CD300f immunoreceptor is associated with major depressive disorder and decreased microglial metabolic fitness.

A role for microglia in neuropsychiatric diseases, including major depressive disorder (MDD), has been postulated. Regulation of microglial phenotype by immune receptors has become a central topic in many neurological conditions. We explored preclinical and clinical evidence for the role of the CD300f immune receptor in the fine regulation of microglial phenotype and its contribution to MDD. We found that a prevalent nonsynonymous single-nucleotide polymorphism (C/T, rs2034310) of the human CD300f receptor cytoplasmic tail inhibits the protein kinase C phosphorylation of a threonine and is associated with protection against MDD, mainly in women. Interestingly, CD300f-/- mice displayed several characteristic MDD traits such as augmented microglial numbers, increased interleukin 6 and interleukin 1 receptor antagonist messenger RNA, alterations in synaptic strength, and noradrenaline-dependent and persistent depressive-like and anhedonic behaviors in females. This behavioral phenotype could be potentiated inducing the lipopolysaccharide depression model. RNA sequencing and biochemical studies revealed an association with impaired microglial metabolic fitness. In conclusion, we report a clear association that links the function of the CD300f immune receptor with MDD in humans, depressive-like and anhedonic behaviors in female mice, and altered microglial metabolic reprogramming.

Allopurinol for fibromyalgia pain in adults: A randomized controlled trial.

BACKGROUND: Allopurinol is a potent inhibitor of the enzyme xanthine oxidase used in the treatment of hyperuricemia and gout. Because it is well known that purines exert multiple affects on pain transmission, we hypothesized that the inhibition of xanthine oxidase by allopurinol could be a valid strategy to treat pain in humans. This study aimed to compare the analgesic efficacy of oral allopurinol versus placebo as an adjuvant therapy in patients displaying fibromyalgia. METHODS: This randomized, double-blinded, placebo-controlled study included 60 women with the diagnosis of fibromyalgia. Patients were randomly assigned to receive either oral allopurinol 300 mg (n = 31) or placebo (n = 29) twice daily during 30 days. The patients were submitted to evaluation for pain sensitivity, anxiety, depression, and functional status before treatment, and 15 and 30 days thereafter. RESULTS: Oral administration of allopurinol 300 mg twice daily was ineffective in improving pain scores measured by several tools up to 30 days of treatment (P > 0.05). Additionally, no significant effects of allopurinol over anxiety, depressive symptoms, and functional status of fibromyalgia patients were observed in the present study. CONCLUSIONS: Although previous findings indicated that allopurinol could present intrinsic analgesic effects in both animals and humans, this study showed no benefit of the use of oral allopurinol as an adjuvant strategy during 30 days in women displaying fibromyalgia. However, considering previous promising results, new prospective studies are still valid to further investigate allopurinol and more selective purine derivatives in the management of pain syndromes.

Allopurinol attenuates postoperative pain and modulates the purinergic system in patients undergoing abdominal hysterectomy: a randomized controlled trial.

PURPOSE: Allopurinol is a potent inhibitor of the enzyme xanthine oxidase used primarily in the treatment of hyperuricemia and gout. The aim of this study was to compare the analgesic efficacy of preanesthetic allopurinol versus placebo on postoperative pain and anxiety in patients undergoing abdominal hysterectomy. METHODS: This is a prospective, double-blinded, placebo-controlled, randomized clinical trial. We investigated 54 patients scheduled to undergo elective abdominal hysterectomy. Patients were randomly assigned to receive either oral allopurinol 300 mg (n = 27) or placebo (n = 27) the night before and 1 h before surgery. Patients were submitted to evaluation of pain and anxiety before the treatment, for 24 h postoperatively, 30 and 90 days after surgery. Cerebrospinal fluid was collected at the time of the spinal anesthesia to perform the measurement of the central levels of purines. RESULTS: Preoperative administration of allopurinol was effective in reducing postoperative pain 2 h after surgery. Allopurinol caused a reduction of approximately 40% in pain scores measured by the visual analogue pain scale after surgery (p < 0.05). No differences were found between groups in anxiety scores after surgery. There was a significant change in the cerebrospinal fluid concentrations of xanthine and uric acid before surgery (p < 0.01). CONCLUSION: This study showed a short-term benefit of the use of allopurinol as a preanesthetic medication since it was related to a reduction on pain scores 2 h after surgery. The purinergic system is a potential target for new analgesic drugs. New studies investigating more selective purine derivatives in the management of pain should be performed. TRIAL NUMBER REGISTRATION: Brazilian Registry of Clinical Trials-ReBEC #RBR-9pw58p.

