Clinic risk associated with comorbidity of (subclinical) psychosis, anxiety and depressive symptoms: A case for stratified medicine in psychiatry

Background Meta-analyses link childhood trauma to depression, mania, anxiety, and psychosis. It is unclear, however, whether these outcomes truly represent distinct disorders following childhood trauma, or that childhood trauma is associated with admixtures of affective, psychotic, anxiety and manic psychopathology throughout life. Aim To investigate the impact of trauma on psychopathological phenotype, functional outcome, and daily life stress reactivity. Methods We used data from a representative general population sample (NEMESIS-2; n  = 6646), of whom respectively 1577 and 1120 had a lifetime diagnosis of mood or anxiety disorder, as well as from a sample of patients with a diagnosis of schizophrenia (GROUP; n  = 825). Multinomial logistic regression was used to assess whether childhood trauma was more strongly associated with isolated affective/psychotic/anxiety/manic symptoms than with their admixture. Additionally, we examined these groups in terms of social functioning, clinical severity, and quality of life. In a separate sample ( n  = 621), daily life (emotional and cortisol) stress reactivity was assessed, using ambulatory assessment. Results In all samples, childhood trauma was considerably more strongly associated with an admixture of symptoms of depression, anxiety, psychosis, and mania, rather than with these symptoms in isolation. Individuals exposed to childhood trauma, who also had an admixture of symptoms, had a lower quality of life, more help-seeking behaviour, higher prevalence of substance use disorders, and lower social functioning, compared with individuals not exposed to trauma, without an admixture of symptoms, or neither. Furthermore, trauma-exposed individuals with an admixed psychopathological phenotype show a higher daily emotional stress reactivity. Conclusion Childhood trauma increases the likelihood of a specific admixture of affective, anxiety and psychotic symptoms cutting across traditional diagnostic boundaries. Stratifying according to childhood trauma exposure thus identifies an admixed phenotype, possibly induced by continuous daily life stress reactivity, that has important clinical relevance. Identification of functionally meaningful aetiological subgroups may aid clinical practice.