Psychiatry Research

Aim: The Patient Safety Screener-3 (PSS-3) is a brief suicide-risk screening tool. Item 1 of this scale assesses depressive mood but is not included in the total score. We examined the association of item 1 with depressive symptom severity and characterized the suicide-related risk captured by PSS-3 total positivity. Methods: We conducted a nationwide cross-sectional survey among resident physicians in Japan. Associations between PSS-3 item 1 endorsement and Patient Health Questionnaire-9 (PHQ-9) scores were evaluated using the Wilcoxon rank-sum test. Diagnostic performance of item 1 was evaluated using PHQ-9 positivity ([&ge;]10) as reference standard. We also compared Short-form Scale for Suicide Ideation (SIS-6) scores according to PSS-3 total positivity and PHQ-9 item 9 positivity. Results: A total of 1,844 participants were included. PSS-3 item 1 was endorsed by 443 physicians (24.0%), and 47 (2.5%) met the criteria for PSS-3 total positivity. Item 1 showed 79.3% sensitivity and 79.5% specificity for PHQ-9 positivity. SIS-6 scores were higher in the PSS-3 total-positive group than in the total-negative group (median [IQR], 6 [5-9] vs 0 [0-1]; p<0.001). The SIS-6 showed a higher area under the receiver operating characteristic curve (AUC) and Youden index using PSS-3 total positivity (AUC, 0.961; optimal cutoff, 3) than PHQ-9 item 9 positivity (AUC, 0.907; optimal cutoff, 2). Discussion: PSS-3 may support brief, simultaneous screening for depressive symptoms and suicide-related risk. Compared with PHQ-9 item 9, PSS-3 may capture a more severe spectrum of suicide-related risk. PSS-3 may facilitate identification of individuals requiring further mental health assessment.

Background: Major depressive disorder (MDD) is a severe mental illness associated with severe clinical consequences and substantial societal burden. It's characterized by immune-inflammatory dysregulation and immune sensitization. Objective: To determine whether in vitro ketamine attenuates phytohemagglutinin (PHA)/lipopolysaccharide (LPS)-induced immune sensitization in patients with MDD and healthy controls (HCs). Methods: Whole blood from 18 patients with MDD and 18 HCs was stimulated with PHA/LPS and exposed to ketamine (0.3 M, 0.6 M, and 6 M) for 72 hours. Cytokines, chemokines, growth factors, and composite immune profiles, including M1/M2 macrophages, T helper (Th)1/2/17, the immune-inflammatory response system (IRS), and compensatory immunoregulatory system (CIRS), were synthesized and determined. Results: Under PHA and LPS stimulation in vitro, the MDD group exhibited markedly elevated immune profiles, including M1, M2, Th1, Th2, Th17, IRS, CIRS, chemokines, and growth factors, consistent with immune sensitization. Significant group-by-treatment interactions were observed for Th1-Th2, M2, growth factors, IL-12(p70), M1, and chemokines. Ketamine produced minimal changes in HCs but broader suppression in MDD, particularly at the highest concentration, without normalizing the sensitized immune phenotype. Among the immune markers with no notable group-by-treatment interactions, ketamine exerted diagnosis-independent effects, decreasing MIP-1{beta}, IL-1&{beta}, Th1, TNF-{beta} IRS, IFN-{gamma}, and IL-2 compared to the control condition. Conclusions: Ketamine exhibited two distinct immunoregulatory patterns: selective, disease-dependent attenuation of sensitized immune pathways and broader, diagnosis-independent suppression of the stimulated immune response, predominantly at higher concentrations. However, these effects were insufficient to normalize the immune-sensitized phenotype of MDD.

