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.

Heritability estimates from twin studies of the multi-faceted phenotype of nicotine dependence (ND) range from moderate to high (31–60%), but vary substantially based on the specific ND-related construct examined. The current study estimated the aggregate role of common genetic variants on key ND constructs.

Genomic-relationship-matrix restricted maximum likelihood (GREML) was used to decompose phenotypic variance across multiple ND indices using 796 125 polymorphisms from 2346 unrelated ‘lifetime ever smokers’ of European ancestry. Measures included DSM-IV ND and Fagerström Test for Nicotine Dependence (FTND) summary measures and constituent constructs (e.g. withdrawal severity, tolerance, heaviness of smoking and time spent smoking). Exploratory and confirmatory factor models were used to describe the covariance structure across ND measures; resulting factor(s) were the subject(s) of GREML analyses.

Factor models indicated highly correlated DSM-IV and FTND factors for ND (0.545, 95% confidence interval 0.50–0.60) that could be represented as a higher-order factor (NIC DEP). Additive genetic influence on NIC DEP was 33% (s.e. = 0.14, p = 0.009). Post-hoc analyses indicated moderate genetic effects on the DSM-IV (34%, s.e. = 0.14, p = 0.008) and FTND (26%, s.e. = 0.14, p = 0.032) factors, both of which were influenced by the same genetic effects (rG-SNP = 1.00, s.e. = 0.09, p < 0.00001).

Overall, common single nucleotide polymorphisms accounted for a large proportion of the genetic influences on ND-related phenotypes that have been observed in twin studies. Genetic contributions across distinct ND scales were largely influenced by shared genetic factors.

Patients with psychosis display the so-called ‘Jumping to Conclusions’ bias (JTC) – a tendency for hasty decision-making in probabilistic reasoning tasks. So far, only a few studies have evaluated the JTC bias in ‘at-risk mental state’ (ARMS) patients, specifically in ARMS samples fulfilling ‘ultra-high risk’ (UHR) criteria, thus not allowing for comparisons between different ARMS subgroups.

In the framework of the PREVENT (secondary prevention of schizophrenia) study, a JTC task was applied to 188 patients either fulfilling UHR criteria or presenting with cognitive basic symptoms (BS). Similar data were available for 30 healthy control participants matched for age, gender, education and premorbid verbal intelligence. ARMS patients were identified by the Structured Interview for Prodromal Symptoms (SIPS) and the Schizophrenia Proneness Instrument – Adult Version (SPI-A).

The mean number of draws to decision (DTD) significantly differed between ARM -subgroups: UHR patients made significantly less draws to make a decision than ARMS patients with only cognitive BS. Furthermore, UHR patients tended to fulfil behavioural criteria for JTC more often than BS patients. In a secondary analysis, ARMS patients were much hastier in their decision-making than controls. In patients, DTD was moderately associated with positive and negative symptoms as well as disorganization and excitement.

Our data indicate an enhanced JTC bias in the UHR group compared to ARMS patients with only cognitive BS. This underscores the importance of reasoning deficits within cognitive theories of the developing psychosis. Interactions with the liability to psychotic transitions and therapeutic interventions should be unravelled in longitudinal studies.

Fronto-limbic structural brain abnormalities have been reported in patients with bipolar disorder (BD), but findings in individuals at increased genetic risk of developing BD have been inconsistent. We conducted a study in adolescents and young adults (12–30 years) comparing measures of fronto-limbic cortical and subcortical brain structure between individuals at increased familial risk of BD (at risk; AR), subjects with BD and controls (CON). We separately examined cortical volume, thickness and surface area as these have distinct neurodevelopmental origins and thus may reflect differential effects of genetic risk.

We compared fronto-limbic measures of grey and white matter volume, cortical thickness and surface area in 72 unaffected-risk individuals with at least one first-degree relative with bipolar disorder (AR), 38 BD subjects and 72 participants with no family history of mental illness (CON).

The AR group had significantly reduced cortical thickness in the left pars orbitalis of the inferior frontal gyrus (IFG) compared with the CON group, and significantly increased left parahippocampal gyral volume compared with those with BD.

