The impact of body mass index on the clinical features of bipolar disorder: A STEP-BD study.

INTRODUCTION: The effects of body mass index (BMI) on the core symptoms of bipolar disorder (BD) and its implications for disease trajectory are largely unexplored. OBJECTIVE: To examine whether BMI impacted hospitalization rate, medical and psychiatric comorbidities, and core symptom domains such as depression and suicidality in BD. METHODS: Participants (15 years and older) were 2790 BD outpatients enrolled in the longitudinal STEP-BD study; all met DSM-IV criteria for BD-I, BD-II, cyclothymia, BD NOS, or schizoaffective disorder, bipolar subtype. BMI, demographic information, psychiatric and medical comorbidities, and other clinical variables such as bipolarity index, history of electroconvulsive therapy (ECT), and history of suicide attempts were collected at baseline. Longitudinal changes in Montgomery-Åsberg Depression Rating Scale (MADRS) score, Young Mania Rating Scale (YMRS) score, and hospitalizations during the study were also assessed. Depending on the variable of interest, odds-ratios, regression analyses, factor analyses, and graph analyses were applied. RESULTS: A robust increase in psychiatric and medical comorbidities was observed, particularly for baseline BMIs >35. A significant relationship was noted between higher BMI and history of suicide attempts, and individuals with BMIs >40 had the highest prevalence of suicide attempts. Obese and overweight individuals had a higher bipolarity index (a questionnaire measuring disease severity) and were more likely to have received ECT. Higher BMIs correlated with worsening trajectory of core depression symptoms and with worsening lassitude and inability to feel. CONCLUSIONS: In BD participants, elevated BMI was associated with worsening clinical features, including higher rates of suicidality, comorbidities, and core depression symptoms.

Trauma history in veterans with bipolar disorder and its impact on suicidality.

OBJECTIVES: Veterans are at increased risk for exposure to trauma, developing serious mental illnesses, and death by suicide. History of trauma correlates with worsening outcomes in patients with bipolar disorder. This study investigated associations between trauma exposure (type and timing) and suicide attempt in Veterans with bipolar disorder. METHODS: One hundred six Veterans with a diagnosis of bipolar disorder and 815 Veterans with no psychiatric history (age rage = 20-72 years old) completed a clinical questionnaire, the Beck Scale for Suicide Ideation, and the Traumatic Live Events Questionnaire. Multinomial logistic regressions investigated correlations between diagnosis, time of trauma (before, during, or after the military), trauma type (attack, illness, accident, child violence, child sexual abuse, and adult sexual abuse), and suicide attempt. RESULTS: Seventy-five Veterans with bipolar disorder had comorbid PTSD. Controlling for PTSD, Veterans with bipolar disorder had a higher prevalence of trauma including physical assault [odds ratio (OR) = 2.85; 95% confidence interval (CI) = 1.39-5.86] and child sexual trauma (OR = 2.89; CI = 1.38-6.05). Veterans with bipolar disorder who endorsed previous suicide attempts (n = 42) had significantly higher levels of exposure to childhood trauma (OR = 5.69; CI = 1.84-17.62). CONCLUSIONS: Results support incorporating history of previous trauma exposure when assessing Veterans at risk for bipolar disorder. Especially, trauma characterized as attack and childhood sexual abuse. Particular attention should be given to Veterans with bipolar disorder and exposure to trauma during childhood, which may be associated with increased risk of suicidality.

Differentiating irritable mood and disruptive behavior in adults.

INTRODUCTION: Irritability has both mood and behavioral manifestations. These frequently co-occur, and it is unclear to what extent they are dissociable domains. We used confirmatory factor analysis and external validators to investigate the independence of mood and behavioral components of irritability. METHODS: The sample comprised 246 patients (mean age 45 years; 63% female) from four outpatient programs (depression, anxiety, bipolar, and schizophrenia) at a tertiary hospital. A clinical instrument rated by trained clinicians was specifically designed to capture irritable mood and disruptive behavior dimensionally, as well as current categorical diagnoses i.e., intermittent explosive disorder (IED); oppositional defiant disorder (ODD); and an adaptation to diagnose disruptive mood dysregulation disorder (DMDD) in adults. Confirmatory factor analysis (CFA) was used to test the best fitting irritability models and regression analyses were used to investigate associations with external validators. RESULTS: Irritable mood and disruptive behavior were both frequent, but diagnoses of disruptive syndromes were rare (IED, 8%; ODD, 2%; DMDD, 2%). A correlated model with two dimensions, and a bifactor model with one general dimension and two specific dimensions (mood and behavior) both had good fit indices. The correlated model had root mean square error of approximation (RMSEA) = 0.077, with 90% confidence interval (90%CI) = 0.071-0.083; comparative fit index (CFI) = 0.99; and Tucker-Lewis index (TLI) = 0.99, while the bifactor model had RMSEA = 0.041; CFI = 0.99; and TLI = 0.99 respectively). In the bifactor model, external validity for differentiation of the mood and behavioral components of irritability was also supported by associations between irritable mood and impairment and clinical measures of depression and mania, which were not associated with disruptive behavior. CONCLUSIONS: Psychometric and external validity data suggest both overlapping and specific features of the mood vs. disruptive behavior dimensions of irritability.

