Cognitive flexibility and its correlation to sleep and neuroplasticity in the course of depression during different treatments

• Applicant: Dr. Jakob Koch
• Subject Area: Clinical Psychiatry, Psychotherapy, Child and Adolescent Psychiatry
• Term: from 2005 to 2009
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5454682

It is a well recognized concept that the pathophysiology of depression is linked to the impairment of neurotrophic mechanisms. Recently, it has been hypothesized that in depression impaired neuroplasticity causes the cognitive deficits usually occuring, most prominently as a decline in tasks of cognitive flexibility and fluency. As yet, however, the evidence for this causal relationship is poor. Only in healthy subjects it could at least partially proved by finding a significant association between the structure of Slow-wave-sleep (SWS), indicating plasticity processes in the cortical cicuitry, and performance concerning cognitive flexibility and fluency. Another focus of recent research on neuroplasticity in mood disorders are neurotrophic effects of antidepressants. In this context the cyclic-AMP-response-element-binding-protein (CREB) is of importance because the phosphorylation and in consequence activation of this transcription factor, essential for synaptic plasticity and memory storage, is increased by antidepressants. To date it is unclear if the activation of pro-plastic signaltransduction cascades by antidepressants is in fact relevant for the remission of cognitive deficits in patients. We will adress this issue by treating patients either with antidepressants or with psychotherapy. Medication comprises either serotonergic or noradrenergic antidepressants considerably differing in their capacity to increase CREB-phosporylation. This enables us to distinguish between those effects that are caused by activation of pro-plastic signaltransduction cascades and those that are generated by other substance-linked effects or psychotherapy. We will investigate to what extent the improvement of cognitive flexibility in the course of treatment is associated with changes in the structure of SWS. Furthermore we will probe CREB-phosphorylation in patients T-lymphocytes previously demonstrated to be a suitable peripheral cellular model. This might facilitate the elucidation of changes in plasticity during treatment on a cellular, network and behavioural level.

• DFG Programme: Research Grants
• Participating Persons: Professor Dr. Josef Aldenhoff; Professor Dr. Robert Göder