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1.
Mol Psychiatry ; 26(11): 6655-6665, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34035475

RESUMO

It remains unclear if previously reported structural abnormalities in children with ADHD are present in adulthood regardless of clinical outcome. In this study, we examined the extent to which focal-rather than diffuse-abnormalities in fiber collinearity of 18 major white matter tracts could distinguish 126 adults with rigorously diagnosed childhood ADHD (ADHD; mean age [SD] = 34.3 [3.6] years; F/M = 12/114) from 58 adults without ADHD histories (non-ADHD; mean age [SD] = 33.9 [4.1] years; F/M = 5/53) and if any of these abnormalities were greater for those with persisting ADHD symptomatology. To this end, a tract profile approach was used. After accounting for age, sex, handedness, and comorbidities, a MANCOVA revealed a main effect of group (ADHD < non-ADHD; F[18,155] = 2.1; p = 0.007) on fractional anisotropy (FA, a measure of fiber collinearity and/or integrity), in focal portions of white matter tracts involved in visuospatial processing and memory (i.e., anterior portion of the left inferior longitudinal fasciculus, and middle portion of the left and right cingulum angular bundle). Only abnormalities in the anterior portion of the left inferior longitudinal fasciculus distinguished probands with persisting versus desisting ADHD symptomatology, suggesting that abnormalities in the cingulum angular bundle might reflect "scarring" effects of childhood ADHD. To our knowledge, this is the first study using a tract profile approach to identify focal or widespread structural abnormalities in adults with ADHD rigorously diagnosed in childhood.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Substância Branca , Adulto , Anisotropia , Encéfalo/diagnóstico por imagem , Criança , Pré-Escolar , Imagem de Tensor de Difusão , Humanos , Rede Nervosa , Substância Branca/diagnóstico por imagem
2.
Eur J Neurol ; 28(2): 525-531, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32986293

RESUMO

BACKGROUND AND PURPOSE: Head down tilt 15° (HDT15°), applied before recanalization, increases collateral flow and improves outcome in experimental ischemic stroke. For its simplicity and low cost, HDT15° holds considerable potential to be developed as an emergency treatment of acute stroke in the prehospital setting, where hemorrhagic stroke is the major mimic of ischemic stroke. In this study, we assessed safety of HDT15° in the acute phase of experimental intracerebral hemorrhage. METHODS: Intracerebral hemorrhage was produced by stereotaxic injection of collagenase in Wistar rats. A randomized noninferiority trial design was used to assign rats to HDT15° or flat position (n = 64). HDT15° was applied for 1 h during the time window of hematoma expansion. The primary outcome was hematoma volume at 24 h. Secondary outcomes were mass effect, mortality, and functional deficit in the main study and acute changes of intracranial pressure, hematoma growth, and cardiorespiratory parameters in separate sets of randomized animals (n = 32). RESULTS: HDT15° achieved the specified criteria of noninferiority for hematoma volume at 24 h. Mass effect, mortality, and functional deficit at 24 h showed no difference in the two groups. HDT15° induced a mild increase in intracranial pressure with respect to the pretreatment values (+2.91 ± 1.76 mmHg). HDT15° had a neutral effect on MRI-based analysis of hematoma growth and cardiorespiratory parameters. CONCLUSIONS: Application of HDT15° in the hyperacute phase of experimental intracerebral hemorrhage does not worsen early outcome. Further research is needed to implement HDT15° as an emergency collateral therapeutic for acute stroke.


Assuntos
Decúbito Inclinado com Rebaixamento da Cabeça , Acidente Vascular Cerebral , Animais , Hemorragia Cerebral/diagnóstico por imagem , Hematoma/diagnóstico por imagem , Humanos , Distribuição Aleatória , Ratos , Ratos Wistar , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/tratamento farmacológico , Resultado do Tratamento
3.
Acta Psychiatr Scand ; 140(5): 468-476, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31418816