Background: Substance use is common among individuals with depression. Transcranial magnetic stimulation (TMS) is an effective treatment for depression, but current clinical guidelines have discouraged TMS treatment for individuals with depression and co-occurring substance use given concerns for limited efficacy. However, limited data exists on whether substance use affects response to TMS. Methods: Using electronic health record data from patients who received a standard course of TMS for major depressive disorder at an academic medical center, we investigated associations between substance use frequency and response to TMS, defined as change in Patient Health Questionnaire-9 (PHQ-9) scores. Substance use frequency was extracted for alcohol, cannabis, nicotine, stimulants, benzodiazepines, opioids, inhalants, psychedelics, and other drugs. We performed ANCOVA and multiple regression analyses to predict change in PHQ-9 score based on substance use frequency, controlling for pre-TMS PHQ-9 score, age, sex, and number of TMS sessions received. Results: We extracted data from 219 TMS courses. Alcohol was the substance used most commonly (34.2%), followed by prescription benzodiazepines (28.3%), and prescription stimulants (21.0%). Across all substance categories, substance use was not associated with change in PHQ-9 score (all p > 0.05, Cohens d=0.00 to 0.30). In multiple regression models to compare individual levels of substance use frequency (e.g., daily use vs. no use), level of substance use was not associated with change in PHQ-9 score (all p > 0.05). The range of plausible effects of substance use frequency on PHQ-9 change was generally below the minimal clinically important difference for PHQ-9, suggesting substance use was unlikely to have a meaningful clinical effect on antidepressant response to TMS. Conclusions: Low to moderate substance use does not have a clinically significant effect on antidepressant response to TMS. Low-level substance use should not exclude individuals with depression from receiving TMS.

Objective: This study examined the prevalence of psychotic experiences (PE) and how early onset and persistence of PE contribute to risk and severity of mental disorders in adolescents at familial high-risk of schizophrenia (FHR-SZ) or bipolar disorder (FHR-BP) and adolescents from a population-based control group (PBC). Methods: This is the second follow-up of a nationwide cohort study including 522 children at FHR-SZ (N=202), FHR-BP (N=120), and PBC (N=200). Participants were assessed at ages 7, 11, and 15 using a semi-structured interview to evaluate PE and mental disorders. Results: At age 15, adolescents at FHR-SZ reported more PE than PBC over the past six months (current) and the past four years, while adolescents at FHR-BP only reported more current PE. PE reported at two or three timepoints (persistent PE) predicted any Axis I disorder in mid-adolescence, corresponding to three- (OR 2.9, 95% CI [1.5-5.7]) and 21-fold (OR 21.4, 95% CI [2.8-162.3]) increased risks, respectively. Persistent PE also predicted multimorbidity, with three- (OR 2.8, 95% CI [1.0-7.6]) and four-fold (OR 4.1, 95% CI [1.2-14.1]) increased risks, respectively. This was after adjustment for sex, early mental disorders, and familial risk. Conclusions: This study demonstrates a strong link between persistent PE and mid-adolescence mental disorders. Our findings emphasize PE as important risk markers for mental disorders during mid-adolescence and highlight the importance of monitoring children with PE before age 7 who develop persistent symptoms.

Background: Previous trauma research includes many limitations, such as the scarcity of pretraumatic health measurements and assessment of traumatic experiences with a broad scope across the lifespan. To respond to these gaps, we aimed to develop a new, prospective, population-based trauma dataset from childhood to middle age. Methods: We used the Young Finns Study that is a population-based, multi-generational, prospective study (n = 3596 for the main generation). It has started in 1980 (baseline assessment) and includes follow-ups in 1983, 1986, 1989, 1992, 1997, 2001, 2007, 2011/2012, and 2018-2020. From the 38-year follow-up and ten measurement points of the YFS, we collected all relevant trauma variables, including both free-format and structured questions that both the participants and their parents responded to. By a data-driven case-to-case analysis, we developed a scale to numerically capture variation in the quality of the experiences. Results: Our final dataset captured a total of 7769 traumatic experiences. We also developed the Traumatic Experience Severity Scale (TESS), including six subscales such as shamefulness, rarity, danger to life or health, effects on everyday life, human-made physical threat, and whether the target person was within or outside one's household. We also preprocessed the dataset to be later easily interleaved with other psychological, cardiovascular, and epigenetic variables of the YFS. Conclusions: We believe this new trauma dataset with thousands of experiences across the lifespan provides new opportunities to multidisciplinary, lifelong trauma research.

