Relationship between structural abnormalities in the cerebellum and dementia, posttraumatic stress disorder and bipolar disorder

Baldaçara, Leonardo; Borgio, João Guilherme Fiorani; Araújo, Célia; Nery-Fernandes, Fabiana; Lacerda, Acioly Luiz Taveres; Moraes, Walter André dos Santos; Montaño, Maria Beatriz Marcondes Macedo; Rocha, Marlos; Quarantini, Lucas C.; Schoedl, Aline; Pupo, Mariana; Mello, Marcelo F.; Andreoli, Sergio B.; Miranda-Scippa, Angela; Ramos, Luiz Roberto; Mari, Jair J.; Bressan, Rodrigo Affonseca; Jackowski, Andrea Parolin

doi:10.1590/S1980-57642012DN06040003

ABSTRACT.

New evidence suggests that the cerebellum has structural and functional abnormalities in psychiatric disorders.

Objective:

In this research, the goal was to measure the volume of the cerebellum and its subregions in individuals with psychiatric disorders and to relate these findings to their symptoms.

Methods:

Patients with different degrees of cognitive impairment (Epidemiology of the Elderly - UNIFESP) and patients with post-traumatic stress disorder (PTSD) from population studies were analyzed. Also, patients with bipolar disorder from an outpatient clinic (Center for the Study of Mood and Anxiety Disorders, Universidade Federal da Bahia) were recruited for this study. All subjects underwent a 1.5T structural magnetic resonance scan. Volumetric measures and symptom measurements, by psychometric scales, were performed and compared between patients and controls.

Results:

The cerebellum volume was reduced in patients with cognitive impairment without dementia and with dementia, in patients with PTSD, and in patients with bipolar disorder compared to controls. In dementia and PTSD, the left cerebellar hemisphere and vermis volume were reduced. In bipolar disorder, volumes of both hemispheres and the vermis were reduced. In the first two studies, these cerebellar volumetric reductions correlated with symptoms of the disease.

Conclusion:

The exact nature of cerebellar involvement in mental processes is still not fully understood. However, abnormalities in cerebellar structure and its functions have been reported in some of these diseases. Future studies with larger samples are needed to clarify these findings and investigate whether they are important for treatment and prognosis.

Key words:
cerebellum; neuroimaging; mental disorders; risk factors; comparative study

RESUMO

Novas evidências sugerem que o cerebelo apresenta alterações estruturais e funcionais nos transtornos psiquiátricos.

Objetivo:

Medir o volume do cerebelo e de suas sub-regiões em indivíduos portadores de transtornos psiquiátricos e relacionar tais achados aos sintomas.

Métodos:

Foi realizada a identificação de pacientes com diferentes graus de prejuízo cognitivo proveniente de um estudo populacional (Epidemiologia do Idoso - UNIFESP), pacientes com transtorno do estresse pós-traumático proveniente de outro estudo populacional e portadores de transtorno bipolar proveniente de um ambulatório especializado (Universidade Federal da Bahia). Todos os sujeitos foram submetidos à ressonância magnética estrutural de 1.5T. As medidas de volume, assim como os sintomas medidos por escalas psicométricas foram comparadas entre pacientes e controles.

Resultados:

Foi observado que o volume do cerebelo está reduzido nos portadores de prejuízo cognitivo sem demência e com demência, no transtorno do estresse pós-traumático e no transtorno bipolar quando comparados aos controles. Na demência e no transtorno do estresse pós-traumático o volume do hemisfério cerebelar esquerdo e do vérmis estão reduzidos. No transtorno bipolar os volumes de ambos os hemisférios e do vérmis estão reduzidos. Nos dois primeiros estudos estas reduções correlacionaram com os sintomas.

Conclusão:

A natureza exata do envolvimento do cerebelo nos processos mentais ainda não é compreendida. Entretanto, anormalidades na estrutura cerebelar e em suas funções têm sido relatadas em algumas dessas doenças. Pesquisas futuras, com amostras maiores, ainda são necessárias para esclarecer tais achados e investigar se são importantes para o tratamento e prognóstico.

Palavras-chave:
cerebelo; neuroimagem; transtornos mentais; fatores de risco; estudo comparativo

Texto completo disponível apenas em PDF.

