Clinical Psychopharmacology and Neurobiology
Interaction of genetic and environmental factors in psychiatric illness
Investigators: O. Agid, K. Kanias, O. Karni, Y. Kohn, R.H. Segman, N. Turetsky, B. Lerer.
The disorders that our Laboratory is studying from a genetic standpoint are all complex in nature with a significant contribution of environmental factors. We are interested in identifying the environmental factors that are of specific importance and in determining how they interact with genetic predisposition. One environmental factor of great interest is early life stress. In this context, we have studied the relationship between early parental loss (EPL) and the development of psychopathology later in life. We find an association of EPL with major depression, bipolar disorder and schizophrenia, the link with depression being the strongest. Younger age at loss and loss due to parental divorce or separation are more strongly associated. We are exploring these issues in other samples and also in animal models (See: Neurobiology and Neurochemistry of Early Separation).
Algorithm - based pharmacological treatment of major depression
Investigators: O. Agid, B. Lerer.
Clinicians who treat major depression are faced with a bewildering choice of antidepressant drugs. Given that all treatments have a lag period before they are effective, choice of the right antidepressant for a particular patient is of great importance. Unfortunately, there is very little evidence upon which to base such a decision. Reliable predictors of response to a particular antidepressant drug or class of drugs do not exist. We have developed a treatment algorithm for non-psychotic, unipolar, major depression. Patients seen in the outpatient clinic undergo extensive clinical evaluation and are then treated according to the algorithm provided that it is in accordance with appropriate clinical practice for that patient. The algorithm involves progression from a specific serotonin reuptake inhibitor (SSRI), usually fluoxetine at a dose of 20 mg, to a 40-mg dose in patients whose response is inadequate after 4 weeks. Response is evaluated by the Clinical Global Impressions Scale (CGI). Non-responders to SSRI receive augmentation with triiodothyronine (T3) at doses of 25mcg-50mcg for up to three weeks. Patients who do not respond, then go on to receive a tricyclic antidepressant (clomipramine according to plasma levels) or a serotonin and norepinephrine reuptake inhibitor (SNRI, venlafaxine, at doses of 150mg-225mg). The algorithm has further steps. Hamilton Depression and Visual Analogue Scales are also recorded. Application of this algorithm allows extensive data to be gathered on clinical, biochemical and genetic predictors of response to antidepressant drugs of different classes. A comprehensive database containing this information has been implemented and is updated on an ongoing basis.
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