Serotonin system genes and childhood-onset aggression

Mik, Helene M.; Ehtesham, Sahar; Baldassarra, Lidia; Luca, Vincenzo De; Davidge, Kristen M.; Bender, Danielle; Tharmalingam, Subi; Kennedy, James L.; Beitchman, Joseph H.

doi:10.1097/ypg.0b013e3280114103

Cited by 12 publications

(6 citation statements)

References 3 publications

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“…Allelic variants in the 5-HTT and TPH1 are associated with aggression in some studies (Davidge et al, 2004;Patkar et al, 2002;Volavka et al, 2004c;Winstanley et al, 2004), and a TPH2 haplotype has been associated with suicidal/parasuicidal behavior and aggression scores (Perez-Rodriguez et al, 2010). Furthermore, the Tyr452 allele of the HTR2A has been associated with childhood onset aggression (Mik et al, 2007). Considered together, studies support the 5-HT hypothesis of aggression, which states that 5-HTergic hypofunction increases aggression.…”

Section: -Ht and Aggressive Behaviormentioning

confidence: 52%

Monoamine-Sensitive Developmental Periods Impacting Adult Emotional and Cognitive Behaviors

Suri

Teixeira

Cagliostro

et al. 2014

Neuropsychopharmacol

145

125

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Development passes through sensitive periods, during which plasticity allows for genetic and environmental factors to exert indelible influence on the maturation of the organism. In the context of central nervous system development, such sensitive periods shape the formation of neurocircuits that mediate, regulate, and control behavior. This general mechanism allows for development to be guided by both the genetic blueprint as well as the environmental context. While allowing for adaptation, such sensitive periods are also vulnerability windows during which external and internal factors can confer risk to disorders by derailing otherwise resilient developmental programs. Here we review developmental periods that are sensitive to monoamine signaling and impact adult behaviors of relevance to psychiatry. Specifically, we review (1) a serotonin-sensitive period that impacts sensory system development, (2) a serotonin-sensitive period that impacts cognition, anxiety-and depressionrelated behaviors, and (3) a dopamine-and serotonin-sensitive period affecting aggression, impulsivity and behavioral response to psychostimulants. We discuss preclinical data to provide mechanistic insight, as well as epidemiological and clinical data to point out translational relevance. The field of translational developmental neuroscience has progressed exponentially providing solid conceptual advances and unprecedented mechanistic insight. With such knowledge at hand and important methodological innovation ongoing, the field is poised for breakthroughs elucidating the developmental origins of neuropsychiatric disorders, and thus understanding pathophysiology. Such knowledge of sensitive periods that determine the developmental trajectory of complex behaviors is a necessary step towards improving prevention and treatment approaches for neuropsychiatric disorders.

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Section: -Ht and Aggressive Behaviormentioning

confidence: 52%

Monoamine-Sensitive Developmental Periods Impacting Adult Emotional and Cognitive Behaviors

Suri

Teixeira

Cagliostro

et al. 2014

Neuropsychopharmacol

145

125

View full text Add to dashboard Cite

show abstract

“…In other words, adolescents genetically predisposed to internalizing disorders may also be predisposed to externalizing psychopathology. Based on similar assumptions, recent reports have examined multiple genes as candidates for both internalizing and externalizing disorders (e.g., serotonin transporter gene – Caspi et al, 2003; Sakai et al, 2006, serotonin 2A receptor gene – Eley et al, 2004; Mik et al, 2007; dopamine D4 receptor gene – Lopez Leon et al, 2005; Rowe et al, 2001). While definitive roles for specific genes in the development of internalizing, externalizing, or co-occurring disorders have not yet been established, these candidate genes may confer risk for both classes of psychopathology.…”

Section: Discussionmentioning

confidence: 99%

Structure and Etiology of Co-occurring Internalizing and Externalizing Disorders in Adolescents

