Social environmental stress, including childhood abuse and deprivation, is associated with increased rates of psychiatric disorders such as schizophrenia and depression. However, the neural mechanisms mediating risk are not completely understood. Functional magnetic resonance imaging (MRI) studies have reported effects of social environmental stress on a variety of brain regions, but interpretation of results is complicated by the variety of environmental risk factors examined and different methods employed.

We examined brain regions consistently showing differences in blood oxygen level-dependent (BOLD) response in individuals exposed to higher levels of environmental stress by performing a coordinate-based meta-analysis on 54 functional MRI studies using activation likelihood estimation (ALE), including an overall sample of 3044 participants. We performed separate ALE analyses on studies examining adults (mean age ⩾18 years) and children/adolescents (mean age <18 years) and a contrast analysis comparing the two types of study.

Across both adult and children/adolescent studies, ALE meta-analysis revealed several clusters in which differences in BOLD response were associated with social environmental stress across multiple studies. These clusters incorporated several brain regions, among which the right amygdala was most frequently implicated.

These findings suggest that a variety of social environmental stressors is associated with differences in the BOLD response of specific brain regions such as the right amygdala in both children/adolescents and adults. What remains unknown is whether these environmental stressors have differential effects on treatment response in these brain regions.

Our knowledge about the developmental change of neuropsychological functioning in attention-deficit/hyperactivity disorder (ADHD) is limited. This prospective longitudinal study examined the changes in neuropsychological functions and their associations with the changes of ADHD symptoms across the developmental stages from early adolescence to young adulthood.

We followed up 53 individuals diagnosed with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) ADHD during childhood (mean age 12.77 years at time 1, 19.81 years at time 2) and 50 non-ADHD controls (mean age 12.80 years at time 1, 19.36 years at time 2) with repeated psychiatric interviews at two time points to confirm ADHD and other psychiatric diagnoses. Neuropsychological functions with high- and low-executive demands, measured by the Cambridge Neuropsychological Testing Automated Battery (CANTAB) at two time points, were compared.

Both groups showed improvements in all neuropsychological tasks except reaction time in the ADHD group. Despite having a greater improvement in spatial working memory (SWM) than controls, individuals with ADHD still performed worse in various neuropsychological tasks than controls at follow-up. Better baseline intra-dimension/extra-dimension shift and parental occupation predicted fewer ADHD symptoms at follow-up independent of baseline ADHD symptoms. The degree of ADHD symptom reduction was not significantly linearly correlated to the magnitude of neuropsychological function improvement.

Individuals with ADHD and controls had parallel developments in neuropsychological functioning, except a catch-up in SWM in ADHD. Almost all neuropsychological functions herein were still impaired in ADHD at late adolescence/young adulthood. There may be a threshold (i.e. non-linear) relationship between neuropsychological functioning and ADHD symptoms.

Emotion dysregulation is a core feature of borderline personality disorder (BPD), which often co-occurs with posttraumatic stress disorder (PTSD). Difficulties in emotion regulation (ER) have been linked to lower high-frequency heart rate variability (HF-HRV), a measure of autonomous nervous system functioning. However, previous research on vagally-mediated heart rate in BPD revealed heterogeneous findings and the effects of comorbid PTSD and dissociation on HF-HRV are not yet completely understood. This study aim to investigate HF-HRV during resting-state and an ER task in female BPD patients with comorbid PTSD (BPD + PTSD), patients without this comorbidity (BPD), and healthy controls (HC).

57 BPD patients (BPD: n = 37, BPD + PTSD: n = 20) and 27 HC performed an ER task with neutral, positive, and negative images. Participants were instructed to either attend these pictures or to down-regulate their upcoming emotions using cognitive reappraisal. Subjective arousal and wellbeing, self-reported dissociation, and electrocardiogram data were assessed.

Independent of ER instruction and picture valence, both patient groups (BPD and BPD + PTSD) reported higher subjective arousal and lower wellbeing; patients with BPD + PTSD further exhibited significantly lower HF-HRV compared with the other groups. Higher self-reported state dissociation predicted higher HF-HRV during down-regulating v. attending negative pictures in BPD + PTSD.

Findings suggest increased emotional reactivity to negative, positive, and neutral pictures, but do not provide evidence for deficits in instructed ER in BPD. Reduced HF-HRV appears to be particularly linked to comorbid PTSD, while dissociation may underlie attempts to increase ER and HF-HRV in BPD patients with this comorbidity.

Changes in positive and negative symptom profiles during acute psychotic episodes may be key drivers in the pathway to violence. Acute episodes are often preceded by fluctuations in affect before psychotic symptoms appear and affective symptoms may play a more important role in the pathway than previously recognised.

