Few studies have examined religiosity as a protective factor using a longitudinal design to predict resilience in persons at high risk for major depressive disorder (MDD).

High-risk offspring selected for having a depressed parent and control offspring of non-depressed parents were evaluated for psychiatric disorders in childhood/adolescence and at 10-year and 20-year follow-ups. Religious/spiritual importance, services attendance and negative life events (NLEs) were assessed at the 10-year follow-up. Models tested differences in relationships between religiosity/spirituality and subsequent disorders among offspring based on parent depression status, history of prior MDD and level of NLE exposure. Resilience was defined as lower odds for disorders with greater religiosity/spirituality in higher-risk versus lower-risk offspring.

Increased attendance was associated with significantly reduced odds for mood disorder (by 43%) and any psychiatric disorder (by 53%) in all offspring; however, odds were significantly lower in offspring of non-depressed parents than in offspring of depressed parents. In analyses confined to offspring of depressed parents, those with high and those with average/low NLE exposure were compared: increased attendance was associated with significantly reduced odds for MDD, mood disorder and any psychiatric disorder (by 76, 69 and 64% respectively) and increased importance was associated with significantly reduced odds for mood disorder (by 74%) only in offspring of depressed parents with high NLE exposure. Moreover, those associations differed significantly between offspring of depressed parents with high NLE exposure and offspring of depressed parents with average/low NLE exposure.

Greater religiosity may contribute to development of resilience in certain high-risk individuals.

Cannabis use by people with schizophrenia has been found to be associated with family distress and poor clinical outcomes. Interventions to reduce drug use in this patient group have had limited efficacy. This study evaluated the effectiveness of a novel intervention for parents of young adults with recent-onset schizophrenia consisting of family-based motivational interviewing and interaction skills (Family Motivational Intervention, FMI) in comparison with routine family support (RFS).

In a trial with 75 patients who used cannabis and received treatment for recent-onset schizophrenia, 97 parents were randomly assigned to either FMI (n=53) or RFS (n=44). Assessments were conducted at baseline and 3 months after completion of the family intervention by an investigator who remained blind throughout the study about the assignment of the parents.

At follow-up, patients' frequency and quantity of cannabis use was significantly more reduced in FMI than in RFS (p<0.05 and p<0.04 respectively). Patients' craving for cannabis was also significantly reduced in FMI whereas there was a small increase in RFS (p=0.01). There was no difference between FMI and RFS with regard to patients' other substance use and general level of functioning. Both groups showed significant improvements in parental distress and sense of burden.

Training parents in motivational interviewing and interaction skills is feasible and effective in reducing cannabis use among young adults with recent-onset schizophrenia. However, FMI was not more effective than RFS in increasing patients' general level of functioning and in reducing parents' stress and sense of burden.

Previous studies have suggested that motivational aspects of executive functioning, which may be disrupted in schizophrenia patients with negative symptoms, are mediated in part by the striatum. Negative symptoms have been linked to impaired recruitment of both the striatum and the dorsolateral prefrontal cortex (DLPFC). Here we tested the hypothesis that negative symptoms are associated primarily with striatal dysfunction, using functional magnetic resonance imaging (fMRI).

Working-memory load-dependent activation and gray matter volumes of the striatum and DLPFC were measured using a region-of-interest (ROI) approach, in 147 schizophrenia patients and 160 healthy controls. In addition to testing for a linear relationships between striatal function and negative symptoms, we chose a second, categorical analytic strategy in which we compared three demographically and behaviorally matched subgroups: patients with a high burden of negative symptoms, patients with minimal negative symptoms, and healthy subjects.

There were no differences in striatal response magnitudes between schizophrenia patients and healthy controls, but right DLPFC activity was higher in patients than in controls. Negative symptoms were inversely associated with striatal, but not DLPFC, activity. In addition, patients with a high burden of negative symptoms exhibited significantly lower bilateral striatal, but not DLPFC, activation than schizophrenia patients with minimal negative symptoms. Working memory performance, antipsychotic exposure and changes in gray matter volumes did not account for these differences.

These data provide further evidence for a robust association between negative symptoms and diminished striatal activity. Future work will determine whether low striatal activity in schizophrenia patients could serve as a reliable biomarker for negative symptoms.

