Healthy Control Subjects Subjects Research Articles

“Back to Braak”: Role of Nucleus Reuniens and Subcortical Pathways in Alzheimer’s Disease Progression

BackgroundPatients with Alzheimer’s Disease (AD) exhibit structural alterations of the thalamus that correlate with clinical symptoms. However, given the anatomical complexity of this brain structure, it is still unclear whether atrophy affects specific thalamic nuclei and modulates the clinical progression from a prodromal stage, known as Mild Cognitive Impairment (MCI), to full-fledged AD.ObjectivesTo characterize the structural integrity of distinct thalamic nuclei across the AD spectrum, testing whether MCI patients who convert to AD (c-MCI) show a distinctive pattern of thalamic structural alterations compared to patients who remain stable (s-MCI).DesignInvestigating between-group differences in the volumetric features of distinct thalamic nuclei across the AD spectrum.SettingProdromal and clinical stages of AD.ParticipantsWe analyzed data from 84 healthy control subjects (HC), 58 individuals with MCI, and 102 AD patients. The dataset was obtained from the AD Neuroimaging Initiative (ADNI-3) database. The MCI group was further divided into two subgroups depending on whether patients remained stable (s-MCI, n=22) or progressed to AD (s-MCI, n=36) in the 48 months following the diagnosis.MeasurementsA multivariate analysis of variance (MANOVA) assessed group differences in the volumetric features of distinct thalamic nuclei obtained from magnetic resonance (MR) images. A stepwise discriminant function analysis identified which feature most effectively predicted the conversion to AD. The corresponding predictive performance was evaluated through a Receiver Operating Characteristic approach.ResultsAD and c-MCI patients showed generalized atrophy of thalamic nuclei compared to HC. In contrast, no significant structural differences were observed between s-MCI and HC subjects. Compared to s-MCI, c-MCI individuals displayed significant atrophy of the nucleus reuniens and a trend toward significant atrophy in the anteroventral and laterodorsal nuclei. The discriminant function analysis confirmed the nucleus reuniens as a significant predictor of AD conversion, with a sensitivity of 0.73 and a specificity of 0.69.ConclusionsIn line with the pathophysiological relevance of the nucleus reuniens proposed by seminal post-mortem studies on patients with AD, we confirm the pivotal role of this nucleus as a critical hub in the clinical progression to AD. We also propose a theoretical model to explain the evolving dysfunction of subcortical brain networks in the disease process.

Self-assessment of olfactory function using the “Sniffin’ Sticks”

BackgroundA precise and reliable test of the olfactory function is indispensable for the diagnosis of the olfactory disorder (OD). Despite of this, in a clinical context, often there is no place in daily routine for time-consuming procedures. This study aimed to examine if the assessment of olfactory function using the “Sniffin’ Sticks” is suitable for self-assessment.MethodsParticipants comprised 84 healthy control subjects (HC) and 37 OD patients. The “Sniffin’ Sticks” test battery consisting of odor threshold (T), discrimination (D) and identification (I) tests was used for self- and assisted assessments. To save time, we applied the 8-item wide step version of the T test and the 8-item D test, whereas the I task remained the same as the original version. The whole test included two sessions, with each session comprising a self-assessment part performed by the participants themselves, and an assisted-assessment part performed by the examiner.ResultsSniffin’ Sticks self-assessment was efficient in distinguishing between self-reported HC subjects and OD patients (p’s < 0.01), and the scores did not differ significantly from the assisted-assessment (p’s > 0.05). In the self-administered I and TDI tests, there was a moderate to excellent test–retest reliability (ICC = 0.51–0.93, p’s < 0.01), and a strong to excellent correlation with the assisted assessment (r = 0.71–0.92, p’s < 0.01). However, the self-administered T and D tests only exhibited low to moderate test–retest reliability (ICC = 0.30–0.72, p’s < 0.05) and correlations with the assisted test (r = 0.31–0.62, p’s < 0.05).ConclusionsThe Identification self-test is appropriate to be solely applied, and is therefore an easy-to-use alternative for olfactory screening in a larger segment of patients. The whole “Sniffin’ Sticks” self-test also shows good measurement properties and is therefore a suitable backup in clinical practice, but improvement is needed due to the simplified D and T self-test.

