Myokines in treatment-naïve patients with cancer-associated cachexia.

Cancer-associated cachexia is a complex metabolic syndrome characterized by weight loss and systemic inflammation. Muscle loss and fatty infiltration into muscle are associated with poor prognosis in cancer patients. Skeletal muscle secretes myokines, factors with autocrine, paracrine and/or endocrine action, which may be modified by or play a role in cachexia. This study examined myokine content in the plasma, skeletal muscle and tumor homogenates from treatment-naïve patients with gastric or colorectal stages I-IV cancer with cachexia (CC, N = 62), or not (weight stable cancer, WSC, N = 32). Myostatin, interleukin (IL) 15, follistatin-like protein 1 (FSTL-1), fatty acid binding protein 3 (FABP3), irisin and brain-derived neurotrophic factor (BDNF) protein content in samples was measured with Multiplex technology; body composition and muscle lipid infiltration were evaluated in computed tomography, and quantification of triacylglycerol (TAG) in the skeletal muscle. Cachectic patients presented lower muscle FSTL-1 expression (p = 0.047), higher FABP3 plasma content (p = 0.0301) and higher tumor tissue expression of FABP3 (p = 0.0182), IL-15 (p = 0.007) and irisin (p = 0.0110), compared to WSC. Neither muscle TAG content, nor muscle attenuation were different between weight stable and cachectic patients. Lumbar adipose tissue (AT) index, visceral AT index and subcutaneous AT index were lower in CC (p = 0.0149, p = 0.0455 and p = 0.0087, respectively), who also presented lower muscularity in the cohort (69.2% of patients; p = 0.0301), compared to WSC. The results indicate the myokine profile in skeletal muscle, plasma and tumor is impacted by cachexia. These findings show that myokines eventually affecting muscle wasting may not solely derive from the muscle itself (as the tumor also may contribute to the systemic scenario), and put forward new perspectives on cachexia treatment targeting myokines and associated receptors and pathways.

Patterns of regional gray matter loss at different stages of schizophrenia: A multisite, cross-sectional VBM study in first-episode and chronic illness.

BACKGROUND: Structural brain abnormalities in schizophrenia have been repeatedly demonstrated in magnetic resonance imaging (MRI) studies, but it remains unclear whether these are static or progressive in nature. While longitudinal MRI studies have been traditionally used to assess the issue of progression of brain abnormalities in schizophrenia, information from cross-sectional neuroimaging studies directly comparing first-episode and chronic schizophrenia patients to healthy controls may also be useful to further clarify this issue. With the recent interest in multisite mega-analyses combining structural MRI data from multiple centers aiming at increased statistical power, the present multisite voxel-based morphometry (VBM) study was carried out to examine patterns of brain structural changes according to the different stages of illness and to ascertain which (if any) of such structural abnormalities would be specifically correlated to potential clinical moderators, including cumulative exposure to antipsychotics, age of onset, illness duration and overall illness severity. METHODS: We gathered a large sample of schizophrenia patients (161, being 99 chronic and 62 first-episode) and controls (151) from four previous morphometric MRI studies (1.5 T) carried out in the same geographical region of Brazil. Image processing and analyses were conducted using Statistical Parametric Mapping (SPM8) software with the diffeomorphic anatomical registration through exponentiated Lie algebra (DARTEL) algorithm. Group effects on regional gray matter (GM) volumes were investigated through whole-brain voxel-wise comparisons using General Linear Model Analysis of Co-variance (ANCOVA), always including total GM volume, scan protocol, age and gender as nuisance variables. Finally, correlation analyses were performed between the aforementioned clinical moderators and regional and global brain volumes. RESULTS: First-episode schizophrenia subjects displayed subtle volumetric deficits relative to controls in a circumscribed brain regional network identified only in small volume-corrected (SVC) analyses (p < 0.05, FWE-corrected), including the insula, temporolimbic structures and striatum. Chronic schizophrenia patients, on the other hand, demonstrated an extensive pattern of regional GM volume decreases relative to controls, involving bilateral superior, inferior and orbital frontal cortices, right middle frontal cortex, bilateral anterior cingulate cortices, bilateral insulae and right superior and middle temporal cortices (p < 0.05, FWE-corrected over the whole brain). GM volumes in several of those brain regions were directly correlated with age of disease onset on SVC analyses for conjoined (first-episode and chronic) schizophrenia groups. There were also widespread foci of significant negative correlation between duration of illness and relative GM volumes, but such findings remained significant only for the right dorsolateral prefrontal cortex after accounting for the influence of age of disease onset. Finally, significant negative correlations were detected between life-time cumulative exposure to antipsychotics and total GM and white matter volumes in schizophrenia patients, but no significant relationship was found between indices of antipsychotic usage and relative GM volume in any specific brain region. CONCLUSION: The above data indicate that brain changes associated with the diagnosis of schizophrenia are more widespread in chronic schizophrenia compared to first-episode patients. Our findings also suggest that relative GM volume deficits may be greater in (presumably more severe) cases with earlier age of onset, as well as varying as a function of illness duration in specific frontal brain regions. Finally, our results highlight the potentially complex effects of the continued use of antipsychotic drugs on structural brain abnormalities in schizophrenia, as we found that cumulative doses of antipsychotics affected brain volumes globally rather than selectively on frontal-temporal regions.

