The role of serotonin receptor alleles and environmental stressors in the development of post‐concussive symptoms after pediatric mild traumatic brain injury

Abstract

Aim To determine whether post‐injury depressive symptoms, and pre‐injury major life stressors and genetic factors (HTR1A C(‐1019)G alleles; rs6295) are more common in children with mild traumatic brain injury (mTBI) who develop postconcussion syndrome (PCS) symptoms compared with children with asymptomatic mTBI. Method This was a cross‐sectional study of 47 symptomatic children (32 males, 15 females; mean age 14y [SD 3y 3mo]) who experienced post‐concussive symptoms for 7 or more days and 42 asymptomatic children (26 males 16 females; mean age 13y 6mo [SD 3y 1mo]) after mTBI. Outcome measures were the Postconcussion Symptoms Inventory (PCSI), the Children's Depression Inventory (CDI), standard questionnaire of previous life events, and buccal DNA analysis to determine genotype and allele frequencies for the HTR1A C(‐1019)G polymorphism. Results Depressive symptoms were uncommon. CDI scores did not differ between groups. Allelic and genotypic frequencies for HTR1A C(‐1019)G were similar in both groups. Symptomatic children continued to have elevated PCS scores compared with asymptomatic children 1.72 (SD 0.69) years later and had experienced significantly more life stressors (Wald (1)=8.51, p=0.004). Interpretation HTR1A polymorphisms do not differ in children with PCS. Children who have experienced more significant life stresses are more likely to develop PCS symptoms after mTBI.

Predictors of postconcussion syndrome after sports-related concussion in young athletes: a matched case-control study

“…In their cross-sectional study of 47 symptomatic children who experienced postconcussive symptoms for 7 or more days, the G allelic frequency and genotypic frequency for HTR1A polymorphisms was similar to that among controls. 64 In another study, S100B, an astroglial calcium-channel binding protein was found to be elevated after mild to severe TBI. 1 S100B is also highly correlated with abnormal cranial CT scans of mTBI patients; sensitivity is remarkable (90%-100%).…”

“…18,48 As a result, many have recently focused efforts on identifying biomarkers that might predict or be hallmarks of PCS development. Noting that the G(-1019) allele of HTR1A is associated with major depression and suicide, a team led by Smyth et al 64 examined the prevalence of the G(-1019) allele in children with mTBI. In their cross-sectional study of 47 symptomatic children who experienced postconcussive symptoms for 7 or more days, the G allelic frequency and genotypic frequency for HTR1A polymorphisms was similar to that among controls.…”

Cross-Phenotype Polygenic Risk Score Analysis of Persistent Post-Concussive Symptoms in U.S. Army Soldiers with Deployment-Acquired Traumatic Brain Injury

“…Those that have been completed investigated the APOE e4 allele and serotonin receptor alleles, with inconsistent results. [13][14][15] Genome-wide investigations have demonstrated that the genetic predisposition to complex traits is highly polygenic (i.e., many variants with small effects). 16 Risk alleles identified by genome-wide association studies (GWAS) can be investigated in cross-phenotype investigations.…”

Anxiety and mood clinical profile following sport-related concussion: From risk factors to treatment.

“…There is evidence of alterations in limbic-frontal circuitry after concussion that resembles the functional alterations seen in major depression (Chen et al, 2008). Other neurochemical changes consistent between mood disorders and concussion are the presence of serotonin disturbance (Smyth et al, 2014) and decreased dopamine in the prefrontal cortex and brainstem (Chen et al, 2008; Sheline, Wang, Gado, Csernansky, & Vannier, 1996; Venzala, Garcia-Garcia, Elizalde, & Tordera, 2013). Organic brain changes may provide an explanation for mood and anxiety symptoms post-injury in the absence of pre-injury mental health conditions.…”