White Matter Hyperintensities and Clinical Phenotype in Late-Onset Psychiatric Disorders: A Multidimensional...

White matter hyperintensities (WMHs) have been implicated in late-onset psychiatric disorders, but their contribution to this clinical phenotype remains insufficiently understood.

We conducted a cross-sectional transdiagnostic study of 90 consecutively admitted acute patients with schizophrenia, bipolar disorder (BD), and major depressive disorder (MDD) meeting the predefined inclusion criteria. Patients with a late onset were compared to earlier onset (EO) psychiatric patients. Late onset was defined as the median age of the disorder onset of the sample (≥40 years). Multidimensional clinical, cognitive, psychomotor, metabolic, and neuroimaging data were evaluated (WHM burden and cerebral atrophy), and a cognitive-psychopathologic composite index was derived. Correlations and sensitivity analysis were performed. A multivariable linear regression was performed to assess the independent effects of age, vascular risk factors, and WMH severity on cognitive performance and psychiatric symptoms.

In patients with LO psychiatric disorders, greater WMH burden was significantly associated with poorer global cognition and specific cognitive domains, lower delusional symptoms severity, and greater suicidal thoughts/behavior intensity. These associations were markedly weaker or not present in EO patients. The regression model explained 36.5% of the variance in the cognitive-psychopathologic composite index. After adjusting for age and cumulative risk factors, Fazekas was the only significant independent predictor (β = -0.495, p = 0.001).

WMH burden was associated with differences in clinical characteristics in LO psychiatric disorders, including cognitive and neuropsychiatric symptoms. Our findings support a possible vascular-neuropsychiatric interaction in LO phenotypes.