) remains a vital challenge in psychiatric care. Emerging evidence indicates that immune dysregulation might play a crucial role in the pathophysiology and progression of psychotic disorders. AimsThis study examined the predictive potential of a plasma cytokine and chemokine panel in anticipating clinical stage transition of FEP patients. MethodUsing multiplex immunoassays, plasma samples from a cohort of 35 FEP patients were screened for the quantification of 21 analytes. Participants were clinically assessed at baseline and follow-up and classified according to a validated staging model. Data was used to predict clinical stability over a 12-month follow-up period. ResultsIL-17A was found to be significantly increased in transitioning patients (p = 0.045), with a medium standardized effect size and wide confidence interval (Hedges g = - 0.687, 95% CI [-1.379, 0.004]). A logistic regression model was determined, which revealed that higher baseline levels of IL-17A were significantly linked to progression to a more advanced clinical stage, while higher baseline levels of MIP-3 and IFN-{gamma} were associated with clinical stability. This combined cytokine model exhibited strong predictive capacity (AUC = 0.853), indicating its potential as a biomarker panel for early risk assessment. ConclusionsThese findings highlight the importance of neuroimmune mechanisms in the development of psychotic disorders and advocate for the inclusion of immunological markers within staging-based models of care. Incorporating cytokine profiling into clinical practice could improve personalised treatment strategies and lead to better long-term outcomes for individuals with FEP.

ObjectiveTo analyze the structure of mental disorders in children in the outpatient practice of a specialized mental health center for optimization of care organization for this patient category. MethodsA retrospective analysis of medical records of 23 children (out of 44 patients) at the Insight Mental Health Center (Dushanbe, Tajikistan) was conducted for the period from December 9, 2025, to January 8, 2026. Diagnosis was performed according to ICD-10 criteria using standardized instruments: M-CHAT-R, ADOS-2, and ADI-R for autism spectrum disorder (ASD); SNAP-IV for attention deficit hyperactivity disorder (ADHD); CGI; and pediatric versions of PHQ and GAD. ResultsChildren accounted for 52% of all patients. Primary school-age children (7-12 years) predominated at 43.5%. Disorders of psychological development (F80-F89) dominated the nosological structure at 82.6%, with ASD comprising 56.5%. ADHD was diagnosed in 30.4% of cases. Comorbidity was registered in 47.7% of patients. ConclusionThe structure of pediatric psychiatric pathology is characterized by a predominance of developmental disorders and high comorbidity levels, justifying the need for a multidisciplinary approach.

The COVID-19 pandemic had substantial impact on healthcare systems across the globe, including psychiatric services. Use of electroconvulsive therapy (ECT), a lifesaving intervention for severe mental illness, was reported to have declined during the pandemic in several countries, but nationwide data remain scarce. Using nationwide data from the Danish National Patient Register, we examined all ECT treatments administered in Denmark from September 2019 to May 2025. Weekly treatment numbers were visualized across the three national COVID-19 lockdowns to descriptively assess changes in ECT use. A notable reduction in ECT treatments was observed in the weeks preceding and during the first lockdown (March 11 to May 18, 2020). A post-hoc estimation indicated approximately 1,366 "missed" treatments during the initial pandemic phase in 2020. When these were added to the 27,033 treatments delivered in 2020, the adjusted total approximated annual treatment volumes in 2019 and 2022, suggesting a temporary disruption rather than sustained decline. In contrast, ECT activity during the second and third lockdowns appeared largely unaffected. These findings suggest that ECT provision in Denmark was temporarily reduced during the initial phase of the pandemic but remained resilient thereafter. In the case of a future pandemic, safeguarding timely access to ECT--particularly in early phases-- should be prioritized given its critical role in the treatment of severe mental illness.

