RESUMO
OBJECTIVES: Approximately 40-60% of obsessive-compulsive disorder patients are nonresponsive to serotonin reuptake inhibitors. Genetic markers associated with treatment response remain largely unknown. We aimed (1) to investigate a possible association of serotonergic polymorphisms in obsessive-compulsive disorder patients and therapeutic response to selective serotonin reuptake inhibitors and (2) to examine the relationship between these polymorphisms and endocrine response to intravenous citalopram challenge in responders and non-responders to serotonin reuptake inhibitors and in healthy volunteers. METHODS: Patients with obsessive-compulsive disorder were classified as either responders or non-responders after long-term treatment with serotonin reuptake inhibitors, and both groups were compared with a control group of healthy volunteers. The investigated genetic markers were the G861C polymorphism of the serotonin receptor 1Dß gene and the T102C and C516T polymorphisms of the serotonin receptor subtype 2A gene. RESULTS: The T allele of the serotonin receptor subtype 2A T102C polymorphism was more frequent among obsessive-compulsive disorder patients (responders and non-responders) than in the controls (p<0.01). The CC genotype of the serotonin receptor subtype 2A C516T polymorphism was more frequent among the non-responders than in the responders (p<0.01). The CC genotype of the serotonin receptor subtype 1Dß G681C polymorphism was associated with higher cortisol and prolactin responses to citalopram (p<0.01 and p<0.001, respectively) and with a higher platelet-rich plasma serotonin concentration among the controls (p<0.05). However, this pattern was not observed in the non-responders with the same CC genotype after chronic treatment with serotonin reuptake inhibitors. This CC homozygosity was not observed in the responders.
Assuntos
Citalopram/uso terapêutico , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Transtorno Obsessivo-Compulsivo/genética , Polimorfismo Genético/genética , Receptores de Serotonina/genética , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Citalopram/administração & dosagem , Sistema Endócrino/efeitos dos fármacos , Feminino , Marcadores Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVES: Approximately 40-60% of obsessive-compulsive disorder patients are nonresponsive to serotonin reuptake inhibitors. Genetic markers associated with treatment response remain largely unknown. We aimed (1) to investigate a possible association of serotonergic polymorphisms in obsessive-compulsive disorder patients and therapeutic response to selective serotonin reuptake inhibitors and (2) to examine the relationship between these polymorphisms and endocrine response to intravenous citalopram challenge in responders and non-responders to serotonin reuptake inhibitors and in healthy volunteers. METHODS: Patients with obsessive-compulsive disorder were classified as either responders or non-responders after long-term treatment with serotonin reuptake inhibitors, and both groups were compared with a control group of healthy volunteers. The investigated genetic markers were the G861C polymorphism of the serotonin receptor 1Dβ gene and the T102C and C516T polymorphisms of the serotonin receptor subtype 2A gene. RESULTS: The T allele of the serotonin receptor subtype 2A T102C polymorphism was more frequent among obsessive-compulsive disorder patients (responders and non-responders) than in the controls (p<0.01). The CC genotype of the serotonin receptor subtype 2A C516T polymorphism was more frequent among the non-responders than in the responders (p<0.01). The CC genotype of the serotonin receptor subtype 1Dβ G681C polymorphism was associated with higher cortisol and prolactin responses to citalopram (p<0.01 and p<0.001, respectively) and with a higher platelet-rich plasma serotonin concentration among the controls (p<0.05). However, this pattern was not observed in the non-responders with the same CC genotype after chronic treatment with serotonin reuptake inhibitors. This CC homozygosity was not observed in the responders.
Assuntos
Adolescente , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Citalopram/uso terapêutico , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Transtorno Obsessivo-Compulsivo/genética , Polimorfismo Genético/genética , Receptores de Serotonina/genética , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Estudos de Casos e Controles , Citalopram/administração & dosagem , Sistema Endócrino/efeitos dos fármacos , Marcadores Genéticos , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Fatores de Tempo , Resultado do TratamentoRESUMO
RATIONALE: Serotonergic pharmacological challenges have failed to produce consensual results in patients with obsessive-compulsive disorder (OCD), suggesting a heterogeneous 5-hydroxytryptamine (5-HT) activity in this disorder. OBJECTIVES: The aim of this study was to compare the neuroendocrine response to a serotonergic challenge in OCD patient responders (RP) and nonresponders (NR) to serotonin reuptake inhibitors treatment and healthy volunteers. MATERIALS AND METHODS: Thirty OCD treatment NR, 30 RP, and 30 controls (CN) matched for sex and age were included. Each subject received 20 mg of intravenous citalopram. Prolactin, cortisol, and growth hormone plasma concentration were measured at times-20, 0, 20, 40, 60, 80, 100, 120, 140, and 160 min after the onset of citalopram infusion. RESULTS: Citalopram did not induce anxiety or OCD symptoms in patients. Citalopram was associated with stronger prolactin response in the CN group (maximal percentage variation [max%Delta] = 65.76 +/- 105.1) than in NR (max%Delta = 17.41 +/- 31.06) and RP groups (max%Delta = 15.87 +/- 31.71; p = 0.032; Friedman chi (2) = 6.87; df = 2). On the other hand, cortisol response did not differ between CN and RP groups and was blunted in the NR group (NR max%Delta = 20.98 +/- 58.14 vs RP max%Delta = 47.69 +/- 66.94; CN max%Delta = 63.58 +/- 88.4; p = 0.015; Friedman chi (2) = 8.60; df = 2). CONCLUSIONS: Compared to CN, both treatment RP and NR patients showed blunted prolactin response to citalopram, but only NR patients showed an attenuated cortisol response, suggesting a more disrupted central serotonergic transmission in this group.
Assuntos
Citalopram/farmacologia , Hormônio do Crescimento/efeitos dos fármacos , Hidrocortisona/sangue , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Prolactina/efeitos dos fármacos , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Adulto , Estudos de Casos e Controles , Feminino , Hormônio do Crescimento/sangue , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Transtorno Obsessivo-Compulsivo/fisiopatologia , Prolactina/sangueRESUMO
The authors present four patients displaying panic disorder and a history of epileptic seizures to illustrate difficulties regarding differential diagnosis between epileptic seizures and panic attacks. The cases describe the aversive properties of epileptic seizures, the role of visual seizure-triggering stimuli as phobic cues, and the effectiveness and safety of clomipramine treatment of panic attacks as an adjunct to concurrent antiepileptic medication.