Patients with depression often report impairments in social functioning. From a patient perspective, improvements in social functioning might be an important outcome in psychotherapy for depression. Therefore, it is important to examine the effects of psychotherapy on social functioning in patients with depression.

We conducted a meta-analysis on studies of psychotherapy for depression that reported results for social functioning at post-treatment. Only studies that compared psychotherapy to a control condition were included (31 studies with 2956 patients).

The effect size of psychotherapy on social functioning was small to moderate, before [Hedges' g = 0.46, 95% confidence interval (CI) 0.32–0.60] and after adjusting for publication bias (g = 0.40, 95% CI 0.25–0.55). Univariate moderator analyses revealed that studies using care as usual as a control group versus other control groups yielded lower effect sizes, whereas studies conducted in the USA versus other countries and studies that used clinician-rated instruments versus self-report yielded higher effect sizes. Higher quality studies yielded lower effect sizes whereas the number of treatment sessions and the effect size of depressive symptoms were positively related to the effect size of social functioning. When controlling for these and additional characteristics simultaneously in multivariate meta-regression, the effect size of depressive symptoms, treatment format and number of sessions were significant predictors. The effect size of social functioning remained marginally significant, indicating that improvements in social functioning are not fully explained by improvements in depressive symptoms.

Psychotherapy for depression results in small to moderate improvements in social functioning. These improvements are strongly associated with, but not fully explained by, improvements in depressive symptoms.

Because cerebral morphological abnormalities in major depressive disorder (MDD) may be modulated by antidepressant treatment, inclusion of medicated patients may have biased previous meta-analyses of voxel-based morphometry (VBM) studies. A meta-analysis of VBM studies on medication-free MDD patients should be able to distinguish the morphological features of the disease itself from those of treatment.

A systematic search was conducted for the relevant studies. Effect-size signed differential mapping was applied to analyse the grey matter differences between all medication-free MDD patients and healthy controls. Meta-regression was used to explore the effects of demographics and clinical characteristics.

A total of 14 datasets comprising 400 medication-free MDD patients and 424 healthy controls met the inclusion criteria. The pooled meta-analysis and subgroup meta-analyses showed robustly reduced grey matter in prefrontal and limbic regions in MDD. Increased right thalamus volume was only seen in first-episode medication-naive patients, and increased grey matter in the bilateral anterior cingulate cortex only in medication wash-out patients. In meta-regression analyses the percentage of female patients in each study was negatively correlated with reduced grey matter in the right hippocampus.

By excluding interference from medication effects, the present study identified grey matter reduction in the prefrontal–limbic network in MDD. The subgroup meta-analysis results suggest that an increased right thalamus volume might be a trait directly related to MDD, while an increased anterior cingulate cortex volume might be an effect of medication. The meta-regression results perhaps reveal the structural underpinning of the sex differences in epidemiological and clinical aspects of MDD.

Major depression is associated with abnormalities in the function and structure of the hippocampus. However, it is unclear whether these abnormalities might also be present in people ‘at risk’ of illness.

We studied 62 young people (mean age 18.8 years) at familial risk of depression (FH+) but who had never been depressed themselves. Participants underwent magnetic resonance imaging to assess hippocampal structure and neural responses to a task designed to activate hippocampal memory networks. Magnetic resonance spectroscopy was used to measure levels of a combination of glutamine and glutamate (Glx) in the right hippocampus. A total of 59 matched controls with no history of mood disorder in a first-degree relative underwent the same investigations.

Hippocampal volume did not differ between FH+ participants and controls; however, relative to controls, during the memory task, FH+ participants showed increased activation in brain regions encompassing the insular cortices, putamen and pallidum as well as the dorsal anterior cingulate cortex (ACC). FH+ participants also had increased hippocampal levels of Glx.

Euthymic individuals with a parental history of depression demonstrate increased activation of hippocampal-related neural networks during a memory task, particularly in brain regions involved in processing the salience of stimuli. Changes in the activity of the ACC replicate previous findings in FH+ participants using different psychological tasks; this suggests that task-related abnormalities in the ACC may be a marker of vulnerability to depression. Increased levels of Glx in the hippocampus might also represent a risk biomarker but follow-up studies will be required to test these various possibilities.

