Biomedical subjects

A Serretti

Publications and source records attributed to A Serretti.

70 records · Page 4Linked to original sources

PubMed1998

Tyrosine hydroxylase gene in linkage disequilibrium with mood disorders.

We studied tyrosine hydroxylase (TH) gene variants in mood disorders using linkage disequilibrium techniques. One hundred and forty-five inpatients affected by bipolar (n = 88) and unipolar (n = 57) disorders, and 84 healthy controls, were typed for TH variants using polymerase chain reaction (PCR) amplification. TH was associated with mood disorder, with all affected subjects presenting an excess of TH*2 allele (chi 2 = 8.30, d.f. = 1; P = 0.004) and lack of the TH*1 allele (chi 2 = 6.90, d.f. = 1, P = 0.009). Linkage disequilibrium analyses confirmed the association. Our results suggest a moderate linkage disequilibrium of TH variants with mood disorders.

Adult↗

PubMed1998

European Collaborative Project on Affective Disorders: interactions between genetic and psychosocial vulnerability factors.

Despite strong evidence provided by genetic epidemiology of genetic involvement in the aetiology of bipolar and unipolar affective disorders, the exact nature of the predisposing gene(s) is still being investigated through linkage and association studies. The interaction of susceptibility genes and environmental factors in these diseases is also of fundamental importance and requires proper investigation. Interesting theories have recently been proposed examining the possible role of various chromosomal regions, candidate genes and mutations in affective disorders. Reliable multicentre-based methodology is currently being employed to examine these theories, with attention given to statistical analysis and the statistical power of the sample. The present article describes the European Collaborative Project on Affective Disorders (ECPAD) 'Interactions between genetic and psychosocial vulnerability factors', involving 15 European centres. A description is given of the association and family samples collected for the project and also the methodology used to analyse interactions in the gene-psychosocial environment. This material provides a powerful tool in the search for susceptibility genes in affective disorders and takes into account non-genetic aetiological factors.

Adolescent↗

PubMed1998

GABAA alpha-1 subunit gene not associated with depressive symptomatology in mood disorders.

Considerable evidence implicates the neurotransmitter gamma-aminobutyric acid (GABA) in the biochemical pathophysiology of mood disorders. In this study, we investigated the possibility that the gene for the gamma-aminobutyric acid type A (GABAA) receptor alpha-1 subunit (GABRA1) might be associated with depressive symptomatology in a sample of mood disorder subjects. Sixty-seven inpatients affected by unipolar (n = 37) and bipolar (n = 30) disorder (DSMIV) were assessed at admission by the Hamilton depression rating scale (HAMD) and were typed using polymerase chain reaction (PCR) techniques. GABRA1 variants were not associated with depressive symptomatology, and consideration of possible stratification effects such as sex, psychiatric diagnosis and illness severity did not reveal any association either. GABAA alpha-1 subunit gene is not, therefore, associated with depressive symptomatology in mood disorder subjects.

Adult↗

PubMed1998

Mode of inheritance in mood disorder families according to fluvoxamine response.

Mood disorders are known to cluster within families, but the mode of transmission remains largely unknown. The purpose of our analysis was to determine whether selection of a sample that was homogeneous in its response to an antidepressant provided stronger evidence for a single major locus. Complex segregation analysis was applied to a sample of 171 Italian families of bipolar and unipolar probands that were responsive to the antidepressant fluvoxamine. We used regressive logistic analyses to determine the best fit from among environmental, arbitrary Mendelian, dominant, recessive and additive models. For the 171 affective families with probands that were responsive to the antidepressant fluvoxamine, a Mendelian model of inheritance was rejected. When considering 68 families of bipolar probands, the best fit was obtained for a Mendelian dominant model of transmission. The identification of a Mendelian mode of transmission in bipolar subjects who were selected according to their response to fluvoxamine supports the use of a pharmacological criterion as a tool for identifying true genetic disorders.

Adult↗

PubMed1998

Analysis of depressive symptomatology in mood disorders.

