Previous studies have reported prefrontal cortex (PFC) pathophysiology in bipolar disorder.

We examined the hemodynamics of the PFC during resting and cognitive tasks in 29 patients with bipolar disorder and 27 healthy controls, matched for age, verbal abilities and education. The cognitive test battery consisted of letter and category fluency (LF and CF), Sets A and B of the Raven's Colored Progressive Matrices (RCPM-A and RCPM-B) and the letter cancellation test (LCT). The tissue oxygenation index (TOI), the ratio of oxygenated hemoglobin (HbO2) concentration to total hemoglobin concentration, was measured in the bilateral PFC by spatially resolved near-infrared spectroscopy. Changes in HbO2 concentration were also measured.

The bipolar group showed slight but significant impairment in performance for the non-verbal tasks (RCPM-A, RCPM-B and LCT), with no significant between-group differences for the two verbal tasks (LF and CF). A group×task×hemisphere analysis of variance (ANOVA) on the TOI revealed an abnormal pattern of prefrontal oxygenation across different types of cognitive processing in the bipolar group. Post hoc analyses following a group×task×hemisphere ANOVA on HbO2 concentration revealed that the bipolar group showed a greater increase in HbO2 concentration in the LCT and in RCPM-B, relative to controls.

Both indices of cortical activation (TOI and HbO2 concentration) indicated a discrepancy in the PFC function between verbal versus non-verbal processing, indicating task-specific abnormalities in the hemodynamic control of the PFC in bipolar disorder.

We investigated whether depressive disorder and Type D personality refer to different forms of distress in the Myocardial INfarction and Depression – Intervention Trial (MIND-IT).

A total of 1205 myocardial infarction (MI) patients were screened at 3, 6, 9 and 12 months post-MI; those with a Beck Depression Inventory (BDI) score ⩾10 underwent the World Health Organization (WHO) Composite International Diagnostic Interview (CIDI). Patients completed the DS14 measure of Type D personality at 12 months and were stratified to one of four subgroups: depressed/Type D, depressed/non-Type D, non-depressed/Type D, or non-distressed.

Two hundred and six (17%) patients were diagnosed with depression and 224 (19%) with Type D. Only 7% (n=90) had both forms of distress, and 60% of Type D patients were free of depression in the first year post-MI. Type D moderated the relationship between depressive and cardiac disorder. Depressed patients without Type D had the worst clinical status (left ventricular dysfunction, heart failure, Killip class ⩾2) as compared to other patients, whereas depressed patients with a Type D personality did not differ in clinical status from non-distressed patients. Contrasting ‘pure’ Type D and depression subgroups showed that Type D patients without depression were less likely to have left ventricular dysfunction [odds ratio (OR) 0.47, 95% confidence interval (CI) 0.35–0.65, p<0.0001] than depressed patients without Type D.

Depression and Type D refer to different forms of distress in post-MI patients; most Type D patients display non-psychiatric levels of distress and Type D moderates the relationship between depressive and cardiac disorder. Different depression/Type D subgroups may be involved in the prediction of cardiac prognosis.

Predictors of outcome for psychosis are poorly understood. Duration of untreated psychosis (DUP) appears to predict short-term outcome although its medium- to long-term role remains unclear. Neurodevelopmental indices such as pre-morbid function and/or neurological soft signs may predict longer-term outcome. We aimed to assess the impact of a range of clinical and demographic variables on long-term outcome of a geographically defined, epidemiological first-episode psychosis cohort.

A 10-year follow-up was undertaken of a consecutively presenting sample of 109 cases of first-episode psychosis aged 16–50 years. Baseline assessments included positive, negative and depression symptoms, DUP, neurological soft signs and pre-morbid functioning. Multi-dimensional outcomes were assessed blind to baseline data.

All participants were traced at a mean of 10.5 years post-index admission: 11 had died, 10 from non-natural causes. Of the surviving cases, 70% were comprehensively re-assessed by interview. Summary data on the remainder were collected from their family practitioner and chart review. Poor 10-year outcomes were predicted independently by poor pre-morbid functioning, baseline negative symptoms and longer DUP. The same measures, plus neurological soft signs, appeared to predict outcomes in a DSM-IV schizophrenia/schizo-affective subgroup.

