Academic psychiatry in Brazil: confronting the challenges.
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Academic Medical Centers↗
Biomedical subjects
V Gentil
Publications and source records attributed to V Gentil.
Dose-related effects of propericiazine in rats.
We evaluated the effects of the neuroleptic agent propericiazine on animal models of anxiety and memory. Adult male Wistar rats (250 to 350 g) received intraperitoneal injections of propericiazine (0.05, 0.075 and 0.1 mg/kg), diazepam (1 mg/kg), saline, or diazepam vehicle (20% propylene glycol and 80% saline) 30 min prior to the experimental procedure. Animals (10-15 for each task) were tested for step-down inhibitory avoidance (0.3-mA footshock) and habituation to an open-field for memory assessment, and submitted to the elevated plus-maze to evaluate the effects of propericiazine in a model of anxiety. Animals treated with 0.075 mg/kg propericiazine showed a reduction in anxiety measures (P<0.05) similar to that observed in those treated with diazepam. Propericiazine at the doses of 0.05 and 0.1 mg/kg had no significant anxiolytic effects (P>0.05) in the elevated plus-maze model of anxiety. Memory was not affected by propericiazine in any of the tests, but was impaired by diazepam. The results indicate a dose-related, inverse U-shaped effect of propericiazine in an anxiety model, but not on memory tasks, perhaps reflecting involvement of the dopaminergic system in the mechanisms of anxiety.
Animals↗
Gender differences in gambling progression.
The authors compared 39 women and 38 men entering an outpatient treatment program for pathological gambling. They were diagnosed according to DSM-IV and selected by SOGS, followed by a semi-structured interview for demography and progression of the gambling behavior prior to treatment. Women were more often single (59% vs. 26%; p = .005) and started gambling significantly later than men (34.2 vs. 20.4 years; p < .001). The progression of the disorder was more than 2 times faster in women than in men. There was no difference in the age of seeking treatment (44.7 vs. 42.3 years). Findings from this study resemble gender differences in other addictions--in particular the faster progression among women--challenge pharmacodynamic hypotheses for this phenomenon, and suggest gender into account when devising treatment strategies for pathological gambling.
Adult↗
A dose-finding and discontinuation study of clomipramine in panic disorder.
Eighty-one panic disorder patients with or without agoraphobia were treated with flexible doses of clomipramine under single-blind conditions. Fifty-seven (70.3%) reached operational criteria for full remission in 16.2 +/- 6.5 weeks, with a mean dose of 89.1 +/- 8.2 mg/day. Fifty-four (81%) of them received a continuous post-remission maintenance treatment at full doses of clomipramine for 4-6 months. No patient relapsed during the clomipramine maintenance phase. Their medication was then tappered and discontinued with placebo substitution under double-blind conditions. Fifty-one (63%) patients were followed-up until relapse or recurrence for up to 3 years, with periodic assessments. Three different outcome groups were identified: the first (n = 19, 19; 37.2%) experienced an early/immediate relapse (5.2 +/- 4.9 weeks after drug discontinuation); the second group (n = 22, 22; 43.1%) experienced recurrence after 42.9 +/- 35 weeks following discontinuation; and the third group (n = 10, 10; 19.6%) remained assymptomatic and functionally well throughout the follow-up. Predictors of early relapse were: (1) higher baseline score in the Beck Depression Inventory; (2) higher global score on the phobic avoidance scale after the full remission criteria; and (3) the need for higher clomipramine doses to reach full remission. The need for long-term or intermittent maintenance for most patients is emphasized.
Adolescent↗
Analysis of the serotonin transporter polymorphism (5-HTTLPR) in Brazilian patients affected by dysthymia, major depression and bipolar disorder.
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Adult↗
Double-blind comparison of venlafaxine and amitriptyline in outpatients with major depression with or without melancholia.
