Cumulative burden from vascular risk factors (VRFs) has been associated with an increased risk of depressive symptoms in mid- and later life. It has been hypothesised that this association arises because VRFs disconnect fronto-subcortical white matter tracts involved in mood regulation, which puts older adults at higher risk of developing depressive symptoms. However, evidence for the hypothesis that disconnection of white matter tracts underlies the association between VRF burden and depressive symptoms from longitudinal studies is scarce.

This preregistered study analysed longitudinal data from 6,964 middle-aged and older adults from the UK Biobank who participated in consecutive assessments of VRFs, brain imaging, and depressive symptoms. Using mediation modelling, we directly tested to what extend white matter microstructure mediates the longitudinal association between VRF burden and depressive symptoms.

VRF burden showed a small association with depressive symptoms at follow-up. However, there was no evidence that fractional anisotropy (FA) of white matter tracts mediated this association. Additional analyses also yielded no mediating effects using alternative operationalisations of VRF burden, mean diffusivity (MD) of single tracts, or overall average of tract-based white matter microstructure (global FA, global MD, white matter hyperintensity volume).

Our results lend no support to the hypothesis that disconnection of white matter tracts underlies the association between VRF burden and depressive symptoms, while highlighting the relevance of using longitudinal data to directly test pathways linking vascular and mental health.

Cognitive deficits are a core feature of schizophrenia and are closely associated with poor functional outcomes. It remains unclear if cognitive deficits progress over time or remain stable. Determining patients at increased risk of progressive worsening might help targeted neurocognitive remediation approaches.

This 20-year follow-up study examined neurocognitive outcomes of 156 participants from the OPUS I trial. Neurocognition was assessed using the brief assessment of cognition in schizophrenia at the 10- and 20-year follow-up, allowing us to examine changes in neurocognition over ten years.

We found that 30.5% of patients had a declining course of neurocognition, 49.2% had a stable course of neurocognition and 20.3% experienced improvements in neurocognition. Good cognitive functioning at the 20-year follow-up was significantly associated with higher levels of social functioning (B 6.86, CI 4.71–9.02, p < 0.001) while increasing experiential negative symptoms were significantly correlated to cognitive worsening (PC-0.231, p = 0.029). Younger age at inclusion (B: 0.23 per 10-years, CI 0.00–0.045, p = 0.047) and low level of education (below ten years) (mean difference: −0.346, CI −0.616 to −0.076, p = 0.012) predicted declining neurocognition.

Our findings support the notion of different schizophrenia subtypes with varying trajectories. Neurocognitive impairment at the 20-year follow-up was associated with other poor outcomes, highlighting the importance of treatments aimed at improving neurocognition in patients with schizophrenia spectrum disorders.

Patients can respond differently to intervention in the early phase of psychosis. Diverse symptomatic and functional outcomes can be distinguished and achieving one outcome may mean achieving another, but not necessarily the other way round, which is difficult to disentangle with cross-sectional data. The present study's goal was to evaluate implicative relationships between diverse functional outcomes to better understand their reciprocal dependencies in a cross-sectional design, by using statistical implication analysis (SIA).

Early psychosis patients of an early intervention program were evaluated for different outcomes (symptomatic response, functional recovery, and working/living independently) after 36 months of treatment. To determine which positive outcomes implied other positive outcomes, SIA was conducted by using the Iota statistical implication index, a newly developed approach allowing to measure asymmetrical bidirectional relationships between outcomes.

Two hundred and nineteen recent onset patients with early psychosis were assessed. Results at the end of the three-years in TIPP showed that working independently statistically implied achieving all other outcomes. Symptomatic and functional recovery reciprocally implied one another. Living independently weakly implied symptomatic and functional recovery and did not imply independent working.

The concept of implication is an interesting way of evaluating dependencies between outcomes as it allows us to overcome the tendency to presume symmetrical relationships between them. We argue that a better understanding of reciprocal dependencies within psychopathology can provide an impetus to tailormade treatments and SIA is a useful tool to address this issue in cross-sectional designs.

