The dopamine transporter gene (DAT1), striatal network dysfunction, and visual memory deficits have been consistently reported to be associated with attention-deficit/hyperactivity disorder (ADHD). This study aimed to examine the effects of the DAT1 rs27048 (C)/rs429699 (T) haplotype on striatal functional connectivity and visual memory performance in youths with ADHD.

After excluding those who had excessive head motion, a total of 96 drug-naïve youths with ADHD and 114 typically developing (TD) youths were assessed with the resting-state functional magnetic resonance imaging and the delayed matching to sample (DMS) task for visual memory. We examined the effects of ADHD, DAT1 CT haplotype, and the ADHD × CT haplotype interaction on the functional connectivity of five striatal seeds. We also correlated visual memory performance with the functional connectivity of striatal subregions, which showed significant diagnosis × genotype interactions.

Compared with TD youths, ADHD youths showed significant hypoconnectivity of the left dorsal caudate (DC) with bilateral sensorimotor clusters. Significant diagnosis × genotype interactions were found in the connectivity between the left DC and the right sensorimotor cluster, and between the right DC and the left dorsolateral prefrontal/bilateral anterior cingulate clusters. Furthermore, the connectivity of the left DC showing significant diagnosis × genotype interactions was associated with DMS performance in youths with ADHD who carried the DAT1 CT haplotype.

A novel gene-brain-behavior association between the left DC functional connectivity and visual memory performance in ADHD youths with the DAT1 rs27048 (C)/rs429699 (T) haplotype suggests a differential effect of DAT1 genotype altering specific brain function causing neuropsychological dysfunction in ADHD.

Cognitive impairment is a core feature of major depressive disorder (MDD). Cognitive remediation may improve cognition in MDD, yet so far, the underlying neural mechanisms are unclear. This study investigated changes in intrinsic neural activity in MDD after a cognitive remediation trial.

In a longitudinal design, 20 patients with MDD and pronounced cognitive deficits and 18 healthy controls (HC) were examined using resting-state functional magnetic resonance imaging. MDD patients received structured cognitive remediation therapy (CRT) over 5 weeks. The whole-brain fractional amplitude of low-frequency fluctuations was computed before the first and after the last training session. Univariate methods were used to address regionally-specific effects, and a multivariate data analysis strategy was employed to investigate functional network strength (FNS).

MDD patients significantly improved in cognitive function after CRT. Baseline comparisons revealed increased right caudate activity and reduced activity in the left frontal cortex, parietal lobule, insula, and precuneus in MDD compared to HC. In patients, reduced FNS was found in a bilateral prefrontal system at baseline (p < 0.05, uncorrected). In MDD, intrinsic neural activity increased in right inferior frontal gyrus after CRT (p < 0.05, small volume corrected). Left inferior parietal lobule, left insula, left precuneus, and right caudate activity showed associations with cognitive improvement (p < 0.05, uncorrected). Prefrontal network strength increased in patients after CRT, but this increase was not associated with improved cognitive performance.

Our findings support the role of intrinsic neural activity of the prefrontal cortex as a possible mediator of cognitive improvement following CRT in MDD.

Previous models suggest biological and behavioral continua among healthy individuals (HC), at-risk condition, and full-blown schizophrenia (SCZ). Part of these continua may be captured by schizotypy, which shares subclinical traits and biological phenotypes with SCZ, including thalamic structural abnormalities. In this regard, previous findings have suggested that multivariate volumetric patterns of individual thalamic nuclei discriminate HC from SCZ. These results were obtained using machine learning, which allows case–control classification at the single-subject level. However, machine learning accuracy is usually unsatisfactory possibly due to phenotype heterogeneity. Indeed, a source of misclassification may be related to thalamic structural characteristics of those HC with high schizotypy, which may resemble structural abnormalities of SCZ. We hypothesized that thalamic structural heterogeneity is related to schizotypy, such that high schizotypal burden would implicate misclassification of those HC whose thalamic patterns resemble SCZ abnormalities.

