Consortium neuroscience of attention deficit/hyperactivity disorder and autism spectrum disorder: The ENIGMA adventure.

Neuroimaging has been extensively used to study brain structure and function in individuals with attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) over the past decades. Two of the main shortcomings of the neuroimaging literature of these disorders are the small sample sizes employed and the heterogeneity of methods used. In 2013 and 2014, the ENIGMA-ADHD and ENIGMA-ASD working groups were respectively, founded with a common goal to address these limitations. Here, we provide a narrative review of the thus far completed and still ongoing projects of these working groups. Due to an implicitly hierarchical psychiatric diagnostic classification system, the fields of ADHD and ASD have developed largely in isolation, despite the considerable overlap in the occurrence of the disorders. The collaboration between the ENIGMA-ADHD and -ASD working groups seeks to bring the neuroimaging efforts of the two disorders closer together. The outcomes of case-control studies of subcortical and cortical structures showed that subcortical volumes are similarly affected in ASD and ADHD, albeit with small effect sizes. Cortical analyses identified unique differences in each disorder, but also considerable overlap between the two, specifically in cortical thickness. Ongoing work is examining alternative research questions, such as brain laterality, prediction of case-control status, and anatomical heterogeneity. In brief, great strides have been made toward fulfilling the aims of the ENIGMA collaborations, while new ideas and follow-up analyses continue that include more imaging modalities (diffusion MRI and resting-state functional MRI), collaborations with other large databases, and samples with dual diagnoses.

Gray Matter Volume in Elderly adults With ADHD: Associations of Symptoms and Comorbidities With Brain Structures.

Objective: To investigate total and selected region-of-interest-based gray matter volume (GMV) in older adults with ADHD. Method: Twenty-five elderly (≥65 years old) patients with ADHD and 34 healthy controls underwent 1.5-T magnetic resonance imaging (MRI). We used voxel-based morphometry to compare GMV between groups and performed a correlation analysis with ADHD symptoms and comorbidities. Results: Findings revealed a smaller total GMV in males with ADHD and a smaller GMV in the right medial frontal orbital area extending toward the medial frontal superior, the frontal superior, and the subgenual anterior cingulate cortex (ACC) besides correlations between inattentiveness and ACC (bilaterally) and left cerebellum, hyperactivity/impulsivity and the left frontal inferior orbital, depression and caudate (bilaterally), and the right inferior parietal lobule. Conclusion: Neural correlates in regions related to attention, executive control, and affective processing suggest that impairments in frontostriatal and frontoparietal-cerebellar areas observed in adults with ADHD persist into old age.

Longitudinal Neuropsychological Assessment in Two Elderly Adults With Attention-Deficit/Hyperactivity Disorder: Case Report.

The neuropsychological deficits in attention-deficit/hyperactivity disorder (ADHD) may present clinical features similar to mild and/or major neurocognitive disorder and may act as a confounding factor, making it difficult to detect cognitive decline. In this paper, we present the results of longitudinal neuropsychological evaluations in two elderly women with ADHD. Three neuropsychological assessments were performed in two women with ADHD (60 and 77 years old) between 2010 and 2013 at intervals varying from 12 to 15 months. We used structural magnetic resonance imaging to rule out significant abnormalities that could account for cognitive impairment. The results showed two different cognitive profiles with fluctuations in performance over these 2 years, sometimes with improvement and sometimes with decline of some functions such as attention, memory, inhibitory control, and reaction time. To minimize confounding aspects of these fluctuations in clinical practice, we used a longer follow-up with the application of a reliable change index and a minimum of three spaced assessments to provide a more consistent baseline cognitive profile. Our findings did not indicate a consistent cognitive decline, suggesting a less pessimistic perspective about cognitive impairments that could be a prodrome of ADHD-related dementia.

Influence of emotional stimulus valence on inhibitory control in adults with and without ADHD.

Human behavior is influenced both by approach and avoidance automatic reactions to positive and negative stimulus, respectively, but these reactions have not been well studied in attention-deficit/hyperactivity disorder (ADHD) patients. Moreover, studies employing spatial stimulus-response compatibility tasks in ADHD and healthy control (HC) subjects are scarce and inconclusive. The present study investigated inhibitory control and emotional processing in ADHD adults with a modified stimulus-response compatibility task in which spatial and emotional features of affective stimuli had to be processed together to select the correct response. Manual responses to figures of Favorite and Rival soccer team players were measured, and compatible or incompatible responses were chosen according to the soccer team figure. Eighteen HC participants and sixteen ADHD adults performed the task. We found an ordinary spatial compatibility effect for the Favorite soccer team and a reversed one for the Rival team in the ADHD group but not in the HC group. The effects may be due to stronger approach and withdrawal reactions toward the Favorite soccer team and away from the Rival one, respectively, indicating poor inhibitory control for the ADHD group. These results show that differences between ADHD and HC subjects become prominent when response selection involves both emotional and spatial features of the stimulus.