Full text available only in PDF format.

REFERENCES

Meneses MS. Neuroanatomia Aplicada. 3a ed. Rio de Janeiro: Guanabara Koogan; 2011.
Baldaçara L, Borgio JGF, Lacerda ALT, Jackowski AP. Cerebellum and psychiatric disorders. Rev Bras Psiquiatr 2008;30:281-289.
Baillieux H, De Smet HJ, Dobbeleir A, Paquier PF, De Deyn PP, Marien P. Cognitive and affective disturbances following focal cerebellar damage in adults: a neuropsychological and SPECT study. Cortex 2010;46:869-879.
Marien P, Baillieux H, De Smet HJ, et al. Cognitive, linguistic and affective disturbances following a right superior cerebellar artery infarction: a case study. Cortex 2009;45:527-536.
Stoodley CJ, Schmahmann JD. Functional topography in the human cerebellum: a meta-analysis of neuroimaging studies. NeuroImage 2009;44:489-501.
Picard H, Amado I, Mouchet-Mages S, Olie JP, Krebs MO. The role of the cerebellum in schizophrenia: an update of clinical, cognitive, and functional evidences. Schizophr bull 2008;34:155-172.
Monkul ES, Hatch JP, Sassi RB, et al. MRI study of the cerebellum in young bipolar patients. Prog Neuropsychopharmacol Biol Psychiatry 2008;32:613-619.
Cheron G, Servais L, Dan B. Cerebellar network plasticity: From genes to fast oscillation. Neuroscience 2008;153:1-19.
De Bellis MD, Kuchibhatla M. Cerebellar volumes in pediatric maltreatment-related posttraumatic stress disorder. Biol Psychiatry 2006;60: 697-703.
Mackie S, Shaw P, Lenroot R, et al. Cerebellar development and clinical outcome in attention deficit hyperactivity disorder. Am J Psychiatry 2007;164:647-655.
Wegiel J, Wisniewski HM, Dziewiatkowski J, et al. Cerebellar atrophy in Alzheimer's disease-clinicopathological correlations. Brain Res 1999; 818:41-50.
Sjobeck M, Englund E. Alzheimer's disease and the cerebellum: a morphologic study on neuronal and glial changes. Dement Geriatr Cogn Disorders 2001;12:211-218.
Thomann PA, Schlafer C, Seidl U, Santos VD, Essig M, Schroder J. The cerebellum in mild cognitive impairment and Alzheimer's disease - a structural MRI study. J Psychiatric Res 2008;42:1198-1202.
Schutter DJ, van Honk J. The cerebellum in emotion regulation: a repetitive transcranial magnetic stimulation study. Cerebellum 2009;8:28-34.
Nashold BS, Jr., Slaughter DG. Effects of stimulating or destroying the deep cerebellar regions in man. J Neurosurg 1969;31:172-86.
Lippmann S, Manshadi M, Baldwin H, Drasin G, Rice J, Alrajeh S. Cerebellar vermis dimensions on computerized tomographic scans of schizophrenic and bipolar patients. Am J Psychiatry 1982;139:667-668.
Nasrallah HA, McCalley-Whitters M, Jacoby CG. Cortical atrophy in schizophrenia and mania: a comparative CT study. J Clin Psychiatry 1982;43:439-441.
Nasrallah HA, Jacoby CG, McCalley-Whitters M. Cerebellar atrophy in schizophrenia and mania. Lancet 1981;8229:1102.
Weinberger DR, DeLisi LE, Perman GP, Targum S, Wyatt RJ. Computed tomography in schizophreniform disorder and other acute psychiatric disorders. Arch Gen Psychi 1982;39:778-783.
Moorhead TW, McKirdy J, Sussmann JE, Hall J, Lawrie SM, Johnstone EC, McIntosh AM. Progressive gray matter loss in patients with bipolar disorder. Biol Psychiatry 2007;62:894-900.
Mills NP, Delbello MP, Adler CM, Strakowski SM. MRI analysis of cerebellar vermal abnormalities in bipolar disorder. Am J Psychiatry 2005; 162:1530-1532.
DelBello MP, Strakowski SM, Zimmerman ME, Hawkins JM, Sax KW. MRI analysis of the cerebellum in bipolar disorder: a pilot study. Neuropsychopharmacol 1999;21:63-68.
Osuch EA, Benson B, Geraci M, Podell D, Herscovitch P, McCann UD, Post RM. Regional cerebral blood flow correlated with flashback intensity in patients with posttraumatic stress disorder. Biol Psychiatry 2001; 50:246-253.
Anderson CM, Teicher MH, Polcari A, Renshaw PF. Abnormal T2 relaxation time in the cerebellar vermis of adults sexually abused in childhood: potential role of the vermis in stress-enhanced risk for drug abuse. Psychoneuroendocrinology 2002;27:231-244.
Pissiota A, Frans O, Fernandez M, von Knorring L, Fischer H, Fredrikson M. Neurofunctional correlates of posttraumatic stress disorder: a PET symptom provocation study. Eur Arch Psychiatry Clin Neurosci 2002; 252:68-75.
