Recent evidence suggests that dopamine (DA) agonist-induced disruption of prepulse inhibition (PPI) depends on basal PPI values, in a manner that suggests an inverted U-shaped relationship between PPI and prefrontal DA levels. This is the first study to examine possible genetic determinants of PPI and the catechol O-methyltransferase (COMT) Val158Met polymorphism, the main catabolic pathway of released DA in the prefrontal cortex (PFC).

PPI was measured in 93 healthy males presented with 75-dB and 85-dB prepulses at 60-ms and 120-ms prepulse–pulse intervals. Subjects were grouped according to their COMT status into a Val/Val, a Val/Met and a Met/Met group.

ANOVAs showed that at all prepulse and interval conditions, Val/Val individuals had the lowest PPI, Met/Met the highest, and Val/Met were intermediate.

These results suggest that PPI is regulated by DA neurotransmission in the PFC and its levels depend on the COMT Val158Met gene polymorphism. These findings enhance the value of the PPI paradigm in examining individual variability of early information processing in healthy subjects and psychiatric disorders associated with changes in PFC DA activity and attentional deficits such as schizophrenia.

Diffusion tensor imaging (DTI) can be used to investigate cerebral structural connectivity in never-medicated individuals with first-episode schizophrenia.

Subjects with first-episode schizophrenia according to DSM-IV-R who had never been exposed to antipsychotic medication (n=25) and healthy controls (n=26) were recruited. Groups were matched for age, gender, best parental socio-economic status and ethnicity. All subjects underwent DTI and structural magnetic resonance imaging (MRI) scans. Voxel-based analysis was performed to investigate brain regions where fractional anisotropy (FA) values differed significantly between groups. A confirmatory region-of-interest (ROI) analysis of FA scores was performed in which regions were placed blind to group membership.

In patients, FA values significantly lower than those in healthy controls were located in the left fronto-occipital fasciculus, left inferior longitudinal fasciculus, white matter adjacent to right precuneus, splenium of corpus callosum, right posterior limb of internal capsule, white matter adjacent to right substantia nigra, and left cerebral peduncle. ROI analysis of the corpus callosum confirmed that the patient group had significantly lower mean FA values than the controls in the splenium but not in the genu. The intra-class correlation coefficient (ICC) for independent ROI measurements was 0.90 (genu) and 0.90 (splenium). There were no regions where FA values were significantly higher in the patients than in the healthy controls.

Widespread structural dysconnectivity, including the subcortical region, is already present in neuroleptic-naive patients in their first episode of illness.

Interrogative suggestibility and compliance are important psychological vulnerabilities during interrogation. The aim of the study was to investigate the relationship of suggestibility and compliance with childhood and current symptoms of attention deficit hyperactivity disorder (ADHD). Compliance has not been studied previously in relation to ADHD. A further aim was to investigate the relationship between ADHD and the reporting of having made a false confession to the police.

The participants were 90 male prisoners, all of whom had completed the Gudjonsson Suggestibility and Compliance Scales (GSS and GCS) within 10 days of admission to the prison. Childhood ADHD symptoms were screened by the Wender Utah Rating Scale (WURS) and current adult symptoms by the DSM-IV Checklist criteria for ADHD.

Half of the prisoners (50%) were found on screening to meet criteria for ADHD in childhood and, of those, over half (60%) were either fully symptomatic or in partial remission of their symptoms. ADHD symptoms were found to be significantly associated with compliance, but not with suggestibility. The relationship with compliance was stronger (effect size) in relation to current than childhood symptoms. The ADHD symptomatic groups were significantly more likely to claim that they had made a false confession to the police in the past.

The findings raise important questions about the potential vulnerability of adults with ADHD symptoms in terms of their ability to cope with interrogation.

Social dysfunction in personality disorder is commonly ascribed to abnormal temperamental traits but may also reflect deficits in social processing. In this study, we examined whether borderline and avoidant personality disorders (BPD, APD) may be differentiated by deficits in different social domains and whether disorganization of social domain functioning uniquely characterizes BPD.

