Associations of Stress with Symptoms in Individuals At Clinical High Risk for Developing Schizophrenia: Implications for the Development of Social Work Interventions

Background and Purpose: Stress plays a central role in the onset and exacerbation of  symptoms in schizophrenia, and is a direct or indirect target of most evidence-based psychosocial interventions. Youth at clinical high risk for schizophrenia may similarly experience a heightened level of stress sensitivity that can potentially be addressed through social work interventions. Establishing targets for psychosocial intervention is especially important for clinical high risk youth given ethical and clinical issues in prescribing antipsychotic medication to this population. Stress sensitivity has previously been associated with concurrent and later positive symptom severity in youth at clinical high risk for psychosis. We build on this literature by examining the temporal associations of stress measures and symptom severity over time in a prospective clinical high risk cohort, hypothesizing that impaired stress tolerance covaries over time with severity of positive symptoms, depression, and functional impairment.

Methods:  Cross-sectional and longitudinal associations between stress measures and symptoms were examined in clinical high risk patients (n=65) and demographically-matched controls. Stress measures included exposure to life events and the experience of impaired tolerance to normal stress, such as daily hassles. Symptoms included attenuated positive and negative symptoms, as well as depression, anxiety, and global function. We then compared the high risk cohort and healthy controls at baseline on measures of symptom severity and stress, and used generalized estimating equation analyses to examine covariation between stress measures and symptoms in high risk patients assessed quarterly for up to 4 years.

Results: Youth at clinical high risk reported greater impaired tolerance to normal stress, t(64)=9.6, p<.001, which was associated over time with positive symptoms (unusual thought content, suspiciousness, conceptual disorganization, and total positive), negative symptoms, depression and poor global function. Associations between impaired tolerance to normal stress and symptoms remained when controlling for demographic variables, medications, and substance use (GEE model with Bonferroni correction, all p<.0025). Exposure to life events did not differ between groups at baseline, t(64)=-1.3, p=.21, and bore no association with any symptoms over time. Months enrolled in the study was negatively associated over time with stress sensitivity, positive symptoms, depression, and function (all p<.0025) suggesting a trajectory of general improvement across the cohort.

Conclusion and Implications: Impaired stress tolerance was associated with a wide range of sub-threshold psychotic symptoms, depression and anxiety, and functioning, consistent with it being a core feature of the psychosis risk state. Self-reported exposure to stressful life events, however,  was not associated with symptoms or function. Impaired tolerance to normal stress may be a prime target for early psychosocial intervention. The prescription of antipsychotic medications has been debated for this population due to severe side effects among this age group and lack of clinical benefit among those who were not going to develop a psychotic disorder regardless of intervention. Psychosocial interventions are therefore likely to become a frontline treatment as the psychosis-risk state gains prominence as a clinical diagnosis, making this a highly relevant area for social work practice and the development of social work interventions.