Background Complementary and Alternative Medicine (CAM) contributes significantly to the utilization of healthcare services in mental health care in sub-Saharan Africa. However, there is limited evidence on the utilization of CAM in the particular setting of post-conflict northern Uganda. This study sought to establish the prevalence, forms, and socio-demographic determinants of CAM use among patients attending the Mental Health Unit at Gulu Regional Referral Hospital (GRRH). Methods This is a cross-sectional study conducted in a hospital setting from June to August 2025. Convenience sampling was employed to recruit 407 participants. A structured questionnaire was employed for data collection. Data analysis was done using STATA software version 18.0. Descriptive statistics were calculated, and bivariate analysis with Prevalence Ratios (PR) with 95% confidence intervals was employed to determine factors that are significantly associated with the use of CAM. Results The lifetime prevalence of CAM use was 63.4% (258/407), with 41.3% (168/407) using CAM currently. The most frequent CAM practices used were herbal medicine (50.4%), spiritual practices (33.7%), and traditional medicine (19.8%). For current users, spiritual practices were most frequent (88.7%). The reasons for using CAM were recommendations from others (84.8%) and cultural or religious beliefs (63.4%). Predictors of CAM use were primary education (PR = 1.36, p = 0.017), living in an urban area (PR = 1.23, p = 0.007), separated (PR = 1.39, p = 0.050), and having a mental health disorder for six or more months (PR range = 1.55-1.72). Catholics (PR = 0.72, p = 0.0007) and Protestants (PR = 0.76, p = 0.011) were less likely to use CAM than Born Again Christians. Conclusion The level of CAM use among patients accessing mental health services in GRRH of northern Uganda is significantly high, while the reporting of CAM use to healthcare providers is remarkably low. This is a challenge that requires urgent attention. Recommendations include integrating the use of CAM into medical practice, developing national policy guidelines on CAM, working in collaboration with traditional/spiritual healers, and conducting public education campaigns.

Major depressive disorder (MDD) involves dysregulated neuroimmune, metabolic, and oxidative stress (NIMETOX) pathways. Recently, it was shown that NIMETOX pathways should be evaluated in MDD patients stratified for metabolic syndrome (MetS). The current study aims to characterize the metabolic hormone and adipokine profiles of Chinese MDD patients stratified for MetS and to delineate their associations with overall severity of depression (OSOD), suicidal ideation (SI), recurrence of illness (ROI), and physiosomatic symptoms. We enrolled 125 MDD inpatients and 40 healthy controls and measured fasting serum insulin, glucose, glucagon, Glucose-dependent Insulinotropic Polypeptide (GIP), Glucagon-Like Peptide-1 (GLP-1), leptin, secretin, Plasminogen Activator Inhibitor-1 (PAI-1), resistin, ghrelin, and adiponectin, as well as the acute-phase inflammatory (API) response using albumin, transferrin (Tf), and monomeric CRP (mCRP). The results revealed a distinct metabolic hormone and adipokine signature in MDD with significantly lower insulin, glucagon, and PAI-1 levels, alongside an elevated API index (after adjusting for age, MetS, and body mass index). A composite GAP index (ghrelin, adiponectin, PAI-1) correlated negatively with OSOD, SI, ROI, physiosomatic symptoms, and adverse childhood experiences (ACEs). Integrative modeling combining the GAP index, API index, and ACEs achieved an area under the receiver operating characteristic (ROC) curve of 0.864 with an accuracy of 80% for discriminating MDD from controls. In conclusion, the findings delineated that many inpatients with severe MDD suffer from suppressed anabolic hormones and lower adipokine levels coupled with a mild, chronic inflammatory response. The deviations in this "hormonal-immune-metabolic" axis are components of the NIMETOX pathways in MDD and are not associated with MetS.

Numerous studies have shown that adults with depression have distinct oculomotor alterations during saccade tasks, but whether similar alterations occur in adolescents is largely unknown. The purpose of this study was to test if eye-tracking during a structured saccade task could distinguish a group of adolescents with depression from healthy controls. We hypothesized that, due to overlapping circuitry between depression pathology and the oculomotor system, adolescents with depression would show alterations in fixation, saccade, and pupil behaviour. 51 adolescents with depression and 66 age-matched healthy controls completed the Interleaved Pro- and Anti-Saccade Task (IPAST) and several self-reported questionnaires for psychiatric symptoms. Oculomotor outcomes included fixation acquisition, fixation breaks, correct rate, saccadic reaction time, rate of correct express-latency pro-saccades, rate of express- and regular-latency anti-saccade errors, baseline pupil size, as well as pupil constriction and dilation sizes following task instruction. In comparison to healthy controls, adolescents with depression displayed impairments acquiring fixation (p<.001), made more fixation breaks in pro- (p=.023) and anti-saccade trials (p=.005), more anti-saccade errors (p=.013), more express-latency saccades overall (ps=.016), had a smaller pupil constriction in pro-saccade trials (p=.047) and had a smaller pupil dilation in pro- (p=.011) and anti-saccade trials (p=.041). No differences were found for saccadic reaction time, rate of correct pro-saccades, rate of regular-latency anti-saccade errors, pupil constriction size during anti-saccade trials, or baseline pupil size. Patients had psychiatric comorbidities and were using psychotropic medication. While this reflected clinical reality, these factors may have influenced oculomotor behaviour. Adolescents with depression had altered fixation, saccade, and pupil behaviour during IPAST. Given that many cases of adolescent depression remain undetected, accessible and objective screening approaches are highly needed. This oculomotor phenotype may be used in the development of such a screening tool to detect those at risk.

