Psychotherapy and antidepressant treatment of depression: evidence for similar neurobiological mechanisms.
Authors: Fritz A Henn, Emmeline Edwards, David Anderson, Barbara Vollmayr
Journal: World Psychiatry (2002)

The neurobiological mechanisms that underlie depression are not yet entirely clear, and their relationship to the psychological changes which accompany depression have not been explored. Cognitively, it appears that there is a change in the processing of information, often exacerbated by stressful events and loss of control. This leads to the overvaluing of negative interpretations and a sense of hopelessness and helplessness, which characterize the psychological state in depression. Antidepressant medications, electroconvulsive therapy (ECT), cognitive behavioral therapy and interpersonal psychotherapy can reverse this process.

Much of our knowledge about the potential neurobiological changes in depression results from studying the factors that change during the medical treatment of depression. Thus far a series of modulating neurotransmitter systems have been implicated. These mainly include norepinephrine (NE), serotonin (5-HT), and some peptides such as corticotropin-releasinghormone (CRH) (1), substance P (2) and the endorphins (3). At times the changes leading to depression appear to arise spontaneously, perhaps driven by genetic factors, while at other times they seem to be related to stressors involving loss and loss of control. This observation led Seligman to attempt to create an animal model of depression using aversive stressors in an unpredictable fashion that would lead to a sense of lost control for the animal. This resulted in the development of the learned helplessness model of depression (4). In this model, animals exposed to unpredictable and uncontrollable aversive stimuli alter their behavior in that they no longer try to escape from aversive situations from which they could escape. These animals also develop many of the signs of depression, including weight loss, sleep changes with decreased rapid eye movement (REM) sleep, decreased libido, and increased cortisol secretion. These changes persist for weeks but can be reversed with antidepressant treatment (3). Using this model we wanted to examine the neurobiological mechanisms by which learning reverses helplessness compared to antidepressant medications.

To date we have been able to show that in learned helplessness both the 5-HT and the NE systems show alterations when the animal becomes helpless. Reliable markers of helplessness in these systems are an increase in hippocampal NE beta receptor (5) and 5-HT-1b receptor density (6). Analogous to the situation seen clinically in depression, cortisol, while increased on average, does not show an increase in all helpless animals (7), so that it cannot be seen as a suitable marker. We followed the NE beta receptor density as a function of various treatments, in an effort to determine if the same neurobiological mechanisms came into play in all cases. Initially, we carried out an experiment to examine how closely the level of noradrenergic beta receptor would correlate with helpless behavior, in order to determine if it would serve as a valid marker of the neurobiological mechanisms brought into play in reversing depression. We used this marker in the current study to monitor neurobiological change as a function of pharmacological or behavioral treatment.