PubMed Health⌕ Search

Biomedical subjects

A Serretti

Publications and source records attributed to A Serretti.

At least 19 recordsLinked to original sources
PubMed2006

Meta-analysis of serotonin transporter gene promoter polymorphism (5-HTTLPR) association with selective serotonin reuptake inhibitor efficacy in depressed patients.

The serotonin transporter gene promoter polymorphism (5-HTTLPR) has been repeatedly associated with antidepressant response in mood disorder patients, but findings are not consistent across studies. A meta-analysis was performed on 15 studies including data of 1435 subjects. We tested three phenotypes: remission rate, response rate and response rate within 4 weeks using the cochrane review manager. We observed a significant association of the s/s variant of 5-HTTLPR with remission rate (P<0.0001) and both s/s and s/l variants with response rate (P=0.0002). Response rate within 4 weeks was associated in both models (P=0.003-P<0.00001). This effect is quite robust to ethnic differences although a significant heterogeneity is present in Asian samples.

Adult↗
PubMed2005

Interaction analysis between 5-HTTLPR and TNFA -238/-308 polymorphisms in schizophrenia.

This study investigated the potential interaction between the polymorphisms of serotonin transporter gene (SLC6A4, a 44 base pair insertion/deletion in the promoter region, 5-HTTLPR) and tumor necrosis factor-alpha gene (TNFA; -238G/A and -308G/A polymorphisms) on the development of schizophrenia, as well as the interaction of the three polymorphisms in relation to symptomatology, family history, onset age and antipsychotic treatment response. Genomic DNA analyses with polymerase chain reaction (PCR) was used for the genotyping. One hundred and fifty-two (152) patients with schizophrenia and 152 normal controls participated in the study. Any associations between the individual polymorphism and schizophrenia were not found. However, marginal association between subjects with both TNFA -238 A allele (genotype AA plus AG) and 5-HTTLPR s allele (ss plus sl) and presence of family history was found (p = 0.023; p = 0.026). The subjects with TNFA -308 AG genotype showed higher change in PANSS total score (p = 0.028). No significant interaction effect between 5-HTTLPR and TNFA -238/-308 polymorphisms either on the development of schizophrenia or on antipsychotics treatment response and psychopathology was found, although a significant interaction effect for subjects carrying TNFA -238 AG and -308 AA genotypes on a positive family history was observed (p = 0.017). These results suggest that the interaction effects between 5-HTTLPR and TNFA -238/-308 polymorphisms gives no significant contribution to the susceptibility to schizophrenia, and is not associated with clinical variables, antipsychotic treatment response and psychopathological features, except for family history of disease, at least in the Korean population.

Adult↗
PubMed2005

Association between COMT (Val158Met) functional polymorphism and early onset in patients with major depressive disorder in a European multicenter genetic association study.

The available data from preclinical and pharmacological studies on the role of the C-O-methyl transferase (COMT) support the hypothesis that abnormal catecholamine transmission has been implicated in the pathogenesis of mood disorders (MD). We examined the relationship of a common functional polymorphism (Val108/158Met) in the COMT gene, which accounts for four-fold variation in enzyme activity, with 'early-onset' (EO) forms (less than or equal to 25 years) of MD, including patients with major depressive disorder (EO-MDD) and bipolar patients (EO-BPD), in a European multicenter case-control sample. Our sample includes 378 MDD (120 EO-MDD), 506 BPD (222 EO-BPD) and 628 controls. An association was found between the high-activity COMT Val allele, particularly the COMT Val/Val genotype and EO-MDD. These findings suggest that the COMT Val/Val genotype may be involved in EO-MDD or may be in linkage disequilibrium with a different causative polymorphism in the vicinity. The COMT gene may have complex and pleiotropic effects on susceptibility and symptomatology of neuropsychiatric disorders.

Age Factors↗
PubMed2004

Social adjustment and self-esteem of bipolar patients: a multicentric study.

The aim of the present study was to investigate impairment in social adjustment and self-esteem of bipolar patients (n=144) in remission for at least 3 months. Patients were recruited among four different centres: Sofia, Athens, Jerusalem and Milan, and were individually matched to control subjects in relation to sex, age and geographical origin. Subjects completed the Rosenberg self-esteem scale (SES) and the self-report version of the social adjustment scale (SAS). Bipolar patients reported to experience more difficulties in social adjustment than controls, specifically for leisure and work activities. Further, our results show that bipolar patients have significantly lower self-esteem compared to controls, even after remission.

Adult↗
PubMed2004

The pharmacogenomics of selective serotonin reuptake inhibitors.

