A Maras

University of São Paulo, Ribeirão Preto, Estado de Sao Paulo, Brazil

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Publications (32)73.76 Total impact

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    ABSTRACT: Recent findings showing significant correlations between phospholipase A2 (PLA2) activity and structural changes in schizophrenic brains contribute to the membrane hypothesis of schizophrenia, which was hampered because a clean functional link between elevated PLA2 activity and brain structure was missing (Neuroimage, 2010; 52: 1314-1327). We measured membrane fluidity parameters and found that brain membranes isolated from the prefrontal cortex of schizophrenic patients showed significantly increased flexibility of fatty acid chains. Our findings support a possible link between elevated PLA2 activity in cortical areas of schizophrenic patients and subsequent alterations of the biophysical parameters of neuronal membranes leading to structural changes in these areas.
    Pharmacopsychiatry 06/2011; 44(4):161-2. · 2.11 Impact Factor
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    ABSTRACT: In this study, the association of aggressive behavior and personality traits with plasma cortisol levels was investigated in a high-risk community sample of adolescents. Plasma cortisol levels were collected in 245 fifteen-year-olds (118 males, 127 females) from an epidemiological cohort study of children at risk for psychopathology. Additionally, measures of reactive and proactive aggression, externalizing behavior and callous-unemotional together with impulsive personality features were assessed. Both subtypes of aggression as well as delinquent behavior and impulsive personality traits showed significant negative correlations with plasma cortisol levels. This association was observed in males, but not in females. In both gender groups, callous-unemotional traits were unrelated to plasma cortisol levels. This result suggests that the association between cortisol levels and aggression in adolescents is mediated rather by impulsivity than by unemotional or psychopathic traits.
    Journal of Neural Transmission 03/2010; 117(5):621-7. · 3.05 Impact Factor
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    ABSTRACT: β-amyloid peptide (Aβ) and several Aβ-fragments decrease the fluidity of human cortex membranes in a concentration dependent fashion. The effect of Aβ on membrane fluidity increases with peptide length, is most pronounced for Afil-43 and can be seen at concentrations as low as 100 nmol/l. While the fragment Aβ25-3′5 is active, scrambled peptide (Aβ35-25) when investigated under similar conditions shows no effects on membrane fluidity. The effect of Aβ peptides on fluidity of the phospholipid bilayer is more pronounced in the hydrocarbon core (labeled with the fluorescence probe 1,6-diphenylhexa-l,3,5-triene) than in the region of the hydrophilic heads (labeled with the fluorescence probe l-[4 '-(trimethylamino)phenyl]-6-phenylhexa-1,3,5-triene). It is suggested that the effect of Aft on neuronal membranes is probably a major initial mechanism in a cascade of events finally leading to neurotoxicity and cell death in Alzheimer's disease.
    Amyloid. 07/2009; 5(1).
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    ABSTRACT: A serotonergic dysfunction, in particular a reduced serotonergic neurotransmission in the frontal cortex and limbic brain regions, has been discussed in connection with the aetiology of aggressive and impulsive behaviour. Assessment of the activity in the central serotonergic system in children and adolescents is limited due to its technical complexity and ethical restrictions. Therefore, peripheral serotonergic parameters have been used as a model to obtain deeper insight into central serotonergic functions. The aim of this investigation is to examine the significance of plasma serotonin measurement with regard to behavioural problems in adolescents at risk for psychopathology. Within the framework of a prospective longitudinal study of children at risk, serotonin levels in platelet-free blood plasma were measured in a group of n = 10 adolescents aged 15 years with persistent externalizing behaviour (T-score > or = 60 on the "Externalizing Problems" scale of the CBCL) and in a control group of n = 20 mentally undisturbed adolescents. Groups were matched according to age and gender. Externalizing behaviour was assessed by means of a parent questionnaire, the Achenbach Child Behavior Checklist (CBCL). Significantly lower levels of plasma serotonin were found in adolescents with persistent behaviour problems than in the control group. Significant negative correlations between serotonin levels and the CBCL scales "Aggressive Behavior" and "Externalizing Problems" were obtained for the total sample. Earlier findings that described a serotonergic deficit as a key mechanism in the manifestation of aggressive and antisocial behaviour are confirmed for adolescents at risk taken from a community sample.
    Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie 01/2006; 34(1):29-35. · 0.99 Impact Factor
  • Zeitschrift Fur Kinder-und Jugendpsychiatrie Und Psychotherapie - Z KINDER JUGENDPSYCHIAT PSYCH. 01/2006; 34(1):29-36.
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    ABSTRACT: Fluoxetine, a selective serotonin reuptake inhibitor (SSRI), and trimipramine, a tricyclic antidepressant (TCA), were compared in terms of efficacy and tolerability in a six-week, parallel group, double-blind pilot study in 41 geriatric patients with major depression (61 - 85 years old). The Hamilton Rating Scale for Depression (HAMD-17), the Montgomery-Asberg Rating Scale (MADRS), the Adjective Mood Scale (Bf-S), the Clinical Global Impression (CGI), and the Patients Global Impression (PGI) were used to measure changes in depressive symptoms. Improvement with treatment was found on all scales. Efficacy and tolerability were similar in both groups. No statistically significant differences were found. These findings suggest that fluoxetine and trimipramine are comparable in terms of efficacy and tolerability in the treatment of major depression in geriatric patients.
    Pharmacopsychiatry 02/2005; 38(1):13-6. · 2.11 Impact Factor
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    ABSTRACT: The atypical antipsychotic olanzapine has extensively been compared with haloperidol, whereas studies vs. other (conventional) neuroleptics are scarce. This exploratory double-blind 4-week study was designed to compare the efficacy and the safety of olanzapine (OLA) and flupenthixol (FLU) which have recently been considered as a "partially atypical" antipsychotics. Twenty-eight inpatients with schizophrenia (DSM-IV) were randomly assigned for treatment with OLA (N = 15, 5-20 mg/d) or FLU (N = 13, 5-20 mg/d). The Brief Psychiatric Rating Scale (BPRS) and the Negative Symptoms Rating Scale (NSRS), plus the Patient Global Impression (PGI) and Clinical Global Impression (CGI) scales, were used to assess the efficacy of both compounds; safety was determined by using the Simpson Angus Scale (SAS) and the Abnormal Involuntary Movement Scale (AIMS) and by assessing treatment-emergent adverse events. Non-parametric statistics were applied. BPRS and NSRS scores improved in both groups (exploratory tests; all p < or = 0.02). Similar results were observed for CGI-Severity, CGI- and PGI-Improvement. There were no significant group differences. Responder rates (at least 40 % decrease in BPRS total) were 9/13 OLA patients (69 %) and 9/12 FLU patients (75 %). EPS events were reported only in the FLU group (p < 0.01); FLU patients needed significantly more anticholinergic medication. Weight gain was higher in OLA patients (p < 0.01). Overall, fewer patients with adverse events were observed in the OLA group (p = 0.04). No significant changes were noted on SAS and AIMS scores. Findings from this study suggest that overall and negative symptomatology improved in both treatment groups, while the safety and tolerability profiles differed for both substances.
    Pharmacopsychiatry 11/2004; 37(6):279-85. · 2.11 Impact Factor
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    ABSTRACT: Membrane lipids are important mediators of neuronal function. In a postmortem study, we measured membrane lipid components in the left thalamus of schizophrenic patients. This region might play an important role in the pathophysiology of schizophrenia and has not been studied thus far with respect to its membrane lipid composition. The study included 18 chronic schizophrenic patients and 23 healthy control subjects. Using lipid extraction and thin-layer chromatography, we measured membrane phospholipids, galactocerebrosides 1 and 2, and sulfatides in thalamus homogenate. The main membrane phospholipid phosphatidylcholine and the major myelin membrane components sphingomyelin and galactocerebrosides 1 and 2 were found to be decreased in schizophrenic patients. In contrast, phosphatidylserine was increased. These lipid contents did not correlate with postmortem intervals and medication doses. There was no difference in the membrane phospholipids lysophosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidylglycerol or in sulfatides. Our results confirm findings of magnetic resonance imaging, postmortem, and gene expression studies. They support the notion of an increased phospholipid breakdown in schizophrenia as a sign for decreased myelination and oligodendrocyte dysfunction.
