Post-traumatic stress symptoms (PTSS) were the most frequently reported mental health concern for youth during COVID-19, yet variations in youth's PTSS responses warrant empirical consideration. Features of the caregiving environment influence youth's responses to environmental stressors, and youth's parasympathetic nervous system regulation may qualify the magnitude and/or direction of these effects. This prospective investigation evaluated diathesis stress and differential susceptibility models of caregiving and parasympathetic influences on youth's PTSS responses to COVID-19.

Participants were 225 caregiver-youth dyads (youth 49.8% female at birth; 88.4% non-white) followed from childhood through adolescence and COVID-19. Youth's resting respiratory sinus arrhythmia (RSA; Mage = 6.11, s.d. = 0.21), caregiving features (i.e. attachment security [youth Mage = 12.24, s.d. = 0.35] and caregiver internalizing psychopathology [caregiver Mage = 39.29, s.d. = 6.78]) were assessed pre-pandemic. Youth's PTSS was assessed one year prior to the US COVID-19 pandemic (Mage = 14.24, s.d. = 0.50) and during the spring of 2020 at the height of the pandemic (Mage = 15.23, s.d. = 0.57).

Youth's PTSS increased during COVID-19. Youth with relatively high resting RSA evidenced the lowest PTSS when their caregiving environment featured high attachment security or low caregiver internalizing problems, but the highest PTSS when their caregiving environment featured low attachment security or high caregiver internalizing problems. In contrast, PTSS levels of youth with relatively low or average resting RSA did not differ significantly depending on attachment security or caregiver internalizing.

Results are consistent with a differential susceptibility hypothesis, wherein relatively high resting RSA conferred heightened sensitivity to caregiving environments in a for-better-and-for-worse manner during COVID-19.

Childhood maltreatment (CM) is a strong risk factor for psychiatric disorders but serves in its current definitions as an umbrella for various fundamentally different childhood experiences. As first step toward a more refined analysis of the impact of CM, our objective is to revisit the relation of abuse and neglect, major subtypes of CM, with symptoms across disorders.

Three longitudinal studies of major depressive disorder (MDD, N = 1240), bipolar disorder (BD, N = 1339), and schizophrenia (SCZ, N = 577), each including controls (N = 881), were analyzed. Multivariate regression models were used to examine the relation between exposure to abuse, neglect, or their combination to the odds for MDD, BD, SCZ, and symptoms across disorders. Bidirectional Mendelian randomization (MR) was used to probe causality, using genetic instruments of abuse and neglect derived from UK Biobank data (N = 143 473).

Abuse was the stronger risk factor for SCZ (OR 3.51, 95% CI 2.17–5.67) and neglect for BD (OR 2.69, 95% CI 2.09–3.46). Combined CM was related to increased risk exceeding additive effects of abuse and neglect for MDD (RERI = 1.4) and BD (RERI = 1.1). Across disorders, abuse was associated with hallucinations (OR 2.16, 95% CI 1.55–3.01) and suicide attempts (OR 2.16, 95% CI 1.55–3.01) whereas neglect was associated with agitation (OR 1.24, 95% CI 1.02–1.51) and reduced need for sleep (OR 1.64, 95% CI 1.08–2.48). MR analyses were consistent with a bidirectional causal effect of abuse with SCZ (IVWforward = 0.13, 95% CI 0.01–0.24).

Childhood abuse and neglect are associated with different risks to psychiatric symptoms and disorders. Unraveling the origin of these differences may advance understanding of disease etiology and ultimately facilitate development of improved personalized treatment strategies.

Maternal vitamin-D and omega-3 fatty acid (DHA) deficiencies during pregnancy have previously been associated with offspring neurodevelopmental traits. However, observational study designs cannot distinguish causal effects from confounding.

First, we conducted Mendelian randomisation (MR) using genetic instruments for vitamin-D and DHA identified in independent genome-wide association studies (GWAS). Outcomes were (1) GWAS for traits related to autism and ADHD, generated in the Norwegian mother, father, and child cohort study (MoBa) from 3 to 8 years, (2) autism and ADHD diagnoses. Second, we used mother–father–child trio-MR in MoBa (1) to test causal effects through maternal nutrient levels, (2) to test effects of child nutrient levels, and (3) as a paternal negative control.