De Bellis MD, Keshavan MS, Frustaci K, et al. Superior temporal gyrus volumes in maltreated children and adolescents with PTSD. Biol Psychiatry 2002;51:544-552.
Thomas LA, De Bellis MD. Pituitary volumes in pediatric maltreatment-related postraumatic stress disorder. Biol Psychiatry 2004;55:752-758.
d'Orsi E, Xavier AJ, Ramos LR. Work, social support and leisure protect the elderly from functional loss: EPIDOSO study. Rev Saude Publica 2011;45:685-692.
Montaño MBMM, Ramos LR. Validade da versão em português da Clinical Dementia Rating. Rev Saúde Pública 2005;39:912-917.
Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E. Mild cognitive impairment: clinical characterization and outcome. Arch Neurol 1999;56:303-308.
Dubois B, Feldman HH, Jacova C, et al. Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria. Lancet Neurol 2007;6:734-746.
Baldaçara L, Borgio JGF, Moraes WAS, et al. Cerebellar volume in patients with dementia. Rev Bras Psiquiatr 2011;33:122-129.
Andreoli SB, Ribeiro WS, Quintana MI, et al. Violence and post-traumatic stress disorder in Sao Paulo and Rio de Janeiro, Brazil: the protocol for an epidemiological and genetic survey. BMC Psychiatry 2009;9:34.
Bressan RA, Quarantini LC, Andreoli SB, et al. The posttraumatic stress disorder project in Brazil: neuropsychological, structural and molecular neuroimaging studies in victims of urban violence. BMC Psychiatry 2009;9:30.
Baldacara L, Jackowski AP, Schoedl A, et al. Reduced cerebellar left hemisphere and vermal volume in adults with PTSD from a community sample. J Psychiatric Res 2011;45:1627-1633.
Baldacara L, Nery-Fernandes F, Rocha M, et al. Is cerebellar volume related to bipolar disorder? J Affect Disorder 2011;135:305-309.
Spitzer RL, Williams JB, Gibbon M, First MB. The Structured Clinical Interview for DSM-III-R (SCID). I: History, rationale, and description. Arch Gen Psychiatry 1992;49:624-629.
Williams JB, Gibbon M, First MB, et al. The Structured Clinical Interview for DSM-III-R (SCID). II. Multisite test-retest reliability. Arch Gen Psychiatry 1992;49:630-636.
Folstein MF, Folstein SE, McHugh PR. Mini-mental state: a practical method for grading the cognitive state of patients for the clinican. J Psychiatric Res 1975;12:189-198.
Pfeffer RI, Kurosaki TT, Harrah CH, Jr., Chance JM, Filos S. Measurement of functional activities in older adults in the community. J Gerontol 1982;37:323-329.
Pupo MC, Jorge MR, Schoedl AF, et al. The accuracy of the Clinician-Administered PTSD Scale (CAPS) to identify PTSD cases in victims of urban violence. Psychiatry Res 2011;185:157-160.
Beck AT, Epstein N, Brown G, Steer RA. An inventory for measuring clinical anxiety: psychometric properties. J Consult Clin Psychol 1988; 56:893-897.
Beck AT, Rial WY, Rickels K. Short form of depression inventory: cross-validation. Psychol Reports 1974;34:1184-1186.
Mello MF, Schoedl AF, Pupo MC, Souza AA, Andreoli SB, Bressan RA, Mari JJ. Early Trauma Inventory (ETI): cross-cultural adaptation and internal consistency. Cad Saude Publica 2010;26:713-724.
Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960;23:56-62.
Young RC, Biggs JT, Ziegler VE, Meyer DA. A rating scale for mania: reliability, validity and sensitivity. Br J Psychiatry 1978;133:429-435.
Bayle FJ, Bourdel MC, Caci H, et al. Factor analysis of french translation of the Barratt impulsivity scale (BIS-10). Can J Psychiatry 2000; 45:156-165.
Ashburner J, Friston KJ. Unified segmentation. Neuroimage 2005; 26: 839-851.
De Bellis MD, Kuchibhatla M. Cerebellar Volumes in Pediatric Maltreatment-Related Posttraumatic Stress Disorder. Biol Psychiatry 2006; 60:697-703.
Luft AR, Skalej M, Schulz JB, et al. Patterns of age-related shrinkage in cerebellum and brainstem observed in vivo using three-dimensional MRI volumetry. Cereb Cortex 1999;9:712-721.
Pierson R, Corson PW, Sears LL, et al. Manual and semiautomated measurement of cerebellar subregions on MR images. Neuroimage 2002;17:61-76.
