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Biomedical subjects

A Serretti

Publications and source records attributed to A Serretti.

At least 55 records · Page 3Linked to original sources
PubMed1999

Dopamine receptor D4 gene is not associated with major psychoses.

We previously reported an association between dopamine receptor D4 (DRD4) gene exon 1 variants and delusional disorder. The aim of this investigation was to study the DRD4 gene exon 1 and 3 variants in schizophrenia, delusional, bipolar, and unipolar disorders. We studied 651 inpatients affected by schizophrenia (n = 229), delusional (n = 86), bipolar (n = 210), and unipolar (n = 126) disorders (DSM III-R) and 471 healthy controls; these were typed for DRD4 variants at the first and third exon using polymerase chain reaction techniques. DRD4 variants were not associated with schizophrenic and delusional subjects even when possible confounders like gender and onset were considered. A marginal association between DRD4 exon 3 variants with unipolar (excess of DRD4*2/4, p = 0.004) and bipolar (excess of DRD4*2/4, p = 0.001) disorders was observed, both associations drop to insignificance when corrected for multiple testing. Our results exclude that coding variants of the DRD4 exon 1 and 3 may play a major role in conferring susceptibility to major psychoses; moreover, we could not replicate the association of DRD4 exon 1 variant with delusional disorder.

Adult↗
PubMed1999

Dopamine D2 receptor gene not associated with symptomatology of mood disorders.

Dopamine D2 receptor gene (DRD2) variants have been implicated in the pathogenesis of psychiatric disorders. Many studies have, however, failed to replicate the original association of DRD2 with schizophrenia and mood disorders. A possible reason for this may lie in the definition of phenotype, which is traditionally based on psychiatric diagnosis. In this study we investigated the possibility that variants of the DRD2 gene might be associated with symptomatology in a sample of mood disorder subjects. Forty-seven inpatients affected by bipolar disorder (Diagnostic and Statistical Manual of Mental Disorders IV) were assessed at admission by the Operational Criteria for Psychotic Illness and were typed for DRD2 variants using polymerase chain reaction techniques. DRD2 was not associated with excitement, depression, delusion, and disorganization symptoms. Gender did not influence results significantly. Among early onset subjects DRD2*1 was associated with disorganized symptoms. In our sample DRD2 variants did not markedly influence psychopathology among mood disorder subjects. We observed a trend toward higher disorganization among DRD2*1 subjects.

Adult↗
PubMed1999

Dopamine receptor D2 and D4 genes, GABA(A) alpha-1 subunit genes and response to lithium prophylaxis in mood disorders.

Lithium is an effective prophylactic agent in mood disorders, and genetic factors are likely to modulate individual susceptibility to lithium treatment. The aim of this study is to investigate the influence of dopamine receptor D2 (DRD2), D4 exon 3 (DRD4), and gamma-aminobutyric acid type A (GABA(A)) receptor alpha-1 subunit (GABRA1) gene variants on the efficacy of lithium prophylaxis in mood disorders. Patients with mood disorders (N = 125: bipolar subtype, n = 100; major depressive disorder subtype, n = 25) were followed prospectively for an average of 53 months and were typed for DRD2 (Ser311/Cys311: n = 121, VNTR: n = 63), DRD4 (n = 125) and GABRA1 (n = 61) variants using polymerase chain reaction (PCR) techniques. DRD2, DRD4 and GABRA1 variants were not associated with response to lithium. A trend was observed toward a better outcome of DRD4* 2/4 subjects, but it was due to only two subjects. Consideration of possible stratification effects like gender, polarity, family history, age at onset and duration of lithium treatment did not reveal any association either. DRD2, DRD4 and GABRA1 variants therefore do not appear to be associated with the outcome of lithium prophylaxis in mood disorders.

Adult↗
PubMed1999

No association between serotonin-2A receptor gene polymorphism and psychotic symptomatology of mood disorders.

Abnormalities of the serotonergic system are involved in the pathophysiology of mood disorders. In the present study, we investigated the possible influence of the T102C polymorphism of the serotonin-2A receptor gene (5-HT2A, 13q14-21) on the symptomatology of mood disorders. Inpatients affected by mood disorders (n = 246, 149 bipolar, 97 major depressive disorder) were assessed with a checklist of operational criteria for psychotic illness (OPCRIT) to score their lifetime psychotic symptomatology. The subjects were also typed for 5-HT2A variants using polymerase chain reaction techniques. No association was found between this polymorphism and psychopathology as defined by the four symptomatologic factors used in phenotype definition (mania, depression, delusion and disorganization). Genetic variation at the 5-HT2A receptor gene does not, therefore, appear to play a major role in the pathogenesis of major mood disorders.