Multiomics implicate gut microbiota in altered lipid and energy metabolism in Parkinson\u2019s disease

We aimed to investigate the link between serum metabolites, gut bacterial community composition, and clinical variables in Parkinson’s disease (PD) and healthy control subjects (HC). A total of 124 subjects were part of the study (63 PD patients and 61 HC subjects). 139 metabolite features were found to be predictive between the PD and Control groups. No associations were found between metabolite features and within-PD clinical variables. The results suggest alterations in serum metabolite profiles in PD, and the results of correlation analysis between metabolite features and microbiota suggest that several bacterial taxa are associated with altered lipid and energy metabolism in PD.

P0760THE INFLUENCE OF MICROBIOME COMPOSITION ON THE DEVELOPMENT OF IGA NEPHROPATHY

Abstract Background and Aims Overall, human microbiota contains 1014 bacterial cells. The human intestine is particularly dense of microbes, 1012 bacteria per g (dry weight), especially at colon level. Under healthy conditions, the human microbiota provides trophic and protective functions. Bacteroidaceae, and Prevotellaceae differed among IgA and Healthy Control subjects (HC). Enterobacteriaceae species were almost the highest in the fecal samples of patients. Bifidobacterium species decreased in the fecal samples of Patients compared to HC subjects. Increasing evidence indicates that changes in the microbiota composition known as Dysbiosis, can affect human health and disease. Altering the balance of the gut microbiota can also affect kidney physiology and pathology, such as IgAN. we hypothesize that the aberrantly IgA1 that produced in IgAN in response to a mucosal infection may be influenced by the composition of the patient microbiome by inducing excessive abnormal mucosal IgA responses. Study aim is to explore if IgAN patients have different microbiome composition compared with the healthy control individuals. Method Stool sample from 26 IgAN patients &amp; from 26 healthy control individuals subjected to microbiome array and to taxonomic analysis, to characterize their microbiome compositions. Serum Creatinine\ albumin and urine proteinuria levels are used for evaluate the renal function of each IgAN patient. The clinical and laboratory evaluations will be crossed with the taxonomic data using statistical analysis methods. Results Based on our preliminary result with 11 IgAN patients and 11 healthy control individuals, there are significant differences in the microbiome composition between the two groups. IgAN patients have a significant increase in the Bacteroides phylum accompanied with a significant decrease in the amount of both the Actinobacteria and Verrucomicrobia phyla, compared with the healthy individuals. At the genus level, there is a significant increase in the Prevotella bacteria in the IgAN subjects compared with the healthy individuals. Conclusion 1. A strong association between specific bacteria population and IgAN disease, we isolate specific population of bacteria that leads to IgAN or even aggravate its manifestation. 2. It may help to predict the tendency of each individual to develop IgAN and even predict the prognosis of each IgAN patient according to their microbiome. 3. it is rational to alter the intestinal barrier, the content of gut microbiota and its metabolites in the realm of CKD using different strategies such Prebiotics and symbiosis. 4. To develop disease-specific therapies based on microbiome modulations and manipulations such as modifying the gut microbiota through diet, antibiotic therapies, probiotic, bariatric surgery, fecal transplants.

Inflammatory microenvironment in ARDS patients polarize clinically utilized MSCs towards a pro-inflammatory MSC phenotype

Background & Aim Background and aim Despite an enormous interest in using MSCs as a cell-based therapy to treat acute respiratory distress syndrome (ARDS), the knowledge of MSC in vivo mechanism of actions are limited. ARDS pathology is driven by an acute severe inflammatory response, but how this inflammatory environment influences MSC behavior is not yet well understood and needs to be extensively studied. Methods, Results & Conclusion Methods Clinically utilized bone marrow-derived human MSCs were exposed to bronchoalveolar lavage fluids (BALF), a surrogate for the in vivo environment, obtained from patients with ARDS or from healthy control subjects (HC). Following exposure, cells and conditioned medium were assessed for different factors including viability, levels of pro- and anti-inflammatory cytokines, and mitochondrial activity. Results Following 24 hours exposure, we found that there were no differences in viability in ARDS BALF-exposed MSCs compared to HC or saline-exposed cells. However, preliminary data indicate that MSCs exposed to ARDS BALF differentiated towards a more pro-inflammatory phenotype with significant increased production of pro-inflammatory mediators such as IL-6, IL-8, and IL-18 compared to saline exposed MSCs. A trend towards increased secretion was also seen in production of IL-6 and IL-8 in ARDS BALF-exposed MSCs compared to HC BALF-exposed cells, however this did not reach significance. Interestingly, a significant increase in HGF was observed in ARDS BALF-exposed MSCs compared to saline control. Furthermore, preliminary metabolomics analysis suggests that MSCs exposed to BALF samples from both ARDS and HC subjects had an altered mitochondrial activity compared to unstimulated MSCs. Conclusion Our data suggest that the inflammatory environment found in ARDS patients activate and polarize MSCs towards a pro-inflammatory phenotype. These results further highlight the need to understand the effect of the in vivo inflammatory environment on systemic or locally administered MSCs.

