Psychiatric Manifestations in Autoimmune Disorders

Multiple Sclerosis and Transverse Myelitis

Director: Adam I. Kaplin, M.D., Ph.D.

This research program is aimed at investigating the effect of the immune system on depression.  In order to coordinate its efforts to combat infections, the immune system produces chemical messengers called cytokines. Our research investigates the effects of these cytokines on the brain, particularly as it relates to mood regulation and cognition.

Our research involves two approaches, the first being the use of animal models to explore the role of cytokines in depression. Several lines of evidence suggest that cytokines, particularly interleukin-6 (IL-6), contribute to the pathogenesis of immune-mediated depression. We are examining the effect of antidepressants, steroids, and cytokines such as IL-6 on neurogenesis and hypothalmus-pituitary-adrenal (HPA) axis regulation in mice, both in the hippocampus and hypothalamus.

The second approach involves investigating the effects of cytokines on the human brain through studying autoimmune neurological disorders, which are associated with a high rate of depression and difficulties in memory and concentration. This research aims specifically at patients with multiple sclerosis (MS) and transverse myelitis (TM). We are determining how changes in cytokine levels and brain activity correlate with mood, cognition and neurologic outcomes. This approach involves cytokine profiling, neurocognitive testing and magnetic resonance spectroscopy. Patients with MS and TM are compared to patients with non-autoimmune myelopathies (e.g. spinal cord stroke or radiation-induced myelopathy). Subjects will be followed longitudinally to determine if changes in cytokine levels and brain metabolites parallel changes in mood, cognition, and neurologic outcomes. Neuroendocrine correlates of depression in TM and MS subjects will be ascertained through examination of the function of their HPA axis.

We anticipate that the results of this study will have direct implications for the psychiatric comorbidities of TM and MS. These findings could significantly expand our ability to diagnose, prognosticate, and treat psychiatric sequelae in patients with diverse types of autoimmune disorders. Our research also has the potential to illuminate immune mechanisms in idiopathic major depression.

FACULTY AND STAFF

Adam Kaplin, M.D., Ph.D.
Assistant Professor of Psychiatry and Neurology
akaplin@jhmi.edu
410-955-2343

Michele Pucak, Ph.D.
Research Associate
mpucak@jhsph.edu
410-614-1445

Edward Hammond, M.D., M.P.H.
ehammon5@jhmi.edu
410-502-2574