Adult↗
PubMed1999

Serotonin transporter gene not associated with psychotic symptomatology of mood disorders.

A functional polymorphism in the upstream regulatory region of the serotonin transporter gene (5-HTTLPR) has been recently reported to be associated with mood disorders. In the present study we investigated the possible influence of 5-HTTLPR on the symptomatology of mood disorders. Two hundred and thirty inpatients affected by mood disorders (160 bipolar and 70 major depressive disorder) were assessed by the Operational Criteria checklist for psychotic illness (OPCRIT) and were also typed for the 5-HTTLPR variants using PCR techniques. Mania, Depression, Delusion and Disorganization were the four symptomatologic factors used as phenotype definition. 5-HTTLPR variants were not associated with these symptomatologic factors, and consideration of possible stratification effects, such as sex, age of onset and polarity, did not reveal any association either. The serotonin transporter gene does not, therefore, appear to be associated with the symptomatology of mood disorders.

Adult↗
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

Serotonin transporter gene is not associated with symptomatology of schizophrenia.

The serotonin transporter gene is a primary candidate for involvement in major psychoses. A functional polymorphism in the upstream regulatory region of the serotonin transporter gene (5-HTTLPR) has recently been reported to be associated with a variety of psychopathological conditions. In the present study, we investigated the potential influence of the 5-HTTLPR on the psychopathology of schizophrenia. One hundred and sixty-one inpatients affected by schizophrenia (DSMIII-R) were assessed by the Operational Criteria checklist for psychotic illness (OPCRIT) and were typed for their 5-HTTLPR variants by PCR techniques. Mania, Depression, Delusion and Disorganization were the four symptomatologic factors used to define phenotype. 5-HTTLPR variants were not associated with these symptomatologic factors, and consideration of possible stratification effects such as sex, and age of onset did not reveal any association either. The serotonin transporter gene is not a liability factor for the symptomatology of schizophrenia.

Adult↗
PubMed1999

Symptomatologic analysis of psychotic and non-psychotic depression.

BACKGROUND: The aim of the present study is to evaluate the symptomatologic presentation of delusional compared to non-delusional major depressive episodes. METHODS: Two hundred and eighty-eight subjects suffering from mood disorder (144 bipolar, 133 unipolar) were assessed at admission by the Hamilton Depression Rating Scale (HAMD-21). RESULTS: Depressive symptomatology was more severe in the delusional sample, even after the exclusion of the items directly involved with delusional symptoms (P = 0.00002). CONCLUSIONS: Our data support the hypothesis of delusional depression as a more severe form of mood disorder.

Bipolar Disorder↗
PubMed1999

Delineating psychopathologic clusters within dysthymia: a study of 512 out-patients without major depression.

BACKGROUND: The literature indicates that emotional-cognitive symptoms are much more characteristic of dysthymia than the vegetative and psychomotor symptoms of major depression, yet this is insufficiently emphasized in the official criteria listed in the criteria of the American Psychiatric Association. Furthermore, as previous studies have examined these symptoms more in relation to prevalence than to possible symptom aggregation, in the present analyses we address both aspects. METHODS: In two multicenter collaborative trials, 512 out-patients meeting the symptom criteria of DSM-III-R dysthymia but without major depression were recruited. In this respect they conformed to the conceptual framework of ICD-10 which tends to restrict dysthymia to a subthreshold depression without excursion into severe depressive episodes. The Montgomery Asberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Rating Scale (HAM-A) were used to assess depressive and anxiety symptoms. RESULTS: Symptoms most frequently observed, besides depressed mood (100% by definition), were 'low energy or fatigue' (96%) and 'poor concentration or indecisiveness' (88%), followed by 'low self-esteem' (80%), 'insomnia or hypersomnia' (77%), 'poor appetite or overeating' (69%) and 'feeling of hopelessness' (42%). Interestingly, in the subjects with fewer than five symptoms, the most frequent were low energy or fatigue (93%), poor concentration or indecisiveness (79%) and low self-esteem (77%), the other symptoms being present in no more than half the sample. MADRS factor analysis identified two main factors: the first consisting of apparent and reported sadness, and the second concentration difficulties and lassitude. HAM-A factor analysis identified two factors clearly differentiating somatic and psychic symptoms. LIMITATIONS: Because suicidal patients were excluded on the ground of human subject concerns, our sample is representative of the milder range of symptomatology within the spectrum of dysthymia. This may in part explain the low prevalence of neurovegetative symptoms. CONCLUSION: Despite this, the present study involves the largest sample of pure dysthymia ever studied. Our results indicate that dysthymic disorder appears to primarily involve psychologic symptoms. The psychological symptoms themselves seem to cluster into sadness versus mental fatigue; as for anxiety symptoms, they appear divisible into somatic and psychic clusters, with the latter prevailing in dysthymia. Dysthymia proper, dominated by negative affectivity, might be distinguishable from a 'neurasthenic' subform dominated by low energy or 'deficit' symptoms at mental and physical levels.

