Despite the substantial heritability of the psychoses and their genuine public health burden, the applicability of the genomic approach in psychiatry has been strongly questioned or prematurely dismissed.

A selective review of the recent literature on molecular genetic and genomic approaches to the psychoses including the early output from genome-wide association studies and the genomic analysis of DNA structural variation.

Susceptibility variants at strong candidate genes have been identified including neuregulin, dysbindin, DISC1 and neurexin 1. Rare but highly penetrant copy number variants and new mutations affecting genes involved in neurodevelopment, cell signalling and synaptic function have been described showing some overlapping genetic architecture with other developmental disorders including autism. The de-novo mutations described offer an explanation for the familial sporadic divide and the persistence of schizophrenia in the population. The functional effects of risk variants at the level of cognition and connectivity has been described and recently, ZNF804A has been identified, and the MHC re-identified as risk loci, and it has been shown that at least a third of the variation in liability is due to multiple common risk variants of small effect with a substantial shared genetic liability between schizophrenia and bipolar affective disorder.

The genomics have done much for the psychoses to date and more is anticipated.

Several studies have reported reduction of auditory hallucinations (AH) after repetitive transcranial magnetic stimulation (rTMS) to the left temporal cortex. This study explored the effects of rTMS to the left and right temporal cortex.

Eighteen subjects with schizophrenia and frequent AH were enrolled in a double-blind, cross-over trial of 3 days of active rTMS to the left or right temporal cortex, or sham rTMS to the vertex (control condition), followed by an open treatment phase. The effects on AH were assessed by a blinded rater, using the Auditory Hallucination Rating Scale (AHRS).

During the double-blind phase, active temporal rTMS did not result in significantly greater improvement in hallucination scores than sham rTMS to the vertex, apart from a reduction in distress scores. Hallucination scores improved during the open continued treatment phase.

This study did not demonstrate an advantage for left temporal rTMS compared to right temporal and sham stimulation, over a 3-day stimulation period, but found modest improvement in hallucinations during continued open label treatment.

Longitudinal studies indicate that future schizophrenia patients exhibit lower IQ than healthy controls. Recent studies suggest that future patients with other mental illnesses obtain lower pre-morbid IQ. The aims of this study were to compare pre-morbid IQ among five diagnostic categories and normal controls, to examine the distribution of pre-morbid IQ, and to investigate the relationship between pre-morbid IQ and risk of mental illness.

A total of 7486 individuals hospitalized with psychiatric disease and 20 531 controls. IQ was measured at the draft board and hospital diagnoses [schizophrenia (Sz), non-schizophrenic, non-affective psychoses (NSAP), affective (AD), personality (PD) and neurotic/stress disorders (ND)] were followed up to ages 43–54 years. Individuals hospitalized ⩽1 year after appearing before the draft board were excluded.

All future patients obtained significantly lower pre-morbid IQ than controls (3–7 IQ points), AD had the highest IQ and PD the lowest. In each diagnostic category, decreasing IQ was associated with an increasing risk of becoming a patient [odds ratios (ORs) 0.5–2.5 over the full IQ spectrum]. IQ distributions was nearly normal and uni-modal.

IQ deficits in each diagnostic category may reflect different functional patterns and temporal vicissitudes of the specific pathogenetic processes involved in different mental disorders.

The habenular complex is composed of important relay nuclei linking the limbic forebrain to the midbrain and brain stem nuclei. Based on clinical observations, experiments with animals and theoretical considerations, it has been speculated that this brain area might be involved in psychiatric diseases (i.e. schizophrenia and depression). However, evidence in favour of this hypothesis is still lacking because the human habenular complex has rarely been studied with regard to mental illness.

We examined habenular volumes in post-mortem brains of 17 schizophrenia patients, 14 patients with depression (six patients with major depression and eight patients with bipolar depression) and 13 matched controls. We further determined the neuronal density, cell number and cell area of the medial habenular nuclei of the same cohorts using a counting box and a computer-assisted instrument.

Significantly reduced habenular volumes of the medial and lateral habenula were estimated in depressive patients in comparison to normal controls and schizophrenia patients. We also found a reduction in neuronal cell number and cell area in depressive patients for the right side compared to controls and schizophrenia patients. No such changes were seen in schizophrenia.

Our anatomical data argue against prominent structural alterations of the habenular nuclei in schizophrenia but demonstrate robust alterations in depressive patients. We are currently applying immunohistochemical markers to better characterize neuronal subpopulations of this brain region in schizophrenia and depression.

Individuals with schizophrenia and individuals with high-functioning autism (HFA) seem to share some social, behavioral and biological features. Although marked impairments in social cognition have been documented in both groups, little empirical work has compared the social cognitive functioning of these two clinical groups.

Forty-four individuals with schizophrenia, 36 with HFA and 41 non-clinical controls completed a battery of social cognitive measures that have been linked previously to specific brain regions.

