Evidence from <Emphasis Type="Italic">in vivo</Emphasis> 31-phosphorus magnetic resonance spectroscopy phosphodiesters that exhaled ethane is a biomarker of cerebral <Emphasis Type="Italic">n</Emphasis>-3 polyunsaturated fatty acid peroxidation in humans

Background

This study tested the hypothesis that exhaled ethane is a biomarker of cerebral n-3 polyunsaturated fatty acid peroxidation in humans. Ethane is released specifically following peroxidation of n-3 polyunsaturated fatty acids. We reasoned that the cerebral source of ethane would be the docosahexaenoic acid component of membrane phospholipids. Breakdown of the latter also releases phosphorylated polar head groups, giving rise to glycerophosphorylcholine and glycerophosphorylethanolamine, which can be measured from the 31-phosphorus neurospectroscopy phosphodiester peak. Schizophrenia patients were chosen because of evidence of increased free radical-mediated damage and cerebral lipid peroxidation in this disorder.

Methods

Samples of alveolar air were obtained from eight patients and ethane was analyzed and quantified by gas chromatography and mass spectrometry (m/z = 30). Cerebral 31-phosphorus spectra were obtained from the same patients at a magnetic field strength of 1.5 T using an image-selected in vivo spectroscopy sequence (TR = 10 s; 64 signal averages localized on a 70 × 70 × 70 mm³ voxel). The quantification of the 31-phosphorus signals using prior knowledge was carried out in the temporal domain after truncating the first 1.92 ms of the signal to remove the broad component present in the 31-phosphorus spectra.

Results

The ethane and phosphodiester levels, expressed as a percentage of the total 31-phosphorus signal, were positively and significantly correlated (r _s = 0.714, p < 0.05).

Conclusion

Our results support the hypothesis that the measurement of exhaled ethane levels indexes cerebral n-3 lipid peroxidation. From a practical viewpoint, if human cerebral n-3 polyunsaturated fatty acid catabolism can be measured by ethane in expired breath, this would be more convenient than determining the area of the 31-phosphorus neurospectroscopy phosphodiester peak.

     

Regional grey matter volumetric changes in forensic schizophrenia patients: an MRI study comparing the brain structure of patients who have seriously and violently offended with that of patients who have not

Background

The aim was to carry out the first voxel-based morphometry study of grey matter changes in the whole brain in schizophrenia associated with a history of seriously and violently offending.

Methods

Structural cerebral magnetic resonance imaging scans of 26 patients with schizophrenia were analyzed using voxel-based morphometry: 13 of the patients had seriously and violently offended directly as a result of schizophrenia prior to admission, the offences consisting of homicide, attempted murder or wounding with intent to cause grievous bodily harm; the other 13 patients did not have a history of violence. There was no history of comorbid psychoactive substance misuse disorder in any of the patients. Voxelwise generalized linear modelling was applied to the processed magnetic resonance data using permutation-based non-parametric testing, forming clusters at t > 2.3 and testing clusters for significance at p < 0.05, corrected for multiple comparisons across space.

Results

The two groups of patients were matched with respect to age, gender and duration of illness, but the group with a history of serious violence was on average receiving a higher dose of antipsychotic medication than the group without a history of violence. There were local regions of reduced grey matter volume in the schizophrenia patient group with a history of serious and violent offending, compared with the schizophrenia patient group without such a history. Significant voxels (p < 0.05, corrected for multiple comparisons) were noted bilaterally in the cerebellum and in BA 39 and 40.

Conclusion

These regions are important in verbal working memory. The cerebellum may integrate inputs from ventrolateral prefrontal cortex and parietal regions, providing a corrective signal that refines the process of rehearing the contents of the phonological store. A strong connection has been hypothesized between the supramarginal region corresponding to BA 39/40 and Broca's area, which may correspond largely to the arcuate fasciculus, with the connectional pattern of the language regions of this model fitting the network of parietotemporal-prefrontal connections that participate in working memory. Therefore our results point to the possibility of an abnormality in neural circuits involved in verbal working memory in this group of patients.

     

A comparison of oxidative stress in smokers and non-smokers: an <Emphasis Type="Italic">in vivo</Emphasis> human quantitative study of <Emphasis Type="Italic">n</Emphasis>-3 lipid peroxidation

Background

Cigarette smoking is believed to cause oxidative stress by several mechanisms, including direct damage by radical species and the inflammatory response induced by smoking, and would therefore be expected to cause increased lipid peroxidation. The aim was to carry out the first study of the relationship of smoking in humans to the level of n-3 lipid peroxidation indexed by the level of ethane in exhaled breath.

Methods

Samples of alveolar air were obtained from 11 smokers and 18 non-smokers. The air samples were analyzed for ethane using mass spectrometry.

Results

The two groups of subjects were matched with respect to age and gender. The mean cumulative smoking status of the smokers was 11.8 (standard error 2.5) pack-years. The mean level of ethane in the alveolar breath of the group of smokers (2.53 (0.55) ppb) was not significantly different from that of the group of non-smokers (2.59 (0.29) ppb; p = 0.92). With all 29 subjects included, the Spearman rank correlation coefficient between ethane levels and cumulative smoking status was -0.11 (p = 0.58), while an analysis including only the smokers yielded a corresponding correlation coefficient of 0.11 (p = 0.75).

Conclusion

Our results show no evidence that cigarette smoking is related to increased n-3 lipid peroxidation as measured by expired ethane.

     

Heart-rate response to alpha<Subscript>2</Subscript>-adrenergic receptor antagonism by antipsychotics

Purpose

To explore the relationship between antipsychotic-associated antagonism of alpha₂-adrenergic receptors and resting heart rate in individuals with schizophrenia.

