Acta Neuropsychiatrica

BackgroundTourette syndrome is a childhood-onset neuropsychiatric disorder characterised by recurrent motor and vocal tics. It shows a marked male predominance and is frequently associated with comorbid conditions such as attention-deficit/hyperactivity disorder (ADHD) and obsessive- compulsive disorder (OCD). Histaminergic dysregulation in the brain has been proposed as one of the mechanisms underlying Tourette syndrome. Vitamin B6, a key cofactor in histamine metabolism, may therefore play a contributory role in its pathophysiology. MethodThe clinical features of 25 children diagnosed with Tourette syndrome were assessed using the Yale Global Tic Severity Scale. Plasma vitamin B6 levels were measured using enzyme-linked immunosorbent assay (ELISA) and compared with those of a control group. ResultMost participants were males, and 16% had comorbid ADHD or OCD. The most common motor tics were eye blinking, shoulder shrugging, head jerking, and orofacial movements. Frequent vocal tics included throat clearing, sniffing, uttering syllables, and breathing-related tics. Coprolalia was observed in four children. The median plasma vitamin B6 level in the Tourette syndrome group was 25.01ng/ml, which was significantly lower than the 36.33ng/ml in the control group (Mann-Whitney U = 225, p = 0.03). The rank-biserial correlation indicated a moderate effect size (r = 0.35). ConclusionTourette syndrome in children predominantly affects males and is commonly associated with ADHD and OCD. Coprolalia-a clinically distressing symptom - was present only in a small subgroup. The lower plasma vitamin B6 levels observed in children with Tourette syndrome suggest a possible role for vitamin B6 in disease pathogenesis, potentially through its involvement in histaminergic and GABAergic neurotransmission, as well as in the modulation of neuroinflammatory processes.

IntroductionSickle cell disease is a chronic hematologic disorder associated with significant physical and psychological challenges, including depression. Children with SCD experience recurrent pain crises, hospitalizations, and social limitations, which can contribute to mental health issues. This study aimed to determine the prevalence of depression and associated factors among school-age children with SCD at Jinja Regional Referral Hospital (JRRH), Eastern Uganda. MethodsA cross-sectional study was conducted among 200 randomly selected children aged 6-12 years receiving care at JRRH. Depression was assessed using the Childrens Depression Inventory (CDI). We assessed the association between depression and several factors including sociodemographic characteristics, clinical factors and health related quality of life. Multivariate logistic regression was used to identify factors that were statistically significantly associated with depression at a 95% confidence interval. ResultsMajority of the participants 55.5% (111/200) were female, 49.5% (99/200) were in pre-primary with a mean age of 6.7 (SD{+/-}1.4) years -The prevalence of depression among children with SCD was 43% (95% CI= 40-46%). Among these, 27.9% had mild depression, 58.1% had moderate depression, and 14.0% had severe depression. Factors significantly associated with depression included lack of assured income among caregivers (AOR=3.67, 95% CI=1.35-7.56, p=0.001), having more than one sibling with SCD (AOR=2.54, 95% CI=1.45-4.72, p=0.02), frequent hospital admissions (AOR=2.12, 95% CI=1.56-4.39, p=0.01), and frequent pain crises (AOR=2.10, 95% CI=1.56-4.67, p<0.001). ConclusionDepression is prevalent among children with SCD at JRRH, with socio-economic status of the caregiver, number of siblings with SCD, health facility admission frequency and frequent pain crises playing significant roles. Improving access to financial and social support for caregivers and ensuring adequate pain management are recommended.

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).

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.

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.

BackgroundGlaucoma is identified as one of the leading causes of blindness worldwide. Its chronic nature and the potential for irreversible vision loss contribute to significant distress among affected individuals. Around 25% of individuals with glaucoma are estimated to experience depression, negatively impacting their quality of life and treatment adherence. However, data on the prevalence of depression among people with glaucoma in Tanzania is limited. This study aimed to determine the prevalence and factors associated with depressive symptoms among adults with glaucoma at Muhimbili National Hospital. Materials and methodsA cross-sectional study was conducted involving 297 adults with glaucoma, who were recruited consecutively from the ophthalmology clinic at Muhimbili National Hospital between July and November 2024. Data on biopsychosocial factors were collected using interviewer-administered questionnaires and medical records. Patient Health Questionnaire-9 and Oslo Social Support Scale assessed depressive symptoms and social support, respectively. Data were analyzed using STATA version 16. Logistic regression analyses identified factors associated with probable depression, with statistical significance set at p-value<0.05. ResultsThe mean age of participants was 63.6 years (SD{+/-}12.8), with 159 (53.5%) being female. Prevalence of probable depression was 11.1%, with 8.7% moderate, 2.4% moderately severe, and none reporting severe depressive symptoms. Having moderate social support (AOR 0.14; CI: 0.04-0.47; P=0.001) and strong social support (AOR 0.08; CI: 0.03-0.25; P<0.000) were significantly associated with lower odds of probable depression. ConclusionApproximately 1 in 10 individuals with glaucoma experience depression. Having good social support was identified as a protective factor against depression in people with glaucoma. These findings underscore the need for a multidisciplinary approach integrating psychosocial services into ophthalmology clinics.

