Background: This review unpacks the emotional presentation of externalizing behaviors in attention deficit hyperactivity disorder (ADHD), by diving into the psychophysiology, neurophysiology, and neurogenetics in relation to executive function. The correlations among these three variables are identified, showing that standard assessments for ADHD leave out the emotional dysregulation element. This may lead to suboptimal management outcomes during the developmental progression into adolescence and adulthood.
Summary: The emotional impulsivity manifestation in adolescence and adulthood related to the under-managed emotional dysregulation in childhood is found to be associated with subtle confounding impact of 5-HTTLPR (serotonin-transporter-linked promoter region) genotype. The genotype of interest affects the neurochemistry, neurophysiology, and psychophysiology of the cognition for executive function. The established practice of using methylphenidate in treating ADHD surprisingly has a neurogenetic effect in targeting the genotype of interest. Methylphenidate provides neuroprotective effects throughout the neurodevelopment timeline from childhood to adulthood.
Key messages: The emotional dysregulation element in ADHD which is often overlooked should be addressed to improve the prognostic outcomes in adolescence and adulthood.
Introduction: Sexual assault and a history of childhood sexual abuse (CSA) are related to posttraumatic stress disorder (PTSD) development. Long interspersed nuclear elements (LINE-1) are transposable elements, and their methylation is used to infer DNA global methylation. DNA methylation can be affected by trauma exposition which in turn would be associated with PTSD. Thus, we investigated if the LINE-1 methylation pattern is related to PTSD symptoms in females with a history of CSA.
Methods: This is a case-control study that examined, at baseline (W1), 64 women victims of sexual assault diagnosed with PTSD and 31 patients with PTSD who completed the 1-year follow-up (W2). Participants were categorized into two groups according to the presence of CSA (PTSDCSA+: NW1 = 19, NW2 = 10; PTSDCSA-: NW1 = 45, NW2 = 21). PTSD symptoms (re-experiencing, avoidance, hyperarousal, alterations in cognition/mood) were assessed using the Clinician-Administered PTSD Scale, and the history of CSA was assessed by the Childhood Trauma Questionnaire. LINE-1 methylation was measured in three sites (CpG1, CpG2, CpG3) located in the 5'UTR region using bisulfite conversion followed by pyrosequencing. Linear regression models were performed to test the relation between LINE-1 CpG sites methylation and PTSD symptoms.
Results: We found a negative association between CpG2 methylation and hyperarousal symptoms among those in the PTSDCSA+ group in W1 (adjusted p = 0.003) compared to the PTSDCSA- group (p > 0.05). Still, no association was observed between other PTSD symptoms and other CpG sites. Further, in the longitudinal analysis, LINE-1 hypomethylation was no longer observed in PTSD participants exposed to CSA.
Conclusion: Our findings suggest that LINE-1 methylation may help understand the relationship between trauma and PTSD. However, more studies are needed to investigate LINE-1 as an epigenetic marker of psychiatric disorders.