People with schizophrenia are often found to have smaller brains and larger brain ventricles than normal, but the role of antipsychotic medication remains unclear.

We conducted a systematic review of magnetic resonance imaging (MRI) studies. We included longitudinal studies of brain changes in patients taking antipsychotic drugs and we examined studies of antipsychotic-naive patients for comparison purposes.

Fourteen out of 26 longitudinal studies showed a decline in global brain or grey-matter volume or an increase in ventricular or cerebrospinal fluid (CSF) volume during the course of drug treatment, including the largest studies conducted. The frontal lobe was most consistently affected, but overall changes were diffuse. One large study found different degrees of volume loss with different antipsychotics, and another found that volume changes were associated with taking medication compared with taking none. Analyses of linear associations between drug exposure and brain volume changes produced mixed results. Five out of 21 studies of patients who were drug naive, or had only minimal prior treatment, showed some differences from controls in volumes of interest. No global differences were reported in three studies of drug-naive patients with long-term illness. Studies of high-risk groups have not demonstrated differences from controls in global or lobar brain volumes.

Some evidence points towards the possibility that antipsychotic drugs reduce the volume of brain matter and increase ventricular or fluid volume. Antipsychotics may contribute to the genesis of some of the abnormalities usually attributed to schizophrenia.

Schizotypy is conceptualized as a subclinical manifestation of the same underlying biological factors that give rise to schizophrenia and other schizophrenia spectrum disorders. Individuals with psychometric schizotypy (PS) experience subthreshold psychotic signs and can be psychometrically identified among the general population. Previous research using magnetic resonance imaging (MRI) has shown gray-matter volume (GMV) abnormalities in chronic schizophrenia, in subjects with an at-risk mental state (ARMS) and in individuals with schizotypal personality disorder (SPD). However, to date, no studies have investigated the neuroanatomical correlates of PS.

Six hundred first- and second-year university students completed the Community Assessment of Psychic Experiences (CAPE), a self-report instrument on psychosis proneness measuring attenuated positive psychotic experiences. A total of 38 subjects with high and low PS were identified and subsequently scanned with MRI. Voxel-based morphometry (VBM) was applied to examine GMV differences between subjects with high and low positive PS.

Subjects with high positive PS showed larger global volumes compared to subjects with low PS, and larger regional volumes in the medial posterior cingulate cortex (PCC) and the precuneus. There were no regions where GMV was greater in low than in high positive PS subjects.

These regions, the PCC and precuneus, have also been sites of volumetric differences in MRI studies of ARMS subjects and schizophrenia, suggesting that psychotic or psychotic-like experiences may have common neuroanatomical correlates across schizophrenia spectrum disorders.

Cognitive models suggest that auditory verbal hallucinations arise through defective self-monitoring and the external attribution of inner speech. We used a paradigm that engages verbal self-monitoring (VSM) to examine whether this process is impaired in people experiencing prodromal symptoms, who have a very high risk of developing psychosis.

We tested 31 individuals with an At-Risk Mental State (ARMS) and 31 healthy volunteers. Participants read single adjectives aloud while the source and pitch of the online auditory verbal feedback was manipulated, then immediately identified the source of the speech they heard (Self/Other/Unsure). Response choice and reaction time were recorded.

When reading aloud with distorted feedback of their own voice, ARMS participants made more errors than controls (misidentifications and unsure responses). ARMS participants misidentified the source of their speech as ‘Other’ when the level of acoustic distortion was severe, and misidentification errors were inversely related to reaction times.

Impaired VSM is evident in people with an ARMS, although the deficit seems to be less marked than in patients with schizophrenia. Follow-up of these participants may clarify the extent to which the severity of this impairment predicts the subsequent onset of psychosis and development of positive symptoms.

Theta cordance is a novel quantitative electroencephalography (QEEG) measure that correlates with cerebral perfusion. A series of clinical studies has demonstrated that the prefrontal theta cordance value decreases after 1 week of treatment in responders to antidepressants and that this effect precedes clinical improvement. Ketamine, a non-competitive antagonist of N-methyl-d-aspartate (NMDA) receptors, has a unique rapid antidepressant effect but its influence on theta cordance is unknown.

