Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are often co-morbid and share performance and brain dysfunctions during working memory (WM). Serotonin agonists modulate WM and there is evidence of positive behavioural effects in both disorders. We therefore used functional magnetic resonance imaging (fMRI) to investigate shared and disorder-specific brain dysfunctions of WM in these disorders, and the effects of a single dose of the selective serotonin reuptake inhibitor (SSRI) fluoxetine.

Age-matched boys with ADHD (n = 17), ASD (n = 17) and controls (n = 22) were compared using fMRI during an N-back WM task. Patients were scanned twice, under either an acute dose of fluoxetine or placebo in a double-blind, placebo-controlled randomized design. Repeated-measures analyses within patients assessed drug effects on performance and brain function. To test for normalization effects of brain dysfunctions, patients under each drug condition were compared to controls.

Under placebo, relative to controls, both ADHD and ASD boys shared underactivation in the right dorsolateral prefrontal cortex (DLPFC). Fluoxetine significantly normalized the DLPFC underactivation in ASD relative to controls whereas it increased posterior cingulate cortex (PCC) deactivation in ADHD relative to control boys. Within-patient analyses showed inverse effects of fluoxetine on PCC deactivation, which it enhanced in ADHD and decreased in ASD.

The findings show that fluoxetine modulates brain activation during WM in a disorder-specific manner by normalizing task-positive DLPFC dysfunction in ASD boys and enhancing task-negative default mode network (DMN) deactivation in ADHD.

Smoking cessation improves physical health but it has been suggested that in vulnerable individuals it may worsen mental health. This study aimed to identify the short- and longer-term effects of stopping smoking on depression and anxiety in the general population and in those with a history of these disorders.

Sociodemographic and smoking characteristics, and mental and physical health were assessed using established measures in the ATTEMPT cohort, an international longitudinal study of smokers (n = 3645). Smokers who had stopped for at least 3 months or less than 3 months at the 12-month follow-up were compared with current smokers (n = 1640).

At follow-up, 9.7% [95% confidence interval (CI) 8.3–11.2] of smokers had stopped for less than 3 months and 7.5% (95% CI 6.3–8.9) for at least 3 months. Compared with current smokers, prevalence of depression prescriptions obtained in the last 2 weeks was lower for those who had stopped for less than 3 months [odds ratio (OR) 0.37, 95% CI 0.14–0.96] or at least 3 months (OR 0.25, 95% CI 0.06–0.94) after adjusting for baseline prescription levels and confounding variables. Adjusted prevalence of recent depression symptoms was also lower for ex-smokers who had stopped for less than 3 months (OR 0.34, 95% CI 0.15–0.78) or at least 3 months (OR 0.24, 95% CI 0.09–0.67) than among continuing smokers. There was no change in anxiety measures in the general population or any increase in anxiety or depression symptoms in ex-smokers with a past history of these conditions.

Smoking cessation does not appear to be associated with an increase in anxiety or depression and may lead to a reduced incidence of depression.

The purpose of this study was to evaluate a programme of lesion surgery carried out on patients with treatment-resistant depression (TRD).

This was a retrospective study looking at clinical and psychometric data from 45 patients with TRD who had undergone bilateral stereotactic anterior capsulotomy surgery over a period of 15 years, with the approval of the Mental Health Act Commission (37 with unipolar depression and eight with bipolar disorder). The Beck Depression Inventory (BDI) before and after surgery was used as the primary outcome measure. The Montgomery–Asberg Depression Rating Scale was administered and cognitive aspects of executive and memory functions were also examined. We carried out a paired-samples t test on the outcome measures to determine any statistically significant change in the group as a consequence of surgery.

Patients improved on the clinical measure of depression after surgery by −21.20 points on the BDI with a 52% change. There were no significant cognitive changes post-surgery. Six patients were followed up in 2013 by phone interview and reported a generally positive experience. No major surgical complications occurred.

With the limitations of an uncontrolled, observational study, our data suggest that capsulotomy can be an effective treatment for otherwise TRD. Performance on neuropsychological tests did not deteriorate.

The high rate of depression among children of depressed mothers is well known. Suggestions that improvement in maternal acute depression has a positive effect on the child have emerged. However, data on the mechanisms of change have been sparse. The aim was to understand how remission and relapse in the mother might explain the changes in the child's outcome.

