Distinct sensitivity to caffeine-induced insomnia related to age.

Caffeine acts by antagonizing the effect of the endogenous homeostatic sleep factor adenosine. In the current study we aimed to evaluate the pattern of caffeine-induced insomnia and its relation to age and sex in a general population sample derived from a web survey. The sample included 75,534 participants (28.1% men) from 18 to 75 years who answered self-report questionnaires by accessing a website in Brazilian Portuguese (BRAINSTEP project). In our sample, 3620 (17.0%) men and 9920 (18.3%) women reported insomnia due to caffeine intake. Caffeine-induced insomnia increased with aging in both men and women. This difference remained after adjusting for sociodemographic, psychiatric and sleep related variables as well as caffeine intake. Women showed higher proportion of caffeine-induced insomnia than men, but this difference did not remain after controlling for covariates. Also, individuals with caffeine-induced insomnia reported poorer sleep quality, higher latency to fall asleep and a higher proportion of psychiatric diagnoses and daily use of hypnotic drugs. In conclusion, our results show an age-associated increase in caffeine-induced insomnia and poorer mental health indicators among people with caffeine-induced insomnia complaints.

Validation of the "rule of three", the "red sign" and temperament as behavioral markers of bipolar spectrum disorders in a large sample.

BACKGROUND: Akiskal proposed the "rule of three" for behavioral indicators with high specificity for bipolarity in patients with major depression episodes. We evaluated these distinctive behaviors in controls and subjects with major depression or bipolar disorder. METHODS: data was collected in the BRAINSTEP project with questions on general behaviors, style and talents. Univariate analysis was first conducted in 36,742 subjects and confirmatory multivariate analysis in further 34,505 subjects (22% with a mood disorder). Odds ratios were calculated adjusting for age. RESULTS: Univariate analysis showed that 29 behavioral markers differentiated bipolar subjects from those with unipolar depression. The most robust differences in those with bipolarity (ORs >4) were ≥3 religion changes, ≥3 marriages, cheating the partner regularly, having ≥60 lifetime sexual partners, pathological love, heavy cursing, speaking ≥3 foreign languages, having ≥2 apparent tattoos, circadian dysregulation and high debts. Most behaviors were expressed in a minority of patients (usually around 5-30%) and usually the "rule of three" was the best numerical marker to distinguish those with bipolarity. However, multivariate analysis confirmed 11 of these markers for differentiating bipolar disorder from unipolar depression (reversed circadian rhythm and high debts for both genders, ≥3 provoked car accidents and talent for poetry in men, and frequent book reading, ≥3 religion changes, ≥60 sexual partners, pathological love ≥2 times, heavy cursing and extravagant dressing style in women). LIMITATIONS: Self-report data collection only. CONCLUSIONS: These behavioral markers should alert the clinician to perform a thorough investigation of bipolarity in patients presenting with a depressive episode.

Thinking about dying and trying and intending to die: results on suicidal behavior from a large Web-based sample.

OBJECTIVE: Suicide is an important worldwide public health problem. The aim of this study was to characterize risk factors of suicidal behavior using a large Web-based sample. METHOD: The data were collected by the Brazilian Internet Study on Temperament and Psychopathology (BRAINSTEP) from November 2010 to July 2011. Suicidal behavior was assessed by an instrument based on the Suicidal Behaviors Questionnaire. The final sample consisted of 48,569 volunteers (25.9% men) with a mean ± SD age of 30.7 ± 10.1 years. RESULTS: More than 60% of the sample reported having had at least a passing thought of killing themselves, and 6.8% of subjects had previously attempted suicide (64% unplanned). The demographic features with the highest risk of attempting suicide were female gender (OR = 1.82, 95% CI = 1.65 to 2.00); elementary school as highest education level completed (OR = 2.84, 95% CI = 2.48 to 3.25); being unable to work (OR = 5.32, 95% CI = 4.15 to 6.81); having no religion (OR = 2.08, 95% CI = 1.90 to 2.29); and, only for female participants, being married (OR = 1.19, 95% CI = 1.08 to 1.32) or divorced (OR = 1.66, 95% CI = 1.41 to 1.96). A family history of a suicide attempt and of a completed suicide showed the same increment in the risk of suicidal behavior. The higher the number of suicide attempts, the higher was the real intention to die (P < .05). Those who really wanted to die reported more emptiness/loneliness (OR = 1.58, 95% CI = 1.35 to 1.85), disconnection (OR = 1.54, 95% CI = 1.30 to 1.81), and hopelessness (OR = 1.74, 95% CI = 1.49 to 2.03), but their methods were not different from the methods of those who did not mean to die. CONCLUSIONS: This large Web survey confirmed results from previous studies on suicidal behavior and pointed out the relevance of the number of previous suicide attempts and of a positive family history, even for a noncompleted suicide, as important risk factors.