RESUMO

OBJECTIVE: The cerebellum is involved in cognitive processing and emotion control. Cerebellar alterations could explain symptoms of schizophrenia spectrum disorder (SZ) and bipolar disorder (BD). In addition, literature suggests that lithium might influence cerebellar anatomy. Our aim was to study cerebellar anatomy in SZ and BD, and investigate the effect of lithium. METHODS: Participants from 7 centers worldwide underwent a 3T MRI. We included 182 patients with SZ, 144 patients with BD, and 322 controls. We automatically segmented the cerebellum using the CERES pipeline. All outputs were visually inspected. RESULTS: Patients with SZ showed a smaller global cerebellar gray matter volume compared to controls, with most of the changes located to the cognitive part of the cerebellum (Crus II and lobule VIIb). This decrease was present in the subgroup of patients with recent-onset SZ. We did not find any alterations in the cerebellum in patients with BD. However, patients medicated with lithium had a larger size of the anterior cerebellum, compared to patients not treated with lithium. CONCLUSION: Our multicenter study supports a distinct pattern of cerebellar alterations in SZ and BD.


Assuntos
Antimaníacos/efeitos adversos , Transtorno Bipolar/patologia , Córtex Cerebelar/patologia , Compostos de Lítio/efeitos adversos , Esquizofrenia/patologia , Adulto , Transtorno Bipolar/diagnóstico por imagem , Transtorno Bipolar/tratamento farmacológico , Córtex Cerebelar/diagnóstico por imagem , Córtex Cerebelar/efeitos dos fármacos , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/tratamento farmacológico , Adulto Jovem
4.
Neuropsychopharmacology ; 44(7): 1182-1188, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30802896

RESUMO

Obsessive-compulsive disorder (OCD) is a disabling condition, often associated with a chronic course. Given its role in attentional control, decision-making, and emotional regulation, the anterior cingulate cortex is considered to have a key role in the pathophysiology of the disorder. Notably, the cingulum bundle, being the major white matter tract connecting to this region, has been historically a target for the surgical treatment of intractable OCD. In this study, we aimed to identify the extent to which focal-more than diffuse-abnormalities in fiber collinearity of the cingulum bundle could distinguish 48 adults with OCD (mean age [SD] = 23.3 [4.5] years; F/M = 30/18) from 45 age- and sex-matched healthy control adults (CONT; mean age [SD] = 23.2 [3.8] years; F/M = 28/17) and further examine if these abnormalities correlated with symptom severity. Use of tract-profiles rather than a conventional diffusion imaging approach allowed us to characterize white matter microstructural properties along (100 segments), as opposed to averaging these measures across, the entire tract. To account for these 100 different segments of the cingulum bundle, a repeated measures analysis of variance revealed a main effect of group (OCD < CONT; F[1,87] = 5.3; P = 0.024) upon fractional anisotropy (FA, a measure of fiber collinearity and/or white matter integrity), in the cingulum bundle, bilaterally. Further analyses revealed that these abnormalities were focal (middle portion) within the left and right cingulum bundle, although did not correlate with symptom severity in OCD. Findings indicate that focal abnormalities in connectivity between the anterior cingulate cortex and other prefrontal cortical regions may represent neural mechanisms of OCD.


Assuntos
Imagem de Tensor de Difusão/métodos , Giro do Cíngulo/patologia , Transtorno Obsessivo-Compulsivo/patologia , Córtex Pré-Frontal/patologia , Substância Branca/patologia , Adulto , Anisotropia , Feminino , Giro do Cíngulo/diagnóstico por imagem , Humanos , Masculino , Fibras Nervosas/patologia , Vias Neurais/diagnóstico por imagem , Vias Neurais/patologia , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Transtorno Obsessivo-Compulsivo/fisiopatologia , Córtex Pré-Frontal/diagnóstico por imagem , Índice de Gravidade de Doença , Substância Branca/diagnóstico por imagem , Adulto Jovem
5.
Neuropsychopharmacology ; 43(11): 2212-2220, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29795244

