A randomized clinical trial of a dietary intervention and mental health associations in adults with increased genetic risk for obesity.

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• The presence of obesity is linked to an increased risk of mental health disorders, particularly when compounded by genetic predisposition to obesity.

• Whilst no overall change in QoL scores was seen in this study, the adoption of a calorie-restricted Mediterranean diet for weight loss may help the mental health of those with a genetic predisposition for the development of obesity.

Introduction –

Individuals with a genetic predisposition for obesity may be at a higher risk for the development of mental health disorders due to genetic factors influencing both obesity and neurobiological pathways. This study aimed to determine the effect of a dietary weight loss intervention on mental health in individuals with a genetic predisposition for obesity.

Methods –

• This was a secondary analysis of individuals enrolled in the iMPROVE study.

• The iMPROVE study was a two-arm, parallel randomised control trial.

• 80 overweight participants were assigned to either a high protein or high carbohydrate diet following the Mediterranean diet principles for 3 months.

• Mental health was assessed using the quality of life (QoL) SF-12 questionnaires.

• 10 target single nucleotide polymorphisms (SNPs) associated with a predisposition for obesity were analysed.

Results –

• Overall, no significant change in QoL scores from baseline to 3-months were found in either dietary arm (p = 0.941 and p = 0.444).

• 2 of the 10 SNPs analysed were shown to be associated with physical health QoL.

• Individuals who carried the G allele of the rs17817449 SNP that is associated with increased body mass index (BMI) had significantly lower levels of change of physical health QoL (Model 1: β = -3.758, p = 0.009; Model 2: β = -4.594, p = 0.005).

• Those with the A allele of the rs9939609 SNP showed a nominally reduced change in physical health QoL also (Model 1: β = -3.202, p = 0.028; Model 2: β = -4.093, p = 0.016).

• Those with the G allele of the rs17817449 SNP had significantly improved mental health QoL (Model 1: β = 5.7, p = 0.002; Model 2: β = 6.602, p = 0.003).

• Further associations were observed between improved mental health QoL and the rs1411085_C, rs1121980_A, and rs9939609_A alleles (Model 1: β = 4.304, p = 0.023; β = 4.108, p = 0.029; β = 4.921, p = 0.011, respectively; Model 2: β = 4.556, p = 0.03; β = 4.266, p = 0.039; β = 5.781, p = 0.012, respectively).

Conclusion –

• Despite the presence of genetic variations associated with higher BMI and the links to increased mental health disorders, dietary intervention can improve the mental health in this high risk group.

• Mediterranean diet patterns regardless of the macronutrient content can improve mental health QoL in those at high risk of obesity.

• Individuals with obesity risk alleles may benefit from monitoring beyond physical parameters and include mental health monitoring.

• Mechanistic studies should be conducted to further understanding in neurotransmitter pathways, neuroinflammation, stress hormones, and gut microbiota.

• Further studies could compare personalised diets based on genotype vs standard dietary advice.

• Further studies should explore whether improvements in mental health outcomes are dependent or independent of weight loss in this high risk group.