Clinical Psychobiology

Jack M. Gorman, M.D., Director
Annissa Abi-Dargham, M.D., Psychiatrist II
Dolores Malaspina, M.D., Psychiatrist II
Laszlo A. Papp, M.D., Psychiatrist II
Jeremy Coplan, M.D., Psychiatrist I

Mood and Anxiety Disorders Research
Dr. Sanjay Mathew’s current research includes proton magnetic resonance spectroscopic imaging (MRSI) in generalized anxiety disorder and adversely reared nonhuman primates. We are interested in the effects of treatment on MRSI measures in order to test the notion that antidepressants and anxiolytics modify measures reflective of neuronal viability and membrane turnover. We are also beginning a clinical trial of a novel anti-glutamatergic agent (riluzole) in the treatment of anxiety disorders. Collaborators include the SUNY Primate Behavioral Laboratory with Jeremy Coplan, M.D. and Leonard Rosenblum, Ph.D. Ongoing collaborations continue with the Department of Radiology at Columbia University.

Dr. Justine Kent presented results of a PET brain imaging study in panic disorder at the American College of Neuropsychopharmacology annual meeting in December of 2001. Drs. Kent, Sullivan, and Kleber presented results from an interim analysis of a prospective longitudinal study of the effect of life stressors on physiologic variables and maintenance of treatment gains in panic disorder at the annual meeting of the Anxiety Disorders Association of America in Austin, Texas in March of 2002. In May of 2002, Dr. Kent was appointed the Associate Director of the Biological Studies Unit of NYSPI.

The focus of Dr. Sullivan’s research is the elucidation of the brain mechanisms involved in anxiety disorders such as panic disorder, social phobia, and PTSD. More specifically, Dr. Sullivan is investigating abnormalities in cerebrovascular regulation, altered regulation in the brain’s control of the cardiac cycle and respiration, and the interactions between these physiological systems in patients with anxiety disorders. Dr. Sullivan has initiated a collaboration with Dr. Randolph Marshall in department of neurology in order to incorporate the use of intracerebral transcranial Doppler ultrasound technology for study of cerebrovascular regulation during pathological anxiety states. Dr. Sullivan received a Junior Faculty Research Award from the Anxiety Disorders Association of America for salary support for the two years between 7/00 and 6/02.

Schizophrenia Research
Cheryl Corcoran, M.D. has recently received two awards and grants – the Sackler Award and a NARSAD Young Investigator Award – to study and follow adolescents and young adults who are identified as prodromal to psychosis. In the new Center of Prevention and Evaluation – the COPE research clinic - clinically at-risk individuals will be offered treatment (symptom-focused pharmacotherapy and supportive psychotherapy.) Also, at-risk individuals will have longitudinal assessments of clinical symptoms, mood, cognition, psychosocial events, and neuroendocrine measures, such as salivary cortisols. The aim of this study is to characterize the pathophysiology of psychosis onset in individuals who may be showing early signs of disorder.

Dr. Holly Moore, a new recruit to the Lieber Center, studies the interactions among prefrontal and limbic corticostriatal circuits and ascending catecholamine systems in rodent models of psychiatric disease. Her approach has been to use validated models of the neuro- or psychopathology of psychiatric disorders to examine functional differences in prefrontal and/or limbic corticostriatal circuits at the behavioral, neurochemical and neurophysiological level. For example, her laboratory has developed a model of the neuropathology of schizophrenia that employs a neuronal DNA methylating agent to disrupt cerebral cortical development. As adults, the affected rats show a pattern of cortical thinning and neuronal packing that is similar to the mophological abnormalities in schizophrenia. Importantly, she has also shown that these rodents show deficits in behaviors known to depend on hippocampal, parahippocampal and/or prefrontal cortico-striatal circuts. Moreoever, the Moore laboratory has also found in this model neurophysiological abnormalities that may, in part, mediate the behavioral deficits. She plans to use this rodent model to study the relationship between specific maladaptive behaviors associated with schizophrenia and the structure and neuronal activity of limbic and paralimbic corticostriatal circuits. Dr. Moore is also working with Drs. Michael Myers, Harry Shair, and Susan Brunelli of the Sackler Institute and Susan Vannucci of Babies Hospital to create a "lifespan behavioral testing core" a core of scientists and resources that would enable researchers to test sensorimotor function, stress responses and performance of specific cognitive tasks in neonatal, prepubertal, postpubertal adult and senescent rodents. Dr. Moore has also begun collaborations with the laboratories of Drs. Alan Brown and Dolores Malaspina on the use of rodent models to explore the effects of infection during pregnancy, paternal age and changes in DNA methylation per se on the structure and function of limbic and paralimbic corticostriatal circuits. She has also begun to work with scientists in the laboratory of Eric Kandel to use in vivo microdialysis to examine the dynamics of extracellular DA in the striatum and cortex of D1 receptor knock-out mice.

Bipolar Disorder Research
Under the continued direction of Dr. David Printz, the Bipolar Disorder Research Clinic entered its third year with two primary areas of focus: (1) treatment strategies for bipolar depression and (2) hormonal effects on mood in bipolar women and medication effects on fertility and reproduction. With regards to the first area, the clinic received funding from NARSAD to conduct the first double-blind, placebo-controlled trial of supraphysiologic T4 augmentation for treatment refractory bipolar depression. As part of this study, subjects will also provide samples of CSF for determination of central levels of T3, T4 and transthyretin before and after T4 treatment. This will allow us to test hypotheses regarding the mechanism behind the therapeutic benefit of T4 augmentation. Other ongoing depression trials in the clinic include a Stanley Foundation supported study of riluzole, a neuroprotective agent, and an investigator initiated Pfizer study of ziprasidone augmentation. Both of these are add-on studies for individuals with break-through bipolar depression on mood stabilizer therapy.

Issues related to bipolar disorder in women are being explored in two studies. In a collaboration with Dr. Martha Morrell and the Columbia Epilepsy Center, we are examining prospectively the relationship between mood stabilizer therapy and polycystic ovary syndrome. This syndrome, a common cause of infertility, has been associated with valproate in women with epilepsy but its relationship to medication use in bipolar disorder has not been adequately explored. The second study is a prospective evaluation of daily mood ratings, frequent clinical ratings and ovarian hormone levels in reproductive age women with bipolar disorder. This study seeks to clarify the relationship between menstrual cycle phase, circulating hormone levels and mood in bipolar women.

Finally, we are conducting reliability and validity studies of the daily prospective mood rating instrument (Columbia Daily Bipolar Symptom Scale) developed in the clinic and utilized in the hormonal and treatment studies. In data to be presented at this year’s NCDEU conference, we have demonstrated robust correlations between the daily mood ratings (in 6 different dimensions of mood) and clinician-administered (HAM-D, YMRS) and self-report (BDI) clinical rating scales. We hope to demonstrate the utility of the CDBSS as an instrument for providing better outcome measures for clinical trials.