Abstract
According to our model of the regulation of appetitive-searching vs. distress-avoiding behaviors, the motivation to display these essential conducts is regulated by two parallel cortico-striato-thalamo-cortical, re-entry circuits, including the core and the shell parts of the nucleus accumbens, respectively. An entire series of basal ganglia, running from the caudate nucleus on one side, to the centromedial amygdala on the other side, controls the intensity of these reward-seeking and misery-fleeing behaviors by stimulating the activity of the (pre)frontal and limbic cortices. Hyperactive motivation to display behavior that potentially results in reward induces feelings of hankering (relief leads to pleasure). Hyperactive motivation to exhibit behavior related to avoidance of misery results in dysphoria (relief leads to happiness). These two systems collaborate in a reciprocal fashion. In clinical depression, a mismatch exists between the activities of these two circuits: the balance is shifted to the misery-avoiding side. Five theories have been developed to explain the mechanism of depressive mood disorders, including the monoamine, biorhythm, neuro-endocrine, neuro-immune, and kindling/neuroplasticity theories. This paper describes these theories in relationship to the model (described above) of the regulation of reward-seeking vs. misery-avoiding behaviors. Chronic stress that leads to structural changes may induce the mismatch between the two systems. This mismatch leads to lack of pleasure, low energy, and indecisiveness, on one hand, and dysphoria, continuous worrying, and negative expectations on the other hand. The neuroplastic effects of monoamines, cortisol, and cytokines may mediate the induction of these structural alterations. Long-term exposure to stressful situations (particularly experienced during childhood) may lead to increased susceptibility for developing this condition. This hypothesis opens up the possibility of treating depression with psychotherapy. Genetic and other biological factors (toxic, infectious, or traumatic) may increase sensitivity to the induction of relevant neuroplastic changes. Reversal or compensation of these neuroplastic adjustments may explain the effects of biological therapies in treating depression.
Highlights
The burden of depression in modern society is enormous
Clinical depression is so common that it may not be considered an illness. It could be concluded from foregoing reflections that, perhaps we should think of depression as the price humans must pay for improving the standard of living and for dramatically increasing life expectancy
Depression may be considered an aberration of a mechanism that originally favored survival, or it may be a necessary mechanism that allows the human species to adapt to dramatic changes in the biotope
Summary
The burden of depression in modern society is enormous. According to the definition of the often applied criteria of the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM), major depressive disorder (MDD) is highly prevalent, and patients with MDD are seriously disabled. Like panic disorder (3.8%), occur far less frequently than MDD (De Graaf et al, 2010) This very high lifetime prevalence of MDD indicates something about its position in the spectrum of mental disorders, and probably about its pathogenesis. A new model was presented that distinguished between two types of cortico-ganglio-thalamo-cortical tracks, which could regulate intuitive (emotional) and skilled (cognitive) behaviors. These tracks were called the limbic and extrapyramidal circuits, respectively (Loonen and Ivanova, 2016a). The biological mechanisms required to accomplish these adaptations comprise neurochemical, neuro-endocrine, neuro-immune, and neurophysiological components These mechanisms will be described here, according to five current theories that postulate different neurobiological backgrounds that give rise to mood disorders (Loonen, 2013a). This situation will be explained by considering how humans have changed their habitat over the last two centuries
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