STRUCTURAL AND

NEUROCHEMICAL BASIS OF MOOD DISORDERS

MOOD DISORDERS

NEUROCHEMICAL BASIS OF MOOD DISORDER

• Monoamine hypothesis

Depression was atleast sometimes due to an absolute or relative depletion of one or all of these neurotransmitters at important receptor sites in brain.

Monoamines-norepinephrine, dopamine , and serotonin.

• Depletion Occurs• Impaired synthesis of neurotransmitters in

presynaptic neuron• Increased degradation of neurotransmitters once

they had been released into synapse• Altered functioning of postsynaptic receptors

The Catecholamine Hypothesis

• Mood disorders are caused by abnormally high or low levels of Noradrenaline (NA).

• If NA levels drop too low, the result is depression.

• If NA levels climb too high, the result is mania. • Bipolar disorders are caused by regular, extreme

fluctuations in NA levels.

The Permissive Amine Hypothesis

• Mood disorders are caused by NA abnormalities, but the real culprit is serotonin.

• Serotonin is necessary to regulate NA activity, so if serotonin levels drop sufficiently, NA levels are allowed to fluctuate to the extent that they cause abnormalities in emotion, such as depression.

The Dopamine Hypothesis

• Depression is caused by a deficiency in dopamine .

• If the brain is either unable to produce enough dopamine, or is partially insensitive to the action of dopamine, then a person will find it difficult to get any reinforcement.

• Consequently, their ability to enjoy things will suffer, and they may lose interest in things.

ABNORMALITIES OF HORMONAL REGULATORY

SYSTEM

Thyroid Axis Activity

• 5 to 10 percent of people evaluated for depression have previously undetected thyroid dysfunction.

• As reflected by an elevated basal thyroid-stimulating hormone (TSH) level or an increased TSH response to a 500-mg infusion of the hypothalamic neuropeptide thyroid-releasing hormone (TRH).

• Such abnormalities are often associated with elevated antithyroid antibody levels and, unless corrected with hormone replacement therapy.

Cortisol

• In normal subjects and in patients with depression, periods of stress are typically associated with increased level of both cortisol and coticotropin – releasing factor(CRF)

• CRF stimulates production of corticotropin, which inturn stimulates the production of cortisol.

• Cortisol inhibits the release of corticotropin from the pituitary and the CRF (Hypothalamus)

• In depression, the sensitivity of this negative feedback system is often decreased, leading to cortisol

Growth Hormone

• Growth hormone (GH) is secreted from the anterior pituitary after stimulation by NE and Dopamine (DA).

• Secretion is inhibited by somatostatin, a hypothalamic neuropeptide, and CRH.

• Decreased CSF somatostatin levels have been reported in depression, and increased levels have been observed in mania.

IMMUNOLOGICAL DISTURBANCE

• Depressive disorders are associated with several immunological abnormalities, including decreased lymphocyte proliferation in response to mitogens and other forms of impaired cellular immunity. These lymphocytes produce neuromodulators, such as corticotropin-releasing factor (CRF), and cytokines, peptides known as interleukins. There appears to be an association with clinical severity, hypercortisolism, and immune dysfunction, and the cytokine interleukin-1 may induce gene activity for glucocorticoid synthesis.

BRAIN AND MOOD DISORDERS

• The most consistent abnormality observed in the depressive disorders is increased frequency of abnormal hyperintensities in subcortical regions, such as periventricular regions, the basal ganglia, and the thalamus.

• Ventricular enlargement, cortical atrophy, and sulcal widening also have been reported in some studies.

• Depressed patients also may have reduced hippocampal or caudate nucleus volumes, or both, suggesting more focal defects in relevant neurobehavioral systems.

• Decreased anterior brain metabolism, which is generally more pronounced on the left side.

• Depression may be associated with a relative increase in nondominant hemispheric activity.

• Left hemisphere reduction- Depression• Right hemisphere reduction- Mania• Specific reductions of reduced cerebral blood flow

or metabolism, or both, in the dopaminergically innervated tracts of the mesocortical and mesolimbic systems in depression

• Increased glucose metabolism has been observed in several limbic regions.

• Orbital and dorsolateral regions of the prefrontal cortex have also been implicated in mood disorder on functional and structural grounds.

• The hippocampal formation has been implicated in mood disorder for two main reasons.

• 1. MRI studies have found smaller hippocampal volumes in major depression and bipolar disorder; there is also a report of decreased weight of the parahippocampal gyrus in elderly depressed patients.

• 2. There is a well‐studied model linking depression, via growth factors and second messengers, to the atrophic effects of glucocorticoids and stress on hippocampal pyramidal neurones and their dendrites.The model is based, in part, on the role of the hippocampus in regulating the hypothalamo‐pituitary–adrenal axis (HPA), thereby relating it to the hypercortisolaemia and other signs of HPA axis dysfunction which occur in mood disorders and which may be a risk factor for them.

• In the prefrontal cortex, the presence of synaptic and dendritic pathology in the hippocampal formation, especially in bipolar disorder.