Parent-of-origin effects of FAS and PDLIM1 in attention-deficit/hyperactivity disorder

Background

Previous studies have suggested that there may be a parent-of-origin effect for attention-deficit/hyperactivity disorder (ADHD) candidate genes. The objective of the present study was to investigate parent-of-origin effects using a genome-wide association analysis of the International Multicentre ADHD Genetics (IMAGE) study sample.

Methods

Family-based association analysis for ADHD using 846 ADHD probands and their parents was performed using the PLINK program, and parent-of-origin effects were studied using a Z score for the difference in paternal versus maternal odds ratios.

Results

We identified 44 single nucleotide polymorphisms (SNPs) showing parent-of-origin effects at a significance level of p < 0.001. The most significant SNP, rs7614907, is at position 3q13.33 in the CDGAP gene (p = 0.000064 for parent-of-origin effect). Furthermore, 2 genes (FAS and PDLIM1) showed moderate parent-of-origin effects (p = 0.00086 for rs9658691 and p = 0.00077 for rs11188249) and strong maternal transmission (p = 0.000059 for rs9658691 and p = 0.0000068 for rs11188249). In addition, ZNF775 showed a moderate parent-of-origin effect (p = 0.00036 for rs7790549) and strong paternal transmission (p = 0.000041 for rs7790549).

Limitations

We only had 1 sample available for analysis.

Conclusion

These results suggest several genes or regions with moderate parent-of-origin effects, and these findings will serve as a resource for replication in other populations to elucidate the potential role of these genetic variants in ADHD.     

Impaired interhemispheric connectivity in medication-naive patients with major depressive disorder

Background

Abnormalities in the anterior interhemispheric connections provided by the corpus callosum (CC) have long been implicated in major depressive disorder (MDD). The purpose of this study was to investigate interhemispheric connectivity in medication-naive patients with MDD by measuring fractional anisotropy in the CC with diffusion tensor imaging (DTI) techniques.

Methods

We obtained DTI scans from medication-naive patients with MDD and from matched healthy controls. Fractional anisotropy values were compared using semiautomatic region of interest methods to localize the regional CC differences between these 2 groups.

Results

We enrolled 27 patients and 27 controls in our study. Fractional anisotropy values were significantly lower in the anterior genu of the CC in the MDD group than in the control group (p = 0.009, corrected); results were not significantly different in any other CC subregions.

Limitations

As patients with MDD were already experiencing acute episodes, future studies of individuals at risk for MDD are warranted to elucidate the interhemispheric connectivity abnormalities associated with the predisposition to MDD.

Conclusion

The findings demonstrate abnormalities in the structural integrity of the anterior genu of the CC in medication-naive individuals with MDD, which may contribute to impairment of interhemispheric connectivity in patients with this disorder.     

Effects of ZNF804A on auditory P300 response in schizophrenia

The common variant rs1344706 within the zinc-finger protein gene ZNF804A has been strongly implicated in schizophrenia (SZ) susceptibility by a series of recent genetic association studies. Although associated with a pattern of altered neural connectivity, evidence that increased risk is mediated by an effect on cognitive deficits associated with the disorder has been equivocal. This study investigated whether the same ZNF804A risk allele was associated with variation in the P300 auditory-evoked response, a cognitively relevant putative endophenotype for SZ. We compared P300 responses in carriers and noncarriers of the ZNF804A risk allele genotype groups in Irish patients and controls (n=97). P300 response was observed to vary according to genotype in this sample, such that risk allele carriers showed relatively higher P300 response compared with noncarriers. This finding accords with behavioural data reported by our group and others. It is also consistent with the idea that ZNF804A may have an impact on cortical efficiency, reflected in the higher levels of activations required to achieve comparable behavioural accuracy on the task used.     