Walter H, Vasic N, Hose A, Spitzer M, Wolf RC. Working memory dysfunction in schizophrenia compared to healthy controls and patients with depression: evidence from event-related fMRI. Neuroimage 2007; 35:1551-1561.
Timmann D, Daum I. Cerebellar contributions to cognitive functions: a progress report after two decades of research. Cerebellum 2007;6: 159-162.
Schmahmann JD, Weilburg JB, Sherman JC. The neuropsychiatry of the cerebellum - insights from the clinic. Cerebellum 2007;6:254-267.
Schmahmann JD. The cerebellum and cognition. Volume 41. San Diego: Academic Press; 1997.
Xu D, Liu T, Ashe J, Bushara KO. Role of the olivo-cerebellar system in timing. J Neurosci 2006;26:5990-5995.
Ito M. Cerebellar circuitry as a neuronal machine. Prog Neurobiol. 2006; 78:272-303.
Schutter DJ, van Honk J. The cerebellum on the rise in human emotion. Cerebellum 2005;4:290-294.
Carrion VG, Weems CF, Watson C, Eliez S, Menon V, Reiss AL. Converging evidence for abnormalities of the prefrontal cortex and evaluation of midsagittal structures in pediatric posttraumatic stress disorder: an MRI study. Psychiatry Res 2009;172:226-234.
Levitt JJ, Chen QC, May FS, Gilbertson MW, Shenton ME, Pitman RK. Volume of cerebellar vermis in monozygotic twins discordant for combat exposure: lack of relationship to post-traumatic stress disorder. Psychiatry Res 2006;148:143-149.
Bonne O, Gilboa A, Louzoun Y, Brandes D, Yona I, Lester H. Resting regional cerebral perfusion in recent posttraumatic stress disorder. Biol Psychiatry 2003;54:1077-1086.
Fernandez M, Pissiota A, Frans O, von Knorring L, Fischer H, Fredrikson M. Brain function in a patient with torture related post-traumatic stress disorder before and after fluoxetine treatment: A positron emission tomography provocation study. Neurosci Lett 2001;297:101-104.
Spinelli S, Chefer S, Suomi SJ, Higley JD, Barr CS, Stein E. Early-life stress induces long-term morphologic changes in primate brain. Arch Gen Psychiatry 2009;66:658-665.
LeardMann CA, Smith B, Ryan MA. Do adverse childhood experiences increase the risk of postdeployment posttraumatic stress disorder in US Marines? BMC Public Health 2010;10:437.
Teicher MH, Tomoda A, Andersen SL. Neurobiological consequences of early stress and childhood maltreatment: Are results from human and animal studies comparable? Ann NY Acad Sci 2006;1071:313-323.
Sanders T, Liu Y, Buchner V, Tchounwou PB. Neurotoxic effects and biomarkers of lead exposure: a review. Rev Environ Health 2009;24:15-45.
Altman J. Morphological and behavioral markers of environmentally induced retardation of brain development: an animal model. Environ Health Perspect 1987;74:153-168.
Martinussen M, Flanders DW, Fischl B, et al. Segmental brain volumes and cognitive and perceptual correlates in 15-year-old adolescents with low birth weight. J Pediatr 2009;155:848-853.
Ferguson SA, Holson RR. Neonatal dexamethasone on day 7 in rats causes mild hyperactivity and cerebellar stunting. Neurotoxicol Teratol 1999;21:71-76.
Mello MF, Faria AA, Mello AF, Carpenter LL, Tyrka AR, Price LH. [Childhood maltreatment and adult psychopathology: pathways to hypothalamic-pituitary-adrenal axis dysfunction]. Rev Bras Psiquiatr 2009;31 Suppl 2:S41-S48.
Coplan JD, Smith EL, Altemus M, et al. Maternal-infant response to variable foraging demand in nonhuman primates: effects of timing of stressor on cerebrospinal fluid corticotropin-releasing factor and circulating glucocorticoid concentrations. Ann N Y Acad Sci 2006;1071: 525-533.
De Bellis MD. Developmental Traumatology: The psychobiological development of maltreated children and its implications for research, treatment, and policy. Dev Psychopathol 2001;13:537-561.
Llorente R, Gallardo ML, Berzal AL, Prada C, Garcia-Segura LM, Viveros MP. Early maternal deprivation in rats induces gender-dependent effects on developing hippocampal and cerebellar cells. Int J Dev Neurosci 2009;3:233-241.
MacKenzie SM, Dewar D, Stewart W, Fraser R, Connell JM, Davies E. The transcription of steroidogenic genes in the human cerebellum and hippocampus: a comparative survey of normal and Alzheimer's tissue. J Endocrinol 2008;196:123-130.