Epidemiological data offer conflicting views of the natural course of binge-eating disorder (BED), with large retrospective studies suggesting a protracted course and small prospective studies suggesting a briefer duration. We thus examined changes in BED diagnostic status in a prospective, community-based study that was larger and more representative with respect to sex, age of onset, and body mass index (BMI) than prior multi-year prospective studies.

Probands and relatives with current DSM-IV BED (n = 156) from a family study of BED (‘baseline’) were selected for follow-up at 2.5 and 5 years. Probands were required to have BMI > 25 (women) or >27 (men). Diagnostic interviews and questionnaires were administered at all timepoints.

Of participants with follow-up data (n = 137), 78.1% were female, and 11.7% and 88.3% reported identifying as Black and White, respectively. At baseline, their mean age was 47.2 years, and mean BMI was 36.1. At 2.5 (and 5) years, 61.3% (45.7%), 23.4% (32.6%), and 15.3% (21.7%) of assessed participants exhibited full, sub-threshold, and no BED, respectively. No participants displayed anorexia or bulimia nervosa at follow-up timepoints. Median time to remission (i.e. no BED) exceeded 60 months, and median time to relapse (i.e. sub-threshold or full BED) after remission was 30 months. Two classes of machine learning methods did not consistently outperform random guessing at predicting time to remission from baseline demographic and clinical variables.

Among community-based adults with higher BMI, BED improves with time, but full remission often takes many years, and relapse is common.

Class and social disadvantage have long been identified as significant factors in the etiology and epidemiology of psychosis. Few studies have explicitly examined the impact of intersecting social disadvantage on long-term employment and financial independence.

We applied latent class analysis (LCA) to 20-year longitudinal data from participants with affective and non-affective psychosis (n = 256) within the Chicago Longitudinal Research. LCA groups were modeled using multiple indicators of pre-morbid disadvantage (parental social class, educational attainment, race, gender, and work and social functioning prior to psychosis onset). The comparative longitudinal work and financial functioning of LCA groups were then examined.

We identified three distinct latent classes: one comprised entirely of White participants, with the highest parental class and highest levels of educational attainment; a second predominantly working-class group, with equal numbers of Black and White participants; and a third with the lowest parental social class, lowest levels of education and a mix of Black and White participants. The latter, our highest social disadvantage group experienced significantly poorer employment and financial outcomes at all time-points, controlling for diagnosis, symptoms, and hospitalizations prior to baseline. Contrary to our hypotheses, on most measures, the two less disadvantaged groups did not significantly differ from each other.

Our analyses add to a growing literature on the impact of multiple forms of social disadvantage on long-term functional trajectories, underscoring the importance of proactive attention to sociostructural disadvantage early in treatment, and the development and evaluation of interventions designed to mitigate ongoing social stratification.

People with schizophrenia-spectrum and bipolar disorders (severe mental illnesses; ‘SMI’) experience excess mortality. Our aim was to explore longer-term trends in mortality, including the COVID-19 pandemic period, with a focus on additional vulnerabilities (psychiatric comorbidities and race/ ethnicity) in SMI.

Retrospective cohort study using electronic health records from secondary mental healthcare, covering a UK region of 1.3 million people. Mortality trends spanning fourteen years, including the COVID-19 pandemic, were assessed in adults with clinician-ascribed ICD-10 diagnoses for schizophrenia-spectrum and bipolar disorders.

The sample comprised 22 361 people with SMI with median follow-up of 10.6 years. Standardized mortality ratios were more than double the population average pre-pandemic, increasing further during the pandemic, particularly in those with SMI and psychiatric comorbidities. Mortality risk increased steadily among people with SMI and comorbid depression, dementia, substance use disorders and anxiety over 13-years, increasing further during the pandemic. COVID-19 mortality was elevated in people with SMI and comorbid depression (sub-Hazard Ratio: 1.48 [95% CI 1.03–2.13]), dementia (sHR:1.96, 1.26–3.04) and learning disabilities (sHR:2.30, 1.30–4.06), compared to people with only SMI. COVID-19 mortality risk was similar for minority ethnic groups and White British people with SMI. Elevated all-cause mortality was evident in Black Caribbean (adjusted Rate Ratio: 1.40, 1.11–1.77) and Black African people with SMI (aRR: 1.59, 1.07–2.37) during the pandemic relative to earlier years.