Whole-Body Muscle MRI in Patients with Hyperkalemic Periodic Paralysis Carrying the SCN4A Mutation T704M: Evidence for Chronic Progressive Myopathy with Selective Muscle Involvement

Background and Purpose

Hyperkalemic periodic paralysis (hyperKPP) is a muscle sodium-ion channelopathy characterized by recurrent paralytic attacks. A proportion of affected individuals develop fixed or chronic progressive weakness that results in significant disability. However, little is known about the pathology of hyperKPP-induced fixed weakness, including the pattern of muscle involvement. The aim of this study was to characterize the patterns of muscle involvement in hyperKPP by whole-body magnetic resonance imaging (MRI).

Methods

We performed whole-body muscle MRI in seven hyperKPP patients carrying the T704M mutation in the SCN4A skeletal sodium-channel gene. Muscle fat infiltration, suggestive of chronic progressive myopathy, was analyzed qualitatively using a grading system and was quantified by the two-point Dixon technique.

Results

Whole-body muscle MRI analysis revealed muscle atrophy and fatty infiltration in hyperKPP patients, especially in older individuals. Muscle involvement followed a selective pattern, primarily affecting the posterior compartment of the lower leg and anterior thigh muscles. The muscle fat fraction increased with patient age in the anterior thigh (r=0.669, p=0.009), in the deep posterior compartment of the lower leg (r=0.617, p=0.019), and in the superficial posterior compartment of the lower leg (r=0.777, p=0.001).

Conclusions

Our whole-body muscle MRI findings provide evidence for chronic progressive myopathy in hyperKPP patients. The reported data suggest that a selective pattern of muscle involvement-affecting the posterior compartment of the lower leg and the anterior thigh-is characteristic of chronic progressive myopathy in hyperKPP.     

ZNF804A and Cortical Structure in Schizophrenia: In Vivo and Postmortem Studies

Recent evidence indicated that the ZNF804A (rs1344706) risk allele A is associated with better cognitive performance in patients with schizophrenia. Moreover, it has been demonstrated that ZNF804A may also be related to relatively intact gray matter volume in patients. To further explore these putatively protective effects, the impact of ZNF804A on cortical thickness and folding was examined in this study. To elucidate potential molecular mechanisms, an allelic-specific gene expression study was also carried out. Magnetic resonance imaging cortical thickness and folding were computed in 55 genotyped patients with schizophrenia and 40 healthy controls. Homozygous risk allele carriers (AA) were compared with AC/CC carriers. ZNF804A gene expression was analyzed in a prefrontal region using postmortem tissue from another cohort of 35 patients. In patients, AA carriers exhibited significantly thicker cortex in prefrontal and temporal regions and less disturbed superior temporal cortical folding, whereas the opposite effect was observed in controls, ie, AA carrier status was associated with thinner cortex and more severe altered cortical folding. Along with this, our expression analysis revealed that the risk allele is associated with lower prefrontal ZNF804A expression in patients, whereas the opposite effect in controls has been observed by prior analyses. In conclusion, our analyses provide convergent support for the hypothesis that the schizophrenia-associated ZNF804A variant mediates protective effects on cortex structure in patients. In particular, the allele-specific expression profile in patients might constitute a molecular mechanism for the observed protective influence of ZNF804A on cortical thickness and folding and potentially other intermediate phenotypes.Key words: rs1344706, ZNF804A, schizophrenia, cortical thickness, cortical folding, susceptibility gene, gene expression, psychosis     

Genomic studies in fragile X premutation carriers

Background

The FMR1 premutation is defined as having 55 to 200 CGG repeats in the 5′ untranslated region of the fragile X mental retardation 1 gene (FMR1). The clinical involvement has been well characterized for fragile X-associated tremor/ataxia syndrome (FXTAS) and fragile X-associated primary ovarian insufficiency (FXPOI). The behavior/psychiatric and other neurological manifestations remain to be specified as well as the molecular mechanisms that will explain the phenotypic variability observed in individuals with the FMR1 premutation.

Methods

Here we describe a small pilot study of copy number variants (CNVs) in 56 participants with a premutation ranging from 55 to 192 repeats. The participants were divided into four different clinical groups for the analysis: those with behavioral problems but no autism spectrum disorder (ASD); those with ASD but without neurological problems; those with ASD and neurological problems including seizures; and those with neurological problems without ASD.

