Significant Main Effect Of Diagnosis Research Articles

Cerebrospinal Fluid Melanin-Concentrating Hormone (MCH) and Hypocretin-1 (HCRT-1, Orexin-A) in Alzheimer’s Disease

Ancillary to decline in cognitive abilities, patients with Alzheimer’s disease (AD) frequently suffer from behavioural and psychological symptoms of dementia (BPSD). Hypothalamic polypeptides such as melanin-concentrating hormone (MCH) and hypocretin-1 (HCRT-1, orexin-A) are promoters of sleep-wake regulation and energy homeostasis and are found to impact on cognitive performance. To investigate the role of MCH and HCRT-1 in AD, cerebrospinal fluid (CSF) levels were measured in 33 patients with AD and 33 healthy subjects (HS) using a fluorescence immunoassay (FIA). A significant main effect of diagnosis (F(1,62) = 8.490, p<0.01) on MCH levels was found between AD (93.76±13.47 pg/mL) and HS (84.65±11.40 pg/mL). MCH correlated with T-tau (r = 0.47; p<0.01) and P-tau (r = 0.404; p<0.05) in the AD but not in the HS. CSF-MCH correlated negatively with MMSE scores in the AD (r = −0.362, p<0.05) and was increased in more severely affected patients (MMSE≤20) compared to HS (p<0.001) and BPSD-positive patients compared to HS (p<0.05). In CSF-HCRT-1, a significant main effect of sex (F(1,31) = 4.400, p<0.05) with elevated levels in females (90.93±17.37 pg/mL vs. 82.73±15.39 pg/mL) was found whereas diagnosis and the sex*diagnosis interaction were not significant. Elevated levels of MCH in patients suffering from AD and correlation with Tau and severity of cognitive impairment point towards an impact of MCH in AD. Gender differences of CSF-HCRT-1 controversially portend a previously reported gender dependence of HCRT-1-regulation. Histochemical and actigraphic explorations are warranted to further elucidate alterations of hypothalamic transmitter regulation in AD.

Striatal dopamine release in schizophrenia comorbid with substance dependence

Dopamine plays a role in the pathophysiology of schizophrenia and addiction. Imaging studies have indicated that striatal dopamine release is increased in schizophrenia, predominantly in the precommissural caudate (preDCA), and blunted in addiction, mostly in the ventral striatum (VST). Therefore we aimed to measure striatal dopamine release in patients with comorbid schizophrenia and substance dependence. We used [11C]raclopride PET and an amphetamine challenge to measure baseline dopamine D2-receptor availability (BPND) and its percent change post-amphetamine (∆BPND, to index amphetamine-induced dopamine release) in striatal subregions in 11 unmedicated, drug-free patients with both schizophrenia and substance dependence and 15 healthy controls. There were no significant group differences in baseline BPND. Linear mixed modeling using ∆BPND as the dependent variable and striatal ROI as a repeated measure indicated a significant main effect of diagnosis, F(1, 24)=8.38, p=.008, with significantly smaller ∆BPND in patients in all striatal subregions (all ps≤.04) except VST. Among patients, change in positive symptoms after amphetamine was significantly associated with ∆BPND in the preDCA (rs=.69, p=.03) and VST (rs=.64, p=.05). In conclusion, patients with comorbid schizophrenia and substance dependence showed significant blunting of striatal dopamine release, in contrast to what has been found in schizophrenia without substance dependence. Despite this blunting, dopamine release was associated with the transient amphetamine-induced positive-symptom change, as observed in schizophrenia. This is the first description of a group of patients with schizophrenia who display low presynaptic dopamine release, yet show a psychotic reaction to increases in D2 stimulation, suggesting abnormal post-synaptic D2 function.

The Erlangen Instrument of Alternating Word Fluency in Dementia (EAWF-D)

The Erlangen Instrument of Alternating Word Fluency in Dementia (EAWF-D) is a new alternating word fluency task that combines set-shifting and semantic word fluency based on psycholinguistic theory that the ability to switch between two different semantic categories should already be impaired in beginning dementia. N = 138 (58.7% female; age: M = 73.9; SD = 7.03) outpatients of a memory clinic were diagnosed according to the ICD-10 criteria: subjective memory complainers (N = 60), mild cognitive impairment (N = 37), and mild to moderate dementia (N = 41). An analysis of variance of the EAWF-D revealed a significant main effect of diagnosis (F(2, 135) = 46.7; p &lt; .001; η² = .41). The EAWF-D score correlates significantly with the MMSE total score (r = .54, p &lt; .001) as well as with MMSE subscores “Orientation” (r = .41, p &lt; .001) and “Recall” (r = .53, p &lt; .001). Ordinal logistic regression analysis confirmed the potential for diagnosis of beginning dementia.

