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Biochemical Influence on Depression and An Associative Disorder
Published on February 19, 2005 By jesseledesma In Health & Medicine
Overview of the Brain’s Biology
Influence on Depression and an Associative Disorder


When we study at university, we have the advantage of learning a subjective at a more in depth level. Sometimes this lends to better perspective. This paper is the result of comparing theory of human behavior with known medical science that explains the brain’s biological influence on human behavior. The focus of this paper is to show examples of how the biology of the human brain, including physiology and chemistry, influence human behavior.

Davidson et al state “ [affective] neuroscience is the sub discipline of the bio-behavioral sciences that examine the underlying neural bases of mood and emotion” (2002). These authors see this discipline of mental health science as “providing a novel and potentially very fruitful approach to subtyping that does not rely on the descriptive [nosology] of psychiatric diagnosis but rather is based upon more objective characterization of the specific affective deficits in patients with mood disorders” (2004).
In addition, these authors add, “ modern cognitive scientist and neuroscientist have developed laboratory tasks to interrogate and reveal…” “…processes that can be studied using imaging methods in humans, lesions methods in animals, and study of human patients with focal brain damage” (Davidson et al 2004).

The previous mentioned techniques are seen as better than interviews, questionnaires, and surveys because a person’s recollection may not be trustworthy. Furthermore, they contribute “abnormalities in activation of prefrontal regions in depression have been reported more frequently than for any other brain region…” (Davidson et al 2002).
Researchers have proposed that the prefrontal cortex holds “the representation of goals and the means to achieve them” (Davidson et al 2002). “[Failure] to anticipate positive incentives and direct behavior toward the acquisition of appetitive goals are symptoms of depression that may arise from abnormalities in the circuitry that implements positive affected-guided anticipation” (Davidson et al 2002).

The symptoms of major depression are varied. For the most, people “appear sad and often speak of feeling low or down” (Barret and Paus 2004). In addition, people have loss of appetite, a reduction in drive, emotion, and social interaction (Barret and Paus 2004).

On the cognitive end, a person with major depression has impaired learning, memory, and attention (Barret and Paus 2004). Speech is often low, quiet, monotonous, and is infrequently initiated (Barret and Paus 2004).

The varieties of symptoms reflect the number of theories of how a person acquires major depression. Barrert and Paus conducted a study where they examined potential rTMS to alleviate the symptoms that may be related to functional abnormalities in a frontocingulate circuit (2004). “Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive tool used to manipulate activity in specific neural circuits of the brain” (Barrett and Paus 2004). In addition, rTMS is seen as a less extreme treatment to ECT. Barret and Paus describe electroconvulsive therapy (ECT) as requiring “general anesthesia, muscular relaxation and induction of a seizure”, along with “side effects, such as memory disturbances” (2004).

At the end of their study, these authors were able to come to certain conclusions. They stated that there is a lack of understanding of the exact mechanism that accounts for the positive contribution of rTMS to major depression patients (Barret and Paus 2004). However, regardless of this previous statement, these authors were able to make two conclusions.

One perspective is that rTMS “may modulate activity in the specific neural circuits that mediate a given group of symptoms (Barret and Paus 2004). Second, rTMS effects may be the result of a facilitation of monoaminergic neurotransmission (Barret and Paus 2004).

This study of Barret and Paus is validated by previous studies “that examined resting cerebral glucose metabolism and blood flow with PET and … found hypometabolism and hypoperfusion localized in the left MD/FC (2004).

Bova et al conducted a research study were they reviewed the contributions Cav1.2 and Cav1.3 L-type channels have on Ca2+ current in the brain, pancreatic B cells, and the cardio vascular system (2004). It is believed that Cav1.2 and Cav1.3 L-type Ca2+ channels lie below “ currents in brain, pancreatic B cells and the cardiovascular system” (Bova et al 2004). In the central nervous system (CNS), these chemicals control excitation-transcription coupling and neuronal plasticity (Bova et al 2004). These authors conclusion is that there is no direct role of Cav1.3

In addition, these authors report “Ca2+ influx through L-type channels is an important modulator of neuronal excitability” (2004). Moreover, “ coupling of neuronal excitation and transcription may critically depend on the activity of the dihydropyridine-sensitive (DHP-sensitive) LTCCs, Cav1.2 and Cav1.3.

