Biological Psychiatry
Harold A. Sackeim, Ph.D., Chief
of Psychiatric Research
D.P. Devanand, M.D., Psychiatrist
(Research) II
Sarah H. Lisanby, M.D., Psychiatrist
(Research) II
James R. Moeller, Ph.D., Research
Scientist V
Bobba J. Moody, M.S.W., Research
Scientist III
Mitchell S. Nobler, M.D., Psychiatrist
(Research) II
Bruce Parsons, M.D., Ph.D., Psychiatrist
(Research) II
Joan Prudic, M.D., Psychiatrist
(Research) II
Yaakov Stern, Ph.D., Research
Scientist VI
The Department of Biological Psychaitry is engaged in a range of preclinical and clincal acitiivies. These include the Brain-Behavior Clinic, the Transcranial Magnetic Stimulation Laboratories (preclinical and clinical), theMemory Diosrders Clinic, the Late Life Depression Clinic, the Huntington's Clinic, the Brain Imaging Program, and the ECT Program.
Brain-Behavior Clinic
The Brain-Behavior Clinic (BBC) supports a range of clinical trials emphasizing neuropsychiatric approaches to the treatment of depression in adults of all ages. Therapeutic strategies under study include Transcranial Magnetic Stimulation (TMS), testosterone (as an augmentation to conventional antidepressant medications and as a stand-alone treatment), and sildenafil for SSRI-related sexual dysfunction. In 2000, we concluded an industry-sponsored, two-center study of TMS augmentation of sertraline therapy for unipolar depression and a study of testosterone replacement in depressed men. Work on the potential antidepressant effects of TMS in the depressed phase of bipolar disorder, funded by the Stanley Foundation, continues. Studies detailing the psychobiology of androgenic stimulation in hypogonadal men and in women with low sexual desire are ongoing. The clinic also provides long-term follow-up of patients who participated in the first clinical trial of vagus nerve stimulation (VNS) for treatment-resistant depression.
Transcranial Magnetic Stimulation (TMS)
TMS, a non-invasive form of brain stimulation using rapidly alternating magnetic fields, is used for probing brain-behavior relationships and may have therapeutic potential. The TMS lab conducts studies in a range of neural processes, including motor physiology, visual processing, and affect modulation. In collaboration with Drs. Nestor Matthews and Ning Quan, we completed a study demonstrating a dissociation between the discrimination of speed and motion detection using TMS. Also in 2000, we completed a study led by Dr. Laura Boylan which demonstrated that TMS to the supplementary motor area was not therapeutic in Parkinson's disease (PD). More work is needed to identify optimal stimulus parameters and coil placements for subconvulsive levels of TMS to exert clinical benefit in conditions such as PD and depression.
An important bridging focus in both clinical and preclinical work in the TMS lab has been the development of magnetic seizure therapy (MST) as a novel convulsive technique that may have fewer cognitive side effects than conventional ECT. After years of device development and preliminary studies in nonhuman primates, we performed the first magnetic seizure therapy (MST) session in a human and have launched the first clinical trial of MST for the treatment of major depression. The aims of this study, supported by a Columbia Clinical Trials Award, are to demonstrate the clinical feasibility of MST as an alternative to ECT and to compare the acute cognitive side effects of MST and conventional ECT. We are in the midst of a large R01-supported study on the long-term cognitive, physiological, neuropathological, and neuroplastic effects of chronic convulsive therapy, contrasting the effects of MST with ECS.
Memory Disorders Clinic
The Memory Disorders Clinic is the site of several ongoing and new research projects. One R01 uses PET with a cognitive challenge paradigm in early Alzheimer's disease. This study attempts to distinguish when patients engage the same brain networks as normal controls in solving cognitive tasks (cognitive reserve) from the use of new brain networks (compensation). Dr. Devanand has obtained an Alzheimer's Association grant to investigate the same paradigm in outpatients with mild cognitive impairment, and to compare the results with Alzheimer's patients and controls. Dr. Devanand also obtained renewal from the NIA for his grant, Questionable Dementia: Course and Predictors of Outcome. This study has led to an important observation on the utility of olfactory identification deficits as an early diagnostic marker for Alzheimer's disease. In addition, clinical trials for experimental medications in Alzheimer's disease are conducted at the General Clinical Research Center at the Columbia-Presbyterian Medical Center. Dr. Sano is heading a multicenter NIA study on the utility of estrogen in preventing cognitive decline in elderly women. Dr. Sano's group is also recruiting for a trial involving melatonin to improve sleep in AD and a double-blind study of idebenone, an anti-oxidant, which is currently used to treat dementia in Japan. We reported recently that the age-at-onset for Alzheimer's disease was significantly later and the relative risk was significantly lower for women who took, compared to women who did not take, estrogen even after adjustment for differences in education, ethnic group, and apolipoprotein-E genotype.