The finding of reduced cortical thickness of the left pars orbitalis in AR subjects is consistent with other evidence supporting the IFG as a key region associated with genetic liability for BD. The greater volume of the left parahippocampal gyrus in those at high risk is in line with some prior reports of regional increases in grey matter volume in at-risk subjects. Assessing multiple complementary morphometric measures may assist in the better understanding of abnormal developmental processes in BD.

Few studies have investigated the impact of parental suicide attempt (SA) on offspring outcomes other than mental health. We investigated the association of parental SA with offspring educational attainment in the Avon Longitudinal Study of Parents and Children (ALSPAC).

Parental SA was prospectively recorded from pregnancy until the study children were 11 years old. National school test results (ages 11–16 years) were obtained by record linkage. Multilevel regression models quantified the association between parental SA and offspring outcomes.

Data were available for 6667 mother–child and 3054 father–child pairs. Adolescents whose mothers had attempted suicide were less likely than their peers to achieve the expected educational level by age 14 years [adjusted odds ratio (aOR) 0.63, 95% confidence interval (CI) 0.41–0.95] in models controlling for relevant confounders, including parental education and depression. At age 16 years, adolescents whose mothers had attempted suicide were less likely to obtain the expected educational level (five or more qualifications at grade A*–C) (aOR 0.66, 95% CI 0.43–1.00) in models controlling for relevant confounders and parental education; however, after additionally controlling for maternal depression the results were consistent with chance (aOR 0.74, 95% CI 0.48–1.13). Findings in relation to paternal SA were consistent with those of maternal SA but power was limited due to lower response rate amongst fathers.

Maternal SA was associated with diminished educational performance at age 14 years. Educational attainment during adolescence can have substantial effect on future opportunities and well-being and these offspring may benefit from interventions.

Because depressive illness is recurrent, recurrence prevention should be a mainstay for reducing its burden on society. One way to reach this goal is to identify malleable risk factors. The ability to attenuate sadness/dysphoria (mood repair) and parasympathetic nervous system functioning, indexed as respiratory sinus arrhythmia (RSA), are impaired during depression and after it has remitted. The present study therefore tested the hypothesis that these two constructs also may mirror risk factors for a recurrent major depressive episode (MDE).

At time 1 (T1), 178 adolescents, whose last MDE had remitted, and their parents, reported on depression and mood repair; youths’ RSA at rest and in response to sad mood induction also were assessed. MDE recurrence was monitored until time 2 (T2) up to 2 years later. Mood repair at T1 (modeled as a latent construct), and resting RSA and RSA response to sadness induction (RSA profile), served to predict onset of first recurrent MDE by T2.

Consistent with expectations, maladaptive mood repair predicted recurrent MDE, above and beyond T1 depression symptoms. Further, atypical RSA profiles at T1 were associated with high levels of maladaptive mood repair, which, in turn, predicted increased risk of recurrent MDE. Thus, maladaptive mood repair mediated the effects of atypical RSA on risk of MDE recurrence.

This study documented that a combination of behavioral and physiological risk factors predicted MDE recurrence in a previously clinically referred sample of adolescents with depression histories. Because mood repair and RSA are malleable, both could be targeted for modification to reduce the risk of recurrent depression in youths.

People with depression tend to have lower heart rate variability (HRV), but the temporal sequence is poorly understood. In a sample of the general population, we prospectively examined whether HRV measures predict subsequent depressive symptoms or whether depressive symptoms predict subsequent levels of HRV.

Data from the fifth (1997–1999) and ninth (2007–2009) phases of the UK Whitehall II longitudinal population-based cohort study were analysed with an average follow-up of 10.5 years. The sample size for the prospective analysis depended on the analysis and ranged from 2334 (644 women) to 2276 (602 women). HRV measures during 5 min of supine rest were obtained. Depressive symptoms were evaluated by four cognitive symptoms of depression from the General Health Questionnaire.

At follow-up assessment, depressive symptoms were inversely associated with HRV measures independently of antidepressant medication use in men but not in women. Prospectively, lower baseline heart rate and higher HRV measures were associated with a lower likelihood of incident depressive symptoms at follow-up in men without depressive symptoms at baseline. Similar but statistically insignificant associations were found in women. Adjustments for known confounders including sociodemographic and lifestyle factors, cardiometabolic conditions or medication did not change the predictive effect of HRV on incident depressive symptoms at follow-up. Depressive symptoms at baseline were not associated with heart rate or HRV at follow-up in either sex.

