Sexual Dysfunction in Male Schizophrenia: Influence of Antipsychotic Drugs, Prolactin and Polymorphisms of the Dopamine D2 Receptor Genes

Zhang, Xiang Rong; Zhang, Zhi Jun; Zhu, Rong; Yuan, Y.F.; Jenkins, Trisha A.; Reynolds, Gavin P.

doi:10.2217/pgs.11.46

Cited by 51 publications

(45 citation statements)

References 59 publications

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“…It has also been hypothesized that sexual dysfunction in men receiving selective 5-HT reuptake inhibitors may be dependent on the variability of the DRD2 gene [7]. Furthermore, Chinese authors reported that sexual dysfunction is found more often in patients with schizophrenia who have a higher frequency of the Ins allele of the DRD2-141C Ins/Del polymorphism [24]. In our investigation there was no association between the DRD2 C313T polymorphism and the sexual scale of AMS.…”

Section: Discussioncontrasting

confidence: 48%

Polymorphic Variants of Neurotransmitter Receptor Genes May Affect Sexual Function in Aging Males: Data from the HALS Study

Jóźków¹,

Słowińska-Lisowska²,

Łaczmański

et al. 2013

Neuroendocrinology

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Background/Aims: Human behavior is influenced by a number of brain neurotransmitters. Central dopamine, serotonin and melanocortin systems have special importance for male sexual function. We searched for associations between male aging symptoms and polymorphic sites of serotonin (5-HTR_1B), melanocortin (MC4R) and dopamine (DRD2, DRD4) receptors. Methods: In a population-based sample, genotyping of 5-HTR1B (polymorphism: G861C), MC4R (polymorphisms: C-2745T, Val103Ile), DRD2 (polymorphism: C313T) and DRD4 (polymorphism: 48-bp VNTR) was performed in 387 healthy men. The Aging Males' Symptoms (AMS) scale was used to evaluate specific ailments of aging men. We analyzed answers to questions from the AMS scale. Five points of the questionnaire addressed sexual symptoms of the aging male: feeling of passing one's peak, decrease in beard growth, decrease in ability/frequency to perform sexually, decrease in the number of morning erections, and decrease in sexual desire/libido (lacking pleasure in sex, lacking desire for sexual intercourse). Relations between reported symptoms and variants of the polymorphic sites of the studied genes were assessed. Results: After adjusting for confounding factors (education, arterial hypertension, physical activity, weight, waist circumference) an association between the sexual dimension of AMS and genetic variants of 5-HTR1B G861C (p = 0.04) was observed. Conclusions: Variability of neurotransmitter receptor genes may be associated with sexual symptoms of aging in men.

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Section: Discussioncontrasting

confidence: 48%

Polymorphic Variants of Neurotransmitter Receptor Genes May Affect Sexual Function in Aging Males: Data from the HALS Study

Jóźków¹,

Słowińska-Lisowska²,

Łaczmański

et al. 2013

Neuroendocrinology

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“…reported the importance of DRD2 − 141 C Ins/Del polymorphism in antipsychotic (any one of the five antipsychotics) response and associated adverse effects in Chinese population (thirty patients received risperidone) and shown a significant association. [15] Similarly, other studies reported the role of serotonin receptor polymorphism 5HTR2C (−759 C>T) in antipsychotic-induced weight gain, prolactin increase, and EPSs. [161718] Due to limited data and involvement of various antipsychotics, none of the studies have established genetic polymorphisms as biomarkers in the clinical setting.…”

Section: Introductionmentioning

confidence: 84%

“…They have reported the association of DRD2 (Taq1A; −141 C Ins/Del) gene polymorphism with elevated prolactin levels in Chinese patients on antipsychotic medication. [15] A recent study by Sukasem et al . reported the DRD2 (Taq1A) variants association with elevated prolactin levels, and Zhang et al .…”

Section: Discussionmentioning

confidence: 99%

Risperidone-Induced Adverse Drug Reactions and Role of DRD2 (−141 C Ins/Del) and 5HTR2C (−759 C>T) Genetic Polymorphisms in Patients with Schizophrenia

