BRAIN MYELINATION IN PREVALENT NEUROPSYCHIATRIC DEVELOPMENTAL DISORDERS: PRIMARY AND COMORBID ADDICTION

Abstract

Current concepts of addiction focus on neuronal neurocircuitry and neurotransmitters and are largely based on animal model data, but the human brain is unique in its high myelin content and extended developmental (myelination) phase that continues until middle age. The biology of our exceptional myelination process and factors that influence it have been synthesized into a recently published myelin model of human brain evolution and normal development that cuts across the current symptom-based classification of neuropsychiatric disorders.The developmental perspective of the model suggests that dysregulations in the myelination process contribute to prevalent early-life neuropsychiatric disorders, as well as to addictions. These disorders share deficits in inhibitory control functions that likely contribute to their high rates of comorbidity with addiction and other impulsive behaviors. The model posits that substances such as alcohol and psychostimulants are toxic to the extremely vulnerable myelination process and contribute to the poor outcomes of primary and comorbid addictive disorders in susceptible individuals.By increasing the scientific focus on myelination, the model provides a rational biological framework for the development of novel, myelin-centered treatments that may have widespread efficacy across multiple disease states and could potentially be used in treating, delaying, or even preventing some of the most prevalent and devastating neuropsychiatric disorders.

Figure 3.1

Quadratic trajectories of myelination of human brain over the life span. Myelination (Y axis) versus age (X axis) in frontal (left) and temporal (right) lobes of normal individuals. Top figures are in vivo data from Bartzokis et al. (2001). Lower figures show postmortem intracortical myelin stain data from Kaes (1907) adapted and reproduced in Kemper (1994). Used with permission. The data were acquired 100 years apart, yet the two samples of normal individuals show remarkably similar myelination trajectories in the two regions. Note that different brain regions have significantly different myelination trajectories even when the regions are similar, as is the case with these two association regions. Peak myelination is reached in the frontal lobe at age 45 and even later in the temporal lobe.