Schizophrenia patients experience severe difficulties in a range of common activities, defined 'functional milestones' (i.e. marriage, employment, self-supported living).

This study investigated the impairment in functional milestones in treatment resistant schizophrenia (TRS), compared to other severe disabling psychiatric conditions. Moreover, we evaluated whether multiple clinical and psychopathological features may be predictors of outcome in such functional milestones.

157 patients were enrolled and subdivided in four groups by diagnosis: anxious-depressive spectrum, bipolar disorder spectrum, schizophrenia responder patients, TRS patients. Demographic, clinical and social data were collected. Patients underwent psychopathological, psychosocial and cognitive functioning assessments. Positive and Negative Syndrome Scale (PANSS), Personal and Social Performance (PSP) scale, Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), List Learning task for Verbal Memory, Digit Sequencing task for Working Memory, Category Instances task for Verbal Fluency and Tower of London task for Problem Solving were administered. Data were analyzed by ×2 test, ANOVA test and Kruskal-Wallis test. Stepwise multivariate regression was used to correlate functional outcomes to clinical and psychopathological variables.

TRS patients were more severely impaired in all psychosocial areas explored, were exposed to higher antipsychotic doses, had a higher number of hospitalizations, had higher scores on psychopathological rating scales and performed worse on the verbal memory task. Outcomes in functional milestones were more correlated to clinical/psychopathological variables in TRS than in the other groups.

Psychosocial impairment, clinical, and psychopathological features generate a vicious circle in TRS, which is less evident in other disabling psychiatric conditions.