The results indicate that the individuals with schizophrenia and HFA were both impaired on a variety of social cognitive tasks relative to the non-clinical controls, but did not differ from one another. When individuals with schizophrenia were divided into negative symptom and paranoid subgroups, exploratory analyses revealed that individuals with HFA may be more similar, in terms of the pattern of social cognition impairments, to the negative symptom group than to the paranoia group.

Our findings provide further support for similarities in social cognition deficits between HFA and schizophrenia, which have a variety of implications for future work on gene–brain–behavior relationships.

Patterns of suicide rates in China differ in many ways from those in the West. This study aimed to identify the risk factors characteristic for young rural Chinese suicides.

This was a case-control psychological autopsy (PA) study. The samples were suicides and living controls (both aged 15–34 years) from 16 rural counties of China. We interviewed two informants for each suicide and each control with pretested and validated instruments to estimate psychosocial, psychiatric and other risk factors for suicides.

The prevalence of mental disorders was higher among the young Chinese who died by suicide than among the living controls, but was lower than among suicides in the West. Marriage was not a protecting factor for suicide among young rural Chinese women, and never-married women who were involved in relationships were about three times more likely to commit suicide than single women who were unattached. Religion/religiosity was not a protecting factor in Chinese suicide, as it tended to be stronger for suicides than for controls. Impulsivity was significantly higher for suicides than for controls. Psychological strain, resulting from conflicting social values between communist gender equalitarianism and Confucian gender discrimination, was associated significantly with suicide in young rural Chinese women, even after accounting for the role of psychiatric illness.

Risk factors for suicide in rural China are different from those in the West. Psychological strain plays a role in suicide. Suicide prevention programs in China should incorporate culture-specific considerations.

Cognitive deficits persist despite clinical recovery in subjects with late-life depression, but more needs to be known about their longer-term outcome and factors affecting their course. To investigate this, we followed the pattern of cognitive impairments over time and examined the effects of current mood, remission status, age of depression onset and antidepressant (AD) treatment on these deficits.

Sixty-seven subjects aged ⩾60 years with DSM-IV major depressive disorder and 36 healthy comparison subjects underwent tests of global cognition, memory, executive functioning and processing speed at baseline, 6 and 18 months, with some subjects tested again after 4 years. z scores were compared between groups, with analyses of clinical factors that may have influenced cognitive performance in depressed subjects.

Half of the patients exhibited a generalized cognitive impairment (GCI) that persisted after 18 months. Patients performed worse across all cognitive domains at all time points, without substantial variability due to current mood, remission status or AD treatment. Late age of onset was associated significantly with decline in memory and executive functioning. Impaired processing speed may be a partial mediator of some deficits, but was insufficient to explain differences between patients and controls. Four-year follow-up data suggest impairments persist, but do not further decline.

Cognitive deficits in late-life depression persist up to 4 years, affect multiple domains and are related to trait rather than state effects. Differences in severity and course between early and late onset depression suggest different pathogenic processes.

Growing evidence suggests that cerebral white-matter changes and depressive symptoms are linked directly along the causal pathway. We investigated whether baseline severity of cerebral white-matter changes predict longer-term future depressive outcomes in a community sample of non-disabled older adults.

In the Leukoaraiosis and Disability in the Elderly (LADIS) study, a longitudinal multi-centre pan-European study, 639 older subjects underwent baseline structural magnetic resonance imaging (MRI) and clinical assessments. Baseline severity of white-matter changes was quantified volumetrically. Depressive outcomes were assessed in terms of depressive episodes and depressive symptoms, as measured by the Geriatric Depression Scale (GDS). Subjects were clinically reassessed annually for up to 3 years. Regression models were constructed to determine whether baseline severity of white-matter changes predicted future depressive outcomes, after controlling for confounding factors.

Baseline severity of white-matter changes independently predicted depressive symptoms at both 2 (p<0.001) and 3 years (p=0.015). Similarly, white-matter changes predicted incident depression (p=0.02). Over the study period the population became significantly more disabled (p<0.001). When regression models were adjusted to account for the influence of the prospective variable transition to disability, baseline severity of white-matter changes no longer predicted depressive symptoms at 3 years (p=0.09) or incident depression (p=0.08).

Our results support the vascular depression hypothesis and strongly implicate white-matter changes in the pathogenesis of late-life depression. Furthermore, the findings indicate that, over time, part of the relationship between white-matter changes and depression may be mediated by loss of functional activity.

People with Down's syndrome (DS) are at high risk for developing dementia in middle age. The biological basis for this is unknown. It has been proposed that non-demented adults with DS may undergo accelerated brain ageing.

We used volumetric magnetic resonance imaging (MRI) and manual tracing to compare brain anatomy and ageing in 39 non-demented adults with DS and 42 healthy controls.