Following a previous report, we used Random Forests to predict diagnosis in a case–control sample (SCZ = 131, HC = 255) based on thalamic nuclei gray matter volumes estimates. Then, we investigated whether the likelihood to be classified as SCZ (π-SCZ) was associated with schizotypy in 174 HC, evaluated with the Schizotypal Personality Questionnaire.

Prediction accuracy was 72.5%. Misclassified HC had higher positive schizotypy scores, which were correlated with π-SCZ. Results were specific to thalamic rather than whole-brain structural features.

These findings strengthen the relevance of thalamic structural abnormalities to SCZ and suggest that multivariate thalamic patterns are correlates of the continuum between schizotypy in HC and the full-blown disease.

Differences between verbal and non-verbal cognitive development from childhood to adulthood may differentiate between those with and without psychotic symptoms and affective symptoms in later life. However, there has been no study exploring this in a population-based cohort.

The sample was drawn from the MRC National Survey of Health and Development, and consisted of 2384 study members with self-reported psychotic experiences and affective symptoms at the age of 53 years, and with complete cognitive data at the ages of 8 and 15 years. The association between verbal and non-verbal cognition at age 8 years and relative developmental lag from age 8 to 15 years, and both adult outcomes were tested with the covariates adjusted, and mutually adjusted for verbal and non-verbal cognition.

Those with psychotic experiences [thought interference (n = 433), strange experience (n = 296), hallucination (n = 88)] had lower cognition at both the ages of 8 and 15 years in both verbal and non-verbal domains. After mutual adjustment, lower verbal cognition at age 8 years and greater verbal developmental lag were associated with higher likelihood of psychotic experiences within individuals, whereas there was no association between non-verbal cognition and any psychotic experience. In contrast, those with case-level affective symptoms (n = 453) had lower non-verbal cognition at age 15 years, and greater developmental lag in the non-verbal domain. After adjustment, lower non-verbal cognition at age 8 years and greater non-verbal developmental lag were associated with higher risk of case-level affective symptoms within individuals.

These results suggest that cognitive profiles in childhood and adolescence differentiate psychiatric disease spectra.

Among Veterans, post-traumatic stress disorder (PTSD) has been shown to be associated with obesity and accelerated weight gain. Less is known among the general population. We sought to determine the impact of PTSD on body mass index (BMI) and weight change among individuals with exposure to the World Trade Center (WTC) disaster.

We examined individuals from the WTC Health Registry. PTSD symptoms were assessed on multiple surveys (Waves 1–4) using the PTSD Checklist-Specific. Three categories of post-9/11 PTSD were derived: no, intermittent, and persistent. We examined two outcomes: (1) Wave 3 BMI (normal, overweight, and obese) and (2) weight change between Waves 3 and 4. We used multivariable logistic regression to assess the association between PTSD and BMI (N = 34 958) and generalized estimating equations to assess the impact of PTSD on weight change (N = 26 532). Sex- and age-stratified analyses were adjusted for a priori confounders.

At Wave 3, the observed prevalence of obesity was highest among the persistent (39.5%) and intermittent PTSD (36.6%) groups, compared to the no PTSD group (29.3%). In adjusted models, persistent and intermittent PTSD were consistently associated with a higher odds of obesity. Weight gain was similar across all groups, but those with persistent and intermittent PTSD had higher estimated group-specific mean weights across time.

Our findings that those with a history of PTSD post-9/11 were more likely to have obesity is consistent with existing literature. These findings reaffirm the need for an interdisciplinary focus on physical and mental health to improve health outcomes.

Depression is increasingly recognized as a chronic and relapsing disorder. However, an important minority of patients who start treatment for their major depressive episode recover to euthymia. It is clinically important to be able to predict such individuals.

