Individual differences in fear and fearlessness have been investigated at their extremes in relation to markedly different forms of psychopathology – anxiety disorders and psychopathy, respectively. A documented neural substrate of fear-related traits and disorders is defensive reactivity as reflected in aversive startle potentiation (ASP).

The current study extended prior work by characterizing, in a sample of adult twins from the community (n=2511), the phenotypic and etiologic structure of self-report measures of fear and fearlessness known to be associated with ASP.

Analyses revealed a hierarchical structure to the trait fear domain, with an overarching, bipolar fear/fearlessness dimension saturating each measure in this domain, and subfactors labeled ‘distress,’ ‘stimulation seeking’ and ‘sociability’ accounting for additional variance in particular measures. The structure of genetic and non-shared environmental associations among the measures closely mirrored the phenotypic structure of the domain.

The findings have implications for proposals to reconceptualize psychopathology in neurobiological terms.

Cannabis varies considerably in levels of its two major constituent cannabinoids – (delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Recently, we found evidence that those who smoked cannabis containing detectable levels of CBD had fewer psychotic-like symptoms than those whose cannabis had no CBD. The present study aimed, first, to replicate those findings and, second, to determine whether protective effects of CBD may extend to other harms of cannabis, such as memory impairment and reduced psychological well-being.

A total of 120 current cannabis smokers, 66 daily users and 54 recreational users were classified into groups according to whether analysis of their hair revealed the presence or absence of CBD and high versus low levels of THC. All were assessed on measures of psychosis-like symptoms, memory (prose recall; source memory) and depression/anxiety.

Lower psychosis-like symptoms were found in those whose hair had CBD compared with those without. However, this was seen only in recreational users, who had higher levels of THC in their hair. Higher THC levels in hair were associated with increased depression and anxiety. Prose recall and source memory were poorer in daily users with high THC levels in hair while recognition memory was better in individuals with CBD present in hair.

CBD attenuates the psychotic-like effects of cannabis over time in recreational users. Higher THC negatively impacts on memory and psychological well-being. These findings raise concerns for the harms stemming from use of varieties such as ‘skunk’ (sensimillia), which lack any CBD but currently dominate the supply of cannabis in many countries.

Hypothalamic–pituitary–adrenal (HPA) axis hyperactivity, associated with increased pituitary volume, may mediate observed alterations in stress reactivity in patients with psychotic disorder. We examined the association between pituitary volume, real-life stress reactivity and genetic liability for psychotic disorder.

Pituitary volumes were derived from magnetic resonance imaging (MRI) scans of 20 patients with psychotic disorder, 37 non-psychotic siblings of these patients, and 32 controls. The Experience Sampling Method (ESM) was used to measure emotional stress reactivity [changes in negative affect (NA) associated with daily life stress] in the three groups, and biological stress reactivity (changes in cortisol associated with daily life stress) in siblings and controls. Interactions between group, stress and pituitary volume in models of NA and cortisol were examined.

Groups did not differ in pituitary volume. Patients showed significantly higher emotional stress reactivity than siblings and controls. In addition, emotional stress reactivity increased with increasing pituitary volume to a greater degree in patients than in controls and siblings. Siblings had higher cortisol levels than controls but did not show increased cortisol reactivity to stress. There was no interaction between pituitary volume, stress and group in the model of cortisol.

Higher pituitary volume was associated with increased emotional stress reactivity in patients with psychotic disorder, siblings and controls. The association was significantly stronger in the patient group, suggesting a process of progressive sensitization mediating clinical outcome.

Generalized anxiety disorder (GAD) is highly co-morbid with depression. Depression is associated with elevated levels of the inflammation marker C-reactive protein (CRP), cross-sectionally and over time. To date, no studies have looked at the association between CRP and GAD.

A total of nine waves of data from the prospective population-based Great Smoky Mountains Study (n=1420) were used, covering children in the community aged 9–16, 19 and 21 years old. Structured interviews were used at each assessment to assess GAD symptoms, diagnosis and cumulative episodes. Blood spots were collected and assayed for high-sensitivity CRP levels.