Objectives: To estimate the prevalence of Post-Exertional Malaise (PEM) among adults with prior COVID-19 and associated mental health and disability outcomes. Methods: We conducted a cross-sectional analysis of data from a survey of 9,620 adults with prior COVID-19 in New York City, collected May - June 2024. PEM was measured with the DePaul Symptom Questionnaire - Post Exertional Malaise, categorized by symptom duration (< 14 vs. [&ge;]14 hours). Weighted prevalence estimates were stratified by socio-demographic and clinical characteristics. Modified Poisson regression was used to assess the association of PEM with depression, anxiety, and disability. Results: The prevalence of PEM symptoms was 20.9% overall and 4.0% with symptom duration [&ge;]14 hours, representing over 800,000 New Yorkers affected and over 150,000 who meet a diagnostic criterion for ME/CFS. PEM prevalence was higher among women, transgender and non-binary adults, people of color, and lower educational attainment, chronic comorbidities, or disabilities. PEM was associated with 3 - 4 times higher prevalence of mental health outcomes and 4 - 5 times higher disability scores. Conclusions: PEM symptoms were common and strongly associated with disability and adverse mental health. Screening, pathways to care, and supportive policies are needed to mitigate long-term consequences, particularly among marginalized populations.

Background: Bipolar disorder is associated with persistent social, cognitive, and functional impairment during euthymia, yet the neural mechanisms underlying these deficits remain unclear. Alterations to self-referential processing are a candidate mechanism, but existing electrophysiological studies rely on emotionally valenced paradigms that potentially confound self-processing with emotional biases. Methods: We analysed electroencephalography from 28 patients with bipolar disorder (type I or II) and 28 age- and sex-matched healthy controls during an emotionally neutral colour judgment task with self-related (preference) and non-self-related (similarity) conditions. Late positive potentials, temporal generalisation decoding, and frequency band decoding (theta, alpha, beta) were used to characterise the temporal dynamics and oscillatory correlates of self versus non-self processing. Results: Controls showed higher overall event-related potential amplitudes and greater self versus non-self differentiation than patients (condition by group interaction, 337 to 946 ms). Broadband temporal generalisation decoding revealed extensive cross-temporal generalisation of the self versus non-self representation in controls, spanning most of the trial, but no significant generalisation in patients. Frequency analyses showed that alpha and beta carried self versus non-self information in both groups, with broader extent in controls, and that anterior theta carried this information in patients but not controls. Exploratory correlations linked decoding measures to rumination and anxiety but not to manic symptoms. Conclusions: The neural representation distinguishing self-referential from externally guided processing was both smaller in amplitude and less temporally sustained in bipolar disorder. Reduced persistence is not detectable by conventional amplitude analyses, and may bear on the self-related and social cognitive difficulties reported in this population.

Background: Higher Body Mass Index (BMI) is an established risk factor of sleep disturbance. It is not known if the effect is homogeneous across the lifecourse or if there is a particular time point in life that might be best to target. Methods: Two-sample Mendelian randomization (MR) was used to investigated the effect of childhood adiposity (adjusting on adulthood adiposity and obstructive sleep apnea (OSA)) on insomnia, morning chronotype, sleep duration, daytime sleepiness and daytime napping. Similarly, total, and direct effect of adulthood adiposity on these outcomes was explored. We used summary statistics from a genome-wide association study (GWAS) of UK Biobank for childhood and adulthood adiposity (n=453,169) and large-scale consortia of OSA (Million Veteran Program) (n=410,268), insomnia, and chronotype (23andMe) (n=1,978,022 and n=248,1000, respectively). Results: Two-sample univariable MR analysis provided no evidence of an effect of genetically predicted childhood adiposity on later life insomnia (Odds ratio (OR)= 0.94, 95% Confidence interval (CI)= 0.87, 1.03). Whereas, multivariable MR (adjusted for adulthood adiposity) analysis provide strong evidence of direct protective effect of genetically predicted childhood adiposity on later life insomnia (OR= 0.70, CI= 0.64, 0.77). Further, both in univariable and multivariable MR, a strong positive effect of increased childhood body size on morning chronotype was observed (OR= 1.16, CI= 1.01, 1.33 and OR= 1.36, CI= 1.15, 1.62, respectively) after accounting for adulthood body size. In both analysis the estimate did not change considerably after aditionally adjusting for OSA. However, childhood and adulthood adiposity found to be associated with OSA and OSA with insomnia. In both univariable and multivariable analysis, increased body size in adulthood increased the risk of having insomnia and a morning chronotype. Conclusions: The findings suggest that higher body size in childhood is not a risk factor for later life insomnia, whereas higher body size in adulthood was. Further, if healthy body size is maintained in adulthood, high childhood adiposity may decrease the risk of insomnia and increase the risk of being a morning person in later life. Keywords: childhood, adulthood, obesity, insomnia, morning chronotype, medelian randomization