Individuals with major depressive disorder (MDD) tested in either the depressed (dMDD) or remitted phase (rMDD) recall fewer specific and more categorical autobiographical memories (AMs) compared to healthy controls (HCs). The current study aimed to replicate findings of AM overgenerality in dMDD or rMDD, and to elucidate differences in neurophysiological correlates of AM recall between these MDD samples and HCs.

Unmedicated participants who met criteria for the dMDD, rMDD or HC groups (n = 16/group) underwent functional magnetic resonance imaging (fMRI) while recalling AMs in response to emotionally valenced cue words. Control tasks involved generating examples from an assigned semantic category and counting the number of risers in a letter string.

The results showed fewer specific and more categorical AMs in both MDD samples versus HCs; dMDDs and rMDDs performed similarly on these measures. The neuroimaging results showed differences between groups in the dorsomedial prefrontal cortex (DMPFC), lateral orbitofrontal cortex (OFC), anterior insula, inferior temporal gyrus and parahippocampus/hippocampus during specific AM recall versus example generation. During specific AM recall cued by positively valenced words, group differences were evident in the DMPFC, middle temporal gyrus, parahippocampus/hippocampus and occipital gyrus, whereas differences during specific AM recall cued by negatively valenced words were evident in the DMPFC, superior temporal gyrus and hippocampus.

AM deficits exist in rMDDs, suggesting that these impairments constitute trait-like abnormalities in MDD. We also found distinct patterns of hemodynamic activity for each group as they recalled specific AMs, raising the possibility that each group used a partly unique strategy for self-referential focus during successful retrieval of specific memories.

Our previous work identified deficits in interference processing and learning/memory in past suicide attempters who were currently depressed and medication-free. In this study, we extend this work to an independent sample studied at various stages of illness and treatment (mild symptoms, on average) to determine if these deficits in past suicide attempters are evident during a less severe clinical state.

A total of 80 individuals with a past history of major depression and suicide attempt were compared with 81 individuals with a history of major depression and no lifetime suicide attempts on a battery of neurocognitive measures assessing attention, memory, abstract/contingent learning, working memory, language fluency and impulse control.

Past attempters performed more poorly in attention, memory and working memory domains, but also in an estimate of pre-morbid intelligence. After correction for this estimate, tests that had previously distinguished past attempters – a computerized Stroop task and the Buschke Selective Reminding Test – remained significantly worse in attempters. In a secondary analysis, similar differences were found among those with the lowest levels of depression (Hamilton Depression Rating Scale score <10), suggesting that these deficits may be trait markers independent of current symptomatology.

Deficits in interference processing and learning/memory constitute an enduring defect in information processing that may contribute to poor adaptation, other higher-order cognitive impairments and risk for suicidal behavior.

Antidepressants reduce depressive symptoms in patients with coronary heart disease, but they may be associated with increased mortality. This study aimed to examine whether the use of tricyclic antidepressants (TCA) or selective serotonin reuptake inhibitors (SSRI) is associated with mortality in patients with coronary heart disease, and to determine whether this association is mediated by autonomic function.

A total of 956 patients with coronary heart disease were followed for a mean duration of 7.2 years. Autonomic function was assessed as heart rate variability, and plasma and 24-h urinary norepinephrine.

Of 956 patients, 44 (4.6%) used TCA, 89 (9.3%) used SSRI, and 823 (86.1%) did not use antidepressants. At baseline, TCA users exhibited lower heart rate variability and higher norepinephrine levels compared with SSRI users and antidepressant non-users. At the end of the observational period, 52.3% of the TCA users had died compared with 38.2% in the SSRI group and 37.3% in the control group. The adjusted hazard ratio (HR) for TCA use compared with non-use was 1.74 [95% confidence interval (CI) 1.12–2.69, p = 0.01]. Further adjustment for measures of autonomic function reduced the association between TCA use and mortality (HR = 1.27, 95% CI 0.67–2.43, p = 0.47). SSRI use was not associated with mortality (HR = 1.15, 95% CI 0.81–1.64, p = 0.44).

The use of TCA was associated with increased mortality. This association was at least partially mediated by differences in autonomic function. Our findings suggest that TCA should be avoided in patients with coronary heart disease.