Patients were recruited from psychiatric clinics in Pittsburgh, USA, to provide a sample with BPD, APD and a no-personality disorder (no-PD) comparison group. Standardized assessments of Axis I and Axis II disorders and social domain dysfunction were conducted, including a new scale of ‘domain disorganization’ (DD).

Pervasive social dysfunction was associated with a 16-fold increase in the odds of an Axis II disorder. Both APD and BPD were associated with elevated social dysfunction. Romantic relationship dysfunction was associated specifically with BPD symptoms and diagnosis. DD was associated specifically with a categorical BPD diagnosis and with a dimensional BPD symptom count.

A focus on the inherently interpersonal properties of personality disorders suggests specific mechanisms (within and across interpersonal domains) that may help to account for the origins and maintenance of some disorders. In particular, BPD reflects disturbances in romantic relationships, consistent with a role for attachment processes, and in the organization of functioning across social domains.

There is increasing evidence that certain environmental factors can modify genetic effects. This is an important area of investigation as such work will help to guide the development of new intervention programs. In this paper, we address whether rural environments moderate the genetic influence on adolescent substance use and rule-breaking behavior (i.e. externalizing psychopathology).

Over 1200 Minnesotan 17-year-old twins were classified as either urban or rural. Externalizing behavior was operationalized as the use and abuse of alcohol and drugs along with symptoms of conduct, oppositional defiant, and antisocial personality disorders. Biometric factor modeling estimated whether the relative contribution of genetic and shared environmental factors varied from urban to rural settings.

Residency effects reached statistical significance in the male sample only. In urban environments, externalizing behavior was substantially influenced by genetic factors, but in rural environments, shared environmental factors became more influential. This was apparent at both the individual-variable and factor levels.

These findings suggest a gene–environment interaction in the development of male adolescents' problem behaviors, including substance use. The results fit within an expanding literature demonstrating both the contextual nature of the heritability statistic and how certain environments may constrain the expression of genetic tendencies.

Ethnicity is an important determinant of mental health outcomes including suicidality (i.e. suicidal ideation and suicide attempt). Understanding ethnic differences in the pathways to suicidality is important for suicide prevention efforts in ethnically diverse populations. These pathways can be conceptualized within a social stress framework.

The study examines ethnic differences in the pathways to suicidality in Canada within a social stress framework. Using data from the Canadian Community Health Survey Cycle 1.1 (CCHS 1.1) and path analysis, we examined the hypotheses that variations in (1) socio-economic status (SES), (2) sense of community belonging (SCB), (3) SES and SCB combined, and (4) SES, SCB and clinical factors combined can explain ethnic differences in suicidality.

Francophone whites and Aboriginals were more likely to report suicidality compared to Anglophone whites whereas visible minorities and Foreign-born whites were least likely. Disadvantages in income, income and education, income and its combined effect with depression and alcohol dependence/abuse led to high rates even among the low-risk visible minority group. Indirect pathways for Asians differed from that of Blacks and South Asians, specifically through SCB. With the exception of SCB, Aboriginals were most disadvantaged, which exacerbated their risk for suicidality. However, their strong SCB buffered the risk for suicidality across pathways. Disadvantages in education, income and SCB were associated with the high risk for suicidality in Francophone whites.

Francophone whites and Aboriginals had higher odds of suicidality compared to Anglophone whites; however, some pathways differed, indicating the need for targeted program planning and prevention efforts.

Few large studies describe links between maternal mental illness and risk of major birth defect in offspring. Evidence is sparser still for how effects vary between maternal diagnoses and no previous study has assessed risk with paternal illnesses.

A population-based birth cohort was created by linking Danish national registers. We identified all singleton live births during 1973–1998 (n=1.45 m), all parental psychiatric admissions from 1969 onwards, and all fatal birth defects until 1 January 1999. Linkage and case ascertainment were almost complete. Relative risks were estimated using Poisson regression.