Temperament and character traits associated with the use of alcohol, cannabis, cocaine, benzodiazepines, and hallucinogens: evidence from a large Brazilian web survey

Objectives: To evaluate how personality traits are associated with occasional use, abuse, and dependence of alcohol, cannabis, cocaine, benzodiazepines, and hallucinogens in a large availability sample of adults via online questionnaires. Methods: The sample consisted of 8,646 individuals (24.7% men and 75.3% women) who completed an anonymous web survey. Involvement with drugs and temperament/character traits were assessed through the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) and the Temperament and Character Inventory - Revised (TCI-R), respectively. Interactions among variables were analyzed using MANOVA with Bonferroni adjustment. Results: Novelty seeking was the trait most associated with increased involvement with alcohol, cannabis, and cocaine. There was a significant association between harm avoidance and benzodiazepine use. Persistence was lower in cannabis-, benzodiazepine-, and cocaine-dependent subjects, as well as in hallucinogen abusers. Self-directedness was reduced in dependents of all drug classes. No strong relationships were found between other temperament or character dimensions and the severity of drug use. Conclusions: Novelty seeking was associated with increased involvement with all drugs studied in this sample, although to a lesser extent with benzodiazepines and hallucinogens. The temperament and character profile for benzodiazepine use was different from that of other drugs due to the relationship with higher harm avoidance and self-transcendence and lower self-directedness. .

Temperament and character traits associated with the use of alcohol, cannabis, cocaine, benzodiazepines, and hallucinogens: evidence from a large Brazilian web survey.

OBJECTIVES: To evaluate how personality traits are associated with occasional use, abuse, and dependence of alcohol, cannabis, cocaine, benzodiazepines, and hallucinogens in a large availability sample of adults via online questionnaires. METHODS: The sample consisted of 8,646 individuals (24.7% men and 75.3% women) who completed an anonymous web survey. Involvement with drugs and temperament/character traits were assessed through the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) and the Temperament and Character Inventory - Revised (TCI-R), respectively. Interactions among variables were analyzed using MANOVA with Bonferroni adjustment. RESULTS: Novelty seeking was the trait most associated with increased involvement with alcohol, cannabis, and cocaine. There was a significant association between harm avoidance and benzodiazepine use. Persistence was lower in cannabis-, benzodiazepine-, and cocaine-dependent subjects, as well as in hallucinogen abusers. Self-directedness was reduced in dependents of all drug classes. No strong relationships were found between other temperament or character dimensions and the severity of drug use. CONCLUSIONS: Novelty seeking was associated with increased involvement with all drugs studied in this sample, although to a lesser extent with benzodiazepines and hallucinogens. The temperament and character profile for benzodiazepine use was different from that of other drugs due to the relationship with higher harm avoidance and self-transcendence and lower self-directedness.

Childhood trauma is associated with maladaptive personality traits.

The association between childhood trauma and personality traits has been poorly characterized and reported. Our aim was to evaluate whether distinct types of childhood abuse and neglect are associated with various personality dimensions using data from a large web-based survey. A total of 12,225 volunteers responded anonymously to the Internet versions of the Temperament and Character Inventory-Revised (TCI-R) and the Childhood Trauma Questionnaire (CTQ) via our research website, but only 8,114 subjects (75.7% women, mean age 34.8±11.3yrs) who met the criteria for validity were included in the analysis. Childhood trauma was positively associated with harm avoidance and was negatively associated with self-directedness and, to a lesser extent, with cooperativeness. The associations were robust with emotional abuse and neglect but were non-significant or mild with physical trauma. Emotional neglect was associated with reduced reward dependence and persistence. All types of abuse, but not neglect, were associated with increased novelty seeking scores. Reporting of childhood trauma, especially of an emotional nature, was associated with maladaptive personality traits. Further investigation of the effects of different types of childhood trauma on psychological and neurobiological parameters is warranted.

Polymorphisms in schizophrenia candidate gene UFD1L may contribute to cognitive deficits.

We aimed to investigate UFD1L polymorphisms in schizophrenia and in relation to cognition. A total of 299 cases and 363 controls were genotyped, and 130 patients completed nine neuropsychological tests. We found that rs5992403 AA-genotype carriers showed lower scores on the set-shifting task. Therefore, UFD1L may participate in the core cognitive deficits observed in schizophrenia.

