No abstract

Traumatic life events (TLEs) have been associated with multiple psychiatric diagnoses, including anxiety disorders, major depression, PTSD, and psychosis. To advance our understanding of the complex interactions between forms of adversity as they manifest across the lifespan, psychosis, and symptom content, we undertook a mixed-methods investigation of TLEs and psychosis. Our research explored the association between cumulative exposures, type of TLE, and proximity to the traumatic event and psychosis; the association between TLEs and clinical symptomology including specific types of delusions and/or hallucinations; and how qualitative data further inform understanding of complex relationships and patterns of past trauma and symptoms as they unfold over time. There were a total of 97 participants in the quantitative study sample, 51 participants with present state psychosis and 46 non-clinical. There were a total of 34 qualitative study participants, all of whom were experiencing psychosis. The quantitative analysis showed that when comparing persons with psychosis to the non-clinical group, there were no group differences in the overall total score of TLEs. However, there was a significant difference in cumulative TLEs that “Happened,” demonstrating that as the number of TLEs increased, the likelihood of clinical psychosis also increased. We also found a correlation between lifetime cumulative TLEs that “Happened” and PANSS five-factor analysis: positive, excitement, depression, thought disorder, activation, and paranoia scores. The qualitative analysis further built on these finding by providing rich narratives regarding the timing of trauma-related onset, relationships between trauma and both trauma-related and religious–spiritual content, and trauma and hallucinatory modality. Analysis of participant narratives suggests the central role of localized cultural and sociopolitical influences on onset, phenomenology, and coping and contributes to a growing literature calling for strengths-based, client-driven approaches to working with distressing voices and beliefs that centers the exploration of the personal and social meaning of such experiences including links to life narratives. Findings also underscore the clinical importance of trauma assessment and trauma-informed care.

Understanding alterations in perceptual experiences as a component of the basic symptom structure of psychosis may improve early detection and the identification of subtle shifts that can precede symptom exacerbation. We explored the phenomenological construct of absorption and psychotic experiences in both clinical (bipolar psychosis and schizophrenia spectrum) and non-clinical participants. Participants with psychosis endorsed significantly higher absorption compared to the non-clinical group. Absorption was positively correlated with all types of hallucinations and multiple types of delusions. The analysis yielded two distinct cluster groups that demarcated a distinction along the continuum of self-disturbance: on characterized by attenuated ego boundaries and the other stable ego boundaries. The study suggests that absorption is a potentially important but under-researched component of psychosis that overlaps with, but is not identical to the more heavily theorized constructs of aberrant salience and hyperreflexivity.

Altered immune function is an established finding in psychotic disorders such as schizophrenia and bipolar disorder with psychosis, though its role in their development and progression remains to be understood. Evidence suggests altered JAK-STAT1 pathway activity in peripheral blood cells from participants with schizophrenia compared to controls. Activation of this pathway leads to increased expression of complement component 4A (C4A), which has recently been implicated in schizophrenia. Here, we examine mRNA expression of C4A in peripheral blood cells from participants with schizophrenia, bipolar disorder and controls. STAT1 and IRF-1 mRNA expression are included as measures of JAK-STAT1 pathway activation in the same participants. Further, we examine the association of each genes mRNA expression with clinical symptom measures using the Positive and Negative Syndrome Scale (PANSS) and the Psychotic Symptom Rating Scale (PSYRATS). We demonstrate that C4A, STAT1 and IRF-1 mRNA expression levels are correlated across the entire sample, indicating shared transcriptional regulatory mechanisms. Further, we show that C4A mRNA expression alone is positively associated with psychotic symptomatology, specifically the presence and severity of delusions. These findings are noteworthy given recent findings that demonstrate a critical role for complement proteins in synaptic pruning, alterations of which are proposed to contribute to psychopathology in psychosis.