Participants were 76 depressed mothers who entered into a medication clinical trial for depression and 135 of their eligible offspring ages 7–17 years. The mothers and children were assessed at baseline and periodically over 9 months by independent teams to understand the relationship between changes in children's symptoms and functioning and maternal remission or relapse. The main outcome measures were, for mothers, the Hamilton Depression Rating Scale (HAMD), the Social Adjustment Scale (SAS) and the Parental Bonding Instrument (PBI) and, for children, the Children's Depression Inventory (CDI), the Columbia Impairment Scale (CIS), the Multidimensional Anxiety Scale for Children (MASC) and the Children's Global Assessment Scale (CGAS).

Maternal remission was associated with a decrease in the child's depressive symptoms. The mother's subsequent relapse was associated with an increase in the child's symptoms over 9 months. The effect of maternal remission on the child's improvement was partially explained by an improvement in the mother's parenting, particularly the change in the mother's ability to listen and talk to her child, but also reflected in her improvement in parental bonding. These findings could not be explained by the child's treatment.

A depressed mother's remission is associated with her improvement in parenting and a decrease in her child's symptoms. Her relapse is associated with an increase in her child's symptoms.

Individuals with attention deficit hyperactivity disorder (ADHD) display excess levels of default mode network (DMN) activity during goal-directed tasks, which are associated with attentional disturbances and performance decrements. One hypothesis is that this is due to attenuated down-regulation of this network during rest-to-task switching. A second related hypothesis is that it may be associated with right anterior insula (rAI) dysfunction – a region thought to control the actual state-switching process.

These hypotheses were tested in the current fMRI study in which 19 adults with ADHD and 21 typically developing controls undertook a novel state-to-state switching paradigm. Advance cues signalled upcoming switches between rest and task periods and switch-related anticipatory modulation of DMN and rAI was measured. To examine whether rest-to-task switching impairments may be a specific example of a more general state regulation deficit, activity upon task-to-rest cues was also analysed.

Against our hypotheses, we found that the process of down-regulating the DMN when preparing to switch from rest to task was unimpaired in ADHD and that there was no switch-specific deficit in rAI modulation. However, individuals with ADHD showed difficulties up-regulating the DMN when switching from task to rest.

Rest-to-task DMN attenuation seems to be intact in adults with ADHD and thus appears unrelated to excess DMN activity observed during tasks. Instead, individuals with ADHD exhibit attenuated up-regulation of the DMN, hence suggesting disturbed re-initiation of a rest state.

The DSM-5 Obsessive-Compulsive Spectrum Sub-Workgroup is recommending the creation of a new diagnostic category named Hoarding Disorder (HD). The validity and acceptability of the proposed diagnostic criteria have yet to be formally tested.

Obsessive-compulsive disorder/hoarding experts and random members of the American Psychiatric Association (APA) were shown eight brief clinical vignettes (four cases meeting criteria for HD, three with hoarding behaviour secondary to other mental disorders, and one with subclinical hoarding behaviour) and asked to decide the most appropriate diagnosis in each case. Participants were also asked about the perceived acceptability of the criteria and whether they supported the inclusion of HD in the main manual.

Altogether, 211 experts and 48 APA members completed the survey (30% and 10% response rates, respectively). The sensitivity and specificity of the HD diagnosis and the individual criteria were high (80–90%) across various types of professionals, irrespective of their experience with hoarding cases. About 90% of participants in both samples thought the criteria would be very/somewhat acceptable for professionals and sufferers. Most experts (70%) supported the inclusion of HD in the main manual, whereas only 50% of the APA members did.

The proposed criteria for HD have high sensitivity and specificity. The criteria are also deemed acceptable for professionals and sufferers alike. Training of professionals and the development and validation of semi-structured diagnostic instruments should improve diagnostic accuracy even further. A field trial is now needed to confirm these encouraging findings with real patients in real clinical settings.

Compulsive behaviors in obsessive-compulsive disorder (OCD) have been related to impairment within the associative cortical-striatal system connecting the caudate and prefrontal cortex that underlies consciously-controlled goal-directed learning and behavior. However, little is known whether this impairment may serve as a biomarker for vulnerability to OCD.

Using resting-state functional magnetic resonance imaging (fMRI), we employed Granger causality analysis (GCA) to measure effective connectivity (EC) in previously validated striatal sub-regions, including the caudate, putamen, and the nucleus accumbens, in 35 OCD patients, 35 unaffected first-degree relatives and 35 matched healthy controls.

