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D Di Bella

Publications and source records attributed to D Di Bella.

At least 19 recordsLinked to original sources
PubMed1999

No interaction of GABA(A) alpha-1 subunit and dopamine receptor D4 exon 3 genes in symptomatology of major psychoses.

Previously, we reported on an association of the dopamine receptor D4 (DRD4) gene with delusional symptomatology of major psychoses. However, despite the strength of the association, it only accounted for 2% of the variance, indicating that contributions from other genes were probable. In the present study, we investigated the original cohort of subjects to evaluate the gene for the gamma-aminobutyric acid type A (GABA(A)) receptor alpha-1 subunit (GABRA1). The possible association of GABRA1 with the psychopathology of major psychoses was tested both alone and in interaction with DRD4. Four hundred and sixty-one inpatients affected by major psychoses were assessed by the operational criteria checklist for psychotic illness (OPCRIT) and were also typed for the DRD4 and GABRA1 variants using PCR techniques. Mania, depression, delusion, and disorganization were the four symptomatologic factors used as phenotype definitions. GABRA1 variants were not associated with these symptomatologic factors, and consideration of possible stratification effects such as sex and psychiatric diagnosis also did not reveal any association. GABRA1 variants did not significantly influence the association of DRD4 with delusional symptoms. No interaction was observed on the other symptom factors. The GABA(A) alpha-1 subunit gene does not, therefore, interact with DRD4 in the symptomatology of major psychoses.

Adult↗
PubMed1999

Excess of high activity monoamine oxidase A gene promoter alleles in female patients with panic disorder.

A genetic contribution to the pathogenesis of panic disorder has been demonstrated by clinical genetic studies. Molecular genetic studies have focused on candidate genes suggested by the molecular mechanisms implied in the action of drugs utilized for therapy or in challenge tests. One class of drugs effective in the treatment of panic disorder is represented by monoamine oxidase A inhibitors. Therefore, the monoamine oxidase A gene on chromosome X is a prime candidate gene. In the present study we investigated a novel repeat polymorphism in the promoter of the monoamine oxidase A gene for association with panic disorder in two independent samples (German sample, n = 80; Italian sample, n = 129). Two alleles (3 and 4 repeats) were most common and constituted >97% of the observed alleles. Functional characterization in a luciferase assay demonstrated that the longer alleles (3a, 4 and 5) were more active than allele 3. Among females of both the German and the Italian samples of panic disorder patients (combined, n = 209) the longer alleles (3a, 4 and 5) were significantly more frequent than among females of the corresponding control samples (combined, n = 190, chi2 = 10.27, df = 1, P = 0.001). Together with the observation that inhibition of monoamine oxidase A is clinically effective in the treatment of panic disorder these findings suggest that increased monoamine oxidase A activity is a risk factor for panic disorder in female patients.

Alleles↗
PubMed1998

Self-esteem in remitted patients with mood disorders is not associated with the dopamine receptor D4 and the serotonin transporter genes.

Disturbances of the dopaminergic and serotoninergic neurotransmitter systems have been implicated in the pathogenesis of depressive symptoms. Associations have been reported between markers of the two neurotransmitter systems and the presence of illness or severity of depressive episodes, but no attention has been focused on the periods of remission. The present report focuses on a possible association of self-esteem in remitted mood disorder patients with the functional polymorphism located in the upstream regulatory region of the serotonin transporter gene (5-HTTLPR) and the dopamine receptor D4 (DRD4). Inpatients (N=162) affected by bipolar (n=103) and unipolar (n=59) disorder (DSM III-R) were assessed by the Self-Esteem Scale (SES, Rosenberg, 1965) and were typed for DRD4 and 5-HTTLPR (n=58 subjects) variants at the third exon using polymerase chain reaction (PCR) techniques. Neither DRD4 nor 5-HTTLPR variants were associated with SES scores, and consideration of possible stratification effects such as sex and psychiatric diagnosis did not reveal any association either. The serotonin transporter and dopamine receptor D4 genes do not, therefore, influence self-esteem in remitted mood disorder subjects.

