Abnormalities in cortical thickness and subcortical structures have been studied in schizophrenia but little is known about corresponding changes in mania and brain structural differences between these two psychiatric conditions, especially early in the stage of the illness. In this study we aimed to compare cortical thickness and shape of the amygdala–hippocampal complex in first-episode schizophrenia (FES) and mania (FEM).

Structural magnetic resonance imaging (MRI) was performed on 28 FES patients, 28 FEM patients and 28 healthy control subjects who were matched for age, gender and handedness.

Overall, the shape of the amygdala was deformed in both patient groups, relative to controls. Compared to FEM patients, FES patients had significant inward shape deformation in the left hippocampal tail, right hippocampal body and a small region in the right amygdala. Cortical thinning was more widespread in FES patients, with significant differences found in the temporal brain regions when compared with FEM and controls.

Significant differences were observed between the two groups of patients with FES and FEM in terms of the hippocampal shape and cortical thickness in the temporal region, highlighting that distinguishable brain structural changes are present early in the course of schizophrenia and mania.

The goal of this study was to explore the notion that anomalies of self-experience (ASE) are a core, ‘not-yet-psychotic’ clinical phenotype of emerging schizophrenia and its spectrum.

To accomplish this goal, we examined the relationship between ASE and commonly accepted risk markers in a sample of 87 help-seeking, non-psychotic adolescents (aged 14–18 years). ASE were assessed with the Examination of Anomalous Self-Experience (EASE), subclinical psychotic symptoms were assessed with the Prodromal Questionnaire and the Structured Interview for Prodromal Syndromes, deterioration in psychosocial functioning was assessed with the Social and Role Functioning Scales, and level of distress with the Mood and Anxiety Symptoms Questionnaire.

About 82 participants completed the entire EASE interview. The number of participants who reported ASE at a clinically meaningful level (n = 18, 22%) was smaller than that who met diagnostic criteria for a prodromal syndrome (n = 28, 34%). The degree of overlap between the two conditions was moderate but statistically significant (χ2(1) = 7.01, p = 0.008). An exploratory factor analysis revealed that ASE load on a different factor than prodromal symptoms and deterioration in functioning, but that there is a moderate correlation between the three factors.

These results suggest that ASE are prevalent among non-psychotic help-seeking adolescents, yet at a considerably lower rate than prodromal symptoms. In addition, they suggest that ASE and prodromal symptoms constitute distinct but moderately related dimensions of potential risk. Taken together, they provide preliminary support for the clinical usefulness of supplementing and refining the methods of early detection of risk with assessment of ASE.

Reduced hippocampal size and increased stress sensitivity are associated with psychotic disorder and familial risk for psychosis. However, to what degree the hippocampus is implicated in daily life stress reactivity has not yet been examined. The current study investigated (i) whether familial risk (the contrast between controls, patients and siblings of patients) moderated the relationship between hippocampal volume (HV) and emotional daily stress reactivity and (ii) whether familial risk (the contrast between controls and siblings of patients) moderated the relationship between HV and cortisol daily stress reactivity.

T1-weighted magnetic resonance imaging (MRI) scans were acquired from 20 patients with schizophrenia, 37 healthy siblings with familial risk for schizophrenia and 32 controls. Freesurfer 5.0.0 was used to measure HV. The experience sampling method (ESM), a structured momentary assessment technique, was used to assess emotional stress reactivity, that is the effect of momentary stress on momentary negative affect (NA). In addition, in the control and sibling groups, cortisol stress reactivity was assessed using momentary cortisol levels extracted from saliva.

Multilevel linear regression analyses revealed a significant three-way interaction between group, HV and momentary stress in both the model of NA and the model of cortisol. Increased emotional stress reactivity was associated with smaller left HV in patients and larger total HV in controls. In line with the results in patients, siblings with small HV demonstrated increased emotional and cortisol stress reactivity compared to those with large HV.

HV may index risk and possibly disease-related mechanisms underlying daily life stress reactivity in psychotic disorder.

