Emerging Temporal Lobe Dysfunction in People at Clinical High Risk for Psychosis

Clinical high-risk (CHR) individuals have been increasingly utilized to investigate the prodromal phases of psychosis and progression to illness. Research has identified medial and lateral temporal lobe abnormalities in CHR individuals. Dysfunction in the medial temporal lobe, particularly the hippocampus, is linked to dysregulation of glutamate and dopamine via a hippocampal–striatal–midbrain network that may lead to aberrant signaling of salience underpinning the formation of delusions. Similarly, lateral temporal dysfunction may be linked to the disorganized speech and language impairments observed in the CHR stage. Here, we summarize the significance of these neurobiological findings in terms of emergent psychotic symptoms and conversion to psychosis in CHR populations. We propose key questions for future work with the aim to identify the neural mechanisms that underlie the development of psychosis

Impaired processing of threat in psychopathy:a systematic review and meta-analysis of factorial data in male offender populations

BackgroundPsychopathy is a personality disorder characterised by two underlying factors. Factor 1 (affective and interpersonal deficits) captures affective deficits, whilst Factor 2 (antisocial and impulsive/disorganised behaviours) captures life course persistent antisocial behaviours. Impaired processing of threat has been proposed as an aetiologically salient factor in the development of psychopathy, but the relationship of this impairment to the factorial structure of the disorder in adult male offenders is unclear.ObjectivesTo investigate whether threat processing deficits are characteristic of psychopathy as a unitary construct or whether such deficits are specifically linked to higher scores on individual factors.Data sourcesA systematic review of the literature was conducted by searching PubMed, Web of Science and PsycINFO.MethodsStudies were included if they (1) reported physiological measures of threat response as the primary outcome measure (2) indexed psychopathy using a well-validated clinician rated instrument such as the PCL-R (3) investigated male offenders between 18 and 60 years of age (4) reported threat processing analyses using both Factor 1 and Factor 2 scores (5) provided sufficient data to calculate effect sizes and (6) were published in English-language peer-reviewed journals. We identified twelve studies with data on 1112 participants for the meta-analysis of the relationship with Factor 1 scores, and nine studies with data on 801 participants for the meta-analysis of the relationship with Factor 2 scores. We conducted the meta-analyses to calculate correlations using random-effects models.ResultsPCL-R/SV Factor 1 scores were significantly and negatively related to threat processing indices (r = -0.22, (95%CI [-0.28, -.017]). Neither PCL-R/SV Factor 2 scores (r = -0.005, 95%CI [-0.10, 0.09]), nor PCL-R total score (r = -0.05, (95%CI [-0.15, -0.04]) were related to threat processing indices. No significant heterogeneity was detected for the Factor score results.ConclusionsThe meta-analyses of the distinct psychopathy factors suggest that the threat processing deficits observed in male offenders with psychopathy are significantly associated with higher scores on Factor 1. A similar relationship does not exist with Factor 2 scores. Our findings highlight the importance of investigating the potentially discrete relationships between aetiological variables and the two factor constructs in the disorder

Reduced cortical GABA and glutamate in high schizotypy

RATIONALE: Abnormal functioning of the inhibitory gamma-aminobutyric acid (GABA) and excitatory (glutamate) systems is proposed to play a role in the development of schizophrenia spectrum disorder. Although results are mixed, previous 1H-magnetic resonance spectroscopy (MRS) studies in schizophrenia and clinical high-risk samples report these metabolites are altered in comparison to healthy controls. Currently, however, there are few studies of these metabolites in schizotypy samples, a personality dimension associated with the experience of schizophrenia and psychosis-like symptoms. OBJECTIVES: We investigated if GABA and glutamate metabolite concentrations are altered in people with high schizotypy. We also explored the relationship between resilience to stress, GABA metabolite concentrations and schizotypy. METHODS: We used MRS to examine GABA and glutamate levels in the medial prefrontal cortex in people with low and high schizotypy traits as assessed with the Schizotypal Personality Questionnaire. Resilience to stress was assessed using the Connor-Davidson Resilience Scale. RESULTS: Compared to individuals with low schizotypy traits, high schizotypy individuals showed lower cortical prefrontal GABA (F (1,38) = 5.18, p = 0.03, η(2) = 0.09) and glutamate metabolite levels (F (1, 49) = 6.25, p = 0.02, η(2) = 0.02). Furthermore, participants with high GABA and high resilience levels were significantly more likely to be in the low schizotypy group than participants with low GABA and high resilience or high GABA and low resilience (95% CI 1.07–1.34, p < .001). CONCLUSIONS: These findings demonstrate that subclinical schizotypal traits are associated with abnormal functioning of both inhibitory and excitatory systems and suggest that these transmitters are implicated in a personality trait believed to be on a continuum with psychosis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00213-021-05867-y

Relationship between depression, prefrontal creatine and grey matter volume

BACKGROUND: Depression and low mood are leading contributors to disability worldwide. Research indicates that clinical depression may be associated with low creatine concentrations in the brain and low prefrontal grey matter volume. Because subclinical depression also contributes to difficulties in day-to-day life, understanding the neural mechanisms of depressive symptoms in all individuals, even at a subclinical level, may aid public health. METHODS: Eighty-four young adult participants completed the Depression, Anxiety and Stress Scale (DASS) to quantify severity of depression, anxiety and stress, and underwent (1)H-Magnetic Resonance Spectroscopy of the medial prefrontal cortex and structural magnetic resonance imaging (MRI) to determine whole-brain grey matter volume. RESULTS/OUTCOMES: DASS depression scores were negatively associated (a) with concentrations of creatine (but not other metabolites) in the prefrontal cortex and (b) with grey matter volume in the right superior medial frontal gyrus. Medial prefrontal creatine concentrations and right superior medial frontal grey matter volume were positively correlated. DASS anxiety and DASS stress scores were not related to prefrontal metabolite concentrations or whole-brain grey matter volume. CONCLUSIONS/INTERPRETATIONS: This study provides preliminary evidence from a representative group of individuals who exhibit a range of depression levels that prefrontal creatine and grey matter volume are negatively associated with depression. While future research is needed to fully understand this relationship, these results provide support for previous findings, which indicate that increasing creatine concentrations in the prefrontal cortex may improve mood and well-being