Belief inflexibility is a thinking style observed in patients with schizophrenia, in which patients tend to refute evidence that runs counter to their prior beliefs. This bias has been related to a dominance of prior expectations (prior beliefs) over incoming sensory evidence. In this study we investigated the reliance on prior expectations for the processing of emotional faces in schizophrenia.

Eighteen patients with schizophrenia and 18 healthy controls were presented with sequences of emotional (happy, fearful, angry or neutral) faces. Perceptual decisions were biased towards a particular expression by a specific instruction at the start of each sequence, referred to as the context in which stimuli occurred. Participants were required to judge the emotion on each face and the effect of the context on emotion discrimination was investigated.

For threatening emotions (anger and fear), there was a performance cost for facial expressions that were incongruent with, and perceptually close to, the expression named in the instruction. For example, for angry faces, participants in both groups made more errors and reaction times (RTs) were longer when they were asked to look out for fearful faces compared with the other contexts. This bias against sensory evidence that runs counter to prior information was stronger in the patients, evidenced by a group by context interaction in accuracy and RTs for anger and fear respectively.

Overall, the present data suggest an overdependence on prior expectations for threatening stimuli, reflecting belief inflexibility, in schizophrenia.

Neurodevelopmental alterations have been described inconsistently in psychosis probably because of lack of standardization among studies. The aim of this study was to conduct the first longitudinal and population-based magnetic resonance imaging (MRI) evaluation of the presence and size of the cavum septum pellucidum (CSP) and adhesio interthalamica (AI) in a large sample of patients with first-episode psychosis (FEP).

FEP patients (n=122) were subdivided into schizophrenia (n=62), mood disorders (n=46) and other psychosis (n=14) groups and compared to 94 healthy next-door neighbour controls. After 13 months, 80 FEP patients and 52 controls underwent a second MRI examination.

We found significant reductions in the AI length in schizophrenia FEP in comparison with the mood disorders and control subgroups (longer length) at the baseline assessment, and no differences in any measure of the CSP. By contrast, there was a diagnosis×time interaction for the CSP length, with a more prominent increase for this measure in the psychosis group. There was an involution of the AI length over time for all groups but no diagnosis×time interaction.

Our findings suggest that the CSP per se may not be linked to the neurobiology of emerging psychotic disorders, although it might be related to the progression of the disease. However, the fact that the AI length was shown to be shorter at the onset of the disorder supports the neurodevelopmental model of schizophrenia and indicates that an alteration in this grey matter junction may be a risk factor for developing psychosis.

Major depressive disorder during pregnancy associates with potentially detrimental consequences for mother and child. The current study examined peripheral blood gene expression as a potential biomarker for prenatal depressive symptoms.

Maternal RNA from whole blood, plasma and the Beck Depression Inventory were collected longitudinally from preconception through the third trimester of pregnancy in 106 women with a lifetime history of mood or anxiety disorders. The expression of 16 genes in whole blood involved in glucorticoid receptor (GR) signaling was assessed using real-time polymerase chain reaction. In parallel, plasma concentrations of progesterone, estradiol and cortisol were measured. Finally, we assessed ex vivo GR sensitivity in peripheral blood cells from a subset of 29 women.

mRNA expression of a number of GR-complex regulating genes was up-regulated over pregnancy. Women with depressive symptoms showed significantly smaller increases in mRNA expression of four of these genes – FKBP5, BAG1, NCOA1 and PPID. Ex vivo stimulation assays showed that GR sensitivity diminished with progression of pregnancy and increasing maternal depressive symptoms. Plasma concentrations of gonadal steroids and cortisol did not differ over pregnancy between women with and without clinically relevant depressive symptoms.

The presence of prenatal depressive symptoms appears to be associated with altered regulation of GR sensitivity. Peripheral expression of GR co-chaperone genes may serve as a biomarker for risk of developing depressive symptoms during pregnancy. The presence of such biomarkers, if confirmed, could be utilized in treatment planning for women with a psychiatric history.

Depression has been associated with functional alterations in several areas of the cingulate cortex. In this study we have taken a systematic approach to examining how alterations in functional connectivity vary across the functionally diverse subregions of the rostral cingulate cortex.

