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High ceruloplasmin levels are associated with obsessive compulsive disorder: a case control study
Background:
Alterations in ceruloplasmin are currently assumed as one of the mechanisms underlying the development of a number of neurodegenerative disorders. Several studies indicate that elevated serum ceruloplasmin levels may play a role in schizophrenia by exacerbating or perpetuating dopaminergic dysregulation. No study investigating the relationship between ceruloplasmin and obsessive-compulsive disorder (OCD) has been published to date. Nowadays OCD is increasingly speculated to be a different disorder than other anxiety disorders, and rather is considered to be more similar to psychotic disorders. The objective of this study to explore whether there is an association of ceruloplasmin with OCD as in schizophrenia.Method26 pure OCD and 9 co-morbid OCD patients from Gaziantep University Sahinbey Research Hospital, Psychiatry Clinics, diagnosed according to the DSM IV and 40 healthy controls were included in the study. Blood samples were collected; ceruloplasmin levels were measured.
Results:
The mean ceruloplasmin level in pure OCD patients, co-morbid OCD patients, and control group persons were 544.46+/-26.53, 424.43+/-31.50 and 222.35+/-8.88 U/L respectively. Results of all 3 groups differ significantly. Positive predictive value of ceruloplasmin for that cut-off point is 31/31 (100 %) and negative predictive value is 40/44 (91 %) in our group.
Conclusion:
Although the nature of relationship is not clear there was an association between ceruloplasmin levels and OCD in our study.
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Can only intelligent children do mind reading: The relationship between intelligence and theory of mind in 8 to 11 years old.
Background:
The mind reading ability of children has evoked wide interest, but its relationship with general cognitive abilities remains obscure.
Methods:
We studied the relationship between the mind reading ability and general intelligence. Children (N=105) between 8 to 11 years from educational institutions were assessed for the mind reading ability using Picture Sequencing Task and Unexpected Contents Theory of Mind task. We used Strengths and Difficulties Questionnaire to rule out psychiatric morbidity. An independent investigator quantified intelligence and adaptive behavior with Binet- Kamat Test of intelligence and Vineland Adaptive Behavior Scale respectively. We employed bivariate and multivariate statistical tests.
Results:
We demonstrated that mind reading ability was not significantly related to general intelligence or its domains except for the social intelligence after controlling the confounders methodologically and statistically.
Conclusions:
These findings argue that mind reading skill exists as an independent cognitive domain and has clinical, research as well as educational implications.
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When moving faces activate the house area: an fMRI study of object-file retrieval
Background:
The visual cortex of the human brain contains specialized modules for processing different visual features of an object. Confronted with multiple objects, the system needs to attribute the correct features to each object (often referred to as 'the binding problem'). The brain is assumed to integrate the features of perceived objects into object files – pointers to the neural representations of these features, which outlive the event they represent in order to maintain stable percepts of objects over time. It has been hypothesized that a new encounter with one of the previously bound features will reactivate the other features in the associated object file according to a kind of pattern-completion process.
Methods:
Fourteen healthy volunteers participated in an fMRI experiment and performed a task designed to measure the aftereffects of binding visual features (houses, faces, motion direction). On each trial, participants viewed a particular combination of features (S1) before carrying out a speeded choice response to a second combination of features (S2). Repetition and alternation of all three features was varied orthogonally.
Results:
The behavioral results showed the standard partial repetition costs: a reaction time increase when one feature was repeated and the other feature alternated between S1 and S2, as compared to complete repetitions or alternations of these features. Importantly, the fMRI results provided evidence that repeating motion direction reactivated the object that previously moved in the same direction. More specifically, perceiving a face moving in the same direction as a just-perceived house increased activation in the parahippocampal place area (PPA). A similar reactivation effect was not observed for faces in the fusiform face area (FFA). Individual differences in the size of the reactivation effects in the PPA and FFA showed a positive correlation with the corresponding partial repetition costs.
Conclusion:
Our study provides the first neural evidence that features are bound together on a single presentation and that reviewing one feature automatically reactivates the features that previously accompanied it.