RESUMO

Bipolar disorder (BD) is highly heritable. Thus, studies in first-degree relatives of individuals with BD could lead to the discovery of objective risk markers of BD. Abnormalities in white matter structure reported in at-risk individuals could play an important role in the pathophysiology of BD. Due to the lack of studies with other at-risk offspring, however, it remains unclear whether such abnormalities reflect BD-specific or generic risk markers for future psychopathology. Using a tract-profile approach, we examined 18 major white matter tracts in 38 offspring of BD parents, 36 offspring of comparison parents with non-BD psychopathology (depression, attention-deficit/hyperactivity disorder), and 41 offspring of healthy parents. Both at-risk groups showed significantly lower fractional anisotropy (FA) in left-sided tracts (cingulum, inferior longitudinal fasciculus, forceps minor), and significantly greater FA in right-sided tracts (uncinate fasciculus and inferior longitudinal fasciculus), relative to offspring of healthy parents (P < 0.05). These abnormalities were present in both healthy and affected youth in at-risk groups. Only offspring (particularly healthy offspring) of BD parents showed lower FA in the right superior longitudinal fasciculus relative to healthy offspring of healthy parents (P < 0.05). We show, for the first time, important similarities, and some differences, in white matter structure between offspring of BD and offspring of non-BD parents. Findings suggest that lower left-sided and higher right-sided FA in tracts important for emotional regulation may represent markers of risk for general, rather than BD-specific, psychopathology. Lower FA in the right superior longitudinal fasciculus may protect against development of BD in offspring of BD parents.


Assuntos
Transtorno Bipolar/diagnóstico por imagem , Transtorno Bipolar/psicologia , Filho de Pais com Deficiência/psicologia , Imagem de Difusão por Ressonância Magnética/tendências , Adolescente , Transtorno Bipolar/genética , Criança , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Humanos , Masculino , Psicopatologia , Fatores de Risco
6.
Neuropediatrics ; 49(3): 209-212, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29471551

RESUMO

Child bilateral striatal necrosis (BSN) is a rare and etiologically heterogeneous condition. An association with group A streptococcus (GAS) infection was previously reported in two cases of BSN in infancy and early childhood. We here report on a 7-year-old boy who developed chorea and dystonia 20 days after symptomatic recovery from Sydenham's chorea. Repeated brain magnetic resonance imaging scans, obtained before, soon after the onset of the post-Sydenham symptoms, and 1 year later were consistent with an evolution from bilateral striatal microbleeding to necrosis, and consequently reduced basal ganglia volume and enlargement of the frontal horns. No support was found for other possible autoimmune, infectious, metabolic, toxic or genetic etiologies for BSN. Prednisone treatment was instituted and continued for 1 year. Two years after the onset of the post-Sydenham symptoms, the child, although much improved, still has generalized dystonic-choreic movements. This case confirms and extends into school age, the link between GAS and BSN.


Assuntos
Encefalopatias/diagnóstico , Encefalopatias/tratamento farmacológico , Coreia/complicações , Corpo Estriado/diagnóstico por imagem , Infecções Estreptocócicas/complicações , Encefalopatias/etiologia , Criança , Coreia/diagnóstico , Corpo Estriado/efeitos dos fármacos , Diagnóstico Diferencial , Seguimentos , Humanos , Masculino , Necrose/diagnóstico , Necrose/tratamento farmacológico , Infecções Estreptocócicas/diagnóstico
7.
Mol Psychiatry ; 23(4): 932-942, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28461699

RESUMO

Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen's d=-0.293; P=1.71 × 10-21), left fusiform gyrus (d=-0.288; P=8.25 × 10-21) and left rostral middle frontal cortex (d=-0.276; P=2.99 × 10-19). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD.


Assuntos
Transtorno Bipolar/diagnóstico por imagem , Transtorno Bipolar/patologia , Substância Cinzenta/patologia , Adolescente , Adulto , Fatores Etários , Transtorno Bipolar/metabolismo , Encéfalo/patologia , Estudos de Casos e Controles , Córtex Cerebral/fisiopatologia , Feminino , Lobo Frontal/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Neuroimagem , Córtex Pré-Frontal/patologia , Transtornos Psicóticos/patologia , Fatores Sexuais , Lobo Temporal/patologia , Adulto Jovem
8.
Psychol Med ; 47(8): 1357-1369, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27998326

