MANCOVA revealed significant between groups differences in SOPS P, GAF, and the 15-Analyte Index. Post-Hoc analyses using Bonferroni correction revealed that CHR- CTrauma subjects with a history of childhood trauma demonstrated significantly higher SOPS positive symptom scores than CHR- CNoTrauma, and CHR- NCTrauma, CHR- NCNoTrauma subjects. Given that criteria for conversion to psychosis is based on increased scores in the SOPS Positive scale, total childhood trauma may be an important independent variable associated with increased baseline SOPS positive symptoms and help identify a category of individual who are highest risk for conversion to psychosis. Further, CHR-CTrauma demonstrated lower GAF as compared to CHRNCNoTrauma subjects, whereas CHR- CNoTrauma did not demonstrate differences in GAF scores compared to either group of CHR-NC subjects. This again may imply that history of childhood trauma may be an important independent variable associated with increased baseline global functioning and thus help identify a category of clinical high-risk subjects who demonstrate the lowest global functioning. Finally, the 15-Analyte index did not differ between CHR-CTrauma and CHR-CNoTrauma subjects but did differ between CHR-NCTrauma and CHR-NCNoTrauma groups. Given that higher scores on the 15-Analyte index are associated with higher SOPS overall symptoms, lower global functioning, and lower social/role functioning, this finding may be interpreted to mean that CHR subjects with any history of trauma may demonstrate a unique population of subjects with worse clinical outcomes who would benefit most from early intervention. There are several possible limitations of this study that may explain the non-significant association between history of childhood trauma and pro-inflammatory cytokines . While sample size was adequate to detect small to medium between subjects’ effects,indoor cannabis grow system due to employing multiple between-subjects comparisons, risk for Type I error was increased.
Future research may consider use of open public data sets or consortium efforts in order to pool resources and maximize recruitment of sufficient samples to conduct analyses that require a large sample of subjects, such as exploratory factor analyses of inflammatory analytes. Further, measurement of childhood trauma in this study prevents evaluation of the effect of chronicity and severity of trauma to be evaluated. Future studies should consider use of the non-abbreviated Childhood Trauma Questionnaire: CTQ, in order to capture severity and chronicity of each individual sub-type of trauma endorsed. A review by Schafer and Fisher determined that instruments assessing childhood trauma, such as the CTQ, that were originally developed for the general population are also appropriate for use among people with psychosis. However, the use of self-report measures of childhood trauma is additionally prone to bias, particularly when subjects are under the age of 18. Thus, in order to prevent bias in reporting, future studies should employ use of informants that may be able to verify experience of childhood trauma in order to increase reliability of reporting. Moreover, inflammatory analytes and childhood trauma were only evaluated from one time point. Due to the age range of the at-risk sample , this might mean that ongoing changes in inflammatory analytes and additional trauma experiences that occurred during the course of the study, were not captured. Ongoing sampling of childhood trauma on inflammation must be evaluated across time in order to establish more reliable measures of these dynamic processes. The use of cross-sectional data for mediation analyses is limited, as temporal precedence cannot be established thereby preventing implications to be drawn regarding the causal effect of childhood trauma or inflammatory markers on clinical outcomes. While a study by Simpson et al. demonstrated that self-report measurement of childhood trauma in a first episode psychosis sample remained stable and consistent across multiple time points, they found that severity of trauma reported did fluctuate across multiple assessments. If unable to collect multiple biological samples from different time points, implementation of a stress test design with blood marker sampling would allow for testing the impact of trauma on stress reactivity and inflammatory response during the course of one visit.
Additionally, the validation of inflammatory markers in psychosis is ongoing; therefore, selection of specific markers of inflammation to measure at various phases of illness is not well established, nor is there a clear understanding of what inflammatory analytes may be differentially impacted by environmental stress as compared to disease progression. Measuring a large panel of serum markers of inflammation is preferable, but studies must be well-powered in order to establish reliable effects. Evaluating profile networks of inflammatory analytes is needed to understand the dynamic activation and suppression of analytes and provide a clearer understanding of immune system regulation as a whole, as compared to understanding of single analytes. Measurement of single inflammatory analytes provides only a small snapshot of a much larger and more complex picture that is the immune system. Finally, this study lacked assessment of variables known to affect inflammatory analyte levels, namely body mass index . While this study controlled for the effects of antipsychotic, antidepressant, tobacco, and cannabis use, BMI is highly associated with inflammation and thus may have confounded findings in inflammatory analytes. Taken together these results confirm existing research that individuals at CHR for psychosis demonstrate higher total childhood trauma as compared to unaffected comparison subjects and that history of childhood trauma is associated with increased positive psychosis-risk symptoms and worse global functioning. However, total childhood trauma was not associated with inflammation in this sample, thus analyses of the mediating effect of inflammatory analytes in the relationships between childhood trauma and clinical outcomes was non-significant. Instead, this study suggests that total childhood trauma and inflammatory analytes independently predict positive psychosis risk symptoms and lower global functioning; thus, these independent effects are additive. These findings confirm the importance of assessing for childhood trauma and blood-based inflammation in at-risk subjects as a means to identify individuals who may be at the highest risk for poor clinical and functional outcome. Childhood trauma and inflammation may seem difficult variables to target through existing evidence-based psychotherapy interventions. However, there is a growing body of research that supports the use of complementary and alternative medicine psychosocial interventions that may effectively target these factors in psychosis. The goal of research of CAM in psychosis is to replicate results from studies conducted in the general population demonstrating that the use of mind-body interventions reduces reactivity to stress and chronic inflammation.
