Associations between parental depression and offspring affective and disruptive disorders are well documented. Few genetically informed studies have explored the processes underlying intergenerational associations.

A semi-structured interview assessing DSM-III-R psychiatric disorders was administered to twins (n=1296) from the Australian Twin Register (ATR), their spouses (n=1046) and offspring (n=2555). We used the Children of Twins (CoT) design to delineate the extent to which intergenerational associations were consistent with a causal influence or due to genetic confounds.

In between-family analyses, parental depression was associated significantly with offspring depression [hazard ratio (HR) 1.52, 95% confidence interval (CI) 1.20–1.93] and conduct disorder (CD; HR 2.27, CI 1.31–3.93). Survival analysis indicated that the intergenerational transmission of depression is consistent with a causal (environmental) inference, with a significant intergenerational association in offspring of discordant monozygotic (MZ) twin pairs (HR 1.39, CI 1.00–1.94). Logistic regression analysis suggested that the parental depression–offspring CD association was due to shared genetic liability in the parents and offspring. No intergenerational association was found when comparing the offspring of discordant MZ twins [odds ratio (OR) 1.41, CI 0.63–3.14], but offspring of discordant dizygotic (DZ) twins differed in their rates of CD (OR 2.53, CI 0.95–6.76). All findings remained after controlling for several measured covariates, including history of depression and CD in the twins' spouses.

The mechanisms underlying associations between parental depression and offspring psychopathology seem to differ depending on the outcome. The results are consistent with a causal environmental role of parental depression in offspring depression whereas common genetic factors account for the association of parental depression and offspring CD.

Both past depressive episodes and the personality trait of depressive rumination are strong risk factors for future depression. Depression is associated with abnormal emotional processing, which may be a neurobiological marker for vulnerability to depression. A consistent picture has yet to emerge as to how a history of depression and the tendency to ruminate influence emotional processing. The aim of this study was to investigate the relationship between rumination, past depression and neural responses when processing face emotions.

The Ruminative Responses Scale (RRS) was completed by 30 remitted depressives and 37 controls who underwent functional magnetic resonance imaging (fMRI) scanning while viewing happy, sad, fearful and neutral faces.

The remitted depressives showed overall reductions in neural responses to negative emotions relative to the controls. However, in the remitted depressives, but not the controls, RRS scores were correlated with increased neural responses to negative emotions and decreased responses to happiness in limbic regions.

Automatic emotion processing biases and rumination seem to be correlated to aspects of vulnerability to depression. However, remission from depression may be maintained by a general suppression of limbic responsiveness to negative emotion.

There are no risk models for the prediction of anxiety that may help in prevention. We aimed to develop a risk algorithm for the onset of generalized anxiety and panic syndromes.

Family practice attendees were recruited between April 2003 and February 2005 and followed over 24 months in the UK, Spain, Portugal and Slovenia (Europe4 countries) and over 6 months in The Netherlands, Estonia and Chile. Our main outcome was generalized anxiety and panic syndromes as measured by the Patient Health Questionnaire. We entered 38 variables into a risk model using stepwise logistic regression in Europe4 data, corrected for over-fitting and tested it in The Netherlands, Estonia and Chile.

There were 4905 attendees in Europe4, 1094 in Estonia, 1221 in The Netherlands and 2825 in Chile. In the algorithm four variables were fixed characteristics (sex, age, lifetime depression screen, family history of psychological difficulties); three current status (Short Form 12 physical health subscale and mental health subscale scores, and unsupported difficulties in paid and/or unpaid work); one concerned country; and one time of follow-up. The overall C-index in Europe4 was 0.752 [95% confidence interval (CI) 0.724–0.780]. The effect size for difference in predicted log odds between developing and not developing anxiety was 0.972 (95% CI 0.837–1.107). The validation of predictA resulted in C-indices of 0.731 (95% CI 0.654–0.809) in Estonia, 0.811 (95% CI 0.736–0.886) in The Netherlands and 0.707 (95% CI 0.671–0.742) in Chile.

PredictA accurately predicts the risk of anxiety syndromes. The algorithm is strikingly similar to the predictD algorithm for major depression, suggesting considerable overlap in the concepts of anxiety and depression.