RESUMO

BACKGROUND: Identifying youth who may engage in future substance use could facilitate early identification of substance use disorder vulnerability. We aimed to identify biomarkers that predicted future substance use in psychiatrically un-well youth. METHOD: LASSO regression for variable selection was used to predict substance use 24.3 months after neuroimaging assessment in 73 behaviorally and emotionally dysregulated youth aged 13.9 (s.d. = 2.0) years, 30 female, from three clinical sites in the Longitudinal Assessment of Manic Symptoms (LAMS) study. Predictor variables included neural activity during a reward task, cortical thickness, and clinical and demographic variables. RESULTS: Future substance use was associated with higher left middle prefrontal cortex activity, lower left ventral anterior insula activity, thicker caudal anterior cingulate cortex, higher depression and lower mania scores, not using antipsychotic medication, more parental stress, older age. This combination of variables explained 60.4% of the variance in future substance use, and accurately classified 83.6%. CONCLUSIONS: These variables explained a large proportion of the variance, were useful classifiers of future substance use, and showed the value of combining multiple domains to provide a comprehensive understanding of substance use development. This may be a step toward identifying neural measures that can identify future substance use disorder risk, and act as targets for therapeutic interventions.


Assuntos
Comportamento do Adolescente/fisiologia , Sintomas Afetivos/fisiopatologia , Córtex Cerebral , Depressão/fisiopatologia , Comportamento Problema , Recompensa , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Adolescente , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/fisiologia , Córtex Cerebral/fisiopatologia , Criança , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Transtornos Relacionados ao Uso de Substâncias/diagnóstico por imagem , Transtornos Relacionados ao Uso de Substâncias/patologia , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia
9.
Mol Psychiatry ; 21(12): 1710-1716, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-26857596

RESUMO

Considerable uncertainty exists about the defining brain changes associated with bipolar disorder (BD). Understanding and quantifying the sources of uncertainty can help generate novel clinical hypotheses about etiology and assist in the development of biomarkers for indexing disease progression and prognosis. Here we were interested in quantifying case-control differences in intracranial volume (ICV) and each of eight subcortical brain measures: nucleus accumbens, amygdala, caudate, hippocampus, globus pallidus, putamen, thalamus, lateral ventricles. In a large study of 1710 BD patients and 2594 healthy controls, we found consistent volumetric reductions in BD patients for mean hippocampus (Cohen's d=-0.232; P=3.50 × 10-7) and thalamus (d=-0.148; P=4.27 × 10-3) and enlarged lateral ventricles (d=-0.260; P=3.93 × 10-5) in patients. No significant effect of age at illness onset was detected. Stratifying patients based on clinical subtype (BD type I or type II) revealed that BDI patients had significantly larger lateral ventricles and smaller hippocampus and amygdala than controls. However, when comparing BDI and BDII patients directly, we did not detect any significant differences in brain volume. This likely represents similar etiology between BD subtype classifications. Exploratory analyses revealed significantly larger thalamic volumes in patients taking lithium compared with patients not taking lithium. We detected no significant differences between BDII patients and controls in the largest such comparison to date. Findings in this study should be interpreted with caution and with careful consideration of the limitations inherent to meta-analyzed neuroimaging comparisons.


Assuntos
Transtorno Bipolar/fisiopatologia , Encéfalo/fisiopatologia , Adulto , Encéfalo/anatomia & histologia , Estudos de Casos e Controles , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão/fisiologia , Estudos Retrospectivos
10.
Mol Psychiatry ; 21(9): 1194-201, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26903272

RESUMO

Behavioral and emotional dysregulation in childhood may be understood as prodromal to adult psychopathology. Additionally, there is a critical need to identify biomarkers reflecting underlying neuropathological processes that predict clinical/behavioral outcomes in youth. We aimed to identify such biomarkers in youth with behavioral and emotional dysregulation in the Longitudinal Assessment of Manic Symptoms (LAMS) study. We examined neuroimaging measures of function and white matter in the whole brain using 80 youth aged 14.0 (s.d.=2.0) from three clinical sites. Linear regression using the LASSO (Least Absolute Shrinkage and Selection Operator) method for variable selection was used to predict severity of future behavioral and emotional dysregulation measured by the Parent General Behavior Inventory-10 Item Mania Scale (PGBI-10M)) at a mean of 14.2 months follow-up after neuroimaging assessment. Neuroimaging measures, together with near-scan PGBI-10M, a score of manic behaviors, depressive behaviors and sex, explained 28% of the variance in follow-up PGBI-10M. Neuroimaging measures alone, after accounting for other identified predictors, explained ~1/3 of the explained variance, in follow-up PGBI-10M. Specifically, greater bilateral cingulum length predicted lower PGBI-10M at follow-up. Greater functional connectivity in parietal-subcortical reward circuitry predicted greater PGBI-10M at follow-up. For the first time, data suggest that multimodal neuroimaging measures of underlying neuropathologic processes account for over a third of the explained variance in clinical outcome in a large sample of behaviorally and emotionally dysregulated youth. This may be an important first step toward identifying neurobiological measures with the potential to act as novel targets for early detection and future therapeutic interventions.