Mapping brain volumetric abnormalities in never-treated pathological gamblers.

Several magnetic resonance imaging (MRI) studies to date have investigated brain abnormalities in association with the diagnosis of pathological gambling (PG), but very few of these have specifically searched for brain volume differences between PG patients and healthy volunteers (HV). To investigate brain volume differences between PG patients and HV, 30 male never-treated PG patients (DSM-IV-TR criteria) and 30 closely matched HV without history of psychiatric disorders in the past 2 years underwent structural magnetic resonance imaging with a 1.5-T instrument. Using Freesurfer software, we performed an exploratory whole-brain voxelwise volume comparison between the PG group and the HV group, with false-discovery rate correction for multiple comparisons (p < 0.05). Using a more flexible statistical threshold (p < 0.01, uncorrected for multiple comparisons), we also measured absolute and regional volumes of several brain structures separately. The voxelwise analysis showed no clusters of significant regional differences between the PG and HV groups. The additional analyses of absolute and regional brain volumes showed increased absolute global gray matter volumes in PG patients relative to the HV group, as well as relatively decreased volumes specifically in the left putamen, right thalamus and right hippocampus (corrected for total gray matter). Our findings indicate that structural brain abnormalities may contribute to the functional changes associated with the symptoms of PG, and they highlight the relevance of the brain reward system to the pathophysiology of this disorder.

Penetrance and clinical features of pheochromocytoma in a six-generation family carrying a germline TMEM127 mutation.

CONTEXT: The phenotype of familial pheochromocytoma (PHEO) associated with germline TMEM127 mutations (TMEM127-related PHEO) has not been clearly defined. OBJECTIVE: This study aimed to investigate the penetrance, full phenotypic spectrum and effectiveness of clinical/genetic screening in TMEM127-related PHEO. DESIGN, SETTING, AND PARTICIPANTS: Clinical and genetic screening, and genetic counseling were offered to 151 individuals from a six-generation family carrying a TMEM127 germline mutation in a referral center. INTERVENTION AND MAIN OUTCOME MEASURES: TMEM127 genetic testing was offered to at-risk relatives and clinical surveillance for pheochromocytoma was performed in mutation-positive carriers. RESULTS: Forty seven individuals carried the c.410-2A>C TMEM127 mutation. Clinical data were obtained from 34 TMEM127-mutation carriers followed up for 8.7 ± 8.1 years (range, 1-20 y). Pheochromocytoma was diagnosed in 11 carriers (32%) at a median age of 43 years. In nine patients, symptoms started at 29 years (range, 10-55 y) and two cases were asymptomatic. Tumors were multicentric in five (45%) and bilateral in five (45%) patients. Six patients (54%) had at least one adrenomedullary nodule less than 10 mm. No paragangliomas, distant metastases, or other manifestations were detected. Cumulative penetrance of pheochromocytoma was 0% at 0-20 years, 3% at 21-30 years, 15% at 31-40 years, 24% at 41-50 years, and 32% at 51-65 years. The youngest case was diagnosed at 22 years and the earliest symptoms were reported at age 10. CONCLUSIONS: Tumor multicentricity, nodular adrenomedullary hyperplasia, and the occurrence of symptoms more than a decade earlier than the age at diagnosis are novel findings in TMEM127-related PHEO. The high penetrance of pheochromocytoma in this condition validates the benefits of genetic testing of at-risk relatives. We thus recommend that TMEM127 genetic testing should be offered to at-risk individuals at age 22 years and mutation carriers should undergo clinical surveillance annually.