ZDHHC8 gene may play a role in cortical volumes of patients with schizophrenia.

ZDHHC8 rs175174 polymorphism is located in 22q11.2 region and its role in brain volume has not been fully addressed. A total of 282 schizophrenia patients and 379 controls were genotyped. A sample of 138 patients underwent brain MRI scan. No association was found between schizophrenia and genotypes. Nevertheless, GG-genotype carriers presented gray matter volume (GMV) reduction in frontal lobe compared to A-allele carriers, and cerebellar hemispheres GMV reductions were found in G-allele carriers compared to AA-genotype. Moreover, A-allele carriers presented posterior brain GMV reductions when compared to GG-genotype. These data suggest that ZDHHC8 may play a role in cortical volumes.

The relationship between affective temperaments, defensive styles and depressive symptoms in a large sample.

BACKGROUND: Affective temperaments may represent heritable subclinical manifestations of mood disorders. The concept of ego defense mechanisms also has provided a model for the comprehension of mood psychopathology. The relationships between affective temperaments, defense styles and depressive symptoms remain unknown. METHODS: We obtained data from a subsample of the Brazilian Internet Study on Temperament and Psychopathology (BRAINSTEP). Socio-demographic information was collected and participants completed the Affective and Emotional Temperament Composite Scale (AFECTS), the defense style questionnaire (DSQ-40) and the Symptom Checklist-90-Revised (SCL-90-R). RESULTS: Among 9937 participants (4472 male; 45%), individuals with hyperthymic or euthymic temperaments were more likely to present a mature defense style, whereas an immature defensive style was predominantly observed in individuals with cyclothymic, volatile, depressive, dysphoric, euphoric and disinhibited temperaments. Higher immature and lower mature defense style scores were independently associated with depressive symptoms. Participants with either euthymic or hyperthymic temperaments were less likely to endorse depressive symptoms. Euthymic and hyperthymic temperaments moderated the correlations of mature/immature defenses with depressive symptoms. LIMITATIONS: The data was collected from a convenience web-based sample. The study was cross-sectional. CONCLUSIONS: Affective temperaments are associated with distinct defense styles. These two personality theories provide distinct but interacting views for comprehension of depressive psychopathology.

Circadian preference is associated with emotional and affective temperaments.

Chronotype has long been associated with mental disorders and temperamental features. This study aims to investigate the association of circadian preference with a new model for emotional and affective temperament. In this Web survey, 6436 subjects (27.2% males) answered the Affective and Emotional Composite Temperament Scale (AFECTS), the Circadian Energy Scale (CIRENS), and questions on subjective sleep parameters for a sleep-based chronotype measure. Temperament was more strongly correlated with daily energy score than with chronotype. For emotional dimensions, Volition, Coping, and Control positively correlated with high and stable daily energy, contrary to Sensitivity. Evening types showed a less adaptive emotional profile than morning and intermediate types, who showed a relatively similar emotional pattern. Focus and order (facets of Control), energy (facet of Volition), caution (facet of Inhibition), and problem facing (facet of Coping) were distinctive for the three circadian types, being particularly low in evening types and high in morning types. Differences between affective temperaments were more pronounced for morning and afternoon than for evening scores. Cyclothymic and euphoric temperaments, which relate to bipolar disorders, and apathetic, volatile, and disinhibited temperaments, which relate to attention-deficit/hyperactivity disorder (ADHD), showed the latest chronotype (i.e., evening preference). In conclusion, temperament was more associated with absolute energy levels than with chronotype. Evening types had less emotional control, coping, volition, and caution, and more affective instability and externalization. The circadian daily energy profile can be very informative about human temperament and vice versa, and their combined assessment may be useful in the evaluation of psychiatric patients.

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.

The Circadian Energy Scale (CIRENS): two simple questions for a reliable chronotype measurement based on energy.

This study presents the Circadian Energy Scale (CIRENS), a very short and simple chronotype measurement tool based on energy. The CIRENS consists of two introspective questions about the usual energy level (very low, low, moderate, high, or very high, scored 1 to 5) in the morning and in the evening. The difference between energy level scores (-4 to 4) felt by respondents in the evening and morning defines the chronotype score and classification. A concurrent validity analysis of the CIRENS with the widely used Horne and Östberg Morningness-Eveningness Questionnaire (MEQ) was conducted using a sample of 225 college students, and with MSFsc, a sleep-based chronotype assessment tool based on the Munich Chronotype Questionnaire (MCTQ), using a sample of 34,530 subjects (18-83 yrs, 27% males). This large sample was collected in a Web survey for behavioral correlates of the CIRENS with variables previously associated with chronotype differences. The correlation of the CIRENS chronotype score was r = -.70 with the MEQ and r = .32 with the MSFsc. CIRENS chronotype scores declined with age and were not affected by sex. Both CIRENS and MSFsc chronotype scores were related to differences in tobacco, caffeine, and cola soft-drink consumption (all higher in evening types). The CIRENS provides a simple chronotype index and a measure of absolute energy throughout the day and seems to be a reliable chronotype assessment tool that may be useful both clinically and for large-scale studies.