Assuntos
Sintomas Afetivos/fisiopatologia , Substância Branca/fisiopatologia , Adolescente , Sintomas Afetivos/genética , Transtorno Bipolar/diagnóstico , Encéfalo/fisiopatologia , Criança , Emoções/fisiologia , Feminino , Previsões/métodos , Humanos , Estudos Longitudinais , Masculino , Pais/psicologia , Escalas de Graduação Psiquiátrica , Recompensa , Resultado do Tratamento
11.
Cephalalgia ; 36(6): 510-7, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26243758

RESUMO

AIM: The aim of this article is to analyze the epidemiological and clinical features of migraine in a pediatric headache center. METHODS: A retrospective study was performed over six years. Hospital record databases were screened for the diagnosis of migraine with aura (MA) or without aura (MO), based on the ICHD-II criteria. STATISTICAL ANALYSIS: Fisher's test or Mann-Whitney U test, significance at p < 0.05. RESULTS: Migraine was diagnosed in 495 children (29.7% MA, 70.3% MO). The majority of diagnoses were made between ages 9 and 14 years. After stratification for age into five groups, we observed an increase of diagnoses in females, with a peak after the age of 15 years, and an increase of MA. In both groups, the attacks were usually severe, infrequent (<1-3/month) lasting <2 hours, and associated with nausea/vomiting, photophobia, phonophobia (more frequent in MO). Osmophobia was reported in 24.7% of the patients with MO. Dizziness was more frequent in patients with MA. Visual auras were the most common occurrence (87.1%). Confusional state was observed in 10.88% of the patients. A positive family history of headache was observed in >88% of the patients. CONCLUSION: We describe the characteristics of pediatric migraine based on the ICHD-II criteria, showing a likely significant loss of diagnoses using the ICHD-III beta. The incidence of migraine increases with age. MO occurs more commonly and shows more frequent attacks and a higher prevalence of associated symptoms, in particular osmophobia. Although males are prevalent in the entire sample, the proportion of females is higher among patients with MA in all of the age groups. Phenotype and sexual prevalence of migraine acquire adult characteristics and become more frequent in females from the onset of puberty.


Assuntos
Transtornos de Enxaqueca/epidemiologia , Adolescente , Distribuição por Idade , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Itália/epidemiologia , Masculino , Prevalência , Estudos Retrospectivos , Distribuição por Sexo
12.
Brain Res ; 1615: 31-41, 2015 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-25912435

RESUMO

Statins have since long been reported to exert acute neuroprotection in experimental stroke models. However, crucial questions still need to be addressed as far as the timing of their cerebral effects after intravascular administration and the role played by the blood brain barrier (BBB) crossing properties. We tested the effects of an hydrophilic statin (pravastatin, 100 nM), which poorly crosses BBB under physiological conditions. Pravastatin was administered either 90 min before or immediately after transient middle cerebral artery occlusion in the in vitro isolated guinea pig brain preparation. A multi-modal outcome assessment was performed, through electrophysiological and cerebral vascular tone recordings, MAP-2 immunohistochemistry, BBB evaluation via ZO-1/FITC-albumin analysis, AKT and ERK activation and whole-cell antioxidant capacity. Pravastatin pre-ischemic administration did not produce any significant effect. Pravastatin post-ischemic administration significantly prevented MAP-2 immunoreactivity loss in ischemic areas, increased ERK phosphorylation in the ischemic hemisphere and enhanced whole-cell antioxidant capacity. Electrophysiological parameters, vascular tone and AKT signaling were unchanged. In all tested ischemic brains, ZO-1 fragmentation and FITC albumin extravasation was observed, starting 30 min from ischemia onset, indicating loss of BBB integrity. Our findings indicate that the rapid anti-ischemic effects of intravascular pravastatin are highly dependent on BBB increased permeability after stroke.