ObjectivesElectroconvulsive Therapy (ECT) is an effective treatment for bipolar disorder, particularly in severe acute cases or for illness resistant to pharmacotherapy. However, the risk of relapse following ECT is high, necessitating intervention to reduce this risk. Based on findings from ECT studies in unipolar depression and its well-known mood-stabilizing properties, it is likely that lithium treatment may reduce the risk of relapse of bipolar disorder following ECT. Therefore, we conducted a target trial emulation using data from Danish nationwide registers to investigate whether lithium protects against relapse following ECT treatment of bipolar disorder. MethodsPatients discharged from their first psychiatric admission with a primary diagnosis of bipolar disorder between January 1, 2006, and June 1, 2024, who received at least six ECT treatments, were included. Follow-up began two weeks after discharge and continued until relapse, death, one year, or January 1, 2025. Patients were considered allocated to lithium treatment if they redeemed a prescription for lithium within the first two weeks after discharge from the index admission (ECT treatment). The outcome was time to relapse, defined by either psychiatric hospital admission or suicide. Cox proportional hazards regression, adjusted for potential confounders, was used to compare the outcome between patients allocated and not allocated to lithium treatment. ResultsAmong the 574 eligible patients (mean age 41.5 years, 61.3% women), 214 (37.3%) were allocated to lithium treatment and 360 (62.7%) were not allocated to lithium treatment. During follow-up, 56 patients (26.2%) in the lithium group and 135 patients (37.5%) in the non-lithium group experienced a relapse. Lithium treatment was associated with a substantially reduced risk of relapse (adjusted hazard rate ratio, 0.60, 95% CI=0.43-0.84). ConclusionLithium treatment after ECT may reduce the risk of relapse in patients with bipolar disorder. These findings should be followed up by a randomized controlled trial.

Background: Depression is associated with an increased risk of subsequent Parkinson's disease. Neuroimaging studies suggest a neurobiological overlap in mechanisms underlying Parkinson's disease and psychomotor retardation in depression. Our aim was to investigate whether, among individuals with depression, the presence of psychomotor retardation was associated with the development of subsequent Parkinson's disease. Methods: In a retrospective cohort study, electronic healthcare records from individuals diagnosed with depression at age 40 or over in a large mental health service in London, UK were examined for the presence of psychomotor retardation. Linkage to general hospital records was used to ascertain diagnoses of Parkinson's disease between 2007 and 2023. Cox regression was used to compare the hazard of Parkinson's disease in individuals with depression with and without psychomotor retardation. Results: Among 6327 patients with depression, 2402 (38.0%) had psychomotor retardation. The adjusted hazard ratio for development of Parkinson's in those with psychomotor retardation was 1.43 (95% CI 1.02 - 2.01, p = 0.04). Secondary analyses demonstrated a significant difference in psychomotor retardation incidence at least 10 years before Parkinson's diagnosis. Conclusions: Psychomotor retardation in later-life depression is associated with increased risk of subsequent Parkinson's diagnosis over an extended period of time, suggesting that the relationship cannot solely be explained by misdiagnosis. Psychomotor retardation may therefore serve as a marker of prodromal Parkinson's disease.

