When does sadness become depression, and depression become a clinical problem? As the biologist Lewis Wolpert asked in his account of his own illness: "Are the same factors involved and are the differences just quantitative, or is there a qualitative change?"
When diagnosing depression, doctors look for classical syndromes: low mood, pessimistic outlook, lack of enjoyment, sleeplessness, reduced energy and lethargy. A clinical problem arises when these elements occur with sufficient severity to disrupt someone's life to an unacceptable degree.
Most psychiatrists now agree that the division of depressive disorders into reactive or endogenous (responses to external or internal events) is unhelpful; both must be considered when assessing the causes of depression. A more useful subdivision does however remain: between manic depression, in which depressed and excessively elated moods alternate, and the "unipolar" form, in which there are no periods of mania.
Although sadness and depression differ in some fundamental way, it is interesting that the root of sad is "sated"-so overfilled by feeling that the range of emotion needed for normal functioning becomes unavailable.
Depression and natural selection
Depression is common-affecting about 10 per cent of the UK population at any time. It has the hallmarks of a beneficial trait that has survived natural selection. It has been suggested that it helps maintain relative equanimity within tight social groups by promoting submission over conflict. The rat swim test is cited in support of this: rats learn to float if they fail to find a platform in a pool. If they are given anti-depressants, they keep searching, swim themselves to exhaustion, and die.
But the distress and disruption caused by depression suggest that it must be an evolutionary adaptation gone awry; any advantage it once conferred is long gone.
An alternative to the adaptation theme is the idea that mild depression may be a "spur." The link between depression and creativity has often been cited in this respect. Writing of Winston Churchill, whose "black dog" of depression was a famous companion, Lord Moran remarked: "Winston has always been wretched unless he was occupied."
nature and nurture
Biologists increasingly agree that, rather than being entirely genetically determined, depression is a combination of nature and nurture. Robert Plomin of the Institute of Psychiatry in London points out that "the same genetic research that has demonstrated the important contribution of genetics also provides the best available evidence for the importance of environmental influence."
There is evidence that brain chemistry, which may be genetically determined, plays an important role. Anti-depressants which alter this chemistry have proved efficient palliatives. Simply stated, they increase the levels of the "amine" neurotransmitters (such as serotonin), which suggests that depression ensues from having too little of them.
Evidence for disturbances in corticosteroid hormones, in particular cortisol, which plays a part in our bodies' responses to stress, is also becoming increasingly compelling. Cortisol levels go up in depression, perhaps in part because negative feedback mechanisms, which normally keep these in check, fail. If a causal link can be found, there would be important implications for treatment.
But the links between chemicals and our moods remain intriguing and are impossible to identify in all their complexity. "Imaging studies" are being done to elucidate them. They involve looking at the activities of the brain and its controlling chemicals in depressed and non-depressed subjects to identify the zones responsible for moods, and what drugs can do to modify them.
The impact of events in our lives is determined in part by their interpretation. Professor Chris Brewin, of London University, has found links between childhood adversity and later depression. He believes that early unprocessed trauma arising from sexual abuse may lead to recurrent problems prompted by factors such as self-blame and bodily shame. If the course of a depressive illness is indeed critically determined by early childhood trauma, trauma processing may have an important place in focused psychotherapy which is increasingly used to treat depression.
The role of social circumstances in depression is also clear. There is evidence that single mothers who try to cope with poverty by finding full-time employment feel guilty, to the point of depression, about leaving their children. Furthermore, poverty and deprivation strain interpersonal relationships; and it is now strongly believed that it is mainly difficulties in the latter that cause depression. But we do not know how these poor interpersonal relationships, brain chemistry and lowered mood are connected.
Age and gender in depression
Given that an interplay of genetic and social factors causes depression, how can we account for age and gender differences? The former are perhaps easier to explain. Genetic influences are known to be stronger or weaker at different stages in our lives. As we grow older, the role of inherited factors in causing depression appears to increase for a time, taking over from the apparently predominating factor of environment in children, and then decreases again in the elderly.