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Effects of dopamine D4 receptor antagonist on spontaneous alternation in rats
Background:
The present study was a component of a series of studies scrutinising the neuroreceptor substrate of behavioural flexibility in a rat model. Spontaneous alternation paradigms model the natural tendency of rodents to spontaneously and flexibly shift between alternative spatial responses. In the study it was tested for the first time if the neurochemical substrate mediating spontaneous alternation behaviour includes the dopamine D4 receptor.
Methods:
The acute effects of the highly selective dopamine D4 receptor antagonist L-745,870 on rats' performance in a spontaneous alternation paradigm in a T-maze were examined. The paradigm was a food-rewarded continuous trial procedure performed for 20 trials.
Results:
The spontaneous alternation rate was not affected by the doses of the drug administered (0.02 mg/kg; 0.2 mg/kg; 2 mg/kg), but the position bias of the group receiving the highest L-745,870 dose (2 mg/kg) was significantly increased compared to the group that received the lowest dose (0.02 mg/kg). No significant effects on position bias were found compared to saline. The drug did not increase response perseveration.
Conclusion:
The results show that the neural substrate mediating the spatial distribution of responses in the spontaneous alternation paradigm includes the D4 receptor. However, the statistically significant effect of L-745,870 on position bias was found comparing a high drug dose with a low drug dose, and not comparing the drug doses with saline. For the tested doses of L-745,870 the effect on position bias was not large enough to affect the alternation rate.
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The influence of serotonin- and other genes on impulsive behavioral aggression and cognitive impulsivity in children with attention-deficit/hyperactivity disorder (ADHD): Findings from a family-based association test (FBAT) analysis
Background:
Low serotonergic (5-HT) activity correlates with increased impulsive-aggressive behavior, while the opposite association may apply to cognitive impulsiveness. Both types of impulsivity are associated with attention-deficit/hyperactivity disorder (ADHD), and genes of functional significance for the 5-HT system are implicated in this disorder. Here we demonstrate the separation of aggressive and cognitive components of impulsivity from symptom ratings and test their association with 5-HT and functionally related genes using a family-based association test (FBAT-PC).
Methods:
Our sample consisted of 1180 offspring from 607 families from the International Multicenter ADHD Genetics (IMAGE) study. Impulsive symptoms were assessed using the long forms of the Conners and the Strengths and Difficulties parent and teacher questionnaires. Factor analysis showed that the symptoms aggregated into parent- and teacher-rated behavioral and cognitive impulsivity. We then selected 582 single nucleotide polymorphisms (SNPs) from 14 genes directly or indirectly related to 5-HT function. Associations between these SNPs and the behavioral/cognitive groupings of impulsive symptoms were evaluated using the FBAT-PC approach.
Results:
In the FBAT-PC analysis for cognitive impulsivity 2 SNPs from the gene encoding phenylethanolamine N-methyltransferase (PNMT, the rate-limiting enzyme for adrenalin synthesis) attained corrected gene-wide significance. Nominal significance was shown for 12 SNPs from BDNF, DRD1, HTR1E, HTR2A, HTR3B, DAT1/SLC6A3, and TPH2 genes replicating reported associations with ADHD. For overt aggressive impulsivity nominal significance was shown for 6 SNPs from BDNF, DRD4, HTR1E, PNMT, and TPH2 genes that have also been reported to be associated with ADHD. Associations for cognitive impulsivity with a SERT/SLC6A4 variant (STin2: 12 repeats) and aggressive behavioral impulsivity with a DRD4 variant (exon 3: 3 repeats) are also described.DiscussionA genetic influence on monoaminergic involvement in impulsivity shown by children with ADHD was found. There were trends for separate and overlapping influences on impulsive-aggressive behavior and cognitive impulsivity, where an association with PNMT (and arousal mechanisms affected by its activity) was more clearly involved in the latter. Serotonergic and dopaminergic mechanisms were implicated in both forms of impulsivity with a wider range of serotonergic mechanisms (each with a small effect) potentially influencing cognitive impulsivity. These preliminary results should be followed up with an examination of environmental influences and associations with performance on tests of impulsivity in the laboratory.
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Sensorimotor cortex as a critical component of an 'extended' mirror neuron system: Does it solve the development, correspondence, and control problems in mirroring?