Leptin in depressive episodes: is there a difference between unipolar and bipolar depression?

OBJECTIVE: The present study investigated whether peripheral leptin levels are associated with current depressive episodes in a cross-sectional study nested within a population-based study. METHODS: The Mini-International Neuropsychiatric Interview (MINI) 5.0 was used to assess the presence of current depressive episodes. The sample was composed of 206 subjects (103 controls and 103 subjects with a current depressive episode) paired by gender, BMI and age. Medication use and lifestyle characteristics were self-reported. RESULTS: Serum leptin levels were lower in currently depressive subjects (10.9 ± 12.0 ng/ml) than in the control group (20.3 ± 24.0 ng/ml; p = 0.023). According to the clinical diagnosis, individuals with bipolar depression present lower leptin levels (8.4 ± 8.1 ng/ml) than those with unipolar depression (12.0 ± 13.4 ng/ml) and the control group (20.3 ± 24.0 ng/ml; p = 0.031). In addition, ANCOVA showed that leptin is an independent factor associated with current depressive episodes (p = 0.018). CONCLUSION: A decreased leptin level might be a useful peripheral marker associated with depressive episodes in the context of bipolar disorder.

Increased serum neurotrophin levels related to alcohol use disorder in a young population sample.

BACKGROUND: The diagnosis of alcohol use disorder is based on clinical signs and on the measurement of biological markers. However, these markers are neither sufficiently sensitive, nor specific enough, for determining the effects of alcohol abuse on the central nervous system. Serum neurotrophins are important regulators of neural survival, development, function, and plasticity and have been found to be reduced in alcohol use disorder. The aim of this study was to investigate the alterations in serum neurotrophin levels (brain-derived neurotrophic factor [BDNF], glial-derived neurotrophic factor [GDNF], and nerve growth factor [NGF]) in alcohol use disorder in a young population, and thus possibly representing the early stages of the illness. METHODS: This is a cross-sectional study, nested in a population-based study of people aged 18 to 35, involving 795 participants. The participants responded to the CAGE questionnaire, and a CAGE score of ≥2 was considered to be a positive screen for the abuse/dependence or moderate to severe alcohol use disorder. Serum BDNF, GDNF, and NGF levels were measured by ELISA. RESULTS: In the CAGE ≥ 2 group, GDNF (p ≤ 0.001) and NGF (p ≤ 0.001) serum levels were significantly increased, and the BDNF elevation was near a statistical significance (p = 0.068) when compared to the CAGE < 2 group. A significantly positive correlation was observed only in the CAGE ≥ 2 group for BDNF/GDNF (r = 0.37, p < 0.001) and GDNF/NGF (r = 0.84, p < 0.001) levels. The correlation between the NGF and BDNF levels was significantly positive in both groups (r = 0.28, p < 0.001 for the CAGE < 2 group, and r = 0.30, p = 0.008 for the CAGE ≥ 2 group). CONCLUSIONS: These results suggest that elevated neurotrophins are candidate markers for the early stages of alcohol misuse.

The side-by-side exploratory test: a simple automated protocol for the evaluation of adult zebrafish behavior simultaneously with social interaction.

The assessment of shoaling in adult zebrafish is technically difficult, but important, given their social nature. The present study aimed to characterize a new protocol using simple automated tracking software to evaluate general behavior and social interaction simultaneously. To this end, we used a single tank with a central transparent glass division and placed one zebrafish on each side for 5 min. This strategy allows fish to interact visually at the same time that individual automated evaluation of behavior can be easily performed. Our results showed that, when two fish are placed side-by-side, there is an increase in their height in the tank compared with isolated fish and they remain close to each other. The pharmacological treatments with benzodiazepines (bromazepam and clonazepam) and the serotonergic drugs buspirone, fluoxetine, and escitalopram did not affect locomotion at the concentrations tested, except for the highest concentration of buspirone. Nevertheless, benzodiazepines increased interfish distance (i.e. reduced shoaling behavior) and serotonergic drugs elevated height in the tank. These results support the use of the side-by-side exploratory test for behavioral studies with the zebrafish, including high-throughput behavioral screening for antidepressants and anxiolytics.

