Based on Psychological Medicine Dec 2015 article Depression as a systemic syndrome: mapping the feedback loops of major depressive disorder
by A. K. Wittenborn, H. Rahmandad, J. Rick and N. Hosseinichimeh, mentioned here
early adversity such as abuse or neglect of a child is processed and stored in the form of negative cognitive representations within an individual’s memory.
Negatively biased attention and processing increases one’s perceived level of stress which leads to negative affect such as sadness and biased interpretations of negative stimuli that often align with one’s negative mental models.
The processing of negative thoughts and affect is encoded and stored in one’s memory, further strengthening existing negative cognitive representations.
negative affect and interpretations intensify one’s propensity for ruminative thought which further compounds perceptions of stress and increases negative affect.
Brain regulatory capacity can inhibit negative feelings and rumination
Negative affect and interpretations contribute to dysfunctional behaviors and strengthen negative cognitive models. Dysfunctional behavior intensifies the perception of oneself as worthless.
Increased negative affect inhibits the efficiency of working memory, leading to less optimal cognitive performance.
Cognitive performance further contributes to dysfunctional behaviors, which lead to biased attentional processes, increased perceptions of stress, negative affect and interpretations, and further
inhibit the efficiency of working memory.
Dysfunctional behaviors contribute to weakened social networks in the form of poor interpersonal relationship quality or social isolation. Stress related to interpersonal relationships contributes to
negative affect and processing and can lead to problematic responses (e.g. aggression), which, in turn, depletes interpersonal relationship quality. As depressed patients become further plagued
by challenging relationships or isolation, their negative cognitive representations are reinforced.
Economic status, including material assets, income and reputation, can be depleted through the effects of poor cognitive performance or behaviors at work and beyond. Absenteeism or presenteeism
can lead to job loss or limits to promotions and underemployment, thereby severing or restricting income. Poor cognitive performance in the face of various risks at work and in society can also cause
economic and reputational damage. Financial stress can produce negative affect and problematic behavioral responses that increase economic adversity and reinforce negative mental models
Perceived psychosocial stress activates the central nervous system by inducing the secretion of corticotrophin-releasing hormone and vasopressin in the hypothalamus that stimulates adrenocorticotrophin
hormone in the anterior pituitary and, in turn, releases cortisol in the adrenal cortex.As concentrations of cortisol increase, glucocorticoid receptors (GRs) become overburdened.
Excess cortisol, cortisol reactivity, and altered GR function inhibit the HPA system and reinforce HPA dysregulation which has negative consequences for physical and mental health.
The effects of brief periods of stress on cortisol are often adaptive and resolve autonomously, but chronic stress is what drives illness.
Early adverse experiences, both in utero and in early childhood, can also initiate changes to basal and stress-related cortisol secretion.
Extensive communication occurs among the immune, endocrine and central nervous systems. During increased periods of stress or
chronic illness, pro-inflammatory cytokines are released. Cytokines are known to inhibit GR function.
Although cortisol is a key anti-inflammatory hormone, when chronic stress sustains cortisol response and GRs become overburdened, cortisol signaling becomes
insufficient and unable to reduce immune responses, which leads to inflammation.
Chronic exposure to cortisol and cytokines reduces the availability of monoamines like serotonin, dopamine and norepinephrine by influencing synthesis and reuptake.
Monoamine neurotransmitters regulate sleep and wakefulness and deficiencies lead to sleep problems. Sleep is vital to long-term memory consolidation, which is necessary for learning, and sleep problems
can disrupt this process.
Monoamines also play an important role in emotion regulation. Serotonin deficiency reduces the brain’s regulatory capacity by not adequately modulating amygdala response to negative stimuli which leads to
sustained emotional responding in the face of stress and plays a key role in reinforcing negative cognitive and emotional processes
High levels of cortisol and cytokines in the context of GR resistance act to suppress neurogenesis and promote neuronal death that leads to hippocampal atrophy. Reduction of hippocampal volume has a negative effect on learning and memory, especially in relation to explicit memory formation,
which leads to memory deficits and impaired cognitive performance.
Physical health also interacts with depression. Dysfunctional behaviors such as medication non-adherence and poor diet (e.g. diets low in omega-3 essential fatty acids or polyunsaturated fatty acids) have a negative effect on health and perceived stress.
Poor behaviors such as physical inactivity due to loss of motivation contributes to chronic medical problems, affecting immune functioning,
HPA axis reactivity, and sleep and eventually reinforcing declines in health.
Declining physical health can limit an individual’s capacity to engage in
physical activity and physical inactivity increases cortisol concentrations.