Gene X Environment Effects of Serotonin Transporter, Dopamine Receptor D4, and Monoamine Oxidase A Genes with Contextual and Parenting risk factors on symptoms of Oppositional Defiant Disorder, Anxiety, and Depression in a Community Sample of 4 Year Old C
Genetic factors can play a key role in the multiple level of analyses approach to understanding the development of child psychopathology. The present study examined gene environment correlations and Gene Environment interactions for polymorphisms of three target genes, the serotonin transporter gene, the D4 dopamine receptor gene, and the monoamine oxidase A gene in relation to symptoms of anxiety, depression, and oppositional behavior. Saliva samples were collected from 175 non Hispanic White, 4 year old children. Psychosocial risk factors included socioeconomic status, life stress, caretaker depression, parental support, hostility, and scaffolding skills. In comparison with the short forms (s/s, s/l) of the serotonin transporter linked polymorphic repeat, the long form (l/l) was associated with greater increases in symptoms of oppositional defiant disorder in interaction with family stress and with greater increases in symptoms of child depression and anxiety in interaction with caretaker depression, family conflict, and socioeconomic status. In boys, low activity monoamine oxidase A gene was associated with increases in child anxiety and depression in interaction with caretaker depression, hostility, family conflict, and family stress. The results highlight the important of gene environment interplay in the development of symptoms of child psychopathology in young children. A key aspect of the developmental psychopathology approach to the study of child disorders is the concept that psychopathology develops through the interactions of risk factors and psychological processes extending across multiple levels, from genetics to larger societal systems (Masten, 2006) a perspective known as a "multiple levels of analysis" approach (Cicchetti Blender, 2006; Cicchetti Curtis, 2007) Examining the role that genetic factors can play in the development of child psychopathology is an important aspect of this approach. Genetic factors may play a role in sequential processes known as developmental cascades, sequences of events in which interactions and transactions between specific variables, within and across domains or levels (e.g. genetic, physiological, cognitive, etc. of functioning, have a cumulative effect on the developing organism (Masten Cicchetti, 2010) The direction of these effects may vary, with some effects being direct and unidirectional, whereas others are bidirectional or indirect. The cumulative effect of these cascading processes can be significant. Explicating these cascading processes may help elucidate where prevention or intervention is needed to have maximum impact on altering a negative cascade or promoting a positive one. Genetic factors may initiate the cascade process in multiple ways, by operating across levels and domains. Through their effects on early childhood temperamental and cognitive characteristics, genes may serve as early control parameters (Cox, Mills Koonce, Propper, Gariepy, 2010) influencing how infants and young children experience their surroundings as well as eliciting differences in parenting (evocative gene/environment correlations) Polymorphic or epigenetic variations also might lead to individual differences in the impact of environmental factors (Gene Environment [G E] interactions) As described more specifically below, certain allelic variations might potentiate the impact of risk factors in various domains or have a protective function. These genetic effects, operating in conjunction with contextual, family, parent, and child factors across domains and functional levels may then have long term negative (or positive) cascading effects that contribute to the development of psychopathology, as well as its stability over time. In some cases, such genetic effects may begin to impact the child's functionAddress correspondence and reprint requests to: John V. Lavigne, Department of Child and Adolescent Psychiatry, Children's Memorial Hospital #10) 2300 Children's Plaza, Chicago, IL 60614; E mail: jlavigne@ childrensmemorial.org. This study was supported by NIMH RO1 MH 063665 (J.V.L. Principal Investigator) and the Illinois Department of Public Aid, Excellence in Academic Medicine Program. Development and Psychopathology 25 (2013) 555 575 Cambridge University Press 2013 doi:10.1017/S0954579412001241