Par-4 deficiency previously has been implicated as a factor in the process of cell self-destruction in neurodegenerative diseases, such as Alzheimer's. Dopamine is known to govern circuits in the brain that regulate motor control, arousal, mood, motivation and endocrine function.

Test results provide evidence that there is a molecular link between impaired dopamine signaling and depression, which affects 16 percent of the adult population in the United States.

Impairment in the function of the dopamine D2 receptor is implicated in various neuropsychiatric disorders, including schizophrenia and drug addiction. The research appears in the July 29 issue of Cell magazine.

Molecular Binding Partnership Essential

Harvard Medical School professor Li-Huei Tsai and colleagues found that the Par-4 molecule acts as a binding partner for the dopamine D2 receptor. If it is deficient, the D2 receptor will not function adequately.

In preliminary studies, when mice deficient in Par-4 were subjected to stress, they exhibited depression-like behaviors, indicating that Par-4 acts as a molecular link between dopamine signaling and depression.

These new findings reveal an unexpected role for Par-4 in the dopamine system and present a rare glimpse of molecular mechanisms behind clinical depression.

Current Antidepression Therapies Lacking

According to Tsai, most antidepression therapies today focus on balancing the serotonin and noradrenaline systems, whereas his study "highlights the importance of the dopamine system, a less-appreciated target in the current anti-depression therapies."

The Par-4 findings are particularly important because drugs that currently are used to treat depression have significant shortcomings: They are ineffective until a sufficient quantity of the chemical builds up in the patient's system, and a large percentage of patients are resistant to them.