GAD was associated with increased levels of CRP in bivariate cross-sectional analyses. These bivariate associations, however, were attenuated after accounting for demographic, substance-use and health-related covariates. In longitudinal models, there was little evidence that CRP predicted later GAD. Associations from GAD to later CRP were attenuated in models adjusted for health-related coavariates and there was evidence that the GAD–CRP association was mediated by body mass index (BMI) and medication use.

Similar to depression, GAD was associated with elevated levels of CRP, but the effect of GAD on CRP levels was explained by the effect of GAD on health-related behaviors such as BMI and medication use. This study suggests differences in the association between inflammation and depression and GAD.

There is now strong evidence that cannabis use increases the risk of psychoses including schizophrenia, but the relationship between cannabis and different psychotic disorders, as well as the mechanisms, are poorly known. We aimed to assess types of psychotic outcomes after use of cannabis in adolescence and variation in risk over time.

A cohort of 50 087 military conscripts with data on cannabis use in late adolescence was followed up during 35 years with regard to in-patient care for psychotic diagnoses.

Odds ratios for psychotic outcomes among frequent cannabis users compared with non-users were 3.7 [95% confidence interval (CI) 2.3–5.8] for schizophrenia, 2.2 (95% CI 1.0–4.7) for brief psychosis and 2.0 (95% CI 0.8–4.7) for other non-affective psychoses. Risk of schizophrenia declined over the decades in moderate users but much less so in frequent users. The presence of a brief psychosis did not increase risk of later schizophrenia more in cannabis users compared with non-users.

Our results confirm an increased risk of schizophrenia in a long-term perspective, although the risk declined over time in moderate users.

Although many studies indicate that maternal smoking during pregnancy (SDP) is correlated with later offspring antisocial behavior (ASB), recent quasi-experimental studies suggest that background familial factors confound the association. The present study sought to test alternative etiological hypotheses using multiple indices of adolescent ASB, comparing differentially exposed siblings, and testing assumptions in the sibling-comparison design.

The study examined the association between maternal SDP and adolescent-reported ASB, criminal convictions and membership in a group of individuals with early-starting and chronic ASB among 6066 offspring of women from the National Longitudinal Survey of Youth, a representative sample of women in the USA. The analyses controlled for statistical covariates and examined associations while comparing differentially exposed siblings.

At the population level, each additional pack of cigarettes per day predicted greater mean adolescent-reported ASB symptoms [ratio of means 1.15, 95% confidence interval (CI) 1.08–1.22], odds of being in the top 10% of ASB [odds ratio (OR) 1.34, 95% CI 1.10–1.65], hazard of a criminal conviction [hazard ratio (HR) 1.51, 95% CI 1.34–1.68] and odds of chronic ASB (OR 1.57, 95% CI 1.25–1.99). SDP robustly predicted most assessments of ASB while controlling for measured covariates. When siblings exposed to differing levels of SDP were compared, however, all of the associations were attenuated and were not statistically significant: adolescent-reported mean ASB (ratio of means 0.86, 95% CI 0.74–1.01), high ASB (OR 0.67, 95% CI 0.41–1.12), criminal conviction (HR 0.98, 95% CI 0.66–1.44) and chronic ASB (OR 0.80, 95% CI 0.46–1.38).

The results strongly suggest that familial factors account for the correlation between SDP and offspring adolescent ASB, rather than a putative causal environmental influence of SDP.

Cognitive behaviour therapy (CBT) is an effective treatment for obsessive–compulsive disorder (OCD) but access to CBT is limited. Internet-based CBT (ICBT) with therapist support is potentially a more accessible treatment. There are no randomized controlled trials testing ICBT for OCD. The aim of this study was to investigate the efficacy of ICBT for OCD in a randomized controlled trial.

Participants (n=101) diagnosed with OCD were randomized to either 10 weeks of ICBT or to an attention control condition, consisting of online supportive therapy. The primary outcome measure was the Yale–Brown Obsessive Compulsive Scale (YBOCS) administered by blinded assessors.