Empathy is crucial for successful social relationships. Despite its importance for social interactions, little is known about empathy in schizophrenia. This study investigated the degree to which schizophrenia patients can accurately infer the affective state of another person (i.e. empathic accuracy).

A group of 30 schizophrenia patients and 22 healthy controls performed an empathic accuracy task on which they continuously rated the affective state of another person shown in a video (referred to as the ‘target’). These ratings were compared with the target's own continuous self-rating of affective state; empathic accuracy was defined as the correlation between participants' ratings and the targets' self-ratings. A separate line-tracking task was administered to measure motoric/attentional factors that could account for group differences in performance. Participants' self-rated empathy was measured using the Interpersonal Reactivity Index, and targets' self-rated emotional expressivity was measured using the Berkeley Expressivity Questionnaire.

Compared with controls, schizophrenia patients showed lower empathic accuracy although they performed the motoric tracking task at high accuracy. There was a significant group×target expressivity interaction such that patients showed a smaller increase in empathic accuracy with higher levels of emotional expressivity by the target, compared with controls. Patients' empathic accuracy was uncorrelated with self-reported empathy or clinical symptoms.

Schizophrenia patients showed lower empathic accuracy than controls, and their empathic accuracy was less influenced by the emotional expressivity of the target. These findings suggest that schizophrenia patients benefit less from social cues of another person when making an empathic judgement.

Patients with schizophrenia (SZ) characteristically exhibit supranormal levels of cortical activity to self-induced sensory stimuli, ostensibly because of abnormalities in the neural signals (corollary discharges, CDs) normatively involved in suppressing the sensory consequences of self-generated actions. The nature of these abnormalities is unknown. This study investigated whether SZ patients experience CDs that are abnormally delayed in their arrival at the sensory cortex.

Twenty-one patients with SZ and 25 matched control participants underwent electroencephalography (EEG). Participants' level of cortical suppression was calculated as the amplitude of the N1 component evoked by a button press-elicited auditory stimulus, subtracted from the N1 amplitude evoked by the same stimulus presented passively. In the three experimental conditions, the auditory stimulus was delivered 0, 50 or 100 ms subsequent to the button-press. Fifteen SZ patients and 17 healthy controls (HCs) also underwent diffusion tensor imaging (DTI), and the fractional anisotropy (FA) of participants' arcuate fasciculus was used to predict their level of cortical suppression in the three conditions.

While the SZ patients exhibited subnormal N1 suppression to undelayed, self-generated auditory stimuli, these deficits were eliminated by imposing a 50-ms, but not a 100-ms, delay between the button-press and the evoked stimulus. Furthermore, the extent to which the 50-ms delay normalized a patient's level of N1 suppression was linearly related to the FA of their arcuate fasciculus.

These data suggest that SZ patients experience temporally delayed CDs to self-generated auditory stimuli, putatively because of structural damage to the white-matter (WM) fasciculus connecting the sites of discharge initiation and destination.

By studying behavior, cognitive abilities and brain functioning in adolescents at high risk for psychosis, we can gain an insight into the vulnerability markers or protective factors in the development of psychotic symptoms. Although many high-risk studies have focused on impairments in neurocognitive functions, such as memory and attention, very few studies have investigated problems in processing social cues such as facial expressions as a possible vulnerability marker for psychosis.

Thirty-six adolescents at ultra-high risk (UHR) for psychosis and 21 non-clinical controls completed a face recognition test, a facial affect labeling test and an inhibitory control test. Schizotypal traits and schizophrenia symptoms were assessed using a schizotypy questionnaire and the Positive and Negative Syndrome Scale (PANSS).

The UHR group showed impairments in labeling facial expressions of others, in addition to a spared ability to recognize facial identity. More specifically, the UHR group made more errors in labeling neutral expressions compared to the controls, and an analysis of error types indicated that neutral faces were misattributed as being angry. The degree of misattribution of neutral-as-angry faces correlated significantly with reduced inhibitory control.

