Major Depressive Disorder Report: Theories and Pathophysiology

This report provides a comprehensive overview of Major Depressive Disorder (MDD). It begins with an introduction to the disorder, outlining its characteristics and prevalence. The report then delves into the pathophysiology of MDD, discussing the abnormalities in neurotransmission and brain functioning, including the role of the HPA axis, neuroplasticity, and structural brain alterations. Furthermore, the report explores contemporary theories of MDD, such as the serotonin-transporter–linked polymorphic region (5HTTLPR) and the monoamine-deficiency hypothesis, supported by research findings. The report aims to offer a clear understanding of the biological underpinnings and current theories surrounding MDD, drawing upon the latest research and studies in the field. The report utilizes APA 6th referencing guidelines. This report is valuable resource for students seeking information on mental health and related research.

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Introduction
The condition of depression is generally associated with the emotions of bereavement
and sadness. The condition of major depressive disorder (MDD) is one of the debilitating
diseases. This condition is characterized by changes in the mood and involves the changes in
the interests along with the vegetative and the cognitive symptoms. Reports suggest that
female population suffers from this disorder in comparison to the number of males. It has also
been revealed that major depressive disorder is one of the leading reasons which contribute to
the burden of chronic diseases (Dean et al., 2014). The condition of MDD also leads to
increase of the other associated disorders like diabetes mellitus accompanied by stroke or
cardiac diseases. This paper aims to highlight the condition of major depressive disorder
along with the pathophysiology of the disease. Additionally the paper discusses the
contemporary theories associated with the disorder from the research findings and studies that
have been conducted in relation to the prevalence of major depressive disorder.
Description of the disorder
The course of the disorder is pleomorphic where the chronicity is variable. It has also
been reported that with the increase in the severity of the symptoms, there is an increased
chance of childhood trauma or psychiatry comorbidity. A study showed that in a population-
based samples, it was perceived that the mean episode duration shows variation between 13
and 30 weeks and also about 70–90% of patients with MDD recover within 1 year of time.
On the other hand it was also perceived that only 25% of the patients remitted within a period
of 6 months and about less than 50% of the patents are seen to have MDD after 2 years (He et

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al., 2014). In terms of the disease burden, the Global Burden of Disease Consortium found
reported that in the year 2013, this disorder was seen to be the second largest contributor of
thee chronic disease burden globally (Otte et al., 2016). The findings from the studies also
suggested that MDD leads to the increase of the risk of diabetes mellitus along with cardiac
diseases and stroke along with hypertension, obesity, cognitive impairment and cancer in
some cases.
Pathophysiology
The pathophysiology of MDD in several cases are dependent on the heritability of this
disorder which increases the risk of the MDD to up to three fold. There might also be overlap
of the genes between the genes of MDD and several other psychiatric disorders like
schizophrenia and bipolar disorder. Neuroendocrinology is one of the contributing factors of
MDD. Evidences for this is provided due to the HPA alterations that correlate with the
cognitive function impairment. A study which used the data obtained from a primary care
database that included more than 370,000 individuals that showed that treatment using the
glucocorticoids that was associated with an increased risk of suicidal tendencies (Slavich &
Irwin, 2014). The antidepressants help to reduce the levels of cortisol for the patients
suffering from MDD. Additionally a study by meta-analysis showed that there were
approximately 50% of the patients who had similar levels of cortisol before and after the
treatment (Schulze et al., 2014). In terms neuroplasticity, there were peripheral changes
occurring in the cortisol levels of the mechanisms of inflammation which was responsible for
affecting the brain and the cellular level of neurogenesis. Towards these lines, the lower
levels of the neurotrophin brain-derived neurotrophic factor (BDNF) there have been
measurements of the sera of patients with MDD. The structural brain alterations also are
responsible for the pathophysiology of the major depressive disorder. There is a combination
between the cellular mechanisms and the molecular mechanisms which is ultimately

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responsible for morphological changes occurring in the brain structure in MDD which is
evidenced by neuroimaging. There are certain difficulties that is observed in the dynamic
modulation of the network that is default and that is present has been proposed to underlie the
excessive self-focus and rumination. The frontoparietal cognitive network of control present
is associated with several cognitive tasks. A meta-analysis recently showed that the evidence
for frontoparietal hypoconnectivity in case of MDD that is especially of the dorsolateral
prefrontal cortex implies that it in goal-directed and there is attention deficits in MDD (Dean
et al., 2014). Additionally, the reduced amount of frontoparietal connectivity which has been
perceived both at rest and in addition to the response to negative stimuli. However no
response is available to positive stimuli, therefore is suggests that this network might be
responsible for contribute to inappropriate cognitive appraisals of negative event.
Contemporary theories of the disorder
The contemporary theories of major depressive disorder as reported several studies
show that there is a presence of a the serotonin-transporter–linked polymorphic region (5-
HTTLPR) that is polymorphic variant, which in turn is responsible for affecting the promoter
of the gene of serotonin-transporter (Snyder, 2013). This in turn leads to the reduced uptake
of serotonin of the neurotransmitter that are associated with the neurotransmitter serotonin
into the presynaptic cells in the brain. Certain studies have also shown that this
polymorphism leads to a predisposition to depression however it also leads to a
predisposition to a personality that is anxious and pessimistic. The imaging of the brain
reveals the functional differences that is associated to the areas that are emotion-related in the
brain and are among carriers of the different common polymorphisms of 5-HTTLPR (Slavich
& Irwin, 2014). Another contemporary theory identified in relation to the occurrences of the
major depressive disorder includes the monoamine-deficiency hypothesis. There are
noradrenergic and serotonergic systems present which originate from deep inside of the brain

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and spread to the entire area of the brain. This suggests that there are systems available that
can modulate the areas of thinking and feeling along with behaving. The pharmacologic
action of these systems are able to increase the presence of the norepinephrine along with
serotonin present in the synapse and also elevates the stimulation of the neurone of post-
synapse (Mullins et al., 2016).

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