Most of our knowledge about borderline personality disorder features has been obtained through the study of clinical samples. Although these studies are important in their own right, they are limited in their ability to address certain important epidemiological and aetiological questions such as the degree to which there is a genetic influence on the manifestation of borderline personality disorder features. Though family history studies of borderline personality disorder indicate genetic influences, there have been very few twin studies and the degree of genetic influence on borderline personality disorder remains unclear.

Data were drawn from twin samples from The Netherlands (n=3918), Belgium (n=904) and Australia (n=674). In total, data were available on 5496 twins between the ages of 18 and 86 years from 3644 families who participated in the study by completion of a mailed self-report questionnaire on borderline personality disorder features.

In all countries, females scored higher than males and there was a general tendency for younger adults to endorse more borderline personality disorder features than older adults. Model-fitting results showed that additive genetic influences explain 42% of the variation in borderline personality disorder features in both men and women and that this heritability estimate is similar across The Netherlands, Belgium and Australia. Unique environmental influences explain the remaining 58% of the variance.

Genetic factors play a role in individual differences in borderline personality disorder features in Western society.

Stress is postulated to play an essential role in the expression of core borderline symptoms. However, the phenomenology of stress reactivity in borderline personality disorder remains unclear. The current study investigated the phenomenology of stress sensitivity in borderline personality disorder in the flow of daily life and compared this with stress sensitivity in patients suffering from psychotic disorders, a group so far known to report the largest reactivity to stress.

A total of 44 borderline patients, 42 patients with psychotic disorder and 49 healthy controls were studied with the Experience Sampling Method (a structured diary technique assessing current context and mood in daily life) to assess: (1) appraised subjective stress related to daily events and activities; and (2) emotional reactivity conceptualized as changes in positive and negative affect.

Multilevel regression analysis revealed that subjects with borderline personality disorder experienced significantly more emotional reactivity to daily life stress compared with both patients with psychosis and healthy controls, as evidenced by a larger increase in negative affect and a larger decrease in positive affect following stress.

These results are the first to ecologically validate the incorporation of stress reactive symptoms in the diagnosis of borderline personality disorder. Borderline patients continually react stronger than patients with psychosis and healthy controls to small disturbances that continually happen in the natural flow of everyday life. Altered emotional stress reactivity may define borderline personality disorder.

Schizophrenia and bipolar disorder have partly overlapping clinical profiles, which include an over-representation of substance-use behaviour. There are few previous studies directly comparing substance-use patterns in the two disorders. The objective of the present study was to compare the prevalence of substance use in schizophrenia and bipolar disorder, and investigate possible differences in pattern and frequency of use.

A total of 336 patients with schizophrenia or bipolar spectrum disorder from a catchment area-based hospital service were included in a cross-sectional study. In addition to thorough clinical assessments, patients were interviewed about drug-use history, habits and patterns of use. The prevalence and drug-use patterns were compared between groups.

Patients with bipolar disorder had higher rates of alcohol consumption, while schizophrenia patients more often used centrally stimulating substances, had more frequent use of non-alcoholic drugs and more often used more than one non-alcoholic drug. Single use of cannabis was more frequent in bipolar disorder.

The present study showed diagnosis-specific patterns of substance use in severe mental disorder. This suggests a need for more disease-specific treatment strategies, and indicates that substance use may be an important factor in studies of overlapping disease mechanisms.

Cannabis use may be a risk factor for schizophrenia. Part of this association may be explained by genotype–environment interaction, and part of it by genotype–environment correlation. The latter issue has not been explored. We investigated whether cannabis use is associated with schizophrenia, and whether gene–environment correlation contributes to this association, by examining the prevalence of cannabis use in groups with different levels of genetic predisposition for schizophrenia.

Case-control study of first-episode schizophrenia. Cases included all non-Western immigrants who made first contact with a physician for schizophrenia in The Hague, The Netherlands, between October 2000 and July 2005 (n=100; highest genetic predisposition). Two matched control groups were recruited, one among siblings of the cases (n=63; intermediate genetic predisposition) and one among immigrants who made contact with non-psychiatric secondary health-care services (n=100; lowest genetic predisposition). Conditional logistic regression analyses were used to predict schizophrenia as a function of cannabis use, and cannabis use as a function of genetic predisposition for schizophrenia.