Adult↗
PubMed1999

Social adjustment and self-esteem in remitted patients with mood disorders.

Mood disorders are characterized by manic and depressive episodes alternating with normal mood. While social function is heavily impaired during episodes of illness, there are conflicting opinions about inter-episode function. The present paper focuses on self-esteem and social adjustment in remitted mood disorders patients. Patients with mood disorders (99 bipolar and 86 major depressive subjects, in remission) were compared with a group of 100 control subjects. The self-esteem scale (SES) and the social adjustment scale (SAS) were used to measure self-esteem and social adjustment, respectively, in both groups of subjects. Patients with mood disorder exhibited worse social adjustment and lower self-esteem than control subjects. These results strongly confirm previous observations of poor inter-episode function in patients with mooddisorder.

Adult↗
PubMed1999

Genetic variants of dopamine receptor D4 and psychopathology.

There is much evidence to indicate that the dopamine receptor D4 (DRD4) gene is involved in psychiatric disorders. We investigated the correlation between DRD4 gene polymorphism and the psychopathology of major psychoses, independently of diagnoses. Some 461 inpatients affected by major psychoses were assessed by the Operational Criteria checklist for psychotic illness and typed for DRD4 variants. The four symptomatologic factors-mania, depression, delusion, and disorganization-were used as phenotype definitions. DRD4 Exon 3 long allele variants were associated with high delusional scores, with the most significant difference between alleles 2 and 7 (p = 0.004). DRD4 variants may, therefore, constitute a liability factor for development of delusional symptomatology in patients with major psychoses.

Adult↗
PubMed1999

Influence of a functional polymorphism within the promoter of the serotonin transporter gene on the effects of total sleep deprivation in bipolar depression.

OBJECTIVE: A functional polymorphism in the transcriptional control region upstream of the coding sequence of the 5-hydroxytryptamine transporter (5-HTT) has been reported. This polymorphism has been shown to influence the antidepressant response to fluvoxamine and paroxetine. The authors tested the hypothesis that the allelic variation of the 5-HTT-linked polymorphic region (5-HTTLPR) could influence the response of depressed patients to total sleep deprivation. METHOD: Sixty-eight drug-free inpatients with bipolar depression underwent a night of total sleep deprivation. 5-HTTLPR was genotyped in these patients. Changes in perceived mood were rated on a visual analogue scale and analyzed by using repeated measures analysis of covariance. RESULTS: Patients who were homozygotic for the long variant of 5-HTTLPR showed a significantly better mood amelioration after total sleep deprivation than those who were heterozygotic and homozygotic for the short variant. CONCLUSIONS: The influence of 5-HTTLPR on response to total sleep deprivation is similar to its observed influence on response to serotonergic drug treatments. This finding supports the hypothesis of a major role for serotonin in the mechanism of action of total sleep deprivation in depression.

Adult↗
PubMed1999

Outcome of affective psychosis.

