The eyes are the windows to the soul.
William Shakespeare

Depression can vary from a mild annoyance to a life threatening illness.  Those of us who have been in it’s clutches, would gladly escape any further experiences of Churchill’s Black Dog, and much time and effort has been spent in searching for ways to effectively treat the first episode  of the disorder and hopefully to prevent recurrence.

Antidepressant medication has had a role to play, but for those who of us who do not fit the rubric of severe depression the effects are barely greater than that of a placebo: leading to papers in psychiatric journals questioning their use. Cognitive therapy approaches have better effects, and are recommended as the first line treatment in mild to moderate depression. In some patients the combination of the two treatments seems to have effects that are greater than the sum of the individual treatment effects.

However, there is a problem with much of the research into depression.  Depression seems to represent a “final common pathway” for many different aetiological and neurophysiological processes.  Scans of depressed patients have shown that some areas of the brain can react in apparently completely opposite ways in different patients with the same diagnosis.  These differences seem to tie in with the effectiveness of different treatment approaches in the differing groups.

Brain imaging has also shown that several areas of the brain have altered functioning, some becoming overactive while others become less reactive in depressed people.  The interplay between these various brain areas seems to help to explain both the type of depressive symptoms, and the differing presentation of depression between sufferers. Studies have highlighted two particular areas, among the many,  for special attention in mood disorders. The amygdala is an almond-shaped area in the limbic system of the brain.  It is involved in processing emotions, and has a significant role to play in our “fight or flight” response to perceived danger.  In depression this area seems to be more active than usual.

Over the last 100,000 years or so the human brain has become considerably larger and more complex. The main area involved in this growth has been the cerebral cortex, the part of the brain that processes much of our sensory input, and considers the likely consequences of our actions. This activity is called executive processing and is carried out in particular by the prefrontal cortex.  In many depressed people this prefrontal cortex is less active than usual.

The combination of an overly reactive amygdala and a slow to respond, cortex plays a role in the onset and maintenance of depression. This allows the negative mood response of the amygdala a free rein, and our minds and bodies respond by being depressed. Antidepressant medication seems to have effects on reducing the over-reactivity of the amygdala, while cognitive therapy approaches seem to reinforce the functioning of the prefrontal cortex, allowing us to stop our emotions running away with us.

This can be seen more easily in the treatment of anxiety.  Here, patients are helped to respond to increased levels of fearful responses which have been triggered by normal situations through a process of challenging the thoughts that accompany the mental state, and so override them – although this does take practice.

A functional magnetic resonance study carried out in 2007, showed that depressed adults had heightened activity levels in their amygdalas while carrying out an emotional based task, and reduced levels of activity in their prefrontal cortex while performing a cognitive task. A follow up after 14 weeks of cognitive behavioural therapy (CBT) almost completely reversed this situation.

It is thought that CBT, which focusses on recognising and challenging unhelpful thoughts re-engages the under-active cortical areas and allows them to override the amygdala. However, we should not read too much into such studies too soon.  The completed studies are still few in number, partly because of the cost and disturbance that is required in performing the scans, and there are a few contradictory findings.

Another area that has been studied in detail is the insula, an area of the brain that has links to both the amygdala and the frontal cortex. One group of patients showed high activity in the insula and another group showed lowered activity. Those who showed a high levels of activity were much more likely to respond to medication, while those with lower activity responded better to CBT. The depression being a reflection of a different type of dysfunction in similar brain pathways.

One interesting finding that has come out of this research has involved the response of the eye. If depressed adults are shown a list of words with negative connotations, the group whose pupils do not dilate much had reduced activity in their frontal cortical areas and were more likely to respond to CBT than those whose pupils dilated more.

These are exciting findings and highlight the increasing knowledge of the way the brain pathways and circuits interact to produce symptoms of mental health disorders. This should enable fine tuning of different treatment approaches for the individual patient, enabling better outcomes from more effective therapies.

The National Institute for Mental Health in America should be lauded for the new project that it has initiated in recent years. This project is designed to develop new ways of describing, understanding, and treating mental health problems. A project based on modern scientific understanding, trying to bring together everything from genetics, to brain function, to the lived experience of the patient.

This is planned to enable the next generation of mental health professionals to access treatments that are focussed much more accurately on bringing about the desired changes in brain function.  Changes that will be mediated by whatever means are shown to be most the most effective, be this medication, psychotherapy, gene therapy, meditation or lifestyle change.

A project that makes me wish I was just starting out in my career as a psychiatrist, and one which I will follow with great interest over the next ten years or so.
Sandy

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