These findings are consistent with an aetiological role of the autonomic nervous system in depression onset.

Cognitive deficits are present from the onset of psychosis and are considered a core feature of the disorder. Increasing evidence suggests that cognitive function is associated with inflammatory processes. This study evaluated the association between cognition and inflammatory biomarkers in first-episode psychosis (FEP), in order to identify cognitive phenotypes from inflammatory expression profiles.

A case-control study of 92 FEP patients and 80 matched controls was used. Neurocognitive assessment, including verbal ability, sustained attention, verbal memory, working memory and executive function, was performed. The expression of pro- and anti-inflammatory mediators of the main intracellular inflammatory pathway was measured in peripheral blood mononuclear cells and plasma.

FEP patients performed worse in all cognitive domains compared to controls and had higher expression of pro-inflammatory mediators and lower expression of anti-inflammatory mediators. In the FEP group, cognition and psychopathology were associated with inflammation. Hierarchical regression analysis showed that association between the anti-inflammatory prostaglandin 15d-PGJ2 and sustained attention on one hand, and COX-2 expression and executive function on the other, were statistically significant.

Our study provides evidence for an association between anti-inflammatory biomarkers and cognition in FEP. The identification of a subgroup of patients based on these measures could be useful to guide treatment programmes by providing tools to select a personalized treatment approach, but longitudinal studies are needed before. In the future, establishment of biomarkers linked to cognition would be useful to monitor the course of cognitive impairment, but substantially more data will be required. Determination of IκBα, the inhibitory protein of the pro-inflammatory transcription factor NFκB, could be useful in early phases to assess clinical severity.

In studies using magnetic resonance imaging (MRI), some have reported specific brain structure–function relationships among first-episode psychosis (FEP) patients, but findings are inconsistent. We aimed to localize the brain regions where cortical thickness (CTh) and surface area (cortical area; CA) relate to neurocognition, by performing an MRI on participants and measuring their neurocognitive performance using the Cambridge Neuropsychological Test Automated Battery (CANTAB), in order to investigate any significant differences between FEP patients and control subjects (CS).

Exploration of potential correlations between specific cognitive functions and brain structure was performed using CANTAB computer-based neurocognitive testing and a vertex-by-vertex whole-brain MRI analysis of 63 FEP patients and 30 CS.

Significant correlations were found between cortical parameters in the frontal, temporal, cingular and occipital brain regions and performance in set-shifting, working memory manipulation, strategy usage and sustained attention tests. These correlations were significantly dissimilar between FEP patients and CS.

Significant correlations between CTh and CA with neurocognitive performance were localized in brain areas known to be involved in cognition. The results also suggested a disrupted structure–function relationship in FEP patients compared with CS.

Hippocampal volume reductions in major depression have been frequently reported. However, evidence for functional abnormalities in the same region in depression has been less clear. We investigated hippocampal function in depression using functional magnetic resonance imaging (fMRI) and neuropsychological tasks tapping spatial memory function, with complementing measures of hippocampal volume and resting blood flow to aid interpretation.

A total of 20 patients with major depressive disorder (MDD) and a matched group of 20 healthy individuals participated. Participants underwent multimodal magnetic resonance imaging (MRI): fMRI during a spatial memory task, and structural MRI and resting blood flow measurements of the hippocampal region using arterial spin labelling. An offline battery of neuropsychological tests, including several measures of spatial memory, was also completed.

The fMRI analysis showed significant group differences in bilateral anterior regions of the hippocampus. While control participants showed task-dependent differences in blood oxygen level-dependent (BOLD) signal, depressed patients did not. No group differences were detected with regard to hippocampal volume or resting blood flow. Patients showed reduced performance in several offline neuropsychological measures. All group differences were independent of differences in hippocampal volume and hippocampal blood flow.

Functional abnormalities of the hippocampus can be observed in patients with MDD even when the volume and resting perfusion in the same region appear normal. This suggests that changes in hippocampal function can be observed independently of structural abnormalities of the hippocampus in depression.