The introduction of selective serotonin (5-HT) reuptake inhibitors (SSRIs) has significantly improved the pharmacological treatment of a range of psychiatric disorders. Nevertheless, despite the undoubted advantages of antidepressant treatment in terms of improved tolerability to therapy while maintaining a high level of efficacy, not all patients benefit from it; an appreciable proportion do not respond adequately, while others may show adverse reactions. The necessary change of the initial treatment choice often requires extended periods for the remission of symptomatology. Such difficulties could be avoided if it should be possible to determine more quickly the most suitable drug. Several factors have been thought to influence the outcome of antidepressant therapy. Among the factors influencing the interindividual variability in response to treatment with SSRI, differences in genetic features may play a significant role. Several genetic polymorphisms have been associated with therapeutic SSRI response, including genetic variants of the 5-HT transporter, 5-HT-2A-receptor, tryptophan hydroxylase, brain-derived neurotrophic factor, G-protein beta3 subunit, interleukin-1beta and angiotensin-converting enzyme, although with conflicting results; also cytochrome P450 drug-metabolising enzymes may bear a particular importance, although further corroboration of the findings is necessary, and further key participating genes remain to be identified. The hope is that the identification of these genetic components will eventually facilitate the development of a customised SSRI treatment.

Antidepressive Agents↗
PubMed2004

Further evidence for a possible association between serotonin transporter gene and lithium prophylaxis in mood disorders.

We previously reported an association between the functional polymorphism in the upstream regulatory region of the serotonin transporter gene (SERTPR) and the prophylactic efficacy of lithium in a sample of 201 Italian subjects affected by Mood disorders. The aim of the present study was to replicate analyses on an independent sample. In total, 83 subjects affected by Bipolar disorder were recruited in the Mood Disorders Clinic of the Eginition Hospital of the Athens University, Medical School Department of Psychiatry. All patients were administered with lithium as prophylactic therapy and they were prospectively observed for at least 3 years. Subjects were typed for their SERTPR variant using polymerase chain reaction techniques. SERTPR variants were associated with lithium outcome among those subjects who had few manic episodes before lithium treatment and, as a trend, among subjects who received a high daily dose of lithium (> or =1200 mg/die). In both cases, subjects with the l/l variant showed a higher probability to develop an illness episode within 3 years of prophylactic treatment with lithium. The present study confirmed our previous observation of a better response of SERTPR*l/s carriers, but could not confirm a poor efficacy in subjects with the SERTPR*s/s genotype. Notwithstanding the conflicting results, SERTPR variants are a possible liability factor for lithium long-term efficacy in mood disorders. Further studies on independent and large samples are required to determine the reliability and direction of the possible association between SERTPR variants and lithium outcome.

Age of Onset↗
PubMed2002

Serotonin transporter gene (5-HTTLPR) and major psychoses.

Serotoninergic neurotransmitter systems have been implicated in the pathogenesis of major psychoses. A functional polymorphism (5-HTTLPR) in the upstream regulatory region of the gene (SLC6A4) has been associated with a number of psychiatric disturbances, but conflicting replication followed. The aim of this study was to investigate the possibility that the 5-HTTLPR might be associated with major psychoses. One thousand, eight hundred and twenty inpatients (789 bipolars, 667 major depressives, 66 delusionals, 261 schizophrenics, 37 psychotics not otherwise specified-NOS) and 457 control subjects were included in this study. A subsample of 1235 patients (523 bipolars, 359 major depressives, 259 schizophrenics, 66 delusionals, 28 psychotic NOS) were evaluated for lifetime psychotic symptomatology using the Operational Criteria for Psychotic illness (OPCRIT) checklist. The subjects were also typed for 5-HTTLPR variants using PCR techniques. 5-HTTLPR allele frequencies were not significantly different between controls and bipolars, major depressives, schizophrenics, delusionals and psychotic NOS; genotype analysis also did not show any association. The analysis of symptomatology did not show significant differences. Consideration of possible stratification factors such as sex and age of onset did not significantly influence results. 5-HTTLPR variants are not therefore a liability factor for major psychoses or for major psychoses symptomatology.

Adult↗
PubMed2002

Excess of allele1 for alpha3 subunit GABA receptor gene (GABRA3) in bipolar patients: a multicentric association study.

The available data from preclinical and pharmacological studies on the role of gamma amino butyric acid (GABA) support the hypothesis that a dysfunction in brain GABAergic system activity contributes to the vulnerability to bipolar affective disorders (BPAD). Moreover, the localization of the alpha3 subunit GABA receptor GABRA3 gene on the Xq28, a region of interest in certain forms of bipolar illness, suggests that GABRA3 may be a candidate gene in BPAD. In the present study, we tested the genetic contribution of the GABRA3 dinucleotide polymorphism in a European multicentric case-control sample, matched for sex and ethnogeographical origin. Allele and genotype (in females) frequencies were compared in 185 BPAD patients and 370 controls. A significant increase of genotype 1-1 was observed in BPAD females compared to controls (P=0.0004). Furthermore, when considering recessivity of allele 1 (females with genotype 1-1 and males carrying allele 1), results were even more significant (P= 0.00002). Our findings suggest that the GABRA3 polymorphism may confer susceptibility to or may be in linkage disequilibrium with another gene involved in the genetic etiology of BPAD.