Immune dysfunction in bipolar disorder and suicide risk: is there an association between peripheral corticotropin-releasing hormone and interleukin-1ß?

OBJECTIVE: The aim of the present study was to investigate the relationship between peripheral levels of corticotropin-releasing hormone (CRH) and interleukin-1ß (IL-1ß) in individuals with bipolar disorder (BD) with and without suicide risk (SR), and controls. METHODS: A total of 120 young adults (40 controls, 40 subjects with BD without SR, and 40 subjects with BD with SR) were enrolled from a population-based study carried out in the city of Pelotas, Brazil. BD and SR were assessed through the Mini International Neuropsychiatric Interview (MINI 5.0), and peripheral markers were evaluated by enzyme-linked immunosorbent assay (ELISA). RESULTS: Levels of CRH were significantly lower both in subjects with BD without SR (p = 0.04) and subjects with BD with SR (p = 0.02) when compared to controls. However, levels of IL-1ß were increased in subjects with BD with SR (p = 0.05) when compared to controls. Sociodemographic and clinical variables, current mood episode, and use of psychiatric medications were not associated with changes in these markers. No correlation was found between peripheral levels of CRH and IL-1ß (p = 0.60) in the population or in the BD with SR group (p = 0.88). CONCLUSIONS: These results suggest that peripheral mechanisms linking stress hormones and the immune system might be critical patterns involved in suicidal behavior associated with BD.

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.

Y-Maze memory task in zebrafish (Danio rerio): the role of glutamatergic and cholinergic systems on the acquisition and consolidation periods.

The interest in the behavioral features of zebrafish has significantly increased over the past two decades. However, most available protocols have used longer training periods and have been based on reinforcement/reward or avoidance. The Y-Maze memory task has the advantage of using a simple and rapid training session, but it has not been established in zebrafish. Here, we have characterized this task for zebrafish, with the addition of pharmacological interventions in the acquisition and consolidation memory phases. The results show that zebrafish spend more time in the novel arm than in the other arms of the Y-Maze, both in response to novelty and spatial memory training-test intervals (TTIs). We have also studied the involvement of the glutamatergic and cholinergic systems with pre- and post-training treatments with the NMDA receptor antagonist MK-801 (20 µM) and the cholinergic blocker scopolamine (200 µM). After 1h of TTI, pre-training MK-801 and scopolamine-treated fish reduced their exploration of the novel arm when compared to the control group, with no changes in their locomotor activity. Post-training of MK-801 treatment also impaired their Y-Maze performance, while post-training of any scopolamine treatment failed to affect novel arm exploration. In conclusion, the Y-Maze memory task can be reliably used for zebrafish, providing a new, rapid, and preference/avoidance independent task for the study of memory in this teleost. In addition, our results highlight the implication of the glutamatergic and cholinergic systems in the memory of zebrafish.

Acute restraint stress in zebrafish: behavioral parameters and purinergic signaling.

Despite the extensive knowledge about the effects of acute restraint stress (ARS) in rodents, zebrafish research is still elementary in this field, and the consequences of stress on purinergic system are unclear. Therefore, we evaluated the effects of ARS on behavior, biochemical, and molecular parameters in zebrafish brain. Animals were submitted to a 90 min ARS protocol and tested for anxiety levels, exploratory behavior, and memory performance. Furthermore, we analyzed ectonucleotidase and adenosine deaminase activities and their gene expression profile, as well as transcription of adenosine receptors. ARS increased anxiety, but did not impair locomotion or cognition. ARS significantly increased ATP hydrolysis, decreased cytosolic ADA activity, and changed the entpd and adora gene expression. In conclusion, ARS disturbed zebrafish behavior, and we hypothesize that the augmentation in adenosine-mediated signaling may be a strategy to reestablish homeostasis and normal behavior after a stressful event.

