Individuals with attention-deficit hyperactivity disorder (ADHD) often display over-response to stimuli that are irrelevant to the ongoing task, and their attentional abilities disproportionately worsen in the presence of competing stimuli. Auditory event-related potentials (ERPs) such as mismatch negativity (MMN) and P3a using the passive oddball paradigm have been studied in children and adolescents with ADHD. Still, there is no such data for adults with ADHD. This study aimed to compare the MMN and P3a and their clinical and neurocognitive correlations between drug-naive adults with ADHD and control adults.

We recruited 52 adults with ADHD (26.5 ± 6.2 years), and 62 age-matched controls (25.6 ± 5.6 years). They received the psychiatric interviews, auditory ERP, the Conners' continuous performance test (CCPT), and the Cambridge gambling test (CGT). They also completed the questionnaires about ADHD symptoms and real-world executive functions. MMN and P3a were assessed during a passive duration-deviant auditory oddball paradigm from the midline electrodes Cz.

Adults with ADHD demonstrated smaller Cz MMN amplitude, more severe ADHD symptoms, poorer attention profiles (CCPT), and a wide range of executive dysfunctions than controls. As for the correlates, Cz peak amplitude of MMN correlated with inattention symptoms, executive dysfunctions, attentional vigilance (CCPT), and decision-making (CGT) in ADHD adults but only with decision-making in controls.

Our findings that smaller amplitude of MMN and its differential associated pattern with inattention, real-world executive dysfunction, and decision-making, in drug-naive adults with ADHD from adult controls, provide evidence to support the potential electrophysiological biomarker for adult ADHD.

The occurrence of early childhood adversity is strongly linked to later self-harm, but there is poor understanding of how this distal risk factor might influence later behaviours. One possible mechanism is through an earlier onset of puberty in children exposed to adversity, since early puberty is associated with an increased risk of adolescent self-harm. We investigated whether early pubertal timing mediates the association between childhood adversity and later self-harm.

Participants were 6698 young people from a UK population-based birth cohort (ALSPAC). We measured exposure to nine types of adversity from 0 to 9 years old, and self-harm when participants were aged 16 and 21 years. Pubertal timing measures were age at peak height velocity (aPHV – males and females) and age at menarche (AAM). We used generalised structural equation modelling for analyses.

For every additional type of adversity; participants had an average 12–14% increased risk of self-harm by 16. Relative risk (RR) estimates were stronger for direct effects when outcomes were self-harm with suicidal intent. There was no evidence that earlier pubertal timing mediated the association between adversity and self-harm [indirect effect RR 1.00, 95% confidence interval (CI) 1.00–1.00 for aPHV and RR 1.00, 95% CI 1.00–1.01 for AAM].

A cumulative measure of exposure to multiple types of adversity does not confer an increased risk of self-harm via early pubertal timing, however both childhood adversity and early puberty are risk factors for later self-harm. Research identifying mechanisms underlying the link between childhood adversity and later self-harm is needed to inform interventions.

A possible role of vitamin D in the pathophysiology of depression is currently speculative, with more rigorous research needed to assess this association in large adult populations. The current study assesses prospective associations between vitamin D status and depression in middle-aged adults enrolled in the UK Biobank.

We assessed prospective associations between vitamin D status at the baseline assessment (2006–2010) and depression measured at the follow-up assessment (2016) in 139 128 adults registered with the UK Biobank.

Amongst participants with no depression at baseline (n = 127 244), logistic regression revealed that those with vitamin D insufficiency [adjusted odds ratio (aOR) = 1.14, 95% confidence interval (CI) = 1.07–1.22] and those with vitamin D deficiency (aOR = 1.24, 95% CI 1.13–1.36) were more likely to develop new-onset depression at follow-up compared with those with optimal vitamin D levels after adjustment for a wide range of relevant covariates. Similar prospective associations were reported for those with depression at baseline (n = 11 884) (insufficiency: aOR = 1.11, 95% CI 1.00–1.23; deficiency: aOR = 1.30, 95% CI 1.13–1.50).

The prospective associations found between vitamin D status and depression suggest that both vitamin D deficiency and insufficiency might be risk factors for the development of new-onset depression in middle-aged adults. Moreover, vitamin D deficiency (and to a lesser extent insufficiency) might be a predictor of sustained depressive symptoms in those who are already depressed. Vitamin D deficiency and insufficiency is very common, meaning that these findings have significant implications for public health.

Apathy is common in Parkinson's disease (PD) but its underlying white matter (WM) architecture is not well understood. Moreover, how apathy affects cognitive functions in PD remains unclear. We investigated apathy-related WM network alterations and the impact of apathy on cognition in the context of PD.