An increased reactivity to stress in the context of daily life is suggested to be an independent risk factor underlying the positive symptoms of psychotic disorder. The aim of this study was to investigate whether positive symptoms moderate the association between everyday stressful events and negative affect (NA), known as stress reactivity. This hypothesis was put to the test in patients with a diagnosis of psychotic disorder.

The Comprehensive Assessment of Symptoms and History (CASH) and the Positive and Negative Syndrome Scale (PANSS) were used to assess positive and negative symptoms. The experience sampling method (ESM), a structured diary technique, was used to measure stress reactivity and psychotic symptoms in daily life.

Higher levels of positive symptoms (CASH: B = 0.14, p = 0.005; PANSS: B = 0.05, p = 0.000; ESM: B = 0.03, p = 0.000) and lower levels of negative symptoms (PANSS: B = − 0.05, p = 0.001) significantly moderate the association between unpleasant events and NA. No significant moderating effect was found for CASH negative symptoms. Moreover, the moderating effect of lifetime and current symptoms on the stress–NA association was significantly larger for those patients with predominantly positive symptoms (CASH: B = 0.09, p = 0.000; PANSS: B = 0.08, p = 0.000; ESM: B = 0.13, p = 0.000).

Patients with a ‘psychotic syndrome’ with high levels of positive symptoms and low levels of negative symptoms show increased reactivity to stress in daily life, indicating that stress reactivity is a possible risk factor underlying this syndrome.

Subsyndromal depression (SD) may increase risk for incident major depressive and other disorders, as well as suicidality. However, little is known about the prevalence, course, and correlates of SD in the US general adult population.

Structured diagnostic interviews were conducted to assess DSM-IV Axis I and II disorders in a nationally representative sample of 34 653 US adults who were interviewed at two time-points 3 years apart.

A total of 11.6% of US adults met study criteria for lifetime SD at Wave 1. The majority (9.3%) had <5 total symptoms required for a diagnosis of major depression; the remainder (2.3%) reported ⩾5 symptoms required for a diagnosis of major depression, but denied clinically significant distress or functional impairment. SD at Wave 1 was associated with increased likelihood of developing incident major depression [odds ratios (ORs) 1.72–2.05], as well as dysthymia, social phobia, and generalized anxiety disorder (GAD) at Wave 2 (ORs 1.41–2.92). Among respondents with SD at Wave 1, Cluster A and B personality disorders, and worse mental health status were associated with increased likelihood of developing incident major depression at Wave 2.

SD is prevalent in the US population, and associated with elevated rates of Axis I and II psychopathology, increased psychosocial disability, and risk for incident major depression, dysthymia, social phobia, and GAD. These results underscore the importance of a dimensional conceptualization of depressive symptoms, as SD may serve as an early prognostic indicator of incident major depression and related disorders, and could help identify individuals who may benefit from preventive interventions.

Official suicide statistics for England are based on deaths given suicide verdicts and most cases given an open verdict following a coroner's inquest. Previous research indicates that some deaths given accidental verdicts are considered to be suicides by clinicians. Changes in coroners' use of different verdicts may bias suicide trend estimates. We investigated whether suicide trends may be over- or underestimated when they are based on deaths given suicide and open verdicts.

Possible suicides assessed by 12 English coroners in 1990/91, 1998 and 2005 and assigned open, accident/misadventure or narrative verdicts were rated by three experienced suicide researchers according to the likelihood that they were suicides. Details of all suicide verdicts given by these coroners were also recorded.

In 1990/91, 72.0% of researcher-defined suicides received a suicide verdict from the coroner, this decreased to 65.4% in 2005 (ptrend < 0.01); equivalent figures for combined suicide and open verdicts were 95.4% (1990/91) and 86.7% (2005). Researcher-defined suicides with a verdict of accident/misadventure doubled over that period, from 4.6% to 9.1% (p < 0.01). Narrative verdict cases rose from zero in 1990/91 to 25 in 2005 (4.2% of researcher-defined suicides that year). In 1998 and 2005, 50.0% of the medicine poisoning deaths given accidental/misadventure verdicts were rated as suicide by the researchers.