Electroconvulsive therapy (ECT) is an effective treatment for depression but the extent and persistence of cognitive side-effects remain uncertain. It has been reported that there is little evidence that impairments last longer than up to 15 days post-ECT. However, relatively few studies have followed patients for even as long as 1 month post-ECT. Here we report results from a brief cognitive battery given prior to ECT and repeated five times up to 6 months post-ECT.

In a retrospective case-note study of routinely collected clinical data 126 patients treated with ECT completed two neuropsychological tests [Cambridge Neuropsychological Test Automated Battery (CANTAB) spatial recognition memory (SRM) and Mini Mental State Examination (MMSE)] and two subjective reports of memory function, prior to ECT. Patients were reassessed following ECT and at 1, 3 and 6 months post-ECT although not all patients completed all assessments.

Performance relative to pre-ECT baseline was significantly poorer at each post-ECT assessment up to 3 months post-ECT using the CANTAB SRM, but was improved at 6 months. Conversely, MMSE score showed improvements relative to baseline from 1 month post-ECT. Mood and subjective memory scores improved following ECT and were correlated with one another, but not with either neuropsychological measure.

The CANTAB SRM task revealed reversible cognitive deficiencies relative to a pre-ECT baseline for at least 3 months following ECT, while MMSE score and patients' subjective reports showed only improvement. Visuospatial memory scores eventually exceeded baseline 6 months post-ECT.

Interpersonal stress generation is an important maintaining factor in major depression; however, little is known about the psychological mechanisms that undermine interpersonal functioning. This study investigated the role of deficits in person perception to this regard.

Depressed patients (n = 20) and healthy controls (n = 20) completed a false recognition task that measured participants' tendencies to make spontaneous trait inferences (STIs), that is to spontaneously ascribe personality traits to other people. Participants then reported interpersonal daily hassles for one week following the task.

Tendencies to make STIs were significantly higher in depressed patients, particularly those with a history of childhood trauma. The degree to which participants made STIs was significantly related to depression severity, and predicted the occurrence of interpersonal daily hassles during follow-up across, but not within groups.

The results suggest that depressed patients show characteristic biases in person perception that may contribute to the generation of interpersonal stress.

This research assesses whether multi-year treatment with antipsychotic medications reduces or eliminates psychosis in schizophrenia. It provides 20 years of longitudinal data on the frequency and severity of psychotic activity in samples of schizophrenia patients (SZ) treated versus those not treated with antipsychotic medications.

A total of 139 early young schizophrenia and mood-disordered patients were assessed at index hospitalization and then reassessed six times over 20 years for psychosis and other major variables.

At each follow-up assessment over the 20 years, a surprisingly high percentage of SZ treated with antipsychotics longitudinally had psychotic activity. More than 70% of SZ continuously prescribed antipsychotics experienced psychotic activity at four or more of six follow-up assessments over 20 years. Longitudinally, SZ not prescribed antipsychotics showed significantly less psychotic activity than those prescribed antipsychotics (p < 0.05).

The 20-year data indicate that, longitudinally, after the first few years, antipsychotic medications do not eliminate or reduce the frequency of psychosis in schizophrenia, or reduce the severity of post-acute psychosis, although it is difficult to reach unambiguous conclusions about the efficacy of treatment in purely naturalistic or observational research. Longitudinally, on the basis of their psychotic activity and the disruption of functioning, the condition of the majority of SZ prescribed antipsychotics for multiple years would raise questions as to how many of them are truly in remission.

Persecutory delusions are a key psychotic experience. A reasoning style known as ‘jumping to conclusions’ (JTC) – limited information gathering before reaching certainty in decision making – has been identified as a contributory factor in the occurrence of delusions. The cognitive processes that underpin JTC need to be determined in order to develop effective interventions for delusions. In the current study two alternative perspectives were tested: that JTC partially results from impairment in information-processing capabilities and that JTC is a motivated strategy to avoid uncertainty.

A group of 123 patients with persistent persecutory delusions completed assessments of JTC (the 60:40 beads task), IQ, working memory, intolerance of uncertainty, and psychiatric symptoms. Patients showing JTC were compared with patients not showing JTC.

A total of 30 (24%) patients with delusions showed JTC. There were no differences between patients who did and did not jump to conclusions in overall psychopathology. Patients who jumped to conclusions had poorer working memory performance, lower IQ, lower intolerance of uncertainty and lower levels of worry. Working memory and worry independently predicted the presence of JTC.

