Pathophysiology of Depression: Anatomy, Physiology, Mechanism, Prevention and Treatment

Running head: PATHOPHYSIOLOGY OF DEPRESSION
PATHOPHYSIOLOGY OF DEPRESSION
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1PATHOPHYSIOLOGY OF DEPRESSION
Introduction
Depression is known as a chronic psychological mood disorder which is characterized by
detrimental changes in an individual’s regulation of moods, emotions, thoughts and attitudes
towards daily life (Miller & Raison, 2016). Taking insights from the Diagnostic and Statistical
Manual of Mental Disorders, symptomatic effects of depression are characterized by the
occurrence of dysphoria or depressed mood, coupled with a loss of desire to engage in previously
enjoyable tasks (Fried et al., 2016). According to the World Health Organization, depression
affects over 450 million of the global population (Kessler et al., 2015). At present, the defects in
the neurotransmission and signaling of dopamine has been associated as the primary
pathophyiosology underlying depression. Such disruptive changes can be attributed to the
reductions in the number of receptors, decreases in the release of dopamine from presynaptic
neurons, alterations in signal processing at the cellular level and impairments in the transduction
of nervous signals (Salamone et al., 2016). The following essay attempts to discuss on the
underlying anatomical and pathological changes emerging in depression and possible preventive
and treatment practices for enhance management.
Normal Anatomy of Affected Body System
One of the key body systems affected by depression is the dopamine system of the
cerebral cortex. The normal anatomy of the dopamine system consists of a group of neurons,
with their originations from the mid-section of the brain. The axons of the neurons associated
with the dopamine system possess extensions towards the forebrain, and consists of three neural
branches performing essential functions which will be discussed in the succeeding sections
(Seitz, Paloutzian & Angel, 2018). Of the three branches, one branch extends to the frontal

2PATHOPHYSIOLOGY OF DEPRESSION
cortex, another branch possesses extensions to the striatum while the third branch, protrudes into
the limbic system of the brain. The limbic system of the brain, alternatively known as the center
of for rewards and perceptions of pleasure, comprise of the primary section affected by the
pathophysiology of depression (Popova et al., 2015).
Normal Physiology of Affected Body System
The mesolimbic dopamine system is of major concern in the pathophysiology of
depression and is associated with neural connections from the midbrain dopamine system to the
cerebral limbic and nucleus accumbens areas. These core cerebal areas of the limbic system are
one of the oldest sections of the brain to have emerged and survived since the evolution of
mankind and are associated with neural structures responsible for determining our mood,
emotions and environmental perceptions in response to stimuli and rewards (Riccelli et al.,
2016). The harbingers of the limbic system considering emotional regulation are the amygdale,
located in the temporal lobe and the hippocampus situation adjacently. These regions are the
primary cerebral centers for housing prolonged memories and thought processes and are highly
receptive to situations of stress, agitation, threat or anxiety. Hence, in the presence of challenging
or demanding situations, activation of the hippocampus results in activation of the hypothalamus
and the resultant stimulation of the hypothalamus-pituitary-adrenal (HPA) axis (Rajagopalan et
al., 2017). Stimulation of the HPA axis results in an endocrinal cascade characterized by
pituitary activation directed by the hypothalamus, further leading to activation of the adenal
glands. Hence, as a normal physiological process, in response to stress, challenging or depressive
life events, such stimulation encourages adrenal secretion of cortisol (Radley et al., 2016).
Cortisol, a steroid hormone, prepares the body for responding to challenging situations through
physiological changes in the form of increased alertness, enhanced blood sugar levels and

3PATHOPHYSIOLOGY OF DEPRESSION
metabolic regulation. Hence, it is through the HPA axis and cortisol secretion functioning that
the human body attempts to maintain physiological and psychological homeostasis in a situation
of stressful life events (Seo et al., 2019).
Mechanism of Pathophysiology
According to Keller et al., (2017), the pathophysiology of depression has been associated
with changes in the HPA axis in situations of excessive and chronic stress, which is a
characteristic resultant of traumatic life events. Exposure to chronic stress in the form of
challenging or traumatic life events, has been associated hyperactivity of the HPA axis. Such
hyper functioning results in continuous elevations in the adrenal secretion of cortisols and
corticosteroids. Steroidal hormones such as corticosteroids pose direct associations with the
pathology of depression, where high levels of the same have been shown to result in reductions
in the secretion of neurotransmitter dopamine as well as decreases in the size of the
hippocampus. The hippocampus is the primary regulator of the HPA axis and hence, it plays a
key role in exerting inhibition upon this axis (Du & Pang, 2015). Hence, as researched by
Dwivedi et al., (2015), stress and corticosteroid induced hippocampul reduction results in lack of
regulation of the HPA axis, further leading to uncontrolled secretion of corticosteroids.
Excessive corticosteroids have been implicated to yield depression like symptoms and alterations
in emotion and further has been associated with reducing the size of the amygdala, the primary
limbic center associated with memory, mood and reward perceptions. Hence, as researched by
Grace (2015), hindrances to the dopamine system, exerted by corticosteroids results in alterations
of the ventral tegmental area and nucleus accumbens - cerebral amygdala areas concerned with
perception of reward responses – leading to reductions in the sensation of pleasure and
malfunctioning brain reward circuit. Indeed, such structural alterations in response to traumatic