Apathetic PD patients (aPD), non-apathetic PD patients (naPD), and matched healthy controls (HCs) underwent brain scans and clinical assessment. Graph-theoretical and network-based analyses were used for group comparisons of WM features derived from diffusion spectrum imaging (DSI). Path analysis was used to determine the direct and indirect effects of apathy and other correlates on different cognitive functions.

The aPD group was impaired on neural integration measured by global efficiency (p = 0.009) and characteristic path length (p = 0.04), executive function (p < 0.001), episodic memory (p < 0.001) and visuospatial ability (p = 0.02), and had reduced connectivity between the bilateral parietal lobes and between the putamen and temporal regions (p < 0.05). In PD, executive function was directly impacted by apathy and motor severity and indirectly influenced by depression; episodic memory was directly and indirectly impacted by apathy and depression, respectively; conversely, visuospatial ability was not related to any of these factors. Neural integration, though being marginally correlated with apathy, was not associated with cognition.

Our results suggest compromised neural integration and reduced structural connectivity in aPD. Apathy, depression, and motor severity showed distinct impacts on different cognitive functions with apathy being the most influential determinant of cognition in PD.

Major depressive disorder is characterized by a high risk of relapse. We aimed to compare the prophylactic effects of different antidepressant medicines (ADMs).

PubMed, Cochrane Central Register of Controlled Trials, Embase and the Web of Science were searched on 4 July 2019. A pooled analysis of parametric survival curves was performed using a Bayesian framework. The main outcomes were hazard ratios (HRs), relapse-free survival and mean relapse-free months.

Forty randomized controlled trials were included. The 1-year relapse-free survival for ADM (76%) was significantly better than that for placebo (56%). Most of the relapse difference (86.5%) occurred in the first 6 months. Most HRs were not constant over time. Proof of benefit after 6 months of follow-up was not established partially because of small differences between the drug and placebo after 6 months. Almost all studies used an ‘enriched’ randomized discontinuation design, which may explain the high relapse rates in the first 6 months after randomization.

The superiority of ADM v. placebo was mainly attributed to the difference in relapse rates that occurred in the first 6 months. Our analysis provided evidence that the prophylactic efficacy was not constant over time. A beneficial effect was observed, but the prevention of new episodes after 6 months was questionable. These findings may have implications for clinical practice.

Cognitive deficits affect a significant proportion of patients with bipolar disorder (BD). Problems with sustained attention have been found independent of mood state and the causes are unclear. We aimed to investigate whether physical parameters such as activity levels, sleep, and body mass index (BMI) may be contributing factors.

Forty-six patients with BD and 42 controls completed a battery of neuropsychological tests and wore a triaxial accelerometer for 21 days which collected information on physical activity, sleep, and circadian rhythm. Ex-Gaussian analyses were used to characterise reaction time distributions. We used hierarchical regression analyses to examine whether physical activity, BMI, circadian rhythm, and sleep predicted variance in the performance of cognitive tasks.

Neither physical activity, BMI, nor circadian rhythm predicted significant variance on any of the cognitive tasks. However, the presence of a sleep abnormality significantly predicted a higher intra-individual variability of the reaction time distributions on the Attention Network Task.

This study suggests that there is an association between sleep abnormalities and cognition in BD, with little or no relationship with physical activity, BMI, and circadian rhythm.

Abnormal processing of social feedback is an important contributor to social dysfunction in depression, however the exact mechanisms remain unclear. One important factor may be the extent to which social processing depends on expectations, in particular whether social feedback confirms or violates expectations.

To answer this question, we studied behavioral and brain responses during the evaluative processing of social feedback in 25 individuals with subthreshold depression (SD) and 25 healthy controls (HCs). Participants completed a Social Judgment Task in which they first indicated expectation about whether a peer would like them or not, and then received peer's feedback indicating acceptance or rejection.

Individuals with SD who reported greater depressive symptoms gave fewer positive expectations. Compared to HCs, individuals with SD showed reduced activation in the medial prefrontal cortex when expecting positive feedback. They also exhibited increased dorsal anterior cingulate cortex after receipt of unexpected social rejection, and reduced ventral striatum activity after receipt of unexpected social acceptance.

The observed alternations are specific to unexpected social feedback processing and highlight an important role of expectancy violation in the brain dysfunction of social feedback perception and evaluation in individuals at risk for depression.

Large population-based cohort studies of neuropsychological factors that characterise or precede depressive symptoms are rare. Most studies use small case-control or cross-sectional designs, which may cause selection bias and cannot test temporality. In a large UK population-based cohort, we investigated cross-sectional and longitudinal associations between inhibitory control of positive and negative information and adolescent depressive symptoms.