Poor pre-morbid functioning, baseline symptoms, DUP and neurological soft signs at onset independently predict poor long-term outcome in first-episode psychosis.

Recent studies among males have reported a genotype–environment interaction (G×E) in which low-activity alleles at the monoamine oxidase A (MAOA) locus conferred greater sensitivity to the effects of childhood adversity on risk for conduct disorder (CD). So far, few studies of females have controlled for gene–environment correlation or used females heterozygous for this X-linked gene.

Logistic regression analysis of a sample of 721 females ages 8–17 years from the longitudinal Virginia Twin Study of Adolescent Behavioral Development (VTSABD) assessed the additive effects of MAOA genotypes on risk for CD, together with the main effect of childhood adversity and parental antisocial personality disorder (ASP), as well as the interaction of MAOA with childhood adversity on risk for CD.

A significant main effect of genotype on risk for CD was detected, where low-activity MAOA imparted the greatest risk to CD in girls while controlling for the significant effects of maternal ASP and childhood adversity. Significant G×E with weak effect was detected when environmental exposure was untransformed, indicating a higher sensitivity to childhood adversity in the presence of the high-activity MAOA allele. The interaction was no longer statistically significant after applying a ridit transformation to reflect the sample sizes exposed at each level of childhood adversity.

The main effect of MAOA on risk for CD in females, its absence in males and directional difference of interaction is suggestive of genotype–sex interaction. As the effect of G×E on risk for CD was weak, its inclusion is not justified.

Borderline personality disorder (BPD) is partly characterized by chronic instability in interpersonal relationships, which exacerbates other symptom dimensions of the disorder and can interfere with treatment engagement. Facial emotion recognition paradigms have been used to investigate the bases of interpersonal impairments in BPD, yielding mixed results. We sought to clarify and extend past findings by using the Reading the Mind in the Eyes Test (RMET), a measure of the capacity to discriminate the mental state of others from expressions in the eye region of the face.

Thirty individuals diagnosed with BPD were compared to 25 healthy controls (HCs) on RMET performance. Participants were also assessed for depression severity, emotional state at the time of assessment, history of childhood abuse, and other Axis I and personality disorders (PDs).

The BPD group performed significantly better than the HC group on the RMET, particularly for the Total Score and Neutral emotional valences. Effect sizes were in the large range for the Total Score and for Neutral RMET performance. The results could not be accounted for by demographics, co-occurring Axis I or II conditions, medication status, abuse history, or emotional state. However, depression severity partially mediated the relationship between RMET and BPD status.

Mental state discrimination based on the eye region of the face is enhanced in BPD. An enhanced sensitivity to the mental states of others may be a basis for the social impairments in BPD.

Prior research on the nature of the vulnerability of neuroticism to psychopathology suggests biases in information processing towards emotional rather than neutral information. It is unclear to what extent this relationship can be explained by genetic or environmental factors.

The genetic relationship between a neuroticism composite score and free recall of pleasant and unpleasant words and the reaction time on negative probes (dot-probe task) was investigated in 125 female twin pairs. Interaction effects were modelled to test whether the correlation between neuroticism and cognitive measures depended on the level of the neuroticism score.

The only significant correlation was between neuroticism and the proportion of recalled unpleasant words (heritability is 30%), and was only detectable at the higher end of the neuroticism distribution. This interaction effect seems to be due to environmental effects that make people in the same family more similar (e.g. parental discipline style), rather than genetic factors. An interesting sub-finding was that faster reaction times for left versus right visual field probes in the dot-probe task suggest that cognitive processing in the right hemisphere is more sensitive to subliminal (biologically relevant) cues and that this characteristic is under substantial genetic control (49%). Individual differences in reaction times on right visual field probes were due to environmental effects only.

There is no evidence that the predisposition of individuals to focus on negative (emotional) stimuli is a possible underlying genetic mechanism of neuroticism.

