تاثیر دیفرانسیلی از ژنوتیپ 5-HTTLPR، روان رنجوری و مواجهه با استرس حاد در زندگی واقعی بر روی اشتها و انرژی دریافتی

Stress or negative mood often promotes energy intake and overeating. Since the serotonin transporter-linked polymorphic region (5-HTTLPR) is found to mediate stress vulnerability as well as to influence energy intake, this gene may also influence the negative effects of stress exposure on overeating. Moreover, since stress proneness also reflects cognitive stress vulnerability – as often defined by trait neuroticism – this may additionally predispose for stress-induced overeating. In the present study it was investigated whether the 5-HTTLPR genotype interacted with neuroticism on changes in mood, appetite and energy intake following exposure to a real-life academic examination stressor. In a balanced-experimental design, homozygous S-allele and L-allele carriers (N = 94) with the lowest and highest neuroticism scores were selected from a large database of 5-HTTLPR genotyped students. Mood, appetite and energy intake were measured before and after a 2-hour academic examination and compared with a control day. Examination influenced appetite for particular sweet snacks differently depending on 5-HTTLPR genotype and neuroticism. S/S compared with L/L subjects reported greater examination stress, and this was accompanied by a more profound post-stress increase in appetite for sweet snacks. Data also revealed a 5-HTTLPR genotype by trait neuroticism interaction on energy intake, regardless of examination. These results consolidate previous assumptions of 5-HTTLPR involvement in stress vulnerability and suggest 5-HTTLPR and neuroticism may influence stress-induced overeating depending on the type of food available. These findings furthermore link previous findings of increased risk for weight gain in S/S-allele carriers, particularly with high scores on trait neuroticism, to increased energy intake.

Emotional distress or negative mood has a clear negative effect on the control of food intake and hence on trying to maintain healthy eating behaviour. While in some individuals, stress can cause hypophagia (Greeno & Wing, 1994), abundant studies have shown that mild to moderate stress or negative mood can increase food intake and body weight (Epel et al, 2001, Oliver et al, 2000 and Rutters et al, 2009) and preference for high-caloric palatable snack foods (Epel et al, 2001, Oliver et al, 2000 and Rutters et al, 2009). Several individual vulnerability factors have been suggested to be involved in this stress-induced “emotional eating” relationship (eating in response to negative affect), including gender (emotional eating appears to be predominant in females (Zellner et al., 2006), trait eating styles (e.g. dietary restraint (Greeno & Wing, 1994) or behavioural disinhibition (Bryant, King, & Blundell, 2008), although findings have been mixed (Goldfield et al, 2008, Oliver et al, 2000 and Rutters et al, 2009), and the mechanism underlying stress-induced overeating are not yet fully understood. Susceptibility to emotional eating may be influenced by disturbances in serotonergic (5-HTergic) functioning. Brain 5-HT not only plays a key role in stress coping and stress-related mood regulation (Chaouloff, 2000 and Van Praag, 2004), but is also directly involved in the regulation of energy intake, body weight and macronutrient selection, including selective intake of sweet carbohydrate-rich foods (Halford et al, 2007, Leibowitz, Alexander, 1998 and Simansky, 1996). In addition, disturbances in brain 5-HT function are related to negative mood and decreased stress-resilience (Firk, Markus, 2007 and Jans et al, 2007) and are often seen in disorders related to pathological overeating (Brewerton, 1995, Jimerson et al, 1990 and Steiger et al, 2011). 5-HTergic dysfunction is promoted by the short (S) allelic variant of the serotonin transporter-linked polymorphic region (5-HTTLPR). This S-allele variant expresses lower transcriptional efficiency than the long (L) allelic variant; resulting in decreased transporter availability (Heils et al, 1996 and Lesch et al, 1996) and, hence, in an increased vulnerability of the 5-HTergic system (Jans et al., 2007). Indeed, consistent with the involvement of 5-HT in stress and stress resilience, people who carry the S-allele 5-HTTLPR show (1) greater brain stress responses to fearful stimuli (see Munafò, Brown, & Hariri, 2008 for a meta-analysis), (2) increased behavioural and hormonal stress responses (Gotlib et al, 2008, Markus, Firk, 2009 and Miller et al, 2013) and (3) increased risk for affective disturbances – including depression – in response to stressful events (Karg, Burmeister, Shedden, & Sen, 2011). Based on these findings, an intriguing question is whether the effects of stress on emotional eating are different depending on this genetic (5-HTTLPR) factor. Although this relationship has not yet been clearly investigated; it receives indirect support from studies revealing associations between 5-HTTLPR and risk for overweight and obesity (Fuemmeler et al, 2008, Sookoian et al, 2007 and Sookoian et al, 2008) as well as between past stressful life events and the incidence of eating problems (Stoltenberg, Anderson, Nag, & Anagnopoulos, 2012). However, direct associations between 5-HTTLPR and food intake or overweight have not always been replicated (Bah et al., 2010), making it more likely that the 5-HTTLPR genotype is a contributing factor instead of a determining factor. To be precise, as mental evaluations guide the perception and experience of stress, these may also affect the influence of stress on eating. This may interact with brain 5-HTergic vulnerability such that 5-HT involvement may be more pronounced with increasing (mental) experience of stress. Support comes from a previous study investigating the association between the 5-HTTLPR S-allele, neuroticism and body weight (Markus & Capello, 2012). In this study, neuroticism was included as a stress-vulnerable personality trait based on findings that neuroticism is often associated with stress vulnerability (Chida, Hamer, 2008 and Penley, Tomaka, 2002) and chronic stress and related affective disorders (Gunthert et al, 1999 and Shoji et al, 2010). In support, data revealed that the previously assumed association between 5-HTTLPR S-allele and body weight (Fuemmeler et al., 2008; Sookoian et al, 2007 and Sookoian et al, 2008) was moderated by trait neuroticism (Markus & Capello, 2012). Other studies investigating gene-by-stress interactions in relation to eating pathology (i.e. emotional eating or bulimia nervosa) similarly found that stress (i.e. experience of stressful life events or depressive symptoms) meditated the influence of the 5-HTTLPR genotype S-allele on eating behaviour (Akkermann et al, 2010, Stoltenberg et al, 2012 and Van Strien et al, 2010). Based on these findings, the present objective was to examine the separate and combined influence of the 5-HTTLPR gene and trait neuroticism on appetite and food intake during acute real-life academic examination stress. In a balanced-experimental design, homozygous S- and L-allele carriers (N = 96) with the lowest and highest neuroticism scores were tested on a day on which they underwent a 2-hour academic examination as well as on a control day. Energy intake from meals and snacks was assessed by means of a food diary, and mood and appetite for sweet and savoury foods were measured before and after examination. The main hypotheses were that S/S-allele carriers with high trait neuroticism would (1) report increased negative mood due to examination stress, and (2) will show greater post-examination appetite and energy intake.