Depressive disorder is a polymorphic syndrome with a wide range of clinical manifestations. Most analyses of depressive symptomatology have been performed by ignoring psychotic symptoms, despite a substantial proportion of depressives presenting psychotic features. The purpose of this study was to include psychotic features in an analysis of depressive symptomatology. Six hundred sixty-nine inpatients affected by major depressive (n = 259) and bipolar (n = 410) disorder were rated for lifetime depressive symptoms using the Operational Criteria checklist for psychotic illness (OPCRIT) and included in a factorial analysis. Three factors were obtained: the first consisted of core depressive symptoms, the second comprised psychotic features, and the third comprised atypical symptoms. Separate analyses performed on major depressive and bipolar samples showed a similar factor structure, though there was some evidence of greater heterogeneity in the major depressive sample. Thus, when scored by the OPCRIT checklist, depressive symptomatology results were composed of core depressive symptoms, psychotic features, and atypical symptoms.

Adult↗

PubMed1996

Identification of symptomatologic patterns common to major psychoses: proposal for a phenotype definition.

Our study was designed to identify the underlying symptomatologic structure common to major psychoses as a preliminary step for a phenotype definition. We investigated 1,004 inpatients affected by mood disorders or the schizophrenia spectrum (DSM-III-R) using the OPCRIT checklist (operational criteria checklist for psychotic illness). Symptomatologic structure was extracted by factor analytic techniques and factor scores were first obtained on 500 subjects. A CFA (confirmatory factor analysis) was then conducted on the remaining 504 subjects to evaluate fitness of the model. We identified four factors: excitement, depression, disorganization, and delusion. These factors accounted for 54.6% of the total variance of the OPCRIT checklist symptomatologic subset of 38 items. CFA indices showed a good fit for the model. We identified symptomatologic structures common to major psychoses. The factors identified were confirmed in an independent sample. Two of these symptomatologic structures are partially overlapping with categorical diagnoses (excitement and depression), and two constitute independent psychopathologic traits (delusion and disorganization). The use of "factor-derived scores" in genetic research may add a dimensional definition to the diagnostic subdivision of major psychoses.

Adult↗

PubMed1996

Effects of fluoxetine at antidepressant doses on short-term outcome of detoxified alcoholics.

Compulsivity in alcohol-dependent patients is a frequent cause of early relapse in the post-detoxification period. The present study is a 2-month trial on detoxified alcoholics undergoing a double-blind placebo-controlled treatment with fluoxetine (20 mg/day). The rating instruments were the Hamilton Depression and Anxiety Scales, a visual analogue scale for alcohol craving and an original scale for evaluating alcohol withdrawal. The abstinence rate for fluoxetine-treated patients was significantly higher than in the placebo group, whereas no difference between treatments was found on the rating scales. Medical problems, additional psychiatric diagnoses, and family alcoholism were negatively correlated with abstinence. Two subgroups of patients having significantly different characteristics were identified as to the outcome, by means of cluster analysis. They are likely to represent two different stages in the evolution of alcoholism. Our results show that, independently from craving, fluoxetine at antidepressant doses is able to prevent relapses in weaned alcoholics. The anticompulsive therapy can positively influence the short-term outcome, while other factors are negatively associated with abstinence.

Adult↗

PubMed1994

Opiate detoxification of methadone maintenance patients using lefetamine, clonidine and buprenorphine.

Thirty-nine methadone maintenance patients were included in a 9-day, double blind, randomized, inpatient detoxification trial. Methadone was tapered to 10 mg/day and then patients were assigned to one of these 3 protocols: clonidine (0.3-0.9 mg/day), lefetamine (60-240 mg/day), buprenorphine (0.15-0.9 mg/day). Buprenorphine treatment was significantly superior to clonidine and to lefetamine (F = 3.96 df = 2, 29 P < 0.05) in controlling objective, subjective and psychological withdrawal symptomatology. Clonidine was more effective than lefetamine in suppressing withdrawal in the first 3 days of treatment (day 3: F = 4.10 df = 2, 30 P < 0.05), and this trend was apparent on the objective and psychological items. In addition to evaluations of the efficacy of the single drugs used, the study showed that tapering methadone to low doses before entering the pharmacologically assisted discontinuation phase was clinically acceptable in detoxification from long-term methadone treatment.