Recent work suggests that heavy use of cannabis is associated with an increased risk of schizophrenia-like psychosis. However, there is a dearth of experimental studies of the effects of the constituents of cannabis, such as Δ9-tetrahydrocannabinol (THC). In a study of intravenous (i.v.) synthetic THC in healthy humans, we aimed to study the relationship of the psychotic symptoms induced by THC to the consequent anxiety and neuropsychological impairment.

Twenty-two healthy adult males aged 28±6 years (mean±s.d.) participated in experimental sessions in which i.v. THC (2.5 mg) was administered under double-blind, placebo-controlled conditions. Self-rated and investigator-rated measurements of mood and psychosis [the University of Wales Institute of Science and Technology Mood Adjective Checklist (UMACL), the Positive and Negative Syndrome Scale (PANSS) and the Community Assessment of Psychic Experiences (CAPE)] were made at baseline and at 30, 80 and 120 min post-injection. Participants also completed a series of neuropsychological tests [the Rey Auditory Verbal Learning Task (RAVLT), Digit Span, Verbal Fluency and the Baddeley Reasoning Task] within 45 min of injection.

THC-induced positive psychotic symptoms, and participant- and investigator-rated measurements of these were highly correlated. Participants showed an increase in anxiety ratings but there was no relationship between either self- or investigator-rated positive psychotic symptoms and anxiety. THC also impaired neuropsychological performance but once again there was no relationship between THC-induced positive psychotic symptoms and deficits in working memory/executive function.

These findings confirm that THC can induce a transient, acute psychotic reaction in psychiatrically well individuals. The extent of the psychotic reaction was not related to the degree of anxiety or cognitive impairment.

Identification of emotional facial expression and emotional prosody (i.e. speech melody) is often impaired in schizophrenia. For facial emotion identification, a recent study suggested that the relative deficit in schizophrenia is enhanced when the presented emotion is easier to recognize. It is unclear whether this effect is specific to face processing or part of a more general emotion recognition deficit.

We used clarity-graded emotional prosodic stimuli without semantic content, and tested 25 in-patients with paranoid schizophrenia, 25 healthy control participants and 25 depressive in-patients on emotional prosody identification. Facial expression identification was used as a control task.

Patients with paranoid schizophrenia performed worse than both control groups in identifying emotional prosody, with no specific deficit in any individual emotion category. This deficit was present in high-clarity but not in low-clarity stimuli. Performance in facial control tasks was also impaired, with identification of emotional facial expression being a better predictor of emotional prosody identification than illness-related factors. Of those, negative symptoms emerged as the best predictor for emotional prosody identification.

This study suggests a general deficit in identifying high-clarity emotional cues. This finding is in line with the hypothesis that schizophrenia is characterized by high noise in internal representations and by increased fluctuations in cerebral networks.

Patients with major depressive disorder are found to show selective attention biases towards mood-congruent information. Although previous studies have identified various structural changes in the brains of these patients, it remains unclear whether the structural abnormalities are associated with these attention biases. In this study, we used voxel-based morphometry (VBM) to explore the structural correlates of attention biases towards depression-related stimuli.

Seventeen female patients with major depressive disorder and 17 female healthy controls, matched on age and intelligence, underwent magnetic resonance imaging (MRI). They also performed positive-priming (PP) and negative-priming (NP) tasks involving neutral and negative words that assessed selective attention biases. The reaction time (RT) to a target word that had been attended to or ignored in a preceding trial was measured on the PP and NP tasks respectively. The structural differences between the two groups were correlated with the indexes of attention biases towards the negative words.

The enhanced facilitation of attention to stimuli in the PP task by the negative valence was only found in the depressed patients, not in the healthy controls. Such attention biases towards negative stimuli were found to be associated with reduced gray-matter concentration (GMC) in the right superior frontal gyrus, the right anterior cingulate gyrus and the right fusiform gyrus. No differential effect in inhibition of attention towards negative stimuli in the NP task was found between the depressed patients and the healthy controls.