Sensitivity is the dimension of temperament most associated with the progression from ideation to suicide attempts.

BACKGROUND: To analyze the association between temperament (emotional and affective) and scrutinize the progression from suicide ideation to attempt, by using data from a large internet-based sample. METHODS: It is a cross-sectional study, based on the Brazilian Internet Study on Temperament and Psychopathology (BRAINSTEP). Temperament was assessed by the Affective and Emotional Composite Temperament Scale (AFECTS), and life-long suicidal behavior was determined by the adapted Suicidal Behaviors Questionnaire (SBQ-17). Odds ratios were obtained through multivariate logistic regression and a multiple linear regression were used in the analysis. According to the "ideation-to-action framework", we performed analyzes using two different reference groups: no suicidal ideation and suicidal ideation. RESULTS: The affective temperaments that showed the greatest association with suicide attempts were depressive, cyclothymic, and volatile. The temperaments that reflected higher associations for progression from ideation to suicide attempt were cyclothymic, depressive, and euphoric. Sensitivity was manifested as the emotional temperament with the strongest positive association with the severity of suicidal behavior, followed by desire and control. Stability was estimated as the emotional trait with the strongest negative association with the severity of suicidal behavior. LIMITATIONS: It is not a population based sample. BRAINSTEP is a self-selected sample whose participants are mostly women, who are highly educated and young. CONCLUSIONS: Our results suggest that temperament assessment using AFECT model may be relevant to assess the risk for the progression from ideation to suicide attempts. These results strengthen the "ideation-to-action" framework that risk factors to suicide ideators can differ from suicide attempters.

Sex-dependent role of CD300f immune receptor in generalized anxiety disorder.

Generalized Anxiety Disorder (GAD) presents a high prevalence in the population, leading to distress and disability. Immune system alterations have been associated with anxiety-related behaviors in rodents and GAD patients. CD300f immune receptors are highly expressed in microglia and participate not only in the modulation of immune responses but also in pruning and reshaping synapses. It was recently demonstrated that CD300f might be influential in the pathogenesis of depression in a sex-dependent manner. Here, we evaluated the role of CD300f immune receptor in anxiety, using CD300f knockout mice (CD300f-/-) and patients with GAD. We observed that male CD300f-/- mice had numerous behavioral changes associated with a low-anxiety phenotype, including increased open field central locomotion and rearing behaviors, more exploration in the open arms of the elevated plus-maze test, and decreased latency to eat in the novelty suppressed feeding test. In a cross-sectional population-based study, including 1111 subjects, we evaluated a common single-nucleotide polymorphism rs2034310 (C/T) in the cytoplasmatic tail of CD300f gene in individuals with GAD. Notably, we observed that the T allele of the rs2034310 polymorphism conferred protection against GAD in men, even after adjusting for confounding variables. Overall, our data demonstrate that CD300f immune receptors are involved in the modulation of pathological anxiety behaviors in a sex-dependent manner. The biological basis of these sex differences is still poorly understood, but it may provide significant clues regarding the neuropathophysiological mechanisms of GAD and can pave the way for future specific pharmacological interventions.

Increased plasma levels of brain derived neurotrophic factor (BDNF) in patients with fibromyalgia.

Brain-derived neurotrophic factor (BDNF) is involved in neuronal survival and synaptic plasticity of the central and peripheral nervous system. BDNF appears to modulate nociceptive sensory inputs and pain hypersensitivity and has been studied in pathological situations, including chronic pain conditions and major depression. Increased serum BDNF levels have been recently reported in fibromyalgia (FM). In the present study, we assessed plasma BDNF levels in patients with FM and controls. Plasma BDNF was measured from 30 female patients with FM and 30 healthy age- and gender-matched volunteers using an enzyme immunoassay. FM patients showed higher levels of BDNF (FM = 167.1 +/- 171.2 pg/mL) when compared with the control group (control = 113.8 +/- 149.6 pg/mL) (P = 0.049; Mann-Whitney test). Six out of 30 controls presented superior values to the medium (15/15) of the patients with fibromyalgia (129 pg/mL) (P = 0.029, Fisher exact test). There was no correlation between plasma BDNF levels and age, disease duration, pain score, number of pain points and HAM-D score. Our results confirm previous findings of increased plasma BDNF levels in patients with FM, suggesting that BDNF may be involved in the pathophysiology of Fibromyalgia, despite high levels of depression.