A core assumption of how humans understand and infer the intentions and beliefs of others is the existence of a functional self-other distinction. At least two neural systems have been proposed to manage such a critical distinction. One system, part of the classic motor system, is specialized for the preparation and execution of motor actions that are self realized and voluntary, while the other appears primarily involved in capturing and understanding the actions of non-self or others. The latter system, of which the mirror neuron system is part, is the canonical action 'resonance' system in the brain that has evolved to share many of the same circuits involved in motor control. Mirroring or 'shared circuit systems' are assumed to be involved in resonating, imitating, and/or simulating the actions of others. A number of researchers have proposed that shared representations of motor actions may form a foundational cornerstone for higher order social processes, such as motor learning, action understanding, imitation, perspective taking, understanding facial emotions, and empathy. However, mirroring systems that evolve from the classic motor system present at least three problems: a development, a correspondence, and a control problem. Developmentally, the question is how does a mirroring system arise? How do humans acquire the ability to simulate through mapping observed onto executed actions? Are mirror neurons innate and therefore genetically programmed? To what extent is learning necessary? In terms of the correspondence problem, the question is how does the observer agent know what the observed agent's resonance activation pattern is? How does the matching of motor activation patterns occur? Finally, in terms of the control problem, the issue is how to efficiently control a mirroring system when it is turned on automatically through observation? Or, as others have stated the problem more succinctly: "Why don't we imitate all the time?" In this review, we argue from an anatomical, physiological, modeling, and functional perspectives that a critical component of the human mirror neuron system is sensorimotor cortex. Not only are sensorimotor transformations necessary for computing the patterns of muscle activation and kinematics during action observation but they provide potential answers to the development, correspondence and control problems.
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Association of RGS4 variants with schizotypy and cognitive endophenotypes at the population level
Background:
While association studies on schizophrenia show conflicting results regarding the importance of the regulator of the G-protein signaling 4 (RGS4) gene, recent work suggests that RGS4 may impact on the structural and functional integrity of the prefrontal cortex. We aimed to study associations of common RGS4 variants with prefrontal dependent cognitive performance and schizotypy endophenotypes at the population level.
Methods:
Four RGS4 single nucleotide polymorphisms (SNP1 [rs10917670], SNP4 [rs951436], SNP7 [rs951439], and SNP18 [rs2661319]) and their haplotypes were selected. Their associations with self-rated schizotypy (SPQ), vigilance, verbal, spatial working memory and antisaccade eye performance were tested with regressions in a representative population of 2,243 young male military conscripts.
Results:
SNP4 was associated with negative schizotypy (higher SPQ negative factor for common T allele, p = 0.009; p = 0.031 for differences across genotypes) and a similar trend was seen also for common A allele of SNP18 (p = 0.039 for allele-load model; but p = 0.12 for genotype differences). Haplotype analyses showed a similar pattern with a dose-response for the most common haplotype (GGGG) on the negative schizotypy score with or without adjustment for age, IQ and their interaction (p = 0.011 and p = 0.024, respectively). There was no clear evidence for any association of the RGS4 variants with cognitive endophenotypes, except for an isolated effect of SNP18 on antisaccade error rate (p = 0.028 for allele-load model).
Conclusion:
Common RGS4 variants were associated with negative schizotypal personality traits amongst a large cohort of young healthy individuals. In accordance with recent findings, this may suggest that RGS4 variants impact on the functional integrity of the prefrontal cortex, thus increasing susceptibility for psychotic spectrum disorders.
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Persistent spatial working memory deficits in rats with bilateral cortical microgyria
Background:
Anomalies of cortical neuronal migration (e.g., microgyria (MG) and/or ectopias) are associated with a variety of language and cognitive deficits in human populations. In rodents, postnatal focal freezing lesions lead to the formation of cortical microgyria similar to those seen in human dyslexic brains, and also cause subsequent deficits in rapid auditory processing similar to those reported in human language impaired populations. Thus convergent findings support the ongoing study of disruptions in neuronal migration in rats as a putative model to provide insight on human language disability. Since deficits in working memory using both verbal and non-verbal tasks also characterize dyslexic populations, the present study examined the effects of neonatally induced bilateral cortical microgyria (MG) on working memory in adult male rats.