Our findings suggest that misattributing social cues might contribute to vulnerability for psychosis. This social cognitive deficit may be related to problems in inhibitory control, which potentially plays an important role in the selection of appropriate social meaning. These findings may have relevance for understanding the mechanisms underlying prodromal social dysfunction, which should be targeted in future remediation interventions.

The different incidence rates of, and risk factors for, depression in different countries argue for the need to have a specific risk algorithm for each country or a supranational risk algorithm. We aimed to develop and validate a predictD-Spain risk algorithm (PSRA) for the onset of major depression and to compare the performance of the PSRA with the predictD-Europe risk algorithm (PERA) in Spanish primary care.

A prospective cohort study with evaluations at baseline, 6 and 12 months. We measured 39 known risk factors and used multi-level logistic regression and inverse probability weighting to build the PSRA. In Spain (4574), Chile (2133) and another five European countries (5184), 11 891 non-depressed adult primary care attendees formed our at-risk population. The main outcome was DSM-IV major depression (CIDI).

Six variables were patient characteristics or past events (sex, age, sex×age interaction, education, physical child abuse, and lifetime depression) and six were current status [Short Form 12 (SF-12) physical score, SF-12 mental score, dissatisfaction with unpaid work, number of serious problems in very close persons, dissatisfaction with living together at home, and taking medication for stress, anxiety or depression]. The C-index of the PSRA was 0.82 [95% confidence interval (CI) 0.79–0.84]. The Integrated Discrimination Improvement (IDI) was 0.0558 [standard error (s.e.)=0.0071, Zexp=7.88, p<0.0001] mainly due to the increase in sensitivity. Both the IDI and calibration plots showed that the PSRA functioned better than the PERA in Spain.

The PSRA included new variables and afforded an improved performance over the PERA for predicting the onset of major depression in Spain. However, the PERA is still the best option in other European countries.

Residual depressive symptomatology constitutes a substantial risk for relapse in depression. Treatment until full remission is achieved is therefore implicated. However, there is a lack of knowledge about the prevalence of (1) residual symptoms in general and (2) the individual residual symptoms in particular.

In a 3-year prospective study of 267 initially depressed primary care patients we established per week the presence/absence of the individual DSM-IV depressive symptoms during subsequent major depressive episodes (MDEs) and episodes of (partial) remission. This was accomplished by means of 12 assessments at 3-monthly intervals with the Composite International Diagnostic Interview (CIDI).

In general, residual depressive symptomatology was substantial, with on average two symptoms present during remissions. Three individual symptoms (cognitive problems, lack of energy and sleeping problems) dominated the course of depression and were present 85–94% of the time during depressive episodes and 39–44% of the time during remissions.

Residual symptoms are prevalent, with some symptoms being present for almost half of the time during periods of remission. Treatment until full remission is achieved is not common practice, yet there is a clear need to do so to prevent relapse. Several treatment suggestions are made.

The clinical picture of schizophrenia is frequently worsened by manifestations of impulsivity. However, the neural correlates of impulsivity in this disorder are poorly known. Although impulsivity has been related to disturbances of the neural processes underlying response inhibition, no studies have yet examined the relationship between these processes and psychometric measures of impulsivity in schizophrenia. This was the aim of the current investigation.

Event-related functional magnetic resonance imaging in conjunction with a Go/NoGo task was employed to probe the neural activity associated with response inhibition in 26 patients with schizophrenia and 30 healthy comparison subjects. All participants also completed the Barratt Impulsiveness Scale – version 11 (BIS-11). Voxel-wise regression analyses were used to examine the relationship between the BIS-11 score and brain activation during response inhibition in each group.

Patients with schizophrenia were more impulsive than healthy subjects, as indicated by higher BIS-11 scores. Patients, but not healthy subjects, were found to display a positive correlation between these scores and cerebral activation associated with response inhibition. This correlation involves a unique cluster localized within the right ventrolateral prefrontal cortex (VLPFC), a key node of the brain network subserving response inhibition.

We evidenced in patients with schizophrenia that greater BIS-11 scores are associated with greater activation within the right VLPFC during response inhibition. This finding suggests that the efficiency of this brain region to process inhibitory control is reduced in the more impulsive patients.