Individuals with DS had significant differences in brain anatomy. Furthermore, individuals with DS had a significantly greater age-related reduction in volume of frontal, temporal and parietal lobes, and a significantly greater age-related increase in volume of peripheral cerebrospinal fluid (CSF).

Non-demented adults with DS have differences in brain anatomy and ‘accelerated’ ageing of some brain regions. This may increase their risk for age-related cognitive decline and Alzheimer's disease (AD).

Growing evidence suggests that perinatal depression is associated with disrupted mother–infant interactions and poor infant outcomes. Antenatal depression may play a key role in this cycle by disrupting the development of a maternal response to infant stimuli. The current study therefore investigated the impact of depressive symptoms on the basic cognitive processing of infant stimuli at the beginning of pregnancy.

A total of 101 women were recruited by community midwives and tested at an average gestation of 11 weeks. An established computerized paradigm measured women's ability to disengage attention from infant and adult faces displaying negative positive and neutral emotions. Depressive symptoms were measured using a computerized interview (the Clinical Interview Schedule).

The effect of infant emotion on women's ability to disengage from infant faces was found to be influenced by depressive symptoms. Non-depressed pregnant women took longer to disengage attention from distressed compared with non-distressed infant faces. This bias was not, however, seen in women experiencing depressive symptoms. There was a difference of −53 (s.d.=0.7) ms (95% confidence interval −90 to −14, p=0.007) between those with and without depressive symptoms in this measure of attentional bias towards distressed infant faces.

Our results suggest that depressive symptoms are already associated with differential attentional processing of infant emotion at the very beginning of childbearing. The findings have potential implications for our understanding of the impact of depressive symptoms during pregnancy on the developing mother–infant relationship.

Previous research suggests, though not consistently, that maternal psychological distress during pregnancy leads to adverse birth outcomes. We investigated whether maternal psychological distress affects fetal growth during the period of mid-pregnancy until birth.

Pregnant women (n=6313) reported levels of psychological distress using the Brief Symptom Inventory (anxious and depressive symptoms) and the Family Assessment Device (family stress) at 20.6 weeks pregnancy and had fetal ultrasound measurements in mid- and late pregnancy. Estimated fetal weight was calculated using head circumference, abdominal circumference and femur length.

In mid-pregnancy, maternal distress was not linked to fetal size. In late pregnancy, however, anxious symptoms were related to fetal size after controlling for potential confounders. Anxious symptoms were also associated with a 37.73 g [95% confidence interval (CI) −69.22 to −6.25, p=0.019] lower birth weight. When we related maternal distress to fetal growth curves using multilevel models, more consistent results emerged. Maternal symptoms of anxiety or depression were associated with impaired fetal weight gain and impaired fetal head and abdominal growth. For example, depressive symptoms reduced fetal weight gain by 2.86 g (95% CI −4.48 to −1.23, p<0.001) per week.

The study suggests that, starting in mid-pregnancy, fetal growth can be affected by different aspects of maternal distress. In particular, children of prenatally anxious mothers seem to display impaired fetal growth patterns during pregnancy. Future work should address the biological mechanisms underlying the association of maternal distress with fetal development and focus on the effects of reducing psychological distress in pregnancy.

Biases in emotional processing and cognitions about the self are thought to play a role in the maintenance of eating disorders (EDs). However, little is known about whether these difficulties exist pre-morbidly and how they might contribute to risk.

Female dieters (n=82) completed a battery of tasks designed to assess the processing of social cues (facial emotion recognition), cognitions about the self [Self-Schema Processing Task (SSPT)] and ED-specific cognitions about eating, weight and shape (emotional Stroop). The 26-item Eating Attitudes Test (EAT-26; Garner et al. 1982) was used to assess subclinical ED symptoms; this was used as an index of vulnerability within this at-risk group.

Regression analyses showed that biases in the processing of both neutral and angry faces were predictive of our measure of vulnerability (EAT-26). In the self-schema task, biases in the processing of negative self descriptors previously found to be common in EDs predicted vulnerability. Biases in the processing of shape-related words on the Stroop task were also predictive; however, these biases were more important in dieters who also displayed biases in the self-schema task. We were also able to demonstrate that these biases are specific and separable from more general negative biases that could be attributed to depressive symptoms.

These results suggest that specific biases in the processing of social cues, cognitions about the self, and also about eating, weight and shape information, may be important in understanding risk and preventing relapse in EDs.

Perinatal factors seem to be implicated in the pathogenesis of anorexia nervosa (AN) and may be involved in the programming of stress response systems in humans. Our aim was to explore one of the possible pathways to explain the association between perinatal complications and a psychiatric disorder. In particular, we tested the hypothesis that neonatal immaturity may confer an enhanced vulnerability to AN after exposure to a severe stressful event, such as childhood abuse.