Specific structural abnormalities in depression are associated with their attention biases towards mood-congruent information.

Morphometric endophenotypes which have been proposed for psychotic disorders include lateral ventricular enlargement and hippocampal volume reductions. Genetic epidemiological studies support an overlap between schizophrenia and bipolar disorder, and COMT, BDNF, 5-HTT, NRG1 and DTNBP1 genes have been implicated in the aetiology of both these disorders. This study examined associations between these candidate genes and morphometric endophenotypes for psychosis.

A total of 383 subjects (128 patients with psychosis, 194 of their unaffected relatives and 61 healthy controls) from the Maudsley Family Psychosis Study underwent structural magnetic resonance imaging and genotyping. The effect of candidate genes on brain morphometry was examined using linear regression models adjusting for clinical group, age, sex and correlations between members of the same family.

The results showed no evidence of association between variation in COMT genotype and lateral ventricular, and left or right hippocampal volumes. Neither was there any effect of the BDNF, 5-HTTLPR, NRG1 and DTNBP1 genotypes on these regional brain volumes.

Abnormal hippocampal and lateral ventricular volumes are among the most replicated endophenotypes for psychosis; however, the influences of COMT, BDNF, 5-HTT, NRG1 and DTNBP1 genes on these key brain regions must be very subtle if at all present.

Although cognitive variables have been shown to be useful in predicting outcomes in late-life depression, there has not yet been a comprehensive study in younger persons with depression.

The clinical symptoms and cognitive performance of participants were evaluated at admission to one of two university teaching hospitals and again at 3 months after remission and discharge. A total of 52 participants with a DSM-IV diagnosis of major depressive disorder, aged between 20 and 60 years and with a Hamilton Depression Rating Scale score ⩾17 entered the study. The sample for this paper comprises the 48 subjects (mean age 37.9 years, s.d.=10.7) who received admission and follow-up assessments; an attrition rate of 7.7%.

More perseverative errors on the shortened Wisconsin Card Sorting Test at admission predicted a worse clinical outcome at follow-up. Poor event-based prospective memory and more perseverative errors on the shortened Wisconsin Card Sorting Test at admission predicted worse social and occupational outcome at follow-up.

These results suggest that a brief cognitive screen at hospital admission, focusing on executive function, would have a useful prognostic value in depression. Determining early predictors of individuals at risk of poorer outcomes is important for identifying those who may need altered or additional treatment approaches.

Although aggravating effects of rumination on dysfunctional cognitions and endocrine stress responses have been proposed, experimental studies testing these assumptions are lacking. In parallel, mindfulness theory suggests beneficial effects of mindfulness on dysfunctional cognitions. This study aimed to investigate the effects of induced rumination, distraction and mindful self-focus on mood and dysfunctional attitudes and to assess the possible impact of induced rumination on participants' cortisol responses.

Sixty university students were subjected to negative mood induction and subsequently randomly assigned to a rumination, distraction or mindful self-focus condition. The latter included statements focusing on self-acceptance and awareness of the breath. Four saliva cortisol samples were selected during the session.

Compared to induced rumination, distraction showed a clear beneficial effect on the course of dysphoric mood, whereas a mindful self-focus did not. In contrast to distraction and mindful self-focus, participants induced to ruminate showed significant increases in dysfunctional attitudes from baseline to post-induction. Although rumination was not itself linked to higher cortisol responses, participants scoring high on the Beck Depression Inventory (BDI)-II who were induced to ruminate showed a smaller decrease in cortisol levels than those scoring low on the BDI-II.

This study indicates that rumination as a dysfunctional mode of cognitive processing is able to maintain depression-linked dysfunctional thought content. Furthermore, our study revealed preliminary indications for a link between induced rumination and the cortisol stress response in vulnerable individuals.

Background. There is uncertainty about the diagnostic significance of specific symptoms of major depressive disorder (MDD). There is also interest in using one or two specific symptoms in the development of brief scales. Our aim was to elucidate the best possible specific symptoms that would assist in ruling in or ruling out a major depressive episode in a psychiatric out-patient setting.

