Neuropsychological and functional outcomes in recent-onset major depression, bipolar disorder and schizophrenia-spectrum disorders: a longitudinal cohort study

Abstract

Functional disability is the lead contributor to burden of mental illness. Cognitive deficits frequently limit functional recovery, although whether changes in cognition and disability are longitudinally associated in recent-onset individuals remains unclear. Using a prospective, cohort design, 311 patients were recruited and assessed at baseline. One hundred and sixty-seven patients met eligibility criteria (M=21.5 years old, s.d.=4.8) and returned for follow-up (M=20.6 months later, s.d.=7.8). Two-hundred and thirty participants were included in the final analysis, comprising clinically stable patients with major depression (n=71), bipolar disorder (BD; n=61), schizophrenia-spectrum disorders (n=35) and 63 healthy controls. Neuropsychological functioning and self-rated functional disability were examined using mixed-design, repeated-measures analysis, across diagnoses and cognitive clusters, covarying for relevant confounds. Clinical, neuropsychological and functional changes did not differ between diagnoses (all P>0.05). Three reliable neuropsychological subgroups emerged through cluster analysis, characterized by psychomotor slowing, improved sustained attention, and improved verbal memory. Controlling for diagnosis and changes in residual symptoms, clusters with improved neuropsychological functioning observed greater reductions in functional disability than the psychomotor slowing cluster, which instead demonstrated a worsening in disability (P<0.01). Improved sustained attention was independently associated with greater likelihood of follow-up employment (P<0.01). Diagnosis of BD uniquely predicted both follow-up employment and independent living. Neuropsychological course appears to be independently predictive of subjective and objective functional outcomes. Importantly, cognitive phenotypes may reflect distinct pathophysiologies shared across major psychiatric conditions, and be ideal targets for personalized early intervention.

Figure 1

Mean standardized neuropsychological performance (±s.e.) at baseline (a) and mean standardized neuropsychological change (±s.e.) at follow-up (b) by diagnosis. At baseline (a), neuropsychological functioning was significantly different between diagnoses across all measures (except FAS). Specifically, patients with schizophrenia-spectrum disorder (SZ) performed worse than healthy controls (HCs; P<0.05) on all measures (except FAS). Major depression (MD) and bipolar disorder (BD) each performed worse than HC (P<0.05) on RVP-A, PAL and LM-Ret. Separately, MD and BD performed worse than HC (P<0.05) on TMT-A and LM-I, respectively. MD and BD each outperformed SZ on TMT-A, PAL, LM-I, LM-Ret and IED (P<0.05). MD and BD did not differ from each other on any measure (P>0.05). At follow-up (b), LM-Ret was the only measure improving significantly over time across diagnoses (P<0.05). All group × time interactions were nonsignificant (P>0.05). FAS, Controlled Oral Word Association Test; IED, Intra-/Extradimensional shift test-total errors; LM-I, Logical Memory I; LM-Ret, Logical Memory II Percent Retention; PAL, Paired Associates Learning-adjusted errors; RVP-A, Rapid Visual Processing Hits A′ TMT-A′, Trail Making Test—Part A.

Figure 2

Mean baseline and follow-up WHODAS-II (a, b) and WHOQoL (c, d) scores (±s.e.). ^aOverall change and group × time interaction is nonsignificant (P>0.05). ^bOverall change is nonsignificant (P>0.05), whereas group × time interaction is significant (P<0.01). Pairwise comparisons showed that the SusAtn+ and VerMem+ clusters were each changing at significantly different rates from the PsySpd− cluster (P<0.01 and P<0.001, respectively). No other pairwise comparison was significant. ^cOverall change and group × time interaction is nonsignificant (P>0.05). ^dOverall change and group × time interaction is nonsignificant (P>0.05). WHODAS-II, World Health Organization Disability Assessment Schedule Version 2.0; WHOQoL, World Health Organization Quality of Life (BREF) Scale.