Previous studies have provided initial evidence that people at risk for psychosis (PR) suffer from stigma and discrimination related to their condition. However, no study has systematically reviewed stigma and discrimination associated with being at PR and the potential underlying mechanisms.

This work aimed to systematically review all studies addressing stigma and discrimination in PR people in order to assess: (1) the occurrence of this phenomenon and its different components (public, internalized, perceived, and labeling-related), (2) whether stigma affects outcomes of the PR state, and (3) whether other factors modulate stigma among PR individuals.

The reviewed studies (n = 38) widely differ in their design, methodological quality, and populations under investigation, thus limiting direct comparison of findings. However, converging evidence suggests that the general public endorses stigmatizing attitudes towards PR individuals, and that this is more frequent in people with a low educational level or with no direct experience of the PR state. PR individuals experience more internalized stigma and perceive more discrimination than healthy subjects or patients with non-psychotic disorders. Further, PR labeling is equally associated with both positive (e.g. validation and relief) and negative effects (e.g. status loss and discrimination). Moreover, stigma increases the likelihood of poor outcome, transition to full-psychosis, disengagement from services, and family stigma among PR individuals. Finally, very limited evidence awaiting replication supports the efficacy of cognitive therapies in mitigating the negative effects of stigma.

Evidence confirms previous concerns about stigma and its negative consequences for PR individuals, thus having important public health implications.

Attention bias modification (ABM) training has been suggested to effectively reduce depressive symptoms, and may be useful in the prevention of the illness in individuals with subthreshold symptoms, yet little is known about the spontaneous brain activity changes associated with ABM training.

Resting-state functional MRI was used to explore the effects of ABM training on subthreshold depression (SubD) and corresponding spontaneous brain activity changes. Participants were 41 young women with SubD and 26 matched non-depressed controls. Participants with SubD were randomized to receive either ABM or placebo training during 28 sessions across 4 weeks. Non-depressed controls were assessed before training only. Attentional bias, depressive severity, and spontaneous brain activity before and after training were assessed in both training groups.

Findings revealed that compared to active control training, ABM training significantly decreased depression symptoms, and increased attention for positive stimuli. Resting-state data found that ABM training significantly reduced amplitude of low-frequency fluctuations (ALFF) of the right anterior insula (AI) and right middle frontal gyrus which showed greater ALFF than non-depressed controls before training; Functional connectivity strength between right AI and the right frontoinsular and right supramarginal gyrus were significantly decreased after training within the ABM group; moreover, the improvement of depression symptoms following ABM significantly correlated with the connectivity strength reductions between right AI and right frontoinsular and right supramarginal gyrus.

These results suggest that ABM has the potential to reshape the abnormal patterns of spontaneous brain activity in relevant neural circuits associated with depression.

We investigated the course of decline in multiple cognitive domains in non-demented subjects from a memory clinic setting, and compared pattern, onset and magnitude of decline between subjects who progressed to Alzheimer's disease (AD) dementia at follow-up and subjects who did not progress.

In this retrospective cohort study 819 consecutive non-demented patients who visited the memory clinics in Maastricht or Amsterdam between 1987 and 2010 were followed until they became demented or for a maximum of 10 years (range 0.5–10 years). Differences in trajectories of episodic memory, executive functioning, verbal fluency, and information processing speed/attention between converters to AD dementia and subjects remaining non-demented were compared by means of random effects modelling.

The cognitive performance of converters and non-converters could already be differentiated seven (episodic memory) to three (verbal fluency and executive functioning) years prior to dementia diagnosis. Converters declined in these three domains, while non-converters remained stable on episodic memory and executive functioning and showed modest decline in verbal fluency. There was no evidence of decline in information processing speed/attention in either group.

Differences in cognitive performance between converters to AD dementia and subjects remaining non-demented could be established 7 years prior to diagnosis for episodic memory, with verbal fluency and executive functioning following several years later. Therefore, in addition to early episodic memory decline, decline in executive functions may also flag incident AD dementia. By contrast, change in information processing speed/attention seems less informative.

Although basic research on neuroimmune interactions suggests that inflammatory processes may play a role in the development of fatigue, population-based evidence on this association is limited. This study examined whether plasma C-reactive protein (CRP) and interleukin-6 (IL-6), biomarkers of systemic inflammation, predict fatigue onset.

The Whitehall II study is a large-scale cohort study conducted in 20 civil service departments in London. Plasma CRP and IL-6 were measured in 4847 non-fatigued participants at phase 3 (1991–1993, aged 39–63 years). Fatigue was assessed using the Vitality subscale of the 36-item Short Form Health Survey (SF-36) at phase 3 and phase 4 (1995–1996).