Emotional memory in bipolar disorder: Impact of multiple episodes and childhood trauma.

BACKGROUND: Emotional memory is a critical amygdala-dependent cognitive function characterized by enhanced memory for emotional events coupled with retrograde amnesia. Our study aims to assess the influence of bipolar disorder (BD), trauma, and the number of mood episodes on emotional memory. METHODS: 53 subjects (33 euthymic patients with BD and 20 healthy controls) answered a clinical assessment, childhood trauma questionnaire (CTQ), and an emotional memory test composed of lists of nouns, including neutral words, one emotional (E), one preceding (E-1) and one following word (E + 1). We assessed for the influence of type, position, diagnosis, trauma, and number of mood episodes in word recall using generalized estimating equations. RESULTS: Controlling for neutral words, BD had a higher recall for E-1 (p = 0.038) and a trend for a higher recall of E (p = 0.055). There was no difference between patients with and without trauma. Patients with BD who suffered multiple mood episodes had a higher recall of E compared to patients with fewer episodes (p = 0.016). LIMITATIONS: Cross-sectional design and small sample size. CONCLUSION: Our results indicate dysfunction in emotional memory in patients with BD, particularly after multiple mood episodes. While we expected an impaired emotional memory, patients with BD showed an increased recall for emotional stimuli and events preceding them. Childhood trauma does not seem to interfere with emotional memory changes in patients with BD. Emotional memory enhancement seems to be a promising marker of progression in BD.

Decoding rumination: A machine learning approach to a transdiagnostic sample of outpatients with anxiety, mood and psychotic disorders.

OBJECTIVE: To employ machine learning algorithms to examine patterns of rumination from RDoC perspective and to determine which variables predict high levels of maladaptive rumination across a transdiagnostic sample. METHOD: Sample of 200 consecutive, consenting outpatient referrals with clinical diagnoses of schizophrenia, schizoaffective, bipolar, depression, anxiety disorders, obsessive compulsive and post-traumatic stress. Machine learning algorithms used a range of variables including sociodemographics, serum levels of immune markers (IL-6, IL-1ß, IL-10, TNF-α and CCL11) and BDNF, psychiatric symptoms and disorders, history of suicide and hospitalizations, functionality, medication use and comorbidities. RESULTS: The best model (with recursive feature elimination) included the following variables: socioeconomic status, illness severity, worry, generalized anxiety and depressive symptoms, and current diagnosis of panic disorder. Linear support vector machine learning differentiated individuals with high levels of rumination from those ones with low (AUC = 0.83, sensitivity = 75, specificity = 71). CONCLUSIONS: Rumination is known to be associated with poor prognosis in mental health. This study suggests that rumination is a maladaptive coping style associated not only with worry, distress and illness severity, but also with socioeconomic status. Also, rumination demonstrated a specific association with panic disorder.

Adjunctive tianeptine treatment for bipolar disorder: A 24-week randomized, placebo-controlled, maintenance trial.