Mortality has increased over time in people with SMI. The pandemic exacerbated pre-existing trends. Actionable solutions are needed which address wider social determinants and address disease silos.

Childhood trauma (CT) may increase vulnerability to psychopathology through affective dysregulation (greater variability, autocorrelation, and instability of emotional symptoms). However, CT associations with dynamic affect fluctuations while considering differences in mean affect levels across CT status have been understudied.

346 adults (age = 49.25 ± 12.55, 67.0% female) from the Netherlands Study of Depression and Anxiety participated in ecological momentary assessment. Positive and negative affect (PA, NA) were measured five times per day for two weeks by electronic diaries. Retrospectively-reported CT included emotional neglect and emotional/physical/sexual abuse. Linear regressions determined associations between CT and affect fluctuations, controlling for age, sex, education, and mean affect levels.

Compared to those without CT, individuals with CT reported significantly lower mean PA levels (Cohen's d = −0.620) and higher mean NA levels (d = 0.556) throughout the two weeks. CT was linked to significantly greater PA variability (d = 0.336), NA variability (d = 0.353), and NA autocorrelation (d = 0.308), with strongest effects for individuals reporting higher CT scores. However, these effects were entirely explained by differences in mean affect levels between the CT groups. Findings suggested consistency of results in adults with and without lifetime depressive/anxiety disorders and across CT types, with sexual abuse showing the smallest effects.

Individuals with CT show greater affective dysregulation during the two-week monitoring of emotional symptoms, likely due to their consistently lower PA and higher NA levels. It is essential to consider mean affect level when interpreting the impact of CT on affect dynamics.

We investigated (a) whether polygenic risk for schizophrenia predicts different trajectories of social development among those who have not developed psychoses and (b) whether possible associations are PRSSCZ-specific or evident also for any polygenic risk for mental disorders, e.g. for major depression.

Participants came from the population-based Young Finns Study (n = 2377). We calculated a polygenic risk score for schizophrenia (PRSSCZ) and for major depression (PRSDEP). Diagnoses of psychotic disorders were derived from the hospital care register. Social development from adolescence to middle age was measured by (a) perceived social support from friends, family, and a close other, (b) perceived sociability, and (c) family structure (partnership status, number of children, age of first-time parenthood).

Among those without manifest psychoses, high PRSSCZ predicted lower experienced support from friends (B = −0.04, p = 0.009–0.035) and family (B = −0.04, p = 0.009–0.035) especially after early adulthood, and also lower perceived sociability (B = −0.05, p = 0.010–0.026). PRSSCZ was not related to family structure. PRSDEP did not predict any domain of social development.

Individuals at high PRSSCZ (not converted to psychosis) seem to experience a lower preference to be with others over being alone. Individuals with high (v. low) PRSSCZ seem to have a similar family structure in terms of partnership status or number of children but, nevertheless, they experience less support from their family. Among those not converted to psychosis in a typical age period, high PRSSCZ may predict a ‘later risk phase’ and reduced functional resilience when approaching middle age.

This article presents the results of two studies investigating increased intra-individual variability (IIV) in the performance of individuals with attention deficit hyperactivity disorder (ADHD), in two cognitive domains: numerosity judgments and quantitative and verbal reasoning.

Study 1, a pre-registered experiment, involved approximately 200 participants (42.66% female; mean age: 36.86; standard deviation of age: 10.70) making numerical judgments at two time-points. ADHD-symptom severity was assessed on a continuous scale. In Study 2, we collected the data of approximately 3000 examinees who had taken a high-stakes admissions test for higher education (assessing quantitative and verbal reasoning). The sample comprised only people formally diagnosed with ADHD. The control group consisted of approximately 200 000 examinees, none of whom presented with ADHD.