Patients with major depression show greater memory improvement if motivation is increased: An exploratory study under real-life-like conditions

ABSTRACTIntroduction: Loss of motivation is a core feature of major depression (MDD) and has been suggested to influence neuropsychological performance. However, previous studies have come to inconsistent results, but they were only done under laboratory test conditions. Thus, the aim of the present study is to experimentally investigate the influence of motivation on neurocognition under real-life-like conditions.Methods: Twenty-two inpatients with MDD (M = 42.5 years) and 27 demographically comparable healthy control subjects (HC) underwent a new memory paradigm under real-life-like conditions: To bridge the “waiting time” before a planned neuropsychological assessment, subjects were shown two videos on the waiting room TV with different motivational appeals. Video 1 (lower motivation) deals with factual information about the research department’s history. Video 2 (higher motivation) consists of information about a current lottery. The video stories were developed by analogy to the established “Logical Memory” test. Subjective motivation was assessed by a short form of the Intrinsic Motivation Inventory. After 30 min, subjects had to perform an unexpected free recall and recognition of the video content during the intended test session.Results: MDD patients, different from HC subjects, rated their intrinsic motivation for the presentation of video 2 as higher compared to video 1. Two-way repeated measures analyses of variance as well as post-hoc tests showed a significant effect of motivation on the MDD patients' memory scores for video 2.Conclusions: The results provide support for an association between motivation and neurocognition in depressed patients and suggest that cognition under real-life-like conditions can be improved more in MDD patients relative to healthy controls with the use of motivational interventions.

Prevalence and Psychopathological Determinants of Sexual Dysfunction and Related Distress in Women With and Without Multiple Sclerosis

IntroductionSexual dysfunction (SD) is common but still underdiagnosed in women with multiple sclerosis (MS); in fact, the lack of a consistent use of validated diagnostic tools makes the prevalence of SD and related distress difficult to define precisely. AimTo assess the prevalence of SD in Italian women with MS compared with age-matched healthy control subjects (HC) and the association with demographic, psychological, and MS-related characteristics. MethodsThe Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale were administered to 153 women with MS and 153 HC. Demographic, gynecologic, and neurologic data were obtained. Disability was assessed using the Expanded Disability Status Scale. Psychological symptoms were evaluated in MS patients with Profile of Mood State and the Beck Depression Inventory II. Main Outcomes MeasuresPrevalence of SD and sexual distress in women with MS compared with HC. ResultsAmong women sexually active in the last month, we found an increased prevalence of SD in MS patients compared with HC subjects (42.0% vs 16.0%, P = .0001). The prevalence of dysfunctional FSFI global scores (<26.55) was higher in women with MS compared with HC (49.6% vs 33.6%, P = .014). In the MS group, the prevalence of SD was similar between pre- and post-menopausal women. Both premenopausal and postmenopausal MS women presented a greater prevalence of SD if compared with the premenopausal and postmenopausal HC groups (30/79 [37.9%] vs. 5/74 [6.8%], P = .0001 and 20/40 [50.0%] vs 16/57 [28.1%], P = .03, respectively). A negative correlation was observed between the FSFI global score and age and Expanded Disability Status Scale. Depressive symptoms were more common in women with MS and SD than in those without. Clinical ImplicationsThis study suggests that sexual function investigation should always be a standard part of the consultation with healthcare professionals for MS. Strength & LimitationsThe strength of this study was the comparison with an age-matched healthy control group and the use of validated questionnaires to assess both sexual function and sexual distress. Larger and multicenter studies may further support our findings. ConclusionIn our cohort, the prevalence of SD and sexual distress was higher in women with MS compared to the HC group. Age, disability, and depressive symptoms were associated with increased SD.Gava G, Visconti M, Salvi F, et al. Prevalence and Psychopathological Determinants of Sexual Dysfunction and Related Distress in Women With and Without Multiple Sclerosis. J Sex Med 2019;16:833–842.