Patterns of regional gray matter loss at different stages of schizophrenia: A multisite, cross-sectional VBM study in first-episode and chronic illness.

BACKGROUND: Structural brain abnormalities in schizophrenia have been repeatedly demonstrated in magnetic resonance imaging (MRI) studies, but it remains unclear whether these are static or progressive in nature. While longitudinal MRI studies have been traditionally used to assess the issue of progression of brain abnormalities in schizophrenia, information from cross-sectional neuroimaging studies directly comparing first-episode and chronic schizophrenia patients to healthy controls may also be useful to further clarify this issue. With the recent interest in multisite mega-analyses combining structural MRI data from multiple centers aiming at increased statistical power, the present multisite voxel-based morphometry (VBM) study was carried out to examine patterns of brain structural changes according to the different stages of illness and to ascertain which (if any) of such structural abnormalities would be specifically correlated to potential clinical moderators, including cumulative exposure to antipsychotics, age of onset, illness duration and overall illness severity. METHODS: We gathered a large sample of schizophrenia patients (161, being 99 chronic and 62 first-episode) and controls (151) from four previous morphometric MRI studies (1.5 T) carried out in the same geographical region of Brazil. Image processing and analyses were conducted using Statistical Parametric Mapping (SPM8) software with the diffeomorphic anatomical registration through exponentiated Lie algebra (DARTEL) algorithm. Group effects on regional gray matter (GM) volumes were investigated through whole-brain voxel-wise comparisons using General Linear Model Analysis of Co-variance (ANCOVA), always including total GM volume, scan protocol, age and gender as nuisance variables. Finally, correlation analyses were performed between the aforementioned clinical moderators and regional and global brain volumes. RESULTS: First-episode schizophrenia subjects displayed subtle volumetric deficits relative to controls in a circumscribed brain regional network identified only in small volume-corrected (SVC) analyses (p < 0.05, FWE-corrected), including the insula, temporolimbic structures and striatum. Chronic schizophrenia patients, on the other hand, demonstrated an extensive pattern of regional GM volume decreases relative to controls, involving bilateral superior, inferior and orbital frontal cortices, right middle frontal cortex, bilateral anterior cingulate cortices, bilateral insulae and right superior and middle temporal cortices (p < 0.05, FWE-corrected over the whole brain). GM volumes in several of those brain regions were directly correlated with age of disease onset on SVC analyses for conjoined (first-episode and chronic) schizophrenia groups. There were also widespread foci of significant negative correlation between duration of illness and relative GM volumes, but such findings remained significant only for the right dorsolateral prefrontal cortex after accounting for the influence of age of disease onset. Finally, significant negative correlations were detected between life-time cumulative exposure to antipsychotics and total GM and white matter volumes in schizophrenia patients, but no significant relationship was found between indices of antipsychotic usage and relative GM volume in any specific brain region. CONCLUSION: The above data indicate that brain changes associated with the diagnosis of schizophrenia are more widespread in chronic schizophrenia compared to first-episode patients. Our findings also suggest that relative GM volume deficits may be greater in (presumably more severe) cases with earlier age of onset, as well as varying as a function of illness duration in specific frontal brain regions. Finally, our results highlight the potentially complex effects of the continued use of antipsychotic drugs on structural brain abnormalities in schizophrenia, as we found that cumulative doses of antipsychotics affected brain volumes globally rather than selectively on frontal-temporal regions.

Cognition and impulsivity in adults with attention deficit hyperactivity disorder with and without cocaine and/or crack dependence.

