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Complications of Pregnancy

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Stress and Cortisol

 

Many scientists have wondered whether there is some quirk in the way depression is inherited, such that a depressed parent or grandparent is more likely to pass on a predisposition for the disorder to female than to male descendants.
Based on studies that trace family histories of depression, the answer to that question appears to be no.

Women and men with similar heritage seem equally likely to develop the disorder. Simply tracing family histories, though, without also considering environmental influences, might not offer a complete picture of how depression is inherited.

A study has not been done in men, leaving open the question of whether environmental stress and genetic risk for depression interact similarly in both sexes. But research is being done to determine whether men and women generally experience similar amounts and types of stress.

Studies of key hormones hint that they do not. Hormones are not new to depression researchers. Many have wondered whether the gonadal steroids estrogen and progesterone— whose cyclic fluctuations in women regulate menstruation—might put women at a greater risk for depression.

There are at least two ways in which they might do so.
First, because of differences between the X and Y chromosomes, male and female brains are exposed to different hormonal milieus in utero. These hormonal differences may affect brain development so that men and women have different vulnerabilities—and different physiological reactions to environmental stressors—later in life. Indeed, animal experiments show that early hormonal influences have marked behavioral consequences later on, although the phenomenon is of course difficult to study in humans.

Second, the fact that postpubertal men and women have different levels of circulating gonadal steroids might somehow put women at higher risk for depression. Research shows girls become more susceptible to depression than boys only after puberty, when they begin menstruating and experience hormonal fluxes.

Even so, scientists have never been able to establish a direct relation between emotional states and levels of estrogen and progesterone in the blood of women. A study reported that manipulations of estrogen and progesterone did not affect mood, except in women who suffer from severe premenstrual mood changes.

It now appears, however, that estrogen might set the stage for depression indirectly by priming the body’s stress response. During stressful times, the adrenal glands—which sit on top of the kidneys and are controlled by the pituitary gland in the brain—secrete higher levels of a hormone called cortisol, which increases the activity of the body’s metabolic and immune systems, among others. In the normal course of events, stress increases cortisol secretion, but these elevated levels have a negative feedback effect on the pituitary, so that cortisol levels gradually return to normal. Evidence is emerging that estrogen might not only increase cortisol secretion but also decrease cortisol’s ability to shut down its own secretion. The result might be a stress response that is not only more pronounced but also cortisol levels, but the two are undoubtedly related.

Over the past few decades, a number of studies have shown that cortisol levels are elevated in about half of all severely depressed people, both men and women. So the idea is this: if estrogen raises cortisol levels after stress or decreases cortisol’s ability to shut down its own secretion, then estrogen might render women more prone to depression— particularly after a stressful event.

Light and Melatonin

Despite their importance, estrogen and cortisol are not the only hormones involved in female depression, and stress is not the only environmental influence that might hold more sway over women than men.

A study indicated that women might be more responsive physiologically than men to changes in exposure to light and dark. These investigators have had a long-standing interest in seasonal affective disorder (SAD), or so called winter depression (although it can occur in the summer as well), and the role that the hormone melatonin might play in the illness.

Similar to the gender ratio in other forms of depression, SAD is three times more common in women than in men. Melatonin has been a prime suspect in SAD because organisms (including humans) secrete it only when they are in the dark and only when the body’s internal clock (located in the hypothalamus) believes it is nighttime.

The pineal gland, a small structure that resides deep in the mammalian brain, begins to secrete melatonin in the evening, as daylight wanes.

Melatonin levels drop in the morning, when light hits the retinas of the eyes. Because nights are longer in winter than in summer, animals living in the wild secrete melatonin for longer periods each day during winter. Among animals that breed in summer, the onset of this extended daily melatonin secretion signals the presence of winter and shuts down the secretion of gonadal steroids that facilitate reproduction.

SAD researchers have long wondered whether a wintertime increase in the duration of melatonin secretion might also trigger depressive symptoms in susceptible individuals.

Under normal living conditions, women were more likely than men to retain a sensitivity to seasonal changes in day length. In other words, for women the duration of nocturnal melatonin secretion was longer in winter than summer; in men, however, there was no seasonal difference.

These results suggest that women are more sensitive to natural light than men—and that in a society where artificial light is everywhere, women somehow still detect seasonal changes in natural day length. Whether this gender difference puts women at increased risk for SAD is unclear; paradoxically, there is evidence that women with SAD symptoms may be less likely than unaffected women to have an increased duration of melatonin secretion in winter.

Researchers are now working to unravel the complicated relations between these hormonal systems and to determine whether, and how, they may influence individuals’ risk for depression.

 


 
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