Cohort study of 2328 UK adolescents who completed an affective go/no-go task at age 18. Depressive symptoms were assessed with the Clinical Interview Schedule Revised (CIS-R) and short Mood and Feeling Questionnaire (sMFQ) at age 18, and with the sMFQ 1 year later (age 19). Analyses were multilevel and traditional linear regressions, before and after adjusting for confounders.

Cross-sectionally, we found little evidence that adolescents with more depressive symptoms made more inhibitory control errors [after adjustments, errors increased by 0.04% per 1 s.d. increase in sMFQ score (95% confidence interval 0.02–0.06)], but this association was not observed for the CIS-R. There was no evidence for an influence of valence. Longitudinally, there was no evidence that reduced inhibitory control was associated with future depressive symptoms.

Inhibitory control of positive and negative information does not appear to be a marker of current or future depressive symptoms in adolescents and would not be a useful target in interventions to prevent adolescent depression. Our lack of convincing evidence for associations with depressive symptoms suggests that the affective go/no-go task is not a promising candidate for future neuroimaging studies of adolescent depression.

Previous research indicates that body dysmorphic disorder (BDD) is associated with risk of suicidality. However, studies have relied on small and/or specialist samples and largely focussed on adults, despite these difficulties commonly emerging in youth. Furthermore, the aetiology of the relationship remains unknown.

Two independent twin samples were identified through the Child and Adolescent Twin Study in Sweden, at ages 18 (N = 6027) and 24 (N = 3454). Participants completed a self-report measure of BDD symptom severity. Young people and parents completed items assessing suicidal ideation/behaviours. Logistic regression models tested the association of suicidality outcomes with: (a) probable BDD, classified using an empirically derived cut-off; and (b) continuous scores of BDD symptoms. Bivariate genetic models examined the aetiology of the association between BDD symptoms and suicidality at both ages.

Suicidal ideation and behaviours were common among those with probable BDD at both ages. BDD symptoms, measured continuously, were linked with all aspects of suicidality, and associations generally remained significant after adjusting for depressive and anxiety symptoms. Genetic factors accounted for most of the covariance between BDD symptoms and suicidality (72.9 and 77.7% at ages 18 and 24, respectively), but with significant non-shared environmental influences (27.1 and 22.3% at ages 18 and 24, respectively).

BDD symptoms are associated with a substantial risk of suicidal ideation and behaviours in late adolescence and early adulthood. This relationship is largely explained by common genetic liability, but non-shared environmental effects are also significant and could provide opportunities for prevention among those at high-risk.

Maternal depressive symptoms (MDSs) are negatively associated with children's academic performance, with stronger effects sometimes reported in boys. However, few studies have tested the mechanisms of this association. We examined the mediating role of school engagement and peer victimization in this association and tested for sex differences.

Participants were 1173 families from a population-based longitudinal Canadian study. MDSs were self-reported annually using the Centre for Epidemiologic Studies Depression Scale (child's age: 5 months to 5 years). Data on mediators (peer victimization, cognitive, behavioral, and emotional school engagement) were reported annually from ages 6–10 by multiple informants including children, parents, and teachers using items from validated scales. Mathematics, reading, and writing exam scores at age 12 were obtained from standardized exams administered by Québec's Ministry of Education and Teaching. Structural equation modeling was used to test mediation by school experiences in boys and girls.

Exposure to MDSs was negatively associated with mathematics, reading, and writing scores in girls and with mathematics only in boys. Cognitive and behavioral engagement significantly mediated the association between MDSs and mathematics, reading, and writing scores in girls. There were no significant mediators for boys.

Prevention and intervention strategies aiming to improve school engagement might be beneficial for daughters of mothers experiencing depressive symptoms. Further research is needed to replicate these findings and to identify the mechanisms explaining this association in boys.

Uncertainty exists about what causes brain structure alterations associated with schizophrenia (SZ) and bipolar disorder (BD). Whether a history of asphyxia-related obstetric complication (ASP) – a common but harmful condition for neural tissue – contributes to variations in adult brain structure is unclear. We investigated ASP and its relationship to intracranial (ICV), global brain volumes and regional cortical and subcortical structures.

A total of 311 patients on the SZ – BD spectrum and 218 healthy control (HC) participants underwent structural magnetic resonance imaging. They were evaluated for ASP using prospective information obtained from the Medical Birth Registry of Norway.

