What are the long-term neurobiological consequences of childhood sexual abuse? Charles Nemeroff, Professor and Chair of the Department of Psychiatry and Behavioral Sciences, argues that early life traumas sensitize the developing brain in permanent ways. Using brain imaging scans and other research tools, the Nemeroff lab has isolated a sub-type of depression that appears unique to adults who suffered abuse or neglect as children.

Funded by two five-year Conte Center grants for the Neurobiology of Major Mental Disorders from NIH, Nemeroff's research seeks to understand the neurobiological makeup of patients who are depressed and who have a history of childhood trauma. Together with Christine Heim, Clinton Kilts, and Helen Mayberg, faculty in the Department of Psychiatry, Nemeroff is discovering that the brains of depressed patients who experienced early abuse or neglect look different from those in the control groups. "We can see it when we look at the size of different structures in the brain, such as the hippocampus, which is smaller than normal," he says. "We also see it in the responsiveness of these patients to stressful situations." Among patients who experienced early abuse or neglect, the body's stress system now stands on 'permanent alert' and has become hyperactive. These findings are casting new light on the persistent effects of early childhood trauma into adulthood.

In addition to his work on depression and early childhood abuse, Nemeroff serves as principal or co-investigator for a number of mental health studies:

• Identifying predictors of anti-depressant response.
  Working with 400 never-treated depressed patients, Nemeroff's team is using genetic studies and brain imaging scans to determine which patients respond positively to one of three possible treatments: antidepressants that target serotonin, antidepressants that target both serotonin and norepinephrine, and cognitive behavior therapy. Researchers plan to devise a genetic test (and possibly a brain imaging test) that will help doctors predict which patients will respond best to a given treatment, thereby eliminating the frustrating trial-and-error period. Says Nemeroff: "If we can predict which patients will respond best to which kinds of treatments, we can shorten the length of time it normally takes doctors to find the right 'fit' for helping a depressed patient."
• Accelerating antidepressant drug discovery.
  In a unique U-19 grant agreement between Emory, Glaxo-SmithKline, and the National Institutes of Health, Nemeroff's lab is testing Glaxo-SmithKline's latest drug candidates to determine their suitability and effectiveness. The partnership allows Emory scientists to test and strengthen the pharmaceutical company's latest research on novel antidepressants without conflicts of interest because none of the funding is provided by the pharmaceutical company. Thanks to a mechanism set up by the NIH, academic institutions can apply for funds in collaboration with a pharmaceutical company, allowing the NIH to pay for accelerating drug discovery in areas where it has a particular interest.
• Developing better antipsychotic medications.
  Nemeroff's team is developing new antipsychotic drugs for persons suffering from schizophrenia and bipolar disorder. The new drugs will hopefully be more effective and cause fewer side effects than current treatments, which can cause weight gain and other problems. The centerpiece of the new medications is neurotensin, a little known (and largely ignored) neurotransmitter in the brain. Nemeroff and his team members have discovered that neurotensin appears to be involved in psychosis and in antipsychotic drug action. Together with Emory professor Clinton Kilts, Nemeroff has a patent for a new transdermal lithium patch for the treatment of bipolar disorder which should have far fewer side effects than oral lithium preparations.
• Understanding depression's role in heart disease.
  Depression comprises a major risk factor for developing heart disease. It is as much of a risk as cigarette smoking or elevated cholesterol levels, says Nemeroff. As he participates in a series of research projects conducted at the interface of depression and heart disease, he seeks to understand the correlation between the two diseases and help devise new treatment methods. "If you have a heart attack and you're depressed, you're four times more likely not to survive in the coming six months," he says. "Depression is a systemic illness that affects not only the brain, but also the heart, the bones, and the entire organism."