Because of their reactions, the above-described chemicals are seen as “interesting and potentially important therapeutic targets in the central nervous system” (Bova et al 2004). “Cav1.2 and Cav1.3 channel blockers…have antidepressant-like actions and can affect fear memory (2004). “LTCC activators…stimulate neurotransmitter release in vitro…but also induce a severe dystonic neurobehavioral syndrome in rodents, including self-biting” (Bova et al 2004).

It is unclear, however, whether there may be other conclusions. Cav1.2 and Cav1.3 have also been seen in “many non-neuronal tissues such as insulin-secretory B cells, vascular smooth muscles cells, and heart atria (Bova et al 2004). This complicates research findings because LTCC blockers also cause cardiodepression and vasodilation (Bova et al 2004).

In addition, the editors and staff of Health and Medicine Week wrote an article that reports a Dutch researcher who has found a correlation between damage to blood vessels and dementia and depression. Niels Prins, the Dutch researcher, shows visible damage of white matter lesions and infarcts of the brain. “Elderly people with a lot of damage to the small blood vessels in the brain have a greater chance of developing dementia or depression” (Health and Medicine Week 2004). In addition, the report states that these people “deteriorate more quickly in their cognitive functioning than peers with fewer abnormalities” (Health and Medicine Week 2004). “The processing of information was worse in the group with more white-mater lesions and infarcts (Health and Medicine Week 2004).

Prins reviewed data form the Rotterdam Scan Study, which is a long-term population study among 1000 healthy volunteers aged 60 years and older. The participants were given an initial MRI and a follow up MRI 3.5 years later. The total length of the study was 5 years. During this time, the participants were given cognitive test and evaluated for depression and dementia (Health and Medicine Week 2004).

Another example of biology playing a part in mental health is a study on depersonalization disorder. Simeon in Depersonalization Disorder: A contemporary Overview describes this disorder as “characterized by prominent depersonalization and often derealisation, without clinically notable memory or identity disturbances” (2004). In addition, this author states the disorder has a 1:1 male/female ratio, the illness is long term, and often continuous” (2004).

Moreover, Simeon describes dissociation as a disruption in the usually integrated functions of consciousness, memory, identity, and perception, leading to a fragmentation of the coherence, unity and continuity of the sense of self. It is sort of like “watching oneself from a distance” (Simeon 2004).

“Neurochemical findings suggest possible involvement of serotonergic, endogenous opioid, and glutamatergic NMDA pathways” (Simeon 2004). “Widespread alterations in metabolic activity in the sensory association cortex, prefrontal hyperactivation, and limbic inhibition in response to aversive stimuli were found in brain imaging studies” (Simeon 2004). In addition, these authors, describes four categories of neurotransmitters that contribute to depersonalization. These are “glutamate (NMDA) receptors antagonist, cannabinoids, hallucinogens, and opioid receptors [agonist]” (Simeon 2004). Temporal lobe epilepsy with left sided foci, inferior parietal and angular gyrus tumors, structural lesions, parietal lobe epilepsy, and focal brain lesions have been associated with depersonalization disorder (Simeon 2004).

Kinoshita et al review of brain biology “elucidate the effects of elctroconvulsive therapy on frontal white matter in late life depressed patients (2004). Their subjects were eight late life depressed patients and 12 healthy age-matched controls (Kinoshita et al 2004).

Substantial white matter FA reduction was found in widespread frontal and temporal brain regions in patients with depression before ECT treatment with controls” (Kinoshita 2004). “A high increase in frontal white matter FA was noted following ECT treatment” (Kinoshita et al 2004).

These findings implicate brain area’s bioprocesses in late term depression. Bilateral reduction in the orbitofrontal cortex volume in elderly was noted on MRI studies (Kinoshita et al 2004). In addition, decreased neuronal and glial density in the prefrontal cortex in unipolar and bipolar disorders was found in histological studies (Kinoshita 2004). There have also been reports of white matter abnormalities in frontal regions associated with “ executive dysfunction and predicted geriatric depression chronocity” (Kinoshita et al 2004). Antidepressant effectiveness in elderly depressed patients is complicated by disorders of the basal ganglia and their prefrontal projections “ (Kinoshita 2004). “The parts of the frontal cortex that are heavily interconnected with limbic structures, such as the amygdala and the caudate, and participate in the limbic-cortico-striatal-pallipadal-thalamic circuits appear to mediate both normal emotion and pathologic emotion states associated with primary mood disorders” (Kinoshita et al 2004). In addition, Kinoshita and associates cite Taylor et al as noting; “smaller orbitofrontal cortex volumes were associated with functional impairment of daily activities in elderly depressed patients” (2004).