Eighteen patients with major depressive disorder, aged 15 to 24 years, were matched with 20 healthy control participants. Using resting-state functional connectivity magnetic resonance imaging (fcMRI), we systematically investigated the functional connectivity of four subregions of the rostral cingulate cortex. Voxelwise statistical maps of each subregion's connectivity with other brain areas were compared between the patient and control groups.

The depressed participants showed altered patterns of connectivity with ventral cingulate subregions. They showed increased connectivity between subgenual anterior cingulate cortex (ACC) and dorsomedial frontal cortex, with connectivity strength showing positive correlation with illness severity. Depressed participants also showed increased connectivity between pregenual ACC and left dorsolateral frontal cortex, and decreased connectivity between pregenual ACC and the caudate nucleus bilaterally.

The results reinforce the importance of subgenual ACC for depression, and show a close link between brain regions that support self-related processes and affective visceromotor function. The pregenual ACC also has an important role, with its increased connectivity with dorsolateral frontal cortex suggesting heightened cognitive regulation of affect; and reduced connectivity with the caudate nucleus potentially underlying symptoms such as anhedonia, reduced motivation and psychomotor dysfunction.

Clinical research on subjective determinants of recovery and health has increased, but no instrument has been developed to assess the subjective experience and meaning of psychoses. We have therefore constructed and validated the Subjective Sense in Psychosis Questionnaire (SUSE) to measure sense making in psychotic disorders.

SUSE was based on an item pool generated by professionals and patients. For pre-testing, 90 psychosis patients completed the instrument. Psychometric properties were assessed using methods of classical test theory. In the main study, SUSE was administered to a representative sample of 400 patients. Factor structure, reliability and validity were assessed and confirmatory factor analyses (CFAs) were used for testing subscale coherence and adequacy of the hypothesized factor structure. Response effects due to clinical settings were tested using multilevel analyses.

The final version of SUSE comprises 34 items measuring distinct aspects of the experience and meaning of psychoses in a consistent overall model with six coherent subscales representing positive and negative meanings throughout the course of psychotic disorders. Multilevel analyses indicate independence from clinical context effects. Patients relating psychotic experiences to life events assessed their symptoms and prospects more positively. 76% of patients assumed a relationship between their biography and the emergence of psychosis, 42% reported positive experience of symptoms and 74% ascribed positive consequences to their psychosis.

SUSE features good psychometric qualities and offers an empirical acquisition to subjective assessment of psychosis. The results highlight the significance of subjective meaning making in psychoses and support a more biographical and in-depth psychological orientation for treatment.

Global brain abnormalities such as brain volume loss and grey- and white-matter deficits are consistently reported in first-episode schizophrenia patients and may already be detectable in the very early stages of the illness. Whether these changes are dependent on medication use or related to intelligence quotient (IQ) is still debated.

Magnetic resonance imaging scans were obtained for 20 medication-naive patients with first-episode schizophrenia and 26 matched healthy subjects. Volume measures of total brain grey and white matter, third and lateral ventricles and cortical thickness/surface were obtained. Differences between the groups were investigated, taking into account the effect of intelligence.

Medication-naive patients showed statistically significant reductions in whole-brain volume and cerebral grey- and white-matter volume together with lateral ventricle enlargement compared to healthy subjects. IQ was significantly lower in patients compared to controls and was positively associated with brain and white-matter volume in the whole group. No significant differences in cortical thickness were found between the groups but medication-naive patients had a significantly smaller surface in the left superior temporal pole, Heschl's gyrus and insula compared to controls.

Our findings suggest that brain volume loss is present at illness onset, and can be explained by the reduced surface of the temporal and insular cortex. These abnormalities are not related to medication, but IQ.

Cognitive therapy has been found to be effective in decreasing the recurrence of suicide attempts. A theoretical aim of cognitive therapy is to improve problem-solving skills so that suicide no longer remains the only available option. This study examined the differential rate of change in problem-solving appraisal following suicide attempts among individuals who participated in a randomized controlled trial for the prevention of suicide.

Changes in problem-solving appraisal from pre- to 6-months post-treatment in individuals with a recent suicide attempt, randomized to either cognitive therapy (n=60) or a control condition (n=60), were assessed by using the Social Problem-Solving Inventory-Revised, Short Form.