Changes also occur in brain chemistry (the activity of the neurotransmitters) and in the structure of the brain with age, while other physical and social factors also alter. Together, these may be responsible for the prevalence of depression in the elderly despite the decrease in influence of hereditary factors.
Work is under way to assess the extent to which cultural variations and social patterns may affect the incidence of depression. It seems reasonable to assume that people who are well looked after, cherished and valued are likely to be happier than those who are not. For example, it will be interesting to see whether there turn out to be variations in the onset of depressive disorders in societies such as India, where the social assumption that it is an honour to care for elderly relatives has meant-at least until recently- that the elderly perceive their position as secure. (Increased emotional support has proved beneficial in reducing the incidence of recurrent schizophrenic breakdowns in people who have suffered one episode).
Depression in children has its puzzles, too. Social and environmental factors unique to this period of life clearly play a role, but again there are biological determinants. The striking ineffectiveness of anti-depressants in children highlights the likelihood that developmental factors are involved. Psychotherapy for childhood depression has also revealed an interesting paradox: the efficacy of cognitive behaviour therapy (CBT), a focused and usually relatively brief intervention designed to encourage the psychological replacement of negative with positive thoughts, is marked. Taken together, the ineffectiveness of anti-depressants and effectiveness of CBT suggest that we are not simply seeing a difference in terminology about feelings in children but that the nature of depression may be fundamentally different from that in adults. The Mental Health Foundation is currently addressing this question with its "Listening to Children" initiative.
European comparisons
The Depression Patient Research in European Society (Depres) project might offer clues about the complex relationship between social status, support and gender in causing depression. Depres is the first pan-European study to look at depression on an individual and social level. Its first phase assessed nearly 80,000 people in six countries for symptoms of depression using a verified rating scale. Results of Depres I were reported in October 1995, and Depres II is underway, studying in more detail 2,000 subjects identified with depression in the first phase.
Seven per cent of Europe's population were found to have symptoms of major depression; 2 per cent minor; and depressive symptoms were present in a further 8 per cent. Depression was most prevalent in France, which also showed the greatest gender discrepancy. These findings are summarised in the graph on the right; they show that the severity of the depression does not differ between men and women, with deep depression accounting for about 40 per cent of sufferers of either gender.
Twice as many women as men suffer from depression during childbearing years, and depression rates are higher in women than in men when studied across a wider age range (see chart on previous page). Myrna Weissman and Mark Olfson, working in New York, last year reviewed epidemiological studies in non-European countries. These confirmed the average twofold higher female prevalence.
Perhaps counter-intuitively, social causes for this gender discrepancy are favoured over biological ones. A recent study led by Professor George Brown began to unpick why this might be. He looked at couples who had shared a life experience likely to impinge on both of them and to cause depression. The events most obviously responsible for the gender difference in depression were those concerning reproduction, children and housing. There was no gender difference when other types of events were looked at.
The gender difference appears to be determined very strongly by role commitments. It will be interesting to see what happens to the epidemiology of the gender difference as, or if, more men enter the small group of partners actively participating in traditional female areas and whether, as this study suggests, the overall burden of depression increases in such couples.
The continuing research spectrum
The interaction between genetic and environmental factors in causing depression is highly complex, but no one doubts that considering them together is a necessity. Questions concerning exactly how and why we feel the way we do at any given time may remain forever unanswered, but research into the causes of depression continues to be fruitful. The biological contribution will continue to be elucidated as our genetic make-up-the human genome-is further understood.
This still leaves us with the bewildering question as to why some people succumb to depression while others do not. We tend to look at vulnerability factors, but what of resilience? What is the nature of protecting factors? These may become more of a focus for research as treatment levels increase. Meanwhile, the spirit of collaboration across the spectrum is vital: the causes of depression must surely lie in the interaction of biological, psychological and social factors.