This study investigated bidirectional associations between maternal sleep and depressive symptoms from preconception to postpartum, and whether infant sleep mediated or moderated these associations. We used data from the Generation R Next Study (N=2,294). Maternal sleep (specifically general sleep disturbance, latency, quality, duration, and midpoint) and depressive symptoms were prospectively assessed at five timepoints from preconception to 12-month postpartum. Sleep was self-assessed with the General Sleep Disturbance Scale and Munich Chronotype Questionnaire; depressive symptoms with the Adult Self Report depression/anxiety subscale and Edinburgh Postnatal Depression Scale. Infant sleep (specifically night awakenings, nocturnal sleep duration, and latency) was parent-reported at 1-month postpartum using the Brief Infant Sleep Questionnaire. Bidirectional associations were examined using Autoregressive Latent Trajectory Models with Structured Residuals. The role of infant sleep was examined using mediation and moderation analyses. We found that maternal sleep and depressive symptoms were both stable over time. For sleep quality and disturbance, bidirectional associations suggested slightly stronger effects from depression to sleep (sleep quality:{beta}depression[-&gt;]sleep quality=0.11, 95%CI:0.07 - 0.14; general sleep disturbance:{beta}depression[-&gt;]sleep disturbance=0.14, 95%CI:0.10 - 0.18) than from sleep to depression ({beta}sleep quality/disturbance[-&gt;]depression=0.07 for both, 95%CIs:0.03 - 0.11). For latency, effects were comparable in both directions ({beta}depression[-&gt;]sleep latency=0.06, 95%CI:0.03 - 0.09; {beta}sleep latency[-&gt;]depression=0.05, 95%CI:0.01 - 0.09). The association between depressive symptoms and sleep latency was both mediated (9.7%) and moderated (p<0.05) by infant sleep latency. In conclusion, general maternal sleep disturbance, sleep quality, and sleep latency showed bidirectional associations with depressive symptoms from preconception/early pregnancy onwards. Infant sleep latency may represent a potential modifiable factor within this cycle.

Background Floods are among the most devastating natural disasters worldwide and are increasingly associated with adverse mental health outcomes, particularly Post-Traumatic Stress Disorder (PTSD). In December 2023, Hanang District in northern Tanzania experienced catastrophic mud floods that resulted in extensive loss of life, destruction of property, displacement of households, and disruption of livelihoods. While emergency humanitarian responses focused primarily on physical needs, limited evidence exists regarding the long-term psychological consequences among survivors. Therefore, this study aimed to determine the patterns of PTSD manifestations and assess cognitive factors associated with PTSD symptoms among flood victims in Hanang District, Tanzania. Methods A community-based cross-sectional study was conducted among 360 flood victims one year after the disaster. PTSD symptoms were assessed using the PTSD Checklist for DSM-5 (PCL-5). Descriptive statistics summarized PTSD severity, while chi-square tests and regression analyses examined associations between socio-demographic characteristics and PTSD manifestations. Cognitive factors were assessed based on participants' exposure to traumatic experiences and perceptions of traumatic events. Results The mean PCL-5 score was 39.2 (SD = 20.6), indicating a high burden of psychological distress. Approximately 45% of respondents had severe PTSD symptoms (PCL-5 [&ge;]45), while another substantial proportion demonstrated moderate symptom severity. PTSD manifestations varied significantly by geographical location (p < 0.001), household income (p = 0.011), and marital status (p = 0.002). Age positively predicted PTSD severity ({beta} = 0.019, p = 0.001), whereas household income negatively predicted symptom severity ({beta} = -0.297, p = 0.001). Exposure to natural disasters constituted the predominant cognitive factor, with 45% directly experiencing the flood and 38.3% witnessing the event. Exposure to secondary traumatic experiences through witnessing or learning about violent events was also common. Cognitive trauma exposure demonstrated a significant association with PTSD symptoms ({chi}2, p < 0.001). Conclusion PTSD remains highly prevalent among flood survivors in Hanang district. Both direct and indirect trauma exposure significantly contributed to PTSD manifestations. Comprehensive disaster recovery programmes should integrate trauma-focused psychological services, cognitive behavioural interventions, routine PTSD screening, and community-based psychosocial support alongside socioeconomic recovery initiatives.