Moreover, Kinoshita et al claim “[a] significant white matter FA reduction…in widespread frontal and temporal brain regions in patients with depression before ECT treatment” (2004). Patients with depression exhibited a “significant decrease” in symptoms after “repetitive ECT sessions” (Kinoshita et al 2004).

Along with this study and the others, there are still others that show how the organism, the human body, influences behavior. Arranz et al studied the brain and depressed violent suicide victims. In this study, “seretonin 5-HT2A binding parameters and their second messengers 1,4,5-inositol triphosphate (IP3) and cyclic adenosyl monophosphate (cAMP) were studied in the frontal cortex, hippocampus, caudate nucleus and amygdala of 19 antidepressant-free violent suicide victims” (Arranz et al 2004). An increase in 5-HT4 and higher secondary messengers were found in the frontal cortex and caudate nucleus (Arranz et al 2004). In the caudate nucleus, “ significantly increased 5-HT2A and IP3 levels” were found along with lower levels 5-HT2A binding sites (Arranz et al 2004).

The brain region with “the highest alteration of the serotonergic system and most diagnostic sensitivity is the caudate nucleus of depressed suicide victims” (Arranz et al 2004). Furthermore, previous research “has clearly proposed a role for the serotonergic system in the pathogenesis of affective disorders and suicidal behavior” (Arranz et al 2004). “Molecular genetic and functional neuroimaging studies have confirmed the impaired serotonergic function in suicidal behavior” (Arranz et al 2004). Arranz et al also state, “that extensive data from clinical experimental studies suggest a major role for signal transduction abnormalities in the pathophysiology of mood disorders…” ( 2004). This has implicated the “limbic-thalamo-cortical circuits, involving the amygdala, orbital and medial prefrontal cortex and limbic-cortical-striatalpallidal thalamic circuits” (Arranz et al 2004).

The results of this study are as follows. Significantly, higher levels of 5-HT4 receptors and cAMP were observed in suicide cases (Arranz et al). This increase levels were noted in the frontal cortex and caudate nucleus (Arranz et al).

Research on IP3 have yielded different results. “Low inositol levels have been reported in the frontal cortex …together with significantly decreased [3HPI] hydrolysis and cAMP synthesis in the prefrontal cortex”, known as Brodmann area 10 (Arranz et al). However, this was not the case “in Brodmann areas 8 and 9 of depressed suicide victrims” (Arranz et al 2004). Instead researchers noted significantly decreased activity of the enzyme adrenylyl cyclase in depressed suicides suffering a violent death” (Arranz et al).

Therefore, we can see how philosophy and biological science can explain complications in human behavior. For many decades, psychology was the dominant theory and philosophy of thought. These years have lent us a lot of understanding. However, neuroscience is beginning to offer more in the effort to understand human behavior.

We are seeing the different brain regions and their biomechanics contribution to human behavior. In this understanding, better therapy and medicine can be offered to the patient.

Works Cited


Belen, A. et al. (2004). Altered 5-HT2A and 5-HT4 postsynaptic receptors and their
Intracellular signaling system IP3 and cAMP in brains from depressed violent suicide
Victims. Neuropsychobiology. (49): 189-195.
Barret, J. & Paus, T.. (2004). Transcranial magnetic stimulation (TMS) of the human
Frontal cortex: implications for repetitive TMS treatment of depression. Journal of
Psychiatric Neuroscience (4):268-79.
Bova, S. et al. (2004). Isoform-specific regulation of mood behavior and pancreatic B
Cell and cardiovascular function by L-type Ca2+ channels. The Journal of Clinical
Investigation. 113: 1430-1439.
Davidson, R. J., Pizzagalli, D., Putman, K., & Nitschke, J. B. (2002). Depression:
perspectives from affective neuroscience. Annual Review of Psychology. (53), 545-
574.
Editors & staff. (2004). Damage to brain vessels increase the chance of dementia and
depression. Health & Medicine Week 5:213.
Kinoshita, T. et al. (2004). Effects of electroconvulsive therapy of frontal white matter in
Late-life depression: a diffusion tensor imaging study. Neuropsychobiology. (50):48-
53.
Simeon, Daphne. (2004). Depersonalisation disorder: a contemporary overview.
Therapy in Practice. (6): 343-354.



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