Cases had used cannabis significantly more often than their siblings and general hospital controls (59, 21 and 21% respectively). Cannabis use predicted schizophrenia [adjusted odds ratio (OR) cases compared to general hospital controls 7.8, 95% confidence interval (CI) 2.7–22.6; adjusted OR cases compared to siblings 15.9 (95% CI 1.5–167.1)], but genetic predisposition for schizophrenia did not predict cannabis use [adjusted OR intermediate predisposition compared to lowest predisposition 1.2 (95% CI 0.4–3.8)].

Cannabis use was associated with schizophrenia but there was no evidence for genotype–environment correlation.

Cannabis use appears to be a risk factor for schizophrenia. Moreover, cannabis abusers show impaired decision-making capacities, linked to the orbitofrontal cortex (OFC). Although there is substantial evidence that first-episode schizophrenia patients show impairments in cognitive tasks associated with the dorsolateral prefrontal cortex (DLPFC), it is not clear whether decision making is impaired at schizophrenia onset. In this study, we examined the association between antecedents of cannabis abuse and cognitive impairment in cognitive tasks associated with the DLPFC and the OFC in a sample of first-episode patients with schizophrenia-spectrum disorders.

One hundred and thirty-two patients experiencing their first episode of a schizophrenia-spectrum psychosis were assessed with a cognitive battery including DLPFC-related tasks [backward digits, verbal fluency (FAS) and the Trail Making Test (TMT)] and an OFC-related task [the Iowa Gambling Task (GT)]. Performance on these tasks was compared between patients who had and had not abused cannabis before their psychosis onset.

No differences were observed between the two groups on the performance of any of the DLPFC-related tasks. However, patients who had abused cannabis before their psychosis onset showed a poorer total performance on the gambling task and a lower improvement on the performance of the task compared to no-abusers.

Pre-psychotic cannabis abuse is associated with decision-making impairment, but not working memory and executive function impairment, among first-episode patients with a schizophrenia-spectrum psychosis. Further studies are needed to examine the direction of causality of this impairment; that is, does the impairment make the patients abuse cannabis, or does cannabis abuse cause the impairment?

The relationship between cannabis use and psychosis is still a matter for debate. Accounting for the individual differences in subjective experiences to recreational cannabis use in the general population may hold some clues to the aetiological relationship between cannabis and psychotic symptoms. We hypothesized that schizotypy would account for the individual differences in subjective experiences after cannabis use but not in patterns of use.

In a sample of 532 young people who had used cannabis at least once, we examined the relationship between the Cannabis Experiences Questionnaire (CEQ) and the Schizotypal Personality Questionnaire (SPQ). Additionally, we examined the psychometric properties of the CEQ.

We replicated our previously reported findings that schizotypy was associated with increased psychosis-like experiences and after-effects, but also found that high-scoring schizotypes reported more pleasurable experiences when smoking cannabis. Using new subscales derived from principal components analysis (PCA), we found that the psychosis-like items were most related to varying rates of schizotypy both during the immediate use of cannabis and in the after-effects of cannabis use. High-scoring schizotypes who used cannabis experienced more psychosis-like symptoms during and after use.

Our results suggest that cannabis use may reveal an underlying vulnerability to psychosis in those with high schizotypal traits.

To investigate the association between nicotine dependence (ND), by cigarette smoking and use of smokeless tobacco (UST), and mental disorders.

Face-to-face surveys (n=43 093) were conducted in the 2001–2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Nicotine use, ND, and mental disorders were assessed using DSM-IV criteria.

UST-ND was associated with a significantly increased likelihood of any anxiety disorder, specific phobia, alcohol abuse and dependence. Consistent with previous findings, cigarette smoking-ND was associated with an increased likelihood of all mental disorders examined. Among those without ND, cigarette smoking was specifically associated with panic attacks and panic disorder; non-dependent UST was not associated with mental disorders.

