Regulation of Motor Function and Behavior by Atypical Chemokine Receptor 1

The final publication is available at Springer via http://dx.doi.org/10.1007/s10519-014-9665-7Atypical Chemokine Receptor 1 (ACKR1), previously known as the Duffy Antigen Receptor for Chemokines, stands out among chemokine receptors for its high selective expression on Purkinje cells of the cerebellum, consistent with the ability of ACKR1 ligands to activate Purkinje cells in vitro. Nevertheless, evidence for ACKR1 regulation of brain function in vivo has been lacking. Here we demonstrate that Ackr1−/− mice have markedly impaired balance and ataxia when placed on a rotating rod and increased tremor when injected with harmaline, a drug that induces whole-body tremor by activating Purkinje cells. Ackr1−/− mice also exhibited impaired exploratory behavior, increased anxiety-like behavior and frequent episodes of marked hypoactivity under low-stress conditions. The behavioral phenotype of Ackr1−/− mice was the opposite of the phenotype occurring in mice with cerebellar degeneration and the defects persisted when Ackr1 was deficient only on non-hematopoietic cells. We conclude that normal motor function and behavior depend in part on negative regulation of Purkinje cell activity by Ackr1

Cerebral metabolism in major depressive disorder: a voxel-based meta-analysis of positron emission tomography studies

BACKGROUND: Major depressive disorder (MDD) is a common mental illness with high lifetime prevalence close to 20%. Positron emission tomography (PET) studies have reported decreased prefrontal, insular and limbic cerebral glucose metabolism in depressed patients compared with healthy controls. However, the literature has not always been consistent. To evaluate current evidence from PET studies, we conducted a voxel-based meta-analysis of cerebral metabolism in MDD. METHOD: Data were collected from databases including PubMed and Web of Science, with the last report up to April 2013. Voxel-based meta-analyses were performed using the revised activation likelihood estimation (ALE) software. RESULTS: Ten whole-brain-based FDG-PET studies in MDD were included in the meta-analysis, comprising 188 MDD patients and 169 healthy controls. ALE analyses showed the brain metabolism in bilateral insula, left lentiform nucleus putamen and extra-nuclear, right caudate and cingulate gyrus were significantly decreased. However, the brain activity in right thalamus pulvinar and declive of posterior lobe, left culmen of vermis in anterior lobe were significantly increased in MDD patients. CONCLUSION: Our meta-analysis demonstrates the specific brain regions where possible dysfunctions are more consistently reported in MDD patients. Altered metabolism in insula, limbic system, basal ganglia, thalamus, and cerebellum and thus these regions are likely to play a key role in the pathophysiology of depression

Abnormal development of monoaminergic neurons is implicated in mood fluctuations and bipolar disorder

Subtle mood fluctuations are normal emotional experiences, whereas drastic mood swings can be a manifestation of bipolar disorder (BPD). Despite their importance for normal and pathological behavior, the mechanisms underlying endogenous mood instability are largely unknown. During embryogenesis, the transcription factor Otx2 orchestrates the genetic networks directing the specification of dopaminergic (DA) and serotonergic (5-HT) neurons. Here we behaviorally phenotyped mouse mutants overexpressing Otx2 in the hindbrain, resulting in an increased number of DA neurons and a decreased number of 5-HT neurons in both developing and mature animals. Over the course of 1 month, control animals exhibited stable locomotor activity in their home cages, whereas mutants showed extended periods of elevated or decreased activity relative to their individual average. Additional behavioral paradigms, testing for manic-and depressive-like behavior, demonstrated that mutants showed an increase in intra-individual fluctuations in locomotor activity, habituation, risk-taking behavioral parameters, social interaction, and hedonic-like behavior. Olanzapine, lithium, and carbamazepine ameliorated the behavioral alterations of the mutants, as did the mixed serotonin receptor agonist quipazine and the specific 5-HT 2C receptor agonist CP-809101. Testing the relevance of the genetic networks specifying monoaminergic neurons for BPD in humans, we applied an interval-based enrichment analysis tool for genome-wide association studies. We observed that the genes specifying DA and 5-HT neurons exhibit a significant level of aggregated association with BPD but not with schizophrenia or major depressive disorder. The results of our translational study suggest that aberrant development of monoaminergic neurons leads to mood fluctuations and may be associated with BPD

Hypomania induced by atypical antipsychotics among schizophrenic patients: Report of three cases

Santa Casa São Paulo Sch Med, Dept Psychiat, Div Gen Adult Psychiat, BR-04017030 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychiat, LINC, Interdisciplinary Lab Clin Neurosci, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychiat, LINC, Interdisciplinary Lab Clin Neurosci, São Paulo, BrazilWeb of Scienc

Is cerebellar volume related to bipolar disorder?