Objectives This study aimed to assess sleep patterns and life satisfaction among employees of a private company in Dubai, United Arab Emirates, and to examine the relationships among sleep quality, life satisfaction, and selected demographic variables. A quantitative descriptive cross-sectional survey design was adopted. Methods A convenience sample of 110 male employees participated in the study. Data were collected using the Sleep Disorder Assessment Scale (16 items; Cronbachs = 0.89) and the Life Satisfaction Scale (5 items). Statistical analysis was performed using SPSS version 29, including descriptive statistics, chi-square tests, and Pearson correlation analysis. Results Most participants (66.4%) were aged 20-30 years, and 82.7% experienced moderate sleep-related problems. Mobile phone use before bedtime was common, with 60.9% reporting occasional use and 35.5% reporting regular use. Overall, 41.8% reported neutral life satisfaction, while 25.5% and 24.6% were slightly and extremely satisfied, respectively. A significant negative correlation was found between poor sleep patterns and life satisfaction (r = -0.389, p < 0.001). Mobile phone use before bedtime and shift work were significantly associated with sleep patterns (p = 0.048). Conclusion Poor sleep quality, particularly among shift workers and frequent bedtime mobile phone users, is associated with lower life satisfaction. Workplace interventions promoting sleep hygiene may enhance employee well-being.

Background: Metabolomic studies of depression have yielded heterogeneous findings, potentially because metabolic correlates differ across symptoms and metabolic states. We examined symptom-specific metabolomic associations and whether body mass index (BMI) modifies these relationships. Methods: We analyzed 83,717 Estonian Biobank participants (70.6% female) with 249 Nightingale metabolite measures and 14 lifetime depressive symptoms. Logistic regression models progressively adjusted for sociodemographic, lifestyle, medication, and BMI factors. BMI-related attenuation and metabolite x BMI interactions were evaluated, followed by self-organizing map analyses of broader metabolic context. Results: Before BMI adjustment, 660 metabolite-symptom associations were Bonferroni-significant; 136 were significant after BMI adjustment, including 105 retained associations. Weight-related associations showed the strongest BMI dependence: none of 199 weight-gain associations and 2 of 115 weight-loss associations were retained. Among 691 preselected metabolite-symptom pairs, 211 (30.5%) showed significant metabolite x BMI interactions after false discovery rate correction. Six systemic metabolic profiles were identified, but only 3 of 211 BMI-sensitive pairs showed additional profile-dependent heterogeneity. Conclusions: Circulating metabolic correlates of depressive symptoms are heterogeneous and strongly dependent on symptom phenotype and BMI-related metabolic context. These findings suggest that metabolic biomarkers in depression should be interpreted in relation to both symptom presentation and metabolic state rather than as uniform correlates of the disorder.