Negative symptoms and cognitive deficits in schizophrenia are partially overlapping. However, the nature of the relationship between negative symptoms and cognition remains equivocal. Recent reviews have demonstrated the presence of two negative symptom subdomains, diminished emotional expression (DEE) and avolition. In view of this, we sought to clarify the relationship between negative symptoms and cognitive domains.

A total of 687 participants with schizophrenia were assessed on measures of psychopathology and cognition. Three cognitive factors, namely executive function, fluency/memory and speed/vigilance were computed from the cognitive tests. Confirmatory factor analysis was utilized to examine if a one-factor or two-factor negative model was applicable to our sample. Subsequently, the relationships between negative symptoms and cognition were examined using structural equation modeling.

Results demonstrated that the two-factor model fitted the data well. While negative symptoms were mildly to moderately associated with cognition, we found that DEE had unique associations with cognition compared to social avolition, contributing to the validity of the constructs and suggesting the possibility of common underlying substrates in negative symptoms and cognition.

Our study highlighted the need to classify DEE and social avolition separately as both are necessary in refining the complex relationship between negative symptoms and cognition as well as potentially guiding treatment and management of schizophrenia.

A considerable proportion of people with schizophrenia spectrum disorders do not take antipsychotic medication but seem to be functioning well. However, little is known about this group. To test the assumption that absence of medication is compensated for by more effective coping and increased social support, this study compared symptoms, functioning, coping strategies and social support in non-medicated and medicated individuals with schizophrenia spectrum disorders.

In all, 48 participants with a DSM-IV schizophrenia spectrum disorder who were taking (n = 25) or not taking antipsychotic medication (n = 23) were included. Assessment consisted of self-ratings of symptoms, symptom-related distress and social support combined with a semi-structured interview that assessed general and social functioning, subjective evaluation of symptoms and coping strategies.

Symptom severity and distress did not differ between the groups. However, the non-medicated participants had significantly higher levels of general functioning than medicated participants and a longer duration of being non-medicated was significantly associated with a higher level of general functioning. In contrast to the hypotheses, not taking medication was not associated with more effective coping strategies or with higher levels of social support. Medicated participants more frequently reported the use of professional help as a coping strategy.

Our results corroborate previous studies finding improved functioning in individuals with schizophrenia spectrum disorders who do not take medication compared with those who take medication, but do not support the notion that this difference is explicable by better coping or higher levels of social support. Alternative explanations and avenues for research are discussed.

Learning and memory impairments in older adults with depression are linked to hippocampal atrophy. However, other subcortical regions may also be contributing to these deficits. We aimed to examine whether anterior caudate nucleus volume is significantly reduced in older adults with depression compared to controls; whether anterior caudate volume is associated with performance on tasks of episodic learning and memory, and if so, whether this association is independent of the effects of the hippocampus.

Eighty-four health-seeking participants meeting criteria for lifetime major depressive disorder (mean age = 64.2, s.d. = 9.1 years) and 27 never-depressed control participants (mean age = 63.9, s.d. = 8.0 years) underwent neuropsychological assessment including verbal episodic memory tests [Rey Auditory Verbal Learning Test and Logical Memory (WMS-III)]. Magnetic resonance imaging was conducted, from which subregions of the caudate nucleus were manually demarcated bilaterally and hippocampal volume was calculated using semi-automated methods.

Depressed subjects had smaller right anterior caudate (RAC) (t = 2.3, p = 0.026) and poorer memory compared to controls (t = 2.5, p < 0.001). For depressed subjects only, smaller RAC was associated with poorer verbal memory (r = 0.3, p = 0.003) and older age (r = −0.46, p < 0.001). Multivariable regression showed that the RAC and hippocampus volume uniquely accounted for 5% and 3% of the variance in memory, respectively (β = 0.25, t = 2.16, p = 0.033; β = 0.19, t = 1.71, p = 0.091).

In older people with depression, the anterior caudate nucleus and the hippocampus play independent roles in mediating memory. While future studies examining this structure should include larger sample sizes and adjust for multiple comparisons, these findings support the critical role of the striatum in depression.

