Schizophrenia is a disorder characterized by significant motivational deficits, including anhedonia, that impair daily functioning. Approach and avoidance behaviors are regulated by two basic motivation systems: the Behavioral Inhibition System (BIS) and the Behavioral Activation System (BAS). Based on Gray's Reinforcement Sensitivity Theory, this study examined the relationships among BIS/BAS activity, depressive symptoms, and anhedonia in individuals with schizophrenia compared to healthy controls. Sixty-one patients with schizophrenia (SZ) and 62 healthy participants participated in the study. Positive and Negative Syndrome Scale, Beck Depression Inventory, Calgary Depression Scale, BIS/BAS Scale, and physical, social, and chemosensory anhedonia scales were administered to the participants. This cross-sectional, between-groups study compared SZ and healthy controls to examine the associations among BIS/BAS activity, depressive symptoms, and anhedonia. T-test, Logistic regression, and regression analyses were performed. Logistic regression analyses determined that BAS activity and anhedonia significantly predicted being in the patient group. It revealed motivational deficits in schizophrenia compared to healthy subjects. Patients with schizophrenia showed reduced BAS activity associated with impaired reward sensitivity and goal-directed behavior. However, no differences in BIS activity were found. While BAS activity and depressive symptoms were found to be predictors of all subscales of anhedonia in healthy controls, they were only found to be predictive of physical anhedonia in schizophrenia. These results suggest that anhedonia in SZ results from deficits in anticipatory pleasure and reward processing, independent of mood-related mechanisms. It suggests that different mechanisms may underlie anhedonia. Future studies should investigate BAS dysregulation in SZ, including cognitive-behavioral therapies and pharmacological strategies that target dopaminergic pathways.

This diagnostic test accuracy meta-analysis aimed to provide clinically interpretable estimates (sensitivity, specificity, likelihood ratios (LR), predictive value (PV) and post‑test probabilities) for machine‑learning (ML) models predicting suicide‑related outcomes. A systematic search of PubMed, Embase, PsycINFO, and Web of Science identified studies published between January 2010 and December 2024. Eligible studies used a single-gate design (cross-sectional or longitudinal), included at least 100 participants, and reported diagnostic performance metrics (e.g., sensitivity, specificity, area under the receiver operating curve (AUC)) for ML algorithms. Models examined included Support Vector Machines (SVM), Logistic Regression, Random Forest, XGBoost, Artificial Neural Networks (ANN), Gradient Boosting, and Ensemble approaches. Two reviewers independently extracted data. Pooled estimates of sensitivity, specificity, PPV, NPV, and AUC were calculated using a bivariate random-effects model. Risk of bias was assessed using QUADAS-2. Of 500 screened records, 22 studies met inclusion criteria. Ensemble models demonstrated the highest pooled AUC (0.95; 95% CI, 0.92-0.96), with specificity of 0.97 (95% CI, 0.95-0.98) and sensitivity of 0.50 (95% CI, 0.29-0.71). Gradient-boosting and ensemble approaches showed strong discriminative performance overall; model-specific estimates are reported in the Results. At a pre-test probability of 25%, post-test probabilities for a positive result ranged from 64% (Logistic Regression) to 88% (Ensemble Models). Machine-learning approaches demonstrated promising diagnostic accuracy for suicide-related outcomes in heterogeneous clinical populations. However, because primary studies rarely reported diagnosis- or outcome-specific performance, these findings should not be assumed to generalize across specific disorders or to suicide mortality. Future research should incorporate diagnosis-stratified and outcome-resolved validation to clarify clinical applicability.