The outcome of delusional depression is generally considered as poor when compared to non-delusional depression. We examined the social adjustment of remitted subjects affected by delusional compared to non-delusional mood disorder. Social adjustment of 135 inpatients (81 delusional and 54 non-delusional subjects), in remission from mood disorders for at least 3 months, were compared using the Social Adjustment Scale [SAS, Weissman et al., 1971]. Social adjustment was marginally lower for delusional subjects. The difference was significant within the "Family" sub-area of the SAS. Stratification by gender or polarity was precluded by the small sample size. These results furnish evidence of poor inter-episode function in patients with delusional mood disorder.

Delusions↗
PubMed1998

Dopamine receptor D2 Ser/Cys311 variant associated with disorganized symptomatology of schizophrenia.

The dopamine D2 receptor gene has been proposed as a genetic risk factor for schizophrenia (Arinami et al., 1994). However, a number of replications failed to confirm the initial report. The finding of a stronger association considering schizophrenics with the absence of negative symptoms (Arinami et al., 1996) suggested that the influence of DRD2 variants should be analyzed more at the level of symptoms rather than syndromes. One hundred and four inpatients affected by schizophrenia (n = 99) and delusional disorder (n = 5) (DSM IV) were assessed at admission by the Operational Criteria for Psychotic Illness (OPCRIT) and were typed for DRD2 variants using polymerase chain reaction (PCR) techniques. Subjects with the S311C variant presented a higher score on the 'Disorganization' factor (P = 0.012). Consideration of possible stratification effects such as sex and age of onset did not reveal any deviation from the whole sample. In conclusion, our preliminary report suggests that the DRD2 S311C variant may be a liability factor for disorganized symptoms among schizophrenics or for a subtype of schizophrenia characterized by highly disorganized symptomatology.

Adult↗
PubMed1998

Dopamine receptor D4 gene is associated with delusional symptomatology in mood disorders.

Disturbances of the dopaminergic neurotransmitter system have been implicated in the pathogenesis of depressive symptoms. Many studies have, however, failed to detect any association between genetic markers for the dopamine system and mood disorders. A possible reason for this may lie in the definition of phenotype, which is traditionally based on psychiatric diagnosis. In this study, we investigated the possibility that functional variants of the dopamine D4 receptor (DRD4) gene might be associated with depressive symptomatology in a sample of mood disorder subjects. Seventy-nine inpatients affected by bipolar (n=37) and major depressive (n=42) disorder (DSM-IV) were assessed at admission by the Hamilton Depression Rating Scale and were typed for DRD4 variants at the third exon using polymerase chain reaction (PCR) techniques. DRD4 was associated with delusional symptoms (F=5.56; d.f.=2,145; P=0.005), with DRD4*7 exhibiting higher scores when compared to DRD4*4 (P=0.006) variants. Polarity of mood disorder did not influence results significantly. The findings are in accordance with our previous report of an association of the DRD4 gene with delusional symptomatology of major psychoses. DRD4*7 should, therefore, be considered a liability factor for delusional symptoms in mood disorders.

Adult↗
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

Tyrosine hydroxylase gene associated with depressive symptomatology in mood disorder.

Tyrosine hydroxylase (TH) is the rate-limiting enzyme in the synthesis of dopamine and norepinephrine. It may be involved in the pathophysiology of psychiatric disorders and positive associations have been reported for TH gene markers in mood disorders. While most replications failed to confirm the initial findings, other papers suggested a potential role of this gene in the etiology of mood disorders. Among the many different reasons for a lack of consistent replications, a critical role is played by the "correct" phenotype identification. Actually, up to now the only classification criteria has been the psychiatric diagnosis, but within the same psychiatric diagnoses the symptomatologic presentation may vary dramatically depending upon severity, presence of psychotic features or other psychopathologic traits. Thus, the aim of our study is to evaluate a possible association for TH gene with symptomatology in a sample of subjects affected by mood disorders. We have developed a phenotype definition based on the observed symptomatology divided into the four factors "Excitement," "Depression," "Delusion," and "Disorganization." Our sample includes 46 mood disorder subjects, investigated by the OPCRIT (operational criteria checklist for psychotic illness) checklist for their symptomatological pattern and typed for TH variants by polymerase chain reaction (PCR) amplification. Depressive factor was associated with TH variants (F = 4.79, df = 4, 87, P = 0.006), with TH*2 subjects presenting lower depressive scores. Subjects with genotype TH*2/2 were the only ones in the sample to report mild depressive episodes. TH variants may be related with depressive symptomatology in subjects affected by mood disorders.

Alleles↗