Results

We found 12 rare CNVs (eight duplications and four deletions) in 11 cases (19.6%) that were not found in approximately 8,000 controls. Three of them were at 10q26 and two at Xp22.3, with small areas of overlap. The CNVs were more commonly identified in individuals with neurological involvement and ASD.

Conclusions

The frequencies were not statistically significant across the groups. There were no significant differences in the psychometric and behavior scores among all groups. Further studies are necessary to determine the frequency of second genetic hits in individuals with the FMR1 premutation; however, these preliminary results suggest that genomic studies can be useful in understanding the molecular etiology of clinical involvement in premutation carriers with ASD and neurological involvement.     

Serotonin2A receptor binding potential in people with aggressive and violent behaviour

Objective

Indexes of brain serotonin_2A (5-HT_2A) density have never been investigated in a sample of humans with violent aggressive behaviour unbiased by medication use or current axis I psychiatric disorders. The objective of this study was to investigate prefrontal cortex 5-HT_2A binding potential (BP_ND), an index of 5-HT_2A density, in an unbiased sample of people with violent aggressive behaviour.

Methods

We used [¹⁸F] setoperone positron emission tomography to measure 5-HT_2A BP_ND in the dorsolateral prefrontal cortex (primarily sampling Brodmann area 9) in 16 participants with violent aggressive behaviour and 16 healthy control participants.

Results

In people with violent aggressive behaviours, the slope of 5-HT_2A BP_ND decline in the dorsolateral prefrontal cortex is 44% less than in healthy control participants (analysis of variance group by age interaction, p = 0.004). Prefrontal cortex 5-HT_2A BP_ND was significantly lower in participants with more severe impulsivity and aggression (multiple linear regression with age and Barratt Impulsivity Scale [BIS] as predictor variables and regional 5-HT_2A BP_ND as dependent variable; effect of BIS, dorsolateral prefrontal cortex: F_1,13 = 7.95, p = 0.014).

Conclusion

Lower prefrontal 5-HT_2A BP_ND is related to violent aggression. Lower 5-HT_2A BP_ND occurs at a younger age, when violent behaviour is more frequent, and is more prominent when impulsivity and aggression are more severe.Medical subject headings: aggression, serotonin, receptors, serotonin, 5-HT_2A, positron emission tomography, setoperone, suicide     

<Emphasis Type="Italic">ZNF804A</Emphasis> rs1344706 interacts with <Emphasis Type="Italic">COMT</Emphasis> rs4680 to affect prefrontal volume in healthy adults

The biological function of ZNF804A rs1344706, the first genome-wide supported risk variant of schizophrenia, remains largely unknown. Based on the upregulating effect of ZNF804A on the expression of COMT, we hypothesize that ZNF804A may affect grey matter volume (GMV) by interacting with COMT. Voxel-based morphometry was applied to analyze the main and interaction effects of ZNF804A rs1344706 and COMT rs4680 on brain GMV in 274 healthy young human subjects. The GMV of the left dorsolateral prefrontal cortex (DLPFC) showed a significant COMT rs4680 × ZNF804A rs1344706 interaction, manifesting as an inverted U-shape modulation by the presumed dopamine signaling. In COMT Met-allele carriers, the ZNF804A TG heterozygotes showed greater GMV in the left DLPFC than both GG and TT homozygotes. In COMT Val/Val homozygotes, however, the ZNF804A TG heterozygotes exhibited smaller GMV in the left DLPFC than GG homozygotes and comparable GMV with TT homozygotes. These findings suggest that ZNF804A affects the GMV of the prefrontal cortex by interacting with COMT, which may improve our understanding of neurobiological effect of ZNF804A and its association with schizophrenia.     

Modulation of mu attenuation to social stimuli in children and adults with 16p11.2 deletions and duplications

Background

Copy number variations (CNV) within the recurrent ~600 kb chromosomal locus of 16p11.2 are associated with a wide range of neurodevelopmental disorders, including autism spectrum disorder (ASD). However, little is known about the social brain phenotype of 16p11.2 CNV and how this phenotype is related to the social impairments associated with CNVs at this locus. The aim of this preliminary study was to use molecular subtyping to establish the social brain phenotype of individuals with 16p11.2 CNV and how these patterns relate to typical development and ASD.