BACKGROUND: Substance use disorder (SUD) is a common comorbidity in adults with attention deficit-hyperactivity disorder (ADHD). However,there have been few studies on cognitive profiles of these patients. Impulsivity is also commonly increased in both disorders. The central aim of this study was to compare cognition and impulsivity in subjects who had ADHD and cocaine dependence (ADHD+COC group) to those with ADHD only (ADHD-noSUD group). We hypothesized that the ADHD+COC group would show more marked cognitive dysfunction and greater impulsivity than their counterparts with ADHD only. METHODS: A total of 70 adult patients diagnosed with ADHD according to (DSM-IV-TR) criteria were enrolled; 36 with ADHD+COC and 34 with ADHD-noSUD. All study participants were evaluated with a sociodemographic questionnaire; the Mini International Neuropsychiatric Interview; the Adult ADHD Self-Report Scale; the Addiction Severity Index; the Alcohol, Smoking and Substance Involvement Screening Test; the Barratt Impulsiveness Scale; and a comprehensive neurocognitive battery. RESULTS: Compared to individuals with ADHD-noSUD, ADHD+COC individuals had significantly lower mean IQ and higher motor impulsivity. On average, the ADHD+COC group also performed more poorly on tasks assessing verbal skills, vigilance, implicit learning during decision making, and ADHD-noSUD performed more poorly on selective attention, information processing, and visual search. CONCLUSIONS: Our results support the integrative theory of ADHD based on the cognitive and affective neuroscience model, and suggests that ADHD-noSUD patients have impairments in cognitive regulation, while ADHD+COC patients have impairments in both cognitive and affective regulation.

Multimodal magnetic resonance imaging study of treatment-naïve adults with attention-deficit/hyperactivity disorder.

BACKGROUND: Attention-Deficit/Hiperactivity Disorder (ADHD) is a prevalent disorder, but its neuroanatomical circuitry is still relatively understudied, especially in the adult population. The few morphometric magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) studies available to date have found heterogeneous results. This may be at least partly attributable to some well-known technical limitations of the conventional voxel-based methods usually employed to analyze such neuroimaging data. Moreover, there is a great paucity of imaging studies of adult ADHD to date that have excluded patients with history of use of stimulant medication. METHODS: A newly validated method named optimally-discriminative voxel-based analysis (ODVBA) was applied to multimodal (structural and DTI) MRI data acquired from 22 treatment-naïve ADHD adults and 19 age- and gender-matched healthy controls (HC). RESULTS: Regarding DTI data, we found higher fractional anisotropy in ADHD relative to HC encompassing the white matter (WM) of the bilateral superior frontal gyrus, right middle frontal left gyrus, left postcentral gyrus, bilateral cingulate gyrus, bilateral middle temporal gyrus and right superior temporal gyrus; reductions in trace (a measure of diffusivity) in ADHD relative to HC were also found in fronto-striatal-parieto-occipital circuits, including the right superior frontal gyrus and bilateral middle frontal gyrus, right precentral gyrus, left middle occipital gyrus and bilateral cingulate gyrus, as well as the left body and right splenium of the corpus callosum, right superior corona radiata, and right superior longitudinal and fronto-occipital fasciculi. Volumetric abnormalities in ADHD subjects were found only at a trend level of significance, including reduced gray matter (GM) in the right angular gyrus, and increased GM in the right supplementary motor area and superior frontal gyrus. CONCLUSIONS: Our results suggest that adult ADHD is associated with neuroanatomical abnormalities mainly affecting the WM microstructure in fronto-parieto-temporal circuits that have been implicated in cognitive, emotional and visuomotor processes.

Influence of stimulant and non-stimulant drug treatment on driving performance in patients with attention deficit hyperactivity disorder: a systematic review.

Adults with Attention Deficit Hyperactivity Disorder (ADHD), especially teenagers and young adults, show important car driving impairments, including risky driving, accidents, fines and suspension of driver׳s license. We systematically reviewed the efficacy of stimulant and non-stimulant drugs on driving performance of ADHD patients. We searched several databases for randomized controlled trials (RCTs) published through March, 2013. Fifteen RCTs (the majority with crossover design) evaluated methylphenidate (MPH) immediate-release (MPH-IR), MPH osmotic-controlled oral system (MPH-OROS), MPH transdermal system (MTS), extended-release mixed amphetamine salts (MAS-XR); atomoxetine (ATX) and lisdexamfetamine (LDX). Methods varied widely; including simulators and/or cars and different courses and scenarios. Various outcomes of driving performance, including a 'composite' or 'overall' driving score were considered. In general, stimulants improved driving performance in ADHD patients (either in RCTs conducted in simulators and/or cars). MPH-OROS improved driving performance compared with MAS-XR, placebo, or no-drug conditions. Although MPH-OROS and MPH-IR produced similar improvements during the day, MPH-IR lost its efficacy in the evening. MAS-XR also improved driving performance, but worsened driving performance in the evening. MTS (one study) showed a positive effect, but drug compliance varied widely across patients. LDX had positive effect on driving (two studies with the same sample). Studies with ATX report conflicting results. Improvement was more consistent in teenagers and young adults. In general, treatment with psychostimulants or ATX in therapeutic dosages had no negative impact on driving performance of ADHD patients. To conclude, treatment with stimulants in therapeutic doses improves driving performance in ADHD patients, especially teenagers and young adults.

