The following is a look at the physiological causes of depression with the help of Mark Rose. The exact causes of clinical depression are unknown. Earlier neurobiological studies of depression focused on the monoamine-deficiency hypothesis as well as the hypothalamic-pituitary-adrenal (HPA) axis theory, although these are no longer taken seriously. It is clear that emotional trauma, especially during one’s formative years, increases the risk of depression. It is generally accepted that 40-50 percent of the cause o depression is genetic, although interaction of genes with environment play a large role as well.
Indeed, intense stress in one’s early years results
“in persistent neuroendocrine, physiological, behavioral, and psychological changes that negatively affect the development of brain systems involved in learning, motivation, and stress response, and that may also reflect a biological priming for the development of depression, especially with additional stress exposure Additionally, a chaotic, unstable caregiving environment during infancy may create a chronically over-reactive stress response system, resulting in subsequent impairments in stress response, emotional regulation, and impulse control.”
Childhood sexual abuse also contributes to the risk of psychiatric disorders in general, including depression. Theories of depression have typically focused on neurotransmitter imbalances, particularly serotonin, norepinephrine and dopamine. These hypotheses have considerable empirical support.
“Considerable evidence does support the notion that major depression involves an alteration in the balance of neurotransmitters and/ or their function, as manifested by impaired neurotransmitter synthesis, increased breakdown or metabolism of neurotransmitters, and increased pump uptake of neurotransmitters. A decrease in the functional balance of specific neurotransmitters has been hypothesized to cause certain types of depression; decreased norepinephrine would cause dullness and lethargy, while decreased serotonin would result in irritability, hostility, and suicidal ideation.”
However, depression is not solely caused by neurotransmitters. Sleep disruptions, poor diet and emotional reactions to difficult events must be taken into account as well. Rose lists the four cognitive domains disturbed in depressed individuals as executive control, memory, affective processing and feedback sensitivity
“Converging evidence from neuroimaging, lesion analysis, and postmortem studies now suggest that these disturbances in cognitive function, and the other signs and symptoms of depression, reflect dysfunction within an extended visceromotor network that interferes with the ability to modulate emotional behavior [58]. The medial prefrontal cortex and related limbic and striato-pallido-thalamic structures organize emotional expression and are part of a larger “default system” of cortical regions that include the dorsal prefrontal cortex, mid- and posterior cingulate cortex, anterior temporal cortex, and entorhinal and parahippocampal cortex. Dysregulation within and between structures in this circuit, and with their interactions with subcortical regions (striatum, thalamus) and temporal lobe structures (amygdala, hippocampus), is believed to underlie the disturbances of emotional processing, cognitive performance, neurotransmission, autonomic regulation, and neuroendocrine responses associated with mood disorders such as major depression.”
Evidence has focused on dysregulations in neural circuitry have recently come under scrutiny, rather than focusing merely on neurotransmitter imbalance. As noted before, depression often ends tragically in suicide. Suicidal behavior is associated with hyperactivity of the HPA axis, excessive activity in the noradrenergic system and serotonergic system dysfunction. The first and second of these seem to be involved in stressful events, whereas serotonergic dysfunction has more to do with individual traits, and correlated with disturbances regulating impulsivity, aggression and anxiety.
“Altered functioning of these systems may stem from both genetic and developmental causes. Exposure to extreme or chronic stress during childhood has developmental consequences on these systems that persist into adulthood. Genetic differences may also contribute to alterations in the functioning of these neurobiological systems, and the interactive effect of adverse childhood experiences, such as physical abuse, sexual abuse, or caregiver abandonment, with genetic vulnerability is increasingly believed to play a role in suicidal behavior.”
Neurologists and psychologists seem to have converged on two of the most important predispositions to suicide: problems with impulse control and overwhelming psychological pain. These affective traits are typically correlated with a disrupted serotonergic system. Serotonergic dysfunction is particularly linked with the dorsal and median raphe nuclei in the midbrain. This part of the brain hosts primary serotonergic cell bodies, whereas the prefrontal cortex (especially the ventral prefrontal cortex) becomes innervated by the serotonergic system:
“In vivo and postmortem examinations have revealed serotonergic hypofunction in these two brain systems in persons who have died by suicide or made serious suicide attempts. The deficient serotonergic input in the ventral prefrontal cortex stemming from this serotonin hypofunction can result in a breakdown in inhibitory function leading to a predisposition to impulsive and aggressive behavior. This vulnerability to deficient impulse control coupled with the development of psychiatric illness or other life stressors elevates the risk of acting on suicidal thoughts.”
