Affective Disorders and Psychosis - MINDLab
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Affective Disorders and Psychosis

 

The monoamine theory of depression postulates abnormal noradrenergic and serotonergic neuromodulation as an important factor. We will test whether depression is associated with dissociated blood flow in hippocampus as a result of dysfunctional stress mechanisms, and that cognitive dysfunction is closely related to local white matter lesions (Videbech et al, 2004). Using fibre-tracking, we recently demonstrated that white matter lesions in late-onset depression interrupt connections to the left orbitofrontal cortex. The effect of antidepressants will be studied in the Chronic Mild Stress model in relation to neuroplasticity. The sensitivity of DWI at 16.4 Tesla, combined with biophysical models is sufficient to estimate dendrite density, and to be correlated with measures of CBF as a test of neurogenesis.

Pain and depression are linked by abnormal monoaminergic ascending and descending output from brainstem raphé nuclei, and the network includes cerebral structures that can be traced and monitored (Kupers 2004). We will test the links in healthy volunteers with experimental pain and in patients with depression, functional disorders (fibromyalgia), or neuropathic pain. Monoaminergic activity will be measured by PET and in CSF. We will also test the hypothesis that chronic pain is a result of maladaptive neuroplasticity (Flor 2006), and we will monitor the reorganization by TMS, dorsal column stimulation, cognitive methods, and deep brain stimulation.


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Revised 7-5-2012