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.

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.

Affective temperaments and ego defense mechanisms associated with somatic symptom severity in a large sample.

BACKGROUND: Several complex mechanisms including biological, psychological and social factors may contribute to the development of bodily symptoms. Affective temperaments may represent heritable subclinical manifestations of mood disorders, and the concept of ego defense mechanisms has also provided a model for the comprehension of psychopathology. The relationship between affective temperaments, defensive functioning and somatic symptom severity remains unknown. METHODS: We obtained data from a subsample of the Brazilian Internet Study on Temperament and Psychopathology (BRAINSTEP). 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). SCL-90-R Somatization scale was used as outcome variable. RESULTS: Among 9937 participants (4472 male; 45%), individuals with dysphoric, cyclothymic and depressive temperaments and those who adopted displacement, somatisation and passive aggression as their predominant defense mechanisms presented high somatic symptom severity. Participants with dysphoric temperament and those with higher displacement scores were more likely to endorse numerous bodily symptoms after controlling for age, gender, education and depressive symptoms. Moderator analysis showed that the relationship of dysphoric temperament with somatic symptom severity was much more powerful in people who adopted displacement as their predominant defense. LIMITATIONS: The data was collected from a convenience web-based sample. The study was cross-sectional. There was no information on the presence of established physical illness. CONCLUSIONS: Affective temperaments and defense mechanisms are associated with somatic symptom severity independently of depressive symptoms. These two personality theories provide distinct but interacting views for comprehension of somatic symptom formation.

Antidepressant, mood stabilizing and procognitive effects of very low dose sublingual ketamine in refractory unipolar and bipolar depression.

Intravenous ketamine (0.5 mg/kg) produces robust, rapid and long-lasting antidepressant effects, but is unpractical. Sublingual administration of ketamine renders better bioavailability (~30%) and less conversion to norketamine than oral administration. We evaluated the therapeutic effects and tolerability of very low dose sublingual (VLDS) racemic ketamine (10 mg from a 100 mg/ml solution for 5 min and swallowed), repeatedly administered every 2-3 d or weekly, in 26 out-patients with refractory unipolar or bipolar depression. According to patients' reports, VLDS ketamine produced rapid, clear and sustained effects, improving mood level and stability, cognition and sleep in 20 patients (77%), with only mild and transient light-headedness as a common side-effect (no euphoria, psychotic or dissociative symptoms). Remission remained in some patients after stopping ketamine. Thus, VLDS ketamine may have broad spectrum effects beyond its antidepressant properties, with rapid onset of action, high efficacy, good tolerability and low cost, allowing extended treatment as needed.

How emotional traits and affective temperaments relate to cocaine experimentation, abuse and dependence in a large sample.

UNLABELLED: The contribution of specific traits in cocaine experimentation, abuse and addiction is not yet clear. Our aim was to evaluate how temperament was associated with cocaine experimentation, abuse and dependence using a recently developed scale for the assessment of emotional traits (e.g. anger, volition) and affective temperaments (e.g. cyclothymic). An anonymous web-survey provides the optimal means to evaluate sensitive issues such as drug related behavior in the general population. METHODS: The data was collected by the Brazilian Internet Study on Temperament and Psychopathology (BRAINSTEP), which included the Affective and Emotional Composite Temperament Scale (AFECTS) and the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST). The final sample consisted of 28,587 subjects (26.6% males, mean age=30.8±9.8yrs). Trait analysis was controlled for age, gender, ethanol and marijuana use. RESULTS: For emotional traits, Caution, Coping and Control were significantly lower in the cocaine-using groups when compared to controls, particularly in those with cocaine dependence. Anger and Desire increased in relation to the degree of cocaine involvement. The associations with Emotional Sensitivity and Volition were less robust. For affective temperaments, greater cocaine use was related to a lower proportion of stable types (obsessive, euthymic and hyperthymic) and the anxious type, and to a higher proportion of cyclothymic and euphoric temperaments in both sexes. CONCLUSIONS: Specific externalized and unstable traits were associated with cocaine related behavior. Addressing these traits may be important for recovery and prevention strategies.

Bullying victimization is associated with dysfunctional emotional traits and affective temperaments.

BACKGROUND: Being bullied has been increasingly recognized as a risk factor for the development of psychiatric disorders, but there is very limited evidence on the association of bullying with temperament. METHODS: The data was collected in a large web-survey on psychological and psychiatric measures (BRAINSTEP). Bullying was assessed with a question on time exposed to bullying (none, <1 year, 1-3 years and >3 years) during childhood and adolescence. Emotional traits and affective temperaments were evaluated with the Affective and Emotional Composite Temperament Scale (AFECTS). The final sample consisted of 50,882 subjects (mean age 30.8 ± 10.4 years, 73.4% females) with valid answers. RESULTS: About half of the sample reported exposure to bullying and ∼10% reported being victimized by peers for longer than 3 years. Longer exposure to bullying was associated with lower Volition, Coping and Control scores, and more Emotional Sensitivity, Anger and Fear, with statistical significance between all groups. To a lower degree, exposure to bullying was associated with lower Caution and higher Desire scores. Bullying victimization was also associated with a much lower proportion of euthymic and hyperthymic types in both genders, which was compensated by an increase mainly in the proportion of depressive, cyclothymic and volatile types. LIMITATIONS: Retrospective assessment of bullying with a single question on time exposed to bullying and use of self-report instruments only. CONCLUSIONS: Being bullied was associated with a broad and profound impact on emotional and cognitive domains in all dimensions of emotional traits, and with internalized and unstable affective temperaments.