    Biological Psychiatry 08/2004; 56(1):41-5. · 9.25 Impact Factor
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    ABSTRACT: In recent years, a growing number of studies has focused on the dopamine D4 receptor gene (DRD4) as mediating the susceptibility to attention-deficit/hyperactivity disorder (ADHD). While their results are contradictory, the reason for this inconsistency remains as yet unclear. The present study sought to examine the association between ADHD and the DRD4 exon III polymorphism during child development using longitudinal data from a high-risk community sample (n = 265, 129 females, 126 males) who have been followed from birth to 11 years of age. Higher rates of ADHD were observed in boys with the 7 repeat allele of exon III than in boys with other alleles at the ages of 4 1/2 (Fisher's exact test, p = .061), 8 (p = .026), and 11 years (p = .005). Boys with this allele also exhibited higher rates of persistent disorder (p = .024). In girls, a trend towards an association (p = .055) with the 7 repeat allele emerged only at preschool age. These findings provide additional evidence for the role of the dopamine D4 receptor in ADHD during the course of child development.
    Journal of Neural Transmission 08/2004; 111(7):883-9. · 3.05 Impact Factor
  • European Neuropsychopharmacology - EUR NEUROPSYCHOPHARMACOL. 01/2004; 14.
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    ABSTRACT: While an association between androgens and different types of aggression has been well documented in male offenders, the influence of androgens on externalizing behavior in adolescents at risk for antisocial behavior has not been investigated so far. Plasma levels of the main androgen metabolites testosterone (T) and 5alpha-dihydrotestosterone (DHT) were measured in N = 87 fourteen-year-old (36 boys, 51 girls) from a prospective longitudinal study of children at risk. Externalizing behavior at age 8, 11 and 14 was assessed using the Achenbach Child Behavior Checklist (CBCL) and Teacher Report Form (TRF). Significant higher androgen levels (T, DHT) were found in male, but not in female adolescents with elevated scores of externalizing behavior. Moreover, boys with persistent externalizing behavior exhibited the highest levels of plasma androgens. There is a link between T, DHT and externalizing behavior in male adolescents at risk for psychopathology. Due to the findings of highest androgen levels in boys with persistent externalizing behavior, a role of androgens in the development of disruptive or later antisocial disorders can be hypothesized.
    Psychoneuroendocrinology 11/2003; 28(7):932-40. · 5.14 Impact Factor
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    ABSTRACT: An increase of intoxications in persons using psychoactive plants and mushrooms can be observed. Mainly adolescents are experimenting with this group of plants for its hallucinogenic effects and easy and cheap availability. A case of a toxic psychosis with hallucinations, disturbances of orientation and psychomotoric agitation and anxiety after the intake of Hawaiian baby wood rose seed, an exotic ergotalkaloid containing plant often misused for its hallucinogenic effect is reported. Other drug-induced psychosis (e.g. LSD-psychosis), schizophrenic episodes or anticholinergic drug-induced intoxications have to be excluded. Regarding the increasing spreading of the misuse of psychoactive plants in Europe and North America intoxications with severe fatal sequelae have to be expected for the future. The knowledge of the clinical picture is important for correct diagnosis and treatment.
    Psychiatrische Praxis 06/2003; 30(4):223-4. · 1.64 Impact Factor
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    ABSTRACT: While an association between androgens and different types of aggression has been well documented in male offenders, the influence of androgens on externalizing behavior in adolescents at risk for antisocial behavior has not been investigated so far. Plasma levels of the main androgen metabolites testosterone (T) and 5a-dihydrotestosterone (DHT) were measured in N = 119 14-year-olds (51 boys, 68 girls) from a prospective longitudinal study of children at risk. The Achenbach Child Behavior Checklist (CBCL) and the Youth Self Report Form (YSR) were used to assess externalizing behavior at age 14. The CBCL revealed significant positive correlations between DHT levels and the subscales "externalizing problems" and the problem scales "aggressive behavior" and "delinquent behavior" in male adolescents. Only the YSR subscale "delinquent behavior" exhibited a marginally significant association with DHT. Neither scale showed any significant correlations between androgen levels and externalizing behavior in female adolescents. Earlier findings of androgen effects on aggressive and antisocial behavior in male offenders were confirmed for male adolescents from a general population sample. The results stress the importance of the androgen metabolite DHT.
    Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie 03/2003; 31(1):7-15. · 0.99 Impact Factor
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    ABSTRACT: Steroid synthesis inhibitors are commonly used in the treatment of patients with Cushing's disease, but may also improve psychopathology in hypercortisolemic depressed patients. Since glucocorticoids exert a negative feedback at pituitary and supra-pituitary levels, the inhibition of steroid synthesis may lead to increased expression of corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP). We studied the effect of treatment with 800 mg ketoconazole (3 weeks) upon the concentrations of basal plasma cortisol in the evening, corticosteroid-binding globulin (CBG), dehydroepiandrosterone-sulfate (DHEA-S), and ACTH as well as the concentrations of cortisol, CRH, and AVP in cerebrospinal fluid (CSF) at 8.30 h in 10 healthy, male volunteers. While we found cortisol plasma concentrations to be unchanged, we noted a significant increase in ACTH (post: 45.1+/-43.5; pre: 14.2+/-5.2 pmol/l; F(1,8)=9.78, p<0.02) and CBG concentrations (post: 38.8+/-4.3; pre: 31.9+/-4.2 microg/l), but DHEA-S plasma concentrations declined (post: 1.75+/-1.83; pre: 2.75+/-2.80 mg/l; F(1,8)=7.9, p<0.03). CRH concentrations in CSF were unchanged after treatment (post: 62.5+/-15.9; pre: 63.7+/-13.9 pg/ml), while there was a trend for AVP concentrations to rise during treatment (post: 2.52+/-1.18; pre: 1.92+/-0.96 pg/ml; paired t=-1.9, p<0.1). Cortisol CSF concentrations declined in the elderly (pre: 52.5+/-23.2; post: 26.7+/-4.6 nmol/l), but not in the young subgroup (pre: 15.6+/-11.3; post: 27.7+/-9.4 nmol/l). We thus conclude that the treatment of healthy controls with steroid-synthesis inhibitors does not lead to a major increase in CRH secretion.
    Neuropsychopharmacology 02/2003; 28(2):379-83. · 8.68 Impact Factor
  • Zeitschrift Fur Kinder-und Jugendpsychiatrie Und Psychotherapie - Z KINDER JUGENDPSYCHIAT PSYCH. 01/2003; 31(1):7-15.
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    ABSTRACT: To date numerous in-vivo (31)P-MRS and in-vitro studies in schizophrenic patients have been able to demonstrate changes in their membrane phospholipid metabolism, which might be relevant for the cause and the therapeutic responsiveness of this disorder. Thus far, however, only limited studies exist regarding the specificity of these findings for schizophrenia and the effect of antipsychotic medication. The present study examined the composition of membrane phospholipids in platelets of 67 neuroleptic-free schizophrenic patients compared to healthy and psychiatric controls. In a subsample of the schizophrenic patients we determined the effect of antipsychotic treatment on the phospholipid metabolism during six-months follow up. While untreated patients showed a decrease in major membrane phospholipid components, i.e. phosphatidylcholine and phosphatidylethanolamine, when compared to control subjects, as well as an increase in their breakdown-product lysophosphatidylcholine (LPC), there was a significant reduction in LPC during three weeks of pharmacotherapy with haloperidol. After six months treatment with different antipsychotics some divergent effects on phospholipid metabolism in schizophrenic patients could be demonstrated. While in the long-term course LPC remained decreased under continuous therapy with typical neuroleptics, patients being treated with the atypical drug zotepine showed an increase in LPC compared to their baseline level before therapy. Thus, specific mechanisms of the different antipsychotic therapies on phospholipid metabolism might serve to explain the divergent findings of (31)P-MRS in medicated patients.