A total of 1523 psychiatric out-patients were evaluated in the Methods to Improve Diagnostic Assessment and Services (MIDAS) project. The accuracy and added value of specific symptoms from a comprehensive item bank were compared against the Structured Clinical Interview for DSM-IV (SCID).

The prevalence of depression in our sample was 54.4%. In this high prevalence setting the optimum specific symptoms for ruling in MDD were psychomotor retardation, diminished interest/pleasure and indecisiveness. The optimum specific symptoms for ruling out MDD were the absence of depressed mood, the absence of diminished drive and the absence of loss of energy. However, some discriminatory items were relatively uncommon. Correcting for frequency, the most clinically valuable rule-in items were depressed mood, diminished interest/pleasure and diminished drive. The most clinically valuable rule-out items were depressed mood, diminished interest/pleasure and poor concentration.

The study supports the use of the questions endorsed by the two-item Patient Health Questionnaire (PHQ-2) with the additional consideration of the item diminished drive as a rule-in test and poor concentration as a rule-out test. The accuracy of these questions may be different in primary care studies where prevalence differs and when they are combined into multi-question tests or algorithmic models.

Despite the increasing development of early intervention services for psychosis, little is known about their cost-effectiveness. We assessed the cost-effectiveness of Outreach and Support in South London (OASIS), a service for people with an at-risk mental state (ARMS) for psychosis.

The costs of OASIS compared to care as usual (CAU) were entered in a decision model and examined for 12- and 24-month periods, using the duration of untreated psychosis (DUP) and rate of transition to psychosis as key parameters. The costs were calculated on the basis of services used following referral and the impact on employment. Sensitivity analysis was used to test the robustness of all the assumptions made in the model.

Over the initial 12 months from presentation, the costs of the OASIS intervention were £1872 higher than CAU. However, after 24 months they were £961 less than CAU.

This model suggests that services that permit early detection of people at high risk of psychosis may be cost saving.

Impaired P300 auditory response has been reported in patients with psychotic bipolar disorder (BPD) and unaffected relatives of psychotic bipolar patients. Deficits in mismatch negativity (MMN), however, have not been observed in bipolar patients. To our knowledge, no family study of MMN in BPD has been reported. The current study combined the Maudsley twin and bipolar family samples using genetic model fitting analyses to: (1) assess the relationship between BPD and MMN, (2) substantiate the association between psychotic BPD and P300 variables, (3) verify the genetic overlap of BPD with P300 amplitude previously reported in the twin sample, and (4) examine the shared genetic influences between BPD and bilateral temporal scalp locations of P300 components.

A total of 301 subjects were included in this study, including 94 twin pairs, 31 bipolar families, and 39 unrelated healthy controls. Statistical analyses were based on structural equation modelling.

Both P300 and MMN are heritable, with heritability estimates of 0.58 for MMN, 0.68–0.80 for P300 amplitude, and 0.21–0.56 for P300 latency. The bipolar patients and their relatives showed normal MMN. No significant association, either genetic or environmental, was found with BPD. BPD was significantly associated with reduced P300 amplitude and prolonged latency on midline and bilateral temporal-posterior scalp areas. Shared genetic factors were the main source of these associations.

The results confirm that MMN is not an endophenotype for psychotic BPD whereas P300 amplitude and latency components are valid endophenotypes for psychotic BPD.

Little is known about factors that predict first lifetime episodes of major depression in middle-aged women. It is not known whether health-related factors and life stress pose more or less of a risk to the onset of clinical depression than does the menopausal transition.

The Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) was used to assess diagnoses of lifetime, annual and current major depression in a community-based sample of premenopausal or early perimenopausal African American and White women. Menstrual cycle characteristics, psychosocial and health-related factors, and blood samples for assay of reproductive hormones were obtained annually. Two hundred and sixty-six women without a history of major depression at baseline constituted the cohort for the current analyses.