The purpose of this study was to compare the efficacy and tolerability of venlafaxine and amitriptyline in outpatients with major depression with or without melancholia. This was an 8-week, multicentre, randomized, double-blind, parallel-group comparison of venlafaxine and amitriptyline. Outpatients with DSM-IV major depression, a minimum score of 20 on the 21-item Hamilton Depression Rating Scale (HAM-D), and depressive symptoms for at least 1 month were eligible. Patients were randomly assigned to venlafaxine or amitriptyline, both drugs titrated to a maximum of 150 mg/day until study day 15. The primary efficacy variables were the final on-therapy scores on the HAM-D, Montgomery-Asberg Depression Rating Scale and Clinical Global Impression severity scales. Data were evaluated on an intent-to-treat basis using the LOCF method. One hundred and 16 patients were randomized, and 115 were evaluated for efficacy. Both drugs showed efficacy in the treatment of depression with or without melancholia. No significant differences were noted between treatments for any efficacy parameter. However, significantly (p < 0.05) more patients in the amitriptyline group had at least one adverse event. These results should support the efficacy and tolerability of venlafaxine in comparison with amitriptyline for treating major depression with or without melancholia.
Adolescent↗
[Lack of gender effect on familial schizophrenia. A Brazilian study].
Epidemiological studies on schizophrenia have showed different age at onset between gender, in which male schizophrenics present symptoms earlier than females. However this gender effect is not observed within familial schizophrenia. The present study investigates the age at onset in 31 RDC-schizophrenics from 13 Brazilian families. No differences in age at onset were found between gender, confirming previous studies in other populations. This result may indicate genetic influences on age at onset in a subgroup of patients affected by schizophrenia and can be explored by molecular genetic studies.
Adolescent↗
Case series: increased vulnerability to obsessive-compulsive symptoms with repeated episodes of Sydenham chorea.
The association between obsessive-compulsive symptoms (OCS) and Sydenham chorea (SC) supports the hypothesis of a common neuroimmunological dysfunction in basal ganglia associated with group A beta-hemolytic streptococcal infection underlying both conditions. Four children with 2 distinct SC episodes were evaluated to assess the course of OCS. All patients developed OCS during their second episodes (3 met criteria for obsessive-compulsive disorder [OCD]), but not in their first episodes (2 developed OCS and met criteria for OCD). These data suggest that the recurrence of SC episodes may result in a cumulative effect, thus increasing the risk of appearance and intensification of OCS.
Acute Disease↗
Structure, function, and regulation of insulin-like growth factors in fish.
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Animals↗
Analysis of a novel functional polymorphism within the promoter region of the serotonin transporter gene (5-HTT) in Brazilian patients affected by bipolar disorder and schizophrenia.
It has been suggested that the serotonin transporter (5-hydroxytryptamine-transporter or 5-HTT) may be involved in the pathogenesis of affective disorders. Recently, Collier et al. (1996) found that the frequency of the low-activity short variant (s) of the 5-HTT-linked polymorphic region (5-HTTLPR) was higher among patients with affective disorders than in normal controls. However, since the observed level of significance was not high, they suggest that these findings should be replicated in independent samples. We have analyzed 86 unrelated patients (47 with bipolar disorder and 39 with schizophrenia) and 98 normal controls from the Brazilian population for the 5-HTTLPR. Statistical analysis revealed that the genotypes (LL, Ls, ss) as well as the estimated allele frequencies (L,s) did not differ significantly among the three studied groups or between bipolar and normal controls. In addition, although not statistically significant, the genotype ss in our sample was less frequent among our bipolar patients than in our normal controls (12.8% versus 16.3%) which is the opposite of what was found by Collier et al. (24% versus 18%) in the European study. Although it will be important to extend the present analysis in a larger sample, our preliminary results suggest that the 5-HTTLPR does not seem to play a major role in the genetics of bipolar and schizophrenic disorders at least in this group of Brazilian psychiatric patients.
Bipolar Disorder↗
Linkage analysis between bipolar affective disorder and markers on chromosome X.
