Charla: Translational Research in Treatment-Resistant Mood Disorder



Psychiatric disorders are the leading cause of years-of-life-lived-with-disability worldwide. Antidepressant medications were discovered around 1960 and more recent developments, such as SSRIs, are no more effective than the original antidepressants. After more than half a century, we still do not understand how antidepressants cause remission from depression, let alone why so many patients do not respond to treatments and remain chronically ill.
In 1991, largely on the basis of animal model studies of human illness, Deakin & Graeff published ‘5-HT and mechanisms of defence’ which has been cited over 600 times and recently reviewed (Deakin, 2014, ‘The origins of ‘5-HT and mechanisms of defence’ by Deakin and Graeff: A personal perspective’, Journal of Psychopharmacology). Despite the original article being highly cited, there have been relatively few attempts at testing the theory in humans and none using instrumental learning tasks during fMRI in patients with treatment-resistant depression. Recently, Prof. Steele published a test of Deakin & Graeff’s predictions (Johnston B, et al, 2015, Brain). The results strongly supported most of Deakin & Graeff’s predictions, extending this to treatment-resistant mood disorder.

The clinical service Prof. Steele worked in until recently uses anterior cingulotomy as a treatment of last resort, in highly treatment-resistant patients who want the procedure and can provide sustained informed consent. Lesions are made in the white matter deep to the anterior mid-cingulate cortex (aMCC). In a recently accepted manuscript (Tolomeo S, et al, 2016, Brain), Prof. Steele argues that the aMCC has a causal role in negative affect and cognitive control. It is plausible that lesions made within a brain region associated with the subjective experience of negative affect and pain may be therapeutic for some patients with otherwise intractable mood, anxiety and pain syndromes.
Prof. Steele will finish by combining ideas from both studies, suggesting implications for future translational mood disorder research.

CV Prof. Douglas Steele, PhD:

La charla se realizará en inglés.


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