Alleles↗
PubMed2001

No association between dopamine D(2) and D(4) receptor gene variants and antidepressant activity of two selective serotonin reuptake inhibitors.

The possible association of the dopamine receptor D(2) (Ser 311Cys) and D(4) exon 3 (48 base pair repeat) gene variants with the antidepressant activity of selective serotonin reuptake inhibitors (SSRIs) was investigated in a sample of 364 inpatients affected by a major depressive episode treated with fluvoxamine, 300 mg/day (n=266), or paroxetine, 20-40 mg/day (n=98). The severity of depressive symptoms was assessed weekly with the Hamilton Rating Scale for Depression. Dopamine receptor D(2) (DRD2) and dopamine receptor D(4) (DRD4) allelic variants were determined in each subject by polymerase chain reaction. We observed that DRD2 and DRD4 variants were not associated with response to SSRI treatment. Possible stratification factors, such as sex, diagnosis, presence of psychotic features, depressive symptoms at baseline, paroxetine and fluvoxamine plasma levels, and pindolol augmentation did not significantly influence the observed results. The investigated DRD2 and DRD4 gene variants therefore do not seem to play a major role in the antidepressant activity of SSRIs, at least in the present sample.

Major Depressive Disorder↗
PubMed2001

Factors affecting fluvoxamine antidepressant activity: influence of pindolol and 5-HTTLPR in delusional and nondelusional depression.

BACKGROUND: It has been recently reported that the short variant of the serotonin transporter (5-HTT) gene-linked functional polymorphic region (5-HTTLPR) influences the antidepressant response to certain selective serotonin reuptake inhibitors. The aim of the present study was to test this finding in a sample of major and bipolar depressives, with or without psychotic features. METHODS: One hundred fifty-five inpatients were treated with fluvoxamine 300 mg and either placebo or pindolol in a double-blind design for 6 weeks. The severity of depressive symptoms was weekly assessed with the Hamilton Rating Scale for Depression. Allelic variation of 5-HTTLPR in each subject was determined using a polymerase chain reaction-based technique. RESULTS: 5-HTTLPR short variant was associated with a poor response to fluvoxamine treatment, independently from the recorded clinical variables. More specifically, the diagnosis, the presence of psychotic features, and the severity of depressive symptomatology did not influence this association. Conversely, pindolol augmentation may ameliorate the rate of response in 5-HTTLPR short variant subjects, thus reducing the difference in the response rate among the genotype variants. CONCLUSIONS: If confirmed, these results may improve patient care by helping the clinician to individualize treatment according to the patient's genetic 5-HTTLPR pattern.

Adult↗
PubMed2001

Tryptophan hydroxylase gene and major psychoses.

Disturbances of the serotoninergic neurotransmitter system have been implicated in the pathogenesis of mood disorders. The tryptophan hydroxylase (TPH) gene, which codes for the rate-limiting enzyme of serotonin biosynthesis, has been recently reported to be associated with bipolar disorder. In this study, we investigated TPH A218C gene variants in a sample of subjects affected by major psychoses. One thousand four hundred and twenty-four inpatients affected by bipolar (n=627), major depressive (n=511), schizophrenic (n=210), delusional (n=48) disorder and psychotic disorder not otherwise specified (n=27) (DSM-IV) were included; all patients and 380 controls were typed for the TPH variants using PCR techniques. A sub-sample of 963 patients was assessed using the Operational Criteria for Psychotic Illness (OPCRIT). TPH variants were not associated with major psychoses, but a trend was observed toward an excess of TPH*A/A in bipolar disorder. The analysis of symptomatology factors did not show any significant difference either; however, a trend was observed for males with the TPH*A genotype to have lower depressive symptoms compared with TPH*C subjects. Possible stratification factors such as current age and age of onset did not affect the observed results. TPH A218C variants are not, therefore, a major liability factor for the symptoms of major psychoses to have in the present sample. TPH*A containing variants may be a protective factor for depressive symptoms among male subjects with mood disorders or for a subtype of mood disorders characterized by a mainly manic form of symptomatology.

Adult↗
PubMed2001

DRD4 exon 3 variants associated with delusional symptomatology in major psychoses: a study on 2,011 affected subjects.

