Depression: Evolutionary Approaches

(This article was first published by the Lundbeck Institute in the Institute Magazine no. 7, 2004.)

Depressive behaviours may have played an important adaptive role in dealing with environmental challenges of conflict and failure.Work based on evolutionary theories may eventually enhance our ability to understand and manage depression.

Major depressive disorder is one of the most prevalent of all psychiatric disorders (Kessler et al., 1994), and depressive phenomena appear to be universal across cultural groups (Sartorius et al., 1983). A broad range of cognitive-affective, neuro-anatomical and neuro-chemical mechanisms have been implicated in the psychogenesis of depression.

More recently, researchers have also begun to theorise about the evolutionary origins of depression, suggesting that it may have evolved to enable animals and humans to adapt to environmental challenges. In this article, we review some of this interesting work.

The symptoms of depression are affective, cognitive and somatic (APA, 2000). Low mood, characterised by feelings of sadness and emptiness, and an inability to experience pleasure or enjoyment, are the primary affective features of depression.

Accompanying cognitive symptoms include negative thoughts about the self, the world and the future, manifested in markedly low self-esteem and a pervasive sense of hopelessness and pessimism. The capacity to cope with ordinary tasks is reduced by the somatic features of depression, which include changes in appetite, sleep disturbances, reduced energy and psychomotor retardation, and slowed thought processes.

Cognitive-affective neuroscience of depression

The affective, psychomotor and cognitive features that characterise depressed mood suggest the involvement of particular neuroanatomical systems. Low positive affect, for example, has been associated with hypoactivation of the left frontal cortex (Mineka et al., 1998),while psychomotor function is mediated by striatal circuits (Stein, 2003).

The bias of depressed people towards recalling negative information (MacLeod and Byrne, 1993) suggests disturbances in the limbic system (amygdala, hippocampus and hypothalamus), which governs emotional memory.

Indeed, there is a broad preclinical literature from animal studies showing that pathways linking limbic structures to a network of frontal, paralimbic (ventral frontal, cingulate, insula, anterior temporal poles), striatal and brainstem regions are crucial in mediating affective and motivational behaviour (Damasio, 1996; MacLean, 1949; Rolls, 1990).

Thus depressed mood appears to rely on a long evolved neurocircuitry that adaptively governs functions such as approach and avoidance.

Functional imaging studies with transiently induced sadness in normal subjects has confirmed the role of a broad network of corticallimbic circuits in the modulation of mood, and in evaluating the emotional significance of stimuli (Lane et al., 1997; Mayberg et al., 1999).

Structural imaging studies have identified abnormalities in prefrontal, limbic/paralimbic (cingulate, hippocampus) and striatal regions in depressed patients (Sheline, 2000), while functional imaging studies similarly suggest that clinical depression is characterised by decreased activity across this range of interconnecting neurocircuits (Videbech, 2000).

However, these conclusions remain tentative: a number of studies of depression have, for example, found not only hypoactivity (e.g. in neocortical areas) but also areas of hyperactivity (e.g. in paralimbic systems or the amygdala) (Drevets, 2000; Mayberg et al., 1999).The precise differences in the neurocircuitry of normal or adaptive decreases in mood and pathological depression remain to be fully delineated.

With regard to the neurochemistry of depressed mood and major depression, a broad range of studies has demonstrated involvement of the serotonergic system, with abnormalities of peripheral serotonergic markers in depression, the most widely reported being decreased serotonin transporter (5-HTTP) binding (Owens and Nemeroff, 1994).

Functional imaging and post-mortem studies have confirmed decreased 5-HTTP binding in depression and suicide (Malison et al., 1988; Mann et al., 2000). Dynamic studies of the 5-HT system in response to serotonergic agonists, or to serotonin depletion, offer methodological advantages over studies of static measures, and in such studies a range of data again points towards aberrant serotonergic neurotransmission in depression (Charney, 1998).

Depletion studies, for example, have shown that decreased 5-HT synthesis precipitates symptoms of depression in healthy and in remitted depressed patients (Bell and Nutt, 2001). A currently influential hypothesis is that selective serotonin reuptake inhibitors (SSRIs) exert their effects by desensitisation of 5-HT1A somatodentritic autoreceptors (which initially serves as a "brake" on serotonin neurotransmission).

This accounts for the relatively slow time of pharmacotherapy response in depression, with only gradual desensitisation and increased neurotransmission (as the "brake" is effectively released) (Stahl, 1998). Ultimately there may be increased serotonergic activity and reversal of dysfunction.

There is a growing literature on the molecular imaging of 5-HT receptor subtypes at baseline and after SSRI treatment, with some evidence (albeit inconsistent) in favour of such a hypothesis (Becker et al., 2001; Sargent et al., 2000; Staley et al., 1998).

Several additional neurochemical systems also play a role in mediating depressed mood and major depression. The noradrenergic system, for example, may play a particularly important role in mediating decreased drive and energy in depression.

The dopamine system is thought to play a crucial part in processing motivation and reward, and thus may also play a role in depression. Dopamine hypofunction may be particularly important in patients with psychomotor retardation; decreased striatal dopamine uptake is present in depressed patients with psychomotor retardation compared with nonretarded depressed patients and healthy patients (Martinot et al., 2001).