Methods

We evaluated the social brain phenotype as expressed by mu attenuation in 48 children and adults characterized as duplication carriers (n = 12), deletion carriers (n = 12), individuals with idiopathic ASD (n = 8), and neurotypical controls (n = 16). Participants watched videos containing social and nonsocial motion during electroencephalogram (EEG) acquisition.

Results

Overall, only the typical group exhibited predicted patterns of mu modulation to social information (e.g., greater mu attenuation for social than nonsocial motion). Both 16p11.2 CNV groups exhibited more mu attenuation for nonsocial than social motion. The ASD group did not discriminate between conditions and demonstrated less mu attenuation compared to the typical and duplication carriers. Single-trial analysis indicated that mu attenuation decreased over time more rapidly for 16p11.2 CNV groups than the typical group. The duplication group did not diverge from typical patterns of mu attenuation until after initial exposure.

Conclusions

These results indicate atypical but unique patterns of mu attenuation for deletion and duplication carriers, highlighting the need to continue characterizing the social brain phenotype associated with 16p11.2 CNVs.

Electronic supplementary material

The online version of this article (doi:10.1186/s11689-015-9118-5) contains supplementary material, which is available to authorized users.     

Variation in Psychosis Gene ZNF804A Is Associated With a Refined Schizotypy Phenotype but Not Neurocognitive Performance in a Large Young Male Population

Genetic variability within the ZNF804A gene has been recently found to be associated with schizophrenia and bipolar disorder, although the pathways by which this gene may confer risk remain largely unknown. We set out to investigate whether common ZNF804A variants affect psychosis-related intermediate phenotypes such as cognitive performance dependent on prefrontal and frontotemporal brain function, schizotypal traits, and attenuated psychotic experiences in a large young male population. Association analyses were performed using all 4 available self-rated schizotypy questionnaires and cognitive data retrospectively drawn from the Athens Study of Psychosis Proneness and Incidence of Schizophrenia (ASPIS). DNA samples from 1507 healthy young men undergoing induction to military training were genotyped for 4 previously studied polymorphic markers in the ZNF804A gene locus. Single-marker analysis revealed significant associations between 2 recently identified candidate schizophrenia susceptibility variants (rs1344706 and rs7597593) and a refined positive schizotypy phenotype characterized primarily by self-rated paranoia/ideas of reference. Nominal associations were noted with all positive, but not negative, schizotypy related factors. ZNF804A genotype effect on paranoia was confirmed at the haplotype level. No significant associations were noted with central indexes of sustained attention or working memory performance. In this study, ZNF804A variation was associated with a population-based self-rated schizotypy phenotype previously suggested to preferentially reflect genetic liability to psychosis and defined by a tendency to misinterpret otherwise neutral social cues and perceptual experiences in one’s immediate environment, as personally relevant and significant information. This suggests a novel route by which schizophrenia-implicated ZNF804A genetic variation may confer risk to clinical psychosis at the general population level.Key words: schizophrenia, aberrant salience, schizotypy, paranoia, psychosis, ZNF804A     

The Psychosis Susceptibility Gene ZNF804A: Associations, Functions, and Phenotypes

As the first gene to have achieved genome-wide significance for psychosis, ZNF804A has predictably been a subject of intense research activity. We review the evidence to date for the association between schizophrenia and the original risk variant rs1344706 identified as well as additional common and rare variants at this locus. We describe the still scant literature on the biological function of ZNF804A and discuss the efforts being made to characterize and refine the associated phenotype using imaging and neuropsychological approaches. We conclude that ZNF804A is robustly, if modestly, associated with schizophrenia risk, with much work still remaining to elucidate its role in schizophrenia biology.     

Do reward-processing deficits in schizophrenia-spectrum disorders promote cannabis use? An investigation of physiological response to natural rewards and drug cues

Background

Dysfunctional reward processing is present in individuals with schizophrenia-spectrum disorders (SSD) and may confer vulnerability to addiction. Our objective was to identify a deficit in patients with SSD on response to rewarding stimuli and determine whether this deficit predicts cannabis use.