Neuropsychological performance in patients with schizophrenia and controls as a function of cigarette smoking status

Schizophrenia is associated with many neurocognitive deficits, some of which are improved by nicotine and cigarette smoking. To better understand the relationship between smoking and cognitive function in schizophrenia, cross-sectional assessment of neuropsychological performance as a function of smoking status (smoker or non-smoker) and smoking history (current, former or never-smoker) in clinically stable outpatients with schizophrenia and controls was evaluated. Subjects (n=140) were divided into subgroups on the basis of self-report and biochemical verification of smoking history. Current smokers with schizophrenia (n=38), former smokers with schizophrenia (n=17), never-smokers with schizophrenia (n=12), control smokers (n=31), control former smokers (n=16), and control never-smokers (n=26) were administered a comprehensive neuropsychological battery. Smokers were studied under non-deprivation conditions. Comparison of neuropsychological performance in schizophrenia and control subjects revealed significant main effects of diagnosis. Analysis of the data as a function of smoking history demonstrated that never-smokers with schizophrenia performed the poorest on measures of sustained attention, processing speed and response inhibition, when compared to the other schizophrenia subgroups. Cigarette smoking did not alter neuropsychological performance in controls. Our findings suggest that smoking status and history differentially alters neuropsychological outcomes in schizophrenia compared to non-psychiatric controls, and that never-smokers may present with more severe neurocognitive impairments.

New structural brain imaging endophenotype in bipolar disorder

Neuroimaging studies suggest anterior-limbic structural brain abnormalities in patients with bipolar disorder (BD), but few studies have shown these abnormalities in unaffected but genetically liable family members. In this study, we report morphometric correlates of genetic risk for BD using voxel-based morphometry. In 35 BD type I (BD-I) patients, 20 unaffected first-degree relatives (UAR) of BD patients and 40 healthy control subjects underwent 3 T magnetic resonance scanner imaging. Preprocessing of images used DARTEL (diffeomorphic anatomical registration through exponentiated lie algebra) for voxel-based morphometry in SPM8 (Wellcome Department of Imaging Neuroscience, London, UK). The whole-brain analysis revealed that the gray matter (GM) volumes of the left anterior insula and right inferior frontal gyrus showed a significant main effect of diagnosis. Multiple comparison analysis showed that the BD-I patients and the UAR subjects had smaller left anterior insular GM volumes compared with the healthy subjects, the BD-I patients had smaller right inferior frontal gyrus compared with the healthy subjects. For white matter (WM) volumes, there was a significant main effect of diagnosis for medial frontal gyrus. The UAR subjects had smaller right medial frontal WM volumes compared with the healthy subjects. These findings suggest that morphometric brain abnormalities of the anterior-limbic neural substrate are associated with family history of BD, which may give insight into the pathophysiology of BD, and be a potential candidate as a morphological endophenotype of BD.

Neuronal Correlates of Brain-derived Neurotrophic Factor Val66Met Polymorphism and Morphometric Abnormalities in Bipolar Disorder

The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has been proposed as a possible candidate for involvement in the pathophysiology of bipolar disorder (BD). To determine whether an association exists between the BDNF Val66Met genotype and morphometric abnormalities of the brain regions involved in memory and learning in BD and healthy subjects. Forty-two BD patients and 42 healthy subjects were studied. Interactions between BDNF Val66Met genotype and diagnosis in gray (GM) volumes were analyzed using an optimized voxel-based morphometry technique. Declarative memory function was assessed with the California Verbal Learning Test II. Left and right anterior cingulate GM volumes showed a significant interaction between genotype and diagnosis such that anterior cingulate GM volumes were significantly smaller in the Val/Met BD patients compared with the Val/Val BD patients (left P=0.01, right P=0.01). Within-group comparisons revealed that the Val/Met carriers showed smaller GM volumes of the dorsolateral prefrontal cortex compared with the Val/Val subjects within the BD patient (P=0.01) and healthy groups (left P=0.03, right P=0.03). The Val/Met healthy subjects had smaller GM volumes of the left hippocampus compared with the Val/Val healthy subjects (P<0.01). There was a significant main effect of diagnosis on memory function (P=0.04), but no interaction between diagnosis and genotype was found (P=0.48). The findings support an association between the BDNF Val66Met genotype and differential gray matter content in brain structures, and suggest that the variation in this gene may play a more prominent role in brain structure differences in subjects affected with BD.