Melatonin, a key regulator of circadian rhythms and sleep-wake cycles, is implicated in the pathophysiology of major depressive disorder (MDD). Emerging evidence supports its anti-inflammatory, cytoprotective, and neuroprotective roles, including promotion of neuroplasticity. This study aims to investigate alterations in serum melatonin, interleukin-6 (IL-6), and brain-derived neurotrophic factor (BDNF) levels in first-episode MDD patients, and explores their clinical correlations. A total of 74 first-episode patients diagnosed with MDD and 72 healthy controls were enrolled in this study. The severity of depressive symptoms was assessed using the 24-item Hamilton Depression Rating Scale (HAMD-24). All blood samples were collected in the morning, and serum levels of melatonin, IL-6, and BDNF were quantified via enzyme-linked immunosorbent assay (ELISA). Baseline serum concentrations of melatonin, IL-6, and BDNF were compared between the MDD group and the control group. Additionally, the discriminative ability of these biomarkers (melatonin, IL-6, and BDNF) in distinguishing MDD patients from healthy controls was evaluated using receiver operating characteristic (ROC) curve analysis. Pearson correlation analysis or Spearman's rank correlation analysis was performed to explore the relationships between serum melatonin levels and clinical disease severity, as well as with IL-6 and BDNF levels, in patients with MDD. Compared with the control group, the MDD group showed significantly higher serum levels of melatonin (Z = -3.861, P < 0.001) and IL-6 (Z = -4.240, P < 0.001), but significantly lower serum BDNF levels (t = 9.537, P < 0.001). Moreover, the combined panel of BDNF, IL-6, and melatonin achieved high accuracy in distinguishing MDD patients from healthy controls, with an area under the curve (AUC) of 0.905. Additionally, no significant correlations were found between serum melatonin levels and clinical disease severity (assessed by HAMD-24 scores), IL-6 levels, or BDNF levels in MDD patients (all P > 0.05). These findings suggest that dysregulation of melatonin, IL-6, and BDNF may contribute to the pathophysiology of first-episode MDD, with their combined measurement offering strong diagnostic potential.

Research suggests that lipid levels may be associated with suicide risk. However, the specific relationship between Apolipoprotein B and suicidal ideation remains unclear. The aim of this study was to investigate the association between ApoB levels and suicidal ideation and to further explore the causal relationship using Mendelian randomization. A cross-sectional study of 6520 U.S. adults was conducted using the 2011-2016 National Health and Nutrition Examination Survey (NHANES) dataset. Multiple logistic regression, smoothed curve fitting, stratified analyses, and interaction tests were used to reveal the relationship between ApoB levels and suicidal ideation. MR analyses were conducted using inverse variance weighting (IVW), GSMR, Maximum likelihood method, and cML-MA-BIC MR method. Sensitivity analyses included MR-Egger intercept test, MR-PRESSO global test, and leave-one-out (LOO) analysis. Multivariate logistic regression analysis showed that serum ApoB levels were positively associated with suicidal ideation, and the association remained significant even after multiple covariates (P = 0.0463). Subgroup analyses showed that the risk of suicidal ideation was significantly increased in the highest tertile (T3) of the population compared to the lowest tertile (T1) of ApoB levels (OR = 1.48, 95% CI: 1.04-2.12, P = 0.0312). In addition, the association between ApoB and suicidal ideation was more significant in the smoking subgroup (P interaction = 0.034). However, MR analysis failed to confirm a significant causal effect of ApoB levels on suicidal ideation (P > 0.05), and these results were robust to sensitivity analyses. The present study found a significant positive association between serum ApoB levels and suicidal ideation, especially among smokers. MR analysis failed to provide causal evidence of ApoB on suicidal ideation. More research is needed to clarify the potential role of ApoB in the development of suicidal ideation.

Medication adherence among patients with psychiatric disorders is a significant challenge that often leads to poor clinical outcomes. Although pharmacist-led interventions have demonstrated the potential to improve medication adherence, evidence remains limited, particularly in patients treated with antipsychotics. This study aimed to evaluate the effectiveness of a brief pharmacist-led interventionin enhancing medication adherence among outpatients receiving antipsychotic therapy. This exploratory, prospective, single-arm study was conducted at a community pharmacy in Japan. Fifty outpatients prescribed antipsychotic medications participated in the study. A brief pharmacist-led intervention was delivered focusing on identifying and addressing barriers to adherence. The primary outcomes were changes in Drug Attitude Inventory-10 (DAI-10) scores and the proportion of participants with unused medications. Participants taking preexisting medications exhibited a significant improvement in DAI-10 scores (mean increase, + 2.05 points; from 5.81 ± 4.00 to 7.86 ± 2.90, p = 0.00619). The proportion of participants who reported non-adherence to medication regimens decreased significantly from 42% to 24% (p= 0.0159). The brief pharmacist-led intervention was effective in improving attitudes toward medication and behavioral adherence among patients receiving antipsychotic treatment in our study group. These findings underscore the importance of active pharmacist engagement for supporting medication adherence.