The study is a secondary analysis of a recently completed pragmatic megatrial examining first- and second-line treatments for hitherto untreated episodes of non-psychotic unipolar major depression (n = 2011). Using the first half of the cohort as the derivation set, we applied multiply-imputed stepwise logistic regression with backward selection to build a prediction model to predict remission, defined as scoring 4 or less on the Patient Health Quetionnaire-9 at week 9. We used three successively richer sets of predictors at baseline only, up to week 1, and up to week 3. We examined the external validity of the derived prediction models with the second half of the cohort.

In total, 37.0% (95% confidence interval 34.8–39.1%) were in remission at week 9. Only the models using data up to week 1 or 3 showed reasonable performance. Age, education, length of episode and depression severity remained in the multivariable prediction models. In the validation set, the discrimination of the prediction model was satisfactory with the area under the curve of 0.73 (0.70–0.77) and 0.82 (0.79–0.85), while the calibration was excellent with non-significant goodness-of-fit χ2 values (p = 0.41 and p = 0.29), respectively.

Patients and clinicians can use these prediction models to estimate their predicted probability of achieving remission after acute antidepressant therapy.

Prevalence estimates for body-focused repetitive behaviors (BFRBs) such as trichotillomania differ greatly across studies owing to several confounding factors (e.g. different criteria). For the present study, we recruited a diverse online sample to provide estimates for nine subtypes of BFRBs and body-focused repetitive disorders (BFRDs).

The final sample comprised 1481 individuals from the general population. Several precautions were taken to recruit a diverse sample and to exclude participants with low reliability. We matched participants on gender, race, education and age range to allow unbiased interpretation.

While almost all participants acknowledged at least one BFRB in their lifetime (97.1%), the rate for BFRDs was 24%. Nail biting (11.4%), dermatophagia (8.7%), skin picking (8.2%), and lip-cheek biting (7.9%) were the most frequent BFRDs. Whereas men showed more lifetime BFRBs, the rate of BFRDs was higher in women than in men. Rates of BFRDs were low in older participants, especially after the age of 40. Overall, BFRBs and BFRDs were more prevalent in White than in non-White individuals. Education did not show a strong association with BFRB/BFRDs.

BFRBs are ubiquitous. More severe forms, BFRDs, manifest in approximately one out of four people. In view of the often-irreversible somatic sequelae (e.g. scars) BFRBs/BFRDs deserve greater diagnostic and therapeutic attention by clinicians working in both psychology/psychiatry and somatic medicine (especially dermatology and dentistry).

Little is known about the effects of physical exercise on sleep-dependent consolidation of procedural memory in individuals with schizophrenia. We conducted a randomized controlled trial (RCT) to assess the effectiveness of physical exercise in improving this cognitive function in schizophrenia.

A three-arm parallel open-labeled RCT took place in a university hospital. Participants were randomized and allocated into either the high-intensity-interval-training group (HIIT), aerobic-endurance exercise group (AE), or psychoeducation group for 12 weeks, with three sessions per week. Seventy-nine individuals with schizophrenia spectrum disorder were contacted and screened for their eligibility. A total of 51 were successfully recruited in the study. The primary outcome was sleep-dependent procedural memory consolidation performance as measured by the finger-tapping motor sequence task (MST). Assessments were conducted during baseline and follow-up on week 12.

The MST performance scored significantly higher in the HIIT (n = 17) compared to the psychoeducation group (n = 18) after the week 12 intervention (p < 0.001). The performance differences between the AE (n = 16) and the psychoeducation (p = 0.057), and between the AE and the HIIT (p = 0.999) were not significant. Yet, both HIIT (p < 0.0001) and AE (p < 0.05) showed significant within-group post-intervention improvement.

Our results show that HIIT and AE were effective at reverting the defective sleep-dependent procedural memory consolidation in individuals with schizophrenia. Moreover, HIIT had a more distinctive effect compared to the control group. These findings suggest that HIIT may be a more effective treatment to improve sleep-dependent memory functions in individuals with schizophrenia than AE alone.

