Clinical and Basic
Neuroscience Research
Training Program in Psychiatry

Molecular Research

The next generation of molecular research in psychiatry promises important advances in the way we think about and confront mental illness.

The Division of Molecular Psychiatry strives to relate molecular and cellular phenomena to other, more traditional disciplines in psychiatric neuroscience and to build causal bridges between molecular, electrophysiological, and behavioral phenomena. The research also strives to integrate preclinical and clinical investigations.

Much of the molecular psychiatry research at Yale focuses on the mechanisms of action of psychotropic drugs. Drugs can be seen as prototypical environmental factors and, as such, represent useful tools to study how the brain adapts to chronic perturbations. Studies range from the molecular mechanisms underlying drug addiction, including opiates, psychostimulants, and alcohol, to those underlying therapeutic agents, such as antidepressant and antipsychotic medications. For example, investigators are actively researching the role of the locus coeruleus in mediating the physical symptoms of opiate dependence through the identification of adaptations in the cyclic AMP second messenger and protein phosphorylation pathway. Related studies on the brain's mesolimbic dopamine system, which is implicated in the psychologically-addicting properties of most drugs of abuse, are demonstrating differential neurochemical vulnerabilities to developing drug addiction in different rat strains due to their different genetic compositions. Related endeavors strive to understand the long-term adaptations which brain regions undergo in response to different classes of antidepressant treatments. These studies have shown altered expression of specific monoamine receptor subtypes regulation, which occurs in part at the level of gene expression. Investigators are now working to identify portions of the neuronal regulatory apparatus and specific nuclear transcription factors that mediate antidepressant and other drug effects.

Taking leads from such preclinical findings, investigators are studying the possible association of genes for various neurotransmitter receptors, signaling proteins, and synthetic enzymes with severe psychiatric disorders, including alcoholism, schizophrenia, tic and obsessive-compulsive disorders, and cocaine abuse. Identification of such genes will revolutionize diagnostic tests and have important consequences for prognosis and choice of treatment. Among the most exciting and recent of initiatives aimed at studying pathological mechanisms of psychiatric illness is the use of transgenic and heterologous recombination technology to breed animals with an extra or deleted gene. Such methods will assist basic neuroscience researchers in empirically determining how a given allele influences specific physiological and behavioral aspects of brain function.

Faculty related to Molecular Research

Aghajanian
Alreja
Bunney
Duman
Gelernter
Picciotto
Russell
Shi, Wei-xing
Taylor

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