Major depressive disorder (MDD) pathogenesis is associated with immune-inflammatory dysregulation. This study investigated the mechanistic role of caspase-1-mediated inflammatory pathways in MDD, exploring their therapeutic targeting potential and clinical predictive utility. Peripheral blood levels of caspase-1, IL-1β, and IL-10 were assessed in MDD patients, with longitudinal analysis of dynamic changes pre-/ post-antidepressant treatment. The predictive performance of the biomarker was validated using leave-one-out cross-validation (LOOCV) and receiver operating characteristic (ROC) analysis. A chronic unpredictable stress (CUS) rat model was established to evaluate the combined therapeutic effects of caspase-1 inhibitors with fluoxetine. Clinical data revealed that expression levels of caspase-1 and IL-1β exhibited an negative correlation with clinical treatment response in patients with MDD, with varying levels observed among patients with differing depression severity. In contrast, IL-10 expression demonstrated a positive correlation with therapeutic efficacy. Following treatment, significant reductions in caspase-1 and IL-1β levels were observed, concurrent with an elevation in IL-10. Caspase-1 demonstrated superior predictive accuracy for treatment response (0.8529 ± 0.3542), yielding an area under the ROC curve (AUC) of 0.72. In animal models, co-administration of a caspase-1 inhibitor with fluoxetine accelerated the onset of antidepressant effects, while simultaneously reducing peripheral blood caspase-1 and IL-1β levels. The caspase-1/IL-1β axis contributes to MDD pathogenesis by disrupting the pro-inflammatory/anti-inflammatory balance. Its mediated immune response pattern represents a potential therapeutic target for novel antidepressant development. Combined caspase-1 modeling provides a reliable tool for predicting clinical efficacy in MDD, while caspase-1-targeted intervention strategies may overcome the limitation of slow onset of action associated with conventional therapies.

BackgroundThe antidepressant vortioxetine is available as an immediate-release (IR) tablet formulation and as a bioequivalent oral drops solution (20 mg/mL) to allow personalised titration.MethodsThis pharmacokinetic modelling analysis used data from a single-dose, crossover study to simulate the time taken to reach steady-state plasma concentrations using ‘low and slow’ titration approaches with drops compared with standard IR-tablet schedules.ResultsAll dosing regimens approached 10 mg steady-state concentrations within 2 weeks. The time to reach full steady-state was 12 days when starting with a 10 mg IR-tablet, 14 days when starting with 5 mg drops and increasing to 10 mg (1 mg/day increments), 17 days when starting with a 5 mg IR-tablet for 7 days before increasing to 10 mg, and 18 days when starting with 1 mg drops and increasing to 10 mg (1 mg/day increments).ConclusionsThese data support the utility of vortioxetine drops in offering flexibility for personalised titration without relevant impact on the time taken to reach steady-state plasma concentrations.

Somatic symptoms are physical symptoms that often arise in response to emotional distress and can significantly impact well-being. Understanding the prevalence and interplay of these symptoms with anxiety and depression is crucial for understanding adolescent health outcomes in Singapore. This study aimed to determine the prevalence of somatic symptoms among adolescents in Singapore and examine their associations with demographic characteristics, life stressors, anxiety, and depression. We conducted a cross-sectional online survey with 601 Singaporean adolescents aged 12 to 19, using the Patient Health Questionnaire Somatic, Anxiety, and Depressive Symptoms Scales (PHQ-SADS) to assess somatic symptoms, anxiety, and depression levels. Demographic information and experiences with stressful life events were also collected. Both descriptive and regression analyses were used to understand the relationships between participants' sociodemographic factors, mental health symptoms, and the presence of somatic symptoms. 32.3% of the adolescents reported clinically significant levels of somatic symptoms, with a higher prevalence observed among those who were females and older. While no significant associations were found between somatic symptoms and demographic factors, adolescents with anxiety or depressive symptoms presented significantly increased odds of reporting somatic symptoms. Specifically, the odds of reporting somatic symptoms were 2.91 times greater for those with anxiety (95%CI: 1.55-5.45, p < 0.001) and 6.54 times greater for those with depression (95%CI: 3.75-11.6, p < 0.001) than for those without these mental health concerns. Furthermore, those with somatic symptoms reported a greater number of stressful life events, with academic pressure emerging as the most prominent stressor. This study highlights the prevalence of somatic symptoms among adolescents in Singapore, emphasising the interconnectedness of mental and physical health during this developmental stage. The strong associations between somatic symptoms, anxiety, depression, and life stressors underscore the need for a holistic approach to adolescent healthcare. Early identification and intervention strategies should focus on addressing mental health concerns, building resilience against stressors, and promoting healthy coping mechanisms to mitigate the burden of somatic symptoms and foster overall well-being in Singaporean adolescents.

