Perceptions of stigma in youth at clinical high risk for psychosis and depressive symptomatology.

It is unclear what types of stigma youth at clinical high risk for psychosis (CHR) experience, and the relationship between them and symptomatology. 94 CHR youth, and a control group of 45 youth with no psychosis spectrum symptoms (NP) were rated for perceived devaluation (i.e. negative views from others) and internalized mental health stigma (i.e. the extent to which they would agree with said views) as well as positive and mood symptomatology. CHR youth reported stigma more frequently than the NP group (χ2(1) = 53.55, p < .001) and at higher levels (perceived devaluation: t (137) = 8.54, p < .001; internalized stigma: t (137) = 7.48, p < .001). Surprisingly, in the CHR group, positive symptoms held no significant relationship to stigma measures. However, ratings of perceived devaluation stigma were associated with depressive symptomatology (ß = 0.27, t = 2.68, p = .0087) and depression scores were conversely associated with perceived devaluation stigma (ß = 0.30, t = 2.05, p = .043). These findings speak to the relationship between depressive symptomatology and perceived devaluation stigma in CHR youth. Perceived devaluation stigma showed greater clinical significance and could have different mechanisms than internalized stigma in CHR youth. It is also noteworthy that while positive symptoms play a central role in defining the CHR syndrome, they seem less relevant to the experience of stigma than mood symptoms. These findings highlight the importance of interventions aimed at ameliorating youth's exposure to negative views about mental health as those managing depressive symptomatology.

Hippocampal subfields, daily stressors, and resting cortisol in individuals at clinical high-risk for psychosis.

INTRODUCTION: The hippocampus, comprised of functionally distinct subfields, both regulates stress and is affected by it during psychosis pathogenesis. Hippocampal abnormalities are evident across psychosis spectrum and are associated with aberrant cortisol levels and greater environmental stressors exposure. These associations, particularly at the subfield-level, are poorly understood in individuals at clinical high-risk (CHR) for psychosis. This represents a significant literature gap given this critical pathogenetic period is characterized by an interplay between environmental stressors and biological susceptibility. METHODS: A total of 121 participants including 51 CHR (mean age=18.61) and 70 healthy controls (HC; mean age=18.3) were enrolled in the study. Participants completed a structural scan, salivary cortisol assays, and a self-report measure assessing distress from daily stressors exposure (DSI). Hippocampal subfield segmentation was conducted using Freesurfer. RESULTS: Smaller hippocampal subfields were associated with greater stress levels. Greater DSI was associated with lower volumes in CA1 (r = -0.38) and CA2/3 (r = -0.29), but not in CA4/DG (r = -0.28), presubiculum (r = -0.09), or subiculum (r = -0.17). Higher resting cortisol was associated with lower volumes in presubiculum (r = -0.4) but not subiculum (r = -0.22), CA1 (r = 0.08), CA2/3 (r = 0.1), or CA4/DG (r = -0.005). Regressions indicated effects for CA1 and DSI (ß = 0.57, p = .03) and presubiculum and cortisol (ß = 0.61, p = .02) are specific to CHR participants relative to HCs. CONCLUSIONS: The findings provided insights into links between stress and brain vulnerability during psychosis-risk period. Regional differences highlighted potentially different mechanisms by which stress impacts specific subfields. Presubiculum may be more susceptible to the impact of early stress on HPA-axis and cornu amonis to acute stressors.

Consistent Exposure to Psychosocial Stressors and Progressive Intolerance to Stress in Individuals at Clinical High Risk for Psychosis.

A body of evidence suggests that exposure to psychosocial stressors and stress sensitivity are involved in psychosis pathogenesis. However, little is known about the temporal course of these domains in those with psychosis-risk syndromes. Furthermore, to date, there have been no studies examining associations between psychosocial stressors and impaired stress tolerance, or how these factors might be implicated in symptom progression prior to psychosis onset. A total of 73 clinical high-risk (CHR) participants and 78 healthy controls (HCs) completed baseline measures of life event (LE) exposure and impaired stress tolerance. Additionally, 54 CHR and 57 HC participants returned to complete the same procedures at a 12-month follow-up assessment. Results indicated that when compared to HCs, CHR individuals exhibited increased LE exposure and impaired stress tolerance at baseline. Longitudinal analyses compared subgroups of CHR participants who exhibited positive symptoms worsening over the 1-year course (CHR-Prog), improved or steady (CHR-Remiss/Persist), and HCs. CHR-Prog individuals showed consistently elevated independent LEs exposure while CHR-Remiss/Persist reported a decline and HCs a steady low level across time. Furthermore, CHR-Prog exhibited increased stress intolerance, while the CHR-Remiss/Persist improved and HCs displayed consistently low levels over time. Analyses examining interrelationships between these domains showed a trend level interaction effect predicting follow-up symptoms. Taken together, results from the present study indicate an important role for exposure to stressors and increasing stress intolerance during psychosis pathogenesis. Additionally, findings indicating that decreases in stress exposure may lead to more favorable outcomes provide a promising target for novel targeted interventions.