In a double-blind, cross-over, placebo-controlled experiment we studied the acute effect of ketamine (0.54 mg/kg within 30 min) on theta cordance in a group of 20 healthy volunteers.

Ketamine infusion induced a decrease in prefrontal theta cordance and an increase in the central region theta cordance after 10 and 30 min. The change in prefrontal theta cordance correlated with ketamine and norketamine blood levels after 10 min of ketamine infusion.

Our data indicate that ketamine infusion immediately induces changes similar to those that monoamineric-based antidepressants induce gradually. The reduction in theta cordance could be a marker and a predictor of the fast-acting antidepressant effect of ketamine, a hypothesis that could be tested in depressive patients treated with ketamine.

Data from a representative community sample were used to explore predictors of lifetime suicidality and to examine associations between distal adolescent and more proximal adult risks.

Data are from a midlife follow-up of the Isle of Wight study, an epidemiological sample of adolescents assessed in 1968. Ratings of psychiatric symptoms and disorder, relationships and family functioning and adversity were made in adolescence; adult assessments included lifetime psychiatric history and suicidality, neuroticism and retrospective reports of childhood sexual abuse and harsh parenting.

A wide range of measures of childhood psychopathology, adverse experiences and interpersonal difficulties were associated with adult suicidality; associations were particularly strong for adolescent irritability, worry and depression. In multivariate analyses, substantial proportions of these effects could be explained by their association with adult psychopathology and neuroticism, but additional effects remained for adolescent irritability and worry.

Factors of importance for long-term suicidality risk are evident in adolescence. These include family and experiential adversities as well as psychopathology. In particular, markers of adolescent worry and irritability appeared both potent risks and ones with additional effects beyond associations with adult disorder and adult neuroticism.

In countries where legal abortion is restricted, many unwanted pregnancies are carried to term. Attempting an unsuccessful abortion may influence women's mental health. This study investigated the common mental disorders (CMDs) of depression and anxiety in the third trimester of pregnancy in women who wanted or had attempted an abortion in a poor region of Brazil.

CMDs were assessed by using the 20-item Self-Reporting Questionnaire (SRQ-20) in all pregnant women aged 18–49 years who were registered with publicly funded primary health care in Recife, Northeast Brazil.

The study achieved a high response rate and 1121 (98.9%) women completed the interview. The prevalence of CMDs for the sample was 43.1% [95% confidence interval (CI) 40.2–46.1], and 63.6% (95% CI 55.4–71.2) among the 13.7% of women who attempted an abortion. The association between CMDs and attempted an abortion [odds ratio (OR) 2.05, 95% CI 1.3–3.1] remained after adjustment for confounders.

This study found that attempting an abortion in the current pregnancy was associated with CMDs. Good access to family planning programs, including access to contraceptive methods and safe abortion, should help to improve the mental health of women.

Major depressive disorder (MDD) co-occurs frequently with personality disorders (PDs). The extent to which this results from shared genetic or environmental risk factors remains uncertain.

Young adult twins (n=2801) from the population-based Norwegian Institute of Public Health Twin Panel were assessed at personal interview for DSM-IV lifetime MDD and the 10 Axis II PDs. The relationship between MDD and dimensional representations of all PDs was explored by stepwise logistic regression. Multivariate Cholesky twin models were fitted using the Mx program, and genetic and environmental correlations were estimated.

Dimensional representations of borderline (BPD), avoidant (AVPD) and paranoid personality disorder (PPD) were independently and significantly associated with increased risk for MDD. Multivariate twin modeling indicated that one latent factor accounted for the genetic covariance between MDD and the three PDs. The genetic correlations between MDD and dimensional representations of BPD, AVPD and PPD were +0.56, +0.22 and +0.40 respectively. No sex differences or shared environmental effects were found. The structure of the individual-specific environmental factors influencing MDD and the three PDs were similar to the genetic factors but the environmental correlations were lower: +0.39, +0.23 and +0.27 respectively.