BackgroundThe study aimed to assess the incidence of lithium-induced hypothyroidism and its associated factors in psychiatric outpatients on long-term lithium therapy.MethodsA retrospective study at Songklanagarind Hospital (January 1, 2013, to September 30, 2022) focused on clinical (overt) and subclinical forms of lithium-induced hypothyroidism. Subclinical hypothyroidism, characterised by elevated thyroid stimulating hormone (TSH) but normal thyroxine (FT4) levels, and clinical hypothyroidism, by low FT4 and high TSH, were analysed. Patients with less than 3 months of lithium therapy or prior thyroid conditions were excluded. We used survival analysis and logistic regression to investigate incidence and factors.ResultsAmong 461 on lithium maintenance therapy, 279 outpatients met the inclusion criteria; however, only 166 (59%) were monitored for thyroid functions during the study period and included in the final analyses, mostly female (53.6%) with bipolar disorder (72.9%), median age 42.0 years. The median duration of maintenance therapy was 3.7 years (IQR = 1.0-9.3). Over a decade, 30 patients developed lithium-induced hypothyroidism, primarily subclinical (28 cases), at an incidence rate of 0.0212 cases per patient-year. Hypothyroidism manifested after 14.4 months of lithium therapy (IQR = 5.2–53.2), with a prominent decline of survival curve within the first year. Younger age (adjusted OR = 0.95, P = 0.001), presence of physical comorbidities (adjusted OR = 2.69, P = 0.039), and higher lithium levels (P = 0.003) were associated with hypothyroidism.ConclusionsDespite low incidence, regular thyroid monitoring is advised for patients on lithium. The study identifies risk factors for lithium-induced hypothyroidism, aiding in patient risk assessment and monitoring protocols.

BackgroundPolycystic ovarian syndrome (PCOS) is a common and increasingly prevalent reproductive and metabolic endocrine disorder that is characterized by metabolic alterations, hyperandrogenism, menstrual irregularities as well as an increased risk of depression. Available evidence suggests PCOS may also be associated with disparate aspects of suicidality. Herein, we sought to determine the prevalence of suicidal ideation, suicidal behaviours and completed suicide in the PCOS population.MethodsWe systematically searched PubMed, Ovid and Scopus databases from inception to January 7, 2024. A manual search was conducted on Google Scholar. Two reviewers independently screened the retrieved studies against the eligibility criteria (S.W. and G.H.L.). Human studies investigating suicide outcomes in women of reproductive age with a confirmed diagnosis of PCOS were included.ResultsEleven studies meeting our eligibility criteria were included. Although results were mixed, available evidence suggests that persons with PCOS are at an increased risk of suicidal ideation, self-harm and suicide attempts and are also differentially affected by psychiatric comorbidities (e.g., depressive disorders). Notwithstanding, suicide risk was not fully accounted for by the presence of mental illness, which suggests that PCOS may also be contributory.ConclusionPCOS is associated with an increased risk of suicidal ideation and behaviour and associated psychiatric comorbidities. Persons with PCOS should be routinely evaluated for the presence of clinically significant suicidality. Whether increased suicidality in PCOS populations is a direct effect of the disease state and/or is largely moderated by psychiatric comorbidity is a future research vista.