Key result
The CNR1 rs1049353 polymorphism was associated with a reduced risk of antipsychotic-induced weight gain (OR 0.41), while the INSIG2 rs7566605 polymorphism increased the risk (OR 3.03).
Why the study?
Weight gain is a frequent and severe adverse reaction to antipsychotics, warranting investigation in a natural setting of risk factors associated with clinically significant weight gain.
Does antipsychotic treatment and specific genetic polymorphisms (CNR1, INSIG2) increase the risk of clinically significant weight gain in patients initiating antipsychotics?
Case-Control (n=137)
Does antipsychotic treatment and specific genetic polymorphisms (CNR1, INSIG2) increase the risk of clinically significant weight gain in patients initiating antipsychotics?
Odds Ratio: 0.41 (95% CI 0.18–0.94)
p-value: p=0.034
Younger age and olanzapine use are associated with an increased risk of antipsychotic-induced weight gain, while quetiapine use is associated with a lower risk, with potential genetic susceptibility linked to CNR1 and INSIG2 polymorphisms.
May indicate genetic risk modifiers for antipsychotic weight gain; leaves open prospective validation before clinical use.
Weight gain is a frequent and severe adverse reaction in patients taking antipsychotics. The objective was to further investigate in a natural setting influential risk factors associated with clinically significant weight gain. An observational follow-up study was conducted. Patients when initiating treatment with whatever antipsychotic were included; a structured questionnaire was applied at baseline, 3 and 6 months later; a blood sample was obtained. In a nested case-control approach, patients with an increase ≥ 7% of their initial weight were considered as cases, the remaining, as controls. The results showed that, out of 185 patients, 137 completed the 6-month follow-up (cases, 38; controls, 99). Weight gain gradually and significantly increased in cases (baseline, 65.0 kg; 6 months, 74.0 kg) but not in controls (65.6 kg and 65.8 kg, respectively). Age (adjusted OR = 0.97, 95% CI = 0.96-0.99, p = 0.004), olanzapine (adjusted OR = 2.98, 95% CI = 1.13-7.80, p = 0.027) and quetiapine (adjusted OR = 0.25, 95% = 0.07-0.92, p = 0.037) significantly associated with weight gain. An association was also found for the CNR1 (rs1049353) and INSIG2 (rs7566605) polymorphisms. In conclusion, an increased risk of antipsychotics-induced weight gain was observed for younger age and olanzapine, and a relative lower risk for quetiapine. A potential role of CNR1 rs1049353 and INSIG2 rs7566605 polymorphisms is suggested.
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Bulnes et al. (2021) conducted a case-control in Antipsychotics-induced weight gain (n=137). CNR1 (rs1049353) and INSIG2 (rs7566605) polymorphisms vs. Non-carriers was evaluated on Weight gain ≥ 7% of initial weight at 6 months (OR 0.41, 95% CI 0.18-0.94, p=0.034). The CNR1 rs1049353 polymorphism was associated with a reduced risk of antipsychotic-induced weight gain (OR 0.41), while the INSIG2 rs7566605 polymorphism increased the risk (OR 3.03).
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