Methods

We divided a group of patients with SSD and nonpsychotic controls into cannabis users and nonusers. Response to emotional and cannabis-associated visual stimuli was assessed using self-report, event-related potentials (using the late positive potential [LPP]), facial electromyography and skin-conductance response.

Results

Our sample comprised 35 patients with SSD and 35 nonpsychotic controls. Compared with controls, the patients with SSD showed blunted LPP response to pleasant stimuli (p = 0.003). Across measures, cannabis-using controls showed greater response to pleasant stimuli than to cannabis stimuli whereas cannabis-using patients showed little bias toward pleasant stimuli. Reduced LPP response to pleasant stimuli was predictive of more frequent subsequent cannabis use (β = −0.24, p = 0.034).

Limitations

It is not clear if the deficit associated with cannabis use is specific to rewarding stimuli or nonspecific to any kind of emotionally salient stimuli.

Conclusion

The LPP captures a reward-processing deficit in patients with SSD and shows potential as a biomarker for identifying patients at risk of heavy cannabis use.     

Brain volumes in psychotic youth with schizophrenia and mood disorders

Background

We sought to test the hypothesis that deficits in grey matter volume are characteristic of psychotic youth with early-onset schizophrenia-spectrum disorders (EOSS) but not of psychotic youth with early-onset mood disorders (EOMD).

Methods

We used magnetic resonance imaging to examine brain volume in 24 psychotic youth (13 male, 11 female) with EOSS (n = 12) or EOMD (n = 12) and 17 healthy controls (10 male, 7 female). We measured the volume of grey and white matter using an automated segmentation program.

Results

After adjustment for age and intracranial volume, whole brain volume was lower in the EOSS patients than in the healthy controls (p = 0.001) and EOMD patients (p = 0.002). The EOSS patients had a deficit in grey matter volume (p = 0.005), especially in the frontal (p = 0.003) and parietal (p = 0.006) lobes, with no significant differences in white matter volume.

Limitations

The main limitations of our study were its small sample size and the inclusion of patients with depression and mania in the affective group.

Conclusion

Adolescents with EOSS have grey matter deficits compared with healthy controls and psychotic adolescents with EOMD. Our results suggest that grey matter deficits are not generally associated with psychosis but may be specifically associated with schizophrenia. Larger studies with consistent methods are needed to reconcile the contradictory findings among imaging studies involving psychotic youth.     

Contralateral Reherniation after Open Lumbar Microdiscectomy : A Comparison with Ipsilateral Reherniation

Objective

To evaluate the risk factors that may be responsible for the development of contralateral reherniations from ipsilateral ones after open lumbar microdiscectomy (OLM), and to compare surgical outcomes of revision OLM for contralateral reherniations with those for ipsilateral ones.

Methods

Seventeen patients who underwent revision OLM for contralateral reherniation were enrolled into Group I, and 35 patients who underwent revision OLM for ipsilateral reherniation were enrolled into Group II. Using medical charts and imaging study results, the differences in the clinical and radiological factors were evaluated between the two groups. Clinical outcomes of each group were compared between the two groups.

Results

Significant differences were found in the interval to reherniation from initial surgery (33 months for Group I and 18.6 months for Group II, p=0.009), as well as in the incidences of both protruded disc (35.3% for Group I and 8.6% for Group II, p=0.045) and mild disc degeneration (29.4% for Group I and 5.7% for Group II, p=0.031) at initial surgery. On binary multi-logistic regression analysis, significant differences were found in the interval to reherniation (p=0.027, Odds ratio=1.051) and incidence of mild disc degeneration (p=0.025, Odds ratio=12.03) between the two groups. There were no significant differences in the improvement of clinical outcomes after revision OLM between the two groups.

Conclusion

The interval to reherniation from initial surgery and the grade of disc degeneration at initial surgery were key factors that distinguished the development of contralateral reherniations from ipsilateral ones. Surgical outcomes of revision OLM were similar in both groups.     

