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Background and Hypothesis Psychotic Like Experiences (PLEs) are widely prevalent in children and adolescents and increase the risk of developing psychosis. Cortical gyrification characterizes brain development from in utero till about the first 2 years of life and can be measured in later years as static gyrification changes demonstrating neurodevelopment and dynamic gyrification changes reflecting brain maturation during adolescence. We hypothesized that PLEs would be associated with static cortical gyrification changes reflecting a neurodevelopmental abnormality. Study Design We studied 1252 adolescents recruited in the IMAGEN consortium. We used a longitudinal study design, with Magnetic Resonance Imaging measurements at age 14 years and age 19 years; measurement of PLEs using the Community Assessment of Psychic Experiences (CAPE) questionnaire at age 19 years; and clinical diagnoses at age 23 years. Study Results Our results show static gyrification changes in adolescents with elevated PLEs on 3 items of the CAPE—voice hearing, unusual experiences of receiving messages, and persecutory ideas—with lower cortical gyrification in fronto-temporal regions in the left hemisphere. This group also demonstrated dynamic gyrification changes with higher cortical gyrification in right parietal cortex in late adolescence; a finding that we replicated in an independent sample of patients with first-episode psychosis. Adolescents with high PLEs were also 5.6 times more likely to transition to psychosis in adulthood by age 23 years. Conclusions This is the largest study in adolescents that demonstrates fronto-temporal abnormality of cortical gyrification as a potential biomarker for vulnerability to PLEs and transition to psychosis. [ABSTRACT FROM AUTHOR]

Increasing evidence suggests that eveningness is associated with increased risk for depression. Eveningness, however, is also associated with poor sleep quality and the unique role of eveningness in depressive symptomatology remains to be elucidated. The goal of the current study, therefore, was to examine the inter-relationships between eveningness, subjective sleep quality and depressive symptoms in healthy participants free of current or previous depression and sleep disorder. Here, 167 healthy participants (mean age 24.16, 129/38 females/males) completed the reduced Morningness–Eveningness Questionnaire (rMEQ), the Pittsburgh Sleep Quality Index (PSQI) and the Centre for Epidemiological Studies Depression Scale (CES-D). Bootstrap mediation analysis for a simple mediation model including rMEQ, PSQI and CES-D was applied. Eveningness was associated with increased depressive symptoms and mediation analysis showed that this relationship was partly mediated by sleep quality. Our results suggest that indicators of depression observed in evening-type individuals cannot be attributed exclusively to disturbed sleep. We suggest that interventions that target both sleep quality and dysfunctional cognitive styles would be optimal to promote well-being in evening-type individuals. [ABSTRACT FROM AUTHOR]

Increasing evidence suggests evening chronotypes are at increased risk for developing depression. Here, we examined if, similar to acutely depressed patients, evening chronotype individuals display biases in emotional face recognition. Two hundred and twenty-six individuals completed an online survey including measures of sleep quality, depression/anxiety and chronotype followed by a simple emotion recognition task presenting male and female faces morphed in 10 steps between 0 (neutral) and 100% sad or happy. Evening chronotype was associated with increased recognition of sad facial expressions independently of sleep quality, mood, age and gender. The current results extend previous work indicating that negative biases in emotional processing are present in evening chronotypes and may have important implications for the prevention and treatment of depression in these vulnerable individuals. [ABSTRACT FROM PUBLISHER]

Background: It is estimated that one third of patients with schizophrenia fail to adequately respond to antipsychotic medication, termed ‘treatment-resistance’. This occurs despite adequate blockade of D2 receptors in the brain. The parsimonious options are that treatment resistance could arise through a failure of cognitive control over the dopaminergic dysfunction in the striatum; or has a different primary non-dopaminergic mechanism that isn’t targeted by current antipsychotics. Contemporary models suggest that schizophrenia is associated with reduced reward prediction errors (RPE) and consequent aberrant salience driven by increased dopamine levels that ‘drown out’ phasic signals. This causes positive symptoms and impaired reward learning. However, RPE signalling in treatment-resistant patients appears intact despite sub-optimal behavioural performance. It is therefore unclear how reward learning is impaired in these patients. Methods: We investigated how reward learning is disrupted at the network level in 21 medicated treatment-responsive and 20 medicated treatment-0resistant patients with schizophrenia compared with 24 healthy controls (HC). Participants learnt to associate one of two emotional faces with a reward during a reinforcement learning task in an MRI scanner. Functional MRI BOLD signal was extracted from four brain regions (fusiform cortex, amygdala, caudate and anterior cingulate cortex (ACC)) activated in response to face cues and RPEs. These formed a network of interacting brain regions supporting reward learning. Dynamic Causal Modelling assessed how effective connectivity between regions in this cortico-striatal-limbic network is disrupted in each patient group compared to HC. Connectivity was also examined with respect to symptoms and salience. Finally, cognitive control and the role of glutamate were assessed by relating top-down connectivity from the ACC with glutamate levels measured from the same region of the ACC. Results: In responsive patients, there was enhanced top-down connectivity from the ACC to sensory regions (fusiform and amygdala) and reduced input to the caudate compared to HC. Increased top-down connectivity was inversely correlated with symptom severity and sensory-salience. This suggests the presence of an effective compensatory mechanism for unreliable sensory information in responsive patients. Resistant patients however showed normal network connectivity compared to HC except abnormal connectivity within the ACC. This supports an alternative, nondopaminergic mechanism disrupting reward learning in this refractory group. Increasing connectivity from ACC to caudate was related to positive symptom severity and salience in this group. Moreover, ACC glutamate levels were related to key top-down connections in HC and responsive patients but were not related to any connections in resistant patients. This suggests that glutamate may not be modulating connectivity effectively in this network to exert cognitive control and update reward predictions. Discussion: In summary, differential mechanisms underlie disrupted reward learning between responsive and resistant groups. Resistant patients show similar RPE signalling and network connectivity to HC suggesting their dopaminergic functioning is intact. Impaired glutamate function may present a key mechanism that disrupts reward learning – and why do-paminergic drugs are ineffective. This finding is important for developing new drugs (e.g. glutamatergic targets) and guiding treatment strategies (e.g. giving clozapine earlier) in resistant patients. Future research probing cognitive control mechanisms and glutamate function will be useful to elucidate this putative pathology in treatment resistance. [ABSTRACT FROM AUTHOR]