Both treatments lead to significant improvements in OCD symptoms, but ICBT resulted in larger improvements than the control condition on the YBOCS, with a significant between-group effect size (Cohen's d) of 1.12 (95% CI 0.69–1.53) at post-treatment. The proportion of participants showing clinically significant improvement was 60% (95% CI 46–72) in the ICBT group compared to 6% (95% CI 1–17) in the control condition. The results were sustained at follow-up.

ICBT is an efficacious treatment for OCD that could substantially increase access to CBT for OCD patients. Replication studies are warranted.

A subgroup of persons with anorexia nervosa (AN) have been proposed to have sociocommunicative problems corresponding to autism spectrum disorders [ASDs, i.e. DSM-IV pervasive developmental disorders (PDDs): autistic disorder, Asperger's disorder, PDD not otherwise specified (NOS)]. Here, clinical problems, personality traits, cognitive test results and outcome are compared across 16 subjects (32%) with teenage-onset AN who meet or have met ASD criteria (AN+ASD), 34 ASD-negative AN subjects and matched controls from a longitudinal Swedish study including four waves of independent assessments from the teens to the early thirties.

The fourth wave included the Structured Clinical Interview for DSM-IV (SCID)-I and the SCID-II (cluster C, i.e. ‘anxious’ PDs) interviews, the Asperger Syndrome Diagnostic Interview, self-assessments by the Autism Spectrum Quotient and the Temperament and Character Inventory, neurocognitive tests by subscales from the Wechsler scales, continuous performance tests, Tower of London, and Happé's cartoons.

The ASD assessments had substantial inter-rater reliability over time (Cohen's κ between 0.70 and 0.80 with previous assessments), even if only six subjects had been assigned a diagnosis of an ASD in all four waves of the study, including retrospective assessments of pre-AN neurodevelopmental problems. The AN+ASD group had the highest prevalence of personality disorders and the lowest Morgan–Russell scores. The non-ASD AN group also differed significantly from controls on personality traits related to poor interpersonal functioning and on neurocognitive tests.

A subgroup of subjects with AN meet criteria for ASDs. They may represent the extreme of neurocognitive and personality problems to be found more generally in AN.

The classification of psychological distress and illness behavior in the setting of medical disease is still controversial. Current psychiatric nosology does not seem to cover the spectrum of disturbances. The aim of this investigation was to assess whether the joint use of DSM-IV categories and the Diagnostic Criteria for Psychosomatic Research (DCPR), that provide identification of syndromes related to somatization, abnormal illness behavior, irritable mood, type A behavior, demoralization and alexithymia, could yield subtyping of psychosocial variables in the medically ill.

A cross-sectional assessment using both DSM-IV and the DCPR was conducted in eight medical centers in the Italian Health System. Data were submitted to cluster analysis. Participants were consecutive medical out-patients and in-patients for whom a psychiatric consultation was requested. A total of 1700 subjects met eligibility criteria and 1560 agreed to participate.

Three clusters were identified: non-specific psychological distress, irritability and affective disturbances with somatization.

Two-step cluster analysis revealed clusters that were found to occur across clinical settings. The findings indicate the need of expanding clinical assessment in the medically ill to include the various manifestations of somatization, illness behavior and subclinical distress encompassed by the DCPR.

When gambling opportunities are made available to the public in a given jurisdiction, some individuals participate occasionally and others more frequently. Among frequent gamblers, some individuals develop problematic involvement and some do not. This study addresses the association among demographic and social risk factors, frequency of gambling and gambling disorders.

Data from an adult community sample (n=1372) were used to identify risk factors for higher-frequency gambling and disordered gambling involvement.

