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Medication-resistant depression (MRD) is associated with poorer
attentional performance and immense socioeconomic costs.
We aimed to investigate the central pathophysiology of MRD, previously
linked to impaired prefrontal cortex function.
A total of 54 participants (22 with MRD, 16 with non-resistant
depression, 16 healthy controls) were recruited. Non-MRD status was
confirmed by a prospective 6-week antidepressant trial. All
medication-free participants underwent a go/no-go task to study
prefrontal cortical function (attention) and positron emission tomography
scans to study regional cerebral glucose metabolism (rCMglu) at rest.
The MRD group had worse attentional ratings and decreased rCMglu compared
with the non-MRD and control groups. Attentional performance was
positively associated with prefrontal cortex rCMglu. The prefrontal
cortex differences between MRD and non-MRD groups remained after
adjusting for past depressive episodes (F(1,35) = 4.154, P = 0.043).
Pronounced hypofrontality, with the associated attentional deficits, has
a key role in the neuropathology of medication-resistant depression.
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