A pharmacogenetic risk score for the evaluation of major depression severity under treatment with antidepressants

The severity of symptoms as well as efficacy of antidepressants in major depressive disorder (MDD) is modified by single nucleotide polymorphisms (SNPs) in different genes, which may contribute in an additive or synergistic fashion. We aimed to investigate depression severity in participants with MDD under treatment with antidepressants in relation to the combinatory effect of selected genetic variants combined using a genetic risk score (GRS). The sample included 150 MDD patients on regular AD therapy from the population-based Swiss PsyCoLaus cohort. We investigated 44 SNPs previously associated with antidepressant response by ranking them with regard to their association to the Center for Epidemiologic Studies Short Depression Scale (CES-D) score using random forest. The three top scoring SNPs (rs12248560, rs878567, rs17710780) were subsequently combined into an unweighted GRS, which was included in linear and logistic regression models using the CES-D score, occurrence of a major depressive episode (MDE) during follow-up and regular antidepressant treatment during the 6 months preceding follow-up assessment as outcomes. The GRS was associated with MDE occurrence (p =.02) and ln CES-D score (p =.001). The HTR1A rs878567 variant was associated with ln CES-D after adjustment for demographic and clinical variables [p =.02, lower scores for minor allele (G) carriers]. Additionally, rs12248560 (CYP2C19) CC homozygotes showed a six-fold higher likelihood of regular AD therapy at follow-up compared to minor allele homozygotes [TT; ultrarapid metabolizers (p =.03)]. Our study suggests that the cumulative consideration of pharmacogenetic risk variants more reliably reflects the impact of the genetic background on depression severity than individual SNPs

Weight loss maintenance in women two to eleven years after participating in a commercial program: a survey

BACKGROUND: After 5 years, most reports show that less than 10% of people maintain a 5% loss from initial body weight. Weight maintenance after 10 years is rarely assessed, especially in commercial programs. The current article reports weight maintenance in individuals who had participated 2 to 11 years earlier in a popular commercial weight loss program based on Canada's Food Guide called Mincavi. METHODS: Randomly picked subjects answered a telephone questionnaire. Participants, 291 adult women from various regions of the province of Quebec, had followed the program 2 to 11 years earlier for at least a month. Body weight at the beginning and at the end of treatment was recorded as well as actual weight, age and height. Existing records allowed partial verification of the sample. RESULTS: Based on corrected weights, percentage of women who maintained at least 5% of their initial weight loss are as following; 2 years = 43.6% (n = 55), 3 years = 33.3% (n = 42), 4 years = 23.8% (n = 42), 5–6 years = 38.2% (n = 55), 7–8 years = 29.4% (n = 51), and 9–11 years; 19.6% (n = 46). Five to eleven years after they had participated in the program 29.1% of all women maintained a weight loss of at least 5%, while 14.3% maintained a loss of at least 10%. CONCLUSIONS: Even though success rate is not as high as could be wished for, results show that participation in the Mincavi program can lead to effective weight maintenance long after individuals have left it. These findings suggest more thorough studies should be conducted on this weight loss program

A pharmacogenetic risk score for the evaluation of major depression severity under treatment with antidepressants

The severity of symptoms as well as efficacy of antidepressants in major depressive disorder (MDD) is modified by single nucleotide polymorphisms (SNPs) in different genes, which may contribute in an additive or synergistic fashion. We aimed to investigate depression severity in participants with MDD under treatment with antidepressants in relation to the combinatory effect of selected genetic variants combined using a genetic risk score (GRS). The sample included 150 MDD patients on regular AD therapy from the population‐based Swiss PsyCoLaus cohort. We investigated 44 SNPs previously associated with antidepressant response by ranking them with regard to their association to the Center for Epidemiologic Studies Short Depression Scale (CES‐D) score using random forest. The three top scoring SNPs (rs12248560, rs878567, rs17710780) were subsequently combined into an unweighted GRS, which was included in linear and logistic regression models using the CES‐D score, occurrence of a major depressive episode (MDE) during follow‐up and regular antidepressant treatment during the 6 months preceding follow‐up assessment as outcomes. The GRS was associated with MDE occurrence (p = .02) and ln CES‐D score (p = .001). The HTR1A rs878567 variant was associated with ln CES‐D after adjustment for demographic and clinical variables [p = .02, lower scores for minor allele (G) carriers]. Additionally, rs12248560 (CYP2C19 ) CC homozygotes showed a six‐fold higher likelihood of regular AD therapy at follow‐up compared to minor allele homozygotes [TT; ultrarapid metabolizers (p = .03)]. Our study suggests that the cumulative consideration of pharmacogenetic risk variants more reliably reflects the impact of the genetic background on depression severity than individual SNPs

Long-term changes in adiposity markers during and after antidepressant therapy in a community cohort

Research on antidepressant-related weight changes over more than 12 months is scarce and adjustment for the effects of depressive episodes has rarely been applied. Accordingly, our aim was to assess the associations of the use of any antidepressants, subclasses of antidepressant and specific compounds prior to baseline and during a 5.5-year follow-up with changes in adiposity markers, and the effect of sex on these associations, with adjustment for multiple confounders including the effects of depressive episodes and their severity. Data stemmed from a prospective cohort study including 2479 randomly selected 35-66 year-old residents of an urban area (mean age 49.9 years, 53.3% women) who underwent physical and psychiatric evaluations at baseline and follow-up. Weight, height, waist circumference, and body fat were measured by trained nurses and information on diagnosis and antidepressant use prior to baseline and during follow-up was collected through standardized interviews. In the fully adjusted models, the number of antidepressants, mainly SSRIs and TCAs, used prior to baseline, was associated with a lower increase of body-mass index (BMI, beta (95%CI) = -0.12 (-0.19, -0.05)) and waist circumference (beta = -0.28 (-0.56, -0.01)), whereas participants treated with antidepressants during the follow-up had a steeper increase in BMI (beta = 0.32 (0.13, 0.50)) and waist circumference (beta = 1.23 (0.44, 2.01)). Within the class of SSRIs, the use of fluoxetine, sertraline or escitalopram during follow-up was associated with a steeper increase in adiposity markers. The associations of SSRIs with BMI and waist circumference were only observed when the SSRIs were used during the second period of the follow-up. Sex did not moderate these associations. Our findings suggest an increase of adiposity markers during sustained treatment with TCAs and SSRIs, which however return to normal levels after cessation of treatment. Hence, the benefit of long-term administration of these antidepressants should be carefully weighed against the potential risk of weight gain