For example, research Breines et al. demonstrated that higher levels of “self-compassion,” defined by Neff as “the attitude of treating oneself with kindness and non-judgmental understanding,” are associated with reduced IL-6 response in reaction to stress. More importantly, it has been demonstrated that self-compassion is not a “trait,” but rather a modifiable and alterable “state.” Cognitively-Based Compassion Training is a meditation-based program derived from Tibetan Buddhist mind-training that has been demonstrated to enhance empathy and compassion for oneself and others. Research on CBCT in medically stable populations by Pace et al. reveals 6 weeks of compassion meditation training reduced stress-induced immune responses in a stress-test design. Further, Pace et al. demonstrate that strength of reduction in immune response was not mediated by time spent meditating, indicating that benefits of compassion training are not dependent on long hours of practice. This is very relevant to the application and effectiveness of such techniques in children or adolescents,equipment for growing weed particularly those currently experiencing mental health concerns, given that it would be impractical to expect children with mental health concerns to engage in lengthy meditation practice. In fact, Pace et al. demonstrated the feasibility of CBCT in not only adolescents, but those in foster care with a history of early life adversity. Moreover, foster care program adolescents with a history of childhood trauma demonstrated significant reductions in salivary CRP after just 6-weeks of compassion training. Compassion training has not yet been evaluated in CHR population, but there is evidence that adapted mindfulness-based interventions are not only safe and therapeutic for use in chronic psychosis populations, but also may help to decrease individual distress around positive psychosis symptoms, such as auditory hallucinations and delusions . A recent systematic review by Louise, Fitzpatrick, Strauss, Rossell, and Thomas on “third-wave” cognitive behavioral interventions in psychosis, reveals that acceptance-based interventions show moderate effects in reducing depressive symptoms, but no effect in reducing distress around psychosis symptoms or improving functional outcome. Randomized-controlled clinical trials utilizing mindfulness-based interventions for early-psychosis are currently lacking. Nonetheless, these techniques represent a promising category of psychosocial intervention warranting further study as they may modify reactivity to stress and immune response. Other CAM interventions that warrant further study in psychosis populations to target immune response and clinical outcomes include exercise, diet, and cannabidiol. Exercise and diet have been shown to have robust effects on reducing chronic inflammation and improving health outcomes in the adolescents . Research on aerobic exercise in psychosis groups has demonstrated very promising findings, indicating that moderately intense exercises, such as walking or bike riding, may improve positive and negative psychosis risk symptomatology, cognition, and functional outcome . Further, these effects have been replicated in CHR populations .For example, a recently review by Stogios et al. reveals that unmedicated individuals with psychosis demonstrate increased appetite and cravings for fatty foods, which contribute to weight gain and metabolic disturbances known to be associated with higher levels of inflammation. Wu, Wang, Bai, Huang, and Lee revealed that a 6-month combined diet and physical activity program in schizophrenia subjects resulted in reduced BMI, improved metabolic profiles of insulin and triglycerides, as well as improved psychotic symptoms. Cahn, Goodman, Peterson, Maturi, and Mills demonstrated a 3- month mindfulness, diet, and yoga combined intervention resulted in increased levels of BDNF and increased cortisol awakening response in a population of medically stable adults.
Research on novel therapeutics, such as cannabidiol , as a potential treatment for psychosis have demonstrated that CBD may not only have neuroprotective, antioxidant, and anti-inflammatory effects, but also improve disease trajectory of psychosis by reducing positive psychosis symptoms, anxiety, and cognitive deficits in first episode psychosis groups . To date, there are no studies evaluating the effects of diet, exercise, CBD, or combined interventions on immune response to stress in CHR psychosis populations; however, there is strong evidence to warrant further study of these interventions in CHR psychosis groups. Finally, therapeutic interventions that are known to improve clinical outcomes for individuals who have experienced childhood trauma may be particularly important in mitigating long term functional impairments in youth at clinical high risk for psychosis. Bendall, AlvarezJimenez, Nelson, and McGorry describe several recommendations to be considered for good, quality, assessment and intervention withing individuals at risk for psychosis endorsing a history of childhood trauma, including, systematic inquiry about childhood trauma for all individuals with psychosis, and development of individualized treatment plan adapted from cognitive behavioral therapy approaches for the treatment of psychosis and trauma, paying particular attention to pacing of treatment and repeated assessment. Evidence based psychotherapies for trauma that include focus on stress management and interpersonal effectiveness such as Skills Training in Affect and Interpersonal Regulation , may be particularly meaningful for CHR subjects who have a history of childhood trauma. Schafer and Fisher demonstrated the effectiveness and tolerability of STAIR for individuals at clinical high risk for psychosis with history of childhood trauma. However, there has been little research evaluating the effectiveness of evidence-based trauma-focused treatments in this complex population. Studies evaluating the effectiveness of trauma focused interventions may include individuals with psychosis as only a small sub-sample of participants included in the research, but co-occurring psychosis spectrum disorders are often included as exclusionary criteria in evaluation of trauma-focused treatments for individuals with a history of trauma . As previously discussed, compassion training, such as CBCT, may represent a unique category of psychosocial intervention that helps to improve stress reactivity in youth who have experienced early life adversity . Moreover, PoehlmannTynan et al. demonstrated when parents completed 8-10 weeks of CBCT their children demonstrated reduced cortisol, indicating that compassion training for parents may have cascading effects of cumulative stress on their children. Although difficult to achieve, prevention of the occurrence of childhood trauma would be an ultimate goal. Varese et al. maintain that if childhood trauma was removed from the population entirely, the number of individuals presenting with psychosis would be reduced by 33%. Thus, assessment of childhood trauma is an essential first step toward not only early intervention in, but also ultimately prevention of psychosis spectrum disorders.