Objective: Major depressive episodes frequently show limited response to first-line treatments, motivating the search for objective biomarkers. EEG/ECG-based support tools aggregating electrophysiological predictors may guide treatment selection. We examined whether antidepressant treatments concordant with an EEG/ECG-biomarker report were associated with higher response rates. Methods: We retrospectively analyzed adults with ICD-10 depressive disorder or bipolar depression treated with electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), (es)ketamine, or selective serotonin reuptake inhibitors (SSRIs) between 2022 and 2024. Resting-state EEG with simultaneous ECG generated individualized biomarker reports with modality-specific response likelihoods. Treatment chosen by clinical teams was classified as concordant or non-concordant; response was derived from routinely collected clinical scales. Results: Among 153 patients (ECT n=53, rTMS n=48, (es)ketamine n=36, SSRIs n=16), response rates were higher for concordant vs non-concordant treatments: ECT 70% vs 50%, rTMS 30% vs 13%, (es)ketamine 31% vs 10%, and SSRIs 100% vs 11%. Overall, 46% (42/92) of concordant vs. 26% (14/54) of non-concordant patients responded (absolute difference +20 percentage points; relative increase {approx}77%; number needed to treat {approx}5). Conclusion: Concordance with EEG/ECG biomarkers correlated with higher treatment response, warranting confirmation in prospective trials. Significance: EEG/ECG-based decision support may enhance antidepressant treatment response in everyday clinical practice.

ObjectiveTo characterize the familial patterns of misophonia and other commonly co-occurring neuropsychiatric conditions. MethodsWe examined cross-sectional survey responses from 101 probands with misophonia and their biological parents enrolled in a genetics study. ResultsProbands had a mean age of 24.6 {+/-} 11.6 years (8-64 years), were predominantly female (88%), and had high rates of co-occurring neuropsychiatric conditions, including anxiety (70%), depression (38%), ADHD (31%), and OCD (25%). Among probands, 39% had a first-degree relative with misophonia, and 48% had at least one any-degree relative with misophonia. In addition, many probands had at least one first-degree relative with anxiety (65%), depression (57%), ADHD (40%), OCD (20%), and autism (13%). Comparing rates of neuropsychiatric conditions reported by parents, mothers had significantly higher rates of misophonia (29% maternal vs. 9% paternal, p = 0.001) and anxiety (44% maternal vs. 26% paternal, p = 0.02) than fathers. ConclusionThese findings provide new insight into the familial patterns of misophonia and co-occurring neuropsychiatric conditions. Future research on underlying genetic and environmental factors is needed to shed light on the observed shared predispositions for misophonia and other neuropsychiatric conditions in families.

Background and HypothesisSchizophrenia is a disease characterized by various symptoms and has severe lifelong impacts on patients and their families. Despite various hypotheses and associated studies, the key mechanism in schizophrenia is not fully elucidated. In the present study, we focused on adropin, a peptide regulating energy metabolism, antioxidation, and neuroprotection. Study DesignIn both the group of healthy volunteers (HV) and the group of patients with some schizophrenia spectrum and other psychotic disorders (SZ), we evaluated adropin along with other variables such as anthropological factors, psychological well-being indicators, and laboratory test results. Study ResultsThe adropin levels in SZ were not significantly different from those in HV. Correlation analysis indicated five significant correlations beyond various natural correlations arising from fundamental proportional relationships and multifaceted psychological well-being indicators: (1) adropin versus right handgrip strength in the SZ group ({tau} = -0.82, P = 0.066); (2) adropin versus selenium in the total group ({tau} = 0.44, P = 0.053); (3) ferritin versus perceived stress in the total group ({tau} = -0.44, P = 0.053); (4) right versus left handgrip strength in the total group ({tau} = 0.70, P = 0.001) and in the SZ group ({tau} = 0.82, P = 0.075); and (5) selenium versus state anxiety in the total group ({tau} = 0.44, P = 0.053) and the SZ group ({tau} = 0.84, P = 0.066). ConclusionsThe present study provides a foundation for future studies and sheds light on the role of adropin in schizophrenia.