OBJECTIVE: The purpose of this study was to assess the efficacy and tolerability of tianeptine as an adjunctive maintenance treatment for bipolar depression. METHODS: This is a multicenter double-blind randomized placebo-controlled maintenance trial of adjunctive tianeptine 37.5 mg/day. Participants ( n=161) had a Montgomery-Asberg Depression Rating Scale ⩾12 at entry. After eight weeks of open-label tianeptine treatment, those who responded to tianeptine ( n=69) were randomized to adjunctive tianeptine ( n=36) or placebo ( n=33) in addition to usual treatment. Kaplan-Meier estimates and the Mantel-Cox log-rank test were used to evaluate differences in time to intervention for a mood episode between the tianeptine and placebo groups. We also assessed overall functioning, biological rhythms, quality of life, rates of manic switch and serum brain-derived neurotrophic factor levels. RESULTS: There were no differences between adjunctive tianeptine or placebo regarding time to intervention or depression scores in the 24-week double-blind controlled phase. Patients in the tianeptine group showed better performance in the letter-number sequencing subtest from the Wechsler Adult Intelligence Scale at the endpoint ( p=0.014). Tianeptine was well tolerated and not associated with higher risk for manic switch compared to placebo. CONCLUSION: Tianeptine was not more effective than placebo in the maintenance treatment of bipolar depression. There is preliminary evidence suggesting a pro-cognitive effect of tianeptine in working memory compared to placebo.

Bipolar disorder and 1513A>C P2RX7 polymorphism frequency.

Although the etiology of Bipolar Disorder (BD) remains unknown, a strong genetic component to the pathogenesis and risk for this disorder has been widely hypothesized. Several risk genes for BD have been identified; of these, the purinergic P2 × 7 receptor (P2 × 7R) constitutes a pro-inflammatory receptor and a potential risk gene candidate. The purpose of the present study was to assess the frequency of the 1513 A > C P2RX7 polymorphism (rs3751143; Glu496Ala), which leads to receptor loss-of-function, in 154 BD patients versus 184 control subjects. The existence of a differential modulation of P2 × 7R was also analyzed in 22 euthymic BD patients, in comparison to 18 healthy controls. Our data show a decrease in 1513C allele frequency (p = 0.045) and a potential increase in 1513 A A/AC (p = 0.055) genotype frequency in BD patients, compared to controls, indicating an enhanced function of the pro-inflammatory P2 × 7 receptor in BD subjects. Interestingly, no differences in P2RX7 gene and protein expression were found between euthymic BD patients and matched healthy controls. In conclusion, our results suggest that P2 × 7R might play a role in the pathophysiology of BD and add new information regarding this receptor as a potential biomarker for the prediction and diagnosis of the disorder.

Differences in coping strategies in adult patients with bipolar disorder and their first-degree relatives in comparison to healthy controls.

INTRODUCTION: The objective of this study was to compare patients with bipolar disorder (BD), their first-degree relatives and a group of healthy controls in terms of use of adaptive and maladaptive coping strategies, exploring differences between specific types of strategies and their correlations with clinical variables. METHODS: This was a cross-sectional study enrolling 36 euthymic patients with BD, 39 of their first-degree relatives and 44 controls. Coping strategies were assessed using the Brief COPE scale. RESULTS: Significant differences were detected in the use of adaptive and maladaptive strategies by patients, their first-degree relatives and controls. Patients used adaptive strategies less often than the patients' relatives (p<0.001) and controls (p = 0.003). There was no significant difference between first-degree relatives and controls (p=0.707). In contrast, patients (p<0.001) and their relatives (p=0.004) both exhibited higher scores for maladaptive coping than controls. There was no significant difference regarding the use of maladaptive strategies between patients and their relatives (p=0.517). CONCLUSIONS: First-degree relatives were at an intermediate level between patients with BD and controls regarding the use of coping skills. This finding supports the development of psychosocial interventions to encourage use of adaptive strategies rather than maladaptive strategies in this population.

Volumetric brain magnetic resonance imaging predicts functioning in bipolar disorder: A machine learning approach.

Neuroimaging studies have been steadily explored in Bipolar Disorder (BD) in the last decades. Neuroanatomical changes tend to be more pronounced in patients with repeated episodes. Although the role of such changes in cognition and memory is well established, daily-life functioning impairments bulge among the consequences of the proposed progression. The objective of this study was to analyze MRI volumetric modifications in BD and healthy controls (HC) as possible predictors of daily-life functioning through a machine learning approach. Ninety-four participants (35 DSM-IV BD type I and 59 HC) underwent clinical and functioning assessments, and structural MRI. Functioning was assessed using the Functioning Assessment Short Test (FAST). The machine learning analysis was used to identify possible candidates of regional brain volumes that could predict functioning status, through a support vector regression algorithm. Patients with BD and HC did not differ in age, education and marital status. There were significant differences between groups in gender, BMI, FAST score, and employment status. There was significant correlation between observed and predicted FAST score for patients with BD, but not for controls. According to the model, the brain structures volumes that could predict FAST scores were: left superior frontal cortex, left rostral medial frontal cortex, right white matter total volume and right lateral ventricle volume. The machine learning approach demonstrated that brain volume changes in MRI were predictors of FAST score in patients with BD and could identify specific brain areas related to functioning impairment.

