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Background Impulsivity is considered a possible phenotype underlying the expression of self-harm and suicidal behaviors. Yet impulsivity is a not a unitary construct and there is evidence that different facets of impulsivity follow different neurodevelopmental trajectories and that some facets may be more strongly associated with such behaviors than others. Moreover, it is unclear whether impulsivity is a useful predictor of self-harm or suicidal behavior in young people, a population already considered to display heightened impulsive behavior. Methods A systematic review and meta-analysis of studies published in Medline, PubMed, PsychInfo or Embase between 1970 and 2017 that used a neurocognitive measure to assess the independent variable of impulsivity and the dependent variable of self-harm and/or suicidal behavior among young people (mean age Results 6183 titles were identified, 141 full texts were reviewed, and 18 studies were included, with 902 young people with a self-harm or suicidal behavior and 1591 controls without a history of these behaviors. Deficits in inhibitory control (13 studies, SMD 0.21, p-value = 0.002, 95% confidence interval (CI) (0.08–0.34), prediction interval (PI) = 0.06–0.35) and impulsive decision-making (14 studies, SMD 0.17, p-value = 0.008, 95% CI (0.045–0.3), PI = 0.03–0.31) were associated with self-harm or suicidal behavior. There were no significant differences between measures of different facets of impulsivity (ie. delay discounting, risky decision-making, cognitive or response inhibition) and self-harm or suicidal behavior. Conclusion Multiple facets of impulsivity are associated with suicidal behavior in young people. Future suicide research should be designed to capture impulsive states and investigate the impact on different subtypes of impulsivity.

Impairments in mismatch negativity (MMN) in schizophrenia are well-established; these findings have been extended to show impairments at early illness stages and in bipolar disorder. A substantial literature supports MMN as an index of NMDA receptor output, however, few studies have conducted in vivo assessments to elucidate the neurochemical underpinnings of MMN. Sixty young (16–33 years) participants with bipolar disorder (n = 47) or schizophrenia (n = 13) underwent 1H-MRS and MMN assessment. Glutamate over creatine (Glu/Cr) levels in the anterior cingulate cortex (ACC) and hippocampus were determined and MMN was measured frontally and temporally. Correlational analyses assessed the relationship between MMN amplitudes and Glu/Cr. Any significant relationships were assessed for specificity with a follow up correlation analysis of MMN and n-acetyleaspartate (NAA/Cr). No associations between frontal or temporal MMN and ACC or hippocampal Glu/Cr were noted in the bipolar group. In the schizophrenia group, frontal and right temporal MMN amplitudes corresponded with increased ACC Glu/Cr at the trend-level. Right temporal MMN was similarly significantly associated with NAA/Cr. MMN was not associated with hippocampal Glu/Cr. This work provides in vivo evidence that glutamatergic processes may underlie MMN generation in early stage schizophrenia but not in early stage bipolar disorder suggesting differences in the MMN mechanism in these groups. The negative association between ACC Glu/Cr and MMN is consistent with findings of reduced MMN and increased in vivo glutamatergic neurometabolite levels in early stage schizophrenia. Furthermore, these results indicate that examining in vivo NAA/Cr may have provide additional insights into the MMN mechanism in schizophrenia.

Background The pervasiveness of subclinical anxiety in children, highlights the need to identify its neurobiological underpinnings to better inform interventions. Given the now well-established link between aberrant emotion processing and anxiety disorders and yet limited neurobiologically-informed research in this area, this study examined the neural correlates of emotion recognition (ER) in children with sub-clinical anxiety. Method Ninety children (aged 9–11 years) with sub-clinical anxiety, completed an emotion recognition task whilst undergoing functional magnetic resonance imaging. The ER task required participants to match shapes and match emotional faces in the context of shape distractors. Participants also completed the Spence Children's Anxiety Scale (SCAS). Results Greater blood oxygenation level dependent (BOLD) changes associated with ER were observed in the lateral occipital cortex, middle frontal gyrus, superior middle frontal gyrus, inferior frontal gyrus, superior parietal lobule, inferior parietal lobule, superior temporal gyrus, and middle temporal gyrus symmetrically. The clusters also included posterior cingulate cortex, insula, hippocampus, amygdala and cerebellum during matching emotions than those matching shapes. Females showed greater BOLD changes associated with ER than males in the right middle frontal gyrus. The BOLD changes associated with ER in the right middle frontal gyrus and right insula were greater in children with SCAS subscale (physical injury fear) scores in the normal range than those with elevated scores. Discussion The findings in this study implicate the right middle frontal gyrus and insula as key regions in the neurobiological underpinnings of sub-clinical anxiety as they relate to attention impairments in anxious children. Conclusion The results of this study indicate there are gender differences in young participants during emotion processing and provides a neurobiological target for attention impairments in anxious children.

