Genes

Vulnerability to bipolar disorders is highly heritable, and, in some types, mood systems are highly unstable (Akiskal & Pinto, 1999; Wilson, 1998). For some unipolar major depressions, there is a genetic vulnerability (McGuffin et al., 1991). It also seems likely that there may be a variety of genotypes for different types of depression. However, consider that cystic fibrosis is an inherited disease, but only if one inherits two copies (one from the father and one from the mother) of the genes. One copy increases lung mucus, but this can be highly protective against some lung diseases. Thus, a gene or genes for a disorder or degree of severity may manifest themselves only when associated with other genes, and in different combinations can give a positive advantage or a milder vulnerability. Or consider sickle-cell anaemia; its gene also protects against malaria (Wilson, 1998). Hence, it remains unclear whether the genes associated with depression also confer benefits, and, if so, which genes in what combinations, and in what contexts do they create serious problems.

The study of the ongoing, reciprocal, dynamic processes of individual-environment interactions suggests that the genotypic possibilities of functions can have unpredictable phenotypic outcomes. For example, there are variations in genetic sensitivity to depressed states possibly related to the 5-HT transporter gene that influences the metabolism of 5-HT. However, cross-fostering research in primates (that is, placing genetically at-risk infants with highly responsive mothers) suggests that such an apparent genetic sensitivity is only manifested in certain contexts. Indeed, animals with this genotype can do exceptionally well in certain developmental (such as high-care) contexts but badly in others (such as low-care) (Suomi, 1997; personal communication, September, 2000). So it is unclear whether genes affect the degree of shift (intensity of a response) to a stressor, and/or make one sensitive to learning in particular social contexts. If the latter, this could mean one's nervous system is more plastic and open to social shaping for good or bad. This seems to be the implication of Suomi's findings. Genes themselves can also be turned on and off by the environment. We cannot explore this here, but for a fascinating and highly readable account of the way the environment—including internal physiological processes such as cortisol—can have gene-controlling effects, see Ridley (2000).

Considering the two (possible) evolved regulators of mood states—attachment loss and social-rank defeat—there is good evidence that for attachment loss there are genetic differences in the intensity and duration of response to separation (Suomi, 1997). It is probable (although there is no good evidence) that the same is true for social rank and defeat. In bipolar spectrum disorders, hypomania is associated with a heightened sense of being up-rank and with sexuality, feeling important and confident, and having energy. Such a profile has been associated with high rank, and recent acquisition of high rank, in many animals (Gardner, 1982). Frenetic activity, including sexual behaviour, may be adaptive, in that one's position may not last for long—so one should make hay while it does (Wilson, 1998). In so far as the mechanisms for this profile may be a form of generalised disinhibition, this can spread through human cognitive systems, giving rise to poorly controlled thinking processes and preoccupation with high-rank (status) activity—being a world leader or the chosen one, or solving the riddles of the meaning of life. Depression is typically associated with the opposite—loss of confidence, feeling inferior and a failure, loss of energy, and social withdrawal. Just as there may be genetic variation in populations in the intensity and ease of triggering protest-despair, so there may be genetic influences underpinning the intensity and ease of triggering in the winner go-for-it strategies and in the loser defeat and failure (stop going for it) strategies (Wilson, 1998). It is unclear whether these are related to the same genetic sensitivities.

Understanding And Treating Bipolar Disorders

Understanding And Treating Bipolar Disorders

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