ObjectiveWe reviewed the epidemiologic and genomic literature and performed genomic analyses to identify population burdens (Eating Disorders, ED and Parkinsons Disease, PD) and shared genetic risk (Anorexia Nervosa, AN and PD), after we previously demonstrated two-to four-fold relative risks of a family history of Parkinsons Disease in families of individuals with ED. MethodWe reviewed the epidemiology of both disorders and published genome-wide association studies (GWAS), searched PD GWAS findings with AN associated genome-wide significant SNPs and associated genes and regions, and performed conditional/conjunctional false discovery rate genomic analyses of AN and PD summary statistics to identify shared genetics. ResultsThe global population burden of ED and PD are similar despite differences in age of onset and sex ratio. GWAS review and linkage disequilibrium analysis showed that genome-wide significant variants from AN GWAS and PD GWAS in the chr3p21.31 region are correlated. We identified a chr3p21.31 variant with joint association with both disorders; this variant has functional linkages to 40 genes. ConclusionsED and PD share neuropsychological, neurobiological, and genetic risk factors, including association with the complex chr3p21.31 locus. Translational analyses leveraging disorder-specific research resources may benefit our understanding of the genetics and neuropsychiatric mechanisms of both disorders. HighlightsO_LIED and PD have similar age-standardized disability life years (AS-DALYS); the burden of both disorders are expected to increase in the future. C_LIO_LIGenomic epidemiology literature review reveals AN and PD genetic architectures are highly polygenic (AN >> PD), and, AN variant discoverability is less than PD variant discoverability. C_LIO_LIAN and PD are jointly associated at rs1352420 at chr3p21.31, a region with multiple AN and PD comorbid and genetically correlated trait associations. C_LIO_LICross-disorder research offers opportunities to identify shared variants and explore mechanistic hypotheses C_LI

AimSurgical interventions such as deep brain stimulation (DBS) have demonstrated efficacy for severe treatment-resistant obsessive-compulsive disorder (TR-OCD) internationally, but surgical treatment has yet to be implemented in Japan. One factor hindering progress is uncertainty regarding domestic clinical demand, so a nationwide survey of psychiatrists was conducted to clarify their perceptions of OCD surgery. We analysed the data with the aim of identifying factors associated with the acceptance of surgical interventions. MethodsA web-based survey was conducted targeting board-certified psychiatrists in Japan. A total of 212 psychiatrists participated, responding to 10 multiple-choice questions assessing their awareness, perceived need, and expectations regarding DBS. Descriptive statistics, correlation analysis, and multiple linear regression models were used to examine associations between key variables. ResultsPerceived inadequacy of standard treatments alone for severe TR-OCD was strongly associated with perceived need for new treatment options including surgical interventions and with justifiability of surgical treatment. Clinical experience with OCD (Q3) showed a modest positive association with surgical acceptability, whereas greater experience with TR-OCD (Q4) corresponded to more cautious attitudes. Awareness of overseas surgical treatment (Q5) was associated with stronger recognition of treatment limitations and greater acceptance of surgical options. ConclusionsPsychiatrists support for OCD surgery in Japan is primarily driven by perceived unmet clinical needs and awareness of international surgical practices. Enhancing education, addressing ethical concerns, and generating domestic clinical evidence may facilitate the responsible introduction of surgical treatment for TR-OCD.

ObjectiveIn response to a clinical observation of an Anorexia Nervosa (AN) patient with family history of Parkinsons Disease (FHoPD), and evidence of similarities in dopamine function, personality, anxiety and weight loss symptoms between AN and PD, we completed a pilot study to estimate FHoPD in families of those with eating disorders (EDs). MethodWe ascertained FHoPD among ED patients and community participants, and estimated relative risks (RRs) for AN, Bulimia Nervosa (BN) and Binge Eating Disorder (BED). ResultsWe observed increased FHoPD among patients and community participants (N=482) meeting criteria for ED diagnoses compared to community participants (N=394) without an ED diagnosis. For AN, FHoPD prevalence was 6.6% vs 3.4%, {chi}2=4.638, p=.031, RR=1.935, 95%CI=1.012-3.768. For BN, FHoPD prevalence was 7.4% vs 3.4%, {chi}2=4.941, p=.026, RR=2.169, 95%CI=1.023-4.620. For BED, FHoPD prevalence was 13.3% vs 3.4%, {chi}2=6.953, p=.008, RR=3.886, 95%CI=1.108-11.524. ConclusionsEDs are associated with an elevated FHoPD. Translational analyses leveraging disorder-specific research resources may benefit our understanding of the genetics and neuroscience of both disorders. HighlightsO_LIAN and PD share premorbid anxiety, harm avoidance and dopaminergic dysfunction. C_LIO_LIFHoPD RRs are two-fold for AN and Bulimia Nervosa (BN) and four-fold for Binge Eating Disorder (BED) in a sample of treatment seeking and community participants. C_LIO_LIED and PD familiality, and advances in PD and ED genetics and neuroscience research provide opportunities for cross-disorder research. C_LI