Association of temperament with subjective sleep patterns.

BACKGROUND: Emotional and cognitive functioning have been involved in insomnia etiology, and sleep disturbances are closely related to psychiatric disorders and personality traits. This study investigates the association of temperament with subjective sleep parameters. METHODS: In this web-survey, 5129 subjects (25.3% males) completed the Combined Emotional and Affective Temperament Scale (CEATS), which assesses emotional (fear, anger, drive and control) and affective (e.g. cyclothymic, hyperthymic) temperaments. Subjects also answered questions regarding subjective sleep parameters, psychiatric diagnosis, psychotropic medication intake and cigarette smoking. RESULTS: As control scores decreased, the later were the bed and the wake up time. Total sleep time was weakly associated with emotional temperaments. The higher the score of anger and the lower the score of control, the higher was the sleep-onset latency. As the anger score increased and the drive, fear and control scores decreased, the higher the number of nightly awakenings. The higher the drive and the control and the lower the anger scores, the better the sleep quality. For affective temperaments, depressives, labiles (related to ADHD) and cyclothymics (related to bipolar II disorders) go to bed and wake up later and have a worse profile regarding other sleep parameters. Hyperthymics and euthymics showed favorable sleep profiles. LIMITATIONS: Sample included a significant number of subjects with psychiatric diseases and on psychotropic medication. CONCLUSION: Dysregulated emotional activation (expressed as higher anger, and lower control and drive), as well as depressive, labile and cyclothymic affective temperaments were related to more dysfunctional sleep patterns.

Validation of the combined emotional and affective temperament scale in a large sample with high prevalence of psychiatric disorders.

BACKGROUND: Based on a model where temperament works as a system with activation, inhibition and control, which produce the affective tone, we developed and validated the Combined Emotional and Affective Temperament Scale (CEATS). This paper aims to validate the CEATS in a large population with high prevalence of psychiatric disorders. METHODS: 4,381 subjects (25.5% males) completed an internet version of the scale on a psychoeducational website on bipolar disorders. The CEATS has both emotional and affective sections and an evaluation of problems and benefits related to temperament. Data were analyzed with standard psychometric batteries. RESULTS: In the emotional section, four factors with an eigenvalue >1 explained 47.3% of the variation. They were interpreted as anger, control, fear and drive. They had a normal distribution and satisfactory Chronbach's alphas. Anger was particularly associated with problems, and drive with benefits. In the Affective section, all 10 categorical affective temperaments were selected, cyclothymic being the most prevalent (32%), and 97.6% of the sample was able to ascribe to at least one affective temperament. Only the euthymic and hyperthymic temperaments were associated with a favorable problem/benefit profile. Each affective temperament had a particular emotional configuration. CONCLUSION: The CEATS is adequate to assess emotional and affective temperament in subjects with high prevalence of psychiatric disorders.

Lower frequency of the low activity adenosine deaminase allelic variant (ADA1*2) in schizophrenic patients / Diminuição da frequência da variante alélica de baixa atividade da adenosina desaminase (ADA1*2) em pacientes esquizofrênicos

OBJECTIVE: Adenosine may play a role in the pathophysiology of schizophrenia, since it modulates the release of several neurotransmitters such as glutamate, dopamine, serotonin and acetylcholine, decreases neuronal activity by pos-synaptic hyperpolarization and inhibits dopaminergic activity. Adenosine deaminase participates in purine metabolism by converting adenosine into inosine. The most frequent functional polymorphism of adenosine deaminase (22G→A) (ADA1*2) exhibits 20-30 percent lower enzymatic activity in individuals with the G/A genotype than individuals with the G/G genotype. The aim of this study was to evaluate the ADA polymorphism 22G→A (ADA1*2) in schizophrenic patients and healthy controls. METHOD: The genotypes of the ADA 22G→A were identified with allele-specific PCR strategy in 152 schizophrenic patients and 111 healthy individuals. RESULTS: A significant decrease in the frequency of the G/A genotype was seen in schizophrenic patients (7/152 - 4.6 percent) relative to controls (13/111 - 11.7 percent, p = 0.032, OR = 2.6). CONCLUSION: These results suggest that the G/A genotype associated with low adenosine deaminase activity and, supposingly, with higher adenosine levels is less frequent among schizophrenic patients.