Switching from oral risperidone to flexibly dosed oral paliperidone extended-release: core symptoms, satisfaction, and quality of life in patients with stable but symptomatic schizophrenia: the RISPALI study.

OBJECTIVE: The purpose of this prospective study was to evaluate the effects of switching from oral risperidone to flexibly dosed oral paliperidone extended-release (ER) in Brazilian adults with schizophrenia because of lack of efficacy, intolerability, or nonadherence after a minimum trial of 30 days on adequate (labeled) doses of oral risperidone, according to individual clinical judgment. RESEARCH DESIGN AND METHODS: Subjects with Positive and Negative Syndrome Scale total scores above 78, and/or intolerable adverse effects, with risperidone received open-label paliperidone ER 3 to 12 mg daily for 26 (main phase) to 52 (extension phase) weeks. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01010776. RESULTS: The intent-to-treat (efficacy) populations comprised 213 subjects in the main phase and 159 in the extension phase. Of 213 subjects with baseline and post-baseline efficacy data, 154 (72.3%) switched from risperidone to paliperidone ER because of a lack of efficacy and 59 (27.7%) because of tolerability issues, according to individual clinical judgment. Paliperidone ER significantly (p < 0.0500) improved a broad spectrum of efficacy endpoints from baseline, as early as the first post-baseline visit (Visit 2; 4 weeks) and persisting through 26 to 52 weeks. On most efficacy endpoints, function improved from baseline to the first post-baseline visit (week 4) and remained significantly improved compared to baseline at each visit for paliperidone ER treatment, at weeks 8, 13, 26, 39, 26, and 52; data are reported herein mainly for 26 and 52 weeks compared to baseline. Significant improvements from baseline were observed for the Positive and Negative Syndrome Scale total score and subscale scores (each p < 0.0001 at 26 and 52 weeks vs. baseline); and personal and social functioning (p < 0.0001 at 26 and 52 weeks). Paliperidone ER also significantly improved health-related quality of life (Short-Form 36) from baseline, particularly on the Mental Component Summary (p = 0.0011 at 26 weeks and p = 0.0019 at 52 weeks). Treatment with paliperidone ER also significantly improved (vs. baseline) sleep quality (according to decreases on the Pittsburgh Sleep Quality Index; p < 0.0001 at each visit vs. baseline) and disease severity (Clinical Global Impression-Severity; p < 0.0001 at each visit vs. baseline). Paliperidone ER was well tolerated. Adverse events occurring in at least 10% of subjects in either phase were insomnia (14.9% in the main phase and 8.8% in the extension phase); increased body weight (10.7% and 12.6%, respectively); and anxiety (10.7% and 2.5%). Most of these adverse events were: 1) rated as mild or moderate; 2) did not prompt interventions such as paliperidone ER dose adjustment or interruption; and 3) decreased in frequency from the main to the extension phase. CONCLUSIONS: Oral paliperidone ER is a rational treatment alternative for patients with schizophrenia whose antipsychotic regimens are switched because of unsuccessful treatment with oral risperidone according to individual clinical judgment. Study limitations included the open-label study design, lack of placebo, and use of subjective clinical judgment to determine lack of efficacy, intolerability, or nonadherence with oral risperidone.

Insight, cognitive dysfunction and symptomatology in schizophrenia.