During a mean follow-up of 3.1 years, 957 new fatigue cases (19.7%) were identified using the pre-established cut-off score of ⩽50 on the Vitality subscale. CRP values were dichotomized as low (<1.0 mg/l ) or high (⩾1.0 mg/l) using the Centers for Disease Control/American Heart Association recommendations. Similarly, IL-6 values were also dichotomized as low (<1.5 pg/ml) or high (⩾1.5 pg/ml). After full adjustment for sociodemographic and biobehavioral covariates, the odds ratios for new-onset fatigue were 1.28 [95% confidence interval (CI) 1.09–1.49, p = 0.003] for high CRP and 1.24 (95% CI 1.06–1.45, p = 0.008) for high IL-6. Similar results were found when CRP and IL-6 were treated as continuous variables.

Plasma CRP and IL-6 were prospectively associated with new-onset fatigue, supporting the hypothesis that low-grade inflammation has a role in the development of fatigue.

Interferon-alpha (IFN-α) treatment for infectious disease and cancer causes high rates of depression and fatigue, and has been used to investigate the impact of inflammatory cytokines on brain and behavior. However, little is known about the transcriptional impact of chronic IFN-α on immune cells in vivo and its relationship to IFN-α-induced behavioral changes.

Genome-wide transcriptional profiling was performed on peripheral blood mononuclear cells (PBMCs) from 21 patients with chronic hepatitis C virus (HCV) either awaiting IFN-α therapy (n=10) or at 12 weeks of IFN-α treatment (n=11).

Significance analysis of microarray data identified 252 up-regulated and 116 down-regulated gene transcripts. Of the up-regulated genes, 2′-5′-oligoadenylate synthetase 2 (OAS2), a gene linked to chronic fatigue syndrome (CFS), was the only gene that was differentially expressed in patients with IFN-α-induced depression/fatigue, and correlated with depression and fatigue scores at 12 weeks (r=0.80, p=0.003 and r=0.70, p=0.017 respectively). Promoter-based bioinformatic analyses linked IFN-α-related transcriptional alterations to transcription factors involved in myeloid differentiation, IFN-α signaling, activator protein-1 (AP1) and cAMP responsive element binding protein/activation transcription factor (CREB/ATF) pathways, which were derived primarily from monocytes and plasmacytoid dendritic cells. IFN-α-treated patients with high depression/fatigue scores demonstrated up-regulation of genes bearing promoter motifs for transcription factors involved in myeloid differentiation, IFN-α and AP1 signaling, and reduced prevalence of motifs for CREB/ATF, which has been implicated in major depression.

Depression and fatigue during chronic IFN-α administration were associated with alterations in the expression (OAS2) and transcriptional control (CREB/ATF) of genes linked to behavioral disorders including CFS and major depression, further supporting an immune contribution to these diseases.

Functional magnetic resonance imaging (fMRI) of multiple neural networks during the brain's ‘resting state’ could facilitate biomarker development in patients with Huntington's disease (HD) and may provide new insights into the relationship between neural dysfunction and clinical symptoms. To date, however, very few studies have examined the functional integrity of multiple resting state networks (RSNs) in manifest HD, and even less is known about whether concomitant brain atrophy affects neural activity in patients.

Using MRI, we investigated brain structure and RSN function in patients with early HD (n = 20) and healthy controls (n = 20). For resting-state fMRI data a group-independent component analysis identified spatiotemporally distinct patterns of motor and prefrontal RSNs of interest. We used voxel-based morphometry to assess regional brain atrophy, and ‘biological parametric mapping’ analyses to investigate the impact of atrophy on neural activity.

Compared with controls, patients showed connectivity changes within distinct neural systems including lateral prefrontal, supplementary motor, thalamic, cingulate, temporal and parietal regions. In patients, supplementary motor area and cingulate cortex connectivity indices were associated with measures of motor function, whereas lateral prefrontal connectivity was associated with cognition.

This study provides evidence for aberrant connectivity of RSNs associated with motor function and cognition in early manifest HD when controlling for brain atrophy. This suggests clinically relevant changes of RSN activity in the presence of HD-associated cortical and subcortical structural abnormalities.

The outcomes of attention deficit hyperactivity disorder (ADHD) have been studied extensively in the first decades of life, but less is known about ADHD in adulthood. Hence we investigated cross-sectional age-related differences in behavioural symptoms, neuropsychological function and severity of co-morbid disorders within a clinically referred adult ADHD population.

We subdivided 439 referrals of individuals with ADHD (aged 16–50 years) into four groups based on decade of life and matched for childhood ADHD severity. We compared the groups on measures of self- and informant-rated current behavioural ADHD symptoms, neuropsychological performance, and self-rated co-morbid mood and anxiety symptoms.

There was a significant age-related reduction in the severity of all ADHD symptoms based on informant-ratings. In contrast, according to self-ratings, inattentive symptoms increased with age. Neuropsychological function improved across age groups on measures of selective attention and response inhibition. There was a mild correlation between the severity of depression symptoms and increasing age.

