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Metabolic and inflammatory dysfunction is prevalent in middle-aged people with major mood disorders, but less is known about young people. We investigated the trajectories of sensitive metabolic (Homeostatic Model Assessment for Insulin Resistance [HOMA2-IR]) and inflammatory markers (C-reactive protein [CRP]) in 155 young people (26.9 ± 5.6 years) accessing mental health services. We examined demographic and clinical correlates, longitudinal trajectories and relationships with specific illness subtypes. Additionally, we compared the HOMA2-IR with fasting blood glucose (FBG) for sensitivity. We observed a significant increase in HOMA2-IR and CRP over time with higher baseline levels predicting greater increases, although the rate of increase diminished in those with higher baseline levels. Body mass index predicted increases in HOMA2-IR (p < 0.001), but not CRP (p = 0.135). Multinomial logistic regression revealed that higher HOMA2-IR levels were associated with 2.3-fold increased odds of the “circadian-bipolar spectrum” subtype (p = 0.033), while higher CRP levels were associated with a reduced risk of the “neurodevelopmental psychosis” subtype (p = 0.033). Standard FBG measures were insensitive in detecting early metabolic dysregulation in young people with depression. The study supports the use of more sensitive markers of metabolic dysfunction to address the longitudinal relationships between immune-metabolic dysregulation and mood disorders in young people.
Neurocognitive impairments robustly predict functional outcome. However, heterogeneity in neurocognition is common within diagnostic groups, and data-driven analyses reveal homogeneous neurocognitive subgroups cutting across diagnostic boundaries.
Aims
To determine whether data-driven neurocognitive subgroups of young people with emerging mental disorders are associated with 3-year functional course.
Method
Model-based cluster analysis was applied to neurocognitive test scores across nine domains from 629 young people accessing mental health clinics. Cluster groups were compared on demographic, clinical and substance-use measures. Mixed-effects models explored associations between cluster-group membership and socio-occupational functioning (using the Social and Occupational Functioning Assessment Scale) over 3 years, adjusted for gender, premorbid IQ, level of education, depressive, positive, negative and manic symptoms, and diagnosis of a primary psychotic disorder.
Results
Cluster analysis of neurocognitive test scores derived three subgroups described as ‘normal range’ (n = 243, 38.6%), ‘intermediate impairment’ (n = 252, 40.1%), and ‘global impairment’ (n = 134, 21.3%). The major mental disorder categories (depressive, anxiety, bipolar, psychotic and other) were represented in each neurocognitive subgroup. The global impairment subgroup had lower functioning for 3 years of follow-up; however, neither the global impairment (B = 0.26, 95% CI −0.67 to 1.20; P = 0.581) or intermediate impairment (B = 0.46, 95% CI −0.26 to 1.19; P = 0.211) subgroups differed from the normal range subgroup in their rate of change in functioning over time.
Conclusions
Neurocognitive impairment may follow a continuum of severity across the major syndrome-based mental disorders, with data-driven neurocognitive subgroups predictive of functional course. Of note, the global impairment subgroup had longstanding functional impairment despite continuing engagement with clinical services.
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