We carried out a prospective cohort study of 409 male and female patients discharged from medium secure services in England and Wales to the community. Measures were taken at baseline (pre-discharge), 6 and 12 months post-discharge using the Positive and Negative Syndrome Scale. Information on violence was obtained using the McArthur Community Violence Instrument and Police National Computer.

The larger the shift in positive symptoms the more likely violence occurred in each 6-month period. However, shifts in angry affect were the main driving factor for positive symptom shifts associated with violence. Shifts in negative symptoms co-occurred with positive and conveyed protective effects, but these were overcome by co-occurring shifts in anger. Severe but stable delusions were independently associated with violence.

Intensification of angry affect during acute episodes of psychosis indicates the need for interventions to prevent violence and is a key driver of associated positive symptoms in the pathway to violence. Protective effects against violence exerted by negative symptoms are not clinically observable during symptom shifts because they are overcome by co-occurring anger.

Executive dysfunction is one of the main cognitive theories of autism spectrum disorder (ASD). Despite evidence of deficits in executive functions in individuals with ASD, little is known about executive dysfunctions as candidate cognitive endophenotypes for ASD. In this study, we investigated executive functions in youths with ASD, their unaffected siblings and typically developing controls (TDC).

We recruited 240 youths with a clinical diagnosis of ASD (aged 6–18 years), 147 unaffected siblings of ASD youths, and 240 TDC youths. TDC youths were recruited based on the age and sex distribution of the ASD youths. Participants were assessed using the verbal Digit Span test and four executive function tasks from the Cambridge Neuropsychological Test Automated Battery, including Intra-dimensional/Extra-dimensional Shift (I/ED), Spatial Span (SSP), Spatial Working Memory (SWM), and Stocking of Cambridge (SoC).

ASD youths, relative to TDC, performed significantly worse in executive function tasks assessing verbal working memory (forward and backward digit span), set-shifting (I/ED), visuospatial working memory (SSP, SWM), and planning/problem solving (SoC). Furthermore, unaffected siblings, relative to TDC, performed worse in forward and backward digit recalls and made more errors in SWM. These results were independent of the effects of age, sex, IQ, and symptoms of attention-deficit/hyperactivity disorder.

Our findings support impaired executive functions in youths with ASD. However, unaffected siblings were mostly unimpaired except in the areas of verbal and spatial working memory, which may be potential cognitive endophenotypes for ASD.

Hippocampal dysfunction is considered central to many neurobiological models of schizophrenia, yet there are few longitudinal in vivo neuroimaging studies that have investigated the relationship between antipsychotic treatment and morphologic changes within specific hippocampal subregions among patients with psychosis.

A total of 29 patients experiencing a first episode of psychosis with little or no prior antipsychotic exposure received structural neuroimaging examinations at illness onset and then following 12 weeks of treatment with either risperidone or aripiprazole in a double-blind randomized clinical trial. In addition, 29 healthy volunteers received structural neuroimaging examinations at baseline and 12-week time points. We manually delineated six hippocampal subregions [i.e. anterior cornu ammonis (CA) 1–3, posterior CA1–3, subiculum, dentate gyrus/CA4, entorhinal cortex, and fimbria] from 3T magnetic resonance images using an established method with high inter- and intra-rater reliability.

Following antipsychotic treatment patients demonstrated significant reductions in dentate gyrus/CA4 volume and increases in subiculum volume. Healthy volunteers demonstrated non-significant volumetric changes in these subregions across the two time points. We observed a significant quadratic (i.e. inverted U) association between changes in dentate gyrus/CA4 volume and cumulative antipsychotic dosage between the scans.

This study provides the first evidence to our knowledge regarding longitudinal in vivo volumetric changes within specific hippocampal subregions in patients with psychosis following antipsychotic treatment. The finding of a non-linear relationship between changes in dentate gyrus/CA4 subregion volume and antipsychotic exposure may provide new avenues into understanding dosing strategies for therapeutic interventions relevant to neurobiological models of hippocampal dysfunction in psychosis.

Altered hypothalamus-pituitary-adrenal (HPA) axis function and reduced hippocampal volume (HV) are established correlates of stress vulnerability. We have previously shown an attenuated cortisol awakening response (CAR) and associations with HV specifically in male first-episode psychosis patients. Findings in individuals at ultra-high risk (UHR) for psychosis regarding these neurobiological markers are inconsistent, and assessment of their interplay, accounting for sex differences, could explain incongruent results.

