Depression, serotonin, and sex differences

by Emily Chao

Girls stress and get depressed. Boys can’t control themselves. And it’s not their fault.

In a study conducted by Dr. Espen Walderhaug and his colleagues, women and men are found to behave differently when serotonin levels were lowered. When given a treatment of acute tryptophan depletion, men became more impulsive and displayed such effects usually demonstrated in impulse control disorders and alcoholism. Surprisingly, they did not appear to demonstrate mood changes. Women, however, reported a worsening of their mood, and became more cautious. Both responses are characteristic of and associated with MDD (Major depressive disorder, commonly known as depression).

What the researchers also discovered was that the women’s moods were influenced by variation in the promoter region of the serotonin transporter gene (5-HTTLPR). The 5-HTTLPR gene is an important part of the serotonin system, which helps to regulate mood in men and women.  It has been shown to control overall response to SSRIs in patients with MDD.

So if men and women have the same brain areas for our serotonergic systems, what makes the result so drastic? Dr. Walderhaug hypothesizes that men and women may use serotonin differently. He hopes the study’s findings will help us understand why women risk a higher chance of mood and anxiety disorders while men have a higher probability of abusing alcohol and suffering from impulse control disorders.

Suicidal thoughts, SSRIs, and genes

by Kelly Long

In a world where illnesses once thought debilitating have become more treatable than ever, the question of whether or not a treatment is available for an affliction like depression has become almost obsolete. The difficulty has shifted to the issue of which drug is best for which patient, and how a balance may be found between treatment and side effects.
Recent government-funded studies, reported in the New York Times, have shown that Celexa, an anti-depressant drug belonging to the class of selective serotonin reuptake inhibitors (SSRIs) may cause patients to experience suicidal thoughts. Interestingly, those same suicidal thoughts tended to be found in patients who did not actually attempt suicide, while it has been noted that the one patient in the study that did actually attempt suicide vehemently denied any thoughts of suicide.

Unsurprisingly, the physiology of the connection may be traced to the brain. Throughout the course of the study, two out of the sixty-eight genetic markers studied were noteworthy, as 36 percent of the subjects in possession of the markers experienced suicidal thoughts after taking Celexa. The markers coded for an amino acid called glutamate, which, aside from working as a natural antidepressant by activating neurons, is involved with learning and memory in the brain. Although the results of the tests were inconclusive, they raise the serious question of how treatment can be achieved without a flurry of undesirable (and sometimes dangerous) side effects. It is also remarkable to think that, with time and more research, a genetic test may be developed that is capable of pinpointing exactly which depression treatment is best for each patient.

[Editor's note: Interested readers may also want to look at this post about why the added caution around SSRIs also causes problems.]

Source:

Carey, Benedict. (2007 September 28). Genes Tied to Bad Reactions to Antidepressant Drug. New York Times. Retrieved September 30, 2007, from http://www.nytimes.com.