Treating the “E” in “G × E”: Trauma-Informed Approaches and Psychological Therapy Interventions in Psychosis

Abstract

Despite advances in genetic research, causal variants affecting risk for schizophrenia remain poorly characterized, and the top 108 loci identified through genome-wide association studies (GWAS) explain only 3.4% of variance in risk profiles. Such work is defining the highly complex nature of this condition, with omnigenic models of schizophrenia suggesting that gene regulatory networks are sufficiently interconnected such that altered expression of any “peripheral” gene in a relevant cell type has the capacity to indirectly modulate the expression of “core” schizophrenia-associated genes. This wealth of associated genes with small effect sizes makes identifying new druggable targets difficult, and current pharmacological treatments for schizophrenia can involve serious side effects. However, the fact that the majority of schizophrenia genome-wide associated variants fall within non-coding DNA is suggestive of their potential to modulate gene regulation. This would be consistent with risks that can be mediated in a “gene × environment” (G × E) manner. Stress and trauma can alter the regulation of key brain-related pathways over the lifetime of an individual, including modulation of brain development, and neurochemistry in the adult. Recent studies demonstrate a significant overlap between psychotic symptoms and trauma, ranging from prior trauma contributing to psychosis, as well as trauma in response to the experience of psychosis itself or in response to treatment. Given the known effects of trauma on both CNS gene expression and severity of psychosis symptoms, it may be that pharmacological treatment alone risks leaving individuals with a highly stressful and unresolved environmental component that continues to act in a “G × E” manner, with the likelihood that this would negatively impact recovery and relapse risk. This review aims to cover the recent advances elucidating the complex genetic architecture of schizophrenia, as well as the long-term effects of early life trauma on brain function and future mental health risk. Further, the evidence demonstrating the role of ongoing responses to trauma or heightened stress sensitivity, and their impact on the course of illness and recovery, is presented. Finally, the need for trauma-informed approaches and psychological therapy-based interventions is discussed, and a brief overview of the evidence to determine their utility is presented.

Childhood maltreatment and treatment outcome in psychotic disorders: a systematic review and meta‐analysis

“…However, more than half of the studies included in this meta‐analysis were published within the last four years, which is in line with the growing interest and empirical findings regarding the importance of CM for psychotic disorders . At the same time, the importance of genetic aetiology factors for the development of psychotic disorders probably is weaker as compared to earlier assumptions and essentially moderated by environmental factors such as CM .…”

“…These mechanisms are less likely to affect treatment in early psychosis patients. Finally, genetic factors are also associated with both CM and the chronicity of psychotic disorders and might contribute to the moderation by chronicity.…”

Childhood maltreatment and social functioning in psychotic disorders: a systematic review protocol

“…If a moderating role of genetic factors was confirmed between CM and social functioning in PD, findings would emphasize the gene × environment perspective about PD and would advocate for trauma-informed approaches and psychosocial therapy-based interventions (Gianfrancesco, Bubb, & Quinn, 2019 ). Although the evidence base has grown on the safe use of trauma-focused psychological interventions in reducing posttraumatic symptoms in individuals with PD, yet results are mixed with regard to secondary effects on additional domains (Adams, Ohlsen, & Wood, 2020 ; Swan, Keen, Reynolds, & Onwumere, 2017 ).…”

“…Moreover, if a mediating role of stress sensitivity is confirmed in the association between CM and social functioning in PD, this would mean that we support the biopsychosocial approach and give further information on socio-cognitive and socio-affective trainings targeting (acute) psychosocial stress related (heightened) responses (Engert, Grant, & Strauss, 2020 ; Engert, Kok, Papassotiriou, Chrousos, & Singer, 2017 ), to help patients cope with stress in their life that may be preventing them from achieving or maintaining recovery (Gianfrancesco et al, 2019 ). Furthermore, if post-traumatic symptoms and other comorbid mood disorders would mediate the association between CM and social functioning, our findings would guide cognitive-behavioural therapies (in adapted formats) for individuals with PD and CM (Fares-Otero et al, 2021 ), may including breathing retraining, education, and cognitive restructuring (Mueser et al 2015 ).…”

Illness Severity Moderated Association Between Trait Anxiety and Amygdala-Based Functional Connectivity in Generalized Anxiety Disorder

“…Increased right amyFC with the bilateral postcentral gyrus (PCG) is also found in the current study. The PCG is the hub of the sensorimotor network (SMN) and is responsible for receiving sensory information from distinct brain regions (Li et al, 2019 ). Increased amyFC with the PCG may cause excessive sensory information input leading to hyperesthesia, which is a common sign in GAD patients.…”