Lack of insight is frequent in schizophrenia and usually influences negatively both patient's treatment and prognosis. This study aimed to investigate the relationship between insight, symptomatology and cognitive dysfunctions in schizophrenia using the PANSS five-factor model (modified from Gaag et al. in Schizophr Res 85:280-287, 2006). Forty patients diagnosed with chronic schizophrenia (DSM-IV) were evaluated with the scale to assess unawareness of mental disorder (SUMD), the PANSS and a neuropsychological battery. Spearman correlation and linear regression analyses were performed to investigate the relationship between clinical, neurocognitive and insight measures. The SUMD current and past awareness of symptoms score showed a correlation with WCST indices (correct answers and non-persevering errors). The negative and disorganization factor of the PANSS showed a positive correlation with current and past awareness of symptoms. However, when submitted to a linear regression model only the disorganization factor emerged as significant contributor for insight. Considering that the core items of the "disorganization factor" of the PANSS are related to cognition (e.g., poor attention, difficult in abstract thinking), insight is associated cognitive symptoms although no direct relationship between insight and neuropsychological tests was observed.

Estudos multicêntricos da ziprasidona oral no tratamento de pacientes com esquizofrenia ou transtorno esquizoafetivo / Multicenter studies of oral ziprazidone for the treatment of patients with schizophrenia and schizoaffective disorder

Introdução: Através de dois estudos seqüenciais a eficácia, segurança e a tolerabilidade da ziprasidona oral foram avaliadas em pacientes brasileiros portadores de transtorno esquizofrênico ou esquizoafetivo. Métodos: Estudos prospectivos e abertos. No primeiro estudo os pacientes receberam entre 80 e 160 mg/dia de ziprasidona durante seis semanas e foram avaliados através da Positive and Negative Symptom Scale (PANSS), Impressão Clinica Global para Gravidade da doença (CGI-S), Questionário de Intensidade de Cuidados (ICQ) e Preferência do Paciente (PPS). A segurança e tolerabilidade foram avaliadas por análises clínica, eletrocardiográfica e laboratoriais, escala de Avaliação dos Sintomas Extrapiramidais (ESRS) e Avaliação de Acatisia de Barnes (BAS). Os pacientes com resposta ao tratamento poderiam ser incluídos no segundo estudo, com duração de até 12 meses. Resultados: No primeiro estudo 162 pacientes foram avaliados quanto à eficácia e 164 quanto à segurança e tolerabilidade. O tratamento reduziu o escore na escala PANSS a partir do início de 94,3 para 76,2 (P<0,0001). Também houve reduções significativas dos escores nas escalas CGI-S e ICQ. Através da PPS 64,8 dos pacientes preferiram a ziprasidona ao medicamento anterior. Não houve sintomas extrapiramidais significativos avaliados pela ESRS e BAS nem alterações eletrocardiográficas. Dos 106 pacientes incluídos no segundo estudo, 86 foram analisados quanto à eficácia. A duração mediana do tratamento foi de 5,6 meses e o escore médio na escala PANSS foi mantido. O perfil de eventos adversos ao longo dos dois estudos foi semelhante. Conclusão: A ziprasidona oral é eficaz e segura no tratamento crônico de pacientes portadores de esquizofrenia e distúrbio esquizoafetivo.

Questões atuais no tratamento farmacológico do TDAH em adultos com metilfenidato / Actual issues in the pharmacological treatment of ADHD in adults with methylphenidate

O tratamento farmacológico do transtorno do déficit de atenção com hiperatividade (TDAH) em adultos inclui o uso de psicoestimulantes, antidepressivos e atomoxetina, sendo o primeiro considerado a indicação de primeira escolha. A eficácia do metilfenidato foi demonstrada em adultos quando se empregavam doses maiores, proporcionalmente similares àquelas usadas em estudos em crianças. O perfil de eventos adversos do metilfenidato, incluindo aqueles relativos ao sistema cardiovascular, parece bastante seguro.

Pharmacotherapy of attention-deficit/hyperactivity disorder in adulthood includes psychostimulants, antidepressants and atomoxetine, the first of them being considered the first choice. Methylphenidate efficacy has been demonstrated in adults when higher doses were used, in a proportionate similar way to what has been described in children. Methylphenidate profile of adverse events, including cardiovascular ones, seems to be safe.

Attention deficit hyperactivity disorder (ADHD) in adults: social-demographic profile from a university hospital ADHD outpatient unit in São Paulo, Brazil.

