Genetica della risposta antidepressiva nei disturbi dell'umore

Translated title of the contribution: Genetics of the response to antidepressants in mood disorders

A. Serretti, R. Zanardi, E. Galbusera, C. Cusin, D. Rossini, E. Lattuada, R. Lilli, C. Lorenzi, B. Corradi, L. Mandelli, E. Pisati, L. Tentoni, C. Facchinetti, M. Catalano, E. Smeraldi

Research output: Contribution to journalArticle

Abstract

Objective Antidepressant drugs are the first-line treatment for major depression and a therapeutic response is reported in approximately two thirds of patients. Among the different reasons which explain this difference, genetic factors play an important role. It has been recently reported that the short variant of the serotonin transporter gene-linked functional polymorphic region (5-HTTLPR) and A218C tryptophan hydroxylase (TPH) gene variants influence antidepressant response to selective serotonin reuptake inhibitors. The aim of the present study was to summarise some of our recent findings of the possible effect of the 5-HTTLPR and A218C TPH gene variants in a sample of major and bipolar depressives, with or without psychotic features. Methods Patients were treated with fluvoxamine 300 mg, paroxetine 20-40 mg, and either placebo or pindolol in a double blind design for 6 weeks. The severity of depressive symptoms was weekly assessed through the Hamilton Rating Scale for Depression (HAM-D). Allelic variation of 5-HTTLPR and TPH in each subject was determined using a PCR-based technique. Results 5-HTTLPR s/s variant and TPH*A/A were both associated with a poor response to fluvoxamine and paroxetine treatment, independently from the recorded clinical variables. More in detail, the diagnosis, the presence of psychotic features and the severity of depressive symptomatology did not influence this association. Differently, pindolol augmentation may ameliorate the rate of response in both 5-HTTLPR and TPH mutated subjects, thus reducing the difference in the response rate among the genotype variants. Conclusion If confirmed, these results may improve patient care by helping the clinician to individualise treatment according to patients individual genetic pattern.

Original languageItalian
Pages (from-to)244-258
Number of pages15
JournalItalian Journal of Psychopathology
Volume7
Issue number3
Publication statusPublished - 2001

Fingerprint

Tryptophan Hydroxylase
Mood Disorders
Antidepressive Agents
Fluvoxamine
Pindolol
Paroxetine
Depression
Genes
Serotonin Plasma Membrane Transport Proteins
Serotonin Uptake Inhibitors
Therapeutics
Patient Care
Genotype
Placebos
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Serretti, A., Zanardi, R., Galbusera, E., Cusin, C., Rossini, D., Lattuada, E., ... Smeraldi, E. (2001). Genetica della risposta antidepressiva nei disturbi dell'umore. Italian Journal of Psychopathology, 7(3), 244-258.

Genetica della risposta antidepressiva nei disturbi dell'umore. / Serretti, A.; Zanardi, R.; Galbusera, E.; Cusin, C.; Rossini, D.; Lattuada, E.; Lilli, R.; Lorenzi, C.; Corradi, B.; Mandelli, L.; Pisati, E.; Tentoni, L.; Facchinetti, C.; Catalano, M.; Smeraldi, E.

In: Italian Journal of Psychopathology, Vol. 7, No. 3, 2001, p. 244-258.