The results of Study 1 revealed a positive correlation between IIV (distance between judgments at the two time-points) and ADHD symptom severity. The results of Study 2 demonstrated that IIV (distance between the scores on two test chapters assessing the same type of reasoning) was greater among examinees diagnosed with ADHD. In both studies, the findings persisted even after controlling for performance level.

The results indicate that individuals with ADHD, v. those without, exhibit less consistent numerosity judgments and greater fluctuation in performance on verbal and quantitative reasoning. The measurement of the same psychological constructs appears to be less precise among individuals with ADHD compared to those without. We discuss the theoretical contributions and practical implications of our results for two fields: judgment and decision-making, and assessment.

Inconsistent results regarding the risk of relapse and better subjective outcomes of previous antipsychotic dose reduction trials in patients with remitted psychosis have not been verified using therapeutic drug monitoring (TDM). This study examined plasma drug concentrations of a dose-tapering trial which exhibited the potential of successful maintenance under lower antipsychotic dosages.

A 2-year open-label randomized prospective trial recruited remitted patients to undergo guided antipsychotic tapering. Blood samples were collected at baseline, annually, and after each dose reduction. Plasma aripiprazole/dehydroaripiprazole concentrations were determined using LC–MS/MS. The relationship between the dose and serum drug levels was examined using Spearman's correlation. Divided at 120 ng/mL, relapse rate, global function, quality of life, and psychopathology were compared between high- and low- drug level groups.

A total of 126 blood samples were collected, after excluding13 samples due of non-adherence. The correlation coefficients between dosage and drug level were 0.853 (aripiprazole) and 0.864 (dehydroaripiprazole), and the dose and concentration plots were parallel along the tapering trajectories, except patients with non-adherence. The concentration-to-dose ratio of aripiprazole in this cohort, 17.79 ± 7.23 ng/mL/mg, was higher than that in Caucasian populations. No significant differences were observed in the clinical outcomes between the high- and low-level groups. Remarkably, 12 of 15 patients maintained remission at plasma aripiprazole concentrations of <120 ng/mL.

The lower-than-expected doses reached in our antipsychotic tapering trial were substantiated to provide adequate prophylactic effects by TDM results in a subset of patients treated with aripiprazole, even considering the differences in pharmacogenomics between ethnicities.

The neuroanatomical alteration in bipolar II depression (BDII-D) and its associations with inflammation, childhood adversity, and psychiatric symptoms are currently unclear. We hypothesize that neuroanatomical deficits will be related to higher inflammation, greater childhood adversity, and worse psychiatric symptoms in BDII-D.

Voxel- and surface-based morphometry was performed using the CAT toolbox in 150 BDII-D patients and 155 healthy controls (HCs). Partial Pearson correlations followed by multiple comparison correction was used to indicate significant relationships between neuroanatomy and inflammation, childhood adversity, and psychiatric symptoms.

Compared with HCs, the BDII-D group demonstrated significantly smaller gray matter volumes (GMVs) in frontostriatal and fronto-cerebellar area, insula, rectus, and temporal gyrus, while significantly thinner cortices were found in frontal and temporal areas. In BDII-D, smaller GMV in the right middle frontal gyrus (MFG) was correlated with greater sexual abuse (r = −0.348, q < 0.001) while larger GMV in the right orbital MFG was correlated with greater physical neglect (r = 0.254, q = 0.03). Higher WBC count (r = −0.227, q = 0.015) and IL-6 levels (r = −0.266, q = 0.015) was associated with smaller GMVs in fronto-cerebellar area in BDII-D. Greater positive symptoms was correlated with larger GMVs of the left middle temporal pole (r = 0.245, q = 0.03).

Neuroanatomical alterations in frontostriatal and fronto-cerebellar area, insula, rectus, temporal gyrus volumes, and frontal-temporal thickness may reflect a core pathophysiological mechanism of BDII-D, which are related to inflammation, trauma, and psychiatric symptoms in BDII-D.