Our findings suggest that the association between ND and mental disorders is relatively specific to the mode of nicotine administration. Among those who are nicotine dependent, cigarette use is associated with most major psychiatric disorders, whereas UST is associated with dysthymia and specific phobia. Among those who use tobacco but are not nicotine dependent, cigarette use is associated with dysthymia and panic disorder; UST is not associated with any major mood or anxiety disorders. The link between mental disorders and nicotine is complex, and is associated primarily with dependence, and not with non-dependent use.

Smoking initiation and persistence are clearly associated with factors commonly thought to be environmental in origin, including socio-economic status. However, twin models that incorporate gene–environment correlation and gene×environment interaction have not been applied to elucidate the genetic or environmental role that socio-economic status plays in smoking initiation and nicotine dependence.

Twin structural equation modelling was used to examine gene–environment correlation and gene×environment interaction of one index of socio-economic status, educational attainment, with smoking initiation and nicotine dependence among 5119 monozygotic and 4295 dizygotic male–male Vietnam-era twins from the Vietnam Era Twin Registry, a national registry of twin pairs who served in the military during the Vietnam era.

Educational attainment correlated significantly with smoking initiation (r=−0.27, p<0.001). Additive genetic (p=0.011), shared environment (p=0.002) and unique environment (p=0.027) components contributed to the correlation between educational attainment and smoking initiation. Educational attainment also significantly moderated the variance in smoking initiation (p<0.001), suggestive of gene×environment interaction, although the interaction with the additive genetic, shared environmental and unique environmental components could not be resolved due to multicollinearity. In contrast, educational attainment neither correlated with nor moderated nicotine dependence, once smokers had initiated.

Our study suggests that educational attainment is associated with smoking initiation, in part due to gene–environment correlation and gene×environment interaction. However, once smoking initiation is taken into account, there are no effects – be they gene–environment correlation or gene×environmental interaction – of educational attainment on nicotine dependence.

We investigated 12 variables and their interactions as correlates of smoking cessation among regular smokers in the population-based Swedish Twin Registry (STR).

Detailed information on tobacco use and personal characteristics were available from 14 715 male and female twins aged 42–64 years who participated in a screening of the population-based STR and reported being regular smokers in their lifetime. A two-stage analytic design was used to examine correlates of smoking cessation. The sample was split at random and significant main effects and interactions identified in the testing set were examined in the validation set. Hazard ratios (HRs) and 95% confidence intervals (CIs) describe the association between correlates and smoking cessation.

Twelve main effects were significantly associated with smoking cessation in the testing set; eight were confirmed in the validation set. Of the nine interactions identified in the testing set, none remained significant when evaluated in the validation set after Bonferroni correction. HRs were highest for Swedish oral smokeless tobacco (snus) use (HR 2.70, 95% CI 2.30–3.20), >11 years of education (HR 1.57, 95% CI 1.43–1.73) and being married or cohabitating (HR 1.51, 95% CI 1.39–1.63). Although not statistically significant after Bonferroni correction, snus use also appeared important in the context of interactions, where lower nicotine dependence score, higher socio-economic status (SES) and greater body size were associated with smoking cessation only among participants who never used snus.

Snus use was the strongest independent correlate of smoking cessation. Further studies should investigate the mechanism of this association.

A large number of studies, reviews and meta-analyses have reported cognitive deficits in ecstasy users. However most ecstasy users are polydrug users, and therefore it cannot be excluded that these deficits are (partly) the result of drugs other than ecstasy. The current study, part of the Netherlands XTC Toxicity (NeXT) study, investigates the specific sustained effects of ecstasy relative to amphetamine, cocaine and cannabis on the brain using neuropsychological examination.

A stratified sample of 67 subjects with such a variation in type and amount of drug use was included that correlations between the consumption of the various drugs were relatively low allowing stepwise linear multiple regression analyses to differentiate between the effects of ecstasy and those of other substances. Subjects were assessed with neuropsychological tests measuring attention, working memory, verbal and visuospatial memory, and visuospatial ability.