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.

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.

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.

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.

Burnout, a state of chronic exhaustion often characterized by feelings of emotional exhaustion, cognitive and emotional dysregulation, and psychological distancing, is an increasingly recognized issue within most professions. This syndrome results in diminished job satisfaction, strained interpersonal relationships, and decreased well-being. Socio-demographic factors have been shown to play a role in burnout risk, while trait mindfulness has been identified as an effective method to mitigate it. This study aimed to identify the prevalence of burnout risk and its relationship with mindfulness and socio-demographics among medical researchers. An anonymous, online, cross-sectional survey was administered to corresponding authors published in MEDLINE. The survey consisted of screening and socio-demographic questions, as well as validated assessment tools (i.e., shortened work-related Burnout Assessment Tool [BAT-12] and shortened Freiburg Mindfulness Inventory [FMI-14]). Responses were analysed according to the BAT and FMI guidelines, alongside regression analyses. A total of 1,732 participants completed the survey, yielding a response rate of 1.88%. Overall, 38.8% of participants were at risk or at very high risk of burnout, and the mean mindfulness score was 37.51. Multiple linear regression analysis indicated that sex, age, and employment status were significant predictors of burnout risk, while age and region significantly predicted mindfulness. Hierarchical regression analysis showed that, after controlling for socio-demographic variables, mindfulness was a strong and independent negative predictor of burnout risk. These findings on burnout risk and the influence of mindfulness and socio-demographics could guide future research in developing tailored interventions and policies that improve the well-being of medical researchers.

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.

BackgroundSuicidal ideation (SI) is a major global concern, yet its dynamic interplay with other symptoms remains poorly understood. ObjectiveTo identify symptoms that co-fluctuate with or temporally precede SI to improve warning signal detection and intervention. MethodsLongitudinal data from three Dutch psychiatric cohorts with lifetime internalizing disorders (16 waves from April 2020 until February 2022) were collected during the COVID-19 pandemic. We analyzed depressive, happiness, anxiety, loneliness, worry symptoms, and COVID-19-specific items only in those participants with SI fluctuations. Dynamic Time Warping (DTW) quantified within-person similarity between symptom trajectories and SI, and results were aggregated at group level. FindingsThe 307 participants (mean age 44.8 years; 61.6% female) showed increasing SI over time (p < .001). SI aligned with four depressive symptoms (i.e., sad mood, low self-esteem, low interest, and reduced happiness), two anxiety-related symptoms (i.e., fear of losing control, faintness), feeling abandoned, and overwhelming worrying. In directed DTW analysis, sad mood, hypersomnia, worrying about projects, and numbness/tingling showed significant temporal precedence before SI. ConclusionSI is embedded in a broad symptom network beyond depression. These results underscore the value of time-sensitive, idiographic monitoring using tools like DTW to capture the person-specific temporal pathways through which SI emerges and intensifies. Clinical implicationsThis study suggests a core group of affective, cognitive, and interpersonal symptoms that could serve as informative signals for evaluating changes in SI and may represent actionable targets for intervention. Summary BoxO_ST_ABSWhat is already known on this topic?C_ST_ABSO_LISuicidal ideation (SI) is a dynamic phenomenon, yet traditional research often relies on static, group-level averages that do not capture individual fluctuations. C_LIO_LIWhile SI is linked to depression, it can emerge independently through complex interactions with other affective and interpersonal states C_LI What this study adds?O_LIThis study identifies a set of affective, cognitive, and interpersonal symptoms, sad mood, overwhelming worry, and feelings of abandonment, that significantly co-fluctuate with SI over weeks and months. Additionally four specific "leading" symptoms, sad mood, hypersomnia, worrying about projects, and somatic numbness, were found that precede increases in SI. C_LI How this study might affect research, practice or policy?O_LIThe identified co-fluctuations and precursors serve as informative "(early) warning signals" that can improve individual risk stratification and clinical monitoring and may represent targets for intervention. C_LIO_LIThe results support a shift toward network-based models in suicidology, emphasizing the need for time-sensitive monitoring to capture the complex and dynamic nature of suicidality. 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.