Since 1969, several classical linkage studies suggested an X-chromosome locus for bipolar affective disorder. However, methods using highly polymorphic DNA markers have provided conflicting evidence for linkage, and an X-chromosomal locus for bipolar disorder remains controversial. More recently, Pekkarinen et al. (1995) found a maximum LOD score of 3.54 at the marker DXS994 in a large bipolar Finnish kindred. In the present study, we attempted to replicate this finding using 43 families multiply affected by bipolar affective disorder. These families were selected for the absence of male-to-male transmission of the disease, and were genotyped for two microsatellte markers, DXS1227 and DXS1062 (which is about 2 cM telomeric to DXS994). Linkage to this region was excluded either using a two-point lod score method with two plausible genetic models, or by a model-free lod score analysis which does not require specification of a particular mode of transmission. We conclude that there is no evidence of a common major gene for bipolar affective disorder at Xq25-q27 in our set of families.
Bipolar Disorder↗
Obsessive-compulsive and related symptoms in children and adolescents with rheumatic fever with and without chorea: a prospective 6-month study.
OBJECTIVE: The incidence and course of neuropsychiatric symptoms were determined in pediatric patients with rheumatic fever. METHOD: The Leyton Obsessional Inventory and National Institute of Mental Health Global Obsessive-Compulsive Scale were used to evaluate children and adolescents who had rheumatic fever with Sydenham's chorea (N=30) or without chorea (N=20). They were assessed three times over 6 months from the onset of rheumatic fever. Psychiatric diagnoses were also determined. RESULTS: Obsessive-compulsive symptoms abruptly appeared and peaked during the 2 months after the onset of rheumatic fever in 21 patients with chorea (70.0%) and were absent in all patients without chorea. Obsessive-compulsive disorder (OCD) was diagnosed in five patients with chorea (16.7%). CONCLUSIONS: The association between Sydenham's chorea and OCD supports suggestions that similar mechanisms involving the basal ganglia underlie both disorders. Obsessive-compulsive symptoms occurred at the beginning of rheumatic fever, so early psychopathological assessments are essential.
Adolescent↗
Mood improvement in 'normal' volunteers.
To test the hypothesis that clomipramine is effective in improving subthreshold non-specific symptoms in subjects without any established psychopathology, we conducted a double-blind, cross-over controlled trial of clomipramine (oral doses of 10-40 mg/day) and propanteline (active placebo) for 5 weeks in nine normal volunteers. Four other subjects completed the first part of the trial. These subjects were selected from 275 respondents to newspaper and radio requests for subjects who considered themselves as normal but were unhappy about their usual moods. They did not reach cut-off scores in the Self-Report Questionnaire and did not meet diagnostic criteria for any lifetime or current ICD-10 or DSM-III-R condition, as assessed by an open psychiatric interview and the Schedules for Clinical Assessment in Neuropsychiatry. Despite the small sample and the low level of initial symptomatology, both subjects and observers consistently detected significant improvements with clomipramine in a number of assessments of mood, notably decreased irritability and anxiety. This controlled trial suggests that it is possible to improve subclinical complaints through psychopharmacological agents, raises questions about the mechanisms of their action and discusses their implications.
Adult↗
Untreated psychopathology of candidates to "normal volunteers".
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Adult↗
Hormonal response during a fenfluramine-associated panic attack.
Secretion curves for prolactin, cortisol, TSH, and GH from a 37-year old woman with dysthymia and panic disorder with agoraphobia were determined one day prior to (day I), and during a panic attack (day II) associated with an oral dose of 60 mg dl-fenfluramine, a drug known to increase anticipatory anxiety. The increased cortisol secretion observed is discussed in relation to the hormonal correlates of anxiety and the possible role of depression, dl-fenfluramine, and serotonergic receptor sensitivity.
Adult↗
Linkage studies in bipolar affective disorder with markers on chromosome 21.
Straub et al. (1994: Nature Genet. 8. 291-296) have suggested that a susceptibility gene for bipolar affective disorder is located at chromosome 21q22.3, on the basis of linkage analysis in one large family. This result has been supported by Gurling et al. (1995: Nature Genet. 10, 8-9) who also found some evidence for linkage to this region under locus heterogeneity. In order to investigate the validity of these results and to estimate how broadly applicable they are, we performed a linkage study between bipolar affective disorder and two DNA markers (D21S171 and PFKL) from 21q22.3 using 60 bipolar pedigrees from three European centres and Brazil. The most positive result obtained was a maximised admixture lod score of 1.2 for the marker PFKI, under the assumption of locus heterogeneity, dominant transmission and a diagnostic classification which included recurrent unipolar depression. However, since lod scores obtained for both markers were substantially negative overall, we conclude that there is no common major gene for bipolar affective disorder at 21q22.3. It remains possible that a gene of major effect in this region operates in a minority of families.