Adult↗
PubMed1998

5HT2C CYS23/SER23 polymorphism is not associated with obsessive-compulsive disorder.

A great deal of evidence suggests that a genetic component underlies obsessive-compulsive disorder (OCD). The response to serotonergic medications and the worsening of obsessive symptoms after administration of serotonergic agonists indicate that serotonergic mechanisms are involved in OCD. We investigated the role of the Cys23Ser mutation of the 5HT2C receptor gene in the etiology of this disorder by performing an association study comparing a sample of 109 OCD patients with a sample of 107 healthy control subjects. No allelic or genotypic association of OCD with the 5HT2C receptor gene mutation was revealed in our data. We also extended the association analysis to a subsample of 39 OCD patients that had previously been submitted to a challenge test with clomipramine. In the subsample of OCD patients that received the challenge with clomipramine, no association between the 5HT2C receptor gene mutation and response to the challenge test was found. Our results exclude any specific role of the Cys23Ser mutation of 5HT2C receptor gene in the etiology of OCD: it seems probable that more complex genetic models are needed to explain the involvement of serotonergic elements in the etiology of this disorder.

Adult↗
PubMed1998

Polymorphism within the promoter of the serotonin transporter gene and antidepressant efficacy of fluvoxamine.

Depression with psychotic features has been shown to respond to selective serotonin reuptake inhibitors (SSRIs). The serotonin transporter (5-HTT) is a prime target for SSRIs. A functional polymorphism within the promoter region of the 5-HTT gene, leading to different transcriptional efficiency, was recently reported. We tested the hypothesis that allelic variation of the 5-HTT promoter could be related to the antidepressant response to fluvoxamine and/or augmentation with pindolol (a serotonin autoreceptors antagonist) which has been suggested as an augmentation therapy for nonresponders. One hundred and two inpatients with major depression with psychotic features were randomly assigned to treatment with a fixed dose of fluvoxamine and either placebo or pindolol for 6 weeks. Depression severity was assessed once a week using the Hamilton Depression Rating Scale. Allelic variation in each subject was determined using a PCR-based method. Data were analyzed with a three-way repeated measures analysis of variance. Both homozygotes for the long variant (l/l) of the 5-HTT promoter and heterozygotes (l/s) showed a better response to fluvoxamine than homozygotes for the short variant (s/s). In the group treated with fluvoxamine plus pindolol all the genotypes acted like l/l treated with fluvoxamine alone. Fluvoxamine efficacy in delusional depression seems to be related to allelic variation within the promoter of the 5-HTT gene. Even though other factors may be implicated, genotyping at 5-HTT promoter may represent a promising tool to individualize the pharmacological treatment of depression.

Antidepressive Agents, Second-Generation↗
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

CO2-induced panic attacks: a twin study.

OBJECTIVE: The authors investigated the role of genetic factors in 35% CO2-induced panic attacks. METHOD: Ninety twins recruited from the general population were challenged with one-vital-capacity inhalations of 35% CO2-65% O2. Probandwise concordance rates were calculated and rates compared for monozygotic and for dizygotic twins. RESULTS: A significantly higher concordance was found for 35% CO2-induced panic attacks among monozygotic than dizygotic twins (55.6% versus 12.5%). CONCLUSIONS: These results suggest a relevant role of genetic factors in 35% CO2-induced panic attacks.

Adult↗
PubMed1997

Functional promoter polymorphism of the human serotonin transporter: lack of association with panic disorder.

To probe the hypothesis of a role for a functionally relevant 44 bp insertion/deletion of the serotonin transporter promoter in the aetiopathogenesis of panic disorder, we determined the allele frequency of the variant in two samples (combined n = 158) of panic disorder patients (DSMIII-R) and compared it with its allele frequency in two ethnically matched control samples (combined n = 169). The fact that no difference could be observed (x 2 analysis) argues against a major role for this serotonin transporter promoter polymorphism in the aetiopathogenesis of panic disorder.