Postoperative Flat Back: Contribution of Posterior Accessed Lumbar Interbody Fusion and Spinopelvic Parameters

Objective

Posterior accessed lumbar interbody fusion (PALIF) has a clear objective to restore disc height and spinal alignment but surgeons may occasionally face the converse situation and lose lumbar lordosis. We analyzed retrospective data for factors contributing to a postoperative flat back.

Methods

A total of 105 patients who underwent PALIF for spondylolisthesis and stenosis were enrolled. The patients were divided according to surgical type [posterior lumbar inter body fusion (PLIF) vs. unilateral transforaminal lumbar interbody fusion (TLIF)], number of levels (single vs. multiple), and diagnosis (spondylolisthesis vs. stenosis). We measured perioperative index level lordosis, lumbar lordosis, pelvic tilt, sacral slope, pelvic incidence, and disc height in standing lateral radiographs. The change and variance in each parameter and comparative group were analyzed with the paired and Student t-test (p<0.05), correlation coefficient, and regression analysis.

Results

A significant perioperative reduction was observed in index-level lordosis following TLIF at the single level and in patients with spondylolisthesis (p=0.002, p=0.005). Pelvic tilt and sacral slope were significantly restored following PLIF multilevel surgery (p=0.009, p=0.003). Sacral slope variance was highly sensitive to perioperative variance of index level lordosis in high sacral sloped pelvis. Perioperative variance of index level lordosis was positively correlated with disc height variance (R²=0.286, p=0.0005).

Conclusion

Unilateral TLIF has the potential to cause postoperative flat back. PLIF is more reliable than unilateral TLIF to restore spinopelvic parameters following multilevel surgery and spondylolisthesis. A high sacral sloped pelvis is more vulnerable to PALIF in terms of a postoperative flat back.     

Prenatal exposure to cigarette smoke interacts with OPRM1 to modulate dietary preference for fat

Background

Preference for fatty foods is a risk factor for obesity. It is a complex behaviour that involves the brain reward system and is regulated by genetic and environmental factors, such as the opioid receptor mu-1 gene (OPRM1) and prenatal exposure to maternal cigarette smoking (PEMCS). We examined whether OPRM1 and PEMCS interact in influencing fat intake and whether exposure-associated epigenetic modifications of OPRM1 may mediate this gene–environment interaction.

Methods

We studied adolescents from a French Canadian genetic founder population, half of whom were exposed prenatally to maternal cigarette smoking. Fat intake was assessed with a 24-hour food recall in the form of a structured interview conducted by a trained nutritionist. The OPRM1 variant rs2281617 was genotyped for the whole sample with the Illumina Human610-Quad and HumanOmniExpress BeadChips. Methylation of blood DNA was assessed at 21 CpGs across OPRM1 in a subset of the sample using the Illumina HumanMethylation450 BeadChip.

Results

We included 956 adolescents in our study. In the whole sample, OPRM1 (T carrier in rs2281617) was associated with lower fat intake (−1.6%, p = 0.017), and PEMCS was associated with higher fat intake (+1.6%, p = 0.005). OPRM1 and PEMCS interacted with each other (p = 0.003); the “protective” (fat intake–lowering) allele of OPRM1 was associated with lower fat intake in nonexposed (−3.2%, p < 0.001) but not in exposed individuals (+0.8%, p = 0.42). Further, PEMCS was associated with lower DNA methylation across multiple CpGs across OPRM1 in exposed versus nonexposed individuals (p = 0.031).

Limitations

A limitation of our study was its cross-sectional design.

Conclusion

Our study suggests that PEMCS may interact with OPRM1 in increasing fat preference. Silencing of the protective OPRM1 allele in exposed adolescents might be related to epigenetic modification of this gene.     

Copy number variation in Han Chinese individuals with autism spectrum disorder

Background

Autism spectrum disorders (ASDs) are a group of neurodevelopmental conditions with a demonstrated genetic etiology. Rare (<1% frequency) copy number variations (CNVs) account for a proportion of the genetic events involved, but the contribution of these events in non-European ASD populations has not been well studied. Here, we report on rare CNVs detected in a cohort of individuals with ASD of Han Chinese background.

