h.ADHD: A Developing Brain Disorder

One need not be a chamber to be haunted;  One need not be a house;  The brain has corridors surpassing;  Material place.                             Emily Dickinson

ADHD is a unique brain disorder that shows signs and symptoms as early as age 4, but perhaps as early as infancy, but diagnosed a long time later and continues with its course throughout the rest of life like a river wild. Therefore the true understanding of ADHD is impossible without having sufficient knowledge of the brain in development.  This has been ignored largely even by the psychiatric agencies and academics, on top by the psychiatric diagnostic bible, i.e. Diagnostic and Statistical Manual (DSM) now in 5th edition by APA(American Psychiatric Association) that has not mentioned even a word that ADHD being a developing brain disorder.  

For more than a century through the works of Freud , Erikson and others we know that life from infancy to the end, consists of different stages with different characteristics, tasks and demands. in modern era, thanks to our advancement in neuroscience we are cognizant of different stages of brain development throughout the life, particularly the early stages until mid 20’s when the brain stops its general growth and development.  Therefore without such knowledge, research, diagnosis and  treatment of children and adolescents with ADHD and grouping all ages together and using the same medications and dosages is pure oblivion!

Research on the development of the human brain has advanced over the past couple of decades due to the novel imaging techniques such as MRI, fMRI (Functional MRI) and DTI (Diffusion Tensor Imaging).  The brain cells, first neurons, then glia cells that glue the neurons together and form the highways of the brain for communication, are born as early as 6 weeks of gestation.  Then soon after birth these cells start their migration to different regions of the brain and by 15 weeks of gestation. Later on the brain like an expert gardener while planting, starts its own pruning and removing the weeds  by Programmed cell death. Around the same time synapses, that are the crossroads of brain cells are formed so the cells can communicate, take nutrients, chemicals and hormones through their receptors.  The last stage of anatomical development of the brain is synaptic pruning and elimination that continues up until mid 20s so to make the garden of the brain very attractive, adaptive and functional. This synaptic reorganization is dependent upon the individuals age, gender, and environment along with many other variables, among them the individuals experiences. Brown and colleagues in 2012, created a statistical model that could predict the age of an individual under the age of 20 from an MRI scan with 92% accuracy. 

The rise and fall of the volume of gray matter in the frontal and parietal lobes peaks at ~12 years of age. The peak for the temporal lobes is ~17 years with the superior temporal cortex being last to mature. The sensory and motor regions mature first after which the rest of the cortex develops and this occurs from the posterior to the anterior region. There is also a differential development as regions linked to emotions e.g. Amygdala and limbic cortex get more increase in gray matter volume in females due to the impact of estradiol, while in males, due to the effect of testosterone there is more development of the parietal cortex gray matter. The brain reaches 90% of its adult size by about age 6 and since it cannot increase in size but still develops, the brain starts to fold during adolescence to increase its coverage and surface area.  The biggest folding and increase in the area of brain occurs during late adolescence into mid 20’s especially in the parts of the cortex that process cognitive and emotional functions. Some of the most developmentally significant changes in the brain occur in the prefrontal cortex, which is involved in decision making, and higher cognitive functions. During adolescence, myelination and synaptic pruning in the prefrontal cortex increases, improving the efficiency of information processing, and neural connections between the prefrontal cortex and other regions of the brain. This leads to better evaluation of risks and rewards, as well as improved control over impulses, specifically by developments in the dorsolateral prefrontal cortex , while development in the ventromedial prefrontal cortex is important for decision making. 

Two neurotransmitters that play important roles in adolescent brain development are glutamate and dopamine. Glutamate, an excitatory neurotransmitter, is involved in the synaptic pruning during adolescence, and that is why an adolescence brain is more excitatory and only by early adulthood the synaptic balance in the brain changes to more inhibitory. On the other hand, dopamine is associated with pleasure, reward, attuning to the environment, planning, decision-making, inhibition and behavioral control, intelligence and other higher cognitive functions. During adolescence, the dopamine levels first increases in the limbic system, then over time as the brain matures, its input of dopamine to the prefrontal cortex increases. The role of dopamine in the brain maturation is well documented and the brain dopaminergic pathway itself has its own developmental timing. At birth, certain structures such as the substantia nigra and nigrostriatal pathway are developed earlier, and structures such as the prefrontal cortex, nucleus accumbens and venrtotegmental pathway are developed later, so defining the differential brain functions at different ages as the brain matures. Also the developing brain exhibits higher plasticity than the adult brain. Therefore in early adolescence, the brain is predominantly excitatory so makes it a life stage of risk-taking and vulnerability to boredom. Then upon brain maturation and development and the increase of dopamine and GABA (the main inhibitory neurotransmitter) and decrease in glutamate (the main excitatory neurotransmitter) activity, there will be a balance between the excitatory and inhibitory system, slowly moving toward more inhibitory as the brain matures.

 ADHD starts in early childhood, when the brain is in its early stages of development, then continues on throughout life if left untreated and disrupts the process of brain maturation. Therefore ADHD symptomatology changes as the brain matures with its differential complications or post-morbidities.  Also due to differentiation in neurotransmission development across life stages, the treatment of ADHD and the dosages of medications, e.g. stimulants differ.  In brief, in contrary to other psychiatric disorders that the medications dose increase per age, in ADHD the medications dose decrease per age!

Read more in the book, “ADHD:Revisited” available at Amazon, Kindle books.