Development and validity data of the Brazilian Internet Study on Temperament and Psychopathology (BRAINSTEP).

BACKGROUND: The internet provides a research opportunity for psychiatry and psychology. This article presents the development and preliminary data of a large web-survey created to study how temperament relates to other psychological measures, behavior and psychiatric disorders. METHODS: We used the Affective and Emotional Composite Temperament Scale (AFECTS) to evaluate temperament and we selected several self-report instruments to evaluate behavior, psychological constructs and mental disorders. The system provides anonymous psychological (phase 1) and psychiatric (phase 2) feedback and includes questions to assess the validity of the answers. Each phase has around 450 questions. This system was broadcast utilizing Brazilian media. RESULTS: After the exclusion of 21.5% of the volunteers (those who failed the validation questions), 41,427 participants concluded the first part of the system (mean age=31.2±10.5 yrs, 26.9% males), and 21,836 (mean age=32.5±10.9 yrs, 25.1% males) completed phase 2. Around 25% have received a psychiatric diagnosis from a mental health professional. Demographic and temperament profiles of those who completed either only 80 questions, only phase 1, or the whole system were similar. The rate of non-serious answers (e.g. on bizarre behaviors) was very low and congruency of answers was very high. The internal consistency of classical trait scales (TCI-R and PANAS) was high (Cronbach's alpha>0.80) for all dimensions. LIMITATIONS: Relatively high dropout rate due to the length of the process and an overrepresentation of female, young and well-educated subjects. CONCLUSIONS: The BRAINSTEP provides valid and abundant data on psychological and psychiatric measures.

The Affective and Emotional Composite Temperament (AFECT) model and scale: a system-based integrative approach.

UNLABELLED: Based on many temperament frameworks, here we propose an integration of emotional and affective temperaments (the AFECT model), forming a common substrate for mood, behavior, personality and part of cognition. Temperament is conceived as a self-regulated system with six emotional dimensions: volition, anger, inhibition, sensitivity, coping and control. The different combinations of these emotional dimensions result in 12 affective temperament types, namely depressive, anxious, apathetic, obsessive, cyclothymic, dysphoric, irritable, volatile, disinhibited, hyperthymic and euphoric. We also developed and validated a self-report scale to evaluate this construct, the Affective and Emotional Composite Temperament Scale (AFECTS). METHODS: Exploratory and confirmatory psychometric analyses were performed with the internet version of the AFECTS in 2947 subjects (72% females, 35±11years old). RESULTS: The factors interpreted as volition, anger, inhibition, sensitivity, coping and control showed very good Cronbach's alphas for 5 dimensions (0.87-0.90) and acceptable alpha for inhibition (0.75). Confirmatory factor analysis corroborated this 6-factor structure when considering inhibition as a second-order factor with fear and caution as first-order factors (SRMR=0.061; RMSEA=0.053). In the Affective section, all 12 categorical affective temperaments were selected in the categorical choice, with 99% of volunteers identifying at least one adequate description of their affective temperament. LIMITATIONS: Only the internet version was used in a general population sample. CONCLUSION: The AFECT model provides an integrated framework of temperament as a self-regulated system, with implications for mental health, psychiatric disorders and their treatment. The AFECTS showed good psychometric properties to further study this model.

Is flunarizine a long-acting oral atypical antipsychotic? A randomized clinical trial versus haloperidol for the treatment of schizophrenia.

BACKGROUND: Flunarizine is known as a nonspecific calcium channel blocker that has been used for decades for the treatment of migraine, vertigo, and cognitive deficits related to cerebrovascular disorders. Flunarizine also has dopamine D2 receptor blocking properties and was effective in animal models of predictive validity for antipsychotics. However, its clinical antipsychotic efficacy has never been investigated. OBJECTIVE: To evaluate the therapeutic efficacy and tolerability of flunarizine compared to haloperidol in outpatients with stable and chronic DSM-IV-defined schizophrenia and schizoaffective disorder. METHOD: Seventy patients from 2 centers were randomly assigned and participated in a double-blind, parallel-group, flexible-dose study comparing flunarizine (10-50 mg/day) and haloperidol (2.5-12.5 mg/day) for 12 weeks. Patients were assessed with the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions-Improvement (CGI-I) scale, the Extrapyramidal Symptom Rating Scale (ESRS), a battery for cognitive performance, and laboratory examinations. The study was conducted from September 2004 to May 2007. RESULTS: Mean doses at endpoint were 29.7 mg/day for flunarizine and 6.4 mg/day for haloperidol. Both groups showed significant symptom improvement during the study, with a reduction of 21% in the flunarizine group and 19% in the haloperidol group in PANSS total scores (p < .05). There were no significant differences in PANSS overall score and all subscales, CGI-I score, or cognitive performance. Dropout rates, ESRS scores, and prolactin levels were not different between groups, but significantly more patients reported emergence of akathisia in the haloperidol group (p = .04), and weight gain was significantly higher with flunarizine (1.2 kg) than with haloperidol (-0.8 kg) (p < .05). CONCLUSION: This is the first study evaluating the antipsychotic properties of flunarizine, which showed good efficacy and tolerability for the treatment of schizophrenia, with a possible atypical profile. Its unique pharmacokinetic profile as an oral drug with long half-life (2-7 weeks), low cost, and low induction of extrapyramidal symptoms warrants further investigation, particularly in psychiatric patients with low adherence to treatment.