Publication Dates

Publication in this collection
Oct-Dec 2012

History

Received
10 June 2012
Accepted
03 Sept 2012

This is an open-access article distributed under the terms of the Creative Commons Attribution License

[1] Meneses MS. Neuroanatomia Aplicada. 3a ed. Rio de Janeiro: Guanabara Koogan; 2011.

[2] Baldaçara L, Borgio JGF, Lacerda ALT, Jackowski AP. Cerebellum and psychiatric disorders. Rev Bras Psiquiatr 2008;30:281-289.

[3] Baillieux H, De Smet HJ, Dobbeleir A, Paquier PF, De Deyn PP, Marien P. Cognitive and affective disturbances following focal cerebellar damage in adults: a neuropsychological and SPECT study. Cortex 2010;46:869-879.

[4] Marien P, Baillieux H, De Smet HJ, et al. Cognitive, linguistic and affective disturbances following a right superior cerebellar artery infarction: a case study. Cortex 2009;45:527-536.

[5] Stoodley CJ, Schmahmann JD. Functional topography in the human cerebellum: a meta-analysis of neuroimaging studies. NeuroImage 2009;44:489-501.

[6] Picard H, Amado I, Mouchet-Mages S, Olie JP, Krebs MO. The role of the cerebellum in schizophrenia: an update of clinical, cognitive, and functional evidences. Schizophr bull 2008;34:155-172.

[7] Monkul ES, Hatch JP, Sassi RB, et al. MRI study of the cerebellum in young bipolar patients. Prog Neuropsychopharmacol Biol Psychiatry 2008;32:613-619.

[8] Cheron G, Servais L, Dan B. Cerebellar network plasticity: From genes to fast oscillation. Neuroscience 2008;153:1-19.

[9] De Bellis MD, Kuchibhatla M. Cerebellar volumes in pediatric maltreatment-related posttraumatic stress disorder. Biol Psychiatry 2006;60: 697-703.

[10] Mackie S, Shaw P, Lenroot R, et al. Cerebellar development and clinical outcome in attention deficit hyperactivity disorder. Am J Psychiatry 2007;164:647-655.

[11] Wegiel J, Wisniewski HM, Dziewiatkowski J, et al. Cerebellar atrophy in Alzheimer's disease-clinicopathological correlations. Brain Res 1999; 818:41-50.

[12] Sjobeck M, Englund E. Alzheimer's disease and the cerebellum: a morphologic study on neuronal and glial changes. Dement Geriatr Cogn Disorders 2001;12:211-218.

