Longitudinal Gray Matter Development Associated With Psychotic Experiences in Young People

Background: Grey matter abnormalities are observed across the psychosis spectrum. The trajectory of these abnormalities in healthy adolescents reporting sub-threshold psychotic experiences (PE) may provide insight into the neural mechanisms underlying psychotic symptoms. The risk of psychosis and additional psychopathology is even higher amongst these individuals who also report childhood adversity/DSM5 diagnoses. Thus, the aims of this longitudinal study are to investigate PE related volumetric changes in young people, noting any effects of childhood adversity/DSM5 diagnosis. Methods: 211 young people aged 11-13 participated in the initial Adolescent Brain Development study. PE classification was determined by expert consensus at each timepoint. Participants underwent neuroimaging at 3 timepoints, over 6 years. 76 participants with at least one scan were included in the final sample; 34 who met criteria for PE at least once across all the timepoints (PE group), and 42 controls. Data from 20 bilateral regions of interest were extracted for Linear Mixed Effects analyses. Results: Right hippocampal volume increased over time in the control group, with no increase in the PE group (p = 0.00352). DSM5 diagnosis and childhood adversity were not significantly associated with right hippocampal volume. There was no significant effect of group or interaction in any other region. Conclusions: These findings further implicate right hippocampal volumetric abnormalities in the pathophysiology underlying psychotic experiences. Furthermore, as suggested by previous studies in those at clinical high risk for psychosis and those with first episode psychosis, it is possible that these deficits may be a marker for later clinical outcomes.</p

Microstructural changes along the cingulum in young adolescents with psychotic experiences: an along-tract analysis

Psychotic experiences (PEs) such as hallucinations and delusions are common among young people without psychiatric diagnoses and are associated with connectivity and white matter abnormalities, particularly in the limbic system. Using diffusion magnetic resonance imaging (MRI) in adolescents with reported PEs and matched controls, we examined the cingulum white matter tract along its length rather than as the usually reported single indivisible structure. Complex regional differences in diffusion metrics were found along the bundle at key loci following Bonferroni significance adjustment (p < .00013) with moderate to large effect sizes (.11-.76) throughout all significant subsegments. In this prospective community-based cohort of school-age children, these findings suggest that white matter alterations in the limbic system may be more common in the general non-clinical adolescent population than previously thought. Such white matter alternations may only be uncovered using a similar more granular along-tract analysis of white matter tracts. </p

Childhood trauma, the HPA axis and psychiatric illnesses: a targeted literature synthesis

Studies of early life stress (ELS) demonstrate the long-lasting effects of acute and chronic stress on developmental trajectories. Such experiences can become biologically consolidated, creating individual vulnerability to psychological and psychiatric issues later in life. The hippocampus, amygdala, and the medial prefrontal cortex are all important limbic structures involved in the processes that undermine mental health. Hyperarousal of the sympathetic nervous system with sustained allostatic load along the Hypothalamic Pituitary Adrenal (HPA) axis and its connections has been theorized as the basis for adult psychopathology following early childhood trauma. In this review we synthesize current understandings and hypotheses concerning the neurobiological link between childhood trauma, the HPA axis, and adult psychiatric illness. We examine the mechanisms at play in the brain of the developing child and discuss how adverse environmental stimuli may become biologically incorporated into the structure and function of the adult brain via a discussion of the neurosequential model of development, sensitive periods and plasticity. The HPA connections and brain areas implicated in ELS and psychopathology are also explored. In a targeted review of HPA activation in mood and psychotic disorders, cortisol is generally elevated across mood and psychotic disorders. However, in bipolar disorder and psychosis patients with previous early life stress, blunted cortisol responses are found to awakening, psychological stressors and physiological manipulation compared to patients without previous early life stress. These attenuated responses occur in bipolar and psychosis patients on a background of increased cortisol turnover. Although cortisol measures are generally raised in depression, the evidence for a different HPA activation profile in those with early life stress is inconclusive. Further research is needed to explore the stress responses commonalities between bipolar disorder and psychosis in those patients with early life stress. </p