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Research suggests decreased cortical dopamine is a neural correlate of cognitive deficits in schizophrenia. Evidence of impaired cognitive task-induced cortical dopamine release was demonstrated in patients with psychosis. However, whether cortical dopamine release in response to a cognitive task in clinical high risk for psychosis (CHR) is also impaired, is currently unknown. We aimed to test dopamine release in the dorsolateral prefrontal cortex (DLPFC) and the anterior cingulate cortex (ACC) in antipsychotic-free CHR participants and healthy controls (HC) performing the Wisconsin Card Sorting Task (WCST). Two [11C]FLB457 PET scans were conducted for 13 CHR and 15 HC while performing the WCST and the sensorimotor control task (SMCT), respectively. A magnetic resonance image was acquired for anatomical delineation. Percentage change in binding potential (ΔBPND) in ACC and DLPFC in WCST were compared with the SMCT between CHR and HC. Mixed model analysis revealed no statistically significant differences in the cognitive task induced ΔBPND in any ROIs. There were no main effect of group (F(1, 26) = 0.348; p = 0.560) or ROI (F(1, 26) = 1.080; p = 0.308) and no significant Group x ROI interaction (F(1, 26) = 0.049; p = 0.826). Our findings suggest no statistically significant difference between CHR and HC in cognitive task-induced cortical dopamine release. This is the first in vivo study to illustrate that the cortical hypodopaminergic state observed in schizophrenia may not be present in its putative high-risk state.

The ability to use feedback to guide optimal decision-making is essential for goal-directed behaviour. While impairments in feedback-driven decision-making have been associated with schizophrenia and depression, this has been examined primarily in the context of binary probabilistic choice paradigms. In real-world decision-making, however, individuals must make choices when there are more than two competing options that vary in the frequency and magnitude of potential rewards and losses. Thus, the current study examined win-stay/lose-shift (WSLS) behaviour on the Iowa Gambling Task (IGT) in order to evaluate the influence of immediate rewards and losses in guiding real-world decision-making in patients with schizophrenia and major depressive disorder. Fifty-one patients with schizophrenia, 43 patients with major depressive disorder, and 51 healthy controls completed the IGT, as well as a series of clinical and cognitive measures. WSLS was assessed by quantifying trial-by-trial behaviour following rewards and losses on the IGT. Multivariate analyses of variance revealed that patients with schizophrenia demonstrated intact lose-shift behaviour, but significantly reduced win-stay rates compared to healthy controls. In contrast, no WSLS impairments emerged in the depressed group. Win-stay impairments in the schizophrenia group were significantly related to deficits in motivation and cognition. Patients with schizophrenia exhibit impaired reward-driven decision-making in the context of multiple choices with concurrent rewards and losses, and this appears to be driven by a reduced propensity for advantageous win-stay behaviour. With the importance of reward learning and decision-making in generating goal-directed behaviour, these findings suggest a potential mechanism contributing to the motivation deficits seen in schizophrenia.

Negative schizotypal traits may be related to anhedonia and/or amotivation; however it is unclear which of these symptoms is related to negative schizotypy to a greater extent. Moreover, the impact of schizotypal traits on overall subjective well-being remains uncertain. The present study examined these two questions in a non-clinical sample assessed for schizotypal traits ( n = 138). Schizotypal traits were measured using the Schizotypal Personality Questionnaire, amotivation was assessed using Marin’s Apathy Evaluation Scale, anhedonia was assessed using the Snaith–Hamilton Pleasure Scale, and happiness was assessed using both the Satisfaction with Life Scale and a single-item happiness measure. Greater schizotypal traits were individually associated with both greater anhedonia and amotivation. Amotivation was a key predictor of negative schizotypy, with no independent predictive value offered by hedonic capacity. Furthermore, schizotypal traits, particularly negative schizotypal traits, were significantly associated with lower levels of happiness. This relationship between negative schizotypy and happiness remained even after controlling for the influence of amotivation. Our findings affirm that negative schizotypal traits are more closely related to symptoms of amotivation rather than anhedonia. Potential mechanisms mediating the relationship between negative schizotypy and happiness are discussed; nonetheless, future research exploring such mechanisms underlying lower well-being in schizotypy is needed.

Background Undiagnosed major depressive disorder (MDD) is associated with increased morbidity in children and adolescents. This study evaluated features of sleep macro- and microarchitecture assessed by polysomnography (PSG) as diagnostic markers for MDD in children and adolescents. Methods MEDLINE, PSYCINFO, EMBASE and PUBMED were searched from their availability dates to March 1st, 2013. The literature search identified 932 abstracts of which 51 studies were retrieved and 28 were included in the analysis. Study design, features of sleep macro- and microarchitecture, demographic and clinical characteristics of study groups were extracted for each study. Results There were modest differences on sleep macroarchitecture between children and adolescents with MDD and healthy controls. The most robust difference was found in sleep latency, 31% of adolescents with MDD had increased sleep latency. Age, suicidal ideation, suicidal behavior, and psychiatric comorbidities were significant predictors of sleep macroarchitecture. Modest differences were found for sleep microarchitecture, intrahemispheric and interhemispheric temporal coherence was decreased in a third of patients with MDD. Age was a significant predictor of sleep microarchitecture. Limitations This meta-analysis is limited by the small number of studies on sleep macroarchitecture in children with MDD and studies on sleep microarchitecture overall and by the heterogeneity in methodology between studies. Conclusions This synthetic review of the existing literature is among the largest to quantitatively assess impaired sleep as a diagnostic marker for MDD in children and adolescents. Knowledge of sleep macro- and microarchitecture in early-onset MDD may aid the clinician in developing a treatment strategy for MDD-related sleep symptoms in a subset of patients.