[13] Thomann PA, Schlafer C, Seidl U, Santos VD, Essig M, Schroder J. The cerebellum in mild cognitive impairment and Alzheimer's disease - a structural MRI study. J Psychiatric Res 2008;42:1198-1202.

[14] Schutter DJ, van Honk J. The cerebellum in emotion regulation: a repetitive transcranial magnetic stimulation study. Cerebellum 2009;8:28-34.

[15] Nashold BS, Jr., Slaughter DG. Effects of stimulating or destroying the deep cerebellar regions in man. J Neurosurg 1969;31:172-86.

[16] Lippmann S, Manshadi M, Baldwin H, Drasin G, Rice J, Alrajeh S. Cerebellar vermis dimensions on computerized tomographic scans of schizophrenic and bipolar patients. Am J Psychiatry 1982;139:667-668.

[17] Nasrallah HA, McCalley-Whitters M, Jacoby CG. Cortical atrophy in schizophrenia and mania: a comparative CT study. J Clin Psychiatry 1982;43:439-441.

[18] Nasrallah HA, Jacoby CG, McCalley-Whitters M. Cerebellar atrophy in schizophrenia and mania. Lancet 1981;8229:1102.

[19] Weinberger DR, DeLisi LE, Perman GP, Targum S, Wyatt RJ. Computed tomography in schizophreniform disorder and other acute psychiatric disorders. Arch Gen Psychi 1982;39:778-783.

[20] Moorhead TW, McKirdy J, Sussmann JE, Hall J, Lawrie SM, Johnstone EC, McIntosh AM. Progressive gray matter loss in patients with bipolar disorder. Biol Psychiatry 2007;62:894-900.

[21] Mills NP, Delbello MP, Adler CM, Strakowski SM. MRI analysis of cerebellar vermal abnormalities in bipolar disorder. Am J Psychiatry 2005; 162:1530-1532.

[22] DelBello MP, Strakowski SM, Zimmerman ME, Hawkins JM, Sax KW. MRI analysis of the cerebellum in bipolar disorder: a pilot study. Neuropsychopharmacol 1999;21:63-68.

[23] Osuch EA, Benson B, Geraci M, Podell D, Herscovitch P, McCann UD, Post RM. Regional cerebral blood flow correlated with flashback intensity in patients with posttraumatic stress disorder. Biol Psychiatry 2001; 50:246-253.

[24] Anderson CM, Teicher MH, Polcari A, Renshaw PF. Abnormal T2 relaxation time in the cerebellar vermis of adults sexually abused in childhood: potential role of the vermis in stress-enhanced risk for drug abuse. Psychoneuroendocrinology 2002;27:231-244.

[25] Pissiota A, Frans O, Fernandez M, von Knorring L, Fischer H, Fredrikson M. Neurofunctional correlates of posttraumatic stress disorder: a PET symptom provocation study. Eur Arch Psychiatry Clin Neurosci 2002; 252:68-75.

[26] De Bellis MD, Keshavan MS, Frustaci K, et al. Superior temporal gyrus volumes in maltreated children and adolescents with PTSD. Biol Psychiatry 2002;51:544-552.

[27] Thomas LA, De Bellis MD. Pituitary volumes in pediatric maltreatment-related postraumatic stress disorder. Biol Psychiatry 2004;55:752-758.

[28] d'Orsi E, Xavier AJ, Ramos LR. Work, social support and leisure protect the elderly from functional loss: EPIDOSO study. Rev Saude Publica 2011;45:685-692.

[29] Montaño MBMM, Ramos LR. Validade da versão em português da Clinical Dementia Rating. Rev Saúde Pública 2005;39:912-917.

[30] Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E. Mild cognitive impairment: clinical characterization and outcome. Arch Neurol 1999;56:303-308.

[31] Dubois B, Feldman HH, Jacova C, et al. Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria. Lancet Neurol 2007;6:734-746.

[32] Baldaçara L, Borgio JGF, Moraes WAS, et al. Cerebellar volume in patients with dementia. Rev Bras Psiquiatr 2011;33:122-129.