Alcohol is one of the most widely used recreational substances worldwide, with drinking frequently initiated during adolescence. The developmental state of the adolescent brain makes it vulnerable to initiating alcohol use, often in high doses, and particularly susceptible to alcohol‐induced brain changes. Microglia, the brain parenchymal macrophages, have been implicated in mediating some of these effects, though the role that these cells play in the progression from alcohol drinking to dependence remains unclear. Microglia are uniquely positioned to sense and respond to central nervous system insult, and are now understood to exhibit innate immune memory, or “priming,” altering their future functional responses based on prior exposures. In alcohol use disorders (AUDs), the role of microglia is debated. Whereas microglial activation can be pathogenic, contributing to neuroinflammation, tissue damage, and behavioral changes, or protective, it can also engage protective functions, providing support and mediating the resolution of damage. Understanding the role of microglia in adolescent AUDs is complicated by the fact that microglia are thought to be involved in developmental processes such as synaptic refinement and myelination, which underlie the functional maturation of multiple brain systems in adolescence. Thus, the role microglia play in the impact of alcohol use in adolescence is likely multifaceted. Long‐term sequelae may be due to a failure to recover from EtOH‐induced tissue damage, altered neurodevelopmental trajectories, and/or persistent changes to microglial responsivity and function. Here, we review critically the literature surrounding the effects of alcohol on microglia in models of adolescent alcohol misuse. We attempt to disentangle what is known about microglia from other neuroimmune effectors, to which we apply recent discoveries on the role of microglia in development and plasticity. Considered altogether, these studies challenge assumptions that proinflammatory microglia drive addiction. Alcohol priming microglia and thereby perturbing their homeostatic roles in neurodevelopment, especially during critical periods of plasticity such as adolescence, may have more serious implications for the neuropathogenesis of AUDs in adolescents.

The role of inner speech in the experience of auditory verbal hallucinations (AVH) and delusions remains unclear. This exploratory study tested for differences in inner speech (assessed via self-report questionnaire) between 89 participants with psychosis and 37 non-clinical controls. We also tested for associations of inner speech with, i) state/trait AVH, ii) AVH-severity; iii) patients' relations with their voices, and; iv) delusion-severity. Persons with psychosis had greater levels of dialogic inner speech, other people in inner speech, and evaluative/motivational inner speech than non-clinical controls. Those with state, but not trait AVH had greater levels of dialogic and evaluative/motivational inner speech than non-clinical controls. After controlling for delusions, there was a positive relation between AVH-severity and both evaluative/motivational inner speech and other people in inner speech. Participants with greater levels of dialogic inner speech reported better relations both with and between their voices. There was no association between delusion-severity and inner speech. These results highlight the importance of better understanding relations between inner speech and AVH, provide avenues for future research, and underscore the need for research into the interrelatedness of inner speech, voices and delusions, and the complexities involved in disentangling these experiences.

No abstract

Objective: Activation of STAT1 is directly downstream of the cytokine receptors that signal from specific proinflammatory cytokines known to be dysregulated in schizophrenia (SZ), such as IFNγ, IL6, IL2 and IL10, as well as hypoxia, viral/bacterial infections and peptide growth factors. If the increased cytokine protein levels repeatedly observed in SZ have biological consequences, then the measurement of pSTAT1 is a logical step forward. Methods: Peripheral blood mononuclear cells (PBMCs) from controls (n = 13) and subjects with SZ (n = 22) were extracted using the Ficoll method. Participants with SZ were diagnosed using the SCID, clinical symptomatology was measured using the Positive and Negative Syndrome Scale (PANSS), and cognitive functioning was measured using the MATRICS Consensus Cognitive Battery. Levels of activated STAT1 (Y701), i.e. phosphorylated STAT1 (pSTAT1), were measured by a commercially available ELISA in nuclear extracts from PBMCs. Results: There was a significant bimodal distribution in the sample, with an SZ subgroup expressing significantly greater levels of activated pSTAT1 than the remainder of the participants. In this subgroup, levels of pSTAT1 were significantly higher than in the control group, as well as significantly higher than in the remainder of the SZ subjects. Furthermore, this subsample of patients manifested significantly poorer cognitive performance on several measures of the MATRICS. Discussion: pSTAT1 levels may provide a measure of the biological relevance of widely reported elevations in levels of cytokines in SZ over the past several decades. Activation of kinase cascades can be used to partition or disassemble the composite immune signal in patients living with SZ.