Role of perinatal long-chain omega-3 fatty acids in cortical circuit maturation: Mechanisms and implications for psychopathology

Abstract

Accumulating translational evidence suggests that the long-chain omega-3 fatty acid docosahexaenoic acid (DHA) plays a role in the maturation and stability of cortical circuits that are impaired in different recurrent psychiatric disorders. Specifically, rodent and cell culture studies find that DHA preferentially accumulates in synaptic and growth cone membranes and promotes neurite outgrowth, dendritic spine stability, and synaptogenesis. Additional evidence suggests that DHA may play a role in microglia-mediated synaptic pruning, as well as myelin development and resilience. In non-human primates n-3 fatty acid insufficiency during perinatal development leads to widespread deficits in functional connectivity in adult frontal cortical networks compared to primates raised on DHA-fortified diet. Preterm delivery in non-human primates and humans is associated with early deficits in cortical DHA accrual. Human preterm birth is associated with long-standing deficits in myelin integrity and cortical circuit connectivity and increased risk for attention deficit/hyperactivity disorder (ADHD), mood, and psychotic disorders. In general, ADHD and mood and psychotic disorders initially emerge during rapid periods of cortical circuit maturation and are characterized by DHA deficits, myelin pathology, and impaired cortical circuit connectivity. Together these associations suggest that early and uncorrected deficits in fetal brain DHA accrual may represent a modifiable risk factor for cortical circuit maturation deficits in psychiatric disorders, and could therefore have significant implications for informing early intervention and prevention strategies.

Epigenetic profiling of ADHD symptoms trajectories: a prospective, methylome-wide study

“…DHA is particularly relevant as it accumulates in brain tissue at a rapid rate during the third trimester of pregnancy and continues to do so throughout early childhood and adolescence, playing an essential role in the maturation and stability of cortical circuits as well as in several other processes (e.g. implication in neurotransmitter systems including dopamine and serotonin) 42. Deficits in DHA have been related to several psychiatric disorders, including ADHD 42,43.…”

“…implication in neurotransmitter systems including dopamine and serotonin) 42. Deficits in DHA have been related to several psychiatric disorders, including ADHD 42,43. For instance, a recent meta-analysis of case control studies has demonstrated that ADHD is associated with robust blood DHA deficits 44.…”

“…For example, one probe was linked to a gene involved in preimplantation development whose differential methylation may be only detectable at birth. In addition, it has been shown that DHA accrual in the brain is particularly important in the third trimester of pregnancy and the first year of life 42. These and other processes that are more salient during early development may lead to enduring individual differences (e.g.…”

Alterations in levels and ratios of n–3 and n–6 polyunsaturated fatty acids in the temporal cortex and liver of vervet monkeys from birth to early adulthood

“…Given the symptomatic onset of many of these diseases typically occurs during periods of rapid cortical circuit maturation from early childhood to adulthood, there is a need to better understand alterations in LC-PUFAs within critical regions of the brain during this period of time [25]. Initial studies by Martinez and Mougan demonstrated that DHA increased while ARA remained constant in forebrains of humans up until 7 years of age [26].…”

The Effects of Omega3 on Oocyte Maturation

“…[10] In non-human primates n-3 fatty acid insufficiency during perinatal development leads to widespread deficits in functional connectivity in adult frontal cortical networks compared to primates raised on DHA-fortified diet. [11] The long chain omega-3 fatty acid also play important role in maturation of various tissues including brain tissue. [12].…”