The Borg CR-10 scale is suitable to quantify aerobic exercise intensity in women with fibromyalgia syndrome

ABSTRACT Patients with Fibromyalgia syndrome (FMS) report higher ratings of perceived exertion (RPE) compared to healthy individuals for the same exercise intensity; however, to our knowledge, no studies have evaluated RPE at the ventilatory anaerobic threshold (VAT) for this population. This study aimed to assess RPE using the Borg CR-10 scale during a cardiopulmonary exercise test (CPET) in women with FMS. Twenty-four women with FMS and twenty healthy control subjects (HC) voluntarily participated in this study. Near the end of every 1-minute period during CPET, subjects were asked to report their RPE for fatigue in the lower limbs (RPE-L) and dyspnea (RPE-D), respectively, according to the Borg CR-10 scale. FMS subjects showed higher RPE-L and RPE-D compared to HC subjects at free wheel and at the first load increment. However, no significant difference was observed between groups for power output. There was no significant difference between groups for RPE-L and RPE-D reported at VAT and peak CPET. However, FMS subjects showed lower power output compared to HC subjects. The present results showed that FMS subjects present higher RPE compared to HC subjects. However, RPE reported at VAT and at peak CPET was not different between groups. The Borg CR-10 scale scores obtained at VAT can be used as an additional parameter for prescribing exercise intensity in aerobic training protocols for women with FMS.

Contribution of IL-10 and its -592 A/C polymorphism to cognitive functions in first-episode drug-naive schizophrenia

Numerous studies have shown that proinflammatory cytokines produced by immune cells in the brain have deleterious effects on cognitive functions. In contrast, IL-10, an anti-inflammatory cytokine, can be neuroprotective and prevent neuronal dysfunction. However, few studies have linked the role of IL-10 to cognitive deficits in schizophrenia. In this study, serum IL-10 levels and genotypes for the IL10 -592 A/C promoter polymorphism were measured in a cohort of first-episode drug-naïve schizophrenic patients (FEDN-S) (n=256) and healthy control subjects (HC) (n=540). All participants were assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and psychopathology was assessed by the Positive and Negative Syndrome Scale (PANSS). In a separate transcriptomic data set containing 577 healthy human brain samples, we analyzed IL-10 and IL-10 RA/B-associated genetic networks in order to ascertain potential functions for IL-10 in the brain. We found a significant difference in allelic frequency between FEDN-S and HC subjects. The A allelic variant was associated with reduced serum IL-10 levels and worse attentional performance in FEDN-S but not in HC subjects. Moreover, serum IL-10 levels were correlated with the extent of cognitive impairment, especially attentional performance in the schizophrenic A-allele carriers. In human brain transcriptomic coexpression analysis, we found that genes most significantly co-expressed with IL10 were associated with synaptic vesicle transportation, and both IL10RA and IL10RB were most significantly co-expressed not only with genes that regulate inflammation but also with those that participate in synaptic formation. The IL10-592 A/C genetic variant was more common in schizophrenic patients than HC and was associated with lower IL-10 serum levels and worse attentional performance in these patients. Furthermore, the IL10 gene and its receptors in the healthy human brain appear to regulate inflammation and synaptic functions that are important for cognition, and hence its deficiency in schizophrenia may contribute to cognitive impairment.

Myeloid dendritic cells are decreased in peripheral blood of Alzheimer's disease patients in association with disease progression and severity of depressive symptoms.

BackgroundDendritic cells (DCs) are major orchestrators of immune responses and inflammation. They are migratory cells, which may play a role in Alzheimer’s disease (AD), as suggested by prior in vitro studies. With the intent to investigate the clinical relevance of DC modifications in vivo, the present study was aimed to evaluate the levels of blood DCs in AD patients, in relation to the progression of the disease, the severity of its symptoms, and the treatment with acetylcholinesterase inhibitors (AChEIs), a class of drugs used to improve cognitive functioning in people with dementia.MethodsThe two main subpopulations of immature blood DCs, namely myeloid (mDCs) and plasmacytoid (pDCs) cells, were evaluated by flow cytometry analysis in 106 AD patients, in comparison with the same cells from 65 individuals with mild cognitive impairment (MCI) and 73 healthy control subjects (HC). The relationship between blood DC levels and symptom severity was also assessed in AD patients, and their blood DC frequency was considered both in the absence or presence of treatment with AChEIs.ResultsA significant depletion in blood mDCs was observed in AD patients, as compared to HC and MCI subjects. At variance, pDC levels were comparable among the three groups of subjects. The mDC decrease was evident only after the emergence of AD clinical symptoms, as confirmed by the follow-up analysis of a subgroup of MCI subjects who exhibited a significant decline in mDCs after their conversion to AD. Notably, the mDC decline was inversely correlated in AD patients with the frequency and severity of depressive symptoms. Eventually, the mDC depletion was not observable in patients treated with AChEIs.ConclusionsOur results provide the first evidence that blood mDC levels are dysregulated in AD. This phenomenon appears mainly linked to AD progression, associated with stronger severity of AD-related symptoms, and influenced by AChEI treatment. Taken all together, these data suggest that blood mDCs may serve as a cell source to test disease-induced and treatment-related changes and support the innovative notion that DCs play a role in AD, as ultimate evidence of the immune system participation in disease progression.

