Cortisol, often referred to as the ‘stress hormone’ is essential for life.  So why should it also be dangerous?  It was Thomas Addison, a 19th century physician from Guys Hospital, who noticed that some of his patients were dying of a slow, remorseless illness that was characterized by progressive fatigue, skin discolouration and muscle weakness.  Unlike most other physicians of the time, he carried out several careful postmortems, and observed that both adrenals had been destroyed by tuberculosis, then a very common illness. Nowadays, patients with Addison’s disease (usually an auto-immune disorder) are kept alive and well by being given cortisol and a second adrenal steroid (an aldosterone-like compound). Otherwise they would die.

Levels of cortisol in the blood fluctuate. They are highest in the morning; there is a further surge about 30 minutes after a person wakes, but then a steady decline throughout the day so that, by nightfall, levels may be almost zero.  But cortisol reacts strongly to a stress, whether this be physical (exertion, an illness ) or psychological (a threat or a demand that is seen to be difficult to handle). Addisonian patients need to take additional cortisol if they become ill or stressed; otherwise they will become very ill indeed.  So the cortisol reaction is a necessary part of coping with the vicissitudes of life.

But problems arise if cortisol levels are raised for prolonged periods, such as in Cushing’s disease, usually the result of secretory tumours of either the adrenal or the pituitary. Cushing’s patients have marked cognitive problems, such as memory impairments; they are also commonly depressed, which may resolve rapidly after cortisol levels are normalized – unlike the cognitive deficits, which may persist. This may be why persistent stress may have similar effects, though this is not so well established.  Artificial cortisol-like steroids are commonly given to patients suffering from a variety of disorders, particularly those characterised by inflammation – such as arthritis.  Nowadays, this treatment is given intermittently, for otherwise there is a risk of either depression or mania.  A huge survey of NHS patients in the UK showed that the association between steroid treatment and depression was actually quite common. 

Levels of cortisol, like everything else, vary from person to person.  Depression commonly begins in adolescence: the risks for this happening is increased with relatively higher levels of morning cortisol.  It is also precipitated – in some people – by adversity: a loss, for example (loved one, job, money etc).  Whether this also depends on the way that their cortisol levels react is an interesting question.  Depression is about twice as common in women as in men: and women have about 20% higher levels of cortisol in the morning.  Is there a connection? Women also report more adverse 'life events', so cortisol and life style may interact.

Experimental studies show that cortisol can damage the brain.  The hippocampus, which is involved in certain types of memory, is particularly vulnerable. The hippocampus is one of the few places in the adult brain that continues to make new nerve cells (neurons).  Neurons of the hippocampus of rats given corticosterone (their version of cortisol) show distorted dendrites and markedly suppressed new neuron formation (neurogenesis).  Does this contribute to depression?  It's been suggested, but not yet proved.  Drugs used as anti-depressants restore neurogenesis, though whether this is how they alleviate depression is still debated. 

Cortisol does something else:  higher levels empower other damaging agents, so that they become more effective.  So head injury is made worse by giving corticoids. The endangering effect of cortisol may have other consequences. Those with a history of repeated depression have about twice the risk of developing Alzheimer’s disease - it may be even greater for some subtypes of depression.  During depression, cortisol levels may be disturbed (in about half the cases).  Levels in the morning may be elevated, but a more common feature is that they remain high throughout the day, so the normal daily rhythm is lost.  Cortisol levels are also raised in Alzheimer’s disease itself.  Do these changes either precipitate Alzheimer’s or accelerate its progression?  We need to know.  But it may not be a coincidence that some of the earliest signs of Alzheimer's occur in the hippocampus and surrounding brain tissue. There has been a curious lack of interest in the role of cortisol in Alzheimer’s (and in depression), but it’s time this was remedied. Cortisol has powerful effects on mood, memory and decision-making, so its influence on brain function and its role in the response to stress should interest neuroscientists, psychiatrists and clinical psychologists.  Persistent, uncontrollable stress, which is particularly liable to raise cortisol levels, really isn't good for the brain.

Thomas Addison suffered from depression all his life and finally committed suicide. We can never know anything about the cortisol levels in this punctilious, hard-working, socially diffident man: but we can wonder.

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