Brain activity patterns during phonological verbal fluency performance with varying levels of difficulty: a functional magnetic resonance imaging study in Portuguese-speaking healthy individuals.

A large number of functional neuroimaging studies have investigated the brain circuitry which is engaged during performance of phonological verbal fluency tasks, and the vast majority of these have been carried out in English. Although there is evidence that this paradigm varies depending on the language spoken, it is unclear if this difference is associated with differences in brain activation patterns. Also, there is neuroimaging evidence that the patterns of regional cerebral activation during verbal fluency tasks may vary with the level of task demanded. In particular, the engagement of the anterior cingulate cortex seems to be relative to cognitive demand. We compared functional magnetic resonance imaging data in healthy Portuguese-speaking subjects during overt production of words beginning with letters classified as easy or hard for word production in Portuguese. Compared to the baseline condition, the two verbal fluency tasks (with either easy or hard letters) engaged a network including the left inferior and middle frontal cortices, anterior cingulate cortex, putamen, thalamus and cerebellum (p < .001). The direct comparison between the two verbal fluency conditions showed greater cerebellar activation in the easy condition relative to the hard condition. In the anterior cingulate cortex, there was a direct correlation between activity changes and verbal fluency performance during the hard condition only. Despite grammatical differences, the changes in patterns of brain activity during verbal fluency performance observed in our study are in accordance with findings of previous neuroimaging studies of verbal fluency carried out in English and other languages, with recruitment of a set of distributed cerebral areas during word production.

Effect of temporal lobe structure volume on memory in elderly depressed patients.

OBJECTIVE: To compare the volume of the hippocampus and parahippocampal gyrus in elderly individuals with and without depressive disorders, and to determine whether the volumes of these regions correlate with scores on memory tests. METHOD: Clinical and demographic differences, as well as differences in regional gray matter volumes, were assessed in 48 elderly patients with depressive disorders and 31 control subjects. Brain (structural MRI) scans were processed using statistical parametric mapping and voxel-based morphometry. Cognitive tests were administered to subjects in both groups. RESULTS: There were no between-group gray matter volume differences in the hippocampus or parahippocampal gyrus. In the elderly depressed group only, the volume of the left parahippocampal gyrus correlated with scores on the delayed naming portion of the visual-verbal learning test. There were also significant direct correlations in depressed subjects between the volumes of the left hippocampus, right and left parahippocampal gyrus and immediate recall scores on verbal episodic memory tests and visual learning tests. In the control group, there were direct correlations only between overall cognitive performance (as assessed with the MMSE) and the volume of right hippocampus, and between the total score on the visual-verbal learning test and the volume of the right and left parahippocampal gyrus. CONCLUSIONS: These findings highlight different patterns of relationship between cognitive performance and volumes of medial temporal structures in depressed individuals and healthy elderly subjects. The direct correlation between delayed visual-verbal memory recall scores with left parahippocampal volumes specifically in elderly depressed individuals provides support to the view that depression in elderly populations may be a risk factor for dementia.

