BASIC SCIENCE RESEARCH
Evidence linking neuronal immediate early genes to enduring forms of neuronal plasticity has heightened interest in their role in mediating behavioral alterations induced by drugs of abuse and other forms of brain stimulation. As these genes are rapidly induced by neuronal stimulation, they represent a mechanism by which drug administration could elicit long-term adaptations in neuronal function that underlie their reinforcing properties. We have focused on one of these immediate early genes, Narp, which clusters AMPA receptors and is expressed selectively in limbic brain regions regulating behavior. A series of studies we have conducted suggest Narp signaling pathways may represent a potential therapeutic target for drug addiction and possibly other motivated behaviors. For example, we have found that Narp knockout mice are deficient in extinction of drug craving. To learn more about molecular mechanisms and circuitry underlying this finding, we are utilizing viral vectors to locally regulate Narp expression in vivo and field recordings to determine how Narp deletion affects learning in brain reward pathways.
Electroconvulsive therapy (ECT) is the most effective available therapy for treating depression however little is known about its mechanism of action. Mice genetically engineered to lack key genes which are inducible by electroconvulsive stimulation and which regulate synaptic plasticity may yield clues to how it works. Although ECT is highly effective, it is not without side-effects and so there has been keen interest in developing alternate forms of therapeutic brain stimulation for depression, such as repetitive transcranial magnetic stimulation (rTMS) and deep brain stimulation, that are more focal and do not involve anesthesia. Many aspects of these brain stimulating techniques can be efficiently and effectively studied in animal behavioral models. We have begun such to learn how to improve efficacy and decrease adverse effects of these treatments.
Although ECT is one the oldest and most established treatments in psychiatry, even in recent years we have continued to learn how we can improve its efficacy and decrease cognitive side-effects associated with the treatment such as by using high dose right unilateral treatment and ultrabrief pulsewidth stimulation. Our team is examining several different aspects of ECT delivery to learn how we can affect and improve on these outcome measures.
Clinical Trial of TMS with Mood Stabilizers in Bipolar Depression
If you are between the ages of 22-68, currently suffering from Bipolar depression, and are currently taking a mood stabilizer you may be eligible to participate in a research study on deep Transcranial Magnetic Stimulation (dTMS). This study is being conducted to evaluate the safety and effectiveness of the H-Coil Transcranial Magnetic Stimulation (TMS) in treating bipolar depression. Participation involves 25 visits over 8 weeks. There are up to three weeks for screening visits to determine eligibility. During this time participants will also need to be gradually taken off of psychiatric medications except for a mood stabilizer. Once eligible, there are 8 weeks of the study procedure including 2 follow-up visits. Participants will have a 50% chance of receiving real TMS or sham TMS once a day, 5 days per week for 4 consecutive weeks, then 3 times during week 5, and once during week 6. Participant safety will be monitored, and each participant will be asked questions pertaining to their mood and anxiety. There will be compensation for participating in this study. For more information please call 410-614-1732. The principal investigator is Dr. Irving Reti. (IRB Protocol # NA_00045624).
Reti IM and Baraban JM (2000): Sustained increase in Narp protein expression following repeated electroconvulsive seizure. Neuropsychopharmacology. 23: 439-43.
Wachtel LE, Kahng SW, Cascella N, Dhossche DM, Reti IM (2008): Electroconvulsive Therapy for Severe Catatonic Deterioration in an Autistic Girl with Mental Retardation and Self-injury: A Case Report. American Journal of Psychiatry, 165: 329-33.
Anderson E and Reti IM (2009). ECT in Pregnancy: A Review of the Literature from 1941 to 2007. Psychosomatic Medicine, 71: 235-242.Dhossche DM, Reti IM, Wachtel LE (2009). Catatonia and autism: a historical review, with implications for electroconvulsive therapy today. J ECT, 25:19-22, Jan 31 Epub.
Wachtel LE, Contrucci-Kuhn S, Griffen M, Reyes C, Reti IM (2010). Electroconvulsive therapy in a man with autism experiencing severe depression, catatonia and self-injury, J ECT, 26:70-3D’Agati D, Bloch Y, Levkovitz Y, Reti IM (2010). rTMS in adolescents: efficacy and safety considerations. Psychiatry Research, 177:280-5
Harel EV, Zangen A, Roth Y, Reti IM, Braw Y, Levkovitz Y (2011). H-coil repetitive Transcranial Magnetic Stimulation for treatment of Bipolar Depression: An Add-on, Safety and Feasibility study. World Journal of Biological Psychiatry, 12:119-26.
Reti IM, Torres J, Morad A, Jayaram G (2011). Pseudocholinesterase deficiency in an ECT patient: a case report. Psychosomatics, Psychosomatics, 52:392-3.
Maixner, D, Hermida AP, Husain MM, Rudowski M, Reti IM (2011). Succinylcholine Shortage and Electroconvulsive Therapy. American Journal of Psychiatry, 168:986-7.
Gallegos J, Vaidya P, D’Agati D, Jayaram G, Ngyugen T, Tripathi A, Trivedi J, Reti IM. Decreasing adverse outcomes associated with unmodified ECT: suggestions and possibilities. J ECT, in press
Vaidya P, Anderson E, Bobb A, Pulia K, Jayaram G, Reti IM. A within-subject comparison of propofol and methohexital anesthesia for electroconvulsive therapy. J ECT, in press
Yi J, Torres J, Azner Y, Vaidya P, Shiavi A, Reti IM. Flumazenil pre-treatment in benzodiazepine-free patients: a novel method for managing declining ECT seizure quality. J ECT, in press
Reti IM, Walker M, Pulia K, Gallegos J, Jayaram G, Vaidya P. Safety considerations for outpatient electroconvulsive therapy. Journal of Psychiatric Practice, in press