Associations between higher maternal vitamin-D levels on lower ADHD related traits at age 5 did not remain after controlling for familial genetic predisposition using trio-MR. Furthermore, we did not find evidence for causal maternal effects of vitamin-D/DHA levels on other offspring traits or diagnoses. In the reverse direction, there was evidence for a causal effect of autism genetic predisposition on lower vitamin-D levels and of ADHD genetic predisposition on lower DHA levels.

Triangulating across study designs, we did not find evidence for maternal effects. We add to a growing body of evidence that suggests that previous observational associations are likely biased by genetic confounding. Consequently, maternal supplementation is unlikely to influence these offspring neurodevelopmental traits. Notably, genetic predisposition to ADHD and autism was associated with lower DHA and vitamin-D levels respectively, suggesting previous associations might have been due to reverse causation.

This longitudinal register study aimed to investigate the association between gambling disorder (GD) and work disability and to map work disability in subgroups of individuals with GD, three years before and three years after diagnosis.

We included individuals aged 19–62 with GD between 2005 and 2018 (n = 2830; 71.1% men, mean age: 35.1) and a matched comparison cohort (n = 28 300). Work disability was operationalized as the aggregated net days of sickness absence and disability pension. Generalized estimating equation models were used to calculate adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for the risk of long-term work disability (>90 days of work disability/year). Secondly, we conducted Group-based Trajectory Models on days of work disability.

Individuals with GD showed a four-year increased risk of long-term work disability compared to the matched cohort, peaking at the time of diagnosis (AOR = 1.89; CI 1.67–2.13). Four trajectory groups of work disability days were identified: constant low (60.3%, 5.6–11.2 days), low and increasing (11.4%, 11.8–152.5 days), medium–high and decreasing (11.1%, 65.1–110 days), and constant high (17.1%, 264–331 days). Individuals who were females, older, with prior psychiatric diagnosis, and had been dispensed a psychotropic medication, particularly antidepressants, were more likely to be assigned to groups other than the constant low.

Individuals with GD have an increased risk of work disability which may add financial and social pressure and is an additional incentive for earlier detection and prevention of GD.

Addressing aggressive behavior in adolescence is a key step toward preventing violence and associated social and economic costs in adulthood. This study examined the secondary effects of the personality-targeted substance use preventive program Preventure on aggressive behavior from ages 13 to 20.

In total, 339 young people from nine independent schools (M age = 13.03 years, s.d. = 0.47, range = 12–15) who rated highly on one of the four personality traits associated with increased substance use and other emotional/behavioral symptoms (i.e. impulsivity, anxiety sensitivity, sensation seeking, and negative thinking) were included in the analyses (n = 145 in Preventure, n = 194 in control). Self-report assessments were administered at baseline and follow-up (6 months, 1, 2, 3, 5.5, and 7 years). Overall aggression and subtypes of aggressive behaviors (proactive, reactive) were examined using multilevel mixed-effects analysis accounting for school-level clustering.

Across the 7-year follow-up period, the average yearly reduction in the frequency of aggressive behaviors (b = −0.42; 95% confidence interval [CI] −0.64 to −0.20; p < 0.001), reactive aggression (b = −0.22; 95% CI 0.35 to −0.10; p = 0.001), and proactive aggression (b = −0.14; 95% CI −0.23 to −0.05; p = 0.002) was greater for the Preventure group compared to the control group.

The study suggests a brief personality-targeted intervention may have long-term impacts on aggression among young people; however, this interpretation is limited by imbalance of sex ratios between study groups.

Major depressive disorder (MDD) contributes to suicide risk. Treating MDD effectively is considered a key suicide prevention intervention. Yet many patients with MDD do not respond to their initial medication and require a ‘next-step’. The relationship between next-step treatments and suicidal thoughts and behaviors is uncharted.

The VA Augmentation and Switching Treatments for Depression trial randomized 1522 participants to one of three next-step treatments: Switching to Bupropion, combining with Bupropion, and augmenting with Aripiprazole. In this secondary analysis, features associated with lifetime suicidal ideation (SI) and attempts (SA) at baseline and current SI during treatment were explored.

Compared to those with SI only, those with lifetime SI + SA were more likely to be female, divorced, or separated, unemployed; and to have experienced more childhood adversity. They had a more severe depressive episode and were more likely to respond to ‘next-step’ treatment. The prevalence of SI decreased from 46.5% (694/1492) at baseline to 21.1% (315/1492) at end-of-treatment. SI during treatment was associated with baseline SI; low positive mental health, more anxiety, greater severity and longer duration of current MDD episode; being male and White; and treatment with S-BUP or C-BUP as compared to A-ARI.