In all groups, ASP was related to smaller ICV, total brain, white and gray matter volumes and total surface area, but not to cortical thickness. Smaller cortical surface areas were found across frontal, parietal, occipital, temporal and insular regions. Smaller hippocampal, amygdala, thalamus, caudate and putamen volumes were reported for all ASP subgroups. ASP effects did not survive ICV correction, except in the caudate, which remained significantly smaller in both patient ASP subgroups, but not in the HC.

Since ASP was associated with smaller brain volumes in all groups, the genetic risk of developing a severe mental illness, alone, cannot easily explain the smaller ICV. Only the smaller caudate volumes of ASP patients specifically suggest that injury from ASP can be related to disease development. Our findings give support for the ICV as a marker of aberrant neurodevelopment and ASP in the etiology of brain development in BD and SZ.

Health anxiety (HA) is associated with increased risk of disability, increased health care utilization and reduced quality of life. However, there is no consensus on which factors are important for the level of HA. The aim of this study was to explore the distribution of HA in a general adult population and to investigate whether demographic and social factors were associated with HA.

This study used cross-sectional data from the seventh Tromsø study. A total of 18 064 participants aged 40 years or older were included in the analysis. The six-item Whiteley Index (WI-6) with a 5-point Likert scale was used to measure HA. Sociodemographic factors included age, sex, education, household income, quality of friendship and participation in an organized activity.

HA showed an exponential distribution among the participants with a median score of 2 points out of 24 points. In total, 75% had a total score of 5 points or less, whereas 1% had a score >14 points. Education, household income, quality of friendship and participation in organized activity were significantly associated with HA. The variable quality of friendship demonstrated the strongest association with HA.

Our study showed an exponential distribution of HA in a general adult population. There was no evident cut-off point to distinguish participants with severe HA based on their WI-6 score, indicating the importance of analysing HA as a complex, continuous construct. HA demonstrated strong associations with quality of friendship and participation in an organized activity.

In 2013, the diagnosis of somatic symptom disorder (SSD) was introduced into the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). This review aims to comprehensively synthesize contemporary evidence related to SSD.

A scoping review was conducted using PubMed, PsycINFO, and Cochrane Library. The main inclusion criteria were SSD and publication in the English language between 01/2009 and 05/2020. Systematic search terms also included subheadings for the DSM-5 text sections; i.e., diagnostic features, prevalence, development and course, risk and prognostic factors, culture, gender, suicide risk, functional consequences, differential diagnosis, and comorbidity.

Eight hundred and eighty-two articles were identified, of which 59 full texts were included for analysis. Empirical evidence supports the reliability, validity, and clinical utility of SSD diagnostic criteria, but the further specification of the psychological SSD B-criteria criteria seems necessary. General population studies using self-report questionnaires reported mean frequencies for SSD of 12.9% [95% confidence interval (CI) 12.5–13.3%], while prevalence studies based on criterion standard interviews are lacking. SSD was associated with increased functional impairment, decreased quality of life, and high comorbidity with anxiety and depressive disorders. Relevant research gaps remain regarding developmental aspects, risk and prognostic factors, suicide risk as well as culture- and gender-associated issues.

Strengths of the SSD diagnosis are its good reliability, validity, and clinical utility, which substantially improved on its predecessors. SSD characterizes a specific patient population that is significantly impaired both physically and psychologically. However, substantial research gaps exist, e.g., regarding SSD prevalence assessed with criterion standard diagnostic interviews.

Although effective treatments exist for diagnostic and subthreshold-level eating disorders (EDs), a significant proportion of affected individuals do not receive help. Interventions translated for delivery through smartphone apps may be one solution towards reducing this treatment gap. However, evidence for the efficacy of smartphones apps for EDs is lacking. We developed a smartphone app based on the principles and techniques of transdiagnostic cognitive-behavioral therapy for EDs and evaluated it through a pre-registered randomized controlled trial.

Symptomatic individuals (those who reported the presence of binge eating) were randomly assigned to the app (n = 197) or waiting list (n = 195). Of the total sample, 42 and 31% exhibited diagnostic-level bulimia nervosa and binge-eating disorder symptoms, respectively. Assessments took place at baseline, 4 weeks, and 8 weeks post-randomization. Analyses were intention-to-treat. The primary outcome was global levels of ED psychopathology. Secondary outcomes were other ED symptoms, impairment, and distress.

Intervention participants reported greater reductions in global ED psychopathology than the control group at post-test (d = −0.80). Significant effects were also observed for secondary outcomes (d's = −0.30 to −0.74), except compensatory behavior frequency. Symptom levels remained stable at follow-up. Participants were largely satisfied with the app, although the overall post-test attrition rate was 35%.