Both OCD patients and their first-degree relatives showed greater EC than controls between the left caudate and the orbital frontal cortex (OFC). Both OCD patients and their first-degree relatives showed lower EC than controls between the left caudate and lateral prefrontal cortex. These results are consistent with findings from task-related fMRI studies which found impairment in the goal-directed system in OCD patients.

The same changes in EC were present in both OCD patients and their unaffected first-degree relatives suggest that impairment in the goal-directed learning system may be a biomarker for OCD.

There is evidence that greater body mass index (BMI) protects against depression, schizophrenia and suicide. However, there is a need for prospective studies.

We examined the association of BMI with future hospital admissions for psychoses or depression/anxiety disorders in a large prospective study of 7036 men and 8327 women. Weight and height were measured at baseline (1972–76) when participants were aged 45–64. Follow-up was for a median of 29 years.

Greater BMI and obesity were associated with a reduced risk of hospital admission for psychoses and depression/anxiety in both genders, with the magnitude of these associations being the same for males and females. With adjustment for age, sex, smoking and social class, a 1 standard deviation (s.d.) greater BMI at baseline was associated with a rate ratio of 0·91 [95% confidence interval (CI) 0·82–1·01] for psychoses and 0·87 (95% CI 0·77–0·98) for depression/anxiety. Further adjustment for baseline psychological distress and total cholesterol did not alter these associations.

Our findings add to the growing body of evidence that suggests that greater BMI is associated with a reduced risk of major psychiatric outcomes. Long-term follow-up of participants in randomized controlled trials of interventions that effectively result in weight loss and the use of genetic variants that are functionally related to obesity as instrumental variables could help to elucidate whether these associations are causal.

To investigate the risk of completed suicide in offspring during adolescence in relation to prior history of the same-sex parent's death by suicide and other causes.

A total of 500 adolescents who died by suicide at age 15–19 years between 1997 and 2007 were identified from the Taiwan Mortality Registration (TMR). For each case, 30 age- and time-matched controls were selected randomly from all adolescents registered in the Taiwan Birth Registry (TBR). A multivariate conditional logistic regression model was used to assess the risk of adolescent completed suicide in relation to their same-sex parent.

Adolescent suicide risk was positively associated with both paternal [odds ratio (OR) 5.38, 95% confidence interval (CI) 2.17–13.33] and maternal suicide (OR 6.59, 95% CI 1.82–23.91). The corresponding risk estimates associated with paternal and maternal deaths from non-suicidal causes were much lower, at 1.88 and 1.94 respectively. The risk of suicide in male adolescents was significantly associated with prior history of paternal death by suicide (OR 8.23, 95% CI 2.96–22.90) but not of maternal death by suicide (OR 3.50, 95% CI 0.41–30.13). On the other contrary, the risk of suicidal death in female adolescents was significantly associated with prior history of maternal suicide (OR 9.71, 95% CI 1.89–49.94) but not of paternal suicide (OR 2.42, 95% CI 0.30–19.57). However, these differences did not reach statistical significance.

Although limited by sample size, our study indicates that adolescent offspring suicidal death is associated with prior history of their same-sex parent's death by suicide.

Prior imaging studies have shown structural, functional and biochemical impairments in patients with generalized anxiety disorder (GAD), particularly in the right hemisphere. In this study we investigated, for the first time to the best of our knowledge, the white-matter microstructure organization in GAD.

A total of 12 patients with DSM-IV GAD and 15 matched healthy controls underwent a magnetic resonance imaging session of diffusion weighted imaging, exploring white-matter water molecules by the means of apparent diffusion coefficients (ADCs). Regions of interests were placed in the frontal, parietal, temporal and occipital lobes and in the splenium and genu of the corpus callosum, bilaterally.

ADC measures were significantly greater in patients with GAD in the right splenium and right parietal cortex compared with healthy controls (p⩽0.002). No significant correlations between ADCs and age or clinical variables were found.

We provide evidence that GAD is associated with disrupted white-matter coherence of posterior right hemisphere regions, which may partly sustain the impaired cognitive regulation of anxiety. Future diffusion imaging investigations are expected to better elucidate the communication between the parietal cortex and other right hemisphere regions in sustaining the cognitive processing of social and emotional stimuli in patients with GAD.