White-matter hyperintensities in first-episode psychosis.

BACKGROUND: White-matter hyperintensities have been associated with both schizophrenia and mood disorders, particularly bipolar disorder, but results are inconsistent across studies. AIMS: To examine whether white-matter hyperintensities are a vulnerability marker for psychosis or are specifically associated with bipolar disorder. METHOD: T(2)-weighted magnetic resonance imaging data were acquired in 129 individuals with first-episode psychosis (either affective or non-affective psychoses) and 102 controls who were randomly selected from the same geographical areas. Visual white-matter hyperintensity ratings were used for group and subgroup comparisons. RESULTS: There were no statistically significant between-group differences in white-matter hyperintensity frequency or severity scores. No significant correlations were found between white-matter hyperintensity scores and duration of illness, duration of untreated psychosis, or severity of psychotic, manic or depressive symptoms. CONCLUSIONS: White-matter hyperintensities are not associated with vulnerability to psychosis in general, or specifically with affective psychoses. Further, first-episode psychosis investigations using more quantitative methods are warranted to confirm these findings.

A randomized comparative study of patients undergoing myocardial revascularization with or without cardiopulmonary bypass surgery: The MASS III Trial.

UNLABELLED: The MASS III Trial is a large project from a single institution, The Heart Institute of the University of Sao Paulo, Brazil (InCor), enrolling patients with coronary artery disease and preserved ventricular function. The aim of the MASS III Trial is to compare medical effectiveness, cerebral injury, quality of life, and the cost-effectiveness of coronary surgery with and without of cardiopulmonary bypass in patients with multivessel coronary disease referred for both strategies. The primary endpoint should be a composite of cardiovascular mortality, cerebrovascular accident, nonfatal myocardial infarction, and refractory angina requiring revascularization. The secondary end points in this trial include noncardiac mortality, presence and severity of angina, quality of life based on the SF-36 Questionnaire, and cost-effectiveness at discharge and at 5-year follow-up. In this scenario, we will analyze the cost of the initial procedure, hospital length of stay, resource utilization, repeat hospitalization, and repeat revascularization events during the follow-up. Exercise capacity will be assessed at 6-months, 12-months, and the end of follow-up. A neurocognitive evaluation will be assessed in a subset of subjects using the Brain Resource Center computerized neurocognitive battery. Furthermore, magnetic resonance imaging will be made to detect any cerebral injury before and after procedures in patients who undergo coronary artery surgery with and without cardiopulmonary bypass. TRIALS REGISTRATION: Clinical Trial registration information ISRCTN59539154 Off-pump vs. on-pump surgery in patients with Stable CAD MASS III.

Proton spectroscopy in Alzheimer's disease and cognitive impairment no dementia: a community-based study.

OBJECTIVE: To describe the findings of proton magnetic resonance spectroscopy ((1)H-MRS) in Alzheimer's disease (AD) and cognitive impairment, no dementia (CIND) elderly from a community-based sample. METHODS: Thirteen patients with AD, 12 with CIND and 15 normal individuals were evaluated. The (1)H-MRS was performed in the right temporal, left parietal and medial occipital regions studying the metabolites N-acetylaspartate (NAA), creatine (Cr), choline (Cho) and myoinositol (mI). The clinical diagnosis was based on standardized cognitive tests - MMSE and CAMDEX - and the results correlated with the (1)H-MRS. RESULTS: Parietal Cho was higher in control individuals and lower in CIND subjects. AD and control groups were better identified by temporal and parietal mI combined with the temporal NAA/Cr ratio. CIND was better identified by parietal Cho. CONCLUSION: The (1)H-MRS findings confirmed the hypothesis that metabolic alterations are present since the first symptoms of cognitively impaired elderly subjects. These results suggest that combining MRS from different cerebral regions can help in the diagnosis and follow-up of community elderly individuals with memory complaints and AD.

Pulmonary paracoccidioidomycosis.