Late Life Depression Research Clinic
The Late Life Depression Research Clinic (LLDRC) specializes in the pharmacological treatment of depression in the elderly. Ongoing research in the LLDRC includes a project examining the phenomenology and treatment of dysthymic disorder in the elderly. Work in the clinic has suggested that elderly patients with dysthymia are not simply younger dysthymic patients who have grown older. Relative to younger samples, the elderly dysthymic patient is less likely to have concomitant personality disorder and is more likely to have comorbid medical conditions and late onset of depressive illness. A placebo-controlled study in the LLDRC examines the short- and long-term efficacy of fluoxetine for elderly dysthymic patients. The outcome of this works suggests that placebo and active medication cannot be distinguished, raising questions about optimal treatment of dysthymia in the elderly.
The LLDRC is also the site of a set of brain imaging studies. This work examines both the pathophysiology contributing to depression in the elderly and the state-dependent changes in functional imaging measures that accompany clinical response. During the past year, work continued on an NIMH R01 that examines whether the serotonin reuptake inhibitors (SSRIs), the antidepressant medication most commonly administered in the elderly, are inferior in efficacy to the tricyclic antidepressants for patients with severe or melancholic symptoms.
Huntington's Disease Society of America Center of Excellence
Since its 1991, the HDSA Center has continued to grow; 40 patients were seen this past year, double the number of new patients seen last year. We have also seen an increase in our presymptomatic testing program begun in 1999, which now averages six presymptomatic individuals annually who undergo a six-session clinical protocol.
Many of the research projects are sponsored by the Huntington Study Group, a consortium of 60 centers. We participated in two multi-center experimental therapeutic trials completed this year. CARE-HD is an NIH-funded study of 343 individuals who have been given either coenzyme Q10 or remacemide, (an NMDA inhibitor). Results will be available spring 2001. A 64-patient trial, funded by the FDA, of riluzole, a glutamate inhibitor, was also completed, and results will be available in spring 2001. PHAROS is an observational multicenter study of 1,000 individuals at risk for the development of HD who are being followed every nine months. Both investigators and participants are blind to genetic status. The goals are to determine the earliest manifestations of HD, determine the false positive rate of diagnosing HD, and to explore the ethical issues and feasibility of conducting this unique study. Ultimately, this information will be used to design a prevention trial.
Karen Anderson, MD has completed a study of Obsessive Compulsive Disorder in HD and has found that a significant proportion of patients had either obsessions or compulsions. The presence of obsessions was related to performance on the symbol digit test. Dr Anderson has received a K23 award to pursue her studies of OCD in HD including detailed ratings of OCD, neuropsychological testing, and fMRI.
Brain Imaging Program
Research in structural (MRI) and functional (PET) brain imaging has been supported by several R01s and other awards and has focused on cerebrovascular abnormalities in late-onset depression, therapeutic and cognitive effects of ECT, abnormalities associated with Lyme disease, brain networks associated with episodic and semantic memory, compensation and reserve in patients with questionable dementia and Alzheimer's disease, and the effects of immune challenges on cerebral blood flow. Dr. Shan Yu was recruited from the French Institute of Computer Science to assist in brain image analyses, and new methods for image segmentation and parcellation have been employed.
Electroconvulsive Therapy Program (ECT)
The core inpatient study at NYSPI on the affective and cognitive consequences of ECT was renewed for years 19-23. The major outcome of the just completed study indicated that at sufficient electrical intensity, right unilateral ECT is as effective as a robust form of bilateral ECT, but retains important cognitive advantages, particularly in the long term. This finding is widely considered as helping to resolve the 40-year debate about the relative merits of right unilateral and bilateral ECT. A new multi-center study was funded this year, with NYSPI as the coordinating center, to examine alternative methods to reduce the relapse following ECT, and replicate the findings concerning the advantages of high dosage right unilateral ECT. In its third year, a multisite services grant has shown that that across various hospitals in the NYC area there is little variability in ECT therapeutic outcome, but differences among hospitals in cognitive effects, which appear attributable to methods of treatment administration.
|
Dr. Harold
Sackeim presenting at the Thirteenth Annual OMH Research Conference
|
Left
to right, Dr. Harold Sackeim, Dr. Andrew Dwork, and Dr. Sarah
Lisanby
|