Hasty decision making in patients with delusions may partly arise from difficulties in keeping information in mind. Interventions for JTC are likely to benefit from addressing working memory performance, while in vivo techniques for patients with delusions will benefit from limiting the demands on working memory. The study provides little evidence for a contribution to JTC from top-down motivational beliefs about uncertainty.

Metacognitive training (MCT) for patients with psychosis is a psychological group intervention that aims to educate patients about common cognitive biases underlying delusion formation and maintenance, and to highlight their negative consequences in daily functioning.

In this randomized controlled trial, 154 schizophrenia spectrum patients with delusions were randomly assigned to either MCT + treatment as usual (TAU) or TAU alone. Both groups were assessed at baseline, and again after 8 and 24 weeks. The trial was completed fully by 111 patients. Efficacy was measured with the Psychotic Symptom Rating Scales (PSYRATS) Delusions Rating Scale (DRS), and with specific secondary measures referring to persecutory ideas and ideas of social reference (the Green Paranoid Thoughts Scale, GPTS), cognitive insight (the Beck Cognitive Insight Scale, BCIS), subjective experiences of cognitive biases (the Davos Assessment of Cognitive Biases Scale, DACOBS) and metacognitive beliefs (the 30-item Metacognitions Questionnaire, MCQ-30). Economic analysis focused on the balance between societal costs and health outcomes (quality-adjusted life years, QALYs).

Both conditions showed a decrease of delusions. MCT was not more efficacious in terms of reducing delusions, nor did it change subjective paranoid thinking and ideas of social reference, cognitive insight or subjective experience of cognitive biases and metacognitive beliefs. The results of the economic analysis were not in favour of MCT + TAU.

In the present study, MCT did not affect delusion scores and self-reported cognitive insight, or subjective experience of cognitive biases and metacognitive beliefs. MCT was not cost-effective.

De novo interictal psychosis, albeit uncommon, can develop in patients following temporal lobe surgery for epilepsy. Pathological alterations of the dentate gyrus, including cytoarchitectural changes, immaturity and axonal reorganization that occur in epilepsy, may also underpin co-morbid psychiatric disorders. Our aim was to study candidate pathways that may be associated with the development of interictal psychosis post-operatively in patients with hippocampal sclerosis (HS).

A total of 11 patients with HS who developed interictal psychosis (HS-P) post-operatively were compared with a matched surgical HS group without psychosis (HS-NP). Resected tissues were investigated for the extent of granule cell dispersion, mossy fibre sprouting and calbindin expression in the granule cells. We quantified doublecortin, mini-chromosome maintenance protein 2 (MCM2) and reelin-expressing neuronal populations in the dentate gyrus as well as the distribution of cannabinoid type 1 receptor (CBR1).

The patterns of neuronal loss and gliosis were similar in both groups. HS-P patients demonstrated less mossy fibre sprouting and granule cell dispersion (p < 0.01) and more frequent reduction in calbindin expression in granule cells. There were no group differences in the densities of immature MCM2, doublecortin and reelin-positive cells. CBR1 labelling was significantly lower in Cornu ammonis area CA4 relative to other subfields (p < 0.01); although reduced staining in all hippocampal regions was noted in HS-P compared with HS-NP patients, the differences were not statistically significant.

The alterations in dentate gyrus pathology found in HS-P patients could indicate underlying differences in the cellular response to seizures. These mechanisms may predispose to the development of psychosis in epilepsy and warrant further investigation.

Previous studies have found that patients with schizophrenia are more likely to be violent than the general population. The aim of this study was to investigate the association between schizophrenia and violent crime in the Israeli population.

Using the Israeli Psychiatric Hospitalization Case Registry we identified 3187 patients with a discharge diagnosis of schizophrenia. For each proband we identified parents and siblings, and gender- and age-matched controls for patients, parents and siblings. Information on violent crimes was obtained from police records.

Patients with schizophrenia were at increased risk for violent crimes compared with controls [odds ratio (OR) 4.3, 95% confidence interval (CI) 3.8–4.9], especially women (OR 9.9, 95% CI 6.2–15.7). Risk for violent crimes was higher among patients with co-morbid substance misuse than in patients without such co-morbidity (OR 5.1, 95% CI 4.2–6.3).