Measurement Invariance of Psychotic-Like Symptoms as Measured With the Prodromal Questionnaire, Brief Version (PQ-B) in Adolescent and Adult Population Samples.

Valid measurement of group differences in self-reported psychotic-like experiences (PLEs) requires knowing any group-specific measurement properties of the instruments. We investigated the measurement invariance of the 21-item Prodromal Questionnaire-Brief (PQ-B) questionnaire across gender, ethnic minority/majority status, and presence of depressive symptoms in two different US non-clinical undergraduate samples (N = 1,099). For each item, endorsement of the experience and the associated distress were combined for analysis. A unidimensional model of the PQ-B fit the data well. Across genders, the PQ-B showed configural and metric, but not full scalar invariance; there were statistically significant differences in eight thresholds of six items, most being higher endorsement thresholds for self-identified females. Partial scalar invariance was also found for ethnic status, with five thresholds of three items being higher for the minority participants. For depressive symptomatology, defined as the top quintile by the Beck Depression Inventory-II, partial scalar invariance required dropping one item, after which there were statistically significant differences only in two response thresholds. Overall, a wide range of PLE questionnaire items were found to be robust to gender and ethnicity effects, strengthening confidence in found group differences in PLEs. Although full scalar invariance could not be ascertained for any of the group comparisons, the few found scalar differences across groups were small, with minimal impact on group PLE estimates. However, since PLEs are easily conceptually entangled with depression symptoms, similar items should be considered for exclusion if separable constructs are the target of investigation.

Altered selection during language processing in individuals at high risk for psychosis.

INTRODUCTION: Performance in the executive function (EF) domain has been linked to symptoms and functional outcomes in psychosis. Studies have found that UHR populations have difficulty with verbal fluency, which involves multiple facets of EF. Two potentially implicated EF facets were examined to explore whether these could be dissociated in UHR populations: selection among alternatives (measured by selection costs) and retrieval from semantic memory retrieval (measured by retrieval costs). METHODS: A total of 45 UHR individuals and 46 healthy controls (HVs) were assessed with a verb generation task. Differences in selection cost (RT difference between high and low selection demand conditions) and retrieval cost (RT difference between high and low retrieval demand conditions) were examined and participants were also assessed for clinical symptoms. RESULTS: The UHR group showed greater selection costs relative to HVs, F (1, 91) = 4.39, p = 0.039. However, there were no group differences on retrieval cost, F (1, 91) = 0.63, p = 0.43. A positive association (r = 0.41) was found between disorganized and negative symptoms and selection costs (but not retrieval costs) in the UHR group. There was no significant association between selection costs and positive symptoms. DISCUSSION: Increased selection costs may reflect impaired performance in the neural inhibition domain of EF in the UHR population, potentially underlying a mechanistically distinct EF subdomain that affects the group's ability to efficiently select between competing options. Findings suggest that UHR individuals may exhibit impairment in selecting among alternatives, but not in retrieval from semantic memory.

Hippocampal Subregions Across the Psychosis Spectrum.

Introduction: Converging evidence suggests that hippocampal subregions subserve different functions, and are differentially affected by psychosis illness progression. Despite this fact, studies have not often studied subregions cross-sectionally across the psychosis spectrum. Furthermore, little is known about associations between subregion volumes and hippocampus-mediated cognition. Methods: A total of 222 participants (61 ultra high risk [UHR], 91 schizophrenia [SCZ], and 70 healthy volunteers) underwent a 3T MRI scan, as well as structured clinical interviews and a cognitive battery. Hippocampal subfield analysis was conducted with Freesurfer. We compared subregion volumes across groups, controlling for age, gender, and intracranial volume. We also examined associations in the UHR and SCZ groups between hippocampal subregion volumes and verbal learning, visual learning, and working memory. Results: We found a dose-dependent relationship such that the SCZ group showed significantly greater subfield volume reductions than the UHR group, which in turn showed significantly greater subfield volume reductions than the healthy volunteer group. We also found associations between subregion volume and cognitive performance in the visual memory, verbal memory, and working memory domains. Discussion: Our study examined hippocampal subregion volumes cross-sectionally in a large sample across the psychosis spectrum, as well as links with hippocampus-mediated cognitive function. Our findings suggest that hippocampal abnormalities emerge before first psychosis episode onset, and may be etiologically informative.

Hypothalamic-pituitary-adrenal axis dysfunction in non-clinical psychosis.

While studies have examined psychosocial stress in non-clinical psychosis (NCP), it is unclear if the elevated cortisol seen in schizophrenia also occurs in this group. Cortisol was sampled in High- and Low-NCP groups, and findings of elevated resting cortisol in the former suggest that hypothalamic-pituitary-adrenal-axis dysfunction underlies a psychosis continuum.