Introduction Hearing loss (HL) affects over 1{middle dot}5 billion people globally and India shares a disproportionately high burden including Disabling Hearing Loss (DHL). HL affects an Individual socio-economically, but there are limited studies on the broader societal economic consequences of HL in India.Methods Using Cost-of-Illness (COI) approach, we studied the societal economic burden of HL in India. This study uses epidemiological and macroeconomic data and modelling to estimate the loss of Gross National Income (GNI) due to HL and DHL across three economic pathways. Uncertainty is evaluated using deterministic and Probabilistic Sensitivity Analyses (PSA).Results The model estimates that there are in India, 289 million and 85{middle dot}9 million people with HL and DHL respectively. Direct Loss of GNI and Indirect Loss of GNI (Caregiver burden) are estimated as INR 4,648{middle dot}4 billion (USD 55{middle dot}6 billion) and INR 3,268 billion (USD 39 billion) respectively. The Loss of GNI due to Low Education amongst those with HL is estimated as INR 1,041{middle dot}9 billion (USD 12{middle dot}45 billion).Discussion Economic burden of HL is presented across three pathways with Direct Loss of GNI due to DHL being the greatest. It also presents age stratified caregiver economic burden. The findings of the study help in estimating similar cost pathways, advocacy, and policy decisions towards reducing HL prevalence in India and LMICs. This study also highlights the need for India specific estimations related to the HL attributable low education, state-wise disaggregates, and prevalence studies. Funding This study has not received any funding.

Suicidal behavior results from complex behavioral and biological changes. Previous cross-sectional studies indicate that proinflammatory immunobiological factors are often increased in close temporal proximity to a suicide attempt. Suicidal individuals may also exhibit a biological trait vulnerability to stress and inflammation, due to persistent epigenetic modifications. We enrolled 130 individuals with major depressive disorder (MDD), 83 with suicidal behavior at intake, and followed them for 12 months with up to eight clinical assessments. Quantification of plasma inflammatory markers and metabolites was performed by high-sensitivity electrochemiluminescence and Ultra High-Performance-Liquid-Mass Spectrometry (UPLC-MS), respectively. Epigenetic changes were identified using Illumina EPIC arrays. We identified 15 genes with altered DNA-methylation associated with suicidal behavior and attempts at baseline. Childhood trauma predicted lifetime suicide attempts and was associated with altered methylation of seven genes. Increased neutrophils and lower plasma serotonin at baseline predicted future suicide attempts over the following year (neutrophil estimate = 0.42, P = 0.016; serotonin OR = 0.58, 95% CI: 0.39-1.13). Utilizing biomarkers from baseline and epigenetic data from the genes with highest predictive values (STBD1 ,PRDM8, and TRIM15), we achieved an area under the curve (AUC) of 0.84 for suicide attempts over the year. Suicidal behavior in MDD was associated with specific epigenetic signatures. Several of the identified genes, such as MAD1L1, have been implicated in psychiatric disease, suicidal behavior and the immune response. These findings support the usefulness of epigenetic and immunometabolic blood markers for identifying suicidal individuals in clinical settings, potentially enhancing preventative efforts.

The Autism Spectrum Quotient (AQ-50) is widely used to assess autistic traits, yet its Hungarian version has not been psychometrically evaluated. We assessed the reliability, factor structure, temporal stability, convergent validity, and clinical utility of the Hungarian AQ-50 and a revised translation (AQ-50-HU-R) in two samples (N1 = 1967; N2 = 423), including autistic and non-autistic participants. The AQ-50-HU-R showed high internal consistency and test-retest reliability. A bifactor model provided the best fit ({chi}2[1125] = 1650.433, p < 0.001; CFI = 0.991; TLI = 0.990; RMSEA = 0.033 [90% CI = 0.030-0.037]; SRMR = 0.083), with 71% of common variance attributable to a general autistic traits factor. The total score distinguished clinically verified autistic participants from participants reporting no ASD diagnosis (AUC = 0.906), with a cutoff of 25. Associations with ADOS scores were weak or nonsignificant. The AQ-50-HU-R is best interpreted as a reliable total-score screening measure, supporting referral for comprehensive autism assessment.