Ecstasy use [mean 327 (s.d.=364) tablets in lifetime] had a specific significant dose-related negative effect on verbal delayed recall after adjusting for the use of other drugs.

These findings strongly suggest a specific sustained negative effect of ecstasy use on verbal memory. The clinical relevance is not immediately clear, because test performance generally remained within the normal range. However the magnitude of the effect is substantial (d>0.5) and long-term consequences cannot be excluded.

Although there have been several reports linking ecstasy use with lowered cognitive function, much previous research suffers from substantial methodological limitations. The present study aimed to examine associations between ecstasy use and higher-level cognitive functions, using a larger sample size than most previous research and better controlling for a range of potential confounds.

A cross-sectional cohort design assessed 45 currently abstinent ecstasy polydrug users (EP), 48 cannabis polydrug users (CP) and 40 legal drug users (LD). Standardized neuropsychological tests were used to measure attention, verbal, visual and working memory and executive function. Prospective memory function was also assessed.

It was not possible to discriminate between groups on the basis of the cognitive functions assessed. Regression analyses showed an inverse association between lifetime dose of ecstasy and verbal memory performance. A combination of drug-use variables, including measures of ecstasy use, contributed to prediction of attention/working memory. However, individual associations were small, explaining 1–6% of variance in cognitive scores.

Although the results suggest that heavy use of ecstasy is associated with some lowering of higher-level cognitive functions, they do not indicate a clinical picture of substantial cognitive dysfunction.

The attention-grabbing properties of drugs to drug-using individuals have been well documented and recent research has begun to suggest that such attentional bias may be related to the severity of drug dependency. Dependence on ketamine has been reported anecdotally but no systematic study has investigated this phenomenon. We aimed to explore attentional biases to incentive stimuli in different populations of ketamine users.

Using a dot-probe paradigm, attentional bias to both drug-related and money-related stimuli was investigated in 150 participants: 30 frequent ketamine users, 30 infrequent ketamine users, 30 ex-ketamine users, 30 poly-drug users and 30 non-drug-using controls. Two stimulus presentation times were used (200 and 2000 ms) to investigate whether attentional bias was as a result of an automatic or a more conscious attentional shift. Participants also rated the degree to which stimuli used in the dot-probe paradigm were pleasurable.

Frequent ketamine users demonstrated an attentional bias to both types of incentive stimuli only at the short stimulus presentation interval and this was significantly correlated with degree of ketamine use. No attentional biases were observed in any of the other groups. All groups rated money stimuli as more pleasurable than neutral stimuli.

These data support incentive models of drug use and demonstrate the ability of the attentional bias paradigm to discriminate recreational drug users from those with more dependent patterns of use. Ketamine is a potentially dependence-forming drug.

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.

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.

The DSM-IV-R classification Pervasive Developmental Disorder – Not otherwise Specified (PDD-NOS) is based on the symptoms for autism and includes a wide variety of phenotypes that do not meet full criteria for autism. As such, PDD-NOS is a broad and poorly defined residual category of the autism spectrum disorders. In order to address the heterogeneity in this residual category it may be helpful to define clinical and neurobiological subtypes. Multiple complex developmental disorder (MCDD) may constitute such a subtype. In order to study the neurobiological specificity of MCDD in comparison with other autism spectrum disorders, we investigated brain morphology in children (age 7–15 years) with MCDD compared to children with autism and typically developing controls.

Structural MRI measures were compared between 22 high-functioning subjects with MCDD and 21 high-functioning subjects with autism, and 21 matched controls.

Subjects with MCDD showed an enlarged cerebellum and a trend towards larger grey-matter volume compared to control subjects. Compared to subjects with autism, subjects with MCDD had smaller intracranial volume.

We report a pattern of volumetric changes in the brains of subjects with MCDD, similar to that seen in autism. However, no enlargement in head size was found. This suggests that although some of the neurobiological changes associated with MCDD overlap with those in autism, others do not. These neurobiological changes may reflect differences in the developmental trajectories associated with these two subtypes of autism spectrum disorders.