We examined the different trajectories of vital exhaustion (VE) over a 12-month period and their impact on prognosis in a sample of myocardial infarction (MI) and chronic heart failure (CHF) patients.

Consecutive MI (n=407) and CHF patients (n=297) were assessed at baseline, and at 3- and 12-month follow-up for symptoms of VE. Latent growth mixture modelling was used to examine the course of VE over time. The combined clinical endpoint was defined as cardiac hospital readmission or death.

Four distinct trajectories for VE were found: low VE, decreasing VE, increasing VE, and severe VE. Sex, marital status, left ventricular ejection fraction, psychotropic medication, sample group (CHF v. MI) and depressive symptoms were associated with VE, varying according to classes. The mean follow-up period was 25.3 months in which 34.7% of the patients experienced an event. Multivariate Cox regression showed that, compared with patients in the low VE class, patients in the increasing VE class [hazard ratio (HR)=1.16, 95% confidence interval (CI) 1.58–3.61, p=0.01], and the severe VE class (HR=1.69, 95% CI 1.31–2.64, p=0.02) had an increased risk for adverse cardiovascular events (i.e. cardiovascular hospital readmission or cardiovascular death). Decreasing VE was not related to adverse cardiovascular events (HR=0.97, 95% CI 0.66–1.69, p=0.81).

VE trajectories varied across cardiac patients, and had a differential effect on cardiovascular outcome. Increasing VE and severe VE classes were predictors of poor cardiovascular prognosis. These results suggest that identification of cardiac patients with an increased risk of adverse health outcomes should be based on multiple assessments of VE.

The determinants of depression following acute coronary syndrome (ACS) are poorly understood. Triggering of ACS by emotional stress and low socio-economic status (SES) are predictors of adverse outcomes. We therefore investigated whether emotional triggering and low SES predict depression and anxiety following ACS.

This prospective observational clinical cohort study involved 298 patients with clinically verified ACS. Emotional stress was assessed for the 2 h before symptom onset and compared with the equivalent period 24 h earlier using case-crossover methods. SES was defined by household income and education. Depression was measured with the Beck Depression Inventory and the Hamilton Rating Scale for Depression and anxiety with the Hospital Anxiety and Depression Scale 3 weeks after ACS and again at 6 and 12 months. Age, gender, ethnicity, marital status, the Global Registry of Acute Coronary Events risk score, duration of hospital stay and history of depression were included as covariates.

Emotional stress during the 2-h hazard period was associated with increased risk of ACS (odds ratio 1.88, 95% confidence interval 1.01–3.61). Both low income and emotional triggering predicted depression and anxiety at 3 weeks and 6/12 months independently of covariates. The two factors interacted, with the greatest depression and anxiety in lower income patients who experienced acute emotional stress. Education was not related to depression.

Patients who experience acute emotional stress during their ACS and are lower SES as defined by current affluence and access to resources are particularly vulnerable to subsequent depression and anxiety.

Despite behavioural signs of flattened affect, patients affected by schizophrenia show enhanced sensitivity to negative stimuli. The current literature concerning neural circuitry for emotions supports dysregulations of cortico-limbic networks, but gives contrasting results. Adverse childhood experiences (ACEs) could persistently influence emotional regulation and neural correlates of response to emotional stimuli in healthy humans. This study evaluated the effect of ACEs and chronic undifferentiated schizophrenia on neural responses to emotional stimuli (negative facial expression).

Brain blood-oxygen-level-dependent functional magnetic resonance imaging neural responses to a face-matching paradigm, and regional grey matter (GM) volumes were studied at 3.0 T in the amygdala, hippocampus, anterior cingulated cortex (ACC) and prefrontal cortex (PFC). The severity of ACEs was assessed. Participants included 20 consecutively admitted in-patients affected by chronic undifferentiated schizophrenia, and 20 unrelated healthy volunteers from the general population.

Patients reported higher ACEs than controls. Worse ACEs proportionally led to decreasing responses in the amygdala and hippocampus, and to increasing responses in the PFC and ACC in all participants. Patients showed higher activations in the amygdala and hippocampus, and lower activations in the PFC and ACC. Higher ACEs were associated with higher GM volumes in the PFC and ACC, and schizophrenia was associated with GM reduction in all studied regions.