Alleles↗
PubMed1996

Systematic screening for mutations in the coding region of the human serotonin transporter (5-HTT) gene using PCR and DGGE.

Dysfunctions in serotonergic pathways may underlie several psychiatric disorders. The reuptake of serotonin (5-HT) from synaptic terminals is mediated by a specific transporter (5-HTT). Genetic variation in the gene coding for the 5-HTT protein might be involved in the predisposition to psychiatric disorders. A systematic screening of the whole coding sequence of the 5-HTT gene in mood disorder (MD) and obsessive-compulsive disorder (OCD) patients, as well as in healthy controls, using PCR and denaturing gradient gel electrophoresis (DGGE) revealed the presence of two mutations. The first was in intron 4, and the second was a C-->A transversion leading to an amino-acid exchange (Leu-->Met) in position 255 of the deduced protein sequence. No further occurrence of this substitution was found in an extended sample of patients and controls. Therefore, structural modifications of the 5-HTT gene do not seem to play either a major or minor role in the genetic predisposition to MD or OCD.

Adult↗
PubMed1996

Liver involvement in white patients with sickle-cell disease.

BACKGROUND: Liver involvement and cholelithiasis are common complications of sickle-cell disease. The incidence of clinically evident hepatic damage reported in the literature for black people varies from 15% to 30%, while no data are reported for white people. OBJECTIVE: To evaluate the liver involvement in 40 patients with homozygous sickle cell anemia (the beta 5 beta 5 form of sickle-cell disease) and 102 patients with double-heterozygous hemoglobin S and beta-thalassemia (65 with the beta 5 beta 0th and 37 with the beta 5 beta +th form of sickle-cell disease). SETTING: The Department of Pediatric Hematology and Oncology, University of Catania, Catania, Italy. PATIENTS: Outpatients with sickle-cell disease. RESULTS: We found that, in our patients, liver disease seems to be clinically irrelevant: only 2 of the 142 patients examined had notable alterations in hepatic function. Cholelithiasis was found in 42.1% of the subjects with the beta 5 beta 5 form of sickle-cell disease and in 26.8% of the subjects with the beta 5 beta th form. Age-related analysis revealed a greater incidence of cholelithiasis during the first years of life in the patients with the beta 5 beta 5 form of the disease than in patients with the beta 5 beta th form. CONCLUSION: Our data showed that liver involvement in sickle-cell disease is clinically irrelevant, reflecting the fact that the clinical expression of sickle-cell disease in Sicilian patients is moderate.

Adolescent↗
PubMed1996

Association study of a null mutation in the dopamine D4 receptor gene in Italian patients with obsessive-compulsive disorder, bipolar mood disorder and schizophrenia.

Although serotonergic dysregulation is a leading pathogenetic hypothesis for obsessive-compulsive disorder (OCD), some evidence also suggests a possible dysregulation of the dopaminergic system in this disorder. Therefore, individual differences in deoxyribonucleic acid (DNA) coding for dopamine receptor proteins might contribute to the genetic background of this disorder. Previously we reported a null mutation in exon 1 of the dopamine D4 receptor gene. The variant type is characterized by a 13 bp deletion and is predicted to code for a truncated, non-functional receptor. We assessed the frequency of this polymorphism in 157 OCD patients, 196 schizophrenics, 111 bipolars and 162 healthy controls of Italian descent. Our findings do not implicate a role for this mutation in conferring a susceptibility to OCD and confirm previous negative results regarding its involvement in schizophrenia and bipolar disorder.

Bipolar Disorder↗
PubMed1996

A novel functional polymorphism within the promoter of the serotonin transporter gene: possible role in susceptibility to affective disorders.