SI declines for most patients during next-step medication treatments. But about 1 in 5 experienced emergent or worsening SI during treatment, so vigilance for suicide risk through the entire 12-week acute treatment period is necessary. Treatment selection may affect the risk of SI.

Childhood is a crucial neurodevelopmental period. We investigated whether childhood reading for pleasure (RfP) was related to young adolescent assessments of cognition, mental health, and brain structure.

We conducted a cross-sectional and longitudinal study in a large-scale US national cohort (10 000 + young adolescents), using the well-established linear mixed model and structural equation methods for twin study, longitudinal and mediation analyses. A 2-sample Mendelian randomization (MR) analysis for potential causal inference was also performed. Important factors including socio-economic status were controlled.

Early-initiated long-standing childhood RfP (early RfP) was highly positively correlated with performance on cognitive tests and significantly negatively correlated with mental health problem scores of young adolescents. These participants with higher early RfP scores exhibited moderately larger total brain cortical areas and volumes, with increased regions including the temporal, frontal, insula, supramarginal; left angular, para-hippocampal; right middle-occipital, anterior-cingulate, orbital areas; and subcortical ventral-diencephalon and thalamus. These brain structures were significantly related to their cognitive and mental health scores, and displayed significant mediation effects. Early RfP was longitudinally associated with higher crystallized cognition and lower attention symptoms at follow-up. Approximately 12 h/week of youth regular RfP was cognitively optimal. We further observed a moderately significant heritability of early RfP, with considerable contribution from environments. MR analysis revealed beneficial causal associations of early RfP with adult cognitive performance and left superior temporal structure.

These findings, for the first time, revealed the important relationships of early RfP with subsequent brain and cognitive development and mental well-being.

Childhood trauma has been linked to increased risk of schizophrenia and social dysfunction, and oxytocin and its receptor gene have been implicated in regulating social behavior. This study investigated the potential role of oxytocin and oxytocin receptor gene (OXTR) in mediating the effects of childhood trauma on social functioning in schizophrenia.

The study consisted of 382 patients with schizophrenia and 178 healthy controls who were assessed using the Taiwanese version of the Childhood Trauma Questionnaire (CTQ-SF), the Social Functioning Scale (SFS), and plasma oxytocin levels. DNA was extracted to genotype the OXTR and ten single-nucleotide polymorphisms (SNPs; rs2254298, rs237885, rs237887, rs237899, rs53576, rs9840864, rs13316193, rs7632287, rs1042778, and rs237895) were selected.

Patients with schizophrenia showed higher CTQ-SF scores (t = 12.549, p < 0.001), lower SFS scores (t = −46.951, p < 0.001), and lower plasma oxytocin levels (t = −5.448, p < 0.001) compared to healthy controls. The study also found significant differences in OXTR SNPs between both groups, with risk alleles being more prevalent in patients with schizophrenia (t = 2.734, p = 0.006). Results indicated a significant moderated mediation effect, with oxytocin and the OXTR SNPs partially mediating the relationship between childhood trauma exposure and social functioning in patients with schizophrenia (index of mediation = 0.038, 95% CI [0.033–0.044]).

The findings suggest that oxytocin and its receptor gene may be promising targets for interventions aimed at improving social functioning in patients with a history of childhood trauma and schizophrenia. However, further research is needed to fully understand these effects and the potential of oxytocin-based interventions in this population.

Insecure attachment styles are associated with retrospectively reported suicide attempts (SAs). It is not known if attachment styles are prospectively associated with medically documented SAs.

A representative sample of US Army soldiers entering service (n = 21 772) was surveyed and followed via administrative records for their first 48 months of service. Attachment style (secure, preoccupied, fearful, dismissing) was assessed at baseline. Administrative medical records identified SAs. Discrete-time survival analysis examined associations of attachment style with future SA during service, adjusting for time in service, socio-demographics, service-related variables, and mental health diagnosis (MH-Dx). We examined whether associations of attachment style with SA differed based on sex and MH-Dx.

