No prior twin study has explored the heritability of clinically diagnosed attention deficit hyperactivity disorder (ADHD). Such studies are needed to resolve conflicting results regarding the importance of genetic effects for ADHD in adults. We aimed to estimate the relative contribution of genetic and environmental influences for clinically diagnosed ADHD across the lifespan with a specific focus on ADHD in adults.

Information on zygosity and sex was obtained from 59514 twins born between 1959 and 2001 included in the nationwide population-based Swedish Twin Registry. Clinical data for ADHD diagnoses (i.e. stimulant or non-stimulant medication for ADHD) were obtained from the Swedish Prescribed Drug Register (PDR) and from the National Patient Register (i.e. ICD-10 diagnosis of ADHD). Twin methods were applied to clinical data of ADHD diagnoses using structural equation modeling with monozygotic (MZ) and dizygotic (DZ) twins.

The best-fitting model revealed a high heritability of ADHD [0.88, 95% confidence interval (CI) 0.83–0.92] for the entire sample. However, shared environmental effects were non-significant and of minimal importance. The heritability of ADHD in adults was also substantial (0.72, 95% CI 0.56–0.84).

This study shows that the heritability of clinically diagnosed ADHD is high across the lifespan. Our finding of high heritability for clinically diagnosed ADHD in adults indicates that the previous reports of low heritability are best explained by rater effects, and that gene-identification studies of ADHD in adults need to consider pervasiveness (e.g. multiple raters) and developmentally (e.g. childhood-onset criteria) informative data.

Research into age of onset in obsessive–compulsive disorder (OCD) has indicated significant differences between patients with early and late onset of the disorder. However, multiple criteria have been used arbitrarily for differentiating between early- and late-onset OCD, rendering inconsistent results that are difficult to interpret.

In the current study, admixture analysis was conducted in a sample of 377 OC patients to determine the number of underlying populations of age of onset and associated demographic and clinical characteristics. Various measures of anxiety, depression, co-morbidity, autism, OCD, tics and attention deficit hyperactivity disorder (ADHD) symptoms were administered.

A bimodal age of onset was established and the best-fitting cut-off score between early and late age of onset was 20 years (early age of onset ⩽19 years). Patients with early age of onset were more likely to be single. Early age of onset patients demonstrated higher levels of OCD severity and increased symptoms on all OCD dimensions along with increased ADHD symptoms and higher rates of bipolar disorder.

It is suggested that 20 years is the recommended cut-off age for the determination of early versus late age of onset in OCD. Early age of onset is associated with a generally graver OCD clinical picture and increased ADHD symptoms and bipolar disorder rates, which may be related to greater functional implications of the disorder. We propose that age of onset could be an important marker for the subtyping of OCD.

Sensitivity to punishment (SP) and sensitivity to reward (SR) are personality characteristics that may have relevance for the pathophysiology of eating disorders (EDs). Moreover, personality characteristics are known to modulate the activity of the hypothalamus–pituitary–adrenal (HPA) axis, which is the main component of the endogenous stress response system. As stress has been implicated in the aetiology and the maintenance of EDs, we aimed to study the HPA axis activity in relation to SP and SR, as conceptualized by Gray's reinforcement sensitivity theory (RST), in patients with anorexia nervosa (AN) or bulimia nervosa (BN).

Twenty-five women with AN, 23 women with BN and 19 healthy women volunteered for the study. HPA axis activity was assessed by measurement of the salivary cortisol awakening response (CAR). The subjects’ SP and SR were measured by the behavioural inhibition system (BIS)/behavioural approach system (BAS) scales.

The CAR was significantly enhanced in AN patients, but not in BN patients, compared to healthy women. The CAR correlated significantly with BAS measures, negatively in healthy controls and positively in binge-purging AN patients and BN women. SP, measured by the BIS scale, was higher in patients than in controls.

These findings confirm the occurrence of an enhanced activity of the HPA axis in symptomatic AN, but not in symptomatic BN, and show for the first time that the CAR is associated with SR, as conceptualized by the RST, negatively in healthy subjects but positively in binge-purging ED patients.

Elucidating the cognitive architecture of schizophrenia promises to advance understanding of the clinical and biological substrates of the illness. Traditional cross-sectional neuropsychological approaches differentiate impaired from normal cognitive abilities but are limited in their ability to determine latent substructure. The current study examined the latent architecture of abnormal cognition in schizophrenia via a systematic approach.

Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were carried out on a large neuropsychological dataset including the Brief Assessment of Cognition in Schizophrenia, Continuous Performance Test, Wisconsin Card Sorting Test, Benton Judgment of Line Orientation Test, and Wechsler Abbreviated Scale of Intelligence matrix reasoning derived from 1012 English-speaking ethnic Chinese healthy controls and 707 schizophrenia cases recruited from in- and out-patient clinics.

An initial six-factor model fit cognitive data in healthy and schizophrenia subjects. Further modeling, which accounted for methodological variance between tests, resulted in a three-factor model of executive functioning, vigilance/speed of processing and memory that appeared to best discriminate schizophrenia cases from controls. Factor analytic-derived g estimands and conventionally calculated g showed similar case–control discrimination. However, agreement analysis suggested systematic differences between both g indices.

Factor structures derived in the current study were broadly similar to those reported previously. However, factor structures between schizophrenia subjects and healthy controls were different. Roles of factor analytic-derived g estimands and conventional composite score g were further discussed. Cognitive structures underlying cognitive deficits in schizophrenia may prove useful for interrogating biological substrates and enriching effect sizes for subsequent work.

As relapse after completed cognitive behavior therapy (CBT) for obsessive–compulsive disorder (OCD) is common, many treatment protocols include booster programs to improve the long-term effects. However, the effects of booster programs are not well studied. In this study, we investigated the long-term efficacy of Internet-based CBT (ICBT) with therapist support for OCD with or without an Internet-based booster program.

A total of 101 participants were included in the long-term follow-up analysis of ICBT. Of these, 93 were randomized to a booster program or no booster program. Outcome assessments were collected at 4, 7, 12 and 24 months after receiving ICBT.

The entire sample had sustained long-term effects from pre-treatment to all follow-up assessments, with large within-group effect sizes (Cohen's d = 1.58–2.09). The booster group had a significant mean reduction in OCD symptoms compared to the control condition from booster baseline (4 months) to 7 months, but not at 12 or 24 months. Participants in the booster group improved significantly in terms of general functioning at 7, 12 and 24 months, and had fewer relapses. Kaplan–Meier analysis also indicated a significantly slower relapse rate in the booster group.

The results suggest that ICBT has sustained long-term effects and that adding an Internet-based booster program can further improve long-term outcome and prevent relapse for some OCD patients.

Persons with severe mental illness (SMI) have excess mortality, which may partly be explained by their high prevalence of diabetes.

We compared the overall and cause-specific mortality in persons with SMI and diabetes with that of the general Danish population between 1997 and 2009 by linking data from Danish national registries.

The cohort counted 4 734 703 persons, and during follow-up 651 080 persons died of whom 1083 persons had SMI and diabetes. Compared with the background population, the overall mortality rate ratios (MRRs) for persons with SMI and diabetes were 4.14 [95% confidence interval (CI) 3.81–4.51] for men and 3.13 (95% CI 2.88–3.40) for women. The cause-specific MRRs for persons with SMI and diabetes were lowest for malignant neoplasms (women: MRR = 1.98, 95% CI 1.64–2.39; men: MRR = 2.08, 95% CI 1.69–2.56) and highest for unnatural causes of death (women: MRR = 12.31, 95% CI 6.80–22.28; men: MRR = 7.89, 95% CI 5.51–11.29). The cumulative risks of death within 7 years of diabetes diagnosis for persons with SMI and diabetes were 15.0% (95% CI 12.4–17.6%) for those younger than 50 years, 30.7% (95% CI 27.8–33.4%) for those aged 50–69 years, and 63.8% (95% CI 58.9–68.2%) for those aged 70 years or older. Among persons suffering from both diseases, 33.4% of natural deaths were attributed to diabetes and 14% of natural deaths were attributed to the interaction between diabetes and SMI.

Long-term mortality is high for persons with SMI and diabetes. This calls for effective intervention from a coordinated and collaborating healthcare system.

Mental health problems are common in primary care, with prevalence rates of up to 40% reported in developing countries. The study aim was to evaluate the impact of a specially designed toolkit used to train primary health care (PHC) workers in mental health on the rates of diagnosed cases of common mental disorders, malaria and non-specific musculoskeletal pains in primary care in Malawi.