Structural and functional brain correlates of emotional reactivity are influenced by both current chronic undifferentiated schizophrenia and the severity of past ACEs.

The amygdala plays a central role in the fronto-limbic network involved in the processing of emotions. Structural and functional abnormalities of the amygdala have recently been found in schizophrenia, although there are still contradictory results about its reduced or preserved volumes.

In order to address these contradictory findings and to further elucidate the possibly underlying pathophysiological process of the amygdala, we employed structural magnetic resonance imaging (MRI) and diffusion weighted imaging (DWI), exploring amygdalar volume and microstructural changes in 69 patients with schizophrenia and 72 matched healthy subjects, relating these indices to psychopathological measures.

Measuring water diffusivity, the apparent diffusion coefficients (ADCs) for the right amygdala were found to be significantly greater in patients with schizophrenia compared with healthy controls, with a trend for abnormally reduced volumes. Also, significant correlations between mood symptoms and amygdalar volumes were found in schizophrenia.

We therefore provide evidence that schizophrenia is associated with disrupted tissue organization of the right amygdala, despite partially preserved size, which may ultimately lead to abnormal emotional processing in schizophrenia. This result confirms the major role of the amygdala in the pathophysiology of schizophrenia and is discussed with respect to amygdalar structural and functional abnormalities found in patients suffering from this illness.

Depressed individuals demonstrate a poorer ability to recognize the emotions of others, which could contribute to difficulties in interpersonal behaviour. This emotion recognition deficit appears related to the depressive state and is particularly pronounced when emotions are labelled semantically. Here, we investigated its neural basis by comparing emotion recognition processing between depressed, recovered and healthy individuals.

Medication-naive patients with a first major depressive episode, medication-free patients who had recovered from a first episode, and a group of matched healthy individuals participated. They were requested to identify the emotion of angry and fearful face stimuli, either by matching them to other emotional faces on a perceptual basis or by matching them to a semantic label, while their brain activity was measured with functional magnetic resonance imaging.

The depressed individuals performed worse than recovered and healthy individuals on the emotion-labelling but not the emotion-matching task. The labelling deficit was related to increased recruitment of the right amygdala, left inferior frontal gyrus and anterior cingulate cortex.

Deficits in semantic labelling of negative emotions are related to increased activation in specific brain regions and these abnormalities are mood state-dependent. These results indicate that accessing semantic knowledge about negative information triggers increased amygdala and left inferior frontal gyrus processing, which subsequently impairs task-relevant behaviour. We propose that this may reflect the activation of negative schemas.

The concept of narcissism has been much researched in psychoanalysis and especially in self psychology. One of the hallmarks of narcissism is altered emotion, including decreased affective resonance (e.g. empathy) with others, the neural underpinnings of which remain unclear. The aim of our exploratory study was to investigate the psychological and neural correlates of empathy in two groups of healthy subjects with high and low narcissistic personality trait. We hypothesized that high narcissistic subjects would show a differential activity pattern in regions such as the anterior insula that are typically associated with empathy.

A sample of 34 non-clinical subjects was divided into high (n=11) and low (n=11) narcissistic groups according to the 66th and 33rd percentiles of their scores on the Narcissism Inventory (NI). Combining the psychological, behavioral and neuronal [i.e. functional magnetic resonance imaging (fMRI)] measurements of empathy, we compared the high and low narcissistic groups of subjects.

High narcissistic subjects showed higher scores on the Symptom Checklist-90 – Revised (SCL-90-R) and the 20-item Toronto Alexithymia Scale (TAS-20) when compared to low narcissistic subjects. High narcissistic subjects also showed significantly decreased deactivation during empathy, especially in the right anterior insula.

Psychological and neuroimaging data indicate respectively higher degrees of alexithymia and lower deactivation during empathy in the insula in high narcissistic subjects. Taken together, our preliminary findings demonstrate, for the first time, psychological and neuronal correlates of narcissism in non-clinical subjects. This might stipulate both novel psychodynamic conceptualization and future psychological–neuronal investigation of narcissism.