Between 1990/91 and 2005, the proportion of researcher-defined suicides given a suicide verdict by coroners decreased, largely due to an increased use of accident/misadventure verdicts, particularly for deaths involving poisoning. Consideration should be given to the inclusion of ‘accidental’ deaths by poisoning with medicines in the statistics available for monitoring suicides rates.

This study aimed to determine whether depression in patients with long-term conditions is associated with the number of morbidities or the type of co-morbidity.

A cohort study of 299 912 participants aged 30–100 years. The prevalence of depression, rates of health-care utilization and costs were evaluated in relation to diagnoses of diabetes mellitus (DM), coronary heart disease (CHD), stroke and colorectal cancer.

The age-standardized prevalence of depression was 7% in men and 14% in women with no morbidity. The frequency of depression increased in single morbidities including DM (men 13%, women 22%), CHD (men 15%, women 24%), stroke (men 14%, women 26%) or colorectal cancer (men 10%, women 21%). Participants with concurrent diabetes, CHD and stroke had a very high prevalence of depression (men 23%, women 49%). The relative rate of depression for one morbidity was 1.63 [95% confidence interval (CI) 1.59–1.66], two morbidities 1.96 (95% CI 1.89–2.03) and three morbidities 2.35 (95% CI 2.03–2.59). Compared to those with no morbidity, depression was associated with higher rates of health-care utilization and increased costs at any level of morbidity. In women aged 55 to 64 years without morbidity, the mean annual health-care cost was £513 without depression and £1074 with depression; when three morbidities were present, the cost was £1495 without depression and £2878 with depression.

Depression prevalence and health-care costs are more strongly associated with the number of morbidities than the nature of the co-morbid diagnosis.

Facial emotion perception (FEP) is a critical human skill for successful social interaction, and a substantial body of literature suggests that explicit FEP is disrupted in major depressive disorder (MDD). Prior research suggests that weakness in FEP may be an important phenomenon underlying patterns of emotion-processing challenges in MDD and the disproportionate frequency of MDD in women.

Women with (n = 24) and without (n = 22) MDD, equivalent in age and education, completed a FEP task during functional magnetic resonance imaging.

The MDD group exhibited greater extents of frontal, parietal and subcortical activation compared with the control group during FEP. Activation in the inferior frontal gyrus (IFG) appeared shifted from a left >right pattern observed in healthy women to a bilateral pattern in MDD women. The ratio of left to right suprathreshold IFG voxels in healthy controls was nearly 3:1, whereas in the MDD group, there was a greater percentage of suprathreshold IFG voxels bilaterally, with no leftward bias. In MDD, relatively greater activation in right IFG compared with left IFG (ratio score) was present and predicted FEP accuracy (r = 0.56, p < 0.004), with an inverse relationship observed between FEP and subgenual cingulate activation (r = − 0.46, p = 0.02).

This study links, for the first time, disrupted IFG activation laterality and increased subgenual cingulate activation with deficient FEP in women with MDD, providing an avenue for imaging-to-assessment translational applications in MDD.

The effectiveness of large-scale interventions to prevent suicide among persons who previously attempted suicide remains to be determined. The National Suicide Surveillance System (NSSS), launched in Taiwan in 2006, is a structured nationwide intervention program for people who survived their suicide attempts. This naturalistic study examined its effectiveness using data from the first 3 years of its operation.

Effectiveness of the NSSS aftercare services was examined using a logistic/proportional odds mixture model, with eventual suicide as the outcome of interest. As well, we examined time until death for those who died and factors associated with eventual suicide.

Receipt of aftercare services was associated with reduced risk for subsequent suicide; for service recipients who eventually killed themselves, there was a prolonged duration between the index and fatal attempts. Elderly attempters were particularly prone to a shorter duration between the index and fatal attempts. Male gender, the lethality potential of the index attempt, and a history of having had a mental disorder also were associated with higher risk.

The structured aftercare program of the NSSS appears to decrease suicides and to delay time to death for those who remained susceptible to suicide.

Moodscope is an entirely service-user-developed online mood-tracking and feedback tool with built-in social support, designed to stabilize and improve mood. Many free internet tools are available with no assessment of acceptability, validity or usefulness. This study provides an exemplar for future assessments.