Assuntos
Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/fisiopatologia , Isquemia Encefálica/metabolismo , Isquemia Encefálica/fisiopatologia , Fármacos Neuroprotetores/administração & dosagem , Pravastatina/administração & dosagem , Animais , Barreira Hematoencefálica/patologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Isquemia Encefálica/prevenção & controle , Permeabilidade Capilar/efeitos dos fármacos , Cobaias , Infarto da Artéria Cerebral Média/complicações , Proteínas Associadas aos Microtúbulos/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fatores de Tempo , Proteína da Zônula de Oclusão-1/metabolismo
13.
Acta Psychiatr Scand ; 131(3): 223-33, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25430729

RESUMO

OBJECTIVE: There is growing evidence that cerebellum plays a crucial role in cognition and emotional regulation. Cerebellum is likely to be involved in the physiopathology of both bipolar disorder and schizophrenia. The objective of our study was to compare cerebellar size between patients with bipolar disorder, patients with schizophrenia, and healthy controls in a multicenter sample. In addition, we studied the influence of psychotic features on cerebellar size in patients with bipolar disorder. METHOD: One hundred and fifteen patients with bipolar I disorder, 32 patients with schizophrenia, and 52 healthy controls underwent 3 Tesla MRI. Automated segmentation of cerebellum was performed using FreeSurfer software. Volumes of cerebellar cortex and white matter were extracted. Analyses of covariance were conducted, and age, sex, and intracranial volume were considered as covariates. RESULTS: Bilateral cerebellar cortical volumes were smaller in patients with schizophrenia compared with patients with bipolar I disorder and healthy controls. We found no significant difference of cerebellar volume between bipolar patients with and without psychotic features. No change was evidenced in white matter. CONCLUSION: Our results suggest that reduction in cerebellar cortical volume is specific to schizophrenia. Cerebellar dysfunction in bipolar disorder, if present, appears to be more subtle than a reduction in cerebellar volume.


Assuntos
Transtorno Bipolar/patologia , Cerebelo/patologia , Transtornos Psicóticos/patologia , Esquizofrenia/patologia , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Software , Adulto Jovem
14.
Atherosclerosis ; 237(2): 471-9, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25463076

RESUMO

OBJECTIVE: Cigarette smokers present early signs of vascular damage and systemic inflammation. Biglycan (BGN), an ubiquitous component of extracellular matrix orchestrating several physiological functions, has recently been indicated as a major source of low-density lipoprotein retention in the normal arterial intima-media layer. We evaluated whether BGN-mRNA expression was enhanced in peripheral monocytes of smokers with no additional cardiovascular risk factors (CVRFs), and if it was associated with altered carotid arterial stiffness (AS) or intima media thickness (cIMT). We also evaluated plasma markers of systemic and vascular inflammation, and correlation with BGN-mRNA. METHODS: Two-hundred-fifty-one young smokers were enrolled, with no additional CVRFs, and 60 controls. Plasma lipids, fibrinogen, C-reactive protein (CRP), interleukin-6 (IL-6), AS and cIMT were assessed. A smoke exposure index (SEIx) was calculated. RESULTS: Fibrinogen, CRP, AS indices, cIMT, and BGN-mRNA were higher in smokers compared to controls; HDL-C levels were lower, no difference was detected in IL-6 levels. After stratification of smokers in quartiles based on SEIx values, smokers in the highest quartiles presented highest fibrinogen, CRP, AS, cIMT, BGN, and also IL-6 values, and lowest HDL-C. CONCLUSION: BGN-mRNA was enhanced in young smokers, compared to controls, and appears associated to a proatherogenic profile, characterized by increased fibrinogen, CRP, and IL-6, lower HDL-C, altered AS and cIMT values, particularly in those with higher SEIx: the more cigarettes smoked over years, the more marked the alterations. Although we cannot state whether BGN have a direct causal role in inducing, maintaining and developing vascular damage, including intima-media wall thickening and arterial stiffening, our data could suggest that it may represent a link between proatherogenic status induced by cigarette smoking, and the development and progression of vascular damage.