Adult↗

PubMed1994

"Separation" of the mother-child couple: pregnancy and maternity of drug-dependent women.

Children of drug addicts are at risk of neglect and scanty maternal care. The objective of the present study was to identify homogeneous subgroups within a sample of drug addicted women, according to the quality of the outcome of the mother-child relationship. A group of 13 opiate-addicted women, followed from the seventh month of pregnancy up until the child was 2 years of age, underwent psychometric evaluation and was subdivided into two distinct groups based on whether the child remained within the family nucleus or was entrusted to a foster family or institution. The psychometric instrument used, an adaptation of Osgood's semantic differential which investigates maternal representations, allowed us to identify items with a very high predictability for the outcome of the mother-child relationship.

Adult↗

PubMedDate not supplied

Factor analysis of delusional disorder symptomatology.

Delusional disorder symptomatology has been poorly investigated with factor analytic studies. Most attempts to identify its symptomatologic structure were made with schizophrenic or mixed psychotic populations and included only delusional symptoms. The purpose of this study was to analyze the whole symptomatologic structure of delusional disorder. One hundred eight inpatients with delusional disorder (DSM-III-R) were evaluated for lifetime symptoms using the Operational Criteria (OPCRIT) checklist for psychotic illness and included in a factorial analysis. Four factors were evaluated: (1) core depressive symptoms, (2) hallucinations, (3) delusions, and (4) irritability symptoms. Thus, when scored by the OPCRIT checklist, delusional symptomatology consisted of four independent factors, indicating a substantial heterogeneity of this diagnostic category.

Adult↗

PubMedDate not supplied

Clinical and demographic features of psychotic and nonpsychotic depression.

The present study evaluated clinical and demographic features of subjects with delusional versus nondelusional major depressive disorder. Two hundred eighty-eight subjects with mood disorder (bipolar disorder, n = 94; major depressive disorder, n = 194) were included in the study. No differences were observed for gender, polarity of mood disorder, age of onset, duration of index episode, number of episodes, number of previous hospital admissions, frequency of illness episodes, and number of suicide attempts. On the other hand, delusional subjects showed a higher rate of cluster A personality disorder and a lower level of education. We also detected a larger number of cluster B personality disorders among nondelusionals. Our data suggest that subjects with delusional mood disorder do not differ substantially from nondelusionals in terms of the clinical and demographic variables considered in this study except for personality disorders.

Adult↗

PubMedDate not supplied

Serotonin receptor 2A, 2C, 1A genes and response to lithium prophylaxis in mood disorders.

The aim of this study was to investigate the influence of serotonin receptors 2A, 2C and 1A gene variants on lithium prophylactic efficacy in mood disorders. One hundred and twenty-four subjects affected by bipolar (n=102) and major depressive (n=22) disorder were followed prospectively for an average of 52 months and were typed for 5-HT2A (T102C: n=111, HTP: n=104), 5-HT2C (n=110) and 5-HT1A (n=61) variants. Both 5-HT2A and 5-HT2C variants were not associated with lithium outcome. Consideration of possible stratification effects like gender, polarity, family history, age at onset and duration of lithium treatment did not influence results. No 5-HT1A gene variant was identified. 5-HT2A and 2C variants are not, therefore, associated with lithium prophylactic efficacy in mood disorders.

Adult↗

PubMedDate not supplied

Influence of 5-HTTLPR and TPH variants on illness time course in mood disorders.