A mixed-methods approach was used. Participants with mild to moderate low mood used the tool for 3 months. Correlations between weekly assessments using the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder Assessment (GAD-7) with daily Moodscope scores were examined to provide validity data. After 3 months, focus groups and questionnaires assessed use and usability of the tool.

Moodscope scores were correlated significantly with scores on the PHQ-9 and the GAD-7 for all weeks, suggesting a valid measure of mood. Low rates of use, particularly toward the end of the trial, demonstrate potential problems relating to ongoing motivation. Questionnaire data indicated that the tool was easy to learn and use, but there were concerns about the mood adjectives, site layout and the buddy system. Participants in the focus groups found the tool acceptable overall, but felt clarification of the role and target group was required.

With appropriate adjustments, Moodscope could be a useful tool for clinicians as a way of initially identifying patterns and influences on mood in individuals experiencing low mood. For those who benefit from ongoing mood tracking and the social support provided by the buddy system, Moodscope could be an ongoing adjunct to therapy.

Anxiety disorders are very common and increase risk for suicide attempts. Little is known about predictors of increased risk specifically among individuals with anxiety disorders. The purpose of this study was to investigate whether specific anxiety disorders and other co-morbid psychiatric disorders, physical health, or work or social functioning increased the future likelihood of a suicide attempts among individuals with anxiety disorders.

In this prospective study, 676 individuals with an anxiety disorder were followed for an average of 12 years.

As hypothesized, we found that post-traumatic stress disorder, major depressive disorder (MDD), intermittent depressive disorder (IDD), epilepsy, pain, and poor work and social functioning all predicted a shorter time to a suicide attempt in univariate analyses. In multivariate analyses, baseline MDD and IDD were independent predictors of time to suicide attempt, even when controlling for a past history of suicide attempt. No specific anxiety disorder was an independent predictor of time to attempt in this anxiety-disordered sample. Adding baseline physical health variables and social functioning did not improve the ability of the model to predict time to suicide attempt.

Mood disorders and past history of suicide attempts are the most powerful predictors of a future suicide attempt in this sample of individuals, all of whom have an anxiety disorder.

The mechanisms that contribute to emotion dysregulation in anxiety disorders are not well understood. Two common disorders, generalized anxiety disorder (GAD) and panic disorder (PD), were examined to test the hypothesis that both disorders are characterized by hypo-activation in prefrontal cortex (PFC) during emotion regulation. A competing hypothesis that GAD in particular is characterized by PFC hyper-activation during emotion regulation (reflecting overactive top-down control) was also evaluated.

Twenty-two medication-free healthy control (HC), 23 GAD, and 18 PD participants underwent functional magnetic resonance imaging (fMRI) during a task that required them to reappraise (i.e. reduce) or maintain emotional responses to negative images.

GAD participants reported the least reappraisal use in daily life, and reappraisal use was inversely associated with anxiety severity and functional impairment in these participants. During fMRI, HCs demonstrated greater activation during both reappraisal and maintenance than either GAD or PD participants (who did not differ) in brain areas important for emotion regulation (e.g. dorsolateral and dorsomedial PFC). Furthermore, across all anxious participants, activation during reappraisal in dorsolateral and dorsomedial PFC was inversely associated with anxiety severity and functional impairment.

Emotion dysregulation in GAD and PD may be the consequence of PFC hypo-activation during emotion regulation, consistent with insufficient top-down control. The relationship between PFC hypo-activation and functional impairment suggests that the failure to engage PFC during emotion regulation may be part of the critical transition from dispositionally high anxiety to an anxiety disorder.

A family history (FH) of alcohol dependence (AD) not only increases the risk for AD, but is also associated with an increased risk for mood and anxiety disorders. However, it is unknown how a FH of AD affects neural substrates in patients with mood and anxiety disorders. In this study we examined the effects of an alcoholic FH on cognitive and emotional functions in these patients using functional magnetic resonance imaging (fMRI).