Methods

DNA samples were obtained from 104 ASD probands and their parents who were recruited from Harbin, China. Samples were genotyped on the Affymetrix CytoScan HD platform. Rare CNVs were identified by comparing data with 873 technology-matched controls from Ontario and 1,235 additional population controls of Han Chinese ethnicity.

Results

Of the probands, 8.6% had at least 1 de novo CNV (overlapping the GIGYF2, SPRY1, 16p13.3, 16p11.2, 17p13.3-17p13.2, DMD, and NAP1L6 genes/loci). Rare inherited CNVs affected other plausible neurodevelopmental candidate genes including GRID2, LINGO2, and SLC39A12. A 24-kb duplication was also identified at YWHAE, a gene previously implicated in ASD and other developmental disorders. This duplication is observed at a similar frequency in cases and in population controls and is likely a benign Asian-specific copy number polymorphism.

Conclusions

Our findings help define genomic features relevant to ASD in the Han Chinese and emphasize the importance of using ancestry-matched controls in medical genetic interpretations.     

Epigenetic Regulation in the Brain after Spinal Cord Injury : A Comparative Study

Objective

After spinal cord injury (SCI), functional and structural reorganization occurs at multiple levels of brain including motor cortex. However, the underlying mechanism still remains unclear. The current study was performed to investigate the alterations in the expression of the main regulators of neuronal development, survival and death, in the brain following thoracic contusive SCI in a mouse model.

Methods

Eight-week-old female imprinting control region mice (n=60; 30-35 g) were used in this study. We analyzed the expression levels of regulators such as brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), nerve growth factor (NGF) and histone deacetylase (HDAC) 1 in the brain following thoracic contusive SCI.

Results

The expression of BDNF levels were elevated significantly compared with control group at 2 weeks after injury (p<0.05). The expression of NGF levels were elevated at 2, 4 weeks compared with control group, but these difference were not significant (p>0.05). The GDNF levels were elevated at 2 week compared with control group, but these differences were not significant (p>0.05). The difference of HDAC1 levels were not significant at 2, 4 and 8 weeks compared with control group (p>0.05).

Conclusion

These results demonstrate that the upregulation of BDNF may play on important role in brain reorganization after SCI.     

Predictors of 30-Day Mortality and 90-Day Functional Recovery after Primary Intracerebral Hemorrhage : Hospital Based Multivariate Analysis in 585 Patients

Objective

The purpose of this study was to identify independent predictors of mortality and functional recovery in patients with primary intracerebral hemorrhage (PICH) and to improve functional outcome in these patients.

Methods

Data were collected retrospectively on 585 patients with supratentorial PICH admitted to the Stroke Unit at our hospital between 1st January 2004 and the 31st July 2008. Using multivariate logistic regression analysis, the associations between all selected variables and 30-day mortality and 90-day functional recoveries after PICH was evaluated.

Results

Ninety-day functional recovery was achieved in 29.1% of the 585 patients and 30-day mortality in 15.9%. Age (OR=7.384, p=0.000), limb weakness (OR=6.927, p=0.000), and hematoma volume (OR=5.293, p=0.000) were found to be powerful predictors of 90-day functional recovery. Furthermore, initial consciousness (OR=3.013, p=0.014) hematoma location (lobar, OR=2.653, p=0.003), ventricular extension of blood (OR=2.077, p=0.013), leukocytosis (OR=2.048, p=0.008), alcohol intake (drinker, OR=1.927, p=0.023), and increased serum aminotransferase (OR=1.892, p=0.035) were found to be independent predictors of 90-day functional recovery after PICH. On the other hand, a pupillary abnormality (OR=4.532, p=0.000) and initial unconsciousness (OR=3.362, p=0.000) were found to be independent predictors of 30-day mortality after PICH.

Conclusion

The predictors of mortality and functional recovery after PICH identified during this analysis may assist during clinical decision-making, when advising patients or family members about the prognosis of PICH and when planning intervention trials.