Prolonged injury symptoms and later visits to psychiatric care after mild traumatic brain injury in school-age.

OBJECTIVE: To investigate demographic and pre-injury factors in Finnish school-aged children admitted to pediatric neurology services after mild traumatic brain injury (mTBI). The relation of these factors to prolonged injury symptoms and later visits into psychiatric care was assessed. METHODS: Demographic information, pre-injury learning status, and neuropsychological test results of 120 patients aged 7-16 years were retrospectively collected from the hospital medical records. Data were compared with self- or parent-reported injury symptoms at 1-3 months post-injury and later visits to psychiatric care. RESULTS: According to medical records, 14.2% of the children with mTBI had a diagnosed neurobehavioral or psychiatric condition pre-injury. Additionally, 53.3% of the children had some neurobehavioral or psychiatric concerns or traits prior to the injury. Over half (56.7%) of the children studied were symptomatic at 1-3 months following the injury. Female gender and presence of prolonged symptoms were predictive for later visit into psychiatric care. CONCLUSIONS: Pre-injury neurobehavioral or psychiatric problems may predict prolonged injury symptoms following pediatric mTBI. In this retrospective patient series, prolonged symptoms and female gender seem to predict the need for later psychiatric care. Monitoring the recovery of children with mTBI and pre-injury risk factors is important for timely interventions.

A variation in the infant oxytocin receptor gene modulates infant hippocampal volumes in association with sex and prenatal maternal anxiety.

Genetic variants in the oxytocin receptor (OTR) have been linked to distinct social phenotypes, psychiatric disorders and brain volume alterations in adults. However, to date, it is unknown how OTR genotype shapes prenatal brain development and whether it interacts with maternal prenatal environmental risk factors on infant brain volumes. In 105 Finnish mother-infant dyads (44 female, 11-54 days old), the association of offspring OTR genotype rs53576 and its interaction with prenatal maternal anxiety (revised Symptom Checklist 90, gestational weeks 14, 24, 34) on infant bilateral amygdalar, hippocampal and caudate volumes were probed. A sex-specific main effect of rs53576 on infant left hippocampal volumes was observed. In boys compared to girls, left hippocampal volumes were significantly larger in GG-homozygotes compared to A-allele carriers. Furthermore, genotype rs53576 and prenatal maternal anxiety significantly interacted on right hippocampal volumes irrespective of sex. Higher maternal anxiety was associated both with larger hippocampal volumes in A-allele carriers than GG-homozygotes, and, though statistically weak, also with smaller right caudate volumes in GG-homozygotes than A-allele carriers. Our study results suggest that OTR genotype enhances hippocampal neurogenesis in male GG-homozygotes. Further, prenatal maternal anxiety might induce brain alterations that render GG-homozygotes compared to A-allele carriers more vulnerable to depression.

Partial Support for an Interaction Between a Polygenic Risk Score for Major Depressive Disorder and Prenatal Maternal Depressive Symptoms on Infant Right Amygdalar Volumes.

Psychiatric disease susceptibility partly originates prenatally and is shaped by an interplay of genetic and environmental risk factors. A recent study has provided preliminary evidence that an offspring polygenic risk score for major depressive disorder (PRS-MDD), based on European ancestry, interacts with prenatal maternal depressive symptoms (GxE) on neonatal right amygdalar (US and Asian cohort) and hippocampal volumes (Asian cohort). However, to date, this GxE interplay has only been addressed by one study and is yet unknown for a European ancestry sample. We investigated in 105 Finnish mother-infant dyads (44 female, 11-54 days old) how offspring PRS-MDD interacts with prenatal maternal depressive symptoms (Edinburgh Postnatal Depression Scale, gestational weeks 14, 24, 34) on infant amygdalar and hippocampal volumes. We found a GxE effect on right amygdalar volumes, significant in the main analysis, but nonsignificant after multiple comparison correction and some of the control analyses, whose direction paralleled the US cohort findings. Additional exploratory analyses suggested a sex-specific GxE effect on right hippocampal volumes. Our study is the first to provide support, though statistically weak, for an interplay of offspring PRS-MDD and prenatal maternal depressive symptoms on infant limbic brain volumes in a cohort matched to the PRS-MDD discovery sample.

Associations of age and sex with brain volumes and asymmetry in 2-5-week-old infants.

Information on normal brain structure and development facilitates the recognition of abnormal developmental trajectories and thus needs to be studied in more detail. We imaged 68 healthy infants aged 2-5 weeks with high-resolution structural MRI (magnetic resonance imaging) and investigated hemispheric asymmetry as well as the associations of various total and lobar brain volumes with infant age and sex. We found similar hemispheric asymmetry in both sexes, seen as larger volumes of the right temporal lobe, and of the left parietal and occipital lobes. The degree of asymmetry did not vary with age. Regardless of controlling for gestational age, gray and white matter had different age-related growth patterns. This is a reflection of gray matter growth being greater in the first years, while white matter growth extends into early adulthood. Sex-dependent differences were seen in gray matter as larger regional absolute volumes in males and as larger regional relative volumes in females. Our results are in line with previous studies and expand our understanding of infant brain development.

Receptor subtype-induced targeting and subtype-specific internalization of human alpha(2)-adrenoceptors in PC12 cells.

The three alpha(2)-adrenergic receptor subtypes have distinct tissue distributions, desensitization properties, and, in some cell types, subtype-specific subcellular localization and trafficking properties. The subtypes also differ in their neuronal physiology. Therefore, we have investigated the localization and targeting of human alpha(2)-adrenoceptors (alpha(2)-AR) in PC12 cells, which were transfected to express the alpha(2)-AR subtypes A, B, and C. Inspection of the receptors by indirect immunofluorescence and confocal microscopy showed that alpha(2A)-AR were mainly targeted to the tips of the neurites, alpha(2B)-AR were evenly distributed in the plasma membrane, and alpha(2C)-AR were mostly located in an intracellular perinuclear compartment. After agonist treatment, alpha(2A)- and alpha(2B)-AR were internalized into partly overlapping populations of intracellular vesicles. Receptor subtype-specific changes in PC12 cell morphology were also discovered: expression of alpha(2A)-AR, but not of alpha(2B)- or alpha(2C)-AR, induced differentiation-like changes in cells not treated with NGF. Also alpha(2B)-AR were targeted to the tips of neurites when they were coexpressed in the same cells with alpha(2A)-AR, indicating that the targeting of receptors to the tips of neurites is a consequence of a change in PC12 cell membrane protein trafficking that the alpha(2A)-subtype induces. The marked agonist-induced internalization of alpha(2A)-AR observed in both nondifferentiated and differentiated PC12 cells contrasts with earlier results from non-neuronal cells and points out the importance of the cellular environment for receptor endocytosis and trafficking. The targeting of alpha(2A)-AR to nerve terminals in PC12 cells is in line with the putative physiological role of this receptor subtype as a presynaptic autoreceptor.