Improvements in problem-solving appraisal were similarly observed for both groups within the 6-month follow-up. However, during this period, individuals assigned to the cognitive therapy condition demonstrated a significantly faster rate of improvement in negative problem orientation and impulsivity/carelessness. More specifically, individuals receiving cognitive therapy were significantly less likely to report a negative view toward life problems and impulsive/carelessness problem-solving style.

Cognitive therapy for the prevention of suicide provides rapid changes within 6 months on negative problem orientation and impulsivity/carelessness problem-solving style. Given that individuals are at the greatest risk for suicide within 6 months of their last suicide attempt, the current study demonstrates that a brief cognitive intervention produces a rapid rate of improvement in two important domains of problem-solving appraisal during this sensitive period.

Few studies have examined the short-term course of cognitive impairments in bipolar disorder (BD). Key questions are whether trajectories in symptoms covary with cognitive function and whether BD is associated with increased intra-individual variability in cognitive abilities.

Forty-two out-patients with BD and 49 normal comparison (NC) subjects were administered a battery of neuropsychological tests at baseline, 6, 12 and 26 weeks, along with concurrent ratings of depressive and manic symptom severity. Mixed-effects regressions were used to model relationships between time, diagnosis and symptom severity on composite cognitive performance. Within-person variance in cognitive functioning across time was calculated for each subject.

BD patients had significantly worse performance in cognitive ability across time points, but both groups showed significant improvement in cognitive performance over repeated assessments (consistent with expected practice effects). BD was associated with significantly greater intra-individual variability in cognitive ability than NCs; within-person variation was negatively related to baseline cognitive ability in BD but not NC subjects. Changes in affective symptoms over time did not predict changes in cognitive ability.

Moderate changes in affective symptoms did not covary with cognitive ability in BD. The finding of elevated intra-individual variability in BD may reduce capacity to estimate trajectories of cognitive ability in observational and treatment studies.

Mortality, including suicide and accidents, is elevated in self-harm populations. Although risk factors for suicide following self-harm are often investigated, rarely have those for accidents been studied. Our aim was to compare risk factors for suicide and accidents.

A prospective cohort (n=30 202) from the Multicentre Study of Self-harm in England, 2000–2007, was followed up to 2010 using national death registers. Risk factors for suicide (intentional self-harm and undetermined intent) and accidents (narcotic poisoning, non-narcotic poisoning, and non-poisoning) following the last hospital presentation for self-harm were estimated using Cox models.

During follow-up, 1833 individuals died, 378 (20.6%) by suicide and 242 (13.2%) by accidents. Independent predictors of both suicide and accidents were: male gender, age ⩾35 years (except accidental narcotic poisoning) and psychiatric treatment (except accidental narcotic poisoning). Factors differentiating suicide from accident risk were previous self-harm, last method of self-harm (twofold increased risks for cutting and violent self-injury versus self-poisoning) and mental health problems. A risk factor specific to accidental narcotic poisoning was recreational/illicit drug problems, and a risk factor specific to accidental non-narcotic poisoning and non-poisoning accidents was alcohol involvement with self-harm.

The similarity of risk factors for suicide and accidents indicates common experiences of socio-economic disadvantage, life problems and psychopathology resulting in a variety of self-destructive behaviour. Of factors associated with the accidental death groups, those for non-narcotic poisoning and other accidents were most similar to suicide; differences seemed to be related to criteria coroners use in reaching verdicts. Our findings support the idea of a continuum of premature death.

Accurate monitoring and integration of both internal and external feedback is crucial for guiding current and future behavior. These aspects of performance monitoring are commonly indexed by two event-related potential (ERP) components: error-related negativity (ERN) and feedback negativity (FN). The ERN indexes internal response monitoring and is sensitive to the commission of erroneous versus correct responses, and the FN indexes external feedback monitoring of positive versus negative outcomes. Although individuals with schizophrenia consistently demonstrate a diminished ERN, the integrity of the FN has received minimal consideration.

The current research sought to clarify the scope of feedback processing impairments in schizophrenia in two studies: study 1 examined the ERN elicited in a flanker task in 16 out-patients and 14 healthy controls; study 2 examined the FN on a simple monetary gambling task in expanded samples of 35 out-patients and 33 healthy controls.

Study 1 replicated prior reports of an impaired ERN in schizophrenia. By contrast, patients and controls demonstrated comparable FN differentiation between reward and non-reward feedback in study 2.