A comparison of the upper limb lift test between women with breast cancer and healthy control subjects

title: A COMPARISON OF THE UPPER LIMB LIFT TEST BETWEEN WOMEN WITH BREAST CANCER AND HEALTHY CONTROL SUBJECTS. Author(s): Fisher M.I., Pfalzer L., Levy E.W., Harrington S.E., Gerber N.L., Stout N. Affiliation(s): University of Dayton, Department of Physical Therapy, Dayton, United States of America, University of Michigan-Flint, Physical Therapy Department, Flint, United States of America, Walter Reed National Military Medical Center, Bethesda, United States of America, Creighton University, Department of Physical Therapy, Omaha, United States of America, George Mason University, Fairfax, United States of America, National Institutes of Health, Department of Rehabilitation Medicine, Bethesda, United States of America Background: Objective measures of upper limb (UL) function specific to breast cancer survivors (BC) are limited. Motion, strength, and muscular endurance are measurable components of UL function. A clinical test that quantifies these components is needed. Purpose: This study compares the Upper Limb Lift Test (ULLT) between women with BC and healthy control subjects (HC) at baseline, 1-3 months, and 12+ months post-operatively enrolled in a prospective surveillance trial with early intervention. A secondary purpose was to validate the ULLT by comparing findings to self-reported UL function, symptom distress, and shoulder motion in a group of women with BC and healthy control subjects. Methods: One hundred sixty BC (53.1+ 11.7 years with a body mass index of 26.7±6.1kg/m) completed ULLT and self-reports of UL function, symptom distress, and shoulder motion preoperatively and at 1-3 months and 2 months post-operatively. Fifty-nine HC subjects (51.4+13.6 years with a body mass index of 26.3±5.7 kg/m) completed the same measures during a single visit. Each subject completed ULLT on each limb (right = RULLT and left = LULLT). The ULLT is a series of repeated shoulder elevations against resistance, moving a dumbbell anthropometrically scaled to the participant weight from a scaled height. Perceived exertion (RPE) using BORG20 was measured post ULLT. Descriptive statistics of all variables including repetitions and PE were calculated for group by time using SPSS ver21. A repeated measures analysis of variance was used to compare HC to BC over time. .The ULLT and shoulder flexion, abduction, internal and external rotation motion were measured by a clinician. Subjects completed the following questionnaires: Disabilities of the Arm, Shoulder, and Hand-Quick (Quick DASH), SF-36 and Symptom Distress questionnaire. Women with BC completed the questionnaires at baseline, 1-3 months and 12 months postoperatively, and were compared to HC at one time point. Results: At baseline the mean (SD) repetitions lifted were 17±5 and for RULLT and LULLT for BC and 15±6 for RULLT and LULLT for HC respectively. Differences between number of repetitions completed for both RULLT, LULLT were significant between HC and BC groups (p=0.003) at baseline. There were no significant differences at 1-3 months and 12+ months between RULLT and LULLT with the mean (SD) for BC was 16±7 and 16±6 for the RULLT respectively, and 15±7 and 16±6 for the LULLT respectively. RPE averaged 12.4± 2.9 for all BC. No significant differences in RPE were found between groups at 1-3 months, however, RPE at 12+ months was significantly lower at 12+ months in the BC (p=0.034). Conclusion(s): The ULLT repetitions were significantly lower in HC compared to BC at baseline for both UL. This suggests that women with BC had adequate lifting capacity at time of cancer diagnosis. There was no significant difference at 1-3 months or 12+ months post-operatively indicating the prospective surveillance and early intervention was effective in improving upper limb lifting capacity. Implications: The ULLT provides an objective measure of UL function (motion, strength, and muscular endurance) which can be used throughout BC treatment to identify if impairments exist and guide rehabilitation strategies. Key-Words: breast cancer; muscle endurance; muscle strength Funding acknowledgements: Funding was provided by the National Institutes of Health (NIH) and Walter Reed Military Medical Center (WRMMC). Ethics approval: This study was an NIH and WRMMC IRB approved trial, and informed consent was obtained from all participants. Preferred Presentation Type: Platform presentation

