McLean Hospital 115 Mill Street Belmont, MA 02478
Eleven McLean Hospital researchers have received Young Investigator Awards from The Brain & Behavior Research Foundation. National Alliance for Research on Schizophrenia and Depression (NARSAD) grants awards to young investigators pursuing brain and behavior research related to depression, bipolar disorder, schizophrenia, autism, attention-deficit hyperactivity disorder, and anxiety disorders like obsessive compulsive and post-traumatic stress disorders.
The 132-member Foundation Scientific Council, a volunteer group of preeminent mental health researchers, leads the rigorous selection process of identifying the most promising ideas for NARSAD Grants. This year, they reviewed applications from 1,030 researchers seeking NARSAD Young Investigator Grants—a grant program that has been the driving force behind thousands of scientific achievements for the past 25 years. From this group, 202 researchers were selected to receive NARSAD Young Investigator Grants to support their innovative research.
Each of the scientists will receive $60,000 from NARSAD over the next two years to study a variety of topics:
William B. Ruzicka, MD, PhD, studies epigenetic changes in brain cells that use the neurotransmitter GABA to communicate with each other are key in generating cognitive symptoms in schizophrenia. These changes in GABAergic cells include decreased activity of the GAD1 gene, which produces the enzyme responsible for synthesizing GABA in the brain. Ruzicka will study the hypothesis that methylation* contributes to the dysfunction of genes in a network that regulates the gene GAD1 and hopes to shed light on the role of epigenetics in disease etiology.
Brian P. Brennan, MD, has developed, with his laboratory, an application of a brain imaging technique called magnetic resonance spectroscopy that allows a more accurate assessment of the glutamate* system than ever before possible. Identifying glutamate-system dysfunction in OCD patients could promote development of novel glutamate-modulating treatments.
Yunjie Tong, PhD, will use multimodal brain imaging to study the response of patients with major depressive disorder to repetitive transcranial magnetic stimulation (rTMS). To establish a biomarker that may predict outcome, the real time hemodynamic reaction of the brain to rTMS during each treatment session will be measured by functional near infrared spectroscopy. The research will contribute to the establishment of novel biomarkers in treatment evaluations, as well as individualization of treatment plans.
Pia Pechtel, PhD, is investigating whether deficits in reward processing are associated with high-risk behavior, specifically in adolescents who develop major depressive disorder following sexual abuse, Pechtel hopes to identify functional mechanisms that motivate maladaptive development in order to identify individuals at risk for psychopathology and to develop more targeted interventions to prevent high-risk behavior.
Elif Engin, PhD, is conducting research that implicates GABAergic neurotransmission in both the development of depression and the therapeutic effects of antidepressants, but only after long delay. Findings from animal studies in Engin’s laboratory point to a specific GABA receptor type as a possible mediator of depression symptoms and drug effects. Enhancing GABAergic effects by enhancing this receptor’s activity may make the receptor a viable target for faster-acting, more effective antidepressants with fewer side effects.
Maya Libben, PhD, is studying language-based disruptions associated with schizophrenia, which can significantly impair a patient’s social and occupational functioning. Libben seeks to determine where in the brain abnormal language activation stems from and at what stage of processing it occurs. She will use a variant of a semantic priming paradigm called masked priming, the defining feature of which is the subliminal presentation of the initial cue. Patients are not consciously aware of the information that is being presented to them, and any processing abnormalities can be attributed to the ‘initial activation stage’ associated with the temporal areas of the brain. Libben will measure the electrical activity produced by the brain while patients are performing these tasks to give exact measures of language activation in real-time.
Sivan Subburaju, PhD, is studying the associations of schizophrenia with pathological dysfunction of the GABA system in the hippocampus. Several genes have been identified whose expression is changed in schizophrenia, specifically factors which control other genes like the GABA-producing enzyme GAD67. Subburaju will test these genes to find out which is capable of changing GAD67 expression and consequently the GABA cell type. Identifying these factors and understanding the mechanisms by which they control GABA cell fate can be exploited to develop new therapeutic approaches for treatment.
D. Bradford Reich, MD, is seeking a neurobiological distinction between borderline personality disorder (BPD) and bipolar disorder (BP), and will lead an fMRI study of BPD and BPII patients examining how they react to various affective stimuli. Among other things, this research could prevent medications for BP patients from being incorrectly prescribed for those suffering from BPD. These medications are often prescribed in lieu of evidence-based psychotherapies known to be effective for BPD patients.
Poornima A. Kumar, PhD, will investigate neural correlates of reinforcement learning using socially relevant feedback stimuli in order to determine whether or not brain regions rich in dopamine activity are involved in both reward and aversive learning as it relates to anhedonia.
Fei Du, PhD, will use advanced functional magnetic resonance spectroscopy to identify and quantify alterations in the function of mitochondria (the energy-producing structures in cells) in patients with bipolar disorder as they undergo a cognitive challenge. The research hypothesis is that they will show decreased ability to meet the energy demands of intensive cognitive activity. The method, once established, would have potential for risk diagnosis and treatment monitoring for BP and related disorders, including depression and schizophrenia.
Nadja Freund, PhD, with her laboratory, created a virus system that they injected into the brains of lab animals, allowing manipulation of the expression of the D1 dopamine receptor (D1R) gene. This induced elevated expression of D1R and behaviors comparable to mania in humans. Virus reduction reduced mania-like behavior and D1R levels fell below control levels, suggestive of a depressive-like state. This cycling will serve as a model for testing novel therapeutic agents for treating bipolar disorder.