Research output: Contribution to journalArticle

Serretti, A, Zanardi, R, Galbusera, E, Cusin, C, Rossini, D, Lattuada, E, Lilli, R, Lorenzi, C, Corradi, B, Mandelli, L, Pisati, E, Tentoni, L, Facchinetti, C, Catalano, M & Smeraldi, E 2001, 'Genetica della risposta antidepressiva nei disturbi dell'umore', Italian Journal of Psychopathology, vol. 7, no. 3, pp. 244-258.
Serretti A, Zanardi R, Galbusera E, Cusin C, Rossini D, Lattuada E et al. Genetica della risposta antidepressiva nei disturbi dell'umore. Italian Journal of Psychopathology. 2001;7(3):244-258.
Serretti, A. ; Zanardi, R. ; Galbusera, E. ; Cusin, C. ; Rossini, D. ; Lattuada, E. ; Lilli, R. ; Lorenzi, C. ; Corradi, B. ; Mandelli, L. ; Pisati, E. ; Tentoni, L. ; Facchinetti, C. ; Catalano, M. ; Smeraldi, E. / Genetica della risposta antidepressiva nei disturbi dell'umore. In: Italian Journal of Psychopathology. 2001 ; Vol. 7, No. 3. pp. 244-258.
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abstract = "Objective Antidepressant drugs are the first-line treatment for major depression and a therapeutic response is reported in approximately two thirds of patients. Among the different reasons which explain this difference, genetic factors play an important role. It has been recently reported that the short variant of the serotonin transporter gene-linked functional polymorphic region (5-HTTLPR) and A218C tryptophan hydroxylase (TPH) gene variants influence antidepressant response to selective serotonin reuptake inhibitors. The aim of the present study was to summarise some of our recent findings of the possible effect of the 5-HTTLPR and A218C TPH gene variants in a sample of major and bipolar depressives, with or without psychotic features. Methods Patients were treated with fluvoxamine 300 mg, paroxetine 20-40 mg, and either placebo or pindolol in a double blind design for 6 weeks. The severity of depressive symptoms was weekly assessed through the Hamilton Rating Scale for Depression (HAM-D). Allelic variation of 5-HTTLPR and TPH in each subject was determined using a PCR-based technique. Results 5-HTTLPR s/s variant and TPH*A/A were both associated with a poor response to fluvoxamine and paroxetine treatment, independently from the recorded clinical variables. More in detail, the diagnosis, the presence of psychotic features and the severity of depressive symptomatology did not influence this association. Differently, pindolol augmentation may ameliorate the rate of response in both 5-HTTLPR and TPH mutated subjects, thus reducing the difference in the response rate among the genotype variants. Conclusion If confirmed, these results may improve patient care by helping the clinician to individualise treatment according to patients individual genetic pattern.",
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T1 - Genetica della risposta antidepressiva nei disturbi dell'umore

AU - Serretti, A.

AU - Zanardi, R.

AU - Galbusera, E.

AU - Cusin, C.

AU - Rossini, D.

AU - Lattuada, E.

AU - Lilli, R.

AU - Lorenzi, C.

AU - Corradi, B.

AU - Mandelli, L.

AU - Pisati, E.

AU - Tentoni, L.

AU - Facchinetti, C.

AU - Catalano, M.

AU - Smeraldi, E.

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N2 - Objective Antidepressant drugs are the first-line treatment for major depression and a therapeutic response is reported in approximately two thirds of patients. Among the different reasons which explain this difference, genetic factors play an important role. It has been recently reported that the short variant of the serotonin transporter gene-linked functional polymorphic region (5-HTTLPR) and A218C tryptophan hydroxylase (TPH) gene variants influence antidepressant response to selective serotonin reuptake inhibitors. The aim of the present study was to summarise some of our recent findings of the possible effect of the 5-HTTLPR and A218C TPH gene variants in a sample of major and bipolar depressives, with or without psychotic features. Methods Patients were treated with fluvoxamine 300 mg, paroxetine 20-40 mg, and either placebo or pindolol in a double blind design for 6 weeks. The severity of depressive symptoms was weekly assessed through the Hamilton Rating Scale for Depression (HAM-D). Allelic variation of 5-HTTLPR and TPH in each subject was determined using a PCR-based technique. Results 5-HTTLPR s/s variant and TPH*A/A were both associated with a poor response to fluvoxamine and paroxetine treatment, independently from the recorded clinical variables. More in detail, the diagnosis, the presence of psychotic features and the severity of depressive symptomatology did not influence this association. Differently, pindolol augmentation may ameliorate the rate of response in both 5-HTTLPR and TPH mutated subjects, thus reducing the difference in the response rate among the genotype variants. Conclusion If confirmed, these results may improve patient care by helping the clinician to individualise treatment according to patients individual genetic pattern.

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KW - Pharmacogenetics

KW - Serotonin transporter

KW - Tryptophan hydroxylase

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