RETRACTED: Increased levels of Th17 cells are associated with non-neuronal acetylcholine in COPD patients

T-lymphocytes, including Th17-cells and T-cells expressing acetylcholine (ACh), are key components of systemic inflammation in chronic obstructive pulmonary disease (COPD). We investigated whether ACh promotes Th17 cells in COPD. ACh, IL-17A, IL-22, RORγt, FOXP3 expression and AChIL-17A, AChIL-22, AChRORγt coexpression was evaluated in peripheral blood mononuclear cells (PBMC) from COPD patients (n=16), healthy smokers (HS) (n=12) and healthy control subjects (HC) (n=13) (cultured for 48 h with PMA) by flow cytometry. Furthermore, we studied the effect of Tiotropium (Spiriva®) (100 nM) and Olodaterol (1nM) alone or in combination, and of hemicholinium-3 (50 μM) on AChIL-17A, AChIL-22, AChRORγt, and FOXP3 expression in CD3+PBT-cells of PBMC from COPD patients (n=6) cultured for 48 h with PMA. CD3+PBT-cells expressing ACh, IL-17A, IL-22 and RORγt together with CD3+PBT-cells co-expressing AChIL-17A, AChIL-22 and AChRORγt were significantly increased in COPD patients compared to HC and HS subjects with higher levels in HS than in HC without a significant difference. CD3+FOXP3+PBT-cells were increased in HS than in HC and COPD. Tiotropium and Olodaterol reduced the percentage of CD3+PBT-cells co-expressing AChIL-17A, AChIL-22, and AChRORγt while increased the CD3+FOXP3+PBT-cells in PBMC from COPD patients, cultured in vitro for 48 h, with an additive effect when used in combination. Hemicholnium-3 reduced the percentage of ACh+IL-17A+, ACh+IL-22+, and ACh+RORγt+ while it did not affect FOXP3+ expression in CD3+PBT-cells from cultured PBMC from COPD patients. We concluded that ACh might promote the increased levels of Th17-cells in systemic inflammation of COPD. Long-acting β2-agonists and anticholinergic drugs might contribute to control this event.

Temperament and character traits in children and adolescents with major depressive disorder: A case–control study

ObjectivesTo evaluate temperament and character traits using the Junior Temperament and Character Inventory (JTCI) in children and adolescents with major depressive disorder (MDD) in comparison with healthy control subjects (HC), and to verify if comorbidity with disruptive behavioral disorders and being currently depressed influence JTCI scores. MethodsA case–control study comprising 41 MDD children/adolescents matched to 40 HC by gender and age (8–17years). All participants were assessed diagnostically with the Kiddie Schedule for Affective Disorders and Schizophrenia – Present and Lifetime (K-SADS-PL). Temperament and character traits were measured with the parent and child versions of JTCI, and depression was evaluated with the Children's Depression Rating Scale (CDRS). ResultsAccording to child and parent data, MDD subjects had significantly higher scores on harm avoidance and novelty seeking, and lower scores on reward dependence, persistence, self-directedness and cooperativeness compared with HC. According to parent data only, MDD subjects significantly differed from HC on self-transcendence (lower spirituality scores and higher fantasy scores). Comorbidity with disruptive behavioral disorders exerted influence on almost all dimensions, in general increasing the mean differences between MDD and HC subjects. Also, being currently depressed did not influence the results, except for reward dependence according to parent data. LimitationsThe cross-sectional nature of the study and its limited sample size. ConclusionsMDD children/adolescents have a different temperament and character profile compared to HC subjects. This study supports previous findings of trait-like characteristics of harm avoidance and self-directedness.

Low Residual CBF Variability in Alzheimer's Disease after Correction for CO(2) Effect.

