Aggression and violence: perspectives on integrating animal and human research approaches.

Aggression and violence are concerns that engage us across society as moral and cultural issues. They are also critical issues for mental health research--both for survivors and for understanding how such behaviors occur. Interpersonal violence often explodes in deliberate acts of physical force leaving survivors behind with a diminished sense of control that is often shadowed by persistent fear and anxiety. The treatment of the victims is a clear and immediate concern; from their perspectives the medical consequences require effective attention whether they suffered as a result of acts of nature, mental disease, ideology, or combinations of these. At the same time preventing violent behavior from happening in the first place is a compelling challenge for public health research.

Introduction: Behavioral neuroscience and childhood mental illness.

Advances in the treatment of mental illness depend, in part, on the elimination of barriers to the use of new basic research findings. Some of the barriers originate in the different research perspectives adopted by clinical and basic researchers. Clinical research is driven by the need to recruit and examine classes of individuals, and so the conceptual framework focuses largely on categories of disorders. Basic researchers, including psychologists and behavioral neuroscientists, investigate fundamental features of behavior such as emotion regulation, attention, or arousal; therefore, disorders are commonly approached from a "dimensional" framework. In the broadest sense dimensions are those features that are common to multiple disorders. Categories are an effort to draw distinctions among disorders. The differences between these frameworks, and the perspectives held among clinicians and basic scientists, are not dichotomous. Many clinicians investigate fundamental aspects of pathophysiology and behavior that apply to multiple disorders, and many basic researchers are developing animal "models" of categorical disorders. It is timely and important to examine these approaches critically, and to work toward formulating perspectives that capture the strengths of each group of researchers so that their common goal of translating research findings into treatments for childhood mental health disorders is strengthened.

Preclinical models: status of basic research in depression.

Approximately one half-century ago several classes of medications, discovered by serendipity, were introduced for the treatment of depression and bipolar disorder. These highly effective medications revolutionized our approach to mood disorders and helped launch the modern era of psychiatry. Yet our progress since those serendipitous discoveries has been disappointing. We still do not understand with certainty how those medications produce their desired clinical effects. We have not introduced newer medications with fundamentally different mechanisms of action than the older agents. We have not identified the genetic and neurobiological mechanisms underlying depression and mania, nor do we understand the mechanisms by which nongenetic factors influence these disorders. We have only a rudimentary understanding of the circuits in the brain responsible for the normal regulation of mood and affect, and of those circuits that function abnormally in mood disorders. In approaching these gaps in our knowledge, this workgroup highlighted four major areas for future investment. These include developing better animal models of mood disorders; identifying genetic determinants of normal and abnormal mood in humans and animals; discovering novel targets and biomarkers of mood disorders and treatments; and increasing the recruitment of investigators from diverse backgrounds to mood disorders research.