Psychotic experiences (PE) are highly prevalent in childhood and are known to be associated with co-morbid mental health disorders and functional difficulties in adolescence. However, little is known about the long-term outcomes of young people who report PE.

As part of the Adolescent Brain Development Study, 211 young people were recruited in childhood (mean age 11.7 years) and underwent detailed clinical interviews, with 25% reporting PE. A 10 year follow-up study was completed and 103 participants returned (mean age 20.9 years). Structured clinical interviews for DSM-5 (SCID-5) and interviewer-rated assessments of functioning were conducted. A detailed neuropsychological battery was also administered. Analyses investigated group differences between those who had ever reported PE and controls in early adulthood.

The PE group was at a significantly higher risk of meeting DSM-5 criteria for a current (OR 4.08, CI 1.16–14.29, p = 0.03) and lifetime psychiatric disorder (OR 3.27, CI 1.43–7.47, p = 0.005). They were also at a significantly higher risk of multi-morbid lifetime psychiatric disorders. Significantly lower scores on current social and global functioning measures were observed for the PE group. Overall, there were no differences in neuropsychological performance between groups apart from significantly lower scores on the Stroop Word task and the Purdue Pegboard task for the PE group.

Our findings suggest that reports of PE are associated with poorer mental health and functional outcomes in early adulthood, with some persisting cognitive and motor deficits. Young people who report such symptoms could be considered a target group for interventions to aid functional outcomes.

Schizophrenia is associated with robust hippocampal volume deficits but subregion volume deficits, their associations with cognition, and contributing genes remain to be determined.

Hippocampal formation (HF) subregion volumes were obtained using FreeSurfer 6.0 from individuals with schizophrenia (n = 176, mean age ± s.d. = 39.0 ± 11.5, 132 males) and healthy volunteers (n = 173, mean age ± s.d. = 37.6 ± 11.3, 123 males) with similar mean age, gender, handedness, and race distributions. Relationships between the HF subregion volume with the largest between group difference, neuropsychological performance, and single-nucleotide polymorphisms were assessed.

This study found a significant group by region interaction on hippocampal subregion volumes. Compared to healthy volunteers, individuals with schizophrenia had significantly smaller dentate gyrus (DG) (Cohen's d = −0.57), Cornu Ammonis (CA) 4, molecular layer of the hippocampus, hippocampal tail, and CA 1 volumes, when statistically controlling for intracranial volume; DG (d = −0.43) and CA 4 volumes remained significantly smaller when statistically controlling for mean hippocampal volume. DG volume showed the largest between group difference and significant positive associations with visual memory and speed of processing in the overall sample. Genome-wide association analysis with DG volume as the quantitative phenotype identified rs56055643 (β = 10.8, p < 5 × 10−8, 95% CI 7.0–14.5) on chromosome 3 in high linkage disequilibrium with MOBP. Gene-based analyses identified associations between SLC25A38 and RPSA and DG volume.

This study suggests that DG dysfunction is fundamentally involved in schizophrenia pathophysiology, that it may contribute to cognitive abnormalities in schizophrenia, and that underlying biological mechanisms may involve contributions from MOBP, SLC25A38, and RPSA.

Serotonin and dopamine neurotransmitter systems are implicated in the regulation of mood, cognition and personality traits and their dysfunction is thought to be implicated in diverse psychopathologies. However, in healthy subjects the relationship between the serotonin and dopamine systems and neuropsychological functioning and personality traits is not clearly established. In the present study we investigated whether neuropsychological functioning, personality traits and mood states of a group of healthy subjects are associated with in vivo measures of serotonin transporters (SERTs) and dopamine transporters (DATs).

A total of 188 young healthy subjects underwent neuropsychological and subjective measurements of memory function, depression and impulsivity. Participants' SERT and DAT availability in predefined regions of interest were assessed using single photon emission computed tomography (SPECT) with the radiotracer [123I]β-CIT. Individual magnetic resonance imaging (MRI) scans served as anatomic reference.

We did not find any significant association between SERT or DAT availability and neuropsychological test performance or self-reported impulsivity and mood. There were no significant sex differences in SERT or DAT availability, but men performed significantly better on some tests of visuospatial functioning than women.

Robust negative findings for striatal DAT availability seriously question earlier findings of positive associations between DAT availability and cognitive functions in healthy subjects. Our results also suggest that subcortical SERT availability is not associated with the neuropsychological functions and personality traits assessed. In summary, the present study suggests that neuropsychological and personality measurements in young healthy people are not associated with subcortical SERT or striatal DAT availabilities in the brain.