In total, 253 respondents attempted suicide. Endorsed attachment styles included secure (46.8%), preoccupied (9.1%), fearful (15.7%), and dismissing (19.2%). Examined separately, insecure attachment styles were associated with increased odds of SA: preoccupied [OR 2.5 (95% CI 1.7–3.4)], fearful [OR 1.6 (95% CI 1.1–2.3)], dismissing [OR 1.8 (95% CI 1.3–2.6)]. Examining attachment styles simultaneously along with other covariates, preoccupied [OR 1.9 (95% CI 1.4–2.7)] and dismissing [OR 1.7 (95% CI 1.2–2.4)] remained significant. The dismissing attachment and MH-Dx interaction was significant. In stratified analyses, dismissing attachment was associated with SA only among soldiers without MH-Dx. Other interactions were non-significant. Soldiers endorsing any insecure attachment style had elevated SA risk across the first 48 months in service, particularly during the first 12 months.

Insecure attachment styles, particularly preoccupied and dismissing, are associated with increased future SA risk among soldiers. Elevated risk is most substantial during first year of service but persists through the first 48 months. Dismissing attachment may indicate risk specifically among soldiers not identified by the mental healthcare system.

Hippocampal hyperperfusion has been observed in people at Clinical High Risk for Psychosis (CHR), is associated with adverse longitudinal outcomes and represents a potential treatment target for novel pharmacotherapies. Whether cannabidiol (CBD) has ameliorative effects on hippocampal blood flow (rCBF) in CHR patients remains unknown.

Using a double-blind, parallel-group design, 33 CHR patients were randomized to a single oral 600 mg dose of CBD or placebo; 19 healthy controls did not receive any drug. Hippocampal rCBF was measured using Arterial Spin Labeling. We examined differences relating to CHR status (controls v. placebo), effects of CBD in CHR (placebo v. CBD) and linear between-group relationships, such that placebo > CBD > controls or controls > CBD > placebo, using a combination of hypothesis-driven and exploratory wholebrain analyses.

Placebo-treated patients had significantly higher hippocampal rCBF bilaterally (all pFWE<0.01) compared to healthy controls. There were no suprathreshold effects in the CBD v. placebo contrast. However, we found a significant linear relationship in the right hippocampus (pFWE = 0.035) such that rCBF was highest in the placebo group, lowest in controls and intermediate in the CBD group. Exploratory wholebrain results replicated previous findings of hyperperfusion in the hippocampus, striatum and midbrain in CHR patients, and provided novel evidence of increased rCBF in inferior-temporal and lateral-occipital regions in patients under CBD compared to placebo.

These findings suggest that hippocampal blood flow is elevated in the CHR state and may be partially normalized by a single dose of CBD. CBD therefore merits further investigation as a potential novel treatment for this population.

Deaths from suicides, drug poisonings, and alcohol-related diseases (‘deaths of despair’) are well-documented among working-age Americans, and have been hypothesized to be largely specific to the U.S. However, support for this assertion–and associated policies to reduce premature mortality–requires tests concerning these deaths in other industrialized countries, with different institutional contexts. We tested whether the concentration and accumulation of health and social disadvantage forecasts deaths of despair, in New Zealand and Denmark.

We used nationwide administrative data. Our observation period was 10 years (NZ = July 2006–June 2016, Denmark = January 2007–December 2016). We identified all NZ-born and Danish-born individuals aged 25–64 in the last observation year (NZ = 1 555 902, Denmark = 2 541 758). We ascertained measures of disadvantage (public-hospital stays for physical- and mental-health difficulties, social-welfare benefit-use, and criminal convictions) across the first nine years. We ascertained deaths from suicide, drugs, alcohol, and all other causes in the last year.

Deaths of despair clustered within a population segment that disproportionately experienced multiple disadvantages. In both countries, individuals in the top 5% of the population in multiple health- and social-service sectors were at elevated risk for deaths from suicide, drugs, and alcohol, and deaths from other causes. Associations were evident across sex and age.

Deaths of despair are a marker of inequalities in countries beyond the U.S. with robust social-safety nets, nationwide healthcare, and strong pharmaceutical regulations. These deaths cluster within a highly disadvantaged population segment identifiable within health- and social-service systems.

Some preliminary research suggests higher rates of gastrointestinal disease in individuals with eating disorders (EDs). However, research is limited, and it remains unknown what etiologic factors account for observed associations. This was the first study to examine how EDs and dimensional ED symptoms (e.g. body dissatisfaction, binge eating) are phenotypically and etiologically associated with gastrointestinal disease in a large, population-based twin sample.