Abnormal processing of social feedback is an important contributor to social dysfunction in depression, however the exact mechanisms remain unclear. One important factor may be the extent to which social processing depends on expectations, in particular whether social feedback confirms or violates expectations.

To answer this question, we studied behavioral and brain responses during the evaluative processing of social feedback in 25 individuals with subthreshold depression (SD) and 25 healthy controls (HCs). Participants completed a Social Judgment Task in which they first indicated expectation about whether a peer would like them or not, and then received peer's feedback indicating acceptance or rejection.

Individuals with SD who reported greater depressive symptoms gave fewer positive expectations. Compared to HCs, individuals with SD showed reduced activation in the medial prefrontal cortex when expecting positive feedback. They also exhibited increased dorsal anterior cingulate cortex after receipt of unexpected social rejection, and reduced ventral striatum activity after receipt of unexpected social acceptance.

The observed alternations are specific to unexpected social feedback processing and highlight an important role of expectancy violation in the brain dysfunction of social feedback perception and evaluation in individuals at risk for depression.

Two single-nucleotide polymorphisms (SNPs) (rs4281084 and rs12155594) within the neuregulin-1 (NRG1) gene have been associated with psychosis transition. However, the neurobiological changes associated with these SNPs remain unclear. We aimed to determine what relationship these two SNPs have on lateral ventricular volume and white matter integrity, as abnormalities in these brain structures are some of the most consistent in schizophrenia.

Structural (n = 370) and diffusion (n = 465) magnetic resonance imaging data were obtained from affected and unaffected individuals predominantly of European descent. The SNPs rs4281084, rs12155594, and their combined allelic load were examined for their effects on lateral ventricular volume, fractional anisotropy (FA) as well as axial (AD) and radial (RD) diffusivity. Additional exploratory analyses assessed NRG1 effects on gray matter volume, cortical thickness, and surface area throughout the brain.

Individuals with a schizophrenia age of onset ⩽25 and a combined allelic load ⩾3 NRG1 risk alleles had significantly larger right (up to 50%, p adj = 0.01) and left (up to 45%, p adj = 0.05) lateral ventricle volumes compared with those with allelic loads of less than three. Furthermore, carriers of three or more risk alleles, regardless of age of onset and case status, had significantly reduced FA and elevated RD but stable AD in the frontal cortex compared with those carrying fewer than three risk alleles.

Our findings build on a growing body of research supporting the functional importance of genetic variation within the NRG1 gene and complement previous findings implicating the rs4281084 and rs12155594 SNPs as markers for psychosis transition.

Co-morbidity among use of different substances can be explained by a shared underlying dimensional factor. What remains unknown is whether the relationship between substance use and various co-morbid mental disorders can be explained solely by the general factor or whether there remain unique contributions of specific substances.

Data were from the 2007 Australian National Survey of Mental Health and Wellbeing (NSMHWB). A unidimensional latent factor was constructed that represented general substance use. The shared and specific relationships between lifetime substance use indicators and internalizing disorders, suicidality and psychotic-like experiences (PLEs) were examined using Multiple Indicators Multiple Causes (MIMIC) models in the total sample. Additional analyses then examined the shared and specific relationships associated with substance dependence diagnoses as indicators of the latent trait focusing on a subsample of substance users.

General levels of latent substance use were significantly and positively related to internalizing disorders, suicidality and psychotic-like experiences. Similar results were found when examining general levels of latent substance dependence in a sample of substance users. There were several direct effects between specific substance use/dependence indicators and the mental health correlates that significantly improved the overall model fit but they were small in magnitude and had relatively little impact on the general relationship.

The majority of pairwise co-morbid relationships between substance use/dependence and mental health correlates can be explained through a general latent factor. Researchers should focus on investigating the commonalities across all substance use and dependence indicators when studying mental health co-morbidity.