The differential pattern across tasks suggests that basic sensitivity to external feedback indicating reward versus non-reward is intact in schizophrenia, at least under the relatively simple task conditions used in this study. Further efforts to specify intact and impaired reward-processing subcomponents in schizophrenia may help to shed light on the diminished motivation and goal-seeking behavior that are commonly seen in this disorder.

Genes for depression may act by making individuals more sensitive to childhood trauma. Given that childhood adversity is a risk factor for adult psychosis and symptoms of depression and psychosis tend to cluster within individuals and families, the aim was to examine whether the association between childhood adversity and psychotic-like symptoms is moderated by genetic liability for depression. A secondary aim was to determine to what degree a depression-related increase in stress sensitivity or depressive symptoms themselves occasioned the moderating effect.

Female twins (n=508) completed both prospective and retrospective questionnaires regarding childhood adversity [the Symptom Checklist-90 – Revised (SCL-90-R) and SCID-I (psychotic symptoms)] and psychotic trait liability [the Community Assessment of Psychic Experiences (CAPE)]. Stress sensitivity was indexed by appraisals of event-related stress and negative affect (NA) in the flow of daily life, assessed with momentary assessment technology for five consecutive days. Multilevel regression analyses were used to examine moderation of childhood adversity by genetic liability for depression in the prediction of follow-up psychotic experiences.

The effect of childhood adversity was significantly moderated by genetic vulnerability for depression in the model of both follow-up psychotic experiences (SCL-90-R) and follow-up psychotic trait liability (CAPE). The moderation by genetic liability was mediated by depressive experience but not by stress sensitivity.

Genetic liability for depression may potentiate the pathway from childhood adversity to psychotic-like symptoms through dysfunctional emotional processing of anomalous experiences associated with childhood trauma.

Depression in the context of bipolar disorder (BDd) is often misdiagnosed as unipolar disorder depression (UDd) leading to poor clinical outcomes for many bipolar sufferers. We examined neural circuitry supporting emotion regulation in females with either BDd or UDd as a first stage toward identifying biomarkers that may differentiate BDd from UDd.

Fifty-seven females aged 18–45 years participated in this study: 23 with UDd, 18 with bipolar disorder type I depression (BDId) and 16 healthy females. During 3-T functional magnetic resonance imaging (fMRI), the participants performed an emotional face n-back (EFNBACK) task, that is an n-back task with high (2-back) and low (0-back) memory load conditions flanked by two positive, negative or neutral face distracters. This paradigm examines executive control with emotional distracters–emotion regulation.

High memory load with neutral face distracters elicited greater bilateral and left dorsal anterior midcingulate cortex (dAMCC) activity in UDd than in healthy and BDId females respectively, and greater bilateral putamen activity in both depressed groups versus healthy females. High memory load with happy face distracters elicited greater left putamen activity in UDd than in healthy females. Psychotropic medication was associated with greater putamen activity to these contrasts in UDd females.

During high memory load with neutral face distracters, elevated dAMCC activity in UDd suggests abnormal recruitment of attentional control circuitry to maintain task performance, whereas elevated putamen activity unrelated to psychotropic medication in BDId females may suggest an attentional bias toward ambiguous neutral face distracters. Differential patterns of functional abnormalities in neural circuitry supporting attentional control during emotion regulation, especially in the dAMCC, is a promising neuroimaging measure to distinguish UDd from BDId in females.

It is not known whether first-episode psychosis is characterized by the same prefrontal cortex functional imaging abnormalities as chronic schizophrenia.

Thirty patients with a first episode of non-affective functional psychosis and 28 healthy controls underwent functional magnetic resonance imaging (fMRI) during performance of the n-back working memory task. Voxel-based analyses of brain activations and deactivations were carried out and compared between groups. The connectivity of regions of significant difference between the patients and controls was also examined.

The first-episode patients did not show significant prefrontal hypo- or hyperactivation compared to controls. However, they showed failure of deactivation in the medial frontal cortex. This area showed high levels of connectivity with the posterior cingulate gyrus/precuneus and parts of the parietal cortex bilaterally. Failure of deactivation was significantly greater in first-episode patients who had or went on to acquire a DSM-IV diagnosis of schizophrenia than in those who did not, and in those who met RDC criteria for schizophrenia compared to those who did not.

