Molecular Imaging and Neuropathology
J. John Mann, MD
Area Leader, Molecular Imaging and Neuropathology
Molecular Imaging and Neuropathology includes 22 faculty as well as postdoctoral research fellows, research staff, and students. We take a multidisciplinary, translational research approach to psychiatric research, particularly studies of mood disorders and suicidal behavior. Our diverse paradigms comprise animal models, in vivo human studies, and postmortem brain research, with methods that include multimodal PET and MRI brain imaging methods as well as molecular genomics and biomarkers to guide clinical trials. We collaborate broadly to use our neuroimaging expertise to examine target engagement of novel treatments for mood disorders and suicide risk. Research in this area is supported principally by the National Institute of Mental Health and includes a Silvio O. Conte Translational Neuroscience Center for the Study of Suicide Behavior, the only such federally-funded suicide research center in the country.
In addition to carrying out research, we provide neuropathology services to the New York State Office of Mental Health (OMH), and we are a resource for suicide prevention expertise in New York State, across the U.S., and overseas.
We also train neuroscientists and clinical researchers at multiple levels, from high school, college, graduate level, and postdoctoral to senior scientists. Our faculty nurture young scientists, including volunteers, observers, interns, and postdoctoral fellows. Recent collaborations with visiting scientists from around the world include researchers from Argentina, China, Egypt, Israel, Iran, Japan, Pakistan, Portugal, Spain, and Sweden.
- Characterize biological factors contributing to risk for mood disorders and suicide using multiple levels of analysis
- Elucidate the Stress-Diathesis Model of Suicidal Behavior
- Develop sophisticated PET analysis methods that simplify PET acquisition and reduce the need for arterial blood sampling
- Understand how childhood adversity affects brain development and risk for future psychiatric illness including the impact on neural circuits, inflammation and lipidomics
- Perform translational work connecting animal models, in vivo human assessments (neuroimaging and genomic analysis), and postmortem human studies
Specific research includes studies of the mechanisms by which genes and environment, such as childhood adversity interact in the genesis of psychopathology. Clinical, cognitive, genomic, brain imaging, gut microbiome and blood tests are used to study causes and protective factors against suicide risk. A major study examines familial transmission of causal and protective factors that are used to identify who is at risk and how mood disorders and suicidal behavior can be prevented before the first symptoms appear. Treatment studies focus on prevention of suicidal behavior, and the use of brain imaging and biomarkers, such as inflammatory molecules, are used to understand the neurobiology of depression and suicide risk. Major accomplishments include:
- Identification of neurotransmitter and other differences in the brain of suicide decedents
- Neurochemical transmitter system differences in the brains of suicide decedents compared to changes associated with major depression or alcoholism
- Early life adversity related differences in adult brains, putting individuals at increased risk for suicide and mood disorders
- Development of sophisticated methods for data quantification that simplify the acquisition of PET images
- Development of novel PET radiotracers to image molecular targets relevant to mood disorders, suicide, and neurological illnesses
- Studies of genomic/epigenetic influences on suicidal behavior
- PET imaging studies of abnormalities in neurotransmitter systems related to major depression and bipolar disorder as well as suicide risk
- MRI studies concerning diagnostic differentiation of unipolar vs. bipolar depression
- The role of polyunsaturated fatty acids in suicide risk via effects on neurotransmitters and inflammation
- In therapeutics, researchers have carried out the two largest, randomized, clinical control studies examining the rapid onset of antidepressant and anti-suicidal actions of ketamine, one of which used MRS imaging during ketamine infusion in depressed patients, examining the real time effects on GABA and glutamate in anterior cingulate.
Programs, Centers, and Laboratories
Molecular Imaging and Neuropathology maintains the New York State Psychiatric Institute Brain Collection, a major scientific resource used for studying the causes of suicide, alcoholism, mood disorders and schizophrenia. It is also used for studies of growth of human nerve cells in health and disease and the effects of psychotropic medications on these cells and how they relate to therapeutic action.
The Brain Imaging Group conducts functional and structural brain imaging studies in animals and humans. This group develops novel imaging tools (radioligands) used in brain positron emission tomography (PET) imaging studies. These radioligands bind to specific molecules in the brain such as neurotransmitter receptors, enzymes and transporters, amyloid protein, synaptic markers, markers of inflammation or mitochondrial disease and peptide receptors. Using brain imaging, this group studies disease processes, effects of genetic and epigenetic variants and childhood adversity on brain biology, predictors of treatment outcome, and biomarkers for studies of drug effects in mood disorders and suicidal behavior.
The Center for Suicide Prevention is the only such federally-funded suicide research center in the country. Its mission is to investigate the neurobiology of mood disorders and suicide risk. We employ a multidisciplinary approach to study how childhood adversity can mold the predisposition to suicidal behavior and affect suicide risk in later life.
The MIND clinic is dedicated to research on mood disorders (major depression and bipolar disorder) and prevention of suicide and self-injury. No-cost treatment is offered in most of our research studies, including standard and novel antidepressant medications or psychotherapy. Both outpatient and inpatient treatments are available. We study mood disorders using state-of-the-art brain imaging techniques and clinical assessments. Our staff include experts and experienced clinicians in the treatment of mood and personality disorders. Our clinical trials involve mood disorders and employ new treatments such as ketamine, lurasidone and D-cycloserine.