The aim of our study was to investigate gene variants in the long-term outcome of mood disorders. We retrospectively studied a sample of inpatients affected by recurrent and rapid cycling mood disorders. The serotonin transporter gene-linked functional polymorphic region (5-HTTLPR) and the A218C tryptophan hydroxylase (TPH) gene variant were determined using a PCR-based technique. For 5-HTTLPR polymorphism we genotyped 435 inpatients affected by major depressive (n=153), bipolar (n=213) and rapid cycling (n=69) mood disorders and 456 controls; for TPH we genotyped 399 inpatients (MD, n=132; BP, n=203; rapid cycling n=64) and 259 controls. Random Regression Model analysis was used to investigate the longitudinal time course of the illness. 5-HTTLPR and TPH polymorphisms were not associated with mood disorders time course. However we observed an excess of 5-HTTLPR*long alleles among rapid cycling subjects compared to both controls (P=0.018) and remitting mood disorders (P=0.006). TPH frequencies did not differ between mood disorders subtypes. Our results suggest that 5-HTTLPR variants may confer a susceptibility toward rapid cycling mood disorders.

Adult↗

PubMedDate not supplied

Familial concordance of fluvoxamine response as a tool for differentiating mood disorder pedigrees.

Concordance to antidepressant response in members of the same family is a common observation in clinical practice. However, few published data support this view; moreover families with affected members responder to the same antidepressant have been poorly studied. We have analyzed 45 pairs consisting of one mood disorder fluvoxamine double-responder proband and one first-degree relative with known outcome to fluvoxamine treatment. Among 45 pairs 30 (67%) were concordant for good response to fluvoxamine. In family pedigrees of concordant pairs we found a significantly higher distribution of bipolar forms in secondary cases than in families of non concordant pairs (14.9% vs 3.9% P = 0.039) suggesting that concordance to antidepressant therapy could select families with higher genetic loading.

Adult↗

PubMedDate not supplied

Tryptophan hydroxylase gene and response to lithium prophylaxis in mood disorders.

Lithium is an effective prophylactic agent in mood disorders but not all patients with mood disorders respond to lithium therapy; it is therefore necessary to identify responders prior to treatment. Clinical predictors account for about half of the variance and it is probable that genetic factors play a substantial role. The aim of this study was to investigate the possible association between the tryptophan hydroxylase (TPH) gene and prophylactic efficacy of lithium in mood disorders. One hundred and eight subjects affected by bipolar (n = 90) and major depressive (n = 18) disorder were followed prospectively for an average of 50.4 months and were typed for their TPH variant using polymerase chain reaction techniques. TPH variants were marginally associated with lithium outcome (F = 3.16; d.f.=2,105; P = 0.046). Subjects with the TPH*A/A variant showed a trend toward a worse response compared to both TPH*A/C and TPH*C/C variants. Consideration of possible stratification effects such as gender, polarity or age at onset did not influence the observed association. TPH variants may be a possible factor influencing the prophylactic efficacy of lithium in mood disorders.

Adult↗

PubMedDate not supplied

Evidence for an association between the dopamine D3 receptor gene DRD3 and schizophrenia.

Association of the dopamine D3 receptor gene (DRD3) and schizophrenia was examined in unrelated Israeli and Italian schizophrenic patients and ethnically matched normal control subjects. In the combined sample, there was a significant excess of DRD3 allele 2 among the schizophrenic patients (chi2 = 4.70, d.f. 1, p = 0.03). Comparison of genotype frequencies revealed an excess of the 2-2 genotype in the combined schizophrenic sample (chi2 = 8.30, d.f. 1, p = 0.01) and in the non-Ashkenazi Israeli schizophrenics alone (chi2 = 5.70, d.f. 2, p = 0.05). DRD3 2-2 genotype conferred a significantly increased risk of schizophrenia (chi2 = 8.21, d.f. 1, p = 0.004; OR = 2.87, CI 95% = 1.36-5.76) in the combined sample and in the non-Ashkenazi Israeli schizophrenics (chi2 = 7.22, d.f. 1, p = 0.04; OR = 7.22, CI 95% = 1.04-24.83). In the combined and Italian samples, allele 2 was associated with early age of onset as was the 2-2 genotype in the combined sample and non-Ashkenazi group. The 2-2 genotype was associated with poor response to neuroleptics, particularly in the non-Ashkenazi, Israeli schizophrenics. The possibility that DRD3 or a locus in linkage disequilibrium with it may play a role in the transmission of schizophrenia, is considered in relation to previous positive and negative reports.

Adult↗