    Fortschritte der Neurologie · Psychiatrie 12/2001; 69(11):503-9. · 0.85 Impact Factor
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    ABSTRACT: There is compelling evidence that depression constitutes an independent risk factor for cardiovascular morbidity and mortality. As exaggerated platelet reactivity is associated with an increased risk of intra-arterial thrombus formation, we studied platelet aggregability in patients with major depression both before and after 5 weeks of anti-depressant therapy as well as in healthy control subjects. Twenty-two depressed patients and 24 healthy control subjects participated in the study. Washed and rediluted platelets were stimulated with the agonists collagen and thrombin in three concentration steps. Depression was associated with a higher aggregability after stimulation with thrombin in the intermediate concentration and with collagen at the low concentration, with ceiling effects for the other concentrations. After 5 weeks of anti-depressant therapy, aggregability was somewhat less exaggerated, although this effect did not reach statistical significance. We thus conclude that major depression is associated with increased platelet aggregability, which seems to persist even under a marked improvement in depressive symptomatology. This effect may contribute to the increased cardiovascular morbidity in depressed patients.
    Psychiatry Research 08/2001; 102(3):255-61. · 2.68 Impact Factor
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    ABSTRACT: The effects of trimipramine, a tricyclic antidepressant (TCA) with atypical pharmacological properties, and fluoxetine, a selective serotonine reuptake inhibitor (SSRI), were compared in an exploratory analysis using mood and polysomnographic parameters during a six-week double-blind trial in 19 depressed geriatric patients. In sleep EEG measures, trimipramine demonstrated clear-cut effects on sleep measures resulting in higher values for sleep efficiency, total sleep time, stage 2 sleep, and shorter wake time. Under fluoxetine treatment, the proportion of REM sleep was decreased and REM latency was lengthened, whereas no change in REM sleep parameters was observed in the trimipramine group. The present data suggest that early antidepressant effects of medication occur independently of drug-induced changes in objective measures of sleep, i.e. suppression of REM sleep.
    Pharmacopsychiatry 04/2001; 34(2):60-5. · 2.11 Impact Factor
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    ABSTRACT: Several studies have shown an increased membrane phospholipid turnover in brain and blood cells of schizophrenic patients. However the specificity of these findings for schizophrenia and the effects of longterm antipsychotic treatment had yet to be demonstrated. In the present study we measured the concentrations of phospholipids in platelet membranes from 67 neuroleptic-free schizophrenic patients compared to both healthy and psychiatric controls, followed by repeated measurements during a 6 months antipsychotic treatment period. At baseline, levels of the main phospholipid components phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were decreased and lysophosphatidylcholine (LPC), a major breakdown product of phospholipid metabolism, was increased in schizophrenic patients compared to healthy and to psychiatric controls, suggesting a specificity of the findings for schizophrenia. During the first 3-weeks on antipsychotic drug treatment LPC levels decreased to control values, but increased again during the following 6 months, reaching significantly higher levels than controls at the end of this period. Thus, at least in peripheral cells an increased breakdown of phospholipids in schizophrenia appears to be present during the acute episode, being influenced only by initial antipsychotic treatment, but without evidence of a long lasting treatment effect on membrane metabolism.
    Journal of Neural Transmission 02/2001; 108(8-9):1081-91. · 3.05 Impact Factor
  • Fortschritte Der Neurologie Psychiatrie - FORTSCHR NEUROL PSYCHIAT. 01/2001; 69(11):503-509.

Publication Stats

576 Citations
73.76 Total Impact Points

Institutions

  • 2011
    • University of São Paulo
      • Instituto de Psiquiatria (iPq)
      Ribeirão Preto, Estado de Sao Paulo, Brazil
  • 1996–2009
    • Central Institute of Mental Health
      • Klinik für Abhängiges Verhalten und Suchtmedizin
      Mannheim, Baden-Württemberg, Germany
  • 2006
    • Leiden University
      Leyden, South Holland, Netherlands
  • 2005
    • Lilly Deutschland GmbH
      Homburg vor der Höhe, Hesse, Germany