Paracoccidioidomycosis (formerly known as South American blastomycosis) is produced by the thermally dimorphic fungus Paracoccidioides brasiliensis. Most often this mycosis runs a chronic progressive course affecting preferentially the lungs followed by the skin, mucous membranes, adrenals, and reticuloendothelial organs. Acute-subacute presentations can be observed in children and immunosuppressed patients. Occasionally, self-limited infections have been documented. Two types of clinical presentations are described, the acute-subacute (juvenile) and the chronic (adult) forms of the disease. Paracoccidioidomycosis predominates in adult males (13:1); this gender difference is not observed in children or adolescents. The mycosis is limited geographically to various Latin American countries, with the greatest number of cases originating in Brazil, The fungus's natural habitat has not been precisely defined, although it is supposed to be a soil-inhabiting microorganism. No outbreaks have been reported. P. brasiliensis is capable of entering into prolonged periods of latency as is demonstrated by its diagnosis in patients who have moved outside the recognized endemic areas. This review updates clinicians and laboratory workers on the characteristics of a mycosis seldom reported outside of the Latin American countries.

Volumetric reduction of the corpus callosum in Alzheimer's disease in vivo as assessed with voxel-based morphometry.

Several recent magnetic resonance imaging studies have employed voxel-based morphometry (VBM) to detect regional gray matter volume abnormalities in Alzheimer's disease (AD). However, investigations of corpus callosum (CC) abnormalities in AD using this automated methodology have been scarce, and no VBM study investigated correlations between regional CC atrophy and cognitive measurements in AD subjects at mild disease stages. We used VBM to compare the topography of CC volume differences between 14 AD subjects (MMSE 14-25) and 14 healthy volunteers. Images were acquired using a 1.5-Telsa scanner, and were spatially normalized and segmented using optimized VBM. Statistical comparisons were performed using the general linear model. Significant CC atrophy was detected in the antero-superior portion of the splenium, the isthmus, the anterior and posterior portions of the CC body, and the rostral portion of the genu. Voxels showing peak statistical difference were all left-sided (P<0.001, uncorrected for multiple comparisons). A cluster of significant positive correlation with MMSE scores was seen on the left anterior CC body. Our results confirm previous findings of diffuse volumetric CC reductions early in the course of AD, and warrant further evaluation of the relevance of atrophic changes in anterior CC portions to the cognitive impairments that characterize the disorder.

Grey matter abnormalities in Brazilians with first-episode psychosis.

BACKGROUND: In low- and middle-income countries people with schizophrenia are reported to experience better outcomes than those in high-income countries. AIMS: To examine structural brain differences in people with first-episode psychosis and controls in Brazil. METHOD: Magnetic resonance imaging using voxel-based morphometry was performed on 122 people with first-episode psychosis and 94 controls. RESULTS: There were significant decreases in grey matter in the left superior temporal and inferior prefrontal cortices, insula bilaterally and the right hippocampal region in first-episode psychosis (P<0.05, corrected for multiple comparisons). The subgroup of people with schizophrenia (n=62) exhibited a similar pattern of decrease in grey matter relative to controls. CONCLUSIONS: Structural abnormalities reported in psychosis in high-income countries are also present in first-episode psychosis in Brazil.

A 1HMRS study of the anterior cingulate gyrus in euthymic bipolar patients.