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.

Emotional and affective temperaments and cigarette smoking in a large sample.

BACKGROUND: Tobacco use has been associated with externalized personality traits. Our aim was to evaluate the association of smoking with emotional and affective temperaments in a large sample. METHODS: In this cross-sectional web-based survey, volunteers completed the Combined Emotional and Affective Temperament Scale (CEATS), which assesses emotional (fear, drive, anger, and control) and affective temperaments (e.g. cyclothymic, irritable), and questions about smoking. RESULTS: Among the 5379 subjects (1370 males), there were 60% non-smokers, 17% quitters and 23% current smokers. Non-smokers had higher fear and control and lower anger than quitters and smokers, and higher drive than smokers. Quitters had higher drive and control and lower anger than smokers. Smoking was lower among apathetics, depressives, euthymics and hyperthymics and higher in cyclothymics and labiles. Lower drive and higher anger were associated with heavier smoking. Less adaptive temperament was related to higher prevalence of and heavier smoking. LIMITATIONS: The data was collected from a convenience sample by the internet, and most volunteers assessed the instrument through a psychoeducational website for bipolar spectrum disorders, leading to a higher proportion of cyclothymics; the assessment of smoking habits was limited to two questions; the study was cross-sectional. CONCLUSIONS: Smoking was associated with lower fear, control and drive, higher anger and unstable externalized affective temperaments. Lower control and higher anger were associated with being a heavy smoker and current smoking. Assessment of temperament may help decision about treatments for smoking cessation.

Low-dose quetiapine for patients with dysregulation of hyperthymic and cyclothymic temperaments.

Patients with hyperthymic and cyclothymic temperaments often develop symptoms that fail to meet diagnostic criteria for bipolar disorders. These patients can be conceived as having bipolar disorder NOS (not otherwise specified), a bipolar spectrum disorder, cyclothymic disorder or cluster B personality traits. Here, we describe four of these patients with mild to moderate symptoms affecting mood, behaviour, emotional reactivity and sleep. Treatment with low-dose quetiapine (25-75 mg/day at night) lead to sustained symptom remission. Two of them were on quetiapine monotherapy. Such low doses occupy a minority of D2 and 5-HT2 receptors, which may nevertheless be of therapeutic value in mild cases. Alternatively, other mechanisms more likely to occur at low doses, such as antagonism of H1, alpha(1B)-adrenergic and other serotonin receptors, as well as reduction cortisol secretion, may be involved in the therapeutic efficacy of quetiapine.

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.

The DSM-IV 'minor depression' disorder in the oldest-old: prevalence rate, sleep patterns, memory function and quality of life in elderly people of Italian descent in Southern Brazil.

OBJECTIVES: (1) To describe the prevalence of minor depression in a community-dwelling population aged 80 years and over. (2) To compare the sleep pattern, memory function and the prevalence rate of other psychiatric diagnoses between normal controls and subjects with minor depressive disorder. DESIGN: A random representative sample (sample=77 subjects/county population of oldest-old =219--35%) aged 80 years or more was selected from the county of Veranópolis in the Brazilian rural southern region. Of this group, eight subjects who met the DSM-IV criteria for minor depression, and 50 subjects without diagnosed delirium disorder, cognitive or affective problems were compared. RESULTS: The prevalence rate of minor depression was 12%. Subjects with this diagnosis were more likely to complain about sleep and memory problems than elderly people without any other affective disorder (major depression or dysthymic disorder). Otherwise, objective evaluation of these two areas, memory and sleep, did not show differences between the groups. Moreover, in terms of factors such as life satisfaction and some domains from the Short-form 36 Quality of Life Scale (SF-36), subjects with minor depression presented worse self-reported evaluations. Female gender was associated (p=0.01) with a more frequent presence of minor depression disorder, and those with this diagnosis were more likely to have co-morbidity with generalized anxiety disorder (p=0.007) when compared with elderly people without any depressive disorder. CONCLUSION: In this study, minor depression has been significantly associated with lower life satisfaction and worse indexes of life quality. The results supported the current concept that minor depression is prevalent in later life, especially among the oldest-old. Subjects with minor depression had worse self-reported opinions about memory and sleep patterns, but when these variables were objectively measured, no meaningful differences could be determined by the research team. Female gender and the concurring presence of generalized anxiety disorder were both significantly associated with the presence of minor depression diagnosis.

Alteraçöes neuroendócrinas nos transtornos do humor: foco no eixo hipotálamo-hipófise-tireoideo / Neuroendocrine changes in mood disordrs: focus on hipothalamic-pituitary-thyroid axis

Estudos recentes com pacientes deprimidos têm evidenciado a presença de perturbaçöes no eixo hipotálamo-hipófise-tireoideo (HDT) e esta tem sido uma área para a qual os estudiosos do assunto têm dirigido seus esforços de pesquisa. Entre as alteraçöes mais freqüentes temos a diminuiçäo da resposta do hormônio estimulante da tireóide (TSH) à diminuiçäo da resposta do hormônio liberador da tireotropina (TRH). Foi demosntrado ainda que a triiodotironina (T3) aumenta os efeitos dos antidepressivos tricíclicos. Os autores fazem revisäo bibliográfica das alteraçöes neuroendócrinas presentes nos transtornos do humor, com foco no eixo HPT e depressäo