The Neurobiological Factors Associated with Depression

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Biology 202
2002 First Paper
On Serendip

The Neurobiological Factors Associated with Depression

Mary Schlimme

Depression is a mood disorder that affects approximately ten percent of men and nearly twenty-five percent of women at least once in their lifetime (1). There are several types of clinical depression, such as unipolar depression and bipolar depression. Unipolar depression consists of primarily depressive states while bipolar depression involves a fluctuation between states of depression and mania (2). Some of the most common symptoms of depression include excessive feelings of sadness, guilt, or worthlessness, a significant change in appetite, insomnia or hypersomnia, energy loss, thoughts or attempts of suicide, and anhedonia (3), (4). While the symptoms of depression are understood fairly well, how the exact causes of the disorder interact in the development of depression remain somewhat of a mystery.

There are several biological factors that may contribute to the increased susceptibility to depression. Genetic links have been made as the result of twin studies suggesting that family members of depressed patients are more likely to be depressed or to develop depression than the general population. However, it is important to note that these results may be due to the similar environments of twins rather than genetic influence (5). Consequently, studies comparing twins who were reared apart have been conducted and the data suggest that the concordance rates for twins reared together or apart is nearly identical, although the rate is slightly lower for twins reared apart. This suggests that while the environment does play an important role in the development of depressive symptoms, genetic influences are also important (6). In addition, other genetic studies have suggested that Chromosomes 18 and 21 may play a role in depression, but these studies have yet to be replicated (5). While some of the findings from these genetic studies are still preliminary, several investigations have indicated that the role of certain neurotransmitters, called monoamines, in depression is immense (7).

Neurotransmitters are chemicals in the brain that bind to receptors in order to excite or inhibit the firing of neurons (6). The Catecholamine Theory of Mood was proposed as a major explanation for the cause of depression in the 1960s by Joseph Schildkraut (7). Schildkraut suggested that a deficiency of the neurotransmitter norepinephrine at receptor sites caused depression while increased levels of norepinephrine caused mania. Some evidence for Schildkraut’s account was established by the success rate of monoamine oxidase (MAO) inhibitor drugs, which block the reuptake of monoamines and facilitate the release of neurotransmitters such as norepinephrine and serotonin (8). Further evidence has been established by studies that found decreased norepinephrine levels in the cerebrospinal fluid of deceased depressed patients (5). More recently, drugs have been developed that selectively block the reuptake of norepinephrine by the presynaptic cell. It has been found in preliminary studies that the level of depression decreases in these patients, which provides further evidence for the role of norepinephrine in depression. While empirical support for the Catecholamine Theory of Mood has grown substantially, evidence from more recent studies highlights the important roles of other monoamines in depression (5).

Norepinephrine is not the only neurotransmitter that may contribute to depression; rather, evidence suggests that serotonin plays an important role in the disorder as well. Decreased serotonin levels at the synapses may actually moderate the decreased norepinephrine levels of a depressed patient. Several sources of support for this hypothesis have been found. For example, studies of depressed patients suggest that decreased levels of serotonin in the brain are associated with decreased mood, while increased levels of serotonin are associated with increased levels of mood (9). In addition, the cerebrospinal fluid of depressed patients contained lower levels of a substance that serotonin produces than the fluid of nondepressed patients, which suggests that the levels of serotonin in the brains of the depressed patients were lower than the levels of the nondepressed patients (5). Further evidence indicates that serotonin is present in regions of the brain that regulate behaviors associated with depression, such as the amygdala, which mediates emotions, and the hypothalamus, which is involved in sleep and hunger (9), (5). Autopsies revealed that a particular subtype of serotonin receptors were more dense in patients with depression than in nondepressed patients, suggesting that these receptors became more dense in order to counterbalance the effect of low serotonin levels (5). Finally, the treatments available for depression suggest that serotonin levels are an important factor in depression. For example, the selective serotonin reuptake inhibitors (SSRIs), which prevent the immediate reuptake of serotonin, are effective in alleviating the symptoms of depression. However, there are caveats in interpreting this data. Despite the fact that the SSRIs begin to affect the reuptake of serotonin almost immediately, the symptoms of depression are not noticeably relieved until approximately one to four weeks after beginning treatment. This discrepancy provides further support for the notion that there is not one particular factor that causes depression; rather, there are multiple factors that interact in the etiology of the disorder (10).

Dopamine, a neurotransmitter that moderates reward, is a third monoamine that may be involved in depression (11). It is believed that the role of dopamine may not be as profound as the role of other factors involved; nevertheless, evidence suggests that drugs that increase dopamine levels reduce the severity of depression that a patient may feel. However, because drugs of this type can become addictive, other drug treatment options are often favored or required (11). Finally, although unusually low levels of dopamine may be present in patients with depression, monoamines are not the only substances that may mediate the disorder.

Cortisol is a hormone that is released increasingly with increased stress (12). This elevated level of cortisol affects serotonin levels and is caused by the hypothalamus producing more corticotropin-releasing factor (CRF). This in turn triggers the production of adrenocorticotropic hormone (ACTH), which stimulates the production of cortisol (5). Research has shown that depressed patients have higher levels of cortisol in the hypothalamic-pituitary-adrenal system, which controls some brain regions that are aversely affected in depression such as those areas responsible for sleep, appetite, arousal, and pleasure (13). Furthermore, when these patients are given dexamethasone, which normally decreases cortisol levels, the amount of cortisol present only briefly decreases. The hypothalamic-pituitary-adrenal system then resumes its production of cortisol and ignores the inhibiting effects of the dexamethasone. This indicates that the person is highly stressed and at a high risk for becoming or remaining depressed (12).

Depression is a mental disorder that causes patients to display serious behavioral symptoms. There are several factors that may affect depression such as a genetic predisposition, abnormal neurotransmitter levels in the brain, and an increased production of cortisol. While many studies suggest that these factors have important roles in depression, further research is necessary in order to understand more completely how they interact in patients suffering from this disorder.


1) Stress. Grief. Postpartum Depression. Depression has many sources.

2) Mental Help Net – Depression (Unipolar)

3)Basic Information about Depression, Basic Information about Depression

4)Depression – Holistic

5)Scientific American Feature Article: The Neurobiology of Depression , Good resource of information about the neurobiological factors involved in depression

6) Papolos, Demitri & Papolos, Janice. Overcoming Depression: The Definitive Resource for Patients and Families Who Live with Depression and Manic Depression. New York: HarperCollins Publishers, 1997.

7)Depression: Beyond the Catecholamine Theory of Mood, A good overview of depression

8) Carlson, Neil. Physiology of Behavior. Massachusetts: Allyn and Bacon, 2001.

9)Carol Hart, Secrets of Serotonin, Chapter 2, Information about Serotonin

10) Depression: Beyond the Catecholamine Theory of Mood, A good overview of depression

11)The Chemistry of Depression

12) Gilbert, Paul. Overcoming Depression: A Step-by-Step Approach to Gaining Control Over Depression. Oxford: Oxford University Press, 2001.

13)Behavior: The Neurobiology of Depression, An interesting article by a psychiatrist at the University of Michigan

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