Background Sleep, mood, and affective states are mutually connected. There is a paucity of studies, however, that have considered bidirectional relationships between daily sleep-affective dyads in naturalistic settings, particularly for shift workers. Objective To evaluate the dynamic and temporal interplay of daily smartphone-based self-reported sleep measurements, dimensions of affective experience and cognitive processing in UK shift working nurses. Methods The EClocker Study prospectively monitored 102 National Health Service (NHS) nurses (aged 25-61 years, 83.3% female) working standard (day shift) and non-standard (fast rotating shifts) schedules over a two-week period. Smartphone-based Experience Sampling Methodology (ESM) recorded daily sleep, mood, momentary affect and cognitive attentional functioning. Self-reported burnout, emotional dysregulation, emotion reactivity and affective dimensions (positive and negative) were also collected. Findings Overall, NHS nurses reported a high prevalence of depressive symptoms, stress, burnout and sleep-circadian rhythm disturbances. Generalised Additive Modelling (GAMs) revealed that NHS nurses higher perceived sleep quality predicted better next-day mood state, while better daytime mood was associated with reduced sleep onset latency, such that participants reported falling asleep faster. In contrast, daytime mood or affect (positive and negative) had no substantial, direct impact on nurses subjective sleep parameters (sleep quality, sleep duration, sleep efficiency). Exposure to fast rotating night shifts across the two-week study was associated with more frequent response errors on a Choice Reaction Time (CRT) cognitive task, while daytime somnolence did not adversely influence nurses momentary reaction time speeds or attentional function. Conclusions Clinically relevant sleep impairments, insomnia-related symptoms, elevated stress, and poor mood were pervasive in a sample of UK NHS nurses, regardless of shift type. Sleep quality impacted next-day mood and daytime mood impacted sleep latency, while rotating shifts led to an increase in cognitive errors. Recognising the impact of shiftwork and designing interventions to promote better sleep quality offer potential to enhance mood and performance in healthcare professionals. Clinical implications We need to implement and evaluate interventions that regularise sleep patterns and promote sleep quality to alleviate mood symptoms among frontline NHS shift workers.

Background: As cannabis policy changes in the United States, secondhand cannabis smoke (SCS) is increasingly common, including within families. However, prevalence of exposure and clinical correlates over time in adolescents are not fully understood. Objectives: (1) To estimate the prevalence of SCS and personal cannabis use in US-based teens exposed to SCS, and (2) examine the cognitive trajectories of adolescents exposed to SCS compared to non-exposed peers. Methods: Data from the Adolescent Brain Cognitive Development (ABCD) Study was used. Participants (n=11,316 of full cohort with follow-up data; n=776 with self-reported family SCS exposure) attended yearly visits from ages 11-17, completing substance use interviews, toxicological testing, and the NIH Toolbox Cognitive battery. Youth with SCS but no personal cannabis use (n=419; 47% female) were matched on prenatal substance exposure, family substance use history, and sociodemographics to non-SCS exposed and non-cannabis-using youth with a 1:2 ratio (Controls n=838). Linear mixed-effects models assessed cognitive performance by SCS*age interactions, accounting for random effects of subject and family. Covariates included sex and alcohol, nicotine, and other substance use. Secondary models analyzed performance by cumulative waves of reported SCS exposure interacting with age. Results: Of the full cohort, 6.9% (n=776) reported exposure to SCS. Of these individuals, 46% endorsed lifetime personal cannabis use by age 17, relative to 20% of non-SCS exposed youth (OR=3.83[95%CI:3.29,4.44]). Within matched participants, SCS*age demonstrated a significant interaction on attention and inhibitory control ({beta}=-0.32, p=.028), with SCS demonstrating reduced improvement over time. More waves of exposure were also associated with worse performance over time ({beta}=-0.39, p=.057). Discussion: Almost half of those who had been exposed to SCS endorsed personal cannabis use. Cognitive findings were domain specific, similar to findings in secondhand tobacco: SCS exposed youth showed restricted improvement in attention and inhibitory control by age 17. Public health and policymakers should make efforts to curb youth SCS exposure, given the potential for risk which has not been fully explored to date.