Metabolic and behavioral effects of chronic olanzapine treatment and cafeteria diet in rats.

Olanzapine and highly palatable diets can alter metabolism and brain function. We investigated the interaction of chronic treatment (4 months) with olanzapine and a cafeteria diet on metabolic parameters, memory tasks (spatial and aversive), the elevated plus maze and locomotor activity induced by d-amphetamine. Male Wistar rats were separated into the following groups: standard diet vehicle, standard diet and olanzapine, cafeteria diet vehicle and cafeteria diet and olanzapine. Olanzapine was administered in the drinking water (approximately 1.5 mg/kg/day), and after 3 days of treatment, the rats exhibited an expected anxiolytic effect and reduced amphetamine-induced hyperlocomotion. After 4 months of treatment, cafeteria diet vehicle and cafeteria diet olanzapine rats exhibited an increased body weight and heavier fat pads compared with the standard diet groups. Olanzapine increased only the epididymal and mesenteric fat pads. The cafeteria diet and olanzapine group showed greater glucose intolerance compared with all other groups. The cafeteria diet altered the effects of chronic olanzapine on the performance in the water maze and inhibitory avoidance tasks. Chronic olanzapine treatment failed to affect amphetamine-induced locomotion and to produce anxiolytic effects in the elevated plus maze task, regardless of the diet. Our results suggest that chronic olanzapine caused an increase in fat pads, which is putatively involved in the etiology of many metabolic diseases. Rats on the cafeteria diet were overweight and exhibited glucose intolerance. We did not observe these effects with olanzapine treatment with the standard diet. Moreover, the chronic treatment regimen caused tolerance to the antipsychotic and anxiolytic effects of olanzapine and seemed to potentiate some of the metabolic effects of the cafeteria diet. The cafeteria diet also modified the effects of chronic treatment with olanzapine on cognitive tasks, which may represent an undesirable effect of poor diets in psychiatric patients.

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.

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.

Does caffeine change the effect of sleep deprivation on moderate to severe depressed patients?

INTRODUCTION: Sleep deprivation (SD) has been used as an alternative approach to treat major depressive disorder (MDD). Caffeine, due to its stimulating effect, could be an alternative to promote sleep deprivation. However, there are no data about its potential influence on the antidepressive effect of SD. The objective of this study is to assess the effect of caffeine on SD in non-psychotic patients with moderate to severe unipolar depression. METHODS: Randomized, double-blind, crossover clinical trial comparing caffeine and placebo in moderate to severe depressed patients who underwent total sleep deprivation (SD). The patients were assessed with items of the Bond-Lader scale, the 6-item Hamilton Depression Rating Scale (HAMD-6), and the Clinical Global Impression (CGI)-Severity/Improvement. RESULTS: Twenty patients participated in this study. The patients who consumed caffeine presented the same level of energy before and after sleep deprivation (lethargic-energetic item of the Bond-Lader scale), while the patients in the placebo group had a reduced level of energy after sleep deprivation (p=0.0045). There was no difference between the caffeine and placebo groups in the other items of the Bond-Lader scale. CONCLUSION: The combined use of caffeine and SD can be a useful strategy to keep the patient awake without impairing the effect of SD on depressed outpatients. However, further studies involving patients who have responded to SD are needed in order to verify if caffeine also does not interfere with the results in this group.

The NMDA antagonist MK-801 induces hyperalgesia and increases CSF excitatory amino acids in rats: reversal by guanosine.