Translation and cross-cultural adaptation of the Brazilian Portuguese version of the Emotional Memory Scale.

Background Emotional memory is an important type of memory that is triggered by positive and negative emotions. It is characterized by an enhanced memory for emotional stimuli which is usually coupled with a decrease in memory of neutral preceding events. Emotional memory is strongly associated with amygdala function and therefore could be disrupted in neuropsychiatric disorders. To our knowledge, there is no translated and culturally adapted instrument for the Brazilian Portuguese speaking population to assess emotional memory. Objective To report the translation and cross-cultural adaptation of a Brazilian Portuguese version of the Emotional Memory Scale, originally published by Strange et al. in 2003. Methods The author of the original scale provided 36 lists with 16 words each. Translation was performed by three independent bilingual translators. Healthy subjects assessed how semantically related each word was within the list (0 to 10) and what the emotional valence of each word was (-6 to +6). Lists without negative words were excluded (negative selection), most positive and most unrelated words were excluded (positive and semantic selection, respectively), and lists with low semantic relationship were excluded (semantic assessment). Results Five lists were excluded during negative selection, four words from each list were excluded in positive and semantic selection, and 11 lists were excluded during semantic assessment. Finally, we reached 20 lists of semantically related words; each list had one negative word and 11 neutral words. Conclusion A scale is now available to evaluate emotional memory in the Brazilian population and requires further validation on its psychometrics properties.

Translation and cross-cultural adaptation of the Brazilian Portuguese version of the Emotional Memory Scale / Tradução e adaptação transcultural da versão brasileira da Escala de Memória Emocional

Abstract Background Emotional memory is an important type of memory that is triggered by positive and negative emotions. It is characterized by an enhanced memory for emotional stimuli which is usually coupled with a decrease in memory of neutral preceding events. Emotional memory is strongly associated with amygdala function and therefore could be disrupted in neuropsychiatric disorders. To our knowledge, there is no translated and culturally adapted instrument for the Brazilian Portuguese speaking population to assess emotional memory. Objective To report the translation and cross-cultural adaptation of a Brazilian Portuguese version of the Emotional Memory Scale, originally published by Strange et al. in 2003. Methods The author of the original scale provided 36 lists with 16 words each. Translation was performed by three independent bilingual translators. Healthy subjects assessed how semantically related each word was within the list (0 to 10) and what the emotional valence of each word was (-6 to +6). Lists without negative words were excluded (negative selection), most positive and most unrelated words were excluded (positive and semantic selection, respectively), and lists with low semantic relationship were excluded (semantic assessment). Results Five lists were excluded during negative selection, four words from each list were excluded in positive and semantic selection, and 11 lists were excluded during semantic assessment. Finally, we reached 20 lists of semantically related words; each list had one negative word and 11 neutral words. Conclusion A scale is now available to evaluate emotional memory in the Brazilian population and requires further validation on its psychometrics properties.

Resumo Introdução Memória emocional é um tipo importante de memória que é acionado por emoções positivas e negativas. Ela é caracterizada por um aumento de memória para estímulos emocionais que normalmente está associado a um prejuízo de memória para eventos neutros que os precedem. Memória emocional é fortemente relacionada à função da amígdala e, portanto, pode estar alterada em transtornos neuropsiquiátricos. Pelo nosso conhecimento, não existe instrumento traduzido e adaptado culturalmente para a população falante de português brasileiro para avaliar memória emocional. Objetivo Descrever a tradução e adaptação transcultural para o português brasileiro da Escala de Memória Emocional, originalmente publicada por Strange et al. em 2003. Métodos O autor da escala original forneceu 36 listas com 16 palavras cada. A tradução foi feita por três tradutores bilíngues e independentes. Sujeitos saudáveis foram selecionados para avaliar o quanto cada palavra era semanticamente relacionada dentro da lista (0 a 10) e qual era a valência emocional de cada palavra (-6 a +6). Listas sem palavras negativas foram excluídas (seleção negativa), palavras mais positivas e menos relacionadas de cada lista foram excluídas (seleções positiva e semântica, respectivamente) e listas com relação semântica fraca foram excluídas (avaliação semântica). Resultados Cinco listas foram excluídas durante a seleção negativa, quatro palavras de cada lista foram excluídas nas seleções positiva e semântica, e 11 listas foram excluídas na avaliação semântica. Por fim, chegamos em 20 listas de palavras semanticamente relacionadas; cada lista com uma palavra negativa e 11 palavras neutras. Conclusão Uma escala está disponível para avaliar memória emocional na população brasileira e requer posterior validação de suas propriedades psicométricas.