Mental disorders and their functional impacts evolve dynamically over time. Neurocognition and clinical symptoms are commonly modelled as predictors of functioning, however, studies tend to rely on static variables and adult samples with chronic disorders, with limited research investigating change in these variables in young people with emerging mental disorders. These relationships were explored in a longitudinal clinical cohort of young people accessing early intervention mental health services in Australia, around three-quarters of whom presented with a mood disorder (N = 176, aged 12-30 at baseline). Bivariate latent change score models quantified associations between neurocognition (a latent variable of working memory, verbal memory, visuospatial memory, and cognitive flexibility), global clinical symptoms, and functioning (self- and clinician-rated) and their relative change over follow-up (median = 20 months). We found that longitudinal changes in functioning were coupled with changes in global clinical symptoms (β = -0.43, P 0.001), such that improvement in functioning was related to improvement in clinical symptoms. Changes in neurocognition were not significantly associated with changes in functioning or clinical symptoms. Main findings were upheld in three sensitivity analyses restricting the sample to: (a) adults aged 18-30; (b) participants with 12-24 months of follow-up; and (c) participants without a psychotic disorder. Our findings show that global symptom reduction and functional improvement are related in young people with emerging mental disorders. More work is needed to determine the temporal precedence of change in these variables. Future studies should apply this methodology to intervention studies to untangle the causal dynamics between neurocognition, symptoms, and functioning.

While disturbances of the sleep-wake cycle are common in people with affective disorders, the characteristics of these disturbances differ greatly between individuals. This heterogeneity is likely to reflect multiple underlying pathophysiologies, with different perturbations in circadian systems contributing to the variation in sleep-wake cycle disturbances. Such disturbances may be particularly relevant in adolescents and young adults with affective disorders as circadian rhythms undergo considerable change during this key developmental period. This study aimed to identify profiles of sleep-wake disturbance in young people with affective disorders and investigate associations with biological circadian rhythms. Fifty young people with affective disorders and 19 control participants (aged 16-31 years) underwent actigraphy monitoring for approximately two weeks to derive sleep-wake cycle parameters, and completed an in-laboratory assessment including evening dim-light saliva collection for melatonin assay and overnight continuous core body temperature measurement. Cluster analysis based on sleep-wake cycle parameters identified three distinct patient groups, characterised by 'delayed sleep-wake', 'disrupted sleep', and 'long sleep' respectively. The 'delayed sleep-wake' group had both delayed melatonin onset and core temperature nadir; whereas the other two cluster groups did not differ from controls on these circadian markers. The three groups did not differ on clinical characteristics. These results provide evidence that only some types of sleep-wake disturbance in young people with affective disorders are associated with fundamental circadian perturbations. Consequently, interventions targeting endogenous circadian rhythms to promote a phase shift may be particularly relevant in youth with affective disorders presenting with delayed sleep-wake cycles.