BackgroundMajor depressive disorder (MDD), a leading cause of disability worldwide, exhibits substantial heterogeneity in treatment outcomes. Patients who do not respond to standard antidepressant therapy account for the majority of MDDs disease burden. Risk factors have been implicated in treatment response, including genes impacting on how antidepressants are metabolised. Yet, despite its clinical importance, risk factors for treatment-resistant depression (TRD) remain unexplored in low- and middle-income countries (LMIC). We used data from the DIVERGE study on MDD to investigate the risk factors of TRD in Pakistan. MethodsDIVERGE is a genetic epidemiological study that recruited adult MDD patients ([&ge;]18 years) between Sep 27,2021 to Jun 30, 2025, from psychiatric care facilities across Pakistan. Detailed phenotypic information was collected by trained interviewers and blood samples taken. Infinium Global Diversity Array with Enhanced PGx-8 from Illumina was used for genotyping followed by DRAGEN calling to infer metaboliser phenotypes for Cytochrome P450 (CYP) enzyme genes. We defined TRD as minimal to no improvement after [&ge;]12 weeks of adherent antidepressant therapy. We conducted multi-level logistic regression to test the association of demographic, clinical and pharmacogenetic variables with TRD. FindingsAmong 3,677 eligible patients, polypharmacy was rampant; 86% were prescribed another psychotropic drug along with an antidepressant. Psychological therapies were uncommon (6%) while 49% of patients had previously visited to a religious leader/faith healer in relation to their mental health problems. TRD was experienced by 34% (95%CI: 32-36%) patients. The TRD group was characterised by more psychotic symptoms and suicidal behaviour (OR=1.39, 95%CI=1.04-1.84, p=0.02; OR=1.03, 95%CI=1.01-1.05, p=0.005). Social support (OR=0.55, 95%CI=0.44-0.69, p=1.4x10-7) and parents being first cousins (OR=0.81, 95%CI=0.69-0.96, p=0.01) were associated with lower odds of TRD. In 1,085 patients with CYP enzyme data, poor (OR=1.85, 95%CI=1.11-3.07, p=0.01) and ultra-rapid (OR=3.11, 95%CI=1.59-6.12, p=0.0009) metabolizers for CYP2C19 had increased risk of TRD compared with normal metabolisers. InterpretationThere was an excessive use of polypharmacy in the treatment of depression while psychological therapies were uncommon highlighting the need for more evidence-based practice. This first large study of MDD from Pakistan uncovered the importance of culture-specific forms of social support in preventing TRD, highlighting opportunities for interventions in low-income settings. Pharmacogenetic markers can be leveraged to predict TRD.

BackgroundAntenatal depressive symptoms (ADS) are common and underdiagnosed, particularly in low- and middle-income countries, and are associated with adverse maternal and offspring outcomes. Current screening relies on subjective symptom reporting, limiting early identification and prevention. Epigenetic modifications, particularly DNA methylation, offer a promising avenue for objective, early biomarkers of depression risk during pregnancy. MethodsIn this nested case-control design within the STRiDE (Stratification of Risk of Diabetes in Early Pregnancy study) prospective cohort, 189 pregnant women with no depressive symptoms in early pregnancy (<16 weeks of gestation. PHQ-9 [&le;]4) were followed longitudinally. 89 ADS individuals were identified by the emergence of depressive symptoms at 24-28 weeks of gestation (PHQ-9 [&ge;]5), while 100 women remained symptom-free (Controls). Genome-wide DNA methylation profiling of early-pregnancy peripheral blood was performed using the Illumina EPIC 850K array. Epigenome-wide association analyses were combined with machine-learning approaches to identify predictive CpG panels. Model robustness was assessed using bootstrap validation, and a methylation risk score (MRS) was constructed. Functional enrichment analyses were conducted to explore biological pathways. ResultsEpigenome-wide analysis identified 2,447 differentially methylated positions associated with subsequent ADS. A robust panel of 10 CpGs in early pregnancy predicted later ADS with excellent performance (testing AUC=0.99. bootstrap-validated AUC=0.91), independent of maternal risk factors. The MRS markedly outperformed traditional clinical predictors (AUC=0.94) and further improved prediction when combined with maternal characteristics (AUC=0.95). ADS-associated methylation changes were enriched in neurodevelopmental, synaptic, immune, and metabolic signaling pathways. Limited concordance with placental methylation suggested maternal-specific epigenetic regulation. ConclusionsEarly-pregnancy DNA methylation signatures can predict antenatal depressive symptoms before clinical onset. This blood-based 10-CpG biomarker panel offers a biologically informed and objective tool for early risk stratification, with the potential to enable preventive interventions and enhance perinatal mental health care, particularly in resource-constrained settings.