Telomere Length, Oxidative Stress, Inflammation and BDNF Levels in Siblings of Patients with Bipolar Disorder: Implications for Accelerated Cellular Aging.

Background: Growing evidence supports the existence of neurobiological trait abnormalities in individuals at genetic risk for bipolar disorder. The aim of this study was to examine potential differences in brain-derived neurotrophic factor, cytokines, oxidative stress, and telomere length markers between patients with bipolar disorder, their siblings, and healthy controls. Methods: Thirty-six patients with bipolar disorder type I, 39 siblings, and 44 healthy controls were assessed. Serum levels of brain-derived neurotrophic factor, interleukin-6, interleukin-10, tumor necrosis factor-α, C-C motif chemokine 11, C-C motif chemokine 24, and 3-nitrotyrosine were measured, as were the activities of glutathione peroxidase, glutathione reductase, and glutathione S-transferase. Telomere length (T/S ratio) was measured using quantitative polymerase chain reaction. Results: Telomere length was different between the 3 groups (P = .041) with both patients and siblings showing a shorter T/S ratio compared with healthy controls. Patients showed increased levels of interleukin-6 (P = .005) and interleukin-10 (P = .002) compared with controls as well as increased levels of interleukin-6 (p = 0.014) and CCL24 (P = .016) compared with their siblings. C-C motif chemokine 11 levels were increased in siblings compared with controls (P = .015), and a similar tendency was found in patients compared with controls (P = .045). Glutathione peroxidase activity was decreased in patients compared with controls (P = .006) and siblings (P = .025). No differences were found for the other markers. Conclusions: The present results suggest that unaffected siblings may present accelerated aging features. These neurobiological findings may be considered as endophenotypic traits. Further prospective studies are warranted.

Cognitive performance and psychosocial functioning in patients with bipolar disorder, unaffected siblings, and healthy controls

Objective: To assess cognitive performance and psychosocial functioning in patients with bipolar disorder (BD), in unaffected siblings, and in healthy controls. Methods: Subjects were patients with BD (n=36), unaffected siblings (n=35), and healthy controls (n=44). Psychosocial functioning was accessed using the Functioning Assessment Short Test (FAST). A sub-group of patients with BD (n=21), unaffected siblings (n=14), and healthy controls (n=22) also underwent a battery of neuropsychological tests: California Verbal Learning Test (CVLT), Stroop Color and Word Test, and Wisconsin Card Sorting Test (WCST). Clinical and sociodemographic characteristics were analyzed using one-way analysis of variance or the chi-square test; multivariate analysis of covariance was used to examine differences in neuropsychological variables. Results: Patients with BD showed higher FAST total scores (23.90±11.35) than healthy controls (5.86±5.47; p < 0.001) and siblings (12.60±11.83; p 0.001). Siblings and healthy controls also showed statistically significant differences in FAST total scores (p = 0.008). Patients performed worse than healthy controls on all CVLT sub-tests (p < 0.030) and in the number of correctly completed categories on WCST (p = 0.030). Siblings did not differ from healthy controls in cognitive tests. Conclusion: Unaffected siblings of patients with BD may show poorer functional performance compared to healthy controls. FAST scores may contribute to the development of markers of vulnerability and endophenotypic traits in at-risk populations.

Peripheral adenosine levels in euthymic patients with bipolar disorder.

Recent evidence points to the involvement of the purinergic signaling in the pathophysiology of bipolar disorder. The aim of this study was to assess the serum levels of adenosine and to evaluate its relation to functioning in 24 euthymic patients with bipolar disorder type I and in 25 matched healthy controls. Subjects were evaluated using the functioning assessment short test. Serum purine levels were measured by high pressure liquid chromatography. Our results show a decrease in serum adenosine levels in bipolar disorder patients compared with controls (t= -4.8, df= 43.96, p<0.001). Moreover, a significant negative correlation was found between patient adenosine levels and depression scale scores (r= -0.642, p= 0.001). Higher functional impairment was linked to lower levels of adenosine in patients (rho= -0.551, p= 0.008). Taken together, our results provide evidence for a purinergic imbalance in bipolar disorder, specifically an adenosinergic dysfunction. Our results also indicate a relation between adenosine levels and the functional impairment caused by the disorder, which could demonstrate a potential relation of adenosine levels in worsening of symptoms.