The sample was composed of subjects who took part in a prevalence study carried out on a representative sample of the general population and cases of AN referred to an out-patient specialist unit. All subjects (n=663) were born in the two obstetric wards of Padua Hospital between 1971 and 1979. We analysed data using both a case-control and a cohort design.

We found that functional signs of neonatal dysmaturity, but not a low birthweight or prematurity, had a significant additive interaction with childhood abuse in determining the risk for this illness. In normal subjects, but not in subjects with AN, neonatal dysmaturity was associated with being small, short or thin for gestational age at birth.

The synergistic effect of neonatal dysmaturity and childhood abuse in increasing the risk for AN provides evidence for the hypothesis that a prenatal programming of stress response systems can result in an impairment of the individual's resilience to severe stressful events.

Behavioral studies show that attention training can alter threat bias, influence vulnerability to stress and reduce clinical anxiety symptoms. The aim of this study was to examine which cognitive functions of attention processing are modulated by attention training, and how a priori anxiety interacts with the attention training procedure. Specifically, we expected modulation in the P1/N1 event-related potential (ERP) complex if early spatial attention was to be affected by training and modulation in later ERP components (P2, N2, P3) had training affected top-down attentional processes.

Thirty anxious and 30 non-anxious adults performed a modified probe detection task. Electroencephalograms (EEGs) were recorded throughout for later ERP analyses. Half the participants in each anxiety group were randomly assigned to undergo a training procedure designed to divert their attention away from threat and the other half received placebo training.

Anxious participants who were trained to avoid threat showed a linear reduction in response time (RT) to targets replacing neutral faces with the progression of training. This change in RT was not observed among non-anxious participants or among anxious participants who were exposed to placebo training. Following training, the anxious participants who were trained to avoid threat showed a reduction in P2 and P3 mean amplitudes and an enhancement in N2 mean amplitude.

Attention training affects anxious participants whereas non-anxious participants seem not to respond to it. The ERP data suggest that attention training modulates top-down processes of attention control rather than processes of early attention orienting.

In this study, 30-year longitudinal data from the Christchurch Health and Development Study (CHDS) were used to examine the associations between childhood exposure to sexual abuse and intimate relationship outcomes at age 30. In addition, a broad range of early childhood and family confounding factors were tested, and the role of intervening factors from adolescence was explored.

The investigation analyzed data from a birth cohort of over 900 New Zealand adults studied to the age of 30. At ages 18 and 21 cohort members reported on any exposure to sexual abuse prior to age 16. This information, along with prospective data gathered in childhood and adolescence, was used to predict partnership outcomes at age 30.

After adjustment for early childhood and family factors, exposure to more severe forms of childhood sexual abuse (CSA) was associated with earlier and more frequent cohabitation, higher rates of perpetrated interpartner violence (IPV), and early parenthood, lower relationship satisfaction and investment. Several factors from adolescence partially or fully mediated these associations, notably a history of early consensual sexual intercourse, higher number of sexual partnerships, substance abuse problems, and self-esteem. After adjustment for intervening factors, exposure to CSA remained significantly associated with IPV.

The findings support a causal chain process, whereby early childhood and family factors place some individuals at risk for CSA. The extent of CSA exposure is related to adolescent risk taking, which in turn leads to early and more frequent cohabitation, risk of IPV, and lower relationship satisfaction and investment.

Patients whose symptoms are ‘unexplained by disease’ often have a poor symptomatic outcome after specialist consultation, but we know little about which patient factors predict this. We therefore aimed to determine predictors of poor subjective outcome for new neurology out-patients with symptoms unexplained by disease 1 year after the initial consultation.

The Scottish Neurological Symptom Study was a 1-year prospective cohort study of patients referred to secondary care National Health Service neurology clinics in Scotland (UK). Patients were included if the neurologist rated their symptoms as ‘not at all’ or only ‘somewhat explained’ by organic disease. Patient-rated change in health was rated on a five-point Clinical Global Improvement (CGI) scale (‘much better’ to ‘much worse’) 1 year later.

The 12-month outcome data were available on 716 of 1144 patients (63%). Poor outcome on the CGI (‘unchanged’, ‘worse’ or ‘much worse’) was reported by 482 (67%) out of 716 patients. The only strong independent baseline predictors were patients' beliefs [expectation of non-recovery (odds ratio [OR] 2.04, 95% confidence interval [CI] 1.40–2.96), non-attribution of symptoms to psychological factors (OR 2.22, 95% CI 1.51–3.26)] and the receipt of illness-related financial benefits (OR 2.30, 95% CI 1.37–3.86). Together, these factors predicted 13% of the variance in outcome.

Of the patients, two-thirds had a poor outcome at 1 year. Illness beliefs and financial benefits are more useful in predicting poor outcome than the number of symptoms, disability and distress.