Williams Syndrome (WS) is a rare neurodevelopmental disorder associated with intellectual disability and increased vulnerability to traits such as anxiety, perseveration, and belief inflexibility. In the general population, these traits are linked to self-reported thought disturbances such as paranoia and delusions. However, little is known about how such disturbances present in WS, largely due to concerns regarding the validity of self-report in this population. To address this gap, we collected self- and caregiver-reported measures characterizing thought disturbances and related cognitive traits in adults with WS, assessing inter-rater reliability and correlations among measures. Total scores were similar across reporters, except for delusional ideation, which participants endorsed more strongly than caregivers. Several participants also reported clinically significant levels of paranoia, delusions, and worry that were not captured by caregiver report. These findings suggest that self-report is a valid method for accurately characterizing the severity and nature of thought disturbances in WS.

BackgroundMajor depressive disorder (MDD) severely impairs individual health and creates heavy societal burdens. Diagnostic and therapeutic research remains hindered by MDDs marked heterogeneity and the absence of valid biomarkers. As a neuro-immune, metabolic, and oxidative stress (NIMETOX) disorder, MDD exhibits metabolomic signatures as a final common pathway in the Chinese population. ObjectivesTo identify lipidomic profile differences between MDD patients and healthy controls and examine associations between lipidomic alterations and clinical phenotypes. MethodsWe recruited 125 MDD patients and 40 healthy controls, and measured serum lipidomic profiles using liquid chromatography-mass spectrometry. A rigorously controlled multistage machine learning pipeline with leakage-prevention measures was utilized to examine disparities between MDD and control groups and to predict phenome features. ResultsWe identified 43 differentially abundant lipids between the MDD and control groups. Subsequent factor analysis clustered the 43 lipids into 3 functional modules, namely the increased ceramide/GM3/LNAPE (CERLNAPE) module, the decreased mitochondrial fatty acid oxidation/acetyl-flux (CARSM) module, and the reduced lysophospholipid/ether-lysolipid (LYSOPE) module. The three lipidomic modules correlated with six previously reported metabolomic functional domains, establishing an integrated metabolomics-lipidomics architecture in MDD. A substantial portion of the variance in the overall severity of depression (74.0%), physiosomatic symptoms (58.5%), suicidal ideation (11.1%), and recurrence of illness (36.6%) was associated with the integrated metabolomics-lipidomics architecture. ConclusionThe MDD lipotype indicates a unified metabolic network linked to the NIMETOX pathophysiology of MDD. Lipidomics provides a robust foundation for subtyping and precision psychiatry. Ceramide, acetyl carnitine, lipotoxicity, and plasmalogens are potential drug targets to treat MDD.

BackgroundMajor depressive disorder (MDD) is a neuro-immune, oxidative, and nitrosative stress (NIMETOX) disorder, in which peripheral immune-redox pathways intersect with metabolic networks leading to neurotoxicity within the limbic-prefrontal affective circuits. Comprehensive metabolomics analysis in well-phenotyped patients is vital to elucidate their metabolic profile. ObjectivesTo identify metabolic abnormalities that differentiate inpatients with severe MDD from healthy controls through high-resolution, untargeted metabolomics. MethodsSerum samples from 125 MDD inpatients and 40 healthy controls were analyzed utilizing liquid chromatography and mass spectrometry. A meticulously regulated multistage machine learning pipeline with leakage-prevention protocols was employed to analyze differences between MDD and controls and to predict phenome scores. ResultsFeature selection showed that 16 metabolites and 6 functional modules reliably distinguished MDD. The functional profile of the metabolites indicates a convergence of lipotoxicity, phospholipid remodeling, disruptions in fatty acid metabolism, mitochondrial redox imbalance, ether-lipid metabolism, and antioxidant depletion. This MDD metabotype was not affected by metabolic syndrome. A substantial portion of the variance in overall depression severity (72.5%), physiosomatic symptoms (55.8%) and suicidal ideation (23.6%) was accounted for by increased lipitoxicity, phospholipid remodeling, and fatty acid storage/signaling. The recurrence of illness (27.7%) was associated with a self-reinforcing-lipid-redox-inflammatory module that maintains cellular stress. DiscussionThe MDD metabotype represents a cohesive metabolic network that is associated with the NIMETOX pathogenesis of MDD. Metabolomics provides a comprehensive foundation for subtyping and precision psychiatry. Lipoxygenase-15, lipotoxicity, phospholipase A2, and lipid-redox intersections are important drug targets to treat MDD.