Assuntos
Aterosclerose/fisiopatologia , Biglicano/metabolismo , Fumar/efeitos adversos , Adolescente , Adulto , Aterosclerose/patologia , Proteína C-Reativa/metabolismo , Artérias Carótidas/patologia , Espessura Intima-Media Carotídea , Colesterol/sangue , Feminino , Humanos , Inflamação , Interleucina-6/sangue , Lipoproteínas LDL/metabolismo , Masculino , Monócitos/citologia , Reação em Cadeia da Polimerase , RNA/metabolismo , RNA Mensageiro/metabolismo , Análise de Regressão , Fatores de Risco , Adulto Jovem
15.
Psychol Med ; 44(12): 2603-15, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24468022

RESUMO

BACKGROUND: Neuroimaging measures of behavioral and emotional dysregulation can yield biomarkers denoting developmental trajectories of psychiatric pathology in youth. We aimed to identify functional abnormalities in emotion regulation (ER) neural circuitry associated with different behavioral and emotional dysregulation trajectories using latent class growth analysis (LCGA) and neuroimaging. METHOD: A total of 61 youth (9-17 years) from the Longitudinal Assessment of Manic Symptoms study, and 24 healthy control youth, completed an emotional face n-back ER task during scanning. LCGA was performed on 12 biannual reports completed over 5 years of the Parent General Behavior Inventory 10-Item Mania Scale (PGBI-10M), a parental report of the child's difficulty regulating positive mood and energy. RESULTS: There were two latent classes of PGBI-10M trajectories: high and decreasing (HighD; n=22) and low and decreasing (LowD; n=39) course of behavioral and emotional dysregulation over the 12 time points. Task performance was >89% in all youth, but more accurate in healthy controls and LowD versus HighD (p<0.001). During ER, LowD had greater activity than HighD and healthy controls in the dorsolateral prefrontal cortex, a key ER region, and greater functional connectivity than HighD between the amygdala and ventrolateral prefrontal cortex (p's<0.001, corrected). CONCLUSIONS: Patterns of function in lateral prefrontal cortical-amygdala circuitry in youth denote the severity of the developmental trajectory of behavioral and emotional dysregulation over time, and may be biological targets to guide differential treatment and novel treatment development for different levels of behavioral and emotional dysregulation in youth.


Assuntos
Desenvolvimento do Adolescente/fisiologia , Sintomas Afetivos/fisiopatologia , Tonsila do Cerebelo/fisiopatologia , Sintomas Comportamentais/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Adolescente , Criança , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino
16.
Mol Psychiatry ; 19(2): 200-8, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23358158

RESUMO

Diffusion tensor imaging (DTI) studies consistently reported abnormalities in fractional anisotropy (FA) and radial diffusivity (RD), measures of the integrity of white matter (WM), in bipolar disorder (BD), that may reflect underlying pathophysiologic processes. There is, however, a pressing need to identify peripheral measures that are related to these WM measures, to help identify easily obtainable peripheral biomarkers of BD. Given the high lipid content of axonal membranes and myelin sheaths, and that elevated serum levels of lipid peroxidation are reported in BD, these serum measures may be promising peripheral biomarkers of underlying WM abnormalities in BD. We used DTI and probabilistic tractography to compare FA and RD in ten prefrontal-centered WM tracts, 8 of which are consistently shown to have abnormal FA (and/or RD) in BD, and also examined serum lipid peroxidation (lipid hydroperoxides, LPH and 4-hydroxy-2-nonenal, 4-HNE), in 24 currently euthymic BD adults (BDE) and 19 age- and gender-matched healthy adults (CONT). There was a significant effect of group upon FA in these a priori WM tracts (BDECONT: F[1,41]=10.3; P=0.003), and a significant between-group difference in LPH (BDE>CONT: t[40]=2.4; P=0.022), but not in 4-HNE. Multivariate multiple regression analyses revealed that LPH variance explained, respectively, 59 and 51% of the variance of FA and RD across all study participants. This is the first study to examine relationships between measures of WM integrity and peripheral measures of lipid peroxidation. Our findings suggest that serum LPH may be useful in the development of a clinically relevant, yet easily obtainable and inexpensive, peripheral biomarkers of BD.