Adult female (N = 2980) and male (N = 2903) twins from the Michigan State University Twin Registry reported whether they had a lifetime ED (anorexia nervosa, bulimia nervosa, or binge-eating disorder) and completed a measure of dimensional ED symptoms. We coded the presence/absence of lifetime gastrointestinal disease (e.g. inflammatory bowel disease) based on responses to questions regarding chronic illnesses and medications. We first examined whether twins with gastrointestinal disease had higher rates of EDs and ED symptoms, then used correlated factors twin models to investigate genetic and environmental contributions to the overlap between disorders.

Twins with gastrointestinal disease had significantly greater dimensional ED symptoms (β = 0.21, p < 0.001) and odds of a lifetime ED (OR 2.90, p = 0.001), regardless of sex. Shared genetic factors fully accounted for the overlap between disorders, with no significant sex differences in etiologic associations.

Comorbidity between EDs and gastrointestinal disease may be explained by overlap in genetic influences, potentially including inflammatory genes implicated in both types of disorders. Screening for gastrointestinal disease in people with EDs, and EDs in those with gastrointestinal disease, is warranted.

Borderline personality disorder (BPD) is a debilitating condition characterized by pervasive instability across multiple major domains of functioning. The majority of persons with BPD engage in self-injury and up to 10% die by suicide – rendering persons with this condition at exceptionally elevated risk of comorbidity and premature mortality. Better characterization of clinical risk factors among persons with BPD who die by suicide is urgently needed.

We examined patterns of medical and psychiatric diagnoses (1580 to 1700 Phecodes) among persons with BPD who died by suicide (n = 379) via a large suicide death data resource and biobank. In phenotype-based phenome-wide association tests, we compared these individuals to three other groups: (1) persons who died by suicide without a history of BPD (n = 9468), (2) persons still living with a history of BPD diagnosis (n = 280), and (3) persons who died by suicide with a different personality disorder (other PD n = 589).

Multivariable logistic regression models revealed that persons with BPD who died by suicide were more likely to present with co-occurring psychiatric diagnoses, and have a documented history of self-harm in the medical system prior to death, relative to suicides without BPD. Posttraumatic stress disorder was more elevated among those with BPD who died by suicide relative to the other PD group.

We found significant differences among persons with BPD who died by suicide and all other comparison groups. Such differences may be clinically informative for identifying high-risk subtypes and providing targeted intervention approaches.

Psychiatric disorders may be a risk factor for long COVID, broadly defined as COVID-19 conditions continuing three months post-acute infection. In US Veterans with high psychiatric burden, we examined associations between psychiatric disorders and clinical diagnosis of long COVID.

We conducted a retrospective cohort study using health records from VA patients with a positive SARS-CoV-2 test from February 2020 to February 2023. Generalized linear models estimated associations between any psychiatric disorder and likelihood of subsequent diagnosis with long COVID (i.e. two or more long COVID clinical codes). Models were adjusted for socio-demographic, medical, and behavioral factors. Secondary models examined individual psychiatric disorders and age-stratified associations.

Among 660 217 VA patients with positive SARS-CoV-2 tests, 56.3% had at least one psychiatric disorder diagnosis and 1.4% were diagnosed with long COVID. Individuals with any psychiatric disorder had higher risk for long COVID diagnosis in models adjusted for socio-demographic factors, vaccination status, smoking, and medical comorbidities (relative risk, RR = 1.28, 95% CI 1.21–1.35), with the strongest associations in younger individuals. Considering specific disorders, depressive, anxiety, and stress-related disorders were associated with increased risk for long COVID diagnoses (RRs = 1.36–1.48), but associations were in the opposite direction for substance use and psychotic disorders (RRs = 0.78–0.88).

Psychiatric disorder diagnoses were associated with increased long COVID diagnosis risk in VA patients, with the strongest associations observed in younger individuals. Improved surveillance, treatment, and prevention for COVID-19 and its long-term sequelae should be considered for individuals with psychiatric conditions.

Controlled research examining maintenance treatments for responders to acute interventions for binge-eating disorder (BED) is limited. This study tested efficacy of lisdexamfetamine (LDX) maintenance treatment amongst acute responders.