Recent large-scale studies have enabled new knowledge about genetic underpinnings of morphological and electrophysiological alterations of the retina. Variation in retinal traits, often of neurodevelopmental origin, have been linked to major psychiatric disorders (MPDs). Here, we investigate the genetic overlap between MPDs and key retinal traits to identify underlying molecular mechanisms. We obtained genome-wide associations studies data for bipolar disorder (BD), major depression (MD), schizophrenia (SCZ), and the retinal traits retinal nerve fibre layer thickness (RNFL), ganglion cell inner plexiform layer thickness (GCIPL), and vertical cup-disc ratio (VCDR). We estimated the number of trait-influencing variants shared between traits with MiXeR and identified shared genetic loci with condFDR. Subsequently, we examined the biological pathways of the genes mapped to shared loci. This revealed that GCIPL shared the most genetic variants with MPDs (~60%), followed by RNFL (~40%), and VCDR (~20%). The genetic variants shared between retinal traits and MPDs showed disorder-specific patterns with more pronounced overlaps of SCZ and BD with RNFL, and MD negatively correlated with GCIPL. Gene-pathway analysis highlighted the importance of GABAergic neurotransmission and a two-stage neurodevelopmental process in SCZ, whereas the role of mitochondria and a weaker developmental component were observed in BD. The results also implicated synaptic functioning and gene-expression processes in MD. Furthermore, polygenic analysis suggested that the genetic architecture of retinal traits can distinguish between MPDs. Our findings indicate shared genetic underpinnings between retinal traits and SCZ, BD, and MD, implicating altered neurodevelopment and neurotransmission underlying the retinal link to major psychiatric disorders.

Background: Cognitive impairment is the leading cause of disability in schizophrenia with limited treatments. A major barrier to treatment development is the absence of reproducible, mechanistically grounded neural targets. Cross-sectional studies have identified dorsomedial prefrontal cortex (DMPFC)-somatomotor connectivity as a neural marker of cognitive performance on the Auditory Continuous performance task (ACPT), a measure of attention. To test the stability of this marker, we tested the relationship between DMPFC-somatomotor connectivity and ACPT performance in a longitudinal psychosis sample. Methods: Individuals with early psychosis (n=251) and matched controls (n=90) were enrolled and underwent resting-state neuroimaging and neurocognitive assessment. A subset completed longitudinal assessments over 2-4 years. We calculated DMPFC-somatomotor resting-state functional connectivity using a previously identified DMPFC region and a seed in the somatomotor cortex. We performed linear mixed effects models to predict ACPT performance based on connectivity, time, psychosis type, and their interaction. Results: In the psychosis sample, time (p=.0037) and affective psychosis diagnosis (p<.0001) predicted better ACPT performance. In a model predicting ACPT performance, we observed a significant interaction effect of DMPFC-somatomotor connectivity*psychosis subtype (p=.0079) such that DMPFC-somatomotor connectivity predicted ACPT performance only in individuals with non-affective psychosis (p=.0051). We then tested the specificity of this connectivity-cognitive performance relationship. In a model predicting DMPFC-somatomotor connectivity, only ACPT performance (p=.017), but not fluid cognition, was a significant predictor. Conclusions: DMPFC-somatomotor connectivity is longitudinally associated with cognitive performance in early psychosis. This relationship is strongest in nonaffective psychosis, suggesting a novel, reliable target for intervention for cognitive deficits in early psychosis.

Background: Multiple sclerosis (MS) is a chronic, immune-mediated disease of the central nervous system marked by demyelination and neurodegeneration. Beyond physical symptoms, MS is often linked to clinically relevant sleep disturbances. The variability and unpredictability of symptoms and disease progression can also fuel fear of relapse (FoR), undermining well-being and potentially increasing morbidity through inflammatory processes. Understanding biopsychosocial risk factors, including childhood maltreatment (CM) and sleep, in relation to FoR remains an important gap in MS management and research. Methods: Data from N = 48 participants were collected via an online survey. We used the Pittsburgh Sleep Quality Index (PSQI), the Fear-of-Relapse Scale (FoR), and the Childhood Trauma Questionnaire (CTQ) to assess the variables of interest. In addition, time points of exposure to different CM subtypes were assessed. Linear regression analyses were conducted to examine associations within the proposed negative triad. Results: A significant negative association between overall sleep quality and FoR was observed. In the total cohort, the interaction between CM and sleep was not a significant predictor of FoR. However, exploratory analysis revealed a significant interaction between CM and sleep among male participants, whereas the same interaction was not significant among female participants. Conclusion: A history of CM and impaired sleep quality introduce new stressors in managing one's own illness that have received little attention to date. However, the present study found that these factors were at least partly influential on the FoR. The results underscore the translational need for additional support services to enhance prevention and personalized care.