We tested the claim that inter-individual CBF variability in Alzheimer’s disease (AD) is substantially reduced after correction for arterial carbon dioxide tension (PaCO2). Specifically, we tested whether the variability of CBF in brain of patients with AD differed significantly from brain of age-matched healthy control subjects (HC). To eliminate the CO2-induced variability, we developed a novel and generally applicable approach to the correction of CBF for changes of PaCO2 and applied the method to positron emission tomographic (PET) measures of CBF in AD and HC groups of subjects. After correction for the differences of CO2 tension, the patients with AD lost the inter-individual CBF variability that continued to characterize the HC subjects. The difference (ΔK1) between the blood-brain clearances (K1) of water (the current measure of CBF) and oxygen (the current measure of oxygen clearance) was reduced globally in AD and particularly in the parietal, occipital, and temporal lobes. We then showed that oxygen gradients calculated for brain tissue were similar in AD and HC, indicating that the low residual variability of CBF in AD may be due to low functional demands for oxidative metabolism of brain tissue rather than impaired delivery of oxygen.

Script-event representation in patients with severe traumatic brain injury

The aim of the present study was to examine the syntactic and semantic dimensions of script representation in patients with structural damage within the cerebral cortex following a severe traumatic brain injury (TBI). Forty TBI patients and 38 healthy control subjects (HC) were asked to sort cards describing actions belonging to eight scripts according to the script to which they belonged and according to their order of execution. Each script included actions which were low in centrality and distinctiveness (NCA & NDA), and high in centrality (CA), distinctiveness (DA), and CA and DA. Actions were presented in three conditions. In the scripts with headers (SH) condition, the actions were given with each script header written on a separate card. In the scripts without headers condition (SwH) no script header was provided. In the scripts with distractor header (SDH) condition, the actions were given with each script header and a distractor header written on separate cards. The results showed that performance of TBI patients was significantly lower in all conditions. Overall, TBI patients made significantly more sequencing and sorting errors (for all types of actions) than HC subjects. These data are consistent with the view that TBI produces impairment of both the syntactic and semantic dimensions of script representation.

Habenula Volume in Bipolar Disorder and Major Depressive Disorder: A High-Resolution Magnetic Resonance Imaging Study

Increased activity of the habenula has been implicated in the etiology of major depressive disorder (MDD), in which reductions in habenula volume are present after death. We conducted the first magnetic resonance imaging analysis of habenula volume in MDD and bipolar disorder (BD). High-resolution images (resolution approximately .4 mm(3)) were acquired with a 3T scanner, and a pulse sequence was optimized for tissue contrast resolution. The habenula was manually segmented by one rater blind to diagnosis. Seventy-four healthy control subjects (HC) were compared with both medicated (lithium/divalproex, n = 15) and unmedicated, depressed BD (n = 22) patients; unmedicated, depressed MDD patients (n = 28); and unmedicated MDD patients in remission (n = 32). The unmedicated BD patients displayed significantly smaller absolute (p < .01) and normalized (p < .05) habenula volumes than the HC subjects. In post hoc assessments analyzing men and women separately, the currently-depressed women with MDD had smaller absolute (p < .05) habenula volumes than the HC women. None of the other psychiatric groups differed significantly from the HC group. We provide further evidence for the involvement of the habenula in affective illness but suggest that a reduction in volume might be more pronounced in unmedicated, depressed BD subjects and female currently depressed MDD subjects. The habenula plays major roles in the long-term modification of monoamine transmission and behavioral responses to stress and in the suppression of dopamine cell activity after the absence of an expected reward. A reduction in habenula volume might thus have functional consequences that contribute to the risk for developing affective disease.

Executive Dysfunctions in Obsessive-Compulsive Patients and Unaffected Relatives: Searching for a New Intermediate Phenotype

Evidence in literature suggests that neurocognitive deficits may represent suitable intermediate-phenotype candidates for the dissection of obsessive-compulsive disorder (OCD) genetic heterogeneity. The aim of this study was to search for possible OCD neurocognitive endophenotypes by assessing decision-making, planning, and mental flexibility profiles in OCD probands, healthy control subjects (HC), and their respective relatives. The sample consisted of 35 pairs of OCD probands without other Axis I comorbidities and unaffected first-degree relatives and 31 pairs of HC subjects without a known family history of OCD and their relatives. Neuropsychological assessment was performed using the Iowa Gambling Task (IGT), the Tower of Hanoi (ToH), and the Wisconsin Card Sorting Test (WCST). Obsessive-compulsive disorder patients showed impairments in decision making, planning, and mental flexibility, given that OCD probands performed significantly poorer than HC probands at the IGT, the ToH, and the WCST. Obsessive-compulsive disorder relatives performed poorer at these tests than HC probands and relatives. Symptom severity was found to have no influence on neurocognitive performance. Analysis of proband/relative concordance in task performance was performed for each task. A significant overall difference was found when comparing the percentages of the different concordance profiles of our OCD and HC samples with regard to IGT and ToH performance. No significant difference was found in the WCST. Executive dysfunctions may qualify as a suitable endophenotype candidate for OCD. Concordance rates in neuropsychological task performance suggest that decision-making and planning deficits aggregate in these families and therefore might be a heritable component of OCD.