The results of this study suggest that increased risk of violence is part of the clinical picture of schizophrenia and needs to be recognized as a legitimate, essential, aspect of clinical management.

The mechanisms by which childhood abuse and family history of suicidal behavior (FHS) lead to an increased risk of suicidal behavior are still unknown. Impulsive aggression may play an intermediate role. We investigated whether greater scores for aggression and impulsivity might be associated with the effects of FHS and/or childhood abuse on the severity of suicidal behavior.

We examined the scores of three scales measuring impulsive aggression in a sample of 696 suicide attempters. We compared the highest and lowest scores with regard to reports of childhood abuse and FHS using adjusted multinomial regression models. Genetic polymorphisms of the serotonergic system known to be associated with impulsive aggression were also analyzed.

Patients with high impulsive aggressive scores showed significant differences in sociodemographic, clinical and suicidal features compared with patients with low impulsive aggressive scores. Adjusted results showed that combinations of some types of childhood abuse and FHS, particularly emotional abuse and emotional neglect, are associated with high impulsivity and hostility scores. The SS genotype of the serotonin transporter gene (5-HTTLPR) was associated with high levels of impulsivity when the subjects reported emotional abuse [odds ratio (OR) 5.55, 95% confidence interval (CI) 1.75–17.5] or physical abuse (OR 5.03, 95% CI 1.50–16.9) in their childhood.

Our results support the role of impulsive aggression as one of the links that may connect childhood abuse and FHS with severity of suicidal behavior.

Bipolar disorder (BD) is associated with adverse childhood experiences (ACE), which worsen the lifetime course of illness, and with signs of widespread disruption of white matter (WM) integrity in adult life. ACE are associated with changes in WM microstructure in healthy humans.

We tested the effects of ACE on diffusion-tensor imaging (DTI) measures of WM integrity in 80 in-patients affected by a major depressive episode in the course of BD. We used whole-brain tract-based spatial statistics in the WM skeleton with threshold-free cluster enhancement of DTI measures of WM microstructure: axial, radial and mean diffusivity, and fractional anisotropy.

ACE hastened the onset of illness. We observed an inverse correlation between the severity of ACE and DTI measures of axial diffusivity in several WM fibre tracts contributing to the functional integrity of the brain and including the corona radiata, thalamic radiations, corpus callosum, cingulum bundle, superior longitudinal fasciculus, inferior fronto-occipital fasciculus and uncinate fasciculus.

Axial diffusivity reflects the integrity of axons and myelin sheaths, and correlates with functional connectivity and with higher-order abilities such as reasoning and experience of emotions. In patients with BD axial diffusivity is increased by lithium treatment. ACE might contribute to BD pathophysiology by hampering structural connectivity in critical cortico-limbic networks.

Recent data suggest trait-like neurocognitive impairments in bipolar disorder (BPD), with deficits about 1 s.d. below average, less severe than deficits noted in schizophrenia. The frequency of significant impairment in BPD is approximately 60%, with 40% of patients characterized as cognitively spared. This contrasts with a more homogeneous presentation in schizophrenia. It is not understood why some BPD patients develop deficits while others do not.

A total of 136 patients with BPD completed the MATRICS Consensus Cognitive Battery and data were entered into hierarchical cluster analyses to: (1) determine the optimal number of clusters (subgroups) that fit the sample; and (2) assign subjects to a specific cluster based on individual profiles. We then compared subgroups on several clinical factors and real-world community functioning.

Three distinct neurocognitive subgroups were found: (1) an intact group with performance comparable with healthy controls on all domains but with superior social cognition; (2) a selective impairment group with moderate deficits on processing speed, attention, verbal learning and social cognition and normal functioning in other domains; and (3) a global impairment group with severe deficits across all cognitive domains comparable with deficits in schizophrenia.

These results suggest the presence of multiple cognitive subgroups in BPD with unique profiles and begin to address the relationships between these subgroups, several clinical factors and functional outcome. Next steps will include using these data to help guide future efforts to target these disabling symptoms with treatment.

Persons with severe mental illness (SMI) have excess mortality, which may partly be explained by their high prevalence of diabetes.

We compared the overall and cause-specific mortality in persons with SMI and diabetes with that of the general Danish population between 1997 and 2009 by linking data from Danish national registries.