OBJETIVO: A adenosina pode ter um papel importante na fisiopatologia da esquizofrenia, uma vez que modula a liberação de vários neurotransmissores, tais como glutamato, dopamina, serotonina e acetilcolina, diminui a atividade neuronal por hiperpolarização pós-sináptica e inibe a atividade dopaminérgica. A adenosina desaminase participa do metabolismo das purinas pela conversão de adenosina em inosina. O mais frequente polimorfismo funcional da adenosina desaminase (22G →A) (ADA1*2) exibe uma diminuição de 20-30 por cento da atividade funcional em indivíduos com genótipo G/A quando comparados com indivíduos com o genótipo G/G. O objetivo deste estudo foi avaliar o polimorfismo 22G→A (ADA1*2) em pacientes esquizofrênicos e em controles saudáveis. MÉTODO: Os genótipos da ADA 22G →A foram identificados através de uma estratégia de PCR alelo-específica em 152 pacientes esquizofrênicos e 111 controles saudáveis. RESULTADOS: Foi observada uma diminuição significativa na frequência do genótipo G/A em pacientes esquizofrênicos (7 - 4,6 por cento) em relação ao grupo controle (13 - 11,7 por cento, p = 0,032, OR = 2,6). CONCLUSÃO: Estes resultados sugerem que o genótipo G/A associado com baixa atividade de adenosina desaminase, e potencialmente com níveis aumentados de adenosina, é menos frequente entre pacientes esquizofrênicos.

Lower frequency of the low activity adenosine deaminase allelic variant (ADA1*2) in schizophrenic patients.

OBJECTIVE: Adenosine may play a role in the pathophysiology of schizophrenia, since it modulates the release of several neurotransmitters such as glutamate, dopamine, serotonin and acetylcholine, decreases neuronal activity by pos-synaptic hyperpolarization and inhibits dopaminergic activity. Adenosine deaminase participates in purine metabolism by converting adenosine into inosine. The most frequent functional polymorphism of adenosine deaminase (22G→A) (ADA1*2) exhibits 20-30% lower enzymatic activity in individuals with the G/A genotype than individuals with the G/G genotype. The aim of this study was to evaluate the ADA polymorphism 22G→A (ADA1*2) in schizophrenic patients and healthy controls. METHOD: The genotypes of the ADA 22G→A were identified with allele-specific PCR strategy in 152 schizophrenic patients and 111 healthy individuals. RESULTS: A significant decrease in the frequency of the G/A genotype was seen in schizophrenic patients (7/152 - 4.6%) relative to controls (13/111 - 11.7%, p = 0.032, OR = 2.6). CONCLUSION: These results suggest that the G/A genotype associated with low adenosine deaminase activity and, supposingly, with higher adenosine levels is less frequent among schizophrenic patients.

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.

Reduced serum BDNF levels in schizophrenic patients on clozapine or typical antipsychotics.

Neurotrophic factors regulate neuronal development and synaptic plasticity, possibly playing a role in the pathophysiology of schizophrenia and other psychiatric disorders. Decreased brain-derived neurotrophic factor (BDNF) levels have been found in brains and in the serum of schizophrenic patients, but results are inconsistent. Also, clozapine may upregulate brain BDNF expression. In the present study, we assessed serum BDNF immunoreactivity in 44 schizophrenic patients (20 on clozapine and 24 on typical antipsychotics) and in 25 healthy volunteers. Serum BDNF levels were measured using an enzyme immunoassay. Healthy controls showed significantly higher levels of BDNF compared to the whole group of schizophrenic patients (p<0.001) as well as to the subgroups on typical antipsychotics and clozapine (p<0.001). Serum BDNF values for controls were 168.8+/-26.3pg/ml, for the clozapine group were 125.4+/-44.5pg/ml and for the group on typicals were 101.3+/-51.6pg/ml. BDNF values from patients on clozapine were non-significantly higher than values from patients on typical antipsychotics (p=0.09). Serum BDNF was strongly and positively correlated with clozapine dose (r=0.643; p=0.002) but not with other demographic characteristics. These results reinforce previous findings of reduced serum BDNF levels in schizophrenic patients and suggest a differential effect of clozapine compared to typical antipsychotics on such levels.