INTRODUCTION: The anterior cingulate region has been implicated in the pathophysiology of mood disorders. Studies have reported anatomical and functional abnormalities in this region in bipolar disorder patients. Few neurochemical studies have evaluated this region, especially on medicated bipolar patients. Lithium has been reported to increase NAA levels but not by all studies. We used proton magnetic spectroscopy ((1)HMRS) to measure the levels of N-acetyl-L-aspartate (NAA) and choline (Cho) relative to creatine (Cr) in the anterior cingulate of euthymic medicated bipolar subjects. METHODS: (1)HMRS was performed using a GE Signa 1.5 Tesla scanner in 13 euthymic bipolar patients who were taking lithium for at least four weeks before the scan and in 15 normal controls. The (1)HMRS signal was collected from an 8 cm(3) voxel placed in the anterior cingulate. Data analysis was performed with the automated PROBE/SV quantification tool. RESULTS: NAA/Cr and Cho/Cr ratios were not significantly different between patients and controls (NAA/Cr: 1.60 +/- 0.34 in patients, 1.68 +/- 0.34 in controls; Cho/Cr: 1.13 +/- 0.13 in patients, 1.11 +/- 0.20 in controls). CONCLUSIONS: We did not find a significant difference in the NAA/Cr and Cho/Cr ratio between bipolar patients and healthy controls. Chronic administration of psychotropic drugs could have had an effect on NAA/Cr levels of bipolar patients.

Espectroscopia de prótons na doença de Alzheimer e no comprometimento cognitivo sem demência: estudo de uma amostra comunitária / Proton spectroscopy in Alzheimer's disease and cognitive impairment not dementia: a community study

OBJETIVO: Descrever os achados da espectroscopia de prótons (¹H-ERM) na doença de Alzheimer (DA) e no comprometimento cognitivo sem demência (CIND) em uma amostra da comunidade. MÉTODO: Foram avaliados seis pacientes com DA, sete com CIND e sete controles normais, originários da comunidade. ¹H-ERM foi realizada com voxel de 8 cm³ nas regiões temporal direita, parietal esquerda e occipital medial e estudados os metabólitos: N-acetilaspartato (NAA), creatina (Cr), colina (Cho) e mio-inositol (mI). RESULTADOS: O NAA foi maior nos indivíduos controles do que nos DA e intermediário no CIND. Análise de função discriminante mostrou que as associações Cr parietal-Cr occipital e Cr parietal-Cho occipital identificaram corretamente 92,3 por cento da amostra comparando Controle vs DA. Na comparação Controle vs CIND O mI temporal identificou corretamente 78,6 por cento dos indivíduos. CONCLUSÃO: A espectroscopia pode contribuir para o diagnóstico e seguimento de indivíduos com comprometimento cognitivo; avaliações de pacientes da comunidade podem revelar achados diferentes quanto à distribuição dos metabólitos cerebrais.

Frontal and anterior cingulate activation during overt verbal fluency in patients with first episode psychosis.

OBJECTIVE: Functional neuroimaging studies using phonological verbal fluency tasks allow the assessment of neural circuits relevant to the neuropsychology of psychosis. There is evidence that the prefrontal cortex and anterior cingulate gyrus present different activation patterns in subjects with chronic schizophrenia relative to healthy controls. We assessed the functioning in these brain regions during phonological verbal fluency in subjects with recent-onset functional psychoses, using functional magnetic resonance imaging (FMRI). METHODS: Seven patients with functional psychoses (3 schizophreniform, 4 affective) and 9 healthy controls were studied. We compared functional magnetic resonance images acquired during articulation of words beginning with letters classified as easy for word production in Portuguese. Statistical comparisons were performed using non-parametric tests. RESULTS: There were no differences between patients and controls in task performance. Controls showed greater activation than patients in the left rostral anterior cingulate gyrus and right inferior prefrontal cortex, whereas patients showed stronger activation than controls in a more dorsal part of the anterior cingulate gyrus bilaterally and in a more superior portion of the right prefrontal cortex. CONCLUSION: Our preliminary findings of attenuated engagement of inferior prefrontal cortex and anterior cingulate gyrus in patients with recent onset psychosis during phonological verbal fluency are consistent with those of previous studies. The greater activation found in other parts of the anterior cingulate gyrus and prefrontal cortex in patients may be related to a compensatory response that is required to maintain normal task performance, and suggests a pattern of disorganized activity of different functional anterior cingulate gyrus units in association with psychotic conditions.