Bipolar Disorder↗
Production of recombinant insulin-like growth factor-II in the development of a radioimmunoassay in rainbow trout (Oncorhynchus mykiss).
Rainbow trout (Oncorhynchus mykiss) insulin-like growth factor-II (IGF-II) cDNA was amplified by reverse transcription-polymerase chain reaction and cloned into an expression vector (parHS3) for production by Escherichia coli. Recombinant rainbow trout IGF-II (rtIGF-II) was recovered from bacterial inclusion bodies, solubilized, and purified by gel filtration chromatography under reducing conditions. After refolding of the peptide by dialysis at basic pH, we obtained a final yield of 820 micrograms/liter culture medium. The rtIGF-II appeared as a single band estimated at 80% and with molecular mass of 7.5 kDa. A homologous radioimmunoassay (RIA) for the measurement of IGF-II in trout plasma has been developed using rtIGF-II as antigen, radiolabeled tracer, and standard. RIA sensitivity was 0.1 ng/ml and the ED50 was 0.75 +/- 0.06 ng/ml. Intra- and interassay coefficients of variation were 4.04% (n = 6) and 4.56% (n = 9), respectively, at ED50 levels. Cross-reactivities of 1 and 0.1% were found for recombinant coho salmon (Oncorhynchus kisutch) IGF-I and coho salmon insulin, respectively. No cross-reactivities were found for recombinant human IGF-I and IGF-II, porcine insulin, or a variety of salmonid pituitary hormones. The interference of IGF binding proteins (IGFBP) in the RIA has been tested with and without extraction (acid/ethanol extraction or C-25 acid chromatography) of fed and fasted trout plasma samples. Parallel displacement curves were obtained for unextracted and C-25-extracted plasma but not for acid/ethanol-extracted plasma. Comparison of IGF-II levels from these samples showed a possible interference of IGFBP in the RIA in fed (19.6 +/- 1.56 ng/ml unextracted and 25.25 +/- 1.21 ng/ml extracted) and fasted (21.58 +/- 1.02 ng/ml unextracted and 9.86 +/- 1.68 ng/ml extracted) trout plasma. Finally, the displacement curves for unextracted plasma from rainbow trout, Couch's sea bream (Pagrus pagrus), and carp (Cyprinus carpio) were parallel to that of the rtIGF-II standard and not strictly parallel for tilapia (Oreochromis niloticus) and catfish (Silurus glanis) plasma. No significant cross-reaction occurred with eel (Anguilla anguilla) plasma. The rainbow trout IGF-II RIA reported in this study has low variability and is highly sensitive. Therefore it is a reliable method for measuring IGF-II levels in salmonids and some nonsalmonid fish species.
Amino Acid Sequence↗
Dysthymia in neurological disorders.
Dysthymia is characterized by long-lasting periods of lowered mood. Epidemiological studies in the USA and Europe have demonstrated that the prevalence of dysthymia is at least 3% of the general population. Its pervasive occurrence makes dysthymia a public health problem worldwide. One feature of this disorder is its co-occurrence with medical and neurological disorders. A World Health Organization meeting on dysthymia in neurological disorders was held in Geneva, 1-3 July 1996 to address this topic. Some of the major goals of this meeting were to clarify the definition of dysthymia in the presence of neurological disorders and to evaluate current research in the field, to point out new areas for investigation, and to discuss current psychological and pharmacological treatments for dysthymia in neurological disorders. The potential roles of neuroendocrine and molecular mechanisms in dysthymia were identified through specific problems related to dysthymia occurring in disorders such as Parkinson's disease, Alzheimer's disease, stroke, multiple sclerosis and epilepsy. This meeting provided direction and opportunity for future studies in the under-recognized and under-investigated relationship between dysthymia and neurological disorders.
Dysthymic Disorder↗