Again, the precise differences in mechanisms responsible for normal adaptive fluctuations in mood from those involved in pathological depression remain to be fully elucidated. Nevertheless, ongoing research, including work on neuronal atrophy in depression, is likely to lead to a better understanding of this distinction in the future.

Evolutionary considerations

Evolutionary medicine attempts to supplement standard accounts of proximal neurobiological mechanisms involved in disease with hypotheses about the evolutionary origins of pathology (Nesse and Williams, 1994).

Although this framework has long been in existence (Darwin, 1872), in recent years there has been renewed theoretical interest, as well as the development of a number of evolutionary models of various psychiatric disorders.

Evolutionary conceptualisations argue that depression is adaptive in situations where continued effort to pursue a major goal will result in either danger or loss of resources. Such situations include, for example, a fight with a dominant figure.

Attempts to access evolutionarily meaningful resources (e.g. territory, mates, or alliances) frequently brings conspecifics into conflict with each other; thus, dealing effectively with competitors is an important evolutionary survival skill. To ensure survival, animals who are likely to lose these conflicts need to have an internal mechanism that inhibits their challenge behaviour and deescalates the conflict (Gilbert, 1992; Price et al., 1994; Stevens and Price, 1996).

Humans may have developed similar mechanisms for dealing with social conflict and competition. Additionally, it is inefficient for humans to continue to invest effort in unreachable goals; thus repeated failures to achieve a major life goal necessitate some regulation of patterns of investment (Nesse, 2000).

In situations of conflict with more dominant competitors, and of persistent failure in major life goals, an inhibitory response (entailing loss of energy, retarded movements, loss of confidence, and a sense of hopelessness) may result in withdrawal from competition and a reduced level of aspiration.

This is adaptive in so far as it reduces actions that may be dangerous (e.g. attempting to do battle with a much stronger figure) or wasteful (e.g. attempting to start a new enterprise without adequate resources): "Just as anxiety inhibits dangerous actions, depression inhibits futile efforts" (Nesse, 2000, p.17).

The advantages of a depressive response to environmental stressors accrue not only to the individual. A yielding subroutine by the "losers" in cases of conflict between conspecifics ultimately preserves the stability, homeostasis and competitive efficiency of the whole social group (Price and Sloman, 1987; Stevens and Price, 1996).

The importance of group selection remains a contentious issue in evolutionary theory. Nevertheless, it may be suggested that, since inhibition in the face of danger or defeat enhances both individual and group survival, attunement to success or failure in social conflict situations and the activation of depressive phenomena in response to an unwinnable conflict, have been selected for in our evolutionary history.

Empirical evidence to support these speculative evolutionary theories is still scarce. Given the involvement of serotonergic systems in depression, it is interesting to note that subordinate rats subject to social stress have reduced 5-HT1A receptor binding in the hippocampus and dentate gyrus (McKittrick et al., 1995), while preclinical and human studies indicate that changes in serotonergic transmission mediate thresholds for adopting passive or waiting attitudes, or accepting situations that necessitate strong inhibitory tendencies (Soubrie, 1986).

Furthermore, Gilbert and Allan (1998) found that a sense of defeat (after a perceived failed struggle or loss of rank) was strongly correlated with depression. Nesse (2000) has suggested several other ways in which evolutionary theories of depression can begin to be tested.

For example, depression should be more common among people who are unable to disengage from unreachable goals (such as failing college students, and people who are chronically unemployed or unsuccessfully trying to lose weight) and among those who lack the resources or power to accomplish their goals, as well as in cultures with rigid hierarchies.

Discussion

Evolutionary approaches suggest that in earlier times depressive behaviours played an important adaptive role in dealing with environmental challenges of conflict and failure. Analogous phenomena are seen in animals after defeat, and as an accompaniment to physical disorder, where there is a need to preserve energy.

Losing or yielding subroutines may therefore provide a distal template for normal adaptive depressive phenomena. "Depressive realism" – the more accurate depiction of reality by people with decreased mood – may provide a particular advantage during adverse circumstances.

While low mood may be an evolved means of adaptation, clinical depression can be argued to be a pathological aberration based on the inappropriate persistent activation of this adaptive mechanism (Stevens and Price, 1996), a phenomenon that may occur only in individuals with particular neurobiological and environmental vulnerabilities.

Evolutionary theory may also shed light on the role of a particularly important vulnerability factor for major depression – early developmental trauma. Disruption of early attachment has long been known to be a risk factor for depression, and the neurobiological sequelae of such development traumas are increasingly understood (Sanchez, 2001).

While depression may be an adaptive response to a brief separation, the consequences of repeated trauma are often pathological. Taken together, there is still insufficient evidence to conclude that depression can be a normal adaptation, or to characterise major depression as involving the inappropriate and persistent activation of mechanisms involved in mood regulation.

Furthermore, some subtypes of depression (e.g. seasonal affective disorder) may have entirely different evolutionary explanations from those highlighted here.

Nevertheless, evolutionary theories and future empirical work based upon these may eventually enhance our ability to understand and manage depression. In particular, evolutionary theory may help inform an understanding of the risks for depression (Nesse, 2000) and may provide fresh ideas for psychotherapy of depression (Gilbert, 1992).

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