Alladi

Mohan

Shewade

et al. 2017

Journal of Pharmacology and Pharmacotherapeutics

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Objective:To determine the adverse drug reaction (ADR) profile of risperidone and their association with dopamine (DRD2 − 141 C Ins/Del/rs1799732) and serotonin receptor (5HTR2C −759 C>T/rs3813929) gene polymorphisms in patients with schizophrenia.Materials and Methods:The study was conducted among 289 patients who were diagnosed with schizophrenia and were on treatment with risperidone (4–8 mg/day)-based therapy for a minimum of 4 weeks. Genotyping was carried by real-time quantitative polymerase chain reaction. All the patients were observed for the occurrences of ADRs during the study. Changes in prolactin levels and body weight were analyzed for a subgroup of 102 and 97 patients, respectively.Results:Risperidone-induced extrapyramidal symptoms (EPSs) were seen in 36.7% of patients. Among them, tremors were the most common symptom 31.8%. Risperidone-induced hyperprolactinemia and weight gain were seen in 87.2% and 53.6% in subgroup patients. Adverse effects such as sedation, gastrointestinal effects, and amenorrhea were seen in 9.7% (28/289), 5.1% (15/289), and 6.1% (7/114), respectively. Occurrence of DRD2 − 141 Ins/Del and Del/Del polymorphisms were significantly associated with increased prolactin levels in response to risperidone (odds ratio [OR] = 10.45; 95% confidence interval = 1.29–84.89, P = 0.004). No such association was observed with 5HTR2C (−759 C>T) polymorphism. Weight gain and EPS were not associated with the above genetic polymorphisms.Conclusion:Hyperprolactinemia, weight gain, and EPSs (>36.7%) were common adverse effects of risperidone. DRD2 – 141C Ins/Del and Del/Del polymorphisms were significantly associated with increased prolactin levels (OR = 10.45) in response to risperidone.

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“…Sexual side effects are most prevalent in those APs that have the most pronounced D2 antagonism, mainly typical APs and risperidone (141). One study suggests that erectile dysfunction and other sexual dysfunctions in men, as a side effect of AP treatment, is linked to a polymorphism of the dopamine D2 receptor ((141C Ins/Del [rs179973]) (142). A case study by Mesa et al suggested the addition of a D2 agonist could eliminate the sexual side effects caused by AP use (143).…”

Section: Pharmacodynamicsmentioning

confidence: 99%

Genetics of antipsychotic drug outcome and implications for the clinician: into the limelight

Changasi

Shams

Pouget

et al. 2014

Translational Developmental Psychiatry

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Background and purpose: Antipsychotics (APs) are the primary method of treatment for schizophrenia and other psychotic disorders. Unfortunately, lengthy trial-and-error approaches are typically required to find the optimal medication and dosage due to a large interindividual variability with outcome to AP treatment. The literature has shown abundant evidence for a genetic component in individuals' responses to APs. Pharmacogenetic studies analyze specific genetic markers and their association with symptom improvement and occurrence of side effects with APs. This research aims to optimize AP drug treatment by usage of predictive testing and to personalize medicine. Recent findings: This review will highlight the most consistent findings in pharmacogenetics of APs and will update the reader on the clinical implications. This will include how genetic variants modulate AP drug levels, side effects, and therapeutic symptom improvement (i.e. response) to AP treatment. Summary: Several promising findings were obtained implicating gene variants of the dopamine receptor genes in addition to gene variants of serotonin receptors for response and common side effects. Notably, effect sizes appear to be particularly high in the genetics of side effects compared to response. One example is antipsychotic-induced weight gain where the leptin, HTR2C and in particular the melanocortin-4-receptor (MC4R) genes have been implicated in weight gain in children and adolescents. Consistent findings were also obtained for genes implicated in tardive dyskinesia and agranulocytosis. However, the most clinically relevant findings pertain to genes involved in drug metabolism such as the CYP2D6 and CYP2C19 genes which have been included in the first genetic test kits such as the Amplichip †

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Sexual Dysfunction in Male Schizophrenia: Influence of Antipsychotic Drugs, Prolactin and Polymorphisms of the Dopamine D2 Receptor Genes

Cited by 51 publications

References 59 publications

Polymorphic Variants of Neurotransmitter Receptor Genes May Affect Sexual Function in Aging Males: Data from the HALS Study

Polymorphic Variants of Neurotransmitter Receptor Genes May Affect Sexual Function in Aging Males: Data from the HALS Study

Risperidone-Induced Adverse Drug Reactions and Role of DRD2 (−141 C Ins/Del) and 5HTR2C (−759 C>T) Genetic Polymorphisms in Patients with Schizophrenia

Genetics of antipsychotic drug outcome and implications for the clinician: into the limelight

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