Theoretical models of neural mechanisms underlying Cognitive Behavior Therapy (CBT) for major depressive disorder (MDD) propose that psychotherapy changes neural functioning of prefrontal cortical structures associated with cognitive-control processes (DeRubeis, Siegle, & Hollon, 2008); however, MDD is persistent and characterized by long-lasting vulnerabilities to recurrence after intervention, suggesting that underlying neural mechanisms of MDD remain despite treatment. It follows that identification of treatment-resistant aberrant neural processes in MDD may inform clinical and research efforts targeting sustained remission. Thus, we sought to identify brain regions showing aberrant neural functioning in MDD that either (1) fail to exhibit substantive change (nonresponse) or (2) exhibit functional changes (response) following CBT.

To identify treatment-resistant neural processes (as well as neural processes exhibiting change after treatment), we collected functional magnetic resonance imaging (fMRI) data of MDD patients (n = 58) before and after CBT as well as never-depressed controls (n = 35) before and after a similar amount of time. We evaluated fMRI data using conjunction analyses, which utilized several contrast-based criteria to characterize brain regions showing both differences between patients and controls at baseline and nonresponse or response to CBT.

Findings revealed nonresponse in a cerebellar region and response in prefrontal and parietal regions.

Results are consistent with prior theoretical models of CBT's direct effect on cortical regulatory processes but expand on them with identification of additional regions (and associated neural systems) of response and nonresponse to CBT.

People with schizophrenia on average are more socially isolated, lonelier, have more social cognitive impairment, and are less socially motivated than healthy individuals. People with bipolar disorder also have social isolation, though typically less than that seen in schizophrenia. We aimed to disentangle whether the social cognitive and social motivation impairments observed in schizophrenia are a specific feature of the clinical condition v. social isolation generally.

We compared four groups (clinically stable patients with schizophrenia or bipolar disorder, individuals drawn from the community with self-described social isolation, and a socially connected community control group) on loneliness, social cognition, and approach and avoidance social motivation.

Individuals with schizophrenia (n = 72) showed intermediate levels of social isolation, loneliness, and social approach motivation between the isolated (n = 96) and connected control (n = 55) groups. However, they showed significant deficits in social cognition compared to both community groups. Individuals with bipolar disorder (n = 48) were intermediate between isolated and control groups for loneliness and social approach. They did not show deficits on social cognition tasks. Both clinical groups had higher social avoidance than both community groups

The results suggest that social cognitive deficits in schizophrenia, and high social avoidance motivation in both schizophrenia and bipolar disorder, are distinct features of the clinical conditions and not byproducts of social isolation. In contrast, differences between clinical and control groups on levels of loneliness and social approach motivation were congruent with the groups' degree of social isolation.

Inducing hallucinations under controlled experimental conditions in non-hallucinating individuals represents a novel research avenue oriented toward understanding complex hallucinatory phenomena, avoiding confounds observed in patients. Auditory-verbal hallucinations (AVH) are one of the most common and distressing psychotic symptoms, whose etiology remains largely unknown. Two prominent accounts portray AVH either as a deficit in auditory-verbal self-monitoring, or as a result of overly strong perceptual priors.

In order to test both theoretical models and evaluate their potential integration, we developed a robotic procedure able to induce self-monitoring perturbations (consisting of sensorimotor conflicts between poking movements and corresponding tactile feedback) and a perceptual prior associated with otherness sensations (i.e. feeling the presence of a non-existing another person).

Here, in two independent studies, we show that this robotic procedure led to AVH-like phenomena in healthy individuals, quantified as an increase in false alarm rate in a voice detection task. Robotically-induced AVH-like sensations were further associated with delusional ideation and to both AVH accounts. Specifically, a condition with stronger sensorimotor conflicts induced more AVH-like sensations (self-monitoring), while, in the otherness-related experimental condition, there were more AVH-like sensations when participants were detecting other-voice stimuli, compared to detecting self-voice stimuli (strong-priors).

By demonstrating an experimental procedure able to induce AVH-like sensations in non-hallucinating individuals, we shed new light on AVH phenomenology, thereby integrating self-monitoring and strong-priors accounts.

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.

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.

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.

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.

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.

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.