Clinics with out-patient services in the designated district were randomly divided into control and intervention arms. Using a two-phase sampling process, Self-Reporting Questionnaire scores, data on diagnoses made by PHC workers and results of the Structured Clinical Interview for DSM-IV for depression were collected from 837 consecutively attending adult patients in the pre-intervention study and 2600 patients in the post-intervention study.

The point prevalence rates for probable common mental disorder and depression were 28.8% and 19%, respectively. Rates for both anxiety and depression diagnoses by PHC workers at baseline were 0% in both arms. Following training, there were significant differences between the two arms in the rates of diagnosed cases of depression [9.2% v. 0.5%, odds ratio (OR) 32.1, 95% confidence interval (CI) 7.4–144.3, p ⩽ 0.001], anxiety (1.2% v. 0%, p ⩽ 0.001) and malaria (31% v. 40%, OR 0.62, 95% CI 0.43–0.89, p = 0.01). The intervention arm had more cases diagnosed with depression and anxiety while the control arm had more cases diagnosed with malaria.

Training of PHC workers in mental health with an appropriate toolkit will contribute significantly to the quality of detection and management of patients seen in primary care in developing countries.

Although attention deficit hyperactivity disorder (ADHD) has been associated with a broad range of deficits across various neuropsychological domains, most studies have assessed only a narrow range of neuropsychological functions. Direct cross-domain comparisons are rare, with almost all studies restricted to less than four domains. Therefore, the relationships between these various domains remain undefined. In addition, almost all studies included previously medicated participants, limiting the conclusions that can be drawn. We present the first study to compare a large cohort of medication-naive boys with ADHD with healthy controls on a broad battery of neuropsychological tasks, assessing six key domains of neuropsychological functioning.

The neuropsychological functioning of 83 medication-naive boys with well-characterized ADHD (mean age 8.9 years) was compared with that of 66 typically developing (TYP) boys (mean age 9.0 years) on a broad battery of validated neuropsychological tasks.

Data reduction using complementary factor analysis (CFA) confirmed six distinct neuropsychological domains: working memory, inhibition, delay aversion, decision making, timing and response variability. Boys with ADHD performed less well across all six domains although, for each domain, only a minority of boys with ADHD had a deficit [effect size (% with deficit) ADHD versus TYP: working memory 0.95 (30.1), inhibition 0.61 (22.9), delay aversion 0.82 (36.1), decision making 0.55 (20.5), timing 0.71 (31.3), response variability 0.37 (18.1)].

The clinical syndrome of ADHD is neuropsychologically heterogeneous. These data highlight the complexity of the relationships between the different neuropsychological profiles associated with ADHD and the clinical symptoms and functional impairment.

Emotional lability (EL), characterized by negative emotional traits and emotional instability, is frequently reported in children and adults with attention deficit hyperactivity disorder (ADHD). However, EL is primarily assessed using retrospective self-report, which is subject to reporting bias and does not consider the potential influence of positive and negative everyday experiences.

Ambulatory assessment was carried out in 41 men with ADHD without co-morbidity, current medication or substance abuse, and 47 healthy control participants. Reports of negative and positive emotions (irritability, frustration, anger, happiness, excitement) and the occurrence of bad and good events were completed eight times daily during a working week. Group differences in emotional intensity and instability were investigated using multilevel models, and explored in relation to bad and good events and the Affective Lability Scale – Short Form (ALS-SF), an EL questionnaire.

The ADHD group reported significantly more frequent bad events, heightened intensity and instability of irritability and frustration, and greater intensity of anger. The results for positive emotions were equivocal or negative. Bad events significantly contributed to the intensity and instability of negative emotions, and showed a stronger influence in the ADHD group. However, covariation for their effect did not eliminate group differences. Small-to-moderate correlations were seen between intensity and instability of negative emotions and the ALS-SF.

Adults with ADHD report heightened intensity and instability of negative emotions in daily life. The results suggest two components of EL in ADHD: a reactive component responsive to bad events and an endogenous component, independent of negative everyday events.

Substantial overlap has been reported between attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Deficits in executive function (EF) are characteristic of both disorders but these impairments have not been compared directly across pure and co-morbid cases using event-related potentials (ERPs).