Assuntos
Transtorno Bipolar/sangue , Transtorno Bipolar/patologia , Encéfalo/patologia , Peroxidação de Lipídeos , Fibras Nervosas Mielinizadas/patologia , Vias Neurais/patologia , Adulto , Aldeídos/sangue , Anisotropia , Biomarcadores/sangue , Transtorno Bipolar/tratamento farmacológico , Imagem de Tensor de Difusão , Feminino , Humanos , Peróxidos Lipídicos/sangue , Masculino , Modelos Estatísticos , Análise Multivariada , Córtex Pré-Frontal/patologia , Processamento de Sinais Assistido por Computador
17.
Minerva Pediatr ; 65(5): 569-74, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24056382

RESUMO

Tuberculosis keeps on representing a serious threat worldwide and one of the major challenge of our century. Different strategies have been developed in order to eradicate the disease, and particular attention is paid to children, who are at great risk for developing severe manifestations and poor outcome. Age at exposure, nutritional conditions and immune status can lead to great variability of disease expressions, with subsequent difficulties in making an appropriate and rapid diagnosis. Moreover, children coming from tuberculosis-endemic areas should be carefully evaluated for M. tuberculosis infection. Here we present a infrequent manifestation of extrapulmonary tuberculosis in a 13-years-old girl coming from Latin America: a superficial persistent cervical lymphadenopathy was associated with a totally asymptomatic retropharyngeal abscess. Diagnostic approach was discussed. Treatment consisted with a combination of surgical drainage of the abscess and a prolonged combined 6-month chemotherapy. The cervical lymphadenopathy disappeared and no relapses were found during the subsequent follow up.


Assuntos
Abscesso Retrofaríngeo/complicações , Abscesso Retrofaríngeo/microbiologia , Tuberculose dos Linfonodos/complicações , Tuberculose/complicações , Adolescente , Feminino , Humanos , Abscesso Retrofaríngeo/diagnóstico , Abscesso Retrofaríngeo/tratamento farmacológico , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico , Tuberculose dos Linfonodos/diagnóstico , Tuberculose dos Linfonodos/tratamento farmacológico
18.
Br J Psychiatry ; 203(3): 310-1, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23969484

RESUMO

Differentiating bipolar from recurrent unipolar depression is a major clinical challenge. In 18 healthy females and 36 females in a depressive episode--18 with bipolar disorder type I, 18 with recurrent unipolar depression--we applied pattern recognition analysis using subdivisions of anterior cingulate cortex (ACC) blood flow at rest, measured with arterial spin labelling. Subgenual ACC blood flow classified unipolar v. bipolar depression with 81% accuracy (83% sensitivity, 78% specificity).


Assuntos
Transtorno Bipolar/diagnóstico , Transtorno Depressivo/diagnóstico , Giro do Cíngulo/irrigação sanguínea , Diagnóstico Diferencial , Feminino , Humanos , Reconhecimento Automatizado de Padrão , Recidiva , Sensibilidade e Especificidade
20.
Psychol Med ; 41(2): 301-11, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20459886

RESUMO

BACKGROUND: The amygdala plays a central role in the fronto-limbic network involved in the processing of emotions. Structural and functional abnormalities of the amygdala have recently been found in schizophrenia, although there are still contradictory results about its reduced or preserved volumes. METHOD: In order to address these contradictory findings and to further elucidate the possibly underlying pathophysiological process of the amygdala, we employed structural magnetic resonance imaging (MRI) and diffusion weighted imaging (DWI), exploring amygdalar volume and microstructural changes in 69 patients with schizophrenia and 72 matched healthy subjects, relating these indices to psychopathological measures. RESULTS: Measuring water diffusivity, the apparent diffusion coefficients (ADCs) for the right amygdala were found to be significantly greater in patients with schizophrenia compared with healthy controls, with a trend for abnormally reduced volumes. Also, significant correlations between mood symptoms and amygdalar volumes were found in schizophrenia. CONCLUSIONS: We therefore provide evidence that schizophrenia is associated with disrupted tissue organization of the right amygdala, despite partially preserved size, which may ultimately lead to abnormal emotional processing in schizophrenia. This result confirms the major role of the amygdala in the pathophysiology of schizophrenia and is discussed with respect to amygdalar structural and functional abnormalities found in patients suffering from this illness.


Assuntos
Tonsila do Cerebelo/patologia , Tonsila do Cerebelo/ultraestrutura , Esquizofrenia/patologia , Adulto , Estudos de Casos e Controles , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Itália , Modelos Lineares , Imageamento por Ressonância Magnética , Masculino , Análise por Pareamento , Tamanho do Órgão
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