There is substantial overlap between liability factors for MDD and BPD from cluster B, PPD from cluster A and AVPD from cluster C. The vulnerability to general PD pathology and MDD seem to be closely related. The patterns of co-morbidity observed between diverse psychiatric disorders might result from just a few liability factors.

High Neuroticism and low Conscientiousness are frequently implicated in health-risk behaviors, such as smoking and overeating, as well as health outcomes, including mortality. Their associations with physiological markers of morbidity and mortality, such as inflammation, are less well documented. The present research examines the association between the five major dimensions of personality and interleukin-6 (IL-6), a pro-inflammatory cytokine often elevated in patients with chronic morbidity and frailty.

A population-based sample (n=4923) from four towns in Sardinia, Italy, had their levels of IL-6 measured and completed a comprehensive personality questionnaire, the NEO-PI-R. Analyses controlled for factors known to have an effect on IL-6: age; sex; smoking; weight; aspirin use; disease burden.

High Neuroticism and low Conscientiousness were both associated with higher levels of IL-6. The findings remained significant after controlling for the relevant covariates. Similar results were found for C-reactive protein, a related marker of chronic inflammation. Further, smoking and weight partially mediated the association between impulsivity-related traits and higher IL-6 levels. Finally, logistic regressions revealed that participants either in the top 10% of the distribution of Neuroticism or the bottom 10% of conscientiousness had an approximately 40% greater risk of exceeding clinically relevant thresholds of IL-6.

Consistent with the literature on personality and self-reported health, individuals high on Neuroticism or low on Conscientiousness show elevated levels of this inflammatory cytokine. Identifying critical medical biomarkers associated with personality may help to elucidate the physiological mechanisms responsible for the observed connections between personality traits and physical health.

Prior research on whether marriage is equally beneficial to the mental health of men and women is inconsistent due to methodological variation. This study addresses some prior methodological limitations and investigates gender differences in the association of first marriage and being previously married, with subsequent first onset of a range of mental disorders.

Cross-sectional household surveys in 15 countries from the WHO World Mental Health survey initiative (n=34493), with structured diagnostic assessment of mental disorders using the Composite International Diagnostic Interview 3.0. Discrete-time survival analyses assessed the interaction of gender and marital status in the association with first onset of mood, anxiety and substance use disorders.

Marriage (versus never married) was associated with reduced risk of first onset of most mental disorders in both genders; but for substance use disorders this reduced risk was stronger among women, and for depression and panic disorder it was confined to men. Being previously married (versus stably married) was associated with increased risk of all disorders in both genders; but for substance use disorders, this increased risk was stronger among women and for depression it was stronger among men.

Marriage was associated with reduced risk of the first onset of most mental disorders in both men and women but there were gender differences in the associations between marital status and onset of depressive and substance use disorders. These differences may be related to gender differences in the experience of multiple role demands within marriage, especially those concerning parenting.

Certain parenting styles are influential in the emergence of later mental health problems, but less is known about the relationship between parenting style and later psychological well-being. Our aim was to examine the association between well-being in midlife and parental behaviour during childhood and adolescence, and the role of personality as a possible mediator of this relationship.

Data from 984 women in the 1946 British birth cohort study were analysed using structural equation modelling. Psychological well-being was assessed at age 52 years using Ryff's scales of psychological well-being. Parenting practices were recollected at age 43 years using the Parental Bonding Instrument. Extraversion and neuroticism were assessed at age 26 years using the Maudsley Personality Inventory.

In this sample, three parenting style factors were identified: care; non-engagement; control. Higher levels of parental care were associated with higher psychological well-being, while higher parental non-engagement or control were associated with lower levels of psychological well-being. The effects of care and non-engagement were largely mediated by the offspring's personality, whereas control had direct effects on psychological well-being. The psychological well-being of adult women was at least as strongly linked to the parenting style of their fathers as to that of their mothers, particularly in relation to the adverse effects of non-engagement and control.