Cognitive performance and psychosocial functioning in patients with bipolar disorder, unaffected siblings, and healthy controls.

OBJECTIVE:: To assess cognitive performance and psychosocial functioning in patients with bipolar disorder (BD), in unaffected siblings, and in healthy controls. METHODS:: Subjects were patients with BD (n=36), unaffected siblings (n=35), and healthy controls (n=44). Psychosocial functioning was accessed using the Functioning Assessment Short Test (FAST). A sub-group of patients with BD (n=21), unaffected siblings (n=14), and healthy controls (n=22) also underwent a battery of neuropsychological tests: California Verbal Learning Test (CVLT), Stroop Color and Word Test, and Wisconsin Card Sorting Test (WCST). Clinical and sociodemographic characteristics were analyzed using one-way analysis of variance or the chi-square test; multivariate analysis of covariance was used to examine differences in neuropsychological variables. RESULTS:: Patients with BD showed higher FAST total scores (23.90±11.35) than healthy controls (5.86±5.47; p < 0.001) and siblings (12.60±11.83; p 0.001). Siblings and healthy controls also showed statistically significant differences in FAST total scores (p = 0.008). Patients performed worse than healthy controls on all CVLT sub-tests (p < 0.030) and in the number of correctly completed categories on WCST (p = 0.030). Siblings did not differ from healthy controls in cognitive tests. CONCLUSION:: Unaffected siblings of patients with BD may show poorer functional performance compared to healthy controls. FAST scores may contribute to the development of markers of vulnerability and endophenotypic traits in at-risk populations.

Hypothalamic-pituitary-adrenal axis dysfunction and illness progression in bipolar disorder.

BACKGROUND: Impaired stress resilience and a dysfunctional hypothalamic-pituitary-adrenal (HPA) axis are suggested to play key roles in the pathophysiology of illness progression in bipolar disorder (BD), but the mechanisms leading to this dysfunction have never been elucidated. This study aimed to examine HPA axis activity and underlying molecular mechanisms in patients with BD and unaffected siblings of BD patients. METHODS: Twenty-four euthymic patients with BD, 18 siblings of BD patients, and 26 healthy controls were recruited for this study. All subjects underwent a dexamethasone suppression test followed by analyses associated with the HPA axis and the glucocorticoid receptor (GR). RESULTS: Patients with BD, particularly those at a late stage of illness, presented increased salivary post-dexamethasone cortisol levels when compared to controls (p = 0.015). Accordingly, these patients presented reduced ex vivo GR responsiveness (p = 0.008) and increased basal protein levels of FK506-binding protein 51 (FKBP51, p = 0.012), a co-chaperone known to desensitize GR, in peripheral blood mononuclear cells. Moreover, BD patients presented increased methylation at the FK506-binding protein 5 (FKBP5) gene. BD siblings presented significantly lower FKBP51 protein levels than BD patients, even though no differences were found in FKBP5 basal mRNA levels. CONCLUSIONS: Our data suggest that the epigenetic modulation of the FKBP5 gene, along with increased FKBP51 levels, is associated with the GR hyporesponsiveness seen in BD patients. Our findings are consistent with the notion that unaffected first-degree relatives of BD patients share biological factors that influence the disorder, and that such changes are more pronounced in the late stages of the illness.

Tryptophan diet reduces aggressive behavior in male mice

A tryptophan diet reduces aggressive behavior in different species, although some controversial findings have been reported. We studied 65 male mice divided into four groups according to increasing dosages of tryptophan (10, 20, 30, and 100 mg/kg) and a control group (vehicle). The first four groups ingested 10, 20, 30, and 100 mg/kg tryptophan together with cellulose vehicle and water by gavage before the behavioral tests that sought to record aggressive behavior. The control group received only the vehicle at the same time that the other groups received the tryptophan solutions. The results showed that low concentrations (10 and 20 mg/kg) of tryptophan decreased (p < .04) the frequency of attack bites and lateral threats (i.e., aggressive components; p < .02) after an encounter with a male intruder without altering locomotor activity. In conclusion, the low concentrations of tryptophan diminished aggressive behavior against a male intruder...