Findings highlight the potential for this app to serve as a cost-effective and easily accessible intervention for those who cannot receive standard treatment. The capacity for apps to be flexibly integrated within current models of mental health care delivery may prove vital for addressing the unmet needs of people with EDs.

Brain imaging studies have shown altered amygdala activity during emotion processing in children and adolescents with oppositional defiant disorder (ODD) and conduct disorder (CD) compared to typically developing children and adolescents (TD). Here we aimed to assess whether aggression-related subtypes (reactive and proactive aggression) and callous-unemotional (CU) traits predicted variation in amygdala activity and skin conductance (SC) response during emotion processing.

We included 177 participants (n = 108 cases with disruptive behaviour and/or ODD/CD and n = 69 TD), aged 8–18 years, across nine sites in Europe, as part of the EU Aggressotype and MATRICS projects. All participants performed an emotional face-matching functional magnetic resonance imaging task.

Differences between cases and TD in affective processing, as well as specificity of activation patterns for aggression subtypes and CU traits, were assessed. Simultaneous SC recordings were acquired in a subsample (n = 63). Cases compared to TDs showed higher amygdala activity in response to negative faces (fearful and angry) v. shapes. Subtyping cases according to aggression-related subtypes did not significantly influence on amygdala activity; while stratification based on CU traits was more sensitive and revealed decreased amygdala activity in the high CU group. SC responses were significantly lower in cases and negatively correlated with CU traits, reactive and proactive aggression.

Our results showed differences in amygdala activity and SC responses to emotional faces between cases with ODD/CD and TD, while CU traits moderate both central (amygdala) and peripheral (SC) responses. Our insights regarding subtypes and trait-specific aggression could be used for improved diagnostics and personalized treatment.

Increasing numbers of children with perinatally acquired HIV (PaHIV) are transitioning into adult care. People living with behaviourally acquired HIV are known to be at more risk of psychosis than uninfected peers. Young adults living with PaHIV face numerous risk factors; biological: lifelong exposure to a neurotrophic virus, antiretroviral medication and immune dysfunction during brain development, and environmental; social deprivation, ethnicity-related discrimination, and migration-related issues. To date, there is little published data on the prevalence of psychotic illness in young people growing up with PaHIV.

We conducted a retrospective case note review of all individuals with PaHIV aged over 18 years registered for follow up at a dedicated clinic in the UK (n = 184).

In total, 12/184 (6.5%), median age 23 years (interquartile range 21–26), had experienced at least one psychotic episode. The presentation and course of the psychotic episodes experienced by our cohort varied from short-lived symptoms to long term illness and nine (75%) appear to have developed a severe and enduring mental illness requiring long term care.

The prevalence of psychosis in our cohort was clearly above the lifetime prevalence of psychosis in UK individuals aged 16–34 years, which has been reported to be 0.5–1.0%. This highlights the importance of clinical vigilance regarding the mental health of young people growing up with PaHIV and the need to integrate direct access to mental health services within the HIV centres providing medical care.

There is growing interest in using composite individualized treatment rules (ITRs) to guide depression treatment selection, but best approaches for doing this are not widely known. We develop an ITR for depression remission based on secondary analysis of a recently published trial for second-line antidepression medication selection using a cutting-edge ensemble machine learning method.

Data come from the SUN(^_^)D trial, an open-label, assessor blinded pragmatic trial of previously-untreated patients with major depressive disorder from 48 clinics in Japan. Initial clinic-level randomization assigned patients to 50 or 100 mg/day sertraline. We focus on the 1549 patients who failed to remit within 3 weeks and were then rerandomized at the individual-level to continuation with sertraline, switching to mirtazapine, or combining mirtazapine with sertraline. The outcome was remission 9 weeks post-baseline. Predictors included socio-demographics, clinical characteristics, baseline symptoms, changes in symptoms between baseline and week 3, and week 3 side effects.

Optimized treatment was associated with significantly increased cross-validated week 9 remission rates in both samples [5.3% (2.4%), p = 0.016 50 mg/day sample; 5.1% (2.7%), p = 0.031 100 mg/day sample] compared to randomization (30.1–30.8%). Optimization was also associated with significantly increased remission in both samples compared to continuation [24.7% in both: 11.2% (3.8%), p = 0.002 50 mg/day sample; 11.7% (3.9%), p = 0.001 100 mg/day sample]. Non-significant gains were found for optimization compared to switching or combining.

An ITR can be developed to improve second-line antidepressant selection, but replication in a larger study with more comprehensive baseline predictors might produce stronger and more stable results.