Individuals with higher intelligence, older individuals and more religious individuals were less frequent gamblers. Males, single individuals and those exposed to gambling environments (friends and family who gamble) and those who started to gamble at a younger age were more frequent gamblers. Excitement-seeking personality traits were also higher among more frequent gamblers. A different set of risk factors was associated with the likelihood of gambling disorder among these higher-frequency gamblers. These variables included mental health indicators, childhood maltreatment and parental gambling involvement. Among higher-frequency gamblers, individuals who smoke cigarettes, those with a diagnosis of alcohol or drug dependence or obsessive–compulsive disorder, those with higher anxiety or depression and those with higher impulsivity and antisocial personality traits were more likely to report gambling-related problems. These individuals were also more likely to report gambling on electronic gambling machines (e.g. slot machines).

These data suggest a model in which higher-frequency gambling, particularly with electronic gambling machines, when combined with any type of emotional vulnerability increased the likelihood of gambling disorder.

One aim of personalized medicine is to determine which treatment is to be preferred for an individual patient, given all patient information available. Particularly in mental health, however, there is a lack of a single objective, reliable measure of outcome that is sensitive to crucial individual differences among patients.

We examined the feasibility of quantifying the total clinical value provided by a treatment (measured by both harms and benefits) in a single metric. An expert panel was asked to compare 100 pairs of patients, one from each treatment group, who had participated in a randomized clinical trial (RCT) involving interpersonal psychotherapy (IPT) and escitalopram, selecting the patient with the preferred outcome considering both benefits and harms.

From these results, an integrated preference score (IPS) was derived, such that the differences between any two patients' IPSs would predict the clinicians' preferences. This IPS was then computed for all patients in the RCT. A second set of 100 pairs was rated by the panel. Their preferences were highly correlated with the IPS differences (r=0.84). Finally, the IPS was used as the outcome measure comparing IPT and escitalopram. The 95% confidence interval (CI) for the effect size comparing treatments indicated clinical equivalence of the treatments.

A metric that combines benefits and harms of treatments could increase the value of RCTs by making clearer which treatments are preferable and, ultimately, for whom. Such methods result in more precise estimation of effect sizes, without increasing the required sample size.

There are no tested methods for conducting epidemiological studies of autism spectrum disorders (ASDs) in adult general population samples. We tested the validity of the Autism Diagnostic Observation Schedule module-4 (ADOS-4) and the 20-item Autism-Spectrum Quotient (AQ-20).

Randomly sampled adults aged ⩾16 years were interviewed throughout England in a general population multi-phase survey. The AQ-20 was self-completed by 7353 adults in phase 1. A random subset completed phase 2, ADOS-4 assessments (n=618); the probability of selection increased with AQ-20 score. In phase 3, informant-based Diagnostic Interview Schedule for Social and Communication Disorders (DISCO) and Autism Diagnostic Interview – Revised (ADI-R) developmental assessments were completed (n=56). Phase 1 and 2 data were presented as vignettes to six experienced clinicians (working in pairs). The probability of respondents having an ASD was compared across the three survey phases.

There was moderate agreement between clinical consensus diagnoses and ADOS-4. A range of ADOS-4 caseness thresholds was identified by clinicians: 5+ to 13+ with greatest area under the curve (AUC) at 5+ (0.88). Modelling of the presence of ASD using 56 DISCO assessments suggested an ADOS-4 threshold in the range of 10+ to 13+ with the highest AUC at ADOS 10+ to 11+ (0.93–0.94). At ADOS 10+, the sensitivity was 1 [95% confidence interval (CI) 0.59–1.0] and the specificity 0.86 (95% CI 0.72–0.94). The AQ-20 was only a weak predictor of ADOS-4 cases.

Clinically recommended ADOS-4 thresholds are also recommended for community cases: 7+ for subthreshold and 10+ for definite cases. Further work on adult population screening methods is needed.

Population data on conduct disorder (CD) symptoms can help determine whether hypothesized subtypes of CD are sufficiently disparate in their familial, psychiatric and life course correlates to distinguish separate diagnostic entities.