Excitatory amino acids (EAAs) and their receptors play a central role in the mechanisms underlying pain transmission. NMDA-receptor antagonists such as MK-801 produce antinociceptive effects against experimental models of chronic pain, but results in acute pain models are conflicting, perhaps due to increased glutamate availability induced by the NMDA-receptor antagonists. Since guanosine and riluzole have recently been shown to stimulate glutamate uptake, the aim of this study was to examine the effects of guanosine or riluzole on changes in nociceptive signaling induced by MK-801 in an acute pain model. Rats received an i.p. injection of vehicle, morphine, guanosine, riluzole or MK-801 or a combined treatment (vehicle, morphine, guanosine or riluzole+MK-801) and were evaluated in the tail flick test, or had a CSF sample drawn after 30 min. Riluzole, guanosine, and MK-801 (0.01 or 0.1 mg/kg) did not affect basal nociceptive responses or CSF EAAs levels. However, MK-801 (0.5 mg/kg) induced hyperalgesia and increased the CSF EAAs levels; both effects were prevented by guanosine, riluzole or morphine. Hyperalgesia was correlated with CSF aspartate and glutamate levels. This study provides additional evidence for the mechanism of action of MK-801, showing that MK-801 induces hyperalgesia with parallel increase in CSF EAAs levels.

The posttraumatic stress disorder project in Brazil: neuropsychological, structural and molecular neuroimaging studies in victims of urban violence.

BACKGROUND: Life trauma is highly prevalent in the general population and posttraumatic stress disorder is among the most prevalent psychiatric consequences of trauma exposure. Brazil has a unique environment to conduct translational research about psychological trauma and posttraumatic stress disorder, since urban violence became a Brazilian phenomenon, being particularly related to the rapid population growth of its cities. This research involves three case-control studies: a neuropsychological, a structural neuroimaging and a molecular neuroimaging study, each focusing on different objectives but providing complementary information. First, it aims to examine cognitive functioning of PTSD subjects and its relationships with symptomatology. The second objective is to evaluate neurostructural integrity of orbitofrontal cortex and hippocampus in PTSD subjects. The third aim is to evaluate if patients with PTSD have decreased dopamine transporter density in the basal ganglia as compared to resilient controls subjects. This paper shows the research rationale and design for these three case-control studies. METHODS AND DESIGN: Cases and controls will be identified through an epidemiologic survey conducted in the city of São Paulo. Subjects exposed to traumatic life experiences resulting in posttraumatic stress disorder (cases) will be compared to resilient victims of traumatic life experiences without PTSD (controls) aiming to identify biological variables that might protect or predispose to PTSD. In the neuropsychological case-control study, 100 patients with PTSD, will be compared with 100 victims of trauma without posttraumatic stress disorder, age- and sex-matched controls. Similarly, 50 cases and 50 controls will be enrolled for the structural study and 25 cases and 25 controls in the functional neuroimaging study. All individuals from the three studies will complete psychometrics and a structured clinical interview (the Structured Clinical Interview for DSM-IV and the Clinician-Administered PTSD Scale, Beck Anxiety Inventory, Beck Depression Inventory, Global Assessment of Function, The Social Adjustment Scale, Medical Outcomes Study 36-Item Short-Form Health Survey, Early Trauma Inventory, Clinical global Impressions, and Peritraumatic Dissociative Experiences Questionnaire). A broad neuropsychological battery will be administered for all participants of the neuropsychological study. Magnetic resonance scans will be performed to acquire structural neuroimaging data. Single photon emission computerized tomography with [(99m)Tc]-TRODAT-1 brain scans will be performed to evaluate dopamine transporters. DISCUSSION: This study protocol will be informative for researchers and clinicians interested in considering, designing and/or conducting translational research in the field of trauma and posttraumatic stress disorder.

Attention deficit hyperactivity disorder and the behavior of "Che" Guevara.

Attention deficit hyperactivity disorder (ADHD) is a childhood onset neuropsychiatric disorder characterized by inattention, hyperactivity and impulsivity. ADHD is related to several co-morbidities, such as opposition defiant disorder, conduct disorder, mood and anxiety disturbances, as well as tics and Tourette's syndrome. The objective of this report is to shed an alternative light on the personality of Ernesto "Che" Guevara, discussing whether he might have had ADHD. Several published biographies of Che Guevara were reviewed. Established ADHD criteria (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition), were used as a framework to evaluate Che's behaviour. In addition, we compared the main features of Che's reported behaviour to the set of abnormalities leading to the diagnosis of ADHD in adults proposed by Wender and colleagues and known as the UTAH ADHD criteria. Analysis of the most renowned biographies of Ernesto "Che" Guevara suggests that he may have had ADHD.