In a sample of non-alcoholic patients with depressive and/or anxiety disorders from the Netherlands Study of Depression and Anxiety (NESDA) neuroimaging study, patients with a first-degree FH of AD (FH + ; n = 31) were compared with patients without a FH (FH–; n = 77) on performance and brain activation during visuospatial planning and emotional word encoding. Results were compared with those of healthy controls (HCs) without a FH of AD (n = 31).

FH+ patients performed slower during planning with increasing task load, coupled with stronger blood oxygen level-dependent responses in dorsal prefrontal areas compared with FH− patients and HCs. FH was not associated with performance differences during word encoding, but right insula activation during positive word encoding was present in FH+ patients, comparable with HCs, but absent in FH− patients.

This study demonstrates subtle impairments during planning in FH+ compared with FH− patients and HCs, whereas activation during mood-incongruent stimuli in FH+ patients was similar to HCs but not FH− patients, suggesting that the presence of a FH of AD is a useful marker for the neurophysiological profile in mood/anxiety disorders and possible predictor for treatment success.

Cannabis abuse in psychotic patients is associated with rehospitalizations, reduced adherence and increased symptom severity. Previous psychosocial interventions have been ineffective in cannabis use, possibly because of low sample sizes and short interventions. We investigated whether adding CapOpus to treatment as usual (TAU) reduces cannabis use in patients with cannabis use disorder and psychosis.

A total of 103 patients with psychosis and cannabis use disorder were centrally randomized to 6 months of CapOpus plus TAU (n = 52) or TAU (n = 51). CapOpus consisted mainly of motivational interviewing and cognitive behaviour therapy (CBT). TAU was targeted primarily at the psychotic disorder. The primary outcome was self-reported days with cannabis use in the preceding month.

Pre-randomization cannabis use frequency was 14.9 [95% confidence interval (CI) 12.7–17.1] days/month. Post-treatment, the ratio of days/month with cannabis use in CapOpus versus TAU was 0.76 (95% CI 0.38–1.50) (p = 0.42), and 0.80 (95% CI 0.21–3.10) (p = 0.75) at the 4-month follow-up. From 46.4 (95% CI 36.4–56.3) monthly joints pre-randomization, consumption fell to 27.3 (95% CI 12.6–41.9) joints in CapOpus and 48.2 (95% CI 31.8–64.6) in TAU (p = 0.06). Follow-up amounts were 28.4 (95% CI 13.5–43.2) and 41.6 (95% CI 25.2–58.0) joints (p = 0.23). Several subgroup analyses suggested benefits of CapOpus.

CapOpus did not reduce the frequency, but possibly the amount, of cannabis use. This is similar to the findings of previous trials in this population. Implementation of CapOpus-type interventions is thus not warranted at present but subgroup analyses call for further trials.

The prevalence of mental disorders among prisoners is considerably higher than in the general population. This is an important public health issue as the vast majority of prisoners stay in custody for less than 9 months and, when not in prison, offenders' lifestyles are frequently chaotic, characterized by social exclusion, instability and unemployment. Multi-disciplinary mental health inreach services were introduced to target care towards prisoners with severe mental illness (SMI) in a similar way to that provided by Community Mental Health Teams outside prison. The aim was to establish the proportion of prisoners with SMI who were assessed and managed by prison mental health inreach services.

A two-phase prevalence survey in six prisons in England measured SMI upon reception into custody. Case-note review established the proportion of those with SMI subsequently assessed and treated by inreach services.

Of 3492 prisoners screened, 23% had SMI. Inreach teams assessed only 25% of these unwell prisoners, and accepted just 13% onto their caseloads.

Inreach teams identified and managed only a small proportion of prisoners with SMI. Prison-based services need to improve screening procedures and develop effective care pathways to ensure access to appropriate services. Improved identification of mental illness is needed in both the community and the Criminal Justice System to better engage with socially transient individuals who have chaotic lifestyles and complex needs.