Obsessive-Compulsive Disorder (OCD) is characterized by persistent and unwanted obsessions generally accompanied by ritualistic behaviors or compulsions. Previous research proposed specific disgust facial emotion recognition deficits in patients with OCD. This research however, remains largely inconsistent. Therefore, the results of 10 studies contrasting facial emotion recognition accuracy in patients with OCD (n=221) and non-psychiatric controls (n=224) were quantitatively reviewed and synthesized using meta-analytic techniques. Patients with OCD were less accurate than controls in recognizing emotional facial expressions. Patients were also less accurate in recognizing negative emotions as a whole; however, this was largely due to significant differences in disgust and anger recognition specifically. The results of this study suggest that patients with OCD have difficulty recognizing specific negative emotions in faces and may misclassify emotional expressions due to symptom characteristics within the disorder. The contribution of state-related emotion perception biases to these findings requires further clarification.

Background Motivational impairments are a core feature of schizophrenia and although there are numerous reports studying this feature using clinical rating scales, objective behavioural assessments are lacking. Here, we use a translational paradigm to measure incentive motivation in individuals with schizophrenia. Methods Sixteen stable outpatients with schizophrenia and sixteen matched healthy controls completed a modified version of the Effort Expenditure for Rewards Task that accounts for differences in motoric ability. Briefly, subjects were presented with a series of trials where they may choose to expend a greater amount of effort for a larger monetary reward versus less effort for a smaller reward. Additionally, the probability of receiving money for a given trial was varied at 12%, 50% and 88%. Clinical and other reward-related variables were also evaluated. Results Patients opted to expend greater effort significantly less than controls for trials of high, but uncertain (i.e. 50% and 88% probability) incentive value, which was related to amotivation and neurocognitive deficits. Other abnormalities were also noted but were related to different clinical variables such as impulsivity (low reward and 12% probability). These motivational deficits were not due to group differences in reward learning, reward valuation or hedonic capacity. Conclusions Our findings offer novel support for incentive motivation deficits in schizophrenia. Clinical amotivation is associated with impairments in the computation of effort during cost-benefit decision-making. This objective translational paradigm may guide future investigations of the neural circuitry underlying these motivational impairments.

Borderline personality disorder (BPD) is a genetically influenced psychiatric illness with disruptions in neural systems supporting cognition and emotion regulation. Volumetric decreases of the hippocampus and amygdala may characterize BPD and serve as putative endophenotypes for the illness. The purpose of the present study was to evaluate whether the magnitude of these volume reductions and their associations with state-of-illness factors and psychiatric disorders which often co-occur with BPD warrant their consideration as potential endophenotypes. Volumetric magnetic resonance imaging results from 11 studies comprising 205 BPD patients and 222 healthy controls were quantitatively synthesized using meta-analytic techniques. Patients showed an average 11% and 13% decrease in the size of the hippocampus and amygdala, respectively. These volumetric differences were not attenuated in patients being treated with psychotropic medications. Comorbid depression, post-traumatic stress disorder, and substance use disorders were unrelated to volumetric decreases in either structure. These findings suggest modest volume reductions of the amygdala and hippocampus bilaterally in BPD which cannot be attributed to illness state or comorbid psychopathology. Decreased volumes of these key limbic structures may hold promise as candidate endophenotypes for BPD.

Dysregulation of hypothalamic-pituitary-adrenal axis activity in major depressive disorder has been found to normalize with successful treatment, though inconsistencies exist. To determine the magnitude of change in cortisol levels from pre to post-treatment in individuals with unipolar depression quantitative methods of meta-analysis were applied. Thirty-four studies met inclusion criteria and consisted of a total of 1049 depressed patients across study samples. The overall mean effect size of pre-post-treatment cortisol measures indicated that approximately 56% of depressed participants had similar cortisol levels before and after treatment regardless of symptom improvement. The mean effect size of pre-post cortisol measures for those who responded to treatment was larger than the mean effect size of non-responders; however, this difference did not reach statistical significance. As well, no significant differences in mean effect size of pre-post cortisol measures based on type of treatment (e.g. antidepressant vs. ECT) were found. Subtype of depressive illness and length of treatment may contribute to the magnitude of change in cortisol measure before and after treatment. Inconsistent findings within the reviewed literature may confound the overall results. The type of treatment and response to treatment do not appear to impact the magnitude of change in cortisol level pre to post-treatment. Our findings suggest that the utility of cortisol as an outcome measure may be limited to specific subsets of the depressed population, and that given the variability in HPA results between studies, it is premature to state that cortisol is not a good outcome measure.

The stability and validity of a neurocognitive typology for schizophrenia were studied in 55 chronic patients who met DSMIII-R criteria for the illness. Subtypes were based on an earlier cluster analytic study by Heinrichs and Awad (1993) that utilized the following variables: IQ (WAIS-R), categories (Wisconsin Card Sorting Test), free recall intrusions (California Verbal Learning Test), and bilateral motor performance (Purdue Pegboard). Stability was examined by analyzing subtype assignment at the original assessment and 3 years later at follow-up. Stability over this interval was variable with an overall kappa of .45 and individual kappas from .12 to .66. Adjunct cognitive and clinical data gathered at follow-up provide evidence for the validity of several subtypes, especially in terms of their cognitive and functional differences. There was no evidence of symptom differences in this relatively asymptomatic medicated sample of patients. The results are discussed in terms of the possibility that several patterns of neurocognitive dysfunction may underlie schizophrenia, with implications for understanding the heterogeneity of the illness and its variable functional outcomes.