Prefrontal cortex dysfunction and depression in atypical parkinsonian syndromes

Abstract

Depressive symptoms are common in patients with neurodegenerative disorders. Imaging studies suggest that a disruption of frontal-subcortical pathways may underlie depression associated with basal ganglia disease. This pilot study tested the hypothesis that frontal dysfunction contributes to depression associated with multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Depressed patients with MSA (n = 11), PSP (n = 9), and age-matched controls (n = 25) underwent measures of cerebral glucose metabolism applying positron emission tomography with (18)F-fluorodeoxyglucose. Regional metabolism in the patient groups was compared to the normal subjects using the voxel-based statistical parametric mapping. Depressive symptom severity (Hamilton Depression Rating) and degree of locomotor disability (Hoehn & Yahr) were assessed in the patient groups. The association between prefrontal metabolism and the occurrence of depressive symptoms and the degree of locomotor disability was investigated. When compared to controls, MSA patients revealed significant metabolic decreases in bilateral frontal, parietal, and cerebellar cortex and in the left putamen. In PSP patients, significant hypometabolism was demonstrated in bilateral frontal cortex, right thalamus, and midbrain. Depression severity but not the patients' functional condition was significantly associated with dorsolateral prefrontal glucose metabolism in both patient groups. The findings of this pilot study support the hypothesis that depressive symptoms in MSA and PSP are associated with prefrontal dysfunction.

Depressive Disorders: Focally Altered Cerebral Perfusion Measured with Arterial Spin-labeling MR Imaging

“…If, as has been argued (34), metabolism in the prefrontal and thalamic areas relates to the production of "normal" emotion, hypometabolism and hypoperfusion in these areas is at least consistent with abnormal production of emotion in depression. This is supported by neuropsychological evidence that lesions of the frontal cortex result in depressive symptoms (35). Addition- ally, reports (36,37) of increased perfusion or metabolism in the dorsolateral prefrontal and thalamic areas after antidepressant therapy in well-responding patients agree with our observations.…”

Clinical characteristics and quality of life in Chinese patients with multiple system atrophy

“…Anxiety (75.5%) and depression (60%) were common symptoms among MSA patients in this study, which is consistent with the findings of a previous study (Zhang et al, ). Regarding the mechanisms of depression and anxiety in MSA, research on cerebral glucose metabolism has revealed that dorsolateral prefrontal dysfunction contributes to depression in MSA (Herting et al, ). In our study, 15.1% of the MSA patients showed cognitive deficits on the MMSE, which was also found in another study that used the MMSE (Cao et al, ).…”

Social cognitive deficits and their neural correlates in progressive supranuclear palsy

“…We suggest that the deficits in social cognition arise from focal atrophy of critical brain regions and that they are likely to contribute to the reduced quality of life and psychiatric comorbidity among patients and carers (Schrag et al ., 2003; Herting et al ., 2007; Bak et al ., 2010). However, in this study, we did not assess quality of life among our patient cohort, nor monitor the progression of these factors over time, and further work would be required to demonstrate any causal association.…”

“…Generally, patients also have akinetic rigidity and progressive dysarthria and dysphagia. However, significant cognitive problems are common, including apathy and a dysexecutive syndrome (Grafman et al ., 1995; Bak and Hodges, 1998; Millar et al ., 2006; Brown et al ., 2010) and psychiatric comorbidity including depression (Schrag et al ., 2003; Herting et al ., 2007; Bak et al ., 2010) or anxiety (Litvan et al ., 1996 b ; Aarsland et al ., 2001; Borroni et al ., 2008). Half of patients also report social impairments as a negative influence on their quality of life (Schrag et al ., 2003).…”