Docosahexaenoic acid (DHA) is a long-chain omega-3 fatty acid naturally present in cold water fatty fish, and in maternal breast milk. DHA is also available in fish oil, in algal supplements, and in fortified milk and eggs. Although DHA can be synthesized from short-chain precursor a-linolenic acid, diet-assumed DHA accumulates more efficiently in erythrocytes, breast milk, and cortical grey matter.

DHA plays an important role in the development of brain from the perinatal period – that is, the third trimester of gestation in humans – to the adolescence. DHA starts to accumulate in frontal cortex during perinatal period. After birth, neonates depend on maternal breast milk as the sole source of DHA. During the first year of life, DHA concentration in frontal cortex represents 9% of total fatty acid composition. DHA levels continue to increase during childhood and adolescence, reaching 15% of total cortical fatty acids.

Neuroimaging studies have revealed that, during childhood and adolescence, frontal cortical regions develop attention and executive function. Moreover, frontal regions mature the connectivity with limbic structures, such as amygdala, that mediate mood.

So, deficiency of DHA during the different development phases of the brain has consequences on the brain structure, and enhances odds of suffering cognitive impairment and psychiatric symptoms during lifespan.

Studies in rodent have suggested a neuroprotective and neurotrophic role for DHA. DHA acts at the biochemical level on the regulation of the activity of a protein-kinase (PKC) involved in the maintenance of the physiological structure of dendritic spines, that are necessary for synaptic connectivity. If DHA levels decrease, PKC increases its activity, leading to cascade reactions that destabilize dendritic actin cytoskeleton. Hence, the collapse of the spines and the impairment of their function.

In regard to the brain structure, DHA deficiency causes significant reductions in cortical grey matter volumes, in the connectivity within prefrontal cortical networks, and in white matter integrity. DHA deficiency in the last months of pregnancy, that is, in preterm birth, leads to long-term deficits in cortical circuits maturation, as studies in non-humane primates prove. To date, it is not known whether early supplementation of DHA can prevent or reverse these deficits.

Impairment at biochemical and structural levels may lead to psychiatric disorders in humans: preterm born children have an increased risk of developing attention deficit/hyperactivity disorder and cognitive impairment prior to being age 7. Moreover, during adolescence, they are more predisposed to depression, anxiety, and psychotic disorders, such as bipolar disorder, schizophrenia and major depressive disorder, independently from genetic and environmental variables.

In summary, depending on the period of the life, there are various critical points in which the lack of DHA accrual in brain can alter its normal development. One critical point is related with preterm births, associated with prefrontal cortical network connectivity deficit: in this case, the impairments can be mitigated by postnatal supplementation of DHA at high doses. Another critical point is related with the duration of breastfeeding: children that have received more than 12 months of breastfeeding have higher indices of neuronal integrity and function compared to children breastfed during less than 12 months. Also, it should be considered the poor intake of long-chain omega-3 fatty acids in the adolescent population diet. Even if DHA is not the only responsible for neurodevelopment and neuroprotection, its presence in the diet can mitigate the effects of cortical circuits impairment and of consequent psychiatric disorders.


DHA plays an important role in the development and maturation of cortical circuits from late pregnancy to adolescence. Low DHA levels in blood and in frontal cortex are associated with the increase of the onset of psychiatric disorders. Early supplementation of DHA in diet of newborns and children may be a strategy to moderate adverse effects.



McNamara R.K. et al. Role of perinatal long-chain omega-3 fatty acids in cortical circuit maturation: Mechanisms and implications for psychopathology. World J Psychiatr 2015 March 22; 5(1): 15-34.



“This work has been financed by the project PI15/01082, as a part of the National Plan of I+D+I and co-financed by the ISCIII – General Deputy Direction for Evaluation and Development of Health Research – and the European Regional Development Fund (ERDF)”