An Association Study between Various Adrenergic Alpha 2 Receptor Polymorphisms and Treatment Response to Mirtazapine in Major Depression

OBJECTIVES: Genetic differences may contribute to the inter-individual differences in treatment response to antidepressants among patients suffering from major depression. This study investigated a possible association of treatment response to mirtazapine with various adrenergic alpha 2 receptor polymorphisms in major depressive patients. METHODS: A 6-week naturalistic treatment study with a blinded outcome examined 84 Korean patients with major depression. Treatment response to mirtazapine was defined as > or =50% decrease in HAM-D scores at six weeks. In this study, four genetic polymorphisms were selected ; ADRA2A MspI, ADRA2A DraI, alpha2BDel301-303, and alpha2CDel322-325. RESULTS: The Del/Del genotype of alpha2CDel322-325 exhibited a significant association with response to mirtazapine through multiple logistic regression. ADRA2A DraI, alpha2BDel301-303, and alpha2CDel322-325 did not showed a significant association with response to mirtazapine. CONCLUSION: Based on the finding that alpha2CDel322-325 polymorphism had an association with the mirtazapine response, we postulate that the polymorphism related to the mechanism of the antidepressant effect is important in predicting the response to antidepressants.

An Association Study between Various Adrenergic Alpha 2 Receptor Polymorphisms and Treatment Response to Mirtazapine in Major Depression

OBJECTIVES: Genetic differences may contribute to the inter-individual differences in treatment response to antidepressants among patients suffering from major depression. This study investigated a possible association of treatment response to mirtazapine with various adrenergic alpha 2 receptor polymorphisms in major depressive patients. METHODS: A 6-week naturalistic treatment study with a blinded outcome examined 84 Korean patients with major depression. Treatment response to mirtazapine was defined as > or =50% decrease in HAM-D scores at six weeks. In this study, four genetic polymorphisms were selected ; ADRA2A MspI, ADRA2A DraI, alpha2BDel301-303, and alpha2CDel322-325. RESULTS: The Del/Del genotype of alpha2CDel322-325 exhibited a significant association with response to mirtazapine through multiple logistic regression. ADRA2A DraI, alpha2BDel301-303, and alpha2CDel322-325 did not showed a significant association with response to mirtazapine. CONCLUSION: Based on the finding that alpha2CDel322-325 polymorphism had an association with the mirtazapine response, we postulate that the polymorphism related to the mechanism of the antidepressant effect is important in predicting the response to antidepressants.

CREB-Phosphorylation as a Predictor of Therapeutic Response to Antidepressants

OBJECTIVES: CREB (c-AMP response element binding protein) is known as a key mediator of the therapeutic response to antidepressants. We investigated the change of CREB-phosphorylation (pCREB) at the early point of the fluoxetine treatment to find out it can be a predictor for antidepressant response. METHODS: We evaluated the pCREB of T - lymphocyte nuclear extracts from 18 depressed patients at 0 and 1th week during fluoxetine treatment (20 mg/day). Responders were defined as the > or = 50% reduction of HAM-D score in 4 weeks. We compared the changes of pCREB at 0 and 1th week between responders and non-responders. RESULTS: The responders showed a significant increase of pCREB at week 1 compared with week 0. The HAM-D difference between week 0 and 4 was positively correlated with the change of pCREB response. CONCLUSION: These results suggest that the early change of pCREB in peripheral lymphocyte can predict the later response of antidepressant. The correlation showed pCREB directly reflects a response status to the antidepressant fluoxetine and clinical improvement.

CREB-Phosphorylation as a Predictor of Therapeutic Response to Antidepressants

OBJECTIVES: CREB (c-AMP response element binding protein) is known as a key mediator of the therapeutic response to antidepressants. We investigated the change of CREB-phosphorylation (pCREB) at the early point of the fluoxetine treatment to find out it can be a predictor for antidepressant response. METHODS: We evaluated the pCREB of T - lymphocyte nuclear extracts from 18 depressed patients at 0 and 1th week during fluoxetine treatment (20 mg/day). Responders were defined as the > or = 50% reduction of HAM-D score in 4 weeks. We compared the changes of pCREB at 0 and 1th week between responders and non-responders. RESULTS: The responders showed a significant increase of pCREB at week 1 compared with week 0. The HAM-D difference between week 0 and 4 was positively correlated with the change of pCREB response. CONCLUSION: These results suggest that the early change of pCREB in peripheral lymphocyte can predict the later response of antidepressant. The correlation showed pCREB directly reflects a response status to the antidepressant fluoxetine and clinical improvement.

A Case of Paraneoplastic Stiff-Person Syndrome Presenting Multiple Somatic Symptoms / 신경정신의학

Stiff-person syndrome (SPS) is an unusual autoimmune neurological disease. We report a woman who developed stiff-person syndrome associated with thymoma. A 42-year-old woman visited a general hospital complaining of progressive rigidity in her neck and both lower legs. She also had other symptoms including whole body pruritus, dysphargia, dysarthria, diplopia, and a visual hallucination-like symptom. Emotional distress preceded her symptoms. After a extensive neurologic workup, she was transferred from the neurologic ward to the psychiatric ward under the impression of conversion or somatoform disorder. During her psychiatric admission, we found a prolonged involuntary MUAP discharge on her electromyograph, and positive anti-GAD and anti-GQ1b antibodies. In addition, a chest CT scan revealed a thymic epithelial tumor. We report a case of stiff-person syndrome presenting multiple unexplained somatic symptoms, which was initially diagnosed as a conversion or somatoform disorder.