The serotonin transporter (5-HTT) is a candidate locus for aetiological involvement in affective disorders. Biochemical studies in suicides and depressed patients suggest that 5-HT uptake function is frequently reduced in affective illness. Furthermore, 5-HTT is targeted by widely used antidepressant drugs such as fluoxetine. We have performed an association study of a short variant of the 5-HTT-linked polymorphic region (5-HTTLPR), which restricts transcriptional activity of the 5-HTT promoter leading to low functional expression of the 5-HTT, in 454 patients with bipolar or unipolar affective disorder and 570 controls, derived from three European Centres (London, Milan and Würzburg). In all three centres, the frequency of the low activity allele was higher in patients than in controls (50% vs 45% in London, 45% vs 43% in Milan, 47% vs 40% in Würzburg). Although these differences were not individually significant, a stratified analysis of all three samples gave a significant overall odds ratio of 1.23 (95% confidence interval 1.02-1.49, P = 0.03). The excess of the homozygous low-activity genotype among the patients was even greater (odds ratio 1.53, 95% confidence interval 1.04-2.23, P = 0.02), suggesting partial recessively of the low-activity allele. Given the functional role of 5-HTT, our findings suggest that 5-HTTLPR-dependent variation in functional 5-HTT expression is a potential genetic susceptibility factor for affective disorders. If this finding is replicated, further work on genetic variants with low 5-HTT activity may facilitate the differential diagnosis of affective disorders, the assessment of suicidal behaviour, and the prediction of good clinical response to antidepressants.

Alleles↗
PubMed1995

Identification of two novel polymorphisms and a rare deletion variant in the human dopamine D4 receptor gene.

We report two novel polymorphisms and a rare deletion variant in the human dopaine D4 receptor gene. The two polymorphisms are characterized by single base pair substitutions, namely a G-->C transversion changing codon 11 from GGG (encoding Gly) to CGG (encoding Arg) and a C-->T transition in position -11 upstream from the start codon. The Arg11 variant occurs at a frequency of about 1% and the C-->T transition at a frequency of about 7% in German control subjects (n = 148). Allele frequencies observed in patients suffering from schizophrenia (n = 256) and bipolar affective disorder (n = 99) were similar. The deletion variant is characterized by a 21 bp deletion affecting codons 36 to 42 coding for amino acids Ala-Ala-Leu-Val-Gly-Gly-Val located in the first transmembrane domain of the dopamine D4 receptor. The mutation was identified in a single individual suffering from obsessive-compulsive disorder and panic disorder. We were unable to detect the deletion in patients with schizophrenia and bipolar affective disorder, nor in healthy controls.

Adult↗
PubMed1994

Lack of association between obsessive-compulsive disorder and the dopamine D3 receptor gene: some preliminary considerations.

Controversial results possibly suggesting an association between Tourette's Syndrome (TS) and excess of homozygosity at a Msc I polymorphism in the Dopamine D3 receptor (DRD3) gene have recently been reported. Since a relationship between Obsessive-Compulsive Disorder (OCD) and Tourette's Syndrome (TS) has been suggested, in this study we assessed the frequency of this 2-allele polymorphism in a sample of 97 OCD patients and in 97 control subjects. No statistically significant differences in allele or genotype frequencies were found. Thus this mutation in the coding sequence of the DRD3 gene is unlikely to confer susceptibility to OCD.

Adolescent↗
PubMed1994

Distribution of the MscI polymorphism of the dopamine D3 receptor in an Italian psychotic population.

The finding of contrasting results regarding an association between schizophrenia and the MscI polymorphism site in the dopamine D3 receptor gene prompted us to study the distribution of this polymorphism in an Italian sample of 52 patients suffering from delusional disorder, 85 schizophrenic patients and 78 control subjects. No significant differences in genotype, allele and homozygosity frequencies between schizophrenics and controls were found, while a significant, albeit modest, association was discovered between delusional disorder and both the 1 allele and the 1-1 genotype. This suggests a contribution of this gene to the liability to develop delusional disorder.

Adult↗
PubMed1991

Familial Jarcho-Levin syndrome.

Jarcho-Levin syndrome is a variety of autosomal recessive spondylocostal dysostosis characterized by severe deformity of the thoracic cage, leading to respiratory failure and early death. There are often associated dysmorphic features. The disease is more frequent in Puerto Ricans and rare in Europe. A Sicilian family with four affected individuals in two interrelated sibships is reported.

Abnormalities, Multiple↗