Psychological traumatic events, such as war or road traffic accidents, are widespread. A small but significant proportion of survivors develop post-traumatic stress disorder (PTSD). Distressing, sensory-based involuntary memories of trauma (henceforth ‘flashbacks’) are the hallmark symptom of PTSD. Understanding the development of flashbacks may aid their prevention. This work is the first to combine the trauma film paradigm (as an experimental analogue for flashback development) with neuroimaging to investigate the neural basis of flashback aetiology. We investigated the hypothesis that involuntary recall of trauma (flashback) is determined during the original event encoding.

A total of 22 healthy volunteers viewed a traumatic film whilst undergoing functional magnetic resonance imaging (fMRI). They kept a 1-week diary to record flashbacks to specific film scenes. Using a novel prospective fMRI design, we compared brain activation for those film scenes that subsequently induced flashbacks with both non-traumatic control scenes and scenes with traumatic content that did not elicit flashbacks (‘potentials’).

Encoding of scenes that later caused flashbacks was associated with widespread increases in activation, including in the amygdala, striatum, rostral anterior cingulate cortex, thalamus and ventral occipital cortex. The left inferior frontal gyrus and bilateral middle temporal gyrus also exhibited increased activation but only relative to ‘potentials’. Thus, these latter regions appeared to distinguish between traumatic content that subsequently flashed back and comparable content that did not.

Results provide the first prospective evidence that the brain behaves differently whilst experiencing emotional events that will subsequently become involuntary memories – flashbacks. Understanding the neural basis of analogue flashback memory formation may aid the development of treatment interventions for this PTSD feature.

Prior studies of adult post-traumatic stress disorder (PTSD) suggest abnormal functioning of prefrontal and limbic regions. Cumulative childhood and adult trauma exposures are major risk factors for developing adult PTSD, yet their contribution to neural dysfunction in PTSD remains poorly understood. This study aimed to examine the neural correlates of childhood and adult trauma exposure and post-traumatic stress symptoms (PTSS) within a single model.

Medication-free male combat veterans (n = 28, average age 26.6 years) with a wide range of PTSS were recruited from the community between 2010 and 2011. Subjects completed an emotional face-morphing task while undergoing functional magnetic resonance imaging (fMRI). Clinical ratings included the Clinician-Administered PTSD Scale (CAPS), Childhood Trauma Questionnaire (CTQ) and Combat Exposure Scale (CES). A priori regions were examined through multivariate voxelwise regression in SPM8, using depressive symptoms and IQ as covariates.

In the angry condition, CAPS scores correlated positively with activation in the medial prefrontal cortex [mPFC; Brodmann area (BA) 10, z = 3.51], hippocampus (z = 3.47), insula (z = 3.62) and, in earlier blocks, the amygdala. CES and CTQ correlated positively with activation in adjacent areas of the dorsal anterior cingulate cortex (dACC; BA 32, z = 3.70 and BA 24, z = 3.88 respectively). In the happy condition, CAPS, CTQ and CES were not correlated significantly with activation patterns.

dACC activation observed in prior studies of PTSD may be attributable to the cumulative effects of childhood and adult trauma exposure. By contrast, insula, hippocampus and amygdala activation may be specific to PTSS. The specificity of these results to threat stimuli, but not to positive stimuli, is consistent with abnormalities in threat processing associated with PTSS.

There is a large body of evidence indicating that eating disorders (EDs) are characterized by particular neuropsychological profiles. We aimed to further explore whether impairments in neuropsychological functioning previously found in ED groups are present prior to onset, or are secondary to the disorder.

This is the first study to explore neuropsychological functioning in children born to a mother with a lifetime ED, who are therefore at high risk of developing an ED, in a large cohort sample. We investigated intelligence and attention at age 8 years (n = 6201) and working memory (WM) and inhibition at age 10 years (6192) in children who are at high risk of developing an ED, compared to children who are not.

The children of women with lifetime anorexia nervosa (AN) showed high full-scale and performance IQ, increased WM capacity, better visuo-spatial functioning, and decreased attentional control. The children of women with lifetime bulimia nervosa (BN) showed comparatively poor visuo-spatial functioning.

Our findings suggest that high intelligence, increased WM capacity and impaired attentional control might be intermediate phenotypes on the pathway between genetic vulnerability and the development of an ED.