Risk of fatal birth defect was elevated in relation to history of any maternal admission and also with affective disorders specifically, although the strongest effect found was with maternal schizophrenia. The rate was more than doubled in this group compared to the general population [relative risk (RR) 2.34, 95% confidence interval (CI) 1.45–3.77], which also represented a significant excess risk compared with all other admitted maternal disorders (p=0.018). Risk of death from causes other than birth defect was no higher with schizophrenia than with other maternal conditions. There was no elevation in risk of fatal birth defect if the father was admitted with schizophrenia or any other psychiatric diagnosis.

There are many possible explanations for a higher risk of fatal birth defect with maternal schizophrenia and affective disorder. These include genetic effects directly linked with maternal illness, lifestyle factors (diet, smoking, alcohol and drugs), poor antenatal care, psychotropic medication toxicity, and gene–environment interactions. Further research is needed to elucidate the causal mechanisms.

Functional imaging studies using working memory tasks have documented both prefrontal cortex (PFC) hypo- and hyperactivation in schizophrenia. However, these studies have often failed to consider the potential role of task-related deactivation.

Thirty-two patients with chronic schizophrenia and 32 age- and sex-matched normal controls underwent functional magnetic resonance imaging (fMRI) scanning while performing baseline, 1-back and 2-back versions of the n-back task. Linear models were used to obtain maps of activations and deactivations in the groups.

The controls showed activation in the expected frontal regions. There were also clusters of deactivation, particularly in the anterior cingulate/ventromedial PFC and the posterior cingulate cortex/precuneus. Compared to the controls, the schizophrenic patients showed reduced activation in the right dorsolateral prefrontal cortex (DLPFC) and other frontal areas. There was also an area in the anterior cingulate/ventromedial PFC where the patients showed apparently greater activation than the controls. This represented a failure of deactivation in the schizophrenic patients. Failure to activate was a function of the patients' impaired performance on the n-back task, whereas the failure to deactivate was less performance dependent.

Patients with schizophrenia show both failure to activate and failure to deactivate during performance of a working memory task. The area of failure of deactivation is in the anterior prefrontal/anterior cingulate cortex and corresponds to one of the two midline components of the ‘default mode network’ implicated in functions related to maintaining one's sense of self.

There is increased interest in assessing the family history of psychiatric disorders for both genetic research and public health screening. It is unclear how best to combine family history reports into an overall score. We compare the predictive validity of different family history scores.

Probands from the Dunedin Study (n=981, 51% male) had their family history assessed for nine different conditions. We computed four family history scores for each disorder: (1) a simple dichotomous categorization of whether or not probands had any disordered first-degree relatives; (2) the observed number of disordered first-degree relatives; (3) the proportion of first-degree relatives who are disordered; and (4) Reed's score, which expressed the observed number of disordered first-degree relatives in terms of the number expected given the age and sex of each relative. We compared the strength of association between each family history score and probands' disorder outcome.

Each score produced significant family history associations for all disorders. The scores that took account of the number of disordered relatives within families (i.e. the observed, proportion, and Reed's scores) produced significantly stronger associations than the dichotomous score for conduct disorder, alcohol dependence and smoking. Taking account of family size (i.e. using the proportion or Reed's score) produced stronger family history associations depending on the prevalence of the disorder among family members.

Dichotomous family history scores can be improved upon by considering the number of disordered relatives in a family and the population prevalence of the disorder.

This study examined the associations between cigarette smoking and suicidal ideation and suicide attempts, both before and after control for potentially confounding using fixed effects regression models.

Data were gathered during the Christchurch Health and Development Study, a 25-year longitudinal study of a birth cohort of New Zealand children (635 males, 630 females). The analysis was based on a sample of 1041 participants with available data on cigarette smoking and suicidal behaviour from ages 16 to 25 years. The main outcome measures were suicidal ideation and suicide attempts, ages 16–18, 18–21, and 21–25.