Latent class analysis (LCA) of CD symptoms occurring before age 15 was conducted in a national sample of adults aged 18–44 years from the National Epidemiological Study of Alcohol and Related Conditions. Associations of latent class membership with parental behavior problems, onset of psychiatric disorders and anti-social behaviors after age 15, adolescent life events (e.g. high school drop-out), and past-year life events (e.g. divorce/separation, bankruptcy) were estimated.

LCA identified a no-CD class with low prevalence of all symptoms, three intermediate classes – deceit/theft, rule violations, aggression – and a severe class. The prevalence of CD, according to DSM-IV criteria, was 0% in the no-CD class, between 13.33% and 33.69% in the intermediate classes and 62.20% in the severe class. Latent class membership is associated with all the familial, psychiatric and life course outcomes examined. Among the intermediate classes, risk for subsequent mood/anxiety disorders and anti-social behavior was higher in the deceit/theft and aggressive classes than in the rule violations class. However, risk for adolescent life events is highest in the rule violations class.

CD symptoms tend to occur in a partially ordered set of classes in the general population. Prognostically meaningful distinctions can be drawn between classes, but only at low levels of symptoms.

When women have a history of anorexia nervosa (AN), the advice given about becoming pregnant, and about the management of pregnancies, has usually been cautious. This study compared the pregnancy outcomes of women with and without a history of AN.

Women with a confirmed diagnosis of AN who had presented to psychiatric services in North East Scotland from 1965 to 2007 were identified. Those women with a pregnancy recorded in the Aberdeen Maternal and Neonatal Databank (AMND) were each matched by age, parity and year of delivery of their first baby with five women with no history of AN. Maternal and foetal outcomes were compared between these two groups of women. Comparisons were also made between the mothers with a history of AN and all other women in the AMND.

A total of 134 women with a history of AN delivered 230 babies and the 670 matched women delivered 1144 babies. Mothers with AN delivered lighter babies but this difference did not persist after adjusting for maternal body mass index (BMI) in early pregnancy. Standardized birthweight (SBW) scores suggested that the AN mothers were more likely to produce babies with intrauterine growth restriction (IUGR) [relative risk (RR) 1.54, 95% confidence interval (CI) 1.11–2.13]. AN mothers were more likely to experience antepartum haemorrhage (RR 1.70, 95% CI 1.09–2.65).

Mothers with a history of AN are at increased risk of adverse pregnancy outcomes. The magnitude of these risks is relatively small and should be appraised holistically by psychiatric and obstetric services.

The hormone ‘cortisol’ has been associated with cognitive deficits in older ages, and also with childhood cognition. The extent to which the associations of cortisol with cognitive deficits in later life reflect associations with childhood cognition ability is unclear. This study aimed to assess associations between adult cortisol levels and subsequent cognitive functions, while considering childhood cognition and other lifetime covariates.

Data are from the 1958 British Birth Cohort. Two morning salivary cortisol samples were obtained at 45 years: 45 min after waking (t1) and 3 h later (t2). Standardized tests assessing immediate and delayed verbal memory, verbal fluency and speed of processing were administered at 50 years. Information on cortisol, cognitive outcomes and covariates [e.g. birthweight, lifetime socio-economic position (SEP), education, smoking and drinking habits, body mass index (BMI), menopausal status, and depression/anxiety] was obtained for 4655 participants.

Worse immediate and delayed verbal memory and verbal fluency at 50 years were predicted by elevated t2 cortisol at 45 years. For instance, for 1 standard deviation (s.d.) increase in t2 cortisol, individuals scored −0.05 s.d. lower on verbal memory and fluency tests. Childhood cognition explained about 30% of these associations, but associations with adult cognition remained.

This study suggests that higher cortisol levels in late morning at 45 years are associated with poorer verbal memory and fluency at 50 years, with a contribution from childhood cognition to these associations.

Cognitive behaviour therapy (CBT) for chronic fatigue syndrome (CFS) is an effective but intensive treatment, requiring trained therapists. A minimal intervention based on CBT for CFS, guided self-instruction, was shown to be an effective treatment when delivered in a tertiary treatment centre. Implementing this intervention in a community-based mental health centre (MHC) will increase the treatment capacity for CFS patients. This study evaluated the effectiveness of guided self-instruction for CFS implemented in an MHC, delivered by nurses.

