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Nursing Pharmacology Chapter 17: Antidepressant Agents
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Etiology of depression (continued)
Although the exact cause of major depressive disorder remains to be elucidated, a number of factors have been suggested.2
These
potential contributors include genetic, psychodynamic,
socioenvironmental and biochemical factors.2
Genetics (continued)
Perhaps as much as 40% of the risk of developing depression may be hereditary; as an example, adopted children whose biological parents exhibited depression have a greater risk of developing depression then those adopted children whose biological parents were unaffected.26
Furthermore, frequency of depression is increased in relatives of patients, with a prevalence rate between about 15%-25% in first-degree relatives.
Depression risk among first-degree relatives is increased comparing 15% to about 1%-2% general population risk.26
Considering "twin studies", for unipolar depressive disorder 40% of monozygotic twins and 11% of same-sex dizygotic twins are affected. (The values for bipolar depressive disorder, for comparison, are 72% [monozygotic] and 14% [same-sex dizygotic]).26,49
Some texts indicate that the serotonin transporter gene allelic variations (polymorphism) may be responsible for depression susceptibility; however, given conflicting reports in the literature, further studies are needed to clarify possible relationships between serotonin transporter gene polymorphism and depression.
The relative risk ratio (RRB, i.e., ratio of risks to first-degree relatives of individuals exhibiting major depressive disorder compared to the general population) is about 2-3.50,51
However, the mode of inheritance remains to be elucidated and significant environmental risk factors include child abuse, neglect, and life stress.50,52
Genetic mapping study utility is based on determining the relative risk ratio associated with each gene or interaction; furthermore, endogenous depression susceptibility may be due to multigenic mechanisms.50
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The relative risk ratio for both recurrent and early-onset major depression has been estimated to be at least 4-5.50
As an aside, although relatives of bipolar disorder patients are at risk for major depression, the converse is not observed.
Other
neuropsychiatric conditions may predict major depressive disorder.50
Neuroticism, characterized by anxiety, dysphoria, tension and emotional reactivity, exhibits heritability on the order of 40%-50% and appears to be a prominent predictor of future major depressive disorder onset.50,53,54,55
Perhaps 55% of genetic risk associated with major depression appear shared with neuroticism.
Genetic factors appear more likely associated with major depressive disorder, neuroticism and generalized anxiety disorder and less likely associated with panic disorder and social phobia.50
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As described earlier, studies on functional polymorphism, defined as DNA sequence alterations that change expression and/or gene product function, have focused on monoamine related genes and on brain-derived neurotrophic factor neuroprotective proteins.50
A recent meta-analysis study considered interaction between serotonin transporter gene, stressful life events and depression risk.58
This analysis considered 26 studies, of which 14 met the authors criteria for the meta-analysis.
In this
meta-analysis of published research results, the number of stressful
life events was associated with depression; however, no association
was noted between the serotonin transporter gene genotype and
depression.
Furthermore, no evidence was found that serotonin transporter gene type interacting with stressful life events was associated with increased depression risk in men alone, women alone, or in both sexes combined.58
The tryptophan hydroxylase 2 isoform, has been identified as the principle enzyme form in the brain.59
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Major
depressive disorder may be associated with single nucleotide
polymorphisms of the gene associated with this isoform.60,63
A recent study analyzed an association between tryptophan hydroxylase 2 isoform and late-onset depression.61
These investigators genotyped 8 single nucleotide polymorphisms in the TPH2 gene in 84 patients with late onset depression and in 79 individuals who served controls.
The study was conducted in the Brazilian population.
Association was found between two single nucleotide polymorphisms and late onset depression.61
A related study involving Caucasians (Northern Swedish) reported association between TPH2 haplotypes and major depression.62
Brain-derived neurotrophic factor (BDNF) is a neuroprotective protein that may be linked to major depressive disorder.50
Brain structural abnormalities may be associated with
geriatric depression.67
These structural changes may be reflected in reduced size i.e., volume and prefrontal cortex, anterior cingulate gyrus, amygdala and hippocampus.
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