AGP: Prenatal brain injury associated with depression

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Infants born prematurely with brain injuries viewable on neonatal ultrasound may be at higher risks for developing a slew of psychiatric disorders, including depression and attention-deficit/hyperactivity disorder (ADHD), according to a study published in the July issue of Archives of General Psychiatry.
Preterm infants face higher risks of brain injury due to increased vascular and cellular vulnerabilities of the laminar and fetal brain, leading researchers to pay particular attention to associations between perinatal brain injury and motor and cognitive deficits.

In contrast, relatively little is known about the relation between these preterm brain injuries and the development of psychological disorders. Most commonly, infants are screened for injury via neonatal head ultrasound, which can visualize germinal matrix/intraventricular hemorrhage (GM/IVH) and parenchymal lesions/ventricular enlargement (PL/VE).

The present study followed 1,105 low-birth-weight (less than 2 kg) participants who underwent multiple neonatal ultrasounds and were followed as part of the Neonatal Brain Hemorrhage Study. Median follow-up lasted 16 years and included 458 eligible participants, most of whom were born prematurely, and included evaluation according to the Diagnostic Interview Schedule for children-IV (DISC-IVP).

A number of DISC-IVP disorders met the authors’ threshold of greater than 3 percent prevalence within the cohort, including (in decreasing frequency) oppositional defiant disorder, specific phobia, ADHD-inattentive type and social phobia. Tic disorders were also present in 3.7 percent of subjects, though no specific disorder within the group met the threshold.

Relative to brain injuries viewed on ultrasound, participants with GM/IVH showed significantly increased risks for current major depressive and obsessive-compulsive disorders, with odds ratios of 2.7 and 9.5, respectively, compared with subjects within the cohort who did not experience injuries. Both of these relationships were significant as current and lifetime disorders, and both held after controlling for biological and social risk factors, as well as cognitive and motor problems.

Individuals with PL/VE showed increased risks for current ADHD-inattentive type (odds ratio, 7.6), as well as any type of tic disorder (odds ratio, 8.4) and obsessive-compulsive disorder (odds ratio, 7.6). These associations likewise held for current and lifetime disorders and other variables, except ADHD, which was not significantly associated with PL/VE as a lifetime disorder.

“This study provides strong evidence for the concept, first promulgated by Pasamanick et al, that injury to the fetal-neonatal brain alters risk for later psychiatric disorder,” wrote Agnes H. Whitaker, MD, from the department of psychiatry at Columbia University Medical Center in New York City, and co-authors.

Citing additional evidence, Whitaker and colleagues argued that the relation of PL/VE to ADHD and tic disorders suggests that PL/VE affects the thalamocortical circuit (which is implicated in ADHD) and the striatocortical circuits (implicated in tic disorders).

Similarly, the authors hypothesized from this and other studies that GM/IVH’s relation to depression suggests that the injury affects the amygdalo-striatal-dorsomedial prefrontal circuits, in which dysfunction has been associated with major depressive disorder. Finally, the researchers offered, the mutual relation between GM/IVH and PL/VE with obsessive-compulsive disorder indicates that the injuries affect the orbitofrontal-anterior cingulate-striatal circuit or the globus pallidus-putamen-thalumus-prefrontal circuits, which also have been implicated in obsessive-compulusive disorder.

Whitaker and co-authors emphasized the importance of their findings in the context of longitudinal follow-up, providing a putative case in which early injuries or abnormalities contribute to psychiatric abnormalities only after prolonged periods. For future study, the authors specifically pointed to such latencies in the context of schizophrenia, which tends to develop later than the disorders examined in the present study.