Methods

Thirty-one inpatients treated with antipsychotics were included in this exploratory analysis. Antipsychotic doses were converted to haloperidol equivalents for alpha₂-adrenergic receptor antagonism. Resting heart rate was measured with the patient in the seated upright posture.

Results

After controlling for confounding variables, the relationship between alpha₂-adrenergic receptor antagonism and resting heart rate demonstrated a positive linear effect (P = 0.002) as well as a nonlinear effect that accounted for an additional 14% of the variability in resting heart rate (P = 0.005).

Conclusion

The observed inverted-U relationship between alpha₂-adrenergic receptor antagonism and resting heart rate can possibly be attributed to an altered response of beta₁-adrenergic receptors to increased norepinephrine release. Further investigations are required to confirm this exploratory finding, taking into account additional variables that include other receptors which either directly or indirectly influence heart rate.

ClinicalTrials.gov Identifier

NCT01392885.

     

Predictors of Moderate-to-Vigorous Physical Activity (MVPA) in African American Young Adolescents

Background

African American adolescents residing in the South are at increased risk for obesity and physical inactivity, yet our understanding of potential influences is limited.

Purpose

Using an ecological framework, this study explored multilevel predictors (individual, family, home, and neighborhood environment) of moderate-to-vigorous physical activity (MVPA) among 116 African American adolescents (ages 12–16).

Methods

Adolescents and their parents completed self-report surveys for hypothesized predictors. Youth physical activity was measured using accelerometry.

Results

In multiple regression models, decreased daily MVPA was associated with female sex (β?=??24.27, p?<?0.0001). Family social support (β?=?1.07, p?=?0.004) and adolescent self efficacy for PA (β?=?6.89, p?=?0.054) were positively associated with daily MVPA.

Conclusions

Adolescent demographics along with family social support and self-efficacy influence younger African American adolescent physical activity. Further exploration of the complex interaction of multiple levels of influence is needed to develop appropriate interventions for this vulnerable group.

     

Does fatigue in Parkinson’s disease correlate with autonomic nervous system dysfunction?

Background

Despite its negative impact on quality of life, fatigue in Parkinson’s disease (PD) remains an under-recognized issue and the underlying pathology is undetermined.

Objective

To contribute at understanding the pathogenesis of fatigue in a naturalistic cohort of cognitively intact PD patients.

Methods

In a Caucasian population of PD patients (n?=?27), we evaluated to what extent fatigue (quantified as PFS-16 score) is associated with PD duration and with autonomic dysfunction, studied by both MIBG scintigraphy and autonomic nervous system testing. The latter included the head-up tilt test, Valsalva maneuver, deep breathing, and handgrip tests.

Results

PFS-16 score correlated with disease duration (R?=?0.57, p?=?0.002). Fatigue showed a clear correlation with deep breathing test (R?=???0.53, p?=?0.004) but not with the MIBG H/M ratios.

Conclusions

Our data are consistent with a multifactorial pathogenesis of fatigue and with effects of dopamine depletion in PD-related fatigue; on the other hand, our findings do not support a role for sympathetic denervation in PD-related fatigue.

     

Autonomic symptoms following Zika virus infection

Purpose

To determine if autonomic symptoms are associated with previous Zika virus infection.

Methods

Case–control study including 35 patients with Zika virus infection without evidence of neurological disease and 105 controls. Symptoms of autonomic dysfunction were assessed with the composite autonomic symptom scale 31 (COMPASS-31).

Results

Patients with previous Zika virus infection had significantly higher COMPASS-31 score than controls regardless of age and sex (p = 0.007). The main drivers for the higher scores where orthostatic intolerance (p = 0.003), secretomotor (p = 0.04) and bladder symptoms (p < 0.001).

Conclusion

Zika virus infection is associated with autonomic dysfunction. The mechanisms remain to be elucidated.

     

Social networks and symptomatic and functional outcomes in schizophrenia: a systematic review and meta-analysis

Purpose

To conduct a systematic review and meta-analysis to examine the strength of associations between social network size and clinical and functional outcomes in schizophrenia.

Method

Studies were identified from a systematic search of electronic databases (EMBASE, Medline, PsycINFO, and Web of Science) from January 1970 to June 2016. Eligible studies included peer-reviewed English language articles that examined associations between a quantitative measure of network size and symptomatic and/or functional outcome in schizophrenia-spectrum diagnoses.

Results

Our search yielded 16 studies with 1,929 participants. Meta-analyses using random effects models to calculate pooled effect sizes (Hedge’s g) found that smaller social network size was moderately associated with more severe overall psychiatric symptoms (N?=?5, n?=?467, g?=???0.53, 95% confidence interval (CI)?=???0.875, ??0.184, p?=?0.003) and negative symptoms (N?=?8, n?=?577, g?=???0.75, 95% CI?=???0.997, ??0.512, p?=?0.000). Statistical heterogeneity was observed I²?=?63.04%; I²?=?35.75%,) which could not be explained by low-quality network measures or sample heterogeneity in sensitivity analyses. There was no effect for positive symptoms (N?=?7, n?=?405, g?=???0.19, 95% CI?=?0.494, 0.110, p?=?0.213) or social functioning (N?=?3, n?=?209, g?=?0.36, 95% CI?=???0.078, 0.801, p?=?0.107). Narrative synthesis suggested that larger network size was associated with improved global functioning, but findings for affective symptoms and quality of life were mixed.

Conclusion

Psychosocial interventions which support individuals to build and maintain social networks may improve outcomes in schizophrenia. The review findings are cross-sectional and thus causal direction cannot be inferred. Further research is required to examine temporal associations between network characteristics and outcomes in schizophrenia and to test theoretical models relating to explanatory or mediating