Mental dysfunction is not based on some structural distortion, such as a lump or an obstruction which, once developed, does not go away. Mental illness comes & goes repeatedly.

Mental illness, like a seizure, a migraine, an asthma attack or an arthritic flare-up, is fundamentally paroxysmal, it comes & it goes.  This is how it works.  You inherit a vulnerability toward the problem.  Mood disorders run in families, just like migraines, but you might never get a migraine, or for that matter a mental illness.  Instead, you may be perfectly normal, without a hint of mental illness at least for now, or on the other hand you may be suffering from entering a prodrome. Prodromes are conditions such as pre-diabetes or pre-cancers where you may not be normal but you don't have the disease either.  Instead you harbor structural or functional abnormalities indicating that you are at risk for developing the full blown disease, depending upon the presence or the elimination of certain provocateurs, factors that may push you over the edge into a disease state.  A simple example is the tendency for further weight gain to convert a pre-diabetic into a florid one, although the flip-side is that weight loss can clearly prevent or even reverse the diabetic state. 

Agents for change

The most prominent factors that alter or activate our genetic vulnerabilities are hormones.  Thus during pregnancy the pre-diabetic woman may declare her diabetic vulnerability for the first time, as she develops gestational diabetes, a condition which resolves itself after delivery.  In the same vein, steroid hormones including cortisol & the sex hormones are pivotal activators for the mental disorders.  It is generally accepted that the stress hormone cortisol is a major mover for a wide variety of mental disorders, and this will be focused upon when we look at the stress response & its role in mental illness & normality.  Drugs that alter cortisol can be highly effective in the treatments of these diseases, but what about the sexual hormones? 

In contrast to our general acceptance of cortisol as a mind-mover, medicine turns a blind eye toward the massive influences of the sexual hormones on brain & mind, simply because they are called 'sexual', but there is no controversy over it.  The sex hormones, including DHEA, testosterone, DHT, progesterone & the estrogens including estradiol, have an enormous brain influence, at the molecular, the cellular, the tissue & the macro levels, & this translates into intellectual, emotional & behavioral effects of large proportion, with major influences on our everyday lives.  Yet knowing all this, we are still foolish.  We study & demonstrate the capacity for testosterone & DHT to prevent or even reverse dementia in men, but ignore its similar role in women, focusing only on the estrogens in female dementia studies.

Sex hormones & the brain

Estradiol & testosterone Influence nerve cell signalling at the synapse, prior to the synapse, across the synapse and after the synapse.  Estradiol influences all of the major neurotransmitter groups involved in feelings and emotions including dopamine, nor epinephrine, acetyl-choline, serotonin, GABA & glutamate.  The sexual hormones are critical regulators of neuroplasticity & neuroplasticity is the basis of memory and the valence of emotional experiences.  These hormones regulate neuroplasticity by controlling the balance between pro-inflammatory & anti-inflammatory cytokines, cytokines being the local hormones that control immunity & inflammation.  Additionally estradiol is a prominent yet often forgotten regulator of the stress response, which appears to be a core mechanism in the regulation of our emotions.  And whereas the sexual influences of the sex hormones tend to be slow, sluggish & lingering because they depend on activation of the classic sex hormone receptors, their impact on the brain is far more complex and involves a rich panoply of fast acting mechanisms they make hormonal patterns matter just as much as hormonal balances. 

Does all of this scientific evidence translate into real influences in the real world?  Indeed it does.  Raising estradiol & testosterone levels in the brain can combat & reverse Alzheimer's dementia.  Major depressive disorder is about twice as frequent in women as in men but only during episodes of major hormonal flux.  Thus the agitated depression & insomnia of PMS are driven by estradiol withdrawal occurring against a progesterone-poor or an allo-pregnanolone-poor context.  Estrogen & testosterone deficiencies also fuel mood problems.  Post-partum depression & psychosis are driven by relative degrees of estradiol withdrawal & depletion and the mood swings, agitation and depression observed at menopause are driven by estradiol & testosterone flux.  Young women taking the contraceptive pill often experience chemical depression.  The synthetic estrogen in combination birth control pills cannot access the brain while at the same time reducing the capacity for natural estradiol to gain access to the central nervous system. 

What all of this adds up to is that since we know that hormonal imbalances and erratic fluxes can fuel major mood disturbances, we should also realize that correcting them should have the power to improve or even control these mental conditions, as indeed we find they do, yet psychiatry insists instead on sticking exclusively to the heavy-handed use of crude, mind-altering drugs, a kind of psychological rape.