Behavioural parameters and ERPs were recorded during a flankered cued-continuous performance test (CPT-OX) administered to 8–13-year-old boys with ASD (n = 19), ADHD (n = 18), co-morbid ASD + ADHD (n = 29) and typically developing controls (TD; n = 26). Preparatory processing (contingent negative variation, CNV) and attentional orienting (Cue-P3) at cues, response execution at targets (Go-P3), inhibitory processing at non-targets (NoGo-P3) and conflict monitoring between target and non-target trials (Go-N2 v. NoGo-N2) were examined.

Categorical diagnoses and quantitative trait measures indicated that participants with ADHD (ADHD/ASD + ADHD) made more omission errors and exhibited increased reaction-time (RT) variability and reduced amplitude of the Cue-P3 and NoGo-P3 compared to TD/ASD participants. Participants with ASD (ASD/ ASD + ADHD) demonstrated reduced N2 enhancement from Go to NoGo trials compared to TD/ADHD participants. Participants with ASD-only displayed enhanced CNV amplitude compared to ASD + ADHD and TD participants.

Children with ADHD show deficits in attentional orienting and inhibitory control whereas children with ASD show abnormalities in conflict monitoring and response preparation. Children with co-morbid ASD + ADHD present as an additive co-occurrence with deficits of both disorders, although non-additive effects are suggested for response preparation. Measuring ERPs that index attention and inhibition is useful in disentangling cognitive markers of ASD and ADHD and elucidating the basis of co-occurring ASD + ADHD to guide clinical assessment.

Studies in borderline personality disorder (BPD) have consistently revealed abnormalities in fronto-limbic brain regions during emotional, somatosensory and cognitive challenges. Here we investigated changes in resting-state functional connectivity (RSFC) of three fronto-limbic core regions of specific importance to BPD.

Functional magnetic resonance imaging data were acquired in 20 unmedicated female BPD patients and 17 healthy controls (HC, matched for age, sex and education) during rest. The amygdala, and the dorsal and ventral anterior cingulate cortex (ACC) were defined as seeds to investigate RSFC patterns of a medial temporal lobe network, the salience network and default mode network. The Dissociation Experience Scale (DES), a measure of trait dissociation, was additionally used as a predictor of RSFC with these seed regions.

Compared with HC, BPD patients showed a trend towards increased RSFC between the amygdala and the insula, orbitofrontal cortex and putamen. Compared with controls, patients furthermore exhibited diminished negative RSFC between the dorsal ACC and posterior cingulate cortex, a core region of the default mode network, and regions of the dorsomedial prefrontal cortex. Last, increased negative RSFC between the ventral ACC and medial occipital regions was observed in BPD patients. DES scores were correlated with amygdala connectivity with the dorsolateral prefrontal cortex and fusiform gyrus.

Our findings suggest alterations in resting-state networks associated with processing of negative emotions, encoding of salient events, and self-referential processing in individuals with BPD compared with HC. These results shed more light on the role of abnormal brain connectivity in BPD.

At present there are no objective, biological markers that can be used to reliably identify individuals with post-traumatic stress disorder (PTSD). This study assessed the diagnostic potential of structural magnetic resonance imaging (sMRI) for identifying trauma-exposed individuals with and without PTSD.

sMRI scans were acquired from 50 survivors of the Sichuan earthquake of 2008 who had developed PTSD, 50 survivors who had not developed PTSD and 40 healthy controls who had not been exposed to the earthquake. Support vector machine (SVM), a multivariate pattern recognition technique, was used to develop an algorithm that distinguished between the three groups at an individual level. The accuracy of the algorithm and its statistical significance were estimated using leave-one-out cross-validation and permutation testing.

When survivors with PTSD were compared against healthy controls, both grey and white matter allowed discrimination with an accuracy of 91% (p < 0.001). When survivors without PTSD were compared against healthy controls, the two groups could be discriminated with accuracies of 76% (p < 0.001) and 85% (p < 0.001) based on grey and white matter, respectively. Finally, when survivors with and without PTSD were compared directly, grey matter allowed discrimination with an accuracy of 67% (p < 0.001); in contrast the two groups could not be distinguished based on white matter.