Background: Recent data suggest that cerebellum influences emotion modulation in humans. the findings of cerebellar abnormalities in bipolar disorder (BD) are especially intriguing given the link between the cerebellum emotional and behavioral regulation. the purpose of this study was to evaluate cerebellar volume in patients with euthymic BD type I compared to controls. Moreover, we investigated the possible relationship between cerebellar volume and suicidal behavior.Methods: Forty-patients with euthymic BD type I, 20 with and 20 without history of suicide attempt, and 22 healthy controls underwent an MRI scan. the participants were interviewed using the Structured Clinical Interview with the DSM-IV axis I (SCID-I), the Hamilton Depression Rating Scale (HDRS), the Young Mania Rating Scale (YMRS) and the Barratt Impulsiveness Scale (BIS-11).Results: Groups were age, gender and years of schooling-matched. the left cerebellum (p = 0.02), right cerebellum (p = 0.02) and vermis (p<0.01) were significantly smaller in the BD group; however, there were no volumetric differences between the BD subjects with and without suicidal attempt. There was no correlation between cerebellar measurements and clinical variables.Limitations: the main strength is that our sample consisted of patients with euthymic BD type I without any comorbidities, however, these results cannot establish causality as the cross-sectional nature of the study.Conclusions: Our findings suggest that the reduction in cerebellar volumes observed in BD type I might be a trait-related characteristic of this disorder. Additional studies with larger samples and subtypes of this heterogeneous disorder are warranted to determine the possible specificity of this cerebellar finding. (C) 2011 Elsevier B.V. All rights reserved.Mood and Anxiety Disorders Program (CETHA), Salvador-Bahia, BrazilConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo, Lab Interdisciplinar Neurociencias Clin LiNC, UNIFESP, BR-04039032 São Paulo, BrazilUniv Fed Tocantins, Tocantins, BrazilUniv Fed Bahia, CETHA, Salvador, BA, BrazilMed Diagnost, Image Mem, Salvador, BA, BrazilUniversidade Federal de São Paulo, Lab Interdisciplinar Neurociencias Clin LiNC, UNIFESP, BR-04039032 São Paulo, BrazilCNPq: 480918/2007-4Web of Scienc

Reduced cerebellar left hemisphere and vermal volume in adults with PTSD from a community sample

Background: Traumatic events exposure is a necessary condition for developing posttraumatic stress disorder (PTSD), but not all individuals exposed to the same trauma will develop PTSD. Human studies have suggested that the cerebellum is involved in human fear perception, anticipation, and recollection. in this context, the current study evaluated whether cerebellar volume is associated with PTSD.Methods: Eighty-four victims of violence, 42 who fulfilled the DSM-IV-TR criteria for PTSD and 42 resilient controls, were identified through an epidemiologic survey conducted in the city of 530 Paulo. Subjects were evaluated using the Clinician-Administered PTSD Scale (CAPS), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), and Early Trauma Inventory (ETI). All subjects underwent a magnetic resonance imaging (MRI) scan to evaluate their cerebellar hemispheres and vermis.Results: PTSD subjects had relative smaller left hemisphere (p = 0.04) and vermis (p < 0.01) volumes persisted after controlling for gender, age, and brain volume. in PTSD group, left cerebellar hemisphere volume correlated negatively with PTSD (p = 0.01) and depressive symptoms (p = 0.04). Vermal volume correlated negatively with PTSD symptoms (p < 0.01), early traumatic life events (p < 0.01), depressive symptoms (p = 0.04) and anxiety (p = 0.01).Conclusion: the cerebellum is involved in emotion modulation, and our results suggest that cerebellar volumetric reduction is associated with mood, anxiety and PTSD symptoms. Early traumatic life experiences are related to vermal volume reduction and may be a risk factor for future PTSD development. (C) 2011 Elsevier B.V. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo UNIFESP, LiNC, Edificio Pesquisas UNIFESP 2, BR-04039032 São Paulo, BrazilUFT, São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, Programa Atendimento & Pesquisa Violencia PROVE, BR-04039032 São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, Nucleo Estat & Metodol Aplicadas NEMAP, BR-04039032 São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, LiNC, Edificio Pesquisas UNIFESP 2, BR-04039032 São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, Programa Atendimento & Pesquisa Violencia PROVE, BR-04039032 São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, Nucleo Estat & Metodol Aplicadas NEMAP, BR-04039032 São Paulo, BrazilFAPESP: 2004/15039-0CNPq: 420122/2005-2Web of Scienc