This study used a prospective longitudinal design to examine the effects of parenting practices on psychological well-being in midlife. The effects of parenting, both positive and negative, persisted well into mid-adulthood.

Body image distortion is a key symptom of anorexia nervosa. In behavioral research two components of body image have been defined: attitudes towards the body and body size experience. Neuroimaging studies concerning own body image distortions in anorexia nervosa have revealed an inconsistent pattern of results and are constrained by the fact that no direct distinction between the different parts of body image has been made.

The present study therefore set out to investigate the neural correlates of two parts of the own body image using functional magnetic resonance imaging (fMRI): satisfaction rating and size estimation for distorted own body photographs in patients with anorexia nervosa and controls.

Anorectic patients were less satisfied with their current body shape than controls. Patients further demonstrated stronger activation of the insula and lateral prefrontal cortex during the satisfaction rating of thin self-images. This indicates a stronger emotional involvement when patients are presented with distorted images close to their own ideal body size. Patients also overestimated their own body size. We were able to show complex differential modulations in activation of the precuneus during body size estimation in control and anorectic subjects. It could be speculated that a deficit in the retrieval of a multimodal coded body schema in precuneus/posterior parietal cortex is related to body size overestimation.

We were able to find specific behavioral responses and neural activation patterns for two parts of body image in anorexia nervosa and healthy controls. Thus, the present results underline the importance of developing research and therapeutic strategies that target the two different aspects of body image separately.

Patients with anorexia nervosa (AN) overestimate their size despite being severely underweight. Whether this misperception echoes an underlying emotional disturbance or also reflects a genuine body-representation deficit is debatable. Current measures inquire directly about subjective perception of body image, thus distinguishing poorly between top-down effects of emotions/attitudes towards the body and disturbances due to proprioceptive disorders/distorted body schema. Disorders of body representation also emerge following damage to the right parietal lobe. The possibility that parietal dysfunction might contribute to AN is suspected, based on the demonstrated association of spatial impairments, comparable to those found after parietal lesion, with this syndrome.

We used a behavioral task to compare body knowledge in severe anorexics (n=8), healthy volunteers (n=11) and stroke patients with focal damage to the left/right parietal lobe (n=4). We applied a psychophysical procedure based on the perception, in the dark, of an approaching visual stimulus that was turned off before reaching the observer. Participants had to predict whether the stimulus would have hit/missed their body, had it continued its linear motion.

Healthy volunteers and left parietal patients estimated body boundaries very close to the real ones. Conversely, anorexics and right parietal patients underestimated eccentricity of their left body boundary.

These findings are in line with the role the parietal cortex plays in developing and maintaining body representation, and support the possibility for a neuropsychological component in the pathogenesis of anorexia, offering alternative approaches to treatment of the disorder.

Body dysmorphic disorder (BDD) is a poorly understood disorder that involves a preoccupation with imagined or minor bodily defects. Only a few studies of neuropsychological function have been conducted. Two previous studies have indicated executive dysfunction in BDD. The current study sought to further define these executive deficits.

Fourteen DSM-IV BDD patients and 14 age- and sex-matched control participants took part. Because of the high incidence of co-morbidity in BDD, patients with co-morbid Axis I disorders were not excluded. Control participants had no history of psychiatric illness. All participants completed the following executive function (EF) tests: Spatial Span (SS), Spatial Working Memory (SWM) and the Stockings of Cambridge (SOC) task. They also completed the Pattern Recognition (PR) test, a test of visual memory (VM).

BDD participants made significantly more between-search errors on the SWM task, an effect that increased with task difficulty. Between-search errors are an example of poor maintenance and manipulation of information. SOC results indicated slower subsequent thinking times (i.e. the time taken to plan) in BDD participants. There were no group differences in SS or PR scores. The severity of BDD, depressive or anxiety symptoms was not correlated with performance on any of the cognitive tasks.

The results of this study indicate that BDD patients have EF deficits in on-line manipulation, planning and organization of information. By contrast, spatial memory capacity, motor speed and visual memory were intact. Considered with evidence from lesion and neuroimaging studies, these results suggest frontal lobe dysfunction in BDD.