A structural neuroanatomical change indicating a reduction in brain tissue is a notable feature of schizophrenia. Several pathophysiological processes such as aberrant cortical maturation, progressive tissue loss and compensatory tissue increase could contribute to the structural changes seen in schizophrenia.

We studied cortical thickness using surface-based morphometry in 98 clinically stable patients with schizophrenia and 83 controls. Using a pattern classification approach, we studied whether the features that discriminate patients from controls vary across the different stages of the illness. Using a covariance analysis, we also investigated if concurrent increases accompany decreases in cortical thickness.

Very high levels of accuracy (96.3%), specificity (98.8%) and sensitivity (88%) were noted when classifying patients with <2 years of illness from controls. Within the patient group, reduced thickness was consistently accompanied by increased thickness in distributed brain regions. A pattern of cortical amelioration or normalization (i.e. reduced deviation from controls) was noted with increasing illness duration. While temporo-limbic and fronto-parietal regions showed reduced thickness, the occipital cortex showed increased thickness, especially in those with a long-standing illness.

A compensatory remodelling process might contribute to the cortical thickness variations in different stages of schizophrenia. Subtle cerebral reorganization reflecting the inherent plasticity of brain may occur concomitantly with processes contributing to tissue reduction in adult patients with schizophrenia.

Post-traumatic stress disorder (PTSD) is associated with elevated risk for metabolic syndrome (MetS). However, the direction of this association is not yet established, as most prior studies employed cross-sectional designs. The primary goal of this study was to evaluate bidirectional associations between PTSD and MetS using a longitudinal design.

A total of 1355 male and female veterans of the conflicts in Iraq and Afghanistan underwent PTSD diagnostic assessments and their biometric profiles pertaining to MetS were extracted from the electronic medical record at two time points (spanning ~2.5 years, n = 971 at time 2).

The prevalence of MetS among veterans with PTSD was just under 40% at both time points and was significantly greater than that for veterans without PTSD; the prevalence of MetS among those with PTSD was also elevated relative to age-matched population estimates. Cross-lagged panel models revealed that PTSD severity predicted subsequent increases in MetS severity (β = 0.08, p = 0.002), after controlling for initial MetS severity, but MetS did not predict later PTSD symptoms. Logistic regression results suggested that for every 10 PTSD symptoms endorsed at time 1, the odds of a subsequent MetS diagnosis increased by 56%.

Results highlight the substantial cardiometabolic concerns of young veterans with PTSD and raise the possibility that PTSD may predispose individuals to accelerated aging, in part, manifested clinically as MetS. This demonstrates the need to identify those with PTSD at greatest risk for MetS and to develop interventions that improve both conditions.

Results of adulthood mental health of those born late-preterm (34 + 0–36 + 6 weeks + days of gestation) are mixed and based on national registers. We examined if late-preterm birth was associated with a higher risk for common mental disorders in young adulthood when using a diagnostic interview, and if this risk decreased as gestational age increased.

A total of 800 young adults (mean = 25.3, s.d. = 0.62 years), born 1985–1986, participated in a follow-up of the Arvo Ylppö Longitudinal Study. Common mental disorders (mood, anxiety and substance use disorders) during the past 12 months were defined using the Composite International Diagnostic Interview (Munich version). Gestational age was extracted from hospital birth records and categorized into early-preterm (<34 + 0, n = 37), late-preterm (34 + 0–36 + 6, n = 106), term (37 + 0–41 + 6, n = 617) and post-term (⩾42 + 0, n = 40).

Those born late-preterm and at term were at a similar risk for any common mental disorder [odds ratio (OR) 1.11, 95% confidence interval (CI) 0.67–1.84], for mood (OR 1.11, 95% CI 0.54–2.25), anxiety (OR 1.00, 95% CI 0.40–2.50) and substance use (OR 1.31, 95% CI 0.74–2.32) disorders, and co-morbidity of these disorders (p = 0.38). While the mental disorder risk decreased significantly as gestational age increased, the trend was driven by a higher risk in those born early-preterm.

Using a cohort born during the advanced neonatal and early childhood care, we found that not all individuals born preterm are at risk for common mental disorders in young adulthood – those born late-preterm are not, while those born early-preterm are at a higher risk. Available resources for prevention and intervention should be targeted towards the preterm group born the earliest.