First-episode psychosis is not characterized by hypo- or hyperfrontality but instead by a failure of deactivation in the medial frontal cortex. The location and connectivity of this area suggest that it is part of the default mode network. The failure of deactivation seems to be particularly marked in first-episode patients who have, or progress to, schizophrenia.

Intellectual deficits are commonly found in schizophrenia patients. These intellectual deficits have been found to be heritable. However, whether the intellectual deficits change over time and, if so, whether the change is related with an increased genetic risk for the disease are not known.

We investigated change of intelligence quotient (IQ) in a twin sample of chronically ill schizophrenia patients, the discordant co-twins and healthy controls during a follow-up period of 5 years. A total of 52 twins completed two IQ assessments: nine patients [three monozygotic (MZ) and six dizygotic (DZ)], 10 unaffected co-twins (three MZ and seven DZ) and 33 healthy control twins (21 MZ and 12 DZ).

A significant interaction effect over time was found between IQ measurement and illness (F=4.22, df=1, p<0.05), indicating that change in IQ over time is significantly different between the groups. A stable course in IQ over time was found in the patients with schizophrenia (mean IQ from 109.78 at baseline to 108.44 at follow-up) relative to both the healthy control twins who showed a small increase (from 114.61 at baseline to 119.18 at follow-up) (t=2.06, p<0.05) and the unaffected co-twins (from 111.60 to 117.60, t=−2.32, p<0.05). IQ change in the unaffected co-twins of schizophrenia patients was comparable with that in healthy control twins (t=−0.49, p=0.63).

Patients with schizophrenia in the chronic phase of the disease, but not the discordant co-twins, show a lack of increase in IQ, which is probably due to environmental (non-genetic) factors related to the disease.

Gays, lesbians and bisexuals (i.e. non-heterosexuals) have been found to be at much greater risk for many psychiatric symptoms and disorders, including depression. This may be due in part to prejudice and discrimination experienced by non-heterosexuals, but studies controlling for minority stress, or performed in very socially liberal countries, suggest that other mechanisms must also play a role. Here we test the viability of common cause (shared genetic or environmental etiology) explanations of elevated depression rates in non-heterosexuals.

A community-based sample of adult twins (n=9884 individuals) completed surveys investigating the genetics of psychiatric disorder, and were also asked about their sexual orientation. Large subsets of the sample were asked about adverse childhood experiences such as sexual abuse, physical abuse and risky family environment, and also about number of older brothers, paternal and maternal age, and number of close friends. Data were analyzed using the classical twin design.

Non-heterosexual males and females had higher rates of lifetime depression than their heterosexual counterparts. Genetic factors accounted for 31% and 44% of variation in sexual orientation and depression respectively. Bivariate analysis revealed that genetic factors accounted for a majority (60%) of the correlation between sexual orientation and depression. In addition, childhood sexual abuse and risky family environment were significant predictors of both sexual orientation and depression, further contributing to their correlation.

Non-heterosexual men and women had elevated rates of lifetime depression, partly due to shared etiological factors, although causality cannot be definitively resolved.

Previous research has shown that stressful life events (SLEs) influence the pattern of individual depressive symptoms. However, we do not know how these differences arise. Two theories about the nature of psychiatric disorders have different predictions about the source of these differences: (1) SLEs influence depressive symptoms and correlations between them indirectly, via an underlying acute liability to develop a dysphoric episode (DE; common cause hypothesis); and (2) SLEs influence depressive symptoms and correlations between them directly (network hypothesis). The present study investigates the predictions of these two theories.

We divided a population-based sample of 2096 Caucasian twins (49.9% female) who reported at least two aggregated depressive symptoms in the last year into four groups, based on the SLE they reported causing their symptoms. For these groups, we calculated tetrachoric correlations between the 14 disaggregated depressive symptoms and, subsequently, tested whether the resulting correlation patterns were significantly different and if those differences could be explained by underlying differences in a single acute liability to develop a DE.

The four SLE groups had markedly different correlation patterns between the depressive symptoms. These differences were significant and could not be explained by underlying differences in the acute liability to develop a DE.

Our results are not compatible with the common cause perspective but are consistent with the predictions of the network hypothesis. We elaborate on the implications of a conceptual shift to the network perspective for our diagnostic and philosophical approach to the concept of what constitutes a psychiatric disorder.