These results reveal patterns of neuroanatomical alterations that could be used to inform the identification of trauma survivors with and without PTSD at the individual level, and provide preliminary support to the development of SVM as a clinically useful diagnostic aid.

Despite evidence of inhibitory control and visual processing impairment in attention deficit hyperactivity disorder (ADHD), knowledge about its corresponding alterations in the brain is still evolving. The current study used counting Stroop functional MRI and the Cambridge Neuropsychological Test Automated Battery (CANTAB) to investigate if brain activation of inhibitory control and visual processing would differ in youths with ADHD relative to neurotypical youths.

We assessed 25 youths with ADHD [mean age 10.9 (s.d. = 2.2) years] and 23 age-, gender- and IQ-matched neurotypical youths [mean age 11.2 (s.d. = 2.9) years]. The participants were assessed by using the Wechsler Intelligence Scale for Children, third edition, and two tests from the CANTAB: rapid visual information processing (RVP) and pattern recognition memory (PRM) outside the scanner.

Youths with ADHD showed more activation than neurotypical youths in the right inferior frontal gyrus [Brodmann area (BA) 45] and anterior cingulate cortex, which were correlated with poorer performance on the RVP test in the CANTAB. In contrast, youths with ADHD showed less activation than neurotypical youths in the left superior parietal lobule (BA 5/7), which was correlated with the percentage of correct responses on the PRM test in the CANTAB.

Our findings suggest that youths with ADHD might need more inhibitory control to suppress interference between number and meaning and may involve less visual processing to process the numbers in the counting Stroop task than neurotypical youths.

Individuals with generalized social anxiety disorder (gSAD) exhibit attentional bias to salient stimuli, which is reduced in patients whose symptoms improve after treatment, indicating that mechanisms of bias mediate treatment success. Therefore, pre-treatment activity in regions implicated in attentional control over socio-emotional signals (e.g. anterior cingulate cortex, dorsolateral prefrontal cortex) may predict response to cognitive behavioral therapy (CBT), evidence-based psychotherapy for gSAD.

During functional magnetic resonance imaging, 21 participants with gSAD viewed images comprising a trio of geometric shapes (circles, rectangles or triangles) alongside a trio of faces (angry, fearful or happy) within the same field of view. Attentional control was evaluated with the instruction to ‘match shapes’, directing attention away from faces, which was contrasted with ‘match faces’, whereby attention was directed to emotional faces.

Whole-brain voxel-wise analyses showed that symptom improvement was predicted by enhanced pre-treatment activity in the presence of emotional face distractors in the dorsal anterior cingulate cortex and dorsal medial prefrontal cortex. Additionally, CBT success was foretold by less activity in the amygdala and/or increased activity in the medial orbitofrontal gyrus during emotion processing.

CBT response was predicted by pre-treatment activity in prefrontal regions and the amygdala. The direction of activity suggests that individuals with intact attentional control in the presence of emotional distractors, regulatory capacity over emotional faces and/or less reactivity to such faces are more likely to benefit from CBT. Findings indicate that baseline neural activity in the context of attentional control and emotion processing may serve as a step towards delineating mechanisms by which CBT exerts its effects.

The evidence is conflicting as to whether body mass index (BMI) is associated with mental health and, if so, to what extent it varies by sex and age. We studied mental health across the full spectrum of BMI among the general population, and conducted subgroup analyses by sex and age.

We undertook a cross-sectional study of a representative sample of the Scottish adult population. The Scottish Health Survey provided data on mental health, measured by the General Health Questionnaire-12 (GHQ), BMI, demographic and life-style information. Good mental health was defined as a GHQ score <4, and poor mental health as a GHQ score ⩾4. Logistic regression models were applied.

Of the 37 272 participants, 5739 (15.4%) had poor mental health. Overall, overweight participants had better mental health than the normal-weight group [adjusted odds ratio (OR) 0.93, 95% confidence interval (CI) 0.87–0.99, p = 0.049], and individuals who were underweight, class II or class III obese had poorer mental health (class III obese group: adjusted OR 1.26, 95% CI 1.05–1.51, p = 0.013). There were significant interactions of BMI with sex (p = 0.013) and with age (p < 0.001). Being overweight was associated with significantly better mental health in middle-aged men only. In contrast, being underweight at all ages or obese at a young age was associated with significantly poorer mental health in women only.