There were significant bivariate associations between the frequency of cigarette smoking and both suicidal ideation and suicide attempts. Cohort members who smoked 20 or more cigarettes per day had odds of suicidal ideation that were 3.39 times (95% CI 2.06–5.59) those of non-smokers, and odds of suicide attempt that were 4.39 (95% CI 2.18–8.85) times those of non-smokers. Control for non-observed fixed confounding factors reduced the association between cigarette smoking and suicidal ideation and suicide attempts to statistical non-significance. After adjustment, those smoking more than 20 cigarettes per day had odds of suicidal ideation that were 1.00 times (95% CI 0.46–2.18) those of non-smokers, and odds of suicide attempt that were 1.84 (95% CI 0.81–4.18) times those of non-smokers.

The findings suggest that the associations between frequency of cigarette smoking and suicidal behaviour may largely be explained by the non-observed background factors and life circumstances that are associated with both cigarette smoking and suicidal behaviour.

Although attention deficit hyperactivity disorder (ADHD) and bipolar disorder (BPD) co-occur frequently and represent a particularly morbid clinical form of both disorders, neuroimaging research addressing this co-morbidity is scarce. Our aim was to evaluate the morphometric magnetic resonance imaging (MRI) underpinnings of the co-morbidity of ADHD with BPD, testing the hypothesis that subjects with this co-morbidity would have neuroanatomical correlates of both disorders.

Morphometric MRI findings were compared between 31 adults with ADHD and BPD and with those of 18 with BPD, 26 with ADHD, and 23 healthy controls. The volumes (cm3) of our regions of interest (ROIs) were estimated as a function of ADHD status, BPD status, age, sex, and omnibus brain volume using linear regression models.

When BPD was associated with a significantly smaller orbital prefrontal cortex and larger right thalamus, this pattern was found in co-morbid subjects with ADHD plus BPD. Likewise, when ADHD was associated with significantly less neocortical gray matter, less overall frontal lobe and superior prefrontal cortex volumes, a smaller right anterior cingulate cortex and less cerebellar gray matter, so did co-morbid ADHD plus BPD subjects.

Our results support the hypothesis that ADHD and BPD independently contribute to volumetric alterations of selective and distinct brain structures. In the co-morbid state of ADHD plus BPD, the profile of brain volumetric abnormalities consists of structures that are altered in both disorders individually. Attention to co-morbidity is necessary to help clarify the heterogeneous neuroanatomy of both BPD and ADHD.

Physical morbidity is a potent risk factor for depression onset and clearly increases with age, yet prior research has often found depressive disorders to decrease with age. This study tests the possibility that the relationship between age and mental disorders differs as a function of physical co-morbidity.

Eighteen general population surveys were carried out among household-residing adults as part of the World Mental Health (WMH) surveys initiative (n=42 697). DSM-IV disorders were assessed using face-to-face interviews with the Composite International Diagnostic Interview (CIDI 3.0). The effect of age was estimated for 12-month depressive and/or anxiety disorders with and without physical or pain co-morbidity, and for physical and/or pain conditions without mental co-morbidity.

Depressive and anxiety disorders decreased with age, a result that cannot be explained by organic exclusion criteria. No significant difference was found in the relationship between mental disorders and age as a function of physical/pain co-morbidity. The majority of older persons have chronic physical or pain conditions without co-morbid mental disorders; by contrast, the majority of those with mental disorders have physical/pain co-morbidity, particularly among the older age groups.

CIDI-diagnosed depressive and anxiety disorders in the general population decrease with age, despite greatly increasing physical morbidity with age. Physical morbidity among persons with mental disorder is the norm, particularly in older populations. Health professionals, including mental health professionals, need to address barriers to the management of physical co-morbidity among those with mental disorders.

Little is known about the prevalence or correlates of DSM-IV pathological gambling (PG).

Data from the US National Comorbidity Survey Replication (NCS-R), a nationally representative US household survey, were used to assess lifetime gambling symptoms and PG along with other DSM-IV disorders. Age of onset (AOO) of each lifetime disorder was assessed retrospectively. AOO reports were used to study associations between temporally primary disorders and the subsequent risk of secondary disorders.