One hundred and twenty-three patients were randomly assigned to either guided self-instruction (n=62) or a waiting list (n=61). Randomization was computer generated, with allocation by numbered sealed envelopes. Group allocation was open to all those involved. Patients fulfilled US Centers for Disease Control and Prevention (CDC) criteria for CFS. Primary outcome variables were fatigue severity and physical and social functioning, measured with the Checklist Individual Strength (CIS) and the Medical Outcomes Survey Short Form-36 (SF-36) respectively.

After 6 months, patients who followed guided self-instruction reported a significantly larger decrease in fatigue compared to the waiting list [mean difference –8.1, 95% confidence interval (CI) −3.8 to −12.4, controlled effect size 0.70]. There was no significant difference in physical and social functioning. However, post-hoc analyses showed a significant decrease in fatigue and physical disabilities following the intervention in a subgroup of patients with physical disabilities at baseline (SF-36 physical functioning ⩽70).

Implementation of guided self-instruction in a community-based MHC was partially successful. The minimal intervention can be effectively implemented for CFS patients with physical impairments.

The increased occurrence of obstetric complications (OCs) in patients with schizophrenia suggests that alterations in neurodevelopment may be of importance to the aetiology of the illness. Abnormal cortical folding may reflect subtle deviation from normal neurodevelopment during the foetal or neonatal period. In the present study, we hypothesized that OCs would be related to cortical folding abnormalities in schizophrenia patients corresponding to areas where patients with schizophrenia display altered cortical folding when compared with healthy controls.

In total, 54 schizophrenia patients and 54 healthy control subjects underwent clinical examination and magnetic resonance image scanning on a 1.5 T scanner. Information on OCs was collected from original birth records. An automated algorithm was used to calculate a three-dimensional local gyrification index (lGI) at numerous points across the cortical mantle.

In both schizophrenia patients and healthy controls, an increasing number of OCs was significantly related to lower lGI in the left pars triangularis (p<0.0005) in Broca's area. For five other anatomical cortical parcellations in the left hemisphere, a similar trend was demonstrated. No significant relationships between OCs and lGI were found in the right hemisphere and there were no significant case–control differences in lGI.

The reduced cortical folding in the left pars triangularis, associated with OCs in both patients and control subjects suggests that the cortical effect of OCs is caused by factors shared by schizophrenia patients and healthy controls rather than factors related to schizophrenia alone.

Dysfunctions in the regulation of emotional responses are related to poor psychological well-being and increased impact of cardiovascular disease. It has been suggested that the relationship between negative affect and higher morbidity could be mediated by a dysregulation of the autonomic nervous system (ANS), for example, of heart rate variability (HRV). Neuroticism is a personality trait associated with a maladaptive emotion regulation and also with alterations in ANS function. However, it is unknown whether subjects with high neuroticism present with specific biases in emotion regulation associated with reduced HRV.

In total, 33 healthy subjects (n=13, highly neurotic) performed an emotion regulation task, during which they were instructed to either passively view negative pictures or attempt to down-regulate the affect elicited by the images. During the task an electrocardiogram was recorded and HRV was measured by calculation of the high frequency spectrum (HF-HRV).

A significant interaction between task condition and personality group was observed on HF-HRV measures (F1,31=6.569, p=0.016). This was driven by subjects with low neuroticism presenting higher HF-HRV during down-regulation compared to passive exposure to negative stimuli, while subjects with high neuroticism reported an opposite tendency.

Our results show reduced HF-HRV during cognitive reappraisal of negative stimuli in high neuroticism and indicate a specific link between loss of flexibility in the parasympathetic cardiovascular tone and emotion regulation, consistent with previous work. Such findings support the importance of exploring the combination of ANS adaptability and emotional dysregulation in neuroticism as different facets of a common psychosomatic vulnerability factor.