This prospective randomized double-blind placebo-controlled single-site trial, conducted March 2019 to September 2023, tested LDX as maintenance treatment for responders to acute treatments with LDX-alone or with cognitive-behavioral therapy (CBT + LDX) for BED with obesity. Sixty-one (83.6% women, mean age 44.3, mean BMI 36.1 kg/m2) acute responders were randomized to LDX (N = 32) or placebo (N = 29) for 12 weeks; 95.1% completed posttreatment assessments. Mixed-models and generalized-estimating equations comparing maintenance LDX v. placebo included main/interactive effects of acute (LDX or CBT + LDX) treatments to examine their predictive/moderating effects.

Relapse rates (to diagnosis-level binge-eating frequency) following maintenance treatments were 10.0% (N = 3/30) for LDX and 17.9% (N = 5/28) for placebo; intention-to-treat binge-eating remission rates were 59.4% (N = 19/32) and 65.5% (N = 19/29), respectively. Maintenance LDX and placebo did not differ significantly in binge-eating but differed in weight-loss and eating-disorder psychopathology. Maintenance LDX was associated with significant weight-loss (−2.3%) whereas placebo had significant weight-gain (+2.2%); LDX and placebo differed significantly in weight-change throughout treatment and at posttreatment. Eating-disorder psychopathology remained unchanged with LDX but increased significantly with placebo. Acute treatments did not significantly predict/moderate maintenance-treatment outcomes.

Adults with BED/obesity who respond to acute lisdexamfetamine treatment (regardless of additionally receiving CBT) had good maintenance during subsequent 12-weeks. Maintenance lisdexamfetamine, relative to placebo, did not provide further benefit for binge-eating but was associated with significantly better eating-disorder psychopathology outcomes and greater weight-loss.

There is growing evidence for the use of acceptance-commitment therapy (ACT) for the treatment of obsessive-compulsive disorder (OCD). However, few fully implemented ACT have been conducted on the neural mechanisms underlying its effect on OCD. Thus, this study aimed to elucidate the neural correlates of ACT in patients with OCD using task-based and resting-state functional magnetic resonance imaging (fMRI).

Patients with OCD were randomly assigned to the ACT (n = 21) or the wait-list control group (n = 21). An 8-week group-format ACT program was provided to the ACT group. All participants underwent an fMRI scan and psychological measurements before and after 8 weeks.

Patients with OCD showed significantly increased activation in the bilateral insula and superior temporal gyri (STG), induced by the thought-action fusion task after ACT intervention. Further psycho-physiological interaction analyses with these regions as seeds revealed that the left insular–left inferior frontal gyrus (IFG) connectivity was strengthened in the ACT group after treatment. Increased resting-state functional connectivity was also found in the posterior cingulate cortex (PCC), precuneus, and lingual gyrus after ACT intervention Most of these regions showed significant correlations with ACT process measures while only the right insula was correlated with the obsessive-compulsive symptom measure.

These findings suggest that the therapeutic effect of ACT on OCD may involve the salience and interoception processes (i.e. insula), multisensory integration (i.e. STG), language (i.e. IFG), and self-referential processes (i.e. PCC and precuneus). These areas or their interactions could be important for understanding how ACT works psychologically.

Attention-deficit hyperactivity disorder (ADHD) is often comorbid with other medical conditions in adult patients. However, ADHD is extremely underdiagnosed in adults and little is known about the medical comorbidities in undiagnosed adult individuals with high ADHD liability. In this study we investigated associations between ADHD genetic liability and electronic health record (EHR)-based ICD-10 diagnoses across all diagnostic categories, in individuals without ADHD diagnosis history.

We used data from the Estonian Biobank cohort (N = 111 261) and generated polygenic risk scores (PRS) for ADHD (PRSADHD) based on the ADHD genome-wide association study. We performed a phenome-wide association study (PheWAS) to test for associations between standardized PRSADHD and 1515 EHR-based ICD-10 diagnoses in the full and sex-stratified sample. We compared the observed significant ICD-10 associations to associations with (1) ADHD diagnosis and (2) questionnaire-based high ADHD risk analyses.

After Bonferroni correction (p = 3.3 × 10−5) we identified 80 medical conditions associated with PRSADHD. The strongest evidence was seen with chronic obstructive pulmonary disease (OR 1.15, CI 1.11–1.18), obesity (OR 1.13, CI 1.11–1.15), and type 2 diabetes (OR 1.11, CI 1.09–1.14). Sex-stratified analysis generally showed similar associations in males and females. Out of all identified associations, 40% and 78% were also observed using ADHD diagnosis or questionnaire-based ADHD, respectively, as the predictor.

