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Abstract
The adult brain has long been considered stable and unchanging, except for the inevitable decline that occurs with aging. This view is now being challenged with clear evidence that structural changes occur in the brain throughout life, including the generation of new neurons and other brain cells, and connections between and among neurons. What is as remarkable is that the changes that occur in the adult brain are influenced by the behaviors an individual engages in, as well as the environment in which an individual lives, works, and plays. Learning how behavior and environment regulate brain structure and function will lead to strategies to live more effective lives and perhaps protect from, or repair, brain damage disease (Gage Fred, 2004).
The fundamental clinical distinction in the classification of mood disorders is between depression and mania. Depressive episodes have been subdivided in various ways, but the results of much of this work have not been particularly useful. However, studies of the longitudinal course of mood disorders have indicated that there are useful clinical distinctions to be made between people who never experience mania or hypomania (recurrent depressive disorder) and those who do (bipolar disorder) (Gelder et al., 2006).
There have been many different approaches to the etiology of mood disorders. There is substantial knowledge about the genetic epidemiology of depression and how certain childhood experiences can lay down a predisposition to mood disorders in adult life. There is also a good understanding of the role of current life difficulties and stresses in provoking mood disorders in predisposed individuals. There is much less knowledge about the mechanism involved in the translation of these predisposing and provoking factors into clinical symptomatology. In trying to elucidate these mechanisms (which, of course, have important implications for treatment), investigators have employed two main conceptual approaches, which can be broadly termed ’psychological’ and ’biological’. It is likely, of course, that these approaches represent different levels of enquiry that will eventually inform each other. In most research areas thee are much more data available concerning the etiology of depression than of mania (Gelder et al., 2006).
There is increasing evidence that severe mood disorders are associated with regional reduction in brain volume, as well as reductions in the number, size, and density of glia and neurons in discrete brain areas. Although the precise pathophysiology underlying these morphometric changes remains to be fully elucidated, the data suggest that severe mood disorders are associated with impairments of structural plasticity and cellular resilience (Du et al., 2004).
Recent investigations have scrutinized the cellular integrity of brain regions implicated in mood disorders, namely the prefrontal cortex, hippocampus, amygdala, raphe nucleus and locus coeruleus. In general, evidence from this burgeoning field supports the hypothesis of altered cell plasticity in MDD occurring mainly in key fronto-limbic areas (Hercher et al., 2009).
Morphological abnormalities detected in mood disorders are most likely related to dysfunction of neural circuits regulating emotional, cognitive, and somatic symptoms exhibited by subjects with MDD or BPD. In fact, alterations in neuronal density and size have been found in the dorsolateral prefrontal, orbitofrontal, and anterior cingulate cortex, the neurons of which give rise to the frontal circuits critical for higher cognitive and limbic functioning. Subtle neuronal alterations are also reported in the hypothalamus and hippocampus, as well as further evidence of dysfunction in the limbic circuits in depression (Alexander et al., 1990).
Neuroimaging has evolved tremendously, providing psychiatrists with unprecedented information about brain structure and function. Computer tomographic (CT) scanners, the first widely used neuroimaging devices, allowed assessment of structural brain lesions such as tumor or strokes. Magnetic resonance imaging (MRI) scans, developed next, distinguished gray and white matter better than CT scans did and allowed visualization of smaller brain lesions as well as white matter abnormalities. In addition, to structural neuroimaging with CT and MRI, a revolution in functional neuroimaging has enabled clinical scientists to obtain unprecedented insights into the diseased human brain. The foremost techniques for functional neuroimaging include positron emission tomography (PET) and single photon emission computer tomography (SPECT) (Sadock & Sadock, 2002).
Plasticity, the ability to undergo and sustain change, is essential for the proper functioning of our nervous system. This capacity for change allows organisms to adapt to complex alterations in both their internal and external environments, a feature fundamentally important for survival and reproduction. Besides the evident need for significant adaptation mechanisms in learning and memory as well as physiological homeostasis, all complex behavioral phenomena - including mood and emotion - are dynamic processes that rely on plastic neural circuitry (Schloesser, et al., 2008a).
Neuroplasticity is a broader term that encapsulates changes in intracellular signaling cascades and gene regulation (McClung and Nestler, 2008), modifications of synaptic number and strength, variations in neurotransmitter release, modeling of axonal and dendritic architecture and, in some areas of the CNS, the generation of new neurons. Modifications arising from neuroplastic mechanisms can be of short duration or long lasting, and this is determined by the qualitative, quantitative, and temporal characteristics of the precipitating stimuli. For instance, compared to acute or single stimuli, chronic and repeated stimuli often lead to qualitatively different, and often times long-lasting alterations (Hyman and Nestler, 1996); furthermore, substantial life events that occur during development of the organism often have a greater impact than they would later in life.