Heterogeneity in schizophrenia spectrum disorders: studies into functional, affective and metabolic outcomes

Heterogeneity in Schizophrenia Spectrum Disorders: Studies on Functional, Affective, and Metabolic Outcomes This dissertation aimed to explore the heterogeneity in schizophrenia spectrum disorders (SSD) by examining long-term clinical and subjective outcomes in older adults and by investigating the role of depressive symptomatology in relation to metabolic risk. Part 1: Long-term Course of Remission and Quality of Life in Older Adults with SSD With an aging population, the number of older individuals with SSD is increasing. Their care needs often differ from those of younger patients. A better understanding of the long-term course of SSD in later life is therefore essential. Contrary to earlier beliefs that schizophrenia inevitably leads to a dementia-like state, more recent evidence suggests a more diverse and sometimes favorable course in older patients. Symptomatic remission, defined as a state of low symptom severity, has become a useful clinical concept. However, recovery must also include the patient’s perspective, especially in terms of subjective quality of life (SQoL). Using data from the SOUL study, we analyzed 77 patients aged 60+ over a 5-year period. We found that 26% of patients improved in terms of symptomatic remission, while 23% remained stable in remission. Key predictors of a favorable course were lower baseline positive symptoms and having a partner. In a separate analysis of 75 patients from the same cohort, we examined changes in SQoL using the Manchester Short Assessment of Quality of Life (MANSA). About 36% showed clinically relevant improvement, while 20% experienced a decline. Factor analysis revealed three SQoL domains: ‘personal circumstances,’ ‘daily life,’ and ‘social relations,’ with the first two showing notable improvement. Older age predicted more change, whereas a higher baseline SQoL score predicted stability. These findings suggest that improvement in both clinical and subjective outcomes is achievable even at later ages. Part 2: Depressive Symptom Profiles and Metabolic Syndrome in SSD People with SSD have higher mortality rates and shorter life expectancy, partly due to somatic conditions like cardiovascular disease, obesity, and diabetes. Recent studies suggest a link between depressive symptoms and metabolic syndrome (MetS), especially symptoms related to energy dysregulation. We compared depressive symptom profiles in 449 individuals with SSD, 816 with depressive disorders (DD), and 417 healthy controls (aged 18–50). Somatic/vegetative symptoms were more similar between SSD and DD groups than cognitive/mood symptoms. Among SSD patients, depressive symptom severity was associated with male gender, lower social functioning, use of benzodiazepines, and higher positive symptom burden. In a second study of 513 individuals with SSD, we examined the relationship between energy-related depressive symptoms (e.g., hypersomnia, hyperphagia, fatigue) and MetS. A third of the sample met criteria for MetS. Energy-related symptoms—but not melancholic symptoms—were significantly associated with both the presence and severity of MetS. Notably, hypersomnia showed the strongest link. Conclusion This dissertation underscores the heterogeneity in SSD, both in long-term outcomes and comorbid conditions. Older individuals with SSD can experience improvements in remission and quality of life, especially with social support. Additionally, specific depressive symptom patterns—particularly energy-related symptoms—may help identify patients at greater metabolic risk, supporting the need for integrated care approaches that address both mental and physical health.