Trajectories of Anatomic Brain Development as a Phenotype

Abstract

Many cognitive, emotional and behavioural traits, as well as psychiatric disorders are highly heritable. However, identifying the specific genes and mechanisms by which this heritability manifests has been elusive. One approach to make this problem more tractable has been to attempt to identify and quantify biological markers that are intermediate steps along the gene-to-behaviour path. The field of neuroimaging offers several anatomic and physiologic possibilities to quantify. Stability over time has been proposed as a desired feature for these intermediate phenotypes.However, in this paper we discuss the value of looking at trajectories of anatomic brain development (i.e. morphometric changes over time), as opposed to static measures, as a phenotype. Examples drawn from longitudinal anatomic magnetic resonance imaging studies of typical development, attention deficit/hyperactivity disorder, and childhood-onset schizophrenia are used to demonstrate the utility of trajectories of brain development as a phenotypic bridge between genes and behaviour in health and in illness.

Child Psychiatry Branch of the National Institute of Mental Health Longitudinal Structural Magnetic Resonance Imaging Study of Human Brain Development

“…Although not of individual diagnostic utility, the imaging data are beginning to elucidate the timing and nature of deviations from typical development that may suggest therapeutic targets. Using trajectories (ie, morphometric measures by age) as an endophenotype may provide discriminating power where static measure do not (Giedd et al, 2008). It is increasingly clear that the same molecular genetic risk can be associated with a range of psychiatric phenotype, including autism, bipolar disorder, schizophrenia, mental retardation, and epilepsy.…”

Growing pains and pleasures: how emotional learning guides development

“…Indeed, in humans, neural development is now thought to extend well beyond puberty, into early adulthood 30 . Over the first several years of life, brain development is marked by neurogenesis and establishment of new synaptic contacts.…”

“…Over the first several years of life, brain development is marked by neurogenesis and establishment of new synaptic contacts. This expansion is then followed by a gradual refinement process which consists of synaptic pruning and myelination 27, 30 . This refinement process follows a developmental sequence, from phylogenetically conserved regions involved in sensory and motor processes to regions involved in more complex functions like multisensory integration and socio-perceptual functions 27, 30, 32 .…”

Decreases in Energy and Increases in Phase Locking of Event-Related Oscillations to Auditory Stimuli Occur during Adolescence in Human and Rodent Brain

“…During adolescence, there are major changes that occur in brain morphology including the selective removal of 40-50% of the synapses (i.e. synaptic pruning) in cortical and subcortical brain regions [3-6], continued myelination of cortical regions [7-9] and dramatic changes in neurotransmitter levels [10-15] as well as receptor levels and their sensitivity [4, 12]. …”