Over 7 years of follow-up, 42 (15.8%) women met criteria for a diagnosis of major depression. Frequent vasomotor symptoms (VMS; hot flashes and/or night sweats) (HR 2.14, p=0.03) were a significant predictor of major depression in univariate analyses. After simultaneous adjustment for multiple predictors in Cox proportional hazards analyses, frequent VMS were no longer significant; lifetime history of an anxiety disorder (HR 2.20, p=0.02) and role limitations due to physical health (HR 1.88, p=0.07) at baseline and a very stressful life event (HR 2.25, p=0.04) prior to depression onset predicted a first episode of major depression.

Both earlier (e.g. history of anxiety disorders) and more proximal factors (e.g. life stress) may be more important than VMS in contributing to a first episode of major depression during midlife.

Memory deficits are common in depressed patients and may persist after recovery. The aim of the present study was to determine whether memory impairments were present in young women at increased familial risk of depression and whether memory performance was related either to cortisol secretion or to allelic variation in the promoter region of the serotonin transporter gene (5-HTT).

Young women (n=35, age range 16–21 years) with no personal history of depression but with a depressed parent (FH+) carried out the Rey Auditory Verbal Learning Test (RAVLT). They also provided samples for the measurement of waking salivary cortisol and for 5-HTT genotyping. An age-matched control group of women (n=31) with no family history of depression were similarly studied.

The FH+ participants had decreased immediate recall and recognition memory compared to controls. The impairment in recall, but not recognition, correlated negatively with increased cortisol secretion in FH+ subjects. There was no significant effect of 5-HTT allelic status on either memory or waking cortisol secretion.

Impairments in declarative memory are present in young women at increased genetic risk of depression and may be partly related to increased cortisol secretion. Further studies are needed to explore the neural mechanisms underlying the memory impairments and whether they predict the development of clinical illness.

Current psychological models of psychotic symptoms suggest that metacognitive beliefs impact on an individual's appraisal of anomalous experiences, and thereby influence whether these lead to distress and become clinical symptoms. This study examined the relationship between maladaptive metacognitive beliefs, anomalous experiences, anomaly-related distress, anxiety and depression and diagnostic status.

The Metacognitions Questionnaire (MCQ), Symptom Checklist 90 – Revised, and Appraisals of Anomalous Experiences interview were administered to 27 people diagnosed with a psychotic disorder, 32 people meeting At Risk Mental State (ARMS) criteria, 24 people with psychotic-like experiences but no need for care, and 32 healthy volunteers.

The two clinical groups scored higher than non-patient controls and individuals experiencing psychotic-like anomalies with no need for care on most subscales of the MCQ, particularly the ‘general negative beliefs about thoughts’ (NEG) subscale. However, most group differences became non-significant when anxiety and depression were controlled for. Few relationships were found between the MCQ subscales and psychotic-like anomalies and anomaly-related distress. Cognitive/attentional difficulty was the only type of anomaly to be significantly associated with maladaptive metacognitive beliefs. Anomaly-related distress was associated with only the NEG subscale of the MCQ.

Maladaptive metacognitive beliefs, as measured by the MCQ, appear to be related more to elevated levels of general psychopathology in psychotic and at-risk groups than to the presence of, and distress associated with, psychotic experiences. Processes by which metacognitions may impact upon the need for care are discussed.

Psychological literature and clinical lore suggest that there may be systematic differences in how various demographic groups experience depressive symptoms, particularly somatic symptoms. The aim of the current study was to use methods based on item response theory (IRT) to examine whether, when equating for levels of depression symptom severity, there are demographic differences in the likelihood of reporting DSM-IV depression symptoms.

We conducted a secondary analysis of a subset (n=13 753) of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) dataset, which includes a large epidemiological sample of English-speaking Americans. We compared data from women and men, Hispanics and non-Hispanic Whites, African Americans and Whites, Asian Americans and Whites, and American Indians and Whites.

There were few differences overall, although the differences that we did find were primarily limited to somatic symptoms, and particularly appetite and weight disturbance.

For the most part, individuals responded similarly to the criteria used to diagnose major depression across gender and across English-speaking racial and ethnic groups in the USA.