Study participants were 42 antipsychotic-naive UHR subjects (24 men) and 46 healthy community controls (23 men). Saliva samples for the assessment of CAR were collected at 0, 30 and 60 min after awakening. HV was determined from high-resolution structural magnetic resonance imaging scans using a semi-automatic segmentation protocol.

Cortisol measures and HV were not significantly different between UHR subjects and controls in total, but repeated-measures multivariate regression analyses revealed reduced cortisol levels 60 min after awakening and smaller left HV in male UHR individuals. In UHR participants only, smaller left and right HV was significantly correlated with a smaller total CAR (ρ = 0.42, p = 0.036 and ρ = 0.44, p = 0.029, respectively), corresponding to 18% and 19% of shared variance (medium effect size).

Our findings suggest that HV reduction in individuals at UHR for psychosis is specific to men and linked to reduced post-awakening cortisol concentrations. Abnormalities in the neuroendocrine circuitry modulating stress vulnerability specifically in male UHR subjects might explain increased psychosis risk and disadvantageous illness outcomes in men compared to women.

Alcohol consumption is influenced by genetic factors. Previous studies have examined the heritability of alcohol consumption, or related phenotypes, from adolescence into adulthood, frequently finding that total heritability changes over time. However, it remains unclear whether the same genes underlie liability to alcohol consumption across development versus whether novel risk genes become important over time.

A population-based study of adult male twins (n=1790) born in Virginia, USA, retrospectively reported on their average monthly alcohol consumption from early adolescence through adulthood. We used twin modeling methods to explore genetic and environmental influences on alcohol consumption over time.

One latent genetic factor accounted for the majority of the heritability in alcohol consumption during mid- to late adolescence, but its influence declined thereafter; from young adulthood forward, heritability was largely attributable to a second genetic factor. The total heritability of alcohol consumption increased from 0 at ages 12–14 years to 0.40 by ages 18–21 years. Shared environmental factors declined in influence over time.

The heritability of alcohol consumption over time is dynamic both quantitatively and qualitatively. These results have important implications for gene identification endeavors. Furthermore, these findings could inform efforts to elucidate developmentally dynamic behaviors, such as antisocial behavior.

Obesity is increasingly prevalent in bipolar disorder (BD) but data about the impact of elevated body mass index (BMI) on brain white-matter integrity in BD are sparse. Based on extant literature largely from structural magnetic resonance imaging (MRI) studies, we hypothesize that increased BMI is associated with decreased fractional anisotropy (FA) in the frontal, temporal, parietal and occipital brain regions early in the course of BD.

A total of 26 euthymic adults (12 normal weight and 14 overweight/obese) with remitted first-episode mania (FEM) and 28 controls (13 normal weight and 15 overweight/obese) matched for age, handedness and years of education underwent structural MRI and diffusion tensor imaging scans.

There are significant effects of diagnosis by BMI interactions observed especially in the right parietal lobe (adjusted F1,48 = 5.02, p = 0.030), occipital lobe (adjusted F1,48 = 10.30, p = 0.002) and temporal lobe (adjusted F1,48 = 7.92, p = 0.007). Specifically, decreased FA is found in the right parietal (F1,23 = 5.864, p = 0.023) and occipital lobes (F1,23 = 4.397, p = 0.047) within overweight/obese patients compared with normal-weight patients with FEM. Compared with overweight/obese controls, decreased FA is observed in right parietal (F1,25 = 6.708, p = 0.015), temporal (F1,25 = 10.751, p = 0.003) and occipital (F1,25 = 9.531, p = 0.005) regions in overweight/obese patients with FEM.

Our findings suggest that increased BMI affects temporo-parietal-occipital brain white-matter integrity in FEM. This highlights the need to further elucidate the relationship between obesity and other neural substrates (including subcortical changes) in BD which may clarify brain circuits subserving the association between obesity and clinical outcomes in BD.

We have previously shown that the selective serotonergic reuptake inhibitor, citalopram, reduces the neural response to reward and aversion in healthy volunteers. We suggest that this inhibitory effect might underlie the emotional blunting reported by patients on these medications. Bupropion is a dopaminergic and noradrenergic reuptake inhibitor and has been suggested to have more therapeutic effects on reward-related deficits. However, how bupropion affects the neural responses to reward and aversion is unclear.

Seventeen healthy volunteers (9 female, 8 male) received 7 days bupropion (150 mg/day) and 7 days placebo treatment, in a double-blind crossover design. Our functional magnetic resonance imaging task consisted of three phases; an anticipatory phase (pleasant or unpleasant cue), an effort phase (button presses to achieve a pleasant taste or to avoid an unpleasant taste) and a consummatory phase (pleasant or unpleasant tastes). Volunteers also rated wanting, pleasantness and intensity of the tastes.