The adverse associations between adiposity and mental health are specific to women. Underweight women and young women who are obese have poorer mental health. In contrast, middle-aged overweight men have better mental health.

Deficits in sustained attention and reaction time are core features of attention deficit hyperactivity disorder (ADHD). However, little is known about attention performance in unaffected siblings. Hence, we examined sustained attention and reaction time in youths with ADHD, unaffected siblings and controls to test whether impaired performance in attention tasks can be a potential endophenotype of ADHD.

We recruited 438 probands with clinical diagnosis of ADHD according to DSM-IV criteria, 180 unaffected siblings, and 173 healthy controls without lifetime ADHD. They were assessed using psychiatric interviews, Conners’ Continuous Performance Test, and the tasks involving attention performance of the Cambridge Neuropsychological Test Automated Battery (CANTAB): Rapid Visual Information Processing (RVP), Reaction Time (RTI) and Match to Sample Visual Search (MTS). Multi-level models were used for data analysis.

Compared with the controls, probands with ADHD and unaffected siblings had significantly higher total misses, lower probability of hits in the RVP task and probands with ADHD performed worse in the RTI and MTS tasks after controlling for sex, age, co-morbidity, parental educational levels and IQ. The duration of methylphenidate use and IQ but not psychiatric co-morbidity or current use of methylphenidate were associated with deficits in sustained attention in probands with ADHD.

Our findings suggest that attention performance assessed by the RVP task, but not the RTI or MTS tasks, of the CANTAB may be a useful cognitive endophenotype for ADHD genetic studies.

Several randomized controlled trials (RCTs) have shown that cognitive behavioural psychotherapy (CBT) is an efficacious treatment for chronic fatigue syndrome (CFS). However, little is known about the mechanisms by which the treatment has its effect. The aim of this study was to investigate potential mechanisms of change underlying the efficacy of CBT for CFS. We applied path analysis and introduce novel model comparison approaches to assess a theoretical CBT model that suggests that fearful cognitions will mediate the relationship between avoidance behaviour and illness outcomes (fatigue and social adjustment).

Data from 389 patients with CFS who received CBT in a specialist service in the UK were collected at baseline, at discharge from treatment, and at 3-, 6- and 12-month follow-ups. Path analyses were used to assess possible mediating effects. Model selection using information criteria was used to compare support for competing mediational models.

Path analyses were consistent with the hypothesized model in which fear avoidance beliefs at the 3-month follow-up partially mediate the relationship between avoidance behaviour at discharge and fatigue and social adjustment respectively at 6 months.

The results strengthen the validity of a theoretical model of CBT by confirming the role of cognitive and behavioural factors in CFS.

The neurobiological underpinnings of attention deficit hyperactivity disorder (ADHD) are inconclusive. Activation abnormalities across brain regions in ADHD compared with healthy controls highlighted in task-based functional magnetic resonance imaging (fMRI) studies are heterogeneous. To identify a consistent pattern of neural dysfunction in ADHD, a meta-analysis of fMRI studies using Go/no-go, Stop and N-back tasks was undertaken.

Several databases were searched using the key words: ‘ADHD and fMRI’ and ‘ADHD and fMRI task’. In all, 20 studies met inclusion criteria comprising 334 patients with ADHD and 372 healthy controls and were split into N-back, Stop task and Go/no-go case–control groups. Using Signed Differential Mapping each batch was meta-analysed individually and meta-regression analyses were used to examine the effects of exposure to methylphenidate (MPH), length of MPH wash-out period, ADHD subtype, age and intelligence quotient (IQ) differences upon neural dysfunction in ADHD.

Across all tasks less activity in frontal lobe regions compared with controls was detected. Less exposure to treatment and lengthier wash-out times resulted in less left medial frontal cortex activation in N-back and Go/no-go studies. Higher percentage of combined-type ADHD resulted in less superior and inferior frontal gyrus activation. Different IQ scores between groups were linked to reduced right caudate activity in ADHD.

Consistent frontal deficits imply homogeneous cognitive strategies involved in ADHD behavioural control. Our findings suggest a link between fMRI results and the potentially normalizing effect of treatment and signify a need for segregated examination and contrast of differences in sample characteristics in future studies.