DNA methylation may partly explain psychotropic drug-induced metabolic side effects: results from a prospective 1-month observational study

Table 1 Clinical and demographic parameters of the study sample, with global methylation change in participants stratified according to early weight gain status

	N	Total sample	Controls^a (n = 40)	Cases^a (n = 39)	p-value^b
Age, median (range), y	79	37 (16–84)	37 (17–84)	39 (16–83)	0.56
Men, n (%)	79	40 (50.6)	20 (50.0)	20 (51.3)	0.9
Smoking, n (%)	79	40 (50.6)	26 (65.0)	14 (35.9)	0.01
Main diagnosis, n (%)	79				0.33
Psychotic disorders (F20-F24; F28-F29)		36 (45.6)	17 (42.5)	19 (48.7)
Schizoaffective disorders (F25)		10 (12.7)	6 (15.0)	4 (10.3)
Bipolar disorders (F30–F31)		18 (22.8)	12 (30.0)	6 (15.4)
Depressive disorders (F32–F33)		8 (10.1)	2 (5.0)	6 (15.4)
Other		7 (8.9)	3 (7.5)	4 (10.3)
Psychotropic treatment group, n (%)^c	79				0.74
Low risk of WG		13 (16.5)	6 (15.0)	7 (18.0)
Medium risk of WG		42 (53.2)	23 (57.5)	19 (48.7)
High risk of WG		24 (30.4)	11 (27.5)	13 (33.3)
BMI, median (range), kg/m²	79
Baseline		23.1 (15.2–37.5)	23.5 (17.1–36.5)	21.9 (15.2–37.5)	0.16
First month		23.9 (17.0–39.5)	23.8 (17.1–36.5)	24.1 (17.0–39.5)	0.81
p-value^d		< 10^–4	< 10^–4	< 10^–4
WG, median (range), %		2.4 (0–23.0)	0.5 (0–2.4)	7 (5.2–23.0)	< 10^–4
Metabolic syndrome prevalence, n (%)^e	51
Baseline		3 (5.9)	3 (11.1)	0 (0.0)	0.09
First month		8 (15.7)	4 (14.8)	4 (16.7)	0.86
p-value^d		0.23	0.32	0.05
Global baseline (T0) methylation (β-value), mean (range), %	79	61.78 (58.52–64.01)	61.80 (58.52–64.01)	61.77 (59.20–63.86)	0.87
Global methylation (β-value) increase (T1–T0), mean (95%CI), %	79	0.187 (0.185–0.190)	0.201 (0.198–0.204)	0.174 (0.170–0.177)	< 2.2 × 10^–16

BMI body mass index, WG weight gain
^aPatients who gained 5% or more of their initial weight were considered cases, and patients whose weight remained stable were considered controls
^bStatistical significance for differences between groups was tested using the Wilcoxon Mann–Whitney rank-sum test for continuous variables (except for the differences in methylation levels which were assessed using Student’s t-test) and Pearson χ² test of independence for categorical variables. Significant p-values (< 0.05) are indicated in bold
^cPsychotropic drugs are considered to confer a low, medium and high risk of metabolic side effects for amisulpride and aripiprazole; risperidone, quetiapine, mirtazapine and lithium; and valproate, clozapine and olanzapine, respectively
^dStatistical significance for differences between baseline and 1-month values was tested using the Wilcoxon signed rank test for matched pairs for continuous variables and McNemar test for categorical variables. Significant p values (< 0.05) are indicated in bold
^eMetabolic syndrome was evaluated according to the definition of the International Diabetes Federation [28]

ISSN: 1868-7083