Most respondents (78.4%) reported lifetime gambling. Lifetime problem gambling (at least one Criterion A symptom of PG) (2.3%) and PG (0.6%) were much less common. PG was significantly associated with being young, male, and Non-Hispanic Black. People with PG reported first gambling significantly earlier than non-problem gamblers (mean age 16.7 v. 23.9 years, z=12.7, p<0.001), with gambling problems typically beginning during the mid-20s and persisting for an average of 9.4 years. During this time the largest annual gambling losses averaged US$4800. Onset and persistence of PG were predicted by a variety of prior DSM-IV anxiety, mood, impulse-control and substance use disorders. PG also predicted the subsequent onset of generalized anxiety disorder, post-traumatic stress disorder (PTSD) and substance dependence. Although none of the NCS-R respondents with PG ever received treatment for gambling problems, 49.0% were treated at some time for other mental disorders.

DSM-IV PG is a comparatively rare, seriously impairing, and undertreated disorder whose symptoms typically start during early adulthood and is frequently secondary to other mental or substance disorders that are associated with both PG onset and persistence.

Psychotic illness is strongly associated with the maternal uniparental disomy (mUPD) genetic subtype of Prader–Willi syndrome (PWS), but not the deletion subtype (delPWS). This study investigates the clinical features of psychiatric illness associated with PWS. We consider possible genetic and other mechanisms that may be responsible for the development of psychotic illness, predominantly in those with mUPD.

The study sample comprised 119 individuals with genetically confirmed PWS, of whom 46 had a history of psychiatric illness. A detailed clinical and family psychiatric history was obtained from these 46 using the PAS-ADD, OPCRIT, Family History and Life Events Questionnaires.

Individuals with mUPD had a higher rate of psychiatric illness than those with delPWS (22/34 v. 24/85, p<0.001). The profile of psychiatric illness in both genetic subtypes resembled an atypical affective disorder with or without psychotic symptoms. Those with delPWS were more likely to have developed a non-psychotic depressive illness (p=0.005) and those with mUPD a bipolar disorder with psychotic symptoms (p=0.00005). Individuals with delPWS and psychotic illness had an increased family history of affective disorder. This was confined exclusively to their mothers.

Psychiatric illness in PWS is predominately affective with atypical features. The prevalence and possibly the severity of illness are greater in those with mUPD. We present a ‘two-hit’ hypothesis, involving imprinted genes on chromosome 15, for the development of affective psychosis in people with PWS, regardless of genetic subtype.

Mental health clinicians are frequently asked to assess the risks presented by patients making threats to kill, but there are almost no data to guide such an evaluation.

This data linkage study examined serious violence following making threats to kill and the potential role of mental disorder. A total of 613 individuals convicted of threats to kill had their prior contact with public mental health services established at the time of the index offence. The group's subsequent criminal convictions were established 10 years later using the police database. Death from suicidal or homicidal violence was also established.

Within 10 years, 44% of threateners were convicted of further violent offending, including 19 (3%) homicides. Those with histories of psychiatric contact (40%) had a higher rate (58%) of subsequent violence. The highest risks were in substance misusers, mentally disordered, young, and those without prior criminal convictions. Homicidal violence was most frequent among threateners with a schizophrenic illness. Sixteen threateners (2.6%) killed themselves, and three were murdered.

In contrast to the claims in the literature that threats are not predictive of subsequent violence, this study revealed high rates of assault and even homicide following threats to kill. The mentally disordered were over-represented among threat offenders and among those at high risk of subsequent violence. The mentally disordered threateners at highest risk of violence were young, substance abusing, but not necessarily with prior convictions. Those who threaten others were also found to be at greater risk of killing themselves or being killed.

Female patients with schizophrenia are less impaired in social life than male patients. Because social impairment in schizophrenia has been found to be associated with deficits in emotion recognition, we examined whether the female advantage in processing emotional prosody and semantics is preserved in schizophrenia.

