As many as two-thirds of multiple sclerosis (MS) patients are unable to retain employment. Neurological and cognitive status are known to be significant predictors of unemployment, but the relationship between the two is unclear. Furthermore, the association between employment status and depression, anxiety, and personality has not been adequately explored in MS patients. This study examined the demographic, neurological, neuropsychological, and personality factors associated with unemployment in MS. We also sought to determine the utility of the Multiple Sclerosis Functional Composite (MSFC), a measure of MS-related disability incorporating physical and cognitive measures, in predicting employment status. A consecutive sample of 106 MS patients (61.3% unemployed) completed the Brief Repeatable Battery of Neuropsychological Tests (BRBN), Hospital Anxiety and Depression Scale (HADS), and NEO Five-Factor Personality Inventory. The MSFC emerged as the most robust predictor of employment status in MS patients, exceeding the predictive value of the EDSS. Together with NEO "Agreeableness" and HADS Depression subscore, the MSFC accounted for 49.8% of the variance in employment status. Unemployment was also associated with a progressive disease course, longer disease duration, and being female. While Global Cognitive Impairment did not differentiate between groups, unemployed patients scored significantly lower on three of five BRBN indices: Symbol Digit Modality Test, Paced Auditory Serial Addition Test, and Word List Generation. The findings highlight the utility of the MSFC as a predictor of unemployment in MS. Furthermore, a strong association was found between unemployment and the personality construct "Agreeableness", and severity of depression.

Depression is common in patients with multiple sclerosis, but to date no studies have explored diffusion tensor imaging indices associated with mood change. This study aimed to determine cerebral correlates of depression in multiple sclerosis patients using diffusion tensor imaging. Sixty-two subjects with multiple sclerosis were assessed for depression with the Beck Depression Inventory (BDI-II). All subjects underwent magnetic resonance imaging. Whole brain and regional volumes were calculated for lesions (hyper/hypointense) and normal-appearing white and grey matter. Fractional anisotropy and mean diffusivity were calculated for each brain region. Magnetic resonance imaging comparisons were undertaken between depressed (Beck Depression Inventory > or = 19) and non-depressed subjects. Depressed subjects (n = 30) had a higher hypointense lesion volume in the right medial inferior frontal region, a smaller normal-appearing white matter volume in the left superior frontal region, and lower fractional anisotropy and higher mean diffusivity in the left anterior temporal normal-appearing white matter and normal-appearing grey matter regions, respectively. Depressed subjects also had higher mean diffusivity in right inferior frontal hyperintense lesions. Magnetic resonance imaging variables contributed to 43% of the depression variance. We conclude that the presence of more marked diffusion tensor imaging abnormalities in the normal-appearing white matter and normal-appearing grey matter of depressed subjects highlights the importance of more subtle measures of structural brain change in the pathogenesis of depression.