Glucose metabolism in the amygdala in depression: Relationship to diagnostic subtype and plasma cortisol levels

In a previous positron emission tomography (PET) study of major depression, we demonstrated that cerebral blood flow was increased in the left amygdala in unipolar depressives with familial pure depressive disease (FPDD) relative to healthy controls [J. Neurosci. 12 (1992) 3628.]. These measures were obtained from relatively low-resolution PET images using a stereotaxic method based upon skull X-ray landmarks. The current experiments aimed to replicate and extend these results using higher-resolution glucose metabolism images and magnetic resonance imaging (MRI)-based region-of-interest (ROI) analysis. The specificity of this finding to FPDD was also investigated by assessing depressed samples with bipolar disorder (BD-D) and depression spectrum disease (DSD). Finally, the relationship between amygdala metabolism and plasma cortisol levels obtained during the scanning procedure was assessed. Glucose metabolism was measured using PET and 18F-fluorodeoxyglucose ( 18FDG) in healthy control ( n=12), FPDD ( n=12), DSD ( n=9) and BD-D ( n=7) samples in the amygdala and the adjacent hippocampus. The left amygdala metabolism differed across groups ( P<.001), being increased in both the FPDD and BD-D groups relative to the control group. The left amygdala metabolism was positively correlated with stressed plasma cortisol levels in both the unipolar ( r=.69; P<.005) and the bipolar depressives ( r=0.68; .1< P<.05). In contrast, neither significant main effects of diagnosis nor significant relationships with plasma cortisol were evident in post hoc analyses of metabolism in the right amygdala or the hippocampus. Preliminary assessment of BD subjects imaged during remission suggested that amygdala metabolism is also elevated in remitted subjects who are not taking mood-stabilizing drugs, but within the normal range in subjects taking mood stabilizers. These data confirm our previous finding that neurophysiological activity is abnormally increased in FPDD, and extend it to BD-D. These abnormalities were not accounted for by spilling in of radioactivity from the adjacent hippocampus. The correlation between left amygdala metabolism and stressed plasma cortisol levels may conceivably reflect either the effect of amygdala activity on corticotropin-releasing hormone (CRH) secretion or the effect of cortisol on amygdala function.

Asymmetrical reductions of hippocampal NMDAR1 glutamate receptor mRNA in the psychoses.

The psychotomimetic properties of NMDA glutamate receptor antagonists suggest there may be disease related changes of this receptor in schizophrenia. Using in situ hybridisation histochemistry (ISHH), we measured mRNA for the obligatory NMDAR1 subunit of the NMDA glutamate receptor in post-mortem samples of hippocampus from schizophrenics, depressives, bipolar patients and normal controls. A significant main effect of diagnosis was observed in the dentate gyrus (ANOVA, p = 0.004) and a trend in the CA3 region (ANOVA, p = 0.06), with all psychiatric groups having reduced NMDAR1 mRNA levels compared to normal controls. In contrast to the affectively ill groups, the reductions in schizophrenics were more pronounced in the left side compared to the right. Expression of poly A mRNA also showed left-sided losses in the dentate gyrus in schizophrenia but reductions in NMDAR1 remained significant when expressed as a ratio of poly A. The findings confirm a recent report of reduced hippocampal NMDAR1 mRNA in schizophrenia. However, our new evidence suggests that this is a feature of both affective and schizophrenic disorders and that schizophrenia is distinguished from the others by left-sided reductions in hippocampal NMDAR1 gene expression.

Electromyographic recordings of 5 types of low back pain subjects and non-pain controls in different positions

Surface EMG recordings of bilateral paraspinal muscle tension were measured on 207 subjects (29 non-back pain controls, 20 individuals with spondyloarthritis, 52 with intervertebral disk disorders, 66 with unspecified musculoskeletal backache, 17 with some combination of the above 3 groups and 23 subjects with other types of back pain, including unknown, scoliosis and psychogenic) in 6 positions: standing, bending from the waist, rising, sitting with back unsupported, sitting with back supported and prone. Results of both individual and group analyses revealed a significant main effect of diagnosis. Post hoc analyses (Duncan's) revealed controls to have significantly lower overall EMG levels than the intervertebral disk disorders and unspecified musculoskeletal backache groups. A significant diagnosis by position interaction was observed. Analysis of simple main effects revealed this to be due primarily to control subjects during the standing position having lower EMG levels than all other groups, and intervertebral disk disorder subjects having higher EMG levels than all other groups during the supported sitting position. The importance of clearly defined diagnostic categories in low back pain research and the utility of measuring subjects in various positions are discussed.