Overall our findings indicate that ADHD genetic liability is associated with an increased risk of a substantial number of medical conditions in undiagnosed individuals. These results highlight the need for timely detection and improved management of ADHD symptoms in adults.

The age-related heterogeneity in major depressive disorder (MDD) has received significant attention. However, the neural mechanisms underlying such heterogeneity still need further investigation. This study aimed to explore the common and distinct functional brain abnormalities across different age groups of MDD patients from a large-sample, multicenter analysis.

The analyzed sample consisted of a total of 1238 individuals including 617 MDD patients (108 adolescents, 12–17 years old; 411 early-middle adults, 18–54 years old; and 98 late adults, > = 55 years old) and 621 demographically matched healthy controls (60 adolescents, 449 early-middle adults, and 112 late adults). MDD-related abnormalities in brain functional connectivity (FC) patterns were investigated in each age group separately and using the whole pooled sample, respectively.

We found shared FC reductions among the sensorimotor, visual, and auditory networks across all three age groups of MDD patients. Furthermore, adolescent patients uniquely exhibited increased sensorimotor-subcortical FC; early-middle adult patients uniquely exhibited decreased visual-subcortical FC; and late adult patients uniquely exhibited wide FC reductions within the subcortical, default-mode, cingulo-opercular, and attention networks. Analysis of covariance models using the whole pooled sample further revealed: (1) significant main effects of age group on FCs within most brain networks, suggesting that they are decreased with aging; and (2) a significant age group × MDD diagnosis interaction on FC within the default-mode network, which may be reflective of an accelerated aging-related decline in default-mode FCs.

To summarize, these findings may deepen our understanding of the age-related biological and clinical heterogeneity in MDD.

While antipsychotic medication reduces the risk of relapse for patients with schizophrenia, high prevalence of adverse effects results in low adherence. Lower doses of antipsychotics have been associated with increased level of function but also with increased risk of relapse. This study presents findings from a specialized deprescribing clinic. In addition, we aim to identify clinical predictors for relapse.

Patients diagnosed with schizophrenia were referred to the clinic, which offers a six-month guided tapering program. Antipsychotic dose was reduced by 10% every four weeks. Patients were monitored closely for symptom progression or decrease in level of function, with defined cut-offs prompting a pause in or cessation of dose reduction.

After 12 months, the antipsychotic dose was reduced from 404 (±320 mg) to 255 (±236 mg) chlorpromazine equivalent. Of the 88 patients included, 22 (27%) experienced relapse during the six-month tapering period, while 29 (37%) experienced relapse at the 12-month follow-up visit and nine patients were antipsychotic free. Patients who remained stable experienced a slightly increased level of functioning and markedly fewer side effects (p < 0.001). Following relapse, patients were clinically stabilized and showed an improved attitude toward antipsychotic medication. The predictive models were weak.

We show that most patients undergoing guided antipsychotic tapering remained stable after one year and improved in level of function, while most patients who relapsed were quickly stabilized. Our inability to create strong predictive models could be due to limitations in the study design, warranting future studies exploring tapering of antipsychotics in patients with schizophrenia.

Extensive research has focused on the potential benefits of education on various mental and physical health outcomes. However, whether the associations reflect a causal effect is harder to establish.

To examine associations between educational duration and specific aspects of well-being, anxiety and mood disorders, and cardiovascular health in a sample of European Ancestry UK Biobank participants born in England and Wales, we apply four different causal inference methods (a natural policy experiment leveraging the minimum school-leaving age, a sibling-control design, Mendelian randomization [MR], and within-family MR), and assess if the methods converge on the same conclusion.

A comparison of results across the four methods reveals that associations between educational duration and these outcomes appears predominantly to be the result of confounding or bias rather than a true causal effect of education on well-being and health outcomes. Although we do consistently find no associations between educational duration and happiness, family satisfaction, work satisfaction, meaning in life, anxiety, and bipolar disorder, we do not find consistent significant associations across all methods for the other phenotypes (health satisfaction, depression, financial satisfaction, friendship satisfaction, neuroticism, and cardiovascular outcomes).

We discuss inconsistencies in results across methods considering their respective limitations and biases, and additionally discuss the generalizability of our findings in light of the sample and phenotype limitations. Overall, this study strengthens the idea that triangulation across different methods is necessary to enhance our understanding of the causal consequences of educational duration.