Childhood maltreatment (CM) is associated with enhanced risk of psychiatric illness and reduced subcortical grey matter in adulthood. The hippocampus and amygdala, due to their involvement in stress and emotion circuitries, have been subject to extensive investigations regarding the effect of CM. However, the complex relationship between CM, subcortical grey matter and mental illness remains poorly understood partially due to a lack of longitudinal studies. Here we used segmentation and linear mixed effect modelling to examine the impact of CM on hippocampal and amygdala development in young people with emerging mental illness. A total of 215 structural magnetic resonance imaging (MRI) scans were acquired from 123 individuals (age: 14-28 years, 79 female), 52 of whom were scanned twice or more. Hippocampal and amygdala volumes increased linearly with age, and their developmental trajectories were not moderated by symptom severity. However, exposure to CM was associated with significantly stunted right hippocampal growth. This finding bridges the gap between child and adult research in the field and provides novel evidence that CM is associated with disrupted hippocampal development in youth. Although CM was associated with worse symptom severity, we did not find evidence that CM-induced structural abnormalities directly underpin psychopathology. This study has important implications for the psychiatric treatment of individuals with CM since they are clinically and neurobiologically distinct from their peers who were not maltreated.

Objective Adult psychosis patients (i.e. over the age of 25 years) who are also lifetime cannabis users (CANN±) appear to exhibit superior cognition compared to never-using patients (CANN-). The objective of this meta-analysis was to evaluate the cognitive differences between CANN- and patients who currently use cannabis (CANN+) (i.e. during the CANN± patients' cannabis-using stage). Specifically, focusing on young patients under the age of 25 years, the typical stage of both psychosis- and cannabis-onset. Method Of the 308 studies identified through database searches and secondary referencing, 14 compared neurocognition of CANN+ and CANN- in young people with psychotic disorders (mean age between 15 and 45 years). Effect sizes were extracted using neurocognitive test performance between CANN+ and CANN- and random effects modelling was conducted on pooled ES and moderator analyses. Results CANN+ performed worse on several cognitive domains (i.e. premorbid IQ, current IQ, verbal learning, verbal working memory, motor inhibition) compared to CANN-. The association between age and performance in CANN+ cognition was varied, with older age predictive of worse performance in processing speed, sustained attention, verbal memory, and better performance in verbal learning and very fluency. Of note, CANN+ outperformed CANN- in tests of conceptual set-shifting. Conclusion These results are consistent with previous findings indicating that CANN+ demonstrate poorer neurocognition than CANN-; and that this is exacerbated with increasing age. Our findings demonstrate significant cognitive differences between patients with CANN+ versus CANN- even at early-onset psychosis, which could suggest a different underlying mechanism towards psychosis for cannabis users.

Risky alcohol consumption and tobacco smoking is highly prevalent in bipolar disorder (BD) and is associated with increased formation of neural reactive oxygen species. Proton magnetic resonance spectroscopy ((1)H-MRS) is an in vivo imaging modality that allows quantification of glutathione (GSH) concentration, the brains primary antioxidant. Sixty-four patients with BD and 49 controls (18-30 years) completed self-report questionnaires regarding alcohol and tobacco use and underwent (1)H-MRS. Levels of GSH in the hippocampus and anterior cingulate cortex (ACC) were determined. Within-group Pearson's correlations were used to explore the relationship between alcohol use and GSH concentration for BD and controls, covarying for age, gender, family history of alcohol dependence and smoking status. Relationships between GSH and presence/severity of alcohol-induced blackouts were determined using Spearman's correlations. In BD, reduced hippocampal-GSH associated with higher alcohol use (R = -0.489, p

Oxidative stress has recently been reported to assume a significant role in the pathophysiology of bipolar disorder. Several studies have demonstrated the replenishment of glutathione (GSH) diminishes oxidative cellular damage and ameliorates depressive symptoms in this disorder. Whilst the mechanism by which GSH exerts any clinical effect is unknown it has been proposed that it involves the bolstering of antioxidant defences by increasing the bioavailability of GSH, which in turn reverses clinical symptoms of depression. Such a proposal is predicated on the implicit assumption that GSH is diminished in these patients prior to GSH supplementation. However hitherto no study has reported in vivo measures of GSH in patients with bipolar disorder. Using magnetic resonance spectroscopy we obtained in vivo measures of GSH in young people with bipolar disorder and contrasted these with matched healthy controls. Young people with bipolar disorder were found to have no diminution in baseline GSH concentration and, furthermore, no significant correlations were found between GSH and clinical scores of depression or mania. The results do not support the hypothesis that oxidative stress is involved in the primary pathophysiology of bipolar disorder.