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Fritz Henn

PhD, Johns Hopkins University 1967
M.D. University of Virginia 1971

Major depression; human imaging; animal models of depression; astrocytic cell function; role of neurogenesis

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Psychiatric diseases present a major challenge in neuroscience research. It has been particularly difficult to translate the full dimensions of human disease into an animal model which can be studied in anatomical and molecular detail. To address this, we have developed an animal model of depression/anxiety  (learned helplessness) by selectively outbreeding two lines of animals. The first is very sensitive to stress and is spontaneously helpless while the second is resistant to stress and resilient. In comparing the neural circuits mediating a stress response in the two lines we discovered that a small brain region above the thalamus, the lateral habenula, may be a control point which modulates depressive like behavior. Using human imaging we verified this in depressed patients and are now studying the pathophysiology in this circuit in order to attempt to develop better treatments for depression. It appears that overactive glutamate receptor can contribute to the changes seen in depression and we are interested in determining if this is in part due to decreased uptake of glutamate by astrocytes. 

The confirmation of circuit abnormalities in patients similar to those in the animal model has led us to look at deep brain stimulation (DBS) as a mechanism that may alleviate intractable depression by reducing activity in the overactive circuit. The initial trial of DBS in a patient has proved to be successful and we are now beginning a study this in a series of intractable patients in conjunction with clinical collaborators.  Concurrently we are using the animal model to study the effect of DBS at a cellular and synaptic level.

Selected Publications

Vollmayr B, Simonis C, Weber S, Gass P, Henn F. Reduced cell proliferation in the dentate gyrus is not correlated with the development of learned helplessness. Biol Psychiatry. 2003 Nov 15; 54 (10) :1035-40.

Zink M, Vollmayr B, Gebicke-Haerter PJ, Henn FA. Reduced expression of glutamate transporters vGluT1, EAAT2 and EAAT4 in learned helpless rats, an animal model of depression. Neuropharmacology. 2010 Feb; 58 (2) :465-73.

Henn FA, Vollmayr B. Neurogenesis and depression: etiology or epiphenomenon?. Biol Psychiatry. 2004 Aug 1; 56 (3) :146-50.

Manganas LN, Zhang X, Li Y, Hazel RD, Smith SD, Wagshul ME, Henn F, Benveniste H, Djuric PM, Enikolopov G, Maletic-Savatic M. Magnetic resonance spectroscopy identifies neural progenitor cells in the live human brain. Science. 2007 Nov 9; 318 (5852) :980-5.

Roiser JP, Levy J, Fromm SJ, Nugent AC, Talagala SL, Hasler G, Henn FA, Sahakian BJ, Drevets WC. The effects of tryptophan depletion on neural responses to emotional words in remitted depression. Biol Psychiatry. 2009 Sep 1; 66 (5) :441-50.