A case series on the hypothesized connection between dementia and bipolar spectrum disorders: bipolar type VI?

BACKGROUND: The concept of bipolar spectrum disorders has opened therapeutic opportunities for patients with atypical and complex affective conditions. The literature has recently described several commonalities in pathophysiological processes of bipolar disorders and dementia. However, this connection has been insufficiently appreciated at the clinical level, in part because affective dysregulation in the elderly and, particularly in the dementia setting, is typically attributed either to secondary depressive states or otherwise relegated to a neurologically understandable behavioral complication resulting from cerebral disease. METHODS: We selected a case series of 10 elderly patients with late-onset mood and related behavioral symptomatology and cognitive decline without past history of clear-cut bipolar disorder. Clinical features, temperament, cognition, family history and pharmacological response were assessed to identify prototypical patients to illustrate the complexities of the dementia-bipolar interface. RESULTS: Mixed and depressive mood symptoms were most commonly observed and all patients had been premorbidly of hyperthymic, cyclothymic and/or irritable temperaments. Most patients had a family history of bipolar disorder or disorders related to the bipolar diathesis. Symptoms were often refractory to or aggravated by antidepressants and acetylcholinesterase inhibitors, whereas mood stabilizers and/or atypical antipsychotics were beneficial, promoting behavioral improvement in all treated patients and marked cognitive recovery in five. LIMITATIONS: Case series with retrospective methodology. CONCLUSION AND CLINICAL IMPLICATIONS: Patients with cognitive decline and frequent mood lability might be manifesting a late-onset bipolar spectrum disorder, which we posit as type VI. We further posit that dementia and/or other biopsychosocial challenges associated with aging might release latent bipolarity in such individuals. Antidepressants, even drugs targeting dementia, might aggravate the behavioral dysregulation in these patients. Evaluation of premorbid temperament and/or family history of bipolarity and related disorders might help in broadening the clinical and biological understanding of such patients, providing a rationale for better customized treatment along the lines of mood stabilization and avoidance of antidepressants.

Involvement of adenosine in the neurobiology of schizophrenia and its therapeutic implications.

Based on the neuromodulatory and homeostatic actions of adenosine, adenosine dysfunction may contribute to the neurobiological and clinical features of schizophrenia. The present model of adenosine dysfunction in schizophrenia takes into consideration the dopamine and glutamate hypotheses, since adenosine exerts neuromodulatory roles on these systems, and proposes that adenosine plays a role in the inhibitory deficit found in schizophrenia. Given the role of adenosine activation of adenosine A1 receptor (A1R) in mediating neurotoxicity in early stages of brain development, pre- and peri-natal complications leading to excessive adenosine release could induce primary brain changes (i.e., first hit). These events would lead to an adenosine inhibitory deficit through a partial loss of A1R that may emerge as reduced control of dopamine activity and increased vulnerability to excitotoxic glutamate action in the mature brain (i.e., second hit). Adenosine dysfunction is reasonably compatible with symptoms, gray and white matter abnormalities, progressive brain loss, pre- and peri-natal risk factors, age of onset, response to current treatments, impaired sensory gating and increased smoking in schizophrenia. Pharmacological treatments enhancing adenosine activity could be effective for symptom control and for alleviating deterioration in the course of the illness. Accordingly, allopurinol, which may indirectly increase adenosine, has been effective and well tolerated in the treatment of schizophrenia. Since much of the evidence for the adenosine hypothesis is preliminary and theoretical, further investigation in the field is warranted.

A clinical trial of adjuvant allopurinol therapy for moderately refractory schizophrenia.

OBJECTIVE: To evaluate the xanthine oxidase inhibitor allopurinol as an adjuvant treatment for patients with moderately refractory schizophrenia, with the objective of increasing the endogenous pool of purines, including the neuro-modulator adenosine. METHOD: A double-blind, placebo-controlled, crossover clinical trial of add-on allopurinol (300 mg b.i.d.) for poorly responsive schizophrenia or schizoaffective disorder (DSM-IV criteria) was conducted. Thirty-five patients were enrolled, of whom 22 completed the 12 weeks of the study. Eighteen of these patients also completed a P50 evoked potential evaluation. RESULTS: Allopurinol was well tolerated and produced significant improvement in Positive and Negative Syndrome Scale (PANSS) total, positive, negative, and general scores, particularly for positive symptoms compared with baseline and with placebo phase. Nine patients improved more than 20% in PANSS total score during allopurinol treatment, whereas none responded in the placebo phase. Responders had a shorter duration of illness than nonresponders. P50 auditory sensory gating failed to improve with allopurinol treatment. CONCLUSIONS: Allopurinol was an effective and well-tolerated adjuvant treatment for poorly responsive schizophrenia, especially for refractory positive symptoms.