Cosgrove

Rhee

Gelhorn

et al. 2010

J Abnorm Child Psychol

241

191

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Several studies suggest that a two-factor model positing internalizing and externalizing factors explains the interrelationships among psychiatric disorders. However, it is unclear whether the covariation between internalizing and externalizing disorders is due to common genetic or environmental influences. We examined whether a model positing two latent factors, internalizing and externalizing, explained the interrelationships among six psychiatric disorders (major depressive disorder, generalized anxiety disorder, separation anxiety disorder, attention-deficit/ hyperactivity disorder, oppositional defiant disorder, and conduct disorder) in adolescents, and whether there are common genetic and environmental influences on internalizing and externalizing latent factors. Multivariate behavior genetic analyses of data from 1162 twin pairs and 426 siblings ascertained from the general population via the Colorado Center for Antisocial Drug Dependence (CADD) were conducted. We found support for a model positing two latent factors (internalizing and externalizing). These factors were moderately heritable and influenced by significant common genetic and nonshared environmental influences. These findings suggest that co-occurrence of internalizing and externalizing psychopathology in adolescents results from both genetic and environmental influences. Keywordsadolescence; psychopathology; comorbidity; genetics; environment Psychiatric comorbidity, or co-occurrence of disorders, is commonly observed in general population samples, and alternative theoretical models explaining the causes of comorbidity have been proposed (Angold, Costello, & Erkanli, 1999). Many behavioral genetic studies have examined the etiology of psychiatric comorbidity in adolescents and adults, as increased knowledge regarding the etiology of comorbidity informs the understanding of the etiology, course, and treatment of psychiatric disorders. An Internalizing-Externalizing Model for Co-Occurring DisordersAn internalizing-externalizing model has received considerable attention as a potential theoretical framework for understanding co-occurring psychiatric disorders (Krueger, 1999). Internalization is the propensity to express distress inwards; common internalizing disorders include mood disorders (e.g., major depressive disorder, dysthymia) and anxiety disorders (e.g., generalized anxiety disorder, separation anxiety disorder, phobias, obsessivecompulsive disorder). In contrast, externalization describes the propensity to express distress outwards; commonly recognized externalizing disorders include attention-deficit/ hyperactivity disorder, oppositional defiant disorder, conduct disorder, antisocial personality disorder, and substance use disorders. NIH Public AccessAuthor Manuscript J Abnorm Child Psychol. Author manuscript; available in PMC 2011 February 10. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptFactor analytic studies of psychiatric disorders have found support for two factors, internalizing and external...

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“…Similar decrements have been observed in adults with histories of physical aggression (e.g., Siever, 2008; Volkow et al, 1995). There deficits are believed to be rooted in heritable predispositions (Moffitt,1993), and a broad array of candidate genes have been identified as playing a role in violent behavior (Brunner et al, 1993; Davridge et al, 20004; Flory et al, 2007; Meyer-Lindenburg et al, 2006; Mik et al, 2007). In contrast, non-violent forms of delinquency are developmentally transient (Stanger et al, 1997), show less genetic stability (Eley, Lichtenstein, & Moffitt, 2003; Burt & Neiderhiser, 2009) and are more strongly influenced by environmental factors (Burt, 2009).…”

Section: Integrating Biological and Social Risk: Gene-environment Intmentioning

confidence: 99%

Gene-environment interplay in the association between pubertal timing and delinquency in adolescent girls.

Harden¹,

Mendle²

2012

Journal of Abnormal Psychology

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Early pubertal timing places girls at elevated risk for a breadth of negative outcomes, including involvement in delinquent behavior. While previous developmental research has emphasized the unique social challenges faced by early maturing girls, this relation is complicated by genetic influences for both delinquent behavior and pubertal timing, which are seldom controlled for in existing research. The current study uses genetically informed data on 924 female-female twin and sibling pairs drawn from the National Longitudinal Study of Adolescent Health to (1) disentangle biological versus environmental mechanisms for the effects of early pubertal timing and (2) test for gene-environment interactions. Results indicate that early pubertal timing influences girls’ delinquency through a complex interplay between biological risk and environmental experiences. Genes related to earlier age at menarche and higher perceived development significantly predict increased involvement in both non-violent and violent delinquency. Moreover, after accounting for this genetic association between pubertal timing and delinquency, the impact of non-shared environmental influences on delinquency are significantly moderated by pubertal timing, such that the non-shared environment is most important among early maturing girls. This interaction effect is particularly evident for non-violent delinquency. Overall, results suggest early maturing girls are vulnerable to an interaction between genetic and environmental risks for delinquent behavior.

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Serotonin system genes and childhood-onset aggression

Cited by 12 publications

References 3 publications

Monoamine-Sensitive Developmental Periods Impacting Adult Emotional and Cognitive Behaviors

Monoamine-Sensitive Developmental Periods Impacting Adult Emotional and Cognitive Behaviors

Structure and Etiology of Co-occurring Internalizing and Externalizing Disorders in Adolescents

Gene-environment interplay in the association between pubertal timing and delinquency in adolescent girls.

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