Only 30% or fewer of individuals at clinical high risk (CHR) convert to full psychosis within 2 years. Efforts are thus underway to refine risk identification strategies to increase their predictive power. Our objective was to develop and validate the predictive accuracy and individualized risk components of a mobile app-based psychosis risk calculator (RC) in a CHR sample from the SHARP (ShangHai At Risk for Psychosis) program.

In total, 400 CHR individuals were identified by the Chinese version of the Structured Interview for Prodromal Syndromes. In the first phase of 300 CHR individuals, 196 subjects (65.3%) who completed neurocognitive assessments and had at least a 2-year follow-up assessment were included in the construction of an RC for psychosis. In the second phase of the SHARP sample of 100 subjects, 93 with data integrity were included to validate the performance of the SHARP-RC.

The SHARP-RC showed good discrimination of subsequent transition to psychosis with an AUC of 0.78 (p < 0.001). The individualized risk generated by the SHARP-RC provided a solid estimation of conversion in the independent validation sample, with an AUC of 0.80 (p = 0.003). A risk estimate of 20% or higher had excellent sensitivity (84%) and moderate specificity (63%) for the prediction of psychosis. The relative contribution of individual risk components can be simultaneously generated. The mobile app-based SHARP-RC was developed as a convenient tool for individualized psychosis risk appraisal.

The SHARP-RC provides a practical tool not only for assessing the probability that an individual at CHR will develop full psychosis, but also personal risk components that might be targeted in early intervention.

Disturbances in Pavlovian valuation systems are reported to follow traumatic stress exposure. However, motivated decisions are also guided by instrumental mechanisms, but to date the effect of traumatic stress on these instrumental systems remain poorly investigated. Here, we examine whether a single episode of severe traumatic stress influences flexible instrumental decisions through an impact on a Pavlovian system.

Twenty-six survivors of the 2011 Norwegian terror attack and 30 matched control subjects performed an instrumental learning task in which Pavlovian and instrumental associations promoted congruent or conflicting responses. We used reinforcement learning models to infer how traumatic stress affected learning and decision-making. Based on the importance of dorsal anterior cingulate cortex (dACC) for cognitive control, we also investigated if individual concentrations of Glx (=glutamate + glutamine) in dACC predicted the Pavlovian bias of choice.

Survivors of traumatic stress expressed a greater Pavlovian interference with instrumental action selection and had significantly lower levels of Glx in the dACC. Across subjects, the degree of Pavlovian interference was negatively associated with dACC Glx concentrations.

Experiencing traumatic stress appears to render instrumental decisions less flexible by increasing the susceptibility to Pavlovian influences. An observed association between prefrontal glutamatergic levels and this Pavlovian bias provides novel insight into the neurochemical basis of decision-making, and suggests a mechanism by which traumatic stress can impair flexible instrumental behaviours.

Neurocognitive performance deficits have been observed in mood disorder patients and their unaffected relatives and may therefore qualify as endophenotypes. However, the precise time course of neurocognitive deficits has not been studied so that it is unknown whether neurocognitive abnormalities reflect the early effects of familial vulnerability to mood disorders or if they emerge at illness onset.

A neuropsychological test battery was administered at baseline and after a 2-year follow-up interval in 111 initially unaffected young adults at high familial risk of mood disorders and 93 healthy controls (HC). During the follow-up period, 20 high-risk subjects developed major depressive disorder (HR-MDD), with the remainder remaining well (HR-well). Linear mixed-effects models were used to investigate differences and longitudinal changes in the domains of attentional processing, working memory, verbal learning and memory, and cognitive flexibility.

Reduced long delay verbal memory and extradimensional set-shifting performance across both time points were found in the HR-well group relative to controls. The HR-MDD group displayed decreased extradimensional set-shifting abilities across both time points as compared with the HC group only. There were no significant performance differences between the two high-risk groups.

Reduced verbal memory and cognitive flexibility are familial trait markers for vulnerability to mood disorders in individuals with a close family history of bipolar disorder. Both neurocognitive performance deficits appear to be relatively stable over a 2-year time period and do not appear to be linked to the onset of MDD. These findings support their use as stable quantitative endophenotypes for mood disorders.