[33] Andreoli SB, Ribeiro WS, Quintana MI, et al. Violence and post-traumatic stress disorder in Sao Paulo and Rio de Janeiro, Brazil: the protocol for an epidemiological and genetic survey. BMC Psychiatry 2009;9:34.

[34] Bressan RA, Quarantini LC, Andreoli SB, et al. The posttraumatic stress disorder project in Brazil: neuropsychological, structural and molecular neuroimaging studies in victims of urban violence. BMC Psychiatry 2009;9:30.

[35] Baldacara L, Jackowski AP, Schoedl A, et al. Reduced cerebellar left hemisphere and vermal volume in adults with PTSD from a community sample. J Psychiatric Res 2011;45:1627-1633.

[36] Baldacara L, Nery-Fernandes F, Rocha M, et al. Is cerebellar volume related to bipolar disorder? J Affect Disorder 2011;135:305-309.

[37] Spitzer RL, Williams JB, Gibbon M, First MB. The Structured Clinical Interview for DSM-III-R (SCID). I: History, rationale, and description. Arch Gen Psychiatry 1992;49:624-629.

[38] Williams JB, Gibbon M, First MB, et al. The Structured Clinical Interview for DSM-III-R (SCID). II. Multisite test-retest reliability. Arch Gen Psychiatry 1992;49:630-636.

[39] Folstein MF, Folstein SE, McHugh PR. Mini-mental state: a practical method for grading the cognitive state of patients for the clinican. J Psychiatric Res 1975;12:189-198.

[40] Pfeffer RI, Kurosaki TT, Harrah CH, Jr., Chance JM, Filos S. Measurement of functional activities in older adults in the community. J Gerontol 1982;37:323-329.

[41] Pupo MC, Jorge MR, Schoedl AF, et al. The accuracy of the Clinician-Administered PTSD Scale (CAPS) to identify PTSD cases in victims of urban violence. Psychiatry Res 2011;185:157-160.

[42] Beck AT, Epstein N, Brown G, Steer RA. An inventory for measuring clinical anxiety: psychometric properties. J Consult Clin Psychol 1988; 56:893-897.

[43] Beck AT, Rial WY, Rickels K. Short form of depression inventory: cross-validation. Psychol Reports 1974;34:1184-1186.

[44] Mello MF, Schoedl AF, Pupo MC, Souza AA, Andreoli SB, Bressan RA, Mari JJ. Early Trauma Inventory (ETI): cross-cultural adaptation and internal consistency. Cad Saude Publica 2010;26:713-724.

[45] Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960;23:56-62.

[46] Young RC, Biggs JT, Ziegler VE, Meyer DA. A rating scale for mania: reliability, validity and sensitivity. Br J Psychiatry 1978;133:429-435.

[47] Bayle FJ, Bourdel MC, Caci H, et al. Factor analysis of french translation of the Barratt impulsivity scale (BIS-10). Can J Psychiatry 2000; 45:156-165.

[48] Ashburner J, Friston KJ. Unified segmentation. Neuroimage 2005; 26: 839-851.

[49] De Bellis MD, Kuchibhatla M. Cerebellar Volumes in Pediatric Maltreatment-Related Posttraumatic Stress Disorder. Biol Psychiatry 2006; 60:697-703.

[50] Luft AR, Skalej M, Schulz JB, et al. Patterns of age-related shrinkage in cerebellum and brainstem observed in vivo using three-dimensional MRI volumetry. Cereb Cortex 1999;9:712-721.

[51] Pierson R, Corson PW, Sears LL, et al. Manual and semiautomated measurement of cerebellar subregions on MR images. Neuroimage 2002;17:61-76.

[52] Walter H, Vasic N, Hose A, Spitzer M, Wolf RC. Working memory dysfunction in schizophrenia compared to healthy controls and patients with depression: evidence from event-related fMRI. Neuroimage 2007; 35:1551-1561.

[53] Timmann D, Daum I. Cerebellar contributions to cognitive functions: a progress report after two decades of research. Cerebellum 2007;6: 159-162.

[54] Schmahmann JD, Weilburg JB, Sherman JC. The neuropsychiatry of the cerebellum - insights from the clinic. Cerebellum 2007;6:254-267.

[55] Schmahmann JD. The cerebellum and cognition. Volume 41. San Diego: Academic Press; 1997.