The cohort counted 4 734 703 persons, and during follow-up 651 080 persons died of whom 1083 persons had SMI and diabetes. Compared with the background population, the overall mortality rate ratios (MRRs) for persons with SMI and diabetes were 4.14 [95% confidence interval (CI) 3.81–4.51] for men and 3.13 (95% CI 2.88–3.40) for women. The cause-specific MRRs for persons with SMI and diabetes were lowest for malignant neoplasms (women: MRR = 1.98, 95% CI 1.64–2.39; men: MRR = 2.08, 95% CI 1.69–2.56) and highest for unnatural causes of death (women: MRR = 12.31, 95% CI 6.80–22.28; men: MRR = 7.89, 95% CI 5.51–11.29). The cumulative risks of death within 7 years of diabetes diagnosis for persons with SMI and diabetes were 15.0% (95% CI 12.4–17.6%) for those younger than 50 years, 30.7% (95% CI 27.8–33.4%) for those aged 50–69 years, and 63.8% (95% CI 58.9–68.2%) for those aged 70 years or older. Among persons suffering from both diseases, 33.4% of natural deaths were attributed to diabetes and 14% of natural deaths were attributed to the interaction between diabetes and SMI.

Long-term mortality is high for persons with SMI and diabetes. This calls for effective intervention from a coordinated and collaborating healthcare system.

Individuals with generalized social anxiety disorder (gSAD) exhibit attentional bias to salient stimuli, which is reduced in patients whose symptoms improve after treatment, indicating that mechanisms of bias mediate treatment success. Therefore, pre-treatment activity in regions implicated in attentional control over socio-emotional signals (e.g. anterior cingulate cortex, dorsolateral prefrontal cortex) may predict response to cognitive behavioral therapy (CBT), evidence-based psychotherapy for gSAD.

During functional magnetic resonance imaging, 21 participants with gSAD viewed images comprising a trio of geometric shapes (circles, rectangles or triangles) alongside a trio of faces (angry, fearful or happy) within the same field of view. Attentional control was evaluated with the instruction to ‘match shapes’, directing attention away from faces, which was contrasted with ‘match faces’, whereby attention was directed to emotional faces.

Whole-brain voxel-wise analyses showed that symptom improvement was predicted by enhanced pre-treatment activity in the presence of emotional face distractors in the dorsal anterior cingulate cortex and dorsal medial prefrontal cortex. Additionally, CBT success was foretold by less activity in the amygdala and/or increased activity in the medial orbitofrontal gyrus during emotion processing.

CBT response was predicted by pre-treatment activity in prefrontal regions and the amygdala. The direction of activity suggests that individuals with intact attentional control in the presence of emotional distractors, regulatory capacity over emotional faces and/or less reactivity to such faces are more likely to benefit from CBT. Findings indicate that baseline neural activity in the context of attentional control and emotion processing may serve as a step towards delineating mechanisms by which CBT exerts its effects.

Despite stress being considered a key factor in the pathophysiology of the functional gastrointestinal (GI) disorder irritable bowel syndrome (IBS), there is a paucity of information regarding the ability of IBS patients to respond to acute experimental stress. Insights into the stress response in IBS could open the way to novel therapeutic interventions. To this end, we assessed the response of a range of physiological and psychological parameters to the Trier Social Stress Test (TSST) in IBS.

Thirteen female patients with IBS and 15 healthy female age-matched control participants underwent a single exposure to the TSST. Salivary cortisol, salivary C-reactive protein (CRP), skin conductance level (SCL), GI symptoms, mood and self-reported stress were measured pre- and post-exposure to the TSST.

The hypothalamic–pituitary–adrenal (HPA) axis response to the TSST was sustained in IBS, as shown by a greater total cortisol output throughout (p = 0.035) and higher cortisol levels measured by an area under the curve with respect to ground (AUCG) analysis (p = 0.044). In IBS patients, GI symptoms increased significantly during the recovery period following exposure to the TSST (p = 0.045). Salivary CRP and SCL activity showed significant changes in relation to stress but with no differential effect between experimental groups.

Patients with IBS exhibit sustained HPA axis activity, and an increase in problematic GI symptoms in response to acute experimental psychosocial stress. These data pave the way for future interventional studies aimed at identifying novel therapeutic approaches to modulate the HPA axis and GI symptom response to acute psychosocial stress in IBS.