Research suggests that psychotic-like experiences (PLEs) in the general population are common, but can reflect either transitory or persistent developmental phenomena. Using a general adolescent population it was examined whether different developmental subtypes of PLEs exist and whether different trajectories of PLEs are associated with certain environmental risk factors, such as victimization and substance use.

Self-reported PLEs were collected from 409 adolescents (mean age 14 years 7 months) at four time points, each 6 months apart. General growth mixture modelling was utilized to identify classes of adolescents who followed distinct trajectories of PLEs across this period. Predictors of class membership included demographics, personality, victimization, depression, anxiety and substance use.

We identified the following three developmental subgroups of PLEs: (1) persistent; (2) increasing; (3) low. Adolescents on the persistent trajectory reported frequent victimization and consistent elevated scores in depression and anxiety. Adolescents on the increasing trajectory were engaging in cigarette use prior to any increases in PLEs and were engaging in cocaine, cannabis and other drug use as PLEs increased at later time points.

The findings suggest that different developmental subgroups of PLEs exist in adolescence and are differentially related to victimization and substance use.

Selective serotonin reuptake inhibitors take several weeks to achieve their full antidepressant effects. Post-synaptic 5-HT2A receptor activation is thought to be involved in this delayed therapeutic effect. Pipamperone acts as a highly selective 5-HT2A/D4 antagonist when administered in low doses. The purpose of this study was to compare citalopram 40 mg once daily plus pipamperone 5 mg twice daily (PipCit) versus citalopram plus placebo twice daily for magnitude and onset of therapeutic effect.

An 8-week, randomized, double-blind study in patients with major depressive disorder was carried out.

The study population comprised 165 patients (citalopram and placebo, n=82; PipCit, n=83) with a mean baseline Montgomery–Asberg Depression Rating Scale (MADRS) score of 32.6 (s.d.=5.5). In the first 4 weeks, more citalopram and placebo than PipCit patients discontinued treatment (18% v. 4%, respectively, p=0.003). PipCit patients had significantly greater improvement in MADRS score at week 1 [observed cases (OC), p=0.021; last observation carried forward (LOCF), p=0.007] and week 4 (LOCF, p=0.025) but not at week 8 compared with citalopram and placebo patients. Significant differences in MADRS scores favoured PipCit in reduced sleep, reduced appetite, concentration difficulties and pessimistic thoughts. Mean Clinical Global Impression–Improvement scores were significantly improved after 1 week of PipCit compared with citalopram and placebo (OC and LOCF, p=0.002).

Although the MADRS score from baseline to 8 weeks did not differ between groups, PipCit provided superior antidepressant effects and fewer discontinuations compared with citalopram and placebo during the first 4 weeks of treatment, especially in the first week.

Although cognitive deficits in bipolar disorder have been associated with diminished functional outcome, this relationship has been studied primarily through cross-sectional designs, and has not been studied in patients early in the course of illness. The purpose of this study was to evaluate the impact of cognitive functioning on longitudinal 6-month functional and clinical outcome in recently diagnosed clinically stable patients with bipolar disorder.

A total of 53 recently diagnosed patients with DSM-IV bipolar disorder type I were assessed within 3 months of their first manic episode using a neuropsychological battery measuring verbal/pre-morbid intellectual functioning, learning/memory, spatial/non-verbal reasoning, attention/processing speed and executive function. Functional outcome was assessed at baseline and 6 months using the Multidimensional Scale of Independent Functioning (MSIF) and DSM-IV Global Assessment of Functioning Scale (GAF). Clinical outcome was assessed with symptom ratings and by monitoring onset of new mood episodes.

Memory, particularly verbal learning/memory, was robustly associated with 6-month functional outcome on the MSIF, even after partialling out the influence of mood symptoms and substance abuse co-morbidity. Depression ratings at 6 months, but not cognitive variables, were associated with 6-month GAF scores. Cognitive functioning was not associated with 6-month clinical outcome.

Memory was associated with 6-month longitudinal functional but not clinical outcome in recently diagnosed patients with bipolar disorder. These data further support the distinction between clinical and functional outcome, and emphasize the need for identification of, and development of treatments for, cognitive impairments early in the course of bipolar disorder.