There is considerable debate surrounding the effective measurement of DSM-IV symptoms used to assess manic disorders in epidemiological samples.

Using two nationally representative datasets, the National Epidemiological Survey of Alcohol and Related Conditions (NESARC, n=43 093 at wave 1, n=34 653 at 3-year follow-up) and the National Comorbidity Survey – Replication (NCS-R, n=9282), we examined the psychometric properties of symptoms used to assess DSM-IV mania. The predictive utility of the mania factor score was tested using the 3-year follow-up data in NESARC.

Criterion B symptoms were unidimensional (single factor) in both samples. The symptoms assessing flight of ideas, distractibility and increased goal-directed activities had high factor loadings (0.70–0.93) with moderate rates of endorsement, thus providing good discrimination between individuals with and without mania. The symptom assessing grandiosity performed less well in both samples. The quantitative mania factor score was a good predictor of more severe disorders at the 3-year follow-up in the NESARC sample, even after controlling for a past history of DSM-IV diagnosis of manic disorder.

These analyses suggest that questions based on some DSM symptoms effectively discriminate between individuals at high and low liability to mania, but others do not. A quantitative mania factor score may aid in predicting recurrence for patients with a history of mania. Methods for assessing mania using structured interviews in the absence of clinical assessment require further refinement.

Psychopathy (PP) is associated with a performance deficit in a variety of stimulus–response and stimulus–reinforcement learning paradigms. We tested the hypothesis that failures in error monitoring underlie these learning deficits.

We measured electrophysiological correlates of error monitoring [error-related negativity (ERN)] during a probabilistic learning task in individuals with PP (n=13) and healthy matched control subjects (n=18). The task consisted of three graded learning conditions in which the amount of learning was manipulated by varying the degree to which the response was predictive of the value of the feedback (50, 80 and 100%).

Behaviourally, we found impaired learning and diminished accuracy in the group of individuals with PP. Amplitudes of the response ERN (rERN) were reduced. No differences in the feedback ERN (fERN) were found.

The results are interpreted in terms of a deficit in initial rule learning and subsequent generalization of these rules to new stimuli. Negative feedback is adequately processed at a neural level but this information is not used to improve behaviour on subsequent trials. As learning is degraded, the process of error detection at the moment of the actual response is diminished. Therefore, the current study demonstrates that disturbed error-monitoring processes play a central role in the often reported learning deficits in individuals with PP.

It has been hypothesized that stressful life events are associated with changes in hypothalamic–pituitary–adrenal (HPA) axis regulation, which increases susceptibility to psychiatric disorders. We investigated the association of early and late life events with HPA axis regulation in older persons.

Within the Longitudinal Aging Study Amsterdam (LASA) 1055 participants (47% male), aged 63–93 years, collected saliva within 30 min after waking and late in the evening. Early and late life events were assessed during a home interview. The associations between life events and cortisol levels were examined using linear regression and analysis of covariance with adjustments for demographics, cardiovascular risk factors and depressive symptoms.

Within our sample, the median morning and evening cortisol levels were 15.0 nmol/l [interdecile range (10–90%): 7.4–27.0 nmol/l] and 2.8 nmol/l (10–90%: 1.5–6.3 nmol/l), respectively. Persons who reported early life events showed lower levels of natural log-transformed morning cortisol [B=−0.10, 95% confidence interval (CI) −0.17 to −0.04] and flattened diurnal variability of cortisol (B=−1.06, 95% CI −2.05 to −0.08). Those reporting two or more late life events showed higher levels of natural log-transformed morning cortisol (B=0.10, 95% CI 0.02–0.18) and higher diurnal variability (B=1.19, 95% CI 0.05–2.33). No associations were found with evening cortisol.

The results of this large population-based study of older persons suggest a differential association of early and late life events with HPA axis regulation; early life events were associated with a relative hypo-secretion of morning cortisol and flattened diurnal variability, while late life events were associated with elevated secretion of morning cortisol and high diurnal variability of cortisol.