The truth about depression

An Australian government study has claimed that every person in this country either suffers from the disorder or knows or works with someone who does. 

Depression is arguably the world's greatest killer. It is the dark shadow lurking behind much heart disease, cancers, suicides, dementia, accidents, blindness and a range of other potentially fatal ailments. Yet few people in authority are prepared to take any effective action to reduce the stress that is at the root of so much of it.

The truth is that we don't know very much about the etiology of depression. Most so-called cures — antidepressants, psychotherapy and the rest — have little, if any, lasting relief and even that little is confined to a very few cases. 

Some lifestyle changes can help. For example, the so-called Mediterranean diet — lots of fish, legumes, whole grains and olive oil and very little red meat, sugary things and processed foods — has been shown to reduce symptoms by 45 per cent in people suffering from major depression. 

One new study also suggested that an hour a week of exercise per week could go a long way to in preventing depression, particularly if done in the company of a friend.

Nearly all researchers see depression not as a single illness, but a "syndrome," a collection of similar symptoms that have no single common cause. We know that about 30 per cent of depression is genetic. We also know that there is no single neurochemical problem connected with it — certainly not the inability of certain specialised cell receptors to "uptake" serotonin effectively. Rather depression has been linked to the malfunctioning of several neurochemical systems — dopamine, oxytocin, cortisol and glutamate. Mood disorders — of which depression is one — can also be caused by the activity and the mix of our gut microbiota. And of course, there's workplace stress, childhood abuse, neglect, criticism, overly high expectations etc. 

Depression is probably the most researched mental illness and some important studies have appeared in just the last few weeks.

Stress causes depression

Undoubtedly, the most important of these is a new study in the journal Trends in Neurosciences. This showed for the first time the causal link between stress — in our time this is mainly work-stress — and depression. 

Stress is a common trigger for nearly all initial depressive episodes, and chronic stress can prevent new cells being formed in the hippocampus — the brain's memory centre — to replace those that have died off. Researchers found stress can also inhibit mesolimbic dopamine neurons (preventing sufferers from feeling pleasure) and sensitise the amygdala's response to negative information. The amygdala is the main fear centre of the brain and this sensitisation tends to make people feel anxious, fearful and more likely to look for what's wrong rather than what's right. 

So, what? Some recent studies have shown that up to 30 per cent of US employees suffer from episodes of major depression. That is up from about 8 per cent 15 years ago. The stress produced by the way we are forced to work — including open plan offices, the fear of job loss, the isolation of working from home, over work, being "on" via smartphone 24/7 — is a major stressor. We are simply not designed to cope with it. 

Depression changes with time

Importantly new research also found that persistent depression may need a different therapeutic approach from all those that have been tried so far. The findings also raised the question: Is clinical depression always the same illness, or does it change over time?

New brain imaging research published in The Lancet Psychiatry shows that the brain alters after years of persistent depression, suggesting the need to change how we think about depression as it progresses. 

The study shows that people with longer periods of untreated depression had significantly more brain inflammation compared to those who had shorter periods of untreated depression. Inflammation is a key causative factor in clinical depression.

This provides the first biological evidence for large brain changes in long-lasting depression, suggesting that it needs different therapeutics.

Yet currently, regardless of how long a person has been ill, major depressive disorder is mainly treated with the same approach. The new findings may lead to the discovery of new and better treatments for people with long-standing depression.

Skewed brain connectivity

A new study in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging looks at the influence of the connectivity between brain regions in depression.

The researchers found that people with major depressive disorders have alterations in the activity and connectivity of brain systems underlying reward and memory. The findings provide clues as to which regions of the brain could be at the root of depressive symptoms, such as reduced happiness and pleasure.

The research uses a new way to measure the influence of one brain region on another, referred to as effective connectivity. "The new method allows the effect of one brain region on another to be measured in depression, in order to discover more about which brain systems make causal contributions to depression," said the lead researcher.

The team found that brain regions involved in reward and subjective pleasure had reduced effective connectivity in depressed patients, which may contribute to the decreased feeling of happiness in depression.

Memory-related areas of the brain had increased activity and connectivity which may be related to heightened memory of unpleasant memories.

"These findings are part of a concerted approach to better understand the brain mechanisms related to depression, and thereby to lead to new ways of understanding and treating depression," said the researchers.

Ketamine has been called the wonder drug for treating major depression. Studies reported in the Harvard Review of Psychiatry suggest that ketamine, a widely used anaesthetic agent, could offer a wholly new approach to treating severe depression — producing a very fast antidepressant response. 
Researchers at the US National Institute of Mental Health claim that ketamine may represent a "paradigm shift" in the treatment of major depressive disorder especially in patients who do not respond to other approaches.

Ketamine is one of several glutamatergic drugs (i.e. those that target the glutamate system) affecting neurotransmitters in the central nervous system. Over the past decade, studies have reported "rapid, robust, and relatively sustained antidepressant response" to ketamine injected intravenously.
Prompted by these studies, some doctors are already using ketamine in patients with severe or treatment-resistant depression. However, many questions remain about its short- and long-term side effects. 

Researchers also reviewed neuroimaging studies evaluating ketamine's effects in the brain. The drug may exert its antidepressant effects by "acutely disabling the emotional resources required to perpetuate the symptoms of depression," as well as by increasing emotional blunting and increasing activity in reward processing.

What we do know is that, at least in the very short term, ketamine works for almost everyone with severe depression. 

The pace of research into depression is quickening, which is very good. However, since the overall stress level in our society is the underlying cause of so much of it, until that is dealt with I am doubtful that we will finally win the battle with the illness.

 
Bob is the author (with Dr Alicia Fortinberry) of best sellers "Creating Optimism" and "Raising an Optimistic Child" (both Mc Graw-Hill). He has lectured at Duke, Tufts, Sydney and California State Universities as well as worked with the University of South Florida on the anti-depression "Uplift Program." He is a consultant with the firm of Fortinberry Murray and is on the Advisory Board of the Mental Health Institute of Legal Professions. His most recent book is "Leading the Future: The human science of law firm strategy and leadership." 

He can be reached at [email protected]