Relative to placebo, bupropion increased activity during the anticipation phase in the ventral medial prefrontal cortex (vmPFC) and caudate. During the effort phase, bupropion increased activity in the vmPFC, striatum, dorsal anterior cingulate cortex and primary motor cortex. Bupropion also increased medial orbitofrontal cortex, amygdala and ventral striatum activity during the consummatory phase.

Our results are the first to show that bupropion can increase neural responses during the anticipation, effort and consummation of rewarding and aversive stimuli. This supports the notion that bupropion might be beneficial for depressed patients with reward-related deficits and blunted affect.

Clinical depression is associated with reductions in white-matter integrity in several long tracts of the brain. The extent to which these findings are localized or related to depressive symptoms or personality traits linked to disease risk remains unclear.

Members of the Lothian Birth Cohort 1936 (LBC936) were assessed in two waves at mean ages of 70 and 73 years. At wave 1, they underwent assessments of depressive symptoms and the personality traits of neuroticism and extraversion. Brain diffusion magnetic resonance imaging (MRI) data were obtained at the second wave and mood assessments were repeated. We tested whether depressive symptoms were related to reduced white-matter tract fractional anisotropy (FA), a measure of integrity, and then examined whether high neuroticism or low extraversion mediated this relationship.

Six hundred and sixty-eight participants provided useable data. Bilateral uncinate fasciculus FA was significantly negatively associated with depressive symptoms at both waves (standardized β=0.12–0.16). Higher neuroticism and lower extraversion were also significantly associated with lower uncinate FA bilaterally (standardized β=0.09–0.15) and significantly mediated the relationship between FA and depressive symptoms.

Trait liability to depression and depressive symptoms are associated with reduced structural connectivity in tracts connecting the prefrontal cortex with the amygdala and anterior temporal cortex. These effects suggest that frontotemporal disconnection is linked to the etiology of depression, in part through personality trait differences.

Although prior genetic studies of interview-assessed fears and phobias have shown that genetic factors predispose individuals to fears and phobias, they have been restricted to the DSM-III to DSM-IV aggregated subtypes of phobias rather than to individual fearful and phobic stimuli.

We examined the lifetime history of fears and/or phobias in response to 21 individual phobic stimuli in 4067 personally interviewed twins from same-sex pairs from the Virginia Adult Twin Study of Psychiatric and Substance Abuse Disorders (VATSPSUD). We performed multivariate statistical analyses using Mx and Mplus.

The best-fitting model for the 21 phobic stimuli included four genetic factors (agora-social-acrophobia, animal phobia, blood-injection-illness phobia and claustrophobia) and three environmental factors (agora-social-hospital phobia, animal phobia, and situational phobia).

This study provides the first view of the architecture of genetic and environmental risk factors for phobic disorders and their subtypes. The genetic factors of the phobias support the DSM-IV and DSM-5 constructs of animal and blood-injection-injury phobias but do not support the separation of agoraphobia from social phobia. The results also do not show a coherent genetic factor for the DSM-IV and DSM-5 situational phobia. Finally, the patterns of co-morbidity across individual fears and phobias produced by genetic and environmental influences differ appreciably.

Feelings of doubt and perseverative behaviours are key symptoms of obsessive–compulsive disorder (OCD) and have been linked to hyperactive error and conflict signals in the brain. While enhanced neural correlates of error monitoring have been robustly shown, far less is known about conflict processing and adaptation in OCD.

We examined event-related potentials during conflict processing in 70 patients with OCD and 70 matched healthy comparison participants, focusing on the stimulus-locked N2 elicited in a flanker task. Conflict adaptation was evaluated by analysing sequential adjustments in N2 and behaviour, i.e. current conflict effects as a function of preceding conflict.

Patients with OCD showed enhanced N2 amplitudes compared with healthy controls. Further, patients showed stronger conflict adaptation effects on reaction times and N2 amplitude. Thus, the effect of previous compatibility was larger in patients than in healthy participants as indicated by greater N2 adjustments in change trials (i.e. iC, cI). As a result of stronger conflict adaptation in patients, N2 amplitudes were comparable between groups in incompatible trials following incompatible trials.

Larger N2 amplitudes and greater conflict adaptation in OCD point to enhanced conflict monitoring leading to increased recruitment of cognitive control in patients. This was most pronounced in change trials and was associated with stronger conflict adjustment in N2 and behaviour. Thus, hyperactive conflict monitoring in OCD may be beneficial in situations that require a high amount of control to resolve conflict, but may also reflect an effortful process that is linked to distress and symptoms of OCD.