We previously reported an association of DRD4 exon3 long allele variants with delusional symptomatology independently from diagnoses. The aim of this investigation was to study DRD4 in major psychoses and to test the association in a larger sample. We studied 2,011 inpatients affected by bipolar disorder (n = 811), major depressive disorder (n = 635), schizophrenia (n = 419), delusional disorder (n = 104), psychotic disorder not otherwise specified (n = 42), and 601 healthy controls. A subsample of 1,264 patients were evaluated using the OPCRIT checklist and differences of symptomatology factor scores among genetic variants were assessed using one-way analysis of variance (ANOVA). DRD4 allele and genotype frequencies in bipolars, schizophrenics, delusionals, and psychotic NOS were not significantly different from controls; major depressives showed a trend toward an excess of DRD4*Short and DRD4*Short/Short variants versus controls. The ANOVA on factor scores in the whole subsample of 1,264 subjects showed a significant difference on delusion factor in allele analysis (P = 0.007), and in genotype one (P = 0.018), with DRD4*Long containing variants associated with severe symptomatology. The analysis in the replication subjects only (n = 803) showed a trend in the same direction, though not reaching the significance level. This analysis in an enlarged sample suggests that DRD4*Long alleles exert a small but significant influence on the delusional symptomatology in subjects affected by major psychoses.

Adult↗
PubMed2001

Tryptophan hydroxylase polymorphism and suicidality in unipolar and bipolar affective disorders: a multicenter association study.

BACKGROUND: Being the rate-limiting enzyme in the biosynthesis of serotonin, the tryptophan hydroxylase gene (TPH) has been considered a possible candidate gene in bipolar and unipolar affective disorders (BPAD and UPAD). Several studies have investigated the possible role of TPH polymorphisms in affective disorders and suicidal behavior. METHODS: The TPH A218C polymorphism has been investigated in 927 patients (527 BPAD and 400 UPAD) and their matched healthy control subjects collected within the European Collaborative Project on Affective Disorders. RESULTS: No difference of genotype distribution or allele distribution was found in BPAD or UPAD. No statistically significant difference was observed for allele frequency and genotypes counts. In a genotype per genotype analysis in UPAD patients with a personal history of suicide attempt, the frequency of the C-C genotype (homozygosity for the short allele) was lower in UPAD patients (24%) than in control subjects (43%) (chi(2) = 4.67, p =.03). There was no difference in allele or genotype frequency between patients presenting violent suicidal behavior (n = 48) and their matched control subjects. CONCLUSIONS: We failed to detect an association between the A218C polymorphism of the TPH gene and BPAD and UPAD in a large European sample. Homozygosity for the short allele is significantly less frequent in a subgroup of UPAD patients with a history of suicide attempt than in control subjects.

Alleles↗
PubMed2001

Major psychoses symptomatology: factor analysis of 2241 psychotic subjects.

Current nosography classifies major psychoses as separate disorders, but their symptomatological presentation during illness episodes largely overlaps and diagnoses may change during a lifetime. Few analyses of major psychoses symptomatology have been performed so far because of the large number of subjects needed to obtain stable factors. The purpose of this study was, therefore, to identify the symptomatologic structure common to major psychoses based on lifetime symptoms. Two thousand and forty-one inpatients affected by schizophrenic (n=1008), bipolar (n=563), major depressive (n=352), delusional (n=108) and psychotic not otherwise specified disorder (n=210) were rated for lifetime symptoms using the Operational Criteria Checklist for Psychotic Illness (OPCRIT) and included in a factorial analysis. Four factors were obtained, the first consisted of excitement symptoms, the second comprised psychotic features (delusions and hallucinations), the third comprised depression and the fourth disorganization. When scored by the OPCRIT checklist, major psychoses symptomatology is composed of excitement, depressive, delusion and disorganization symptoms.

Adult↗
PubMed2001

Tryptophan hydroxylase gene associated with paroxetine antidepressant activity.

The possible association of the A218C tryptophan hydroxylase (TPH) gene variant with the antidepressant activity of paroxetine was investigated in a sample of 121 inpatients affected by a major depressive episode and treated with paroxetine 20-40 mg with either placebo or pindolol in a double blind design for 4 weeks. The severity of depressive symptoms was weekly assessed with the Hamilton Rating Scale for Depression. TPH allelic variants were determined in each subject using a PCR-based technique. TPH*A/A and TPH*A/C variants were associated with a poorer response to paroxetine treatment when compared to TPH*C/C (P=0.005); this difference was not present in the pindolol augmented group. Other variables, such as sex, diagnosis, presence of psychotic features, severity of depressive symptomatology at baseline and paroxetine plasma level, were not associated with the outcome. TPH gene variants are therefore a possible modulator of paroxetine antidepressant activity.

Antidepressive Agents, Second-Generation↗