No oxygen delivery limitation in hepatic encephalopathy

Hepatic encephalopathy is a condition of reduced brain functioning in which both blood flow and brain energy metabolism declined. It is not known whether blood flow or metabolism is the primary limiting factor of brain function in this condition. We used calculations of mitochondrial oxygen tension to choose between cause and effect in three groups of volunteers, including healthy control subjects (HC), patients with cirrhosis of the liver without hepatic encephalopathy (CL), and patients with cirrhosis with acute hepatic encephalopathy. Compared to HC subjects, blood flow and energy metabolism had declined in all gray matter regions of the brain in patients with HE but not significantly in patients with CL. Analysis of flow-metabolism coupling indicated that blood flow declined in HE as a consequence of reduced brain energy metabolism implied by the calculation of increased mitochondrial oxygen tensions that patients with HE were unable to utilize. We ascribe the inability to use the delivered oxygen of patients with HE to a specific inhibition associated with oxidative metabolism in mitochondria.

Serotonin 1B Receptor Imaging in Alcohol Dependence

Although animal models suggest that alcohol dependence (AD) is associated with elevations in the number of serotonin 1B receptors (5-HT(1B)R), 5-HT(1B)R levels have not been investigated in people with AD. The selective 5-HT(1B)R antagonist radioligand, [(11)C]P943, permits in vivo assessment of central 5-HT(1B)R binding potential (BP(ND)) with positron emission tomography. Because of its central role in AD, we were particularly interested in ventral striatal 5-HT(1B)R BP(ND) values. Twelve medication-free, recently abstinent (at least 4 weeks) patients with AD (mean age 35.2 +/- 10.2 years, 5 women) and 12 healthy control subjects (HC) (mean age 30.6 +/- 9.2 years, 5 women) completed [(11)C]P943 positron emission tomography on a high-resolution research tomograph. Individual magnetic resonance imaging scans were collected to exclude individuals with anatomical abnormalities and for coregistration. Imaging data were analyzed with a multilinear reference tissue model. Ventral striatal 5-HT(1B)R BP(ND) values (2.01 +/- .57% and 1.55 +/- .09%, respectively; 29% between-group difference, p = .006) were increased in AD compared with HC subjects. No influence of demographic or clinical variables or amount of injected radiotracer was observed. This study provides the first evidence that AD in humans is, like in rodent models, associated with increased levels of ventral striatal 5-HT(1B)Rs.

Temporal and right frontal lobe alterations in panic disorder: a quantitative volumetric and voxel-based morphometric MRI study

With regard to current neurobiological theories, the aim of our study was to examine possible alterations of temporal and frontal lobe volume in panic disorder (PD). Seventeen in-patients with PD and a group of healthy control subjects (HC) matched for age and gender were investigated by quantitative volumetric magnetic resonance imaging (MRI). Structures of interest were: the temporal lobe, the amygdala-hippocampus complex (AHC) and the frontal lobe. In addition, a voxel-based morphometry (VBM) analysis implemented in Statistical Parametric Mapping 5 (SPM5) was used for a more detailed assessment of possible volume alterations. Modulated grey matter (GM) images were used to test our a priori hypotheses and to present the volumetric results. Quantitative volumetric MRI revealed a bilateral reduction in temporal lobe volume in patients with PD compared to HC subjects. The AHC was normal. The right frontal lobe volume was also decreased. Using VBM we detected a significant GM volume reduction in the right middle temporal gyrus [Brodmann area (BA) 21] in patients with PD. In addition, there was a reduction in GM volume in the medial part of the orbitofrontal cortex (BA 11). Our results of reduced temporal and frontal lobe volume in PD are in agreement with prior studies. By using a recent VBM approach we were able to assess the abnormalities more precisely. The location of GM volume reduction in the right middle temporal gyrus and medial orbitofrontal cortex lends further support to recent aetiological models of PD.