Forty-eight patients (25 males, 23 females) and 46 controls (23 males, 23 females) were assessed using an emotional language task (in which healthy women generally outperform healthy men), consisting of 96 sentences in four conditions: (1) neutral-content/emotional-tone (happy, sad, angry or anxious); (2) neutral-tone/emotional-content; (3) emotional-tone/incongruous emotional-content; and (4) emotional-content/incongruous emotional-tone. Participants had to ignore the emotional-content in the third condition and the emotional-tone in the fourth condition. In addition, participants were assessed with a visuospatial task (in which healthy men typically excel). Correlation coefficients were computed for associations between emotional language data, visuospatial data, IQ measures and patient variables.

Overall, on the emotional language task, patients made more errors than control subjects, and women outperformed men across diagnostic groups. Controlling for IQ revealed a significant effect on task performance in all groups, especially in the incongruent tasks. On the rotation task, healthy men outperformed healthy women, but male patients, female patients and female controls obtained similar scores.

The advantage in emotional prosodic and semantic processing in healthy women is preserved in schizophrenia, whereas the male advantage in visuospatial processing is lost. These findings may explain, in part, why social functioning is less compromised in women with schizophrenia than in men.

Predicting cognitive deficits in early psychosis may well be crucial to identify those individuals most in need of receiving intensive intervention. As yet, however, the identification of potential pretreatment predictors for cognitive performance has been hampered by inconsistent findings across studies. We aimed to examine the associations of functional and clinical pretreatment variables with cognitive functioning after a first psychotic episode.

One hundred and thirty-one patients experiencing first-episode psychosis were assessed for psychopathology, pre-morbid functioning, duration of illness, age of onset, and family history of psychosis and neurocognitive functioning. Multiple regression analyses were conducted for six basic cognitive dimensions known to be affected in this population: verbal learning, verbal memory, verbal comprehensive abilities, executive functioning, motor dexterity and sustained attention.

Pre-morbid functioning was the main predictor for five out of the six basic cognitive domains. Pre-morbid social adjustment difficulties were associated with worse performance in executive functioning, motor dexterity and sustained attention. Academic functioning was associated with verbal comprehension, and verbal learning and memory. Gender, age of onset, duration of untreated psychosis, and family history of psychosis had no or limited value as predictors of neurocognitive outcome.

Poor pre-morbid functioning was related to a worse performance in the six basic cognitive dimensions evaluated; however, this accounted for only a small amount of the explained variance. Cognitive impairment is a prominent feature in patients with early psychosis regardless of favorable prognostic features such as short duration of illness, female gender, later age of onset, and non-family history of psychosis.

A potential association between schizophrenia and osteoporosis or osteopenia has recently been reported. Various factors affect bone mineral density (BMD) such as polydipsia, nicotine, alcohol abuse, lack of physical activity, an unbalanced diet, a lack of ultraviolet exposure and/or vitamin D. In addition, decreased BMD in women with schizophrenia has been attributed to drug-induced hyperprolactinaemia and/or secondary hypogonadism. This study was undertaken because empirical evidence from larger patient cohorts is limited and the data are still controversial.

Seventy-two premenopausal, regularly menstruating women suffering from schizophrenia and 71 age- and sex-matched healthy controls were included in the study. Biochemical markers of bone turnover (serum osteocalcin, urinary pyridinium crosslinks), parathyroid hormone and 25-hydroxyvitamin D were measured. BMD at the femoral neck and lumbar spine was determined by dual-energy X-ray absorptiometry in a subgroup of 59 patients. In addition, 17β-oestradiol, prolactin, testosterone, gonadotrophins and dehydroepiandrosterone sulfate were measured.

Compared with healthy controls, both markers of formation and resorption were increased in women with schizophrenia. However, in the subgroup of 59 patients, BMD was within the normal range. In women suffering from schizophrenia, testosterone levels were higher than in controls, and serum oestradiol levels were lower compared with the normal range.

Despite significantly increased bone turnover, we conclude that premenopausal and regularly menstruating women suffering from schizophrenia have normal spine and hip BMD. This may be due to the opposite effects of the various parameters influencing bone metabolism, especially of the gonadal hormones, and due to an intact coupling mechanism.