[56] Xu D, Liu T, Ashe J, Bushara KO. Role of the olivo-cerebellar system in timing. J Neurosci 2006;26:5990-5995.

[57] Ito M. Cerebellar circuitry as a neuronal machine. Prog Neurobiol. 2006; 78:272-303.

[58] Schutter DJ, van Honk J. The cerebellum on the rise in human emotion. Cerebellum 2005;4:290-294.

[59] Carrion VG, Weems CF, Watson C, Eliez S, Menon V, Reiss AL. Converging evidence for abnormalities of the prefrontal cortex and evaluation of midsagittal structures in pediatric posttraumatic stress disorder: an MRI study. Psychiatry Res 2009;172:226-234.

[60] Levitt JJ, Chen QC, May FS, Gilbertson MW, Shenton ME, Pitman RK. Volume of cerebellar vermis in monozygotic twins discordant for combat exposure: lack of relationship to post-traumatic stress disorder. Psychiatry Res 2006;148:143-149.

[61] Bonne O, Gilboa A, Louzoun Y, Brandes D, Yona I, Lester H. Resting regional cerebral perfusion in recent posttraumatic stress disorder. Biol Psychiatry 2003;54:1077-1086.

[62] Fernandez M, Pissiota A, Frans O, von Knorring L, Fischer H, Fredrikson M. Brain function in a patient with torture related post-traumatic stress disorder before and after fluoxetine treatment: A positron emission tomography provocation study. Neurosci Lett 2001;297:101-104.

[63] Spinelli S, Chefer S, Suomi SJ, Higley JD, Barr CS, Stein E. Early-life stress induces long-term morphologic changes in primate brain. Arch Gen Psychiatry 2009;66:658-665.

[64] LeardMann CA, Smith B, Ryan MA. Do adverse childhood experiences increase the risk of postdeployment posttraumatic stress disorder in US Marines? BMC Public Health 2010;10:437.

[65] Teicher MH, Tomoda A, Andersen SL. Neurobiological consequences of early stress and childhood maltreatment: Are results from human and animal studies comparable? Ann NY Acad Sci 2006;1071:313-323.

[66] Sanders T, Liu Y, Buchner V, Tchounwou PB. Neurotoxic effects and biomarkers of lead exposure: a review. Rev Environ Health 2009;24:15-45.

[67] Altman J. Morphological and behavioral markers of environmentally induced retardation of brain development: an animal model. Environ Health Perspect 1987;74:153-168.

[68] Martinussen M, Flanders DW, Fischl B, et al. Segmental brain volumes and cognitive and perceptual correlates in 15-year-old adolescents with low birth weight. J Pediatr 2009;155:848-853.

[69] Ferguson SA, Holson RR. Neonatal dexamethasone on day 7 in rats causes mild hyperactivity and cerebellar stunting. Neurotoxicol Teratol 1999;21:71-76.

[70] Mello MF, Faria AA, Mello AF, Carpenter LL, Tyrka AR, Price LH. [Childhood maltreatment and adult psychopathology: pathways to hypothalamic-pituitary-adrenal axis dysfunction]. Rev Bras Psiquiatr 2009;31 Suppl 2:S41-S48.

[71] Coplan JD, Smith EL, Altemus M, et al. Maternal-infant response to variable foraging demand in nonhuman primates: effects of timing of stressor on cerebrospinal fluid corticotropin-releasing factor and circulating glucocorticoid concentrations. Ann N Y Acad Sci 2006;1071: 525-533.

[72] De Bellis MD. Developmental Traumatology: The psychobiological development of maltreated children and its implications for research, treatment, and policy. Dev Psychopathol 2001;13:537-561.

[73] Llorente R, Gallardo ML, Berzal AL, Prada C, Garcia-Segura LM, Viveros MP. Early maternal deprivation in rats induces gender-dependent effects on developing hippocampal and cerebellar cells. Int J Dev Neurosci 2009;3:233-241.

[74] MacKenzie SM, Dewar D, Stewart W, Fraser R, Connell JM, Davies E. The transcription of steroidogenic genes in the human cerebellum and hippocampus: a comparative survey of normal and Alzheimer's tissue. J Endocrinol 2008;196:123-130.

Brasil