Methods:
A delayed match-to-sample radial water maze task, in which the goal arm was altered among eight locations on a daily basis, was used to assess working memory performance in MG (n = 8) and sham (n = 10) littermates.
Results:
Over a period of 60 sessions of testing (each session comprising one pre-delay sample trial, and one post-delay test trial), all rats showed learning as evidenced by a significant decrease in overall test errors. However, MG rats made significantly more errors than shams during initial testing, and this memory deficit was still evident after 60 days (12 weeks) of testing. Analyses performed on daily error patterns showed that over the course of testing, MG rats utilized a strategy similar to shams (but with less effectiveness, as indicated by more errors).
Conclusion:
These results indicate persistent abnormalities in the spatial working memory system in rats with induced disruptions of neocortical neuronal migration.
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Evidence of inflammatory immune signaling in chronic fatigue syndrome: A pilot study of gene expression in peripheral blood
Background:
Genomic profiling of peripheral blood reveals altered immunity in chronic fatigue syndrome (CFS) however interpretation remains challenging without immune demographic context. The object of this work is to identify modulation of specific immune functional components and restructuring of co-expression networks characteristic of CFS using the quantitative genomics of peripheral blood.
Methods:
Gene sets were constructed a priori for CD4+ T cells, CD8+ T cells, CD19+ B cells, CD14+ monocytes and CD16+ neutrophils from published data. A group of 111 women were classified using empiric case definition (U.S. Centers for Disease Control and Prevention) and unsupervised latent cluster analysis (LCA). Microarray profiles of peripheral blood were analyzed for expression of leukocyte-specific gene sets and characteristic changes in co-expression identified from topological evaluation of linear correlation networks.
Results:
Median expression for a set of 6 genes preferentially up-regulated in CD19+ B cells was significantly lower in CFS (p = 0.01) due mainly to PTPRK and TSPAN3 expression. Although no other gene set was differentially expressed at p < 0.05, patterns of co-expression in each group differed markedly. Significant co-expression of CD14+ monocyte with CD16+ neutrophil (p = 0.01) and CD19+ B cell sets (p = 0.00) characterized CFS and fatigue phenotype groups. Also in CFS was a significant negative correlation between CD8+ and both CD19+ up-regulated (p = 0.02) and NK gene sets (p = 0.08). These patterns were absent in controls.
Conclusion:
Dissection of blood microarray profiles points to B cell dysfunction with coordinated immune activation supporting persistent inflammation and antibody-mediated NK cell modulation of T cell activity. This has clinical implications as the CD19+ genes identified could provide robust and biologically meaningful basis for the early detection and unambiguous phenotyping of CFS.
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Cortical and subcortical anatomy of chronic spatial neglect following vascular damage
Background:
The role of the inferior parietal lobule (IPL) and superior temporal gyrus (STG) or subcortical pathways as possible anatomical correlates of spatial neglect is currently intensely discussed. Some of the conflicting results might have arisen because patients were examined in the acute stage of disease.
Methods:
We examined the anatomical basis of spatial neglect in a sample of patients examined in the post-acute stage following right-hemispheric vascular brain damage. Lesions of 28 patients with chronic spatial neglect were contrasted to lesions of 22 control patients without neglect using lesion subtraction techniques and voxel-wise comparisons.
Results:
The comparisons identified the temporo-parietal junction (TPJ) with underlying white matter, the supramarginal gyrus, the posterior STG, and the insula as brain regions damaged significantly more often in neglect compared to non-neglect patients. In a subgroup of neglect patients showing particularly large cancellation bias together with small errors on line bisection damage was prevalent deep in the frontal lobe while damage of patients with the reverse pattern was located in the white matter of the TPJ.
Conclusion:
Considering our results and the findings of previous studies, spatial neglect appears to be associated with a network of regions involving the TPJ, inferior IPL, posterior STG, the insular cortex, and posterior-frontal projections. Frontal structures or projections may be of particular relevance for spatial exploration, while the IPL may be important for object-based attention as required for line bisection.
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