PURPOSE: To describe the social-demographic variables, including interpersonal, academic, and professional performance in adult individuals with the diagnoses of attention deficit hyperactivity disorder (ADHD). There are no reports of this kind in the Brazilian population with ADHD. The ADHD is a common disorder, which can reach up to 3% of the general population. METHOD: Descriptive study of adults with ADHD, according to the DSM-IV criteria (American Psychiatric Association). The sample was selected from a specialized outpatient service in São Paulo city. The social-demographic data was obtained by personal interviews. RESULTS: There was a predominance of males in the sample (61.2%) and a high education level (90.2% had at least a high school degree) and 52% of the 102 patients had repeated their class at a least once during their school lives. In addition, 22.5% of the population sample were unemployed at the time of the interview. CONCLUSION: The distribution of the socio-demographic variables in adult ADHD is similar to other ADHD samples reported in other countries, despite the high education level met in our sample. Similarities between child and adult ADHD could also be traced.

Attention deficit hyperactivity disorder (ADHD) in adults: social-demographic profile from a university hospital ADHD outpatient unit in São Paulo, Brazil / Transtorno de déficit de atenção e hiperatividade (TDAH) no adulto: perfil sócio-demográfico de pacientes com TDAH atendidos em ambulatório de um hospital universitário de São Paulo, Brasil

PURPOSE: To describe the social-demographic variables, including interpersonal, academic, and professional performance in adult individuals with the diagnoses of attention deficit hyperactivity disorder (ADHD). There are no reports of this kind in the Brazilian population with ADHD. The ADHD is a common disorder, which can reach up to 3 percent of the general population. METHOD: Descriptive study of adults with ADHD, according to the DSM-IV criteria (American Psychiatric Association). The sample was selected from a specialized outpatient service in São Paulo city. The social-demographic data was obtained by personal interviews. RESULTS: There was a predominance of males in the sample (61.2 percent) and a high education level (90.2 percent had at least a high school degree) and 52 percent of the 102 patients had repeated their class at a least once during their school lives. In addition, 22.5 percent of the population sample were unemployed at the time of the interview. CONCLUSION: The distribution of the socio-demographic variables in adult ADHD is similar to other ADHD samples reported in other countries, despite the high education level met in our sample. Similarities between child and adult ADHD could also be traced.

OBJETIVO: Descrever as variáveis sócio-demográficas incluindo desempenho acadêmico, profissional e interpessoal em uma população adulta com diagnóstico de transtorno de déficit de atenção e hiperatividade (TDAH). Até o momento não há relato na literatura do perfil desses pacientes na população brasileira. O TDAH é comum na população geral, podendo chegar a 3 por cento das pessoas. MÉTODO: Foram avaliados adultos que tomaram conhecimento do serviço de atendimento especializado em TDAH através da mídia. O diagnóstico de TDAH foi realizado utilizando-se os critérios da Associação Psiquiátrica Americana (DSM-IV). Os dados sócio-demográficos foram obtidos através de entrevista pessoal com cada paciente. RESULTADOS: 102 indivíduos preencheram critérios para TDAH. Houve predomínio do sexo masculino (61,2 por cento) com alto nível de escolaridade (90,2 por cento tinham no mínimo 2° grau completo). Cinquenta e três pacientes (52 por cento) foram reprovados pelo menos uma vez durante vida estudantil. No momento da entrevista, 22,5 por cento encontravam-se desempregados. CONCLUSÃO: Observou-se uma semelhança da distribuição das variáveis sócio-demográficas com os indivíduos adultos com TDAH de outros países, apesar da escolaridade ser acima da média nacional. Além disso, pode-se também observar semelhanças entre as populações infantil e adulta com TDAH.

Conjugated estrogens as adjuvant therapy in the treatment of acute schizophrenia: a double-blind study.

In a double-blind, placebo controlled study, conjugated estrogens (CE) (0.625 mg/day) were added to a fixed dosage of haloperidol (5 mg daily). Forty-four female inpatients with acute schizophrenia were included in the study and randomized to one of the groups; 40 patients completed the trial. They were followed for 28 days and evaluated periodically with the BPRS, Negative Symptoms Rating Scale, Simpson Angus Extrapyramidal Rating Scale and UKU rating scale. Hormonal concentrations (estradiol, estrone, progesterone, FSH, LH and prolactine) were measured at baseline and weekly throughout the trial. Both groups showed similar clinical improvement during the evaluation, although there was a trend for the CE group to show a better improvement than the placebo group (p < 0.10). Side effects and the use of anticholinergics were similar in both groups. Conjugated estrogens caused elevation only of estrone levels in the CE group; estradiol and prolactin showed a similar profile for both groups. Our negative findings regarding the antipsychotic effect of conjugated estrogens does not preclude, however, a possible efficacy of other estrogens, such as 17-beta-estradiol, in schizophrenia.