Culture as a mediator of gene-environment interaction: Cultural consonance, childhood adversity, a 2A serotonin receptor polymorphism, and depression in urban Brazil

Abstract

Research on gene-environment interaction was facilitated by breakthroughs in molecular biology in the late 20th century, especially in the study of mental health. There is a reliable interaction between candidate genes for depression and childhood adversity in relation to mental health outcomes. The aim of this paper is to explore the role of culture in this process in an urban community in Brazil. The specific cultural factor examined is cultural consonance, or the degree to which individuals are able to successfully incorporate salient cultural models into their own beliefs and behaviors. It was hypothesized that cultural consonance in family life would mediate the interaction of genotype and childhood adversity. In a study of 402 adult Brazilians from diverse socioeconomic backgrounds, conducted from 2011 to 2014, the interaction of reported childhood adversity and a polymorphism in the 2A serotonin receptor was associated with higher depressive symptoms. Further analysis showed that the gene-environment interaction was mediated by cultural consonance in family life, and that these effects were more pronounced in lower social class neighborhoods. The findings reinforce the role of the serotonergic system in the regulation of stress response and learning and memory, and how these processes in turn interact with environmental events and circumstances. Furthermore, these results suggest that gene-environment interaction models should incorporate a wider range of environmental experience and more complex pathways to better understand how genes and the environment combine to influence mental health outcomes.

Serotonin and brain function: a tale of two receptors

“…Crucially, 5-HT2AR polymorphisms have been associated with: (1) increased sensitivity to stressful and enriching environments ( Dressler et al, 2016 ; Fiocco et al, 2007 ; Jiang et al, 2016 ; Jokela et al, 2007 ; Lebe et al, 2013 ; Salo et al, 2011 ); (2) early life stress and maternal deprivation increases the availability of 5-HT2ARs and their sensitivity to excitation ( Benekareddy et al, 2010 ; Vazquez et al, 2000 ); (3) time-dependent sensitisation stress which models post-traumatic stress disorder (PTSD) in rodents, increases 5-HT2AR affinity ( Harvey et al, 2003 ); (4) chronic glucocorticoid administration to rodents increases 5-HT2AR densities ( Katagiri et al, 2001 ); (5) 5-HT2AR availability is highest during critical development periods ( Sheline et al, 2002 ); (6) 5-HT2AR signalling mediates behavioural responses to stress in non-human animals ( Aloyo and Dave, 2007 ) and (7) humans experiencing psychedelic drug trips are, like children, exquisitely sensitive to their environment ( Eisner, 1997 ; Hartogsohn, 2016 ), with the provision of a supportive, nurturing environment being strongly advocated for psychedelic ‘trippers’ ( Johnson et al, 2008 ) – as for children. In summary, all these findings lend support to the notion that a key function of 5-HT2AR signalling is to mediate plasticity and associated change, especially in situations where change would be functionally advantageous.…”

The Therapeutic Potential of Psychedelic Drugs: Past, Present, and Future

“…serotonergic modulation); however, they also possess some important differences. Regarding similarities, an altered relationship with the environment may be critical to recovery with selective serotonin reuptake inhibitors (Belsky, 2016;Harmer & Cowen, 2013) and heightened sensitivity to the environment is a cardinal feature of the psychedelic state (Carhart-Harris, Kaelen, Whalley, Bolstridge, Feilding & Nutt, 2015;Hartogsohn, 2016;Kaelen et al, 2015), perhaps due to psychedelics' direct agonist action at the 5-HT2AR (Dressler, Balieiro, Ferreira de Araujo, Silva & Ernesto Dos Santos, 2016;Fiocco, Joober, Poirier & Lupien, 2007;Jokela et al, 2007). Regarding differences, the chronic antidepressant action of SSRIs includes reduced limbic responsiveness and emotional moderation or blunting, likely via post-synaptic 5-HT1A receptor signalling (Cowen & Browning, 2015;Deakin & Graeff, 1991;McCabe, Mishor, Cowen & Harmer, 2010); this contrasts with the greater role for 5-HT2AR signalling with psychedelics, and emphasis on emotional release (Carhart-Harris et al, 2012b;Roseman et al, 2017;Watts et al, 2017).…”

The behavioural constellation of deprivation: Causes and consequences

“…Low cultural consonance measured across gradients of environmental quality has been associated with low subjective well-being (Reyes-García et al 2010), depression (Dressler et al 2007a;2007b;, hypertension (Dressler et al 2005), substance use (Dressler et al 2004;Reyes-García et al 2010), inflammatory immune response (Dressler et al 2016;, and so forth. Finally, cultural consonance has been shown to mediate the effects of socioeconomic status (SES), genetics, and early life adversity on depression; this mediation is especially pronounced in lower-SES communities (Dressler et al 2016). These chronic health effects indicate "internal prediction" (Rickard et al 2014) and somatic feedback for life-history strategies with less planning, early reproduction, and so forth, as described in P&N's BCD model.…”