This observational study suggests that, in adulthood, ADHD symptoms as measured using informant-ratings and neuropsychological measures continue to improve with increasing age. However the subjective experience of people with ADHD is that their symptoms worsen. This dichotomy may be partially explained by the presence of co-morbid affective symptoms. The main limitation of the study is that it is cross-sectional rather than longitudinal, and the latter design would provide more conclusive evidence regarding age-related changes in an adult ADHD population.

Although early life adversity (ELA) increases risk for psychopathology, mechanisms linking ELA with the onset of psychopathology remain poorly understood. Conceptual models have argued that ELA accelerates development. It is unknown whether all forms of ELA are associated with accelerated development or whether early maturation is a potential mechanism linking ELA with psychopathology. We examine whether two distinct dimensions of ELA – threat and deprivation – have differential associations with pubertal timing in girls, and evaluate whether accelerated pubertal timing is a mechanism linking ELA with the onset of adolescent psychopathology.

Data were drawn from a large, nationally representative sample of 4937 adolescent girls. Multiple forms of ELA characterized by threat and deprivation were assessed along with age at menarche (AAM) and the onset of DSM-IV fear, distress, externalizing, and eating disorders.

Greater exposure to threat was associated with earlier AAM (B = −0.1, p = 0.001). Each 1-year increase in AAM was associated with reduced odds of fear, distress, and externalizing disorders post-menarche (ORs = 0.74–0.85). Earlier AAM significantly mediated the association between exposure to threat and post-menarche onset of distress (proportion mediated = 6.2%), fear (proportion mediated = 16.3%), and externalizing disorders (proportion mediated = 2.9%).

Accelerated pubertal development in girls may be one transdiagnostic pathway through which threat-related experiences confer risk for the adolescent onset of mental disorders. Early pubertal maturation is a marker that could be used in both medical and mental health settings to identify trauma-exposed youth that are at risk for developing a mental disorder during adolescence in order to better target early interventions.

Youths with obsessive–compulsive disorder (OCD) experience severe distress and impaired functioning at school and at home. Critical cognitive domains for daily functioning and academic success are learning, memory, cognitive flexibility and goal-directed behavioural control. Performance in these important domains among teenagers with OCD was therefore investigated in this study.

A total of 36 youths with OCD and 36 healthy comparison subjects completed two memory tasks: Pattern Recognition Memory (PRM) and Paired Associates Learning (PAL); as well as the Intra-Extra Dimensional Set Shift (IED) task to quantitatively gauge learning as well as cognitive flexibility. A subset of 30 participants of each group also completed a Differential-Outcome Effect (DOE) task followed by a Slips-of-Action Task, designed to assess the balance of goal-directed and habitual behavioural control.

Adolescent OCD patients showed a significant learning and memory impairment. Compared with healthy comparison subjects, they made more errors on PRM and PAL and in the first stages of IED involving discrimination and reversal learning. Patients were also slower to learn about contingencies in the DOE task and were less sensitive to outcome devaluation, suggesting an impairment in goal-directed control.

This study advances the characterization of juvenile OCD. Patients demonstrated impairments in all learning and memory tasks. We also provide the first experimental evidence of impaired goal-directed control and lack of cognitive plasticity early in the development of OCD. The extent to which the impairments in these cognitive domains impact academic performance and symptom development warrants further investigation.

The Hierarchical Taxonomy of Psychopathology (HiTOP) is a classification system that seeks to organize psychopathology using quantitative evidence – yet the current model was established by narrative review. This meta-analysis provides a quantitative synthesis of literature on transdiagnostic dimensions of psychopathology to evaluate the validity of the HiTOP framework.

Published studies estimating factor-analytic models from diagnostic and statistical manual of mental disorders (DSM) diagnoses were screened. A total of 120,596 participants from 35 studies assessing 23 DSM diagnoses were included in the meta-analytic models. Data were pooled into a meta-analytic correlation matrix using a random effects model. Exploratory factor analyses were conducted using the pooled correlation matrix. A hierarchical structure was estimated by extracting one to five factors representing levels of the HiTOP framework, then calculating congruence coefficients between factors at sequential levels.

Five transdiagnostic dimensions fit the DSM diagnoses well (comparative fit index = 0.92, root mean square error of approximation = 0.07, and standardized root-mean-square residual = 0.03). Most diagnoses had factor loadings >|0.30| on the expected factors, and congruence coefficients between factors indicated a hierarchical structure consistent with the HiTOP framework.

A model closely resembling the HiTOP framework fit the data well and placement of DSM diagnoses within transdiagnostic dimensions were largely confirmed, supporting it as valid structure for conceptualizing and organizing psychopathology. Results also suggest transdiagnostic research should (1) use traits, narrow symptoms, and dimensional measures of psychopathology instead of DSM diagnoses, (2) assess a broader array of constructs, and (3) increase focus on understudied pathologies.