Frontal and anterior cingulate activation during overt verbal fluency in patients with first episode psychosis

OBJETIVO: Estudos de neuroimagem funcional empregando tarefa de fluência verbal fonológica têm permitido a avaliacão dos circuitos neurais relevantes à neuropsicologia das psicoses. Pacientes com esquizofrenia crônica apresentam diferenca nos padrões de ativacão em córtex pré-frontal e giro do cíngulo anterior em relacão a controles normais. Essas regiões cerebrais foram avaliadas por ressonância magnética funcional, durante tarefa de fluência verbal fonológica, em pacientes com psicose funcional de início recente. MÉTODOS: Sete pacientes com psicose funcional (3 esquizofreniformes, 4 afetivos) e nove controles saudáveis foram estudados. Foram comparadas as imagens de ressonância magnética funcional adquiridas durante a articulacão de palavras que comecassem com letras classificadas como "fáceis" para a producão de palavras em Português. Comparacões estatísticas foram obtidas com métodos não-paramétricos. RESULTADOS: Os grupos não diferiram em relacão ao desempenho da tarefa. Os controles apresentaram maior ativacão em cíngulo anterior rostral esquerdo e em córtex pré-frontal inferior direito, enquanto os pacientes mostraram maior ativacão em uma região mais dorsal do cíngulo anterior bilateralmente e em uma porcão mais superior do córtex pré-frontal direito. CONCLUSAO: Nossos resultados preliminares são consistentes com estudos prévios e demonstram menor ativacão em córtex pré-frontal e cíngulo anterior em pacientes com psicose de início recente durante tarefa de fluência verbal fonológica. A maior ativacão em outras partes do cíngulo anterior e do córtex pré-frontal em pacientes pode estar relacionada a uma resposta compensatória necessária para a manutencão do desempenho normal da tarefa e sugere que uma alteracão do padrão de atividade das diversas unidades funcionais do cíngulo anterior está associada aos transtornos psicóticos.

Relationship between regional cerebral blood flow and separate symptom clusters of major depression: a single photon emission computed tomography study using statistical parametric mapping.

This study examined the relationship between resting regional cerebral blood flow (rCBF) patterns in patients with major depressive disorder (MDD) and specific symptom clusters derived from ratings on the Hamilton Rating Scale for Depression (HRSD) and the Mini Mental State Examination. We hypothesized that the functional activity in frontal, parietal, anterior cingulate, basal ganglia and limbic regions would be related to specific symptom domains. Fifteen patients fulfilling DSM-IV criteria for MDD who were off all psychotropic medications for >4 weeks and 15 normal volunteers were recruited. Single photon emission computed tomography (SPECT) images were obtained after (99m)Tc-ECD injection, and correlations between rCBF patterns and symptom severity ratings were calculated on a voxel-by-voxel basis, using statistical parametric mapping (SPM). Severity of depressive mood was inversely correlated with rCBF in the left amygdala, lentiform nucleus, and parahippocampal gyrus, and directly correlated with rCBF in the right postero-lateral parietal cortex (p < 0.001, uncorrected for multiple comparisons). Insomnia severity was inversely correlated with rCBF in the right rostral and subgenual anterior cingulate cortices, insula and claustrum. Anxiety severity was directly correlated with rCBF in the right antero-lateral orbitofrontal cortex, while cognitive performance was directly correlated with rCBF in the right postero-medial orbitofrontal cortex and in the left lentiform nucleus. Our findings confirmed the prediction that separate symptom domains of the MDD syndrome are related to specific rCBF patterns, and extend results from prior studies that suggested the involvement of anterior cingulate, frontal, limbic and basal ganglia regions in the pathophysiology of MDD.

Regional gray matter abnormalities in obsessive-compulsive disorder: a voxel-based morphometry study.

BACKGROUND: Several structural magnetic resonance imaging (MRI) studies have investigated the presence of brain abnormalities in obsessive-compulsive disorder (OCD) but have not produced consistent findings. This might be partly related to their use of a regions-of-interest approach. We assessed gray matter volumes in 19 OCD subjects and 15 healthy volunteers, using voxel-based morphometry (VBM). METHODS: Images were acquired with a 1.5-T MRI scanner, spatially normalized, and segmented with optimized VBM. Statistical comparisons were performed with the general linear model. RESULTS: Significant findings were detected in regions predicted a priori to be implicated in OCD, including increased gray matter in OCD subjects relative to control subjects in posterior orbitofrontal and parahippocampal regions; decreased gray matter in OCD patients in the left anterior cingulate cortex; and inverse correlations between obsessive-compulsive symptom severity and gray matter in the medial thalamus (p < .001, uncorrected for multiple comparisons). Also, an unpredicted site of gray matter reduction in OCD patients in the right parietal associative cortex approached significance (p = .052, corrected for multiple comparisons). CONCLUSIONS: Our findings are consistent with previous studies implicating dysfunction of orbitofrontal, cingulate, thalamic, and temporolimbic regions in OCD and suggest that the involvement of the parietal cortex in the pathophysiology of OCD warrants further investigation.

Reduced phospholipid breakdown in Alzheimer's brains: a 31P spectroscopy study.

BACKGROUND: Abnormalities of membrane phospholipid metabolism have been described in Alzheimer's disease (AD). We investigated, with the aid of (31)P magnetic resonance spectroscopy, the in vivo intracerebral availability of phosphomonoesters (PME) and phosphodiesters (PDE) in patients with AD. METHODS: Eighteen outpatients with mild or moderate probable AD and 16 nondemented elderly volunteers were assessed with the Cambridge Examination for Mental Disorders of the Elderly (CAMDEX) and its cognitive subscale of the CAMDEX schedule (CAMCOG). Scans were performed on a 1.5 T magnetic resonance imager addressing a 40-cm(3) voxel in the left prefrontal cortex. Main outcome measures were mean relative peak areas of PME and PDE, which provide an estimate of membrane phospholipid metabolism. RESULTS: PME resonance and the PME/PDE ratio were increased in AD patients as compared to controls (p<0.05). PME was negatively correlated with global cognitive performance as shown by the Mini-Mental State Examination (r(s)=-0.36, p=0.05) and CAMCOG scores (r(s)=-0.49, p=0.007), as well as with discrete neuropsychological functions, namely, memory (r(s)=-0.53, p=0.004), visual perception (r(s)=-0.54, p=0.003), orientation (r(s)=-0.36, p=0.05), and abstract thinking (r(s)=-0.48, p=0.01). CONCLUSIONS: We provide evidence of reduced membrane phospholipid breakdown in the prefrontal cortex of mild and moderately demented AD patients. These abnormalities correlate with neuropsychological deficits that are characteristic of AD.

[Proton spectroscopy in Alzheimer's disease and cognitive impairment not dementia: a community study]. / Espectroscopia de prótons na doença de Alzheimer e no comprometimento cognitivo sem demência: estudo de uma amostra comunitária.

OBJECTIVE: To describe the proton magnetic resonance spectroscopy (1H-ERM) data in Alzheimer's disease (AD) and Cognitive Impairment Not Dementia (CIND) in a community sample. METHOD: We investigated subjects with AD (n=6), CIND (n=7) and normal control (n=7). 1H-ERM was performed with single voxel (8 cm3) placed in temporal, parietal and occipital regions and studied metabolites were: N-acetylaspartate (NAA), creatine (Cr), choline (Cho) and myo-inositol (mI). RESULTS: NAA concentration was higher in control subjects than AD and intermediated in CIND patients. Cho parietal plus occipital and Cr parietal plus Cho occipital classified correctly 92.3% of subjects Control vs AD. Temporal mI classified 78.6% of subjects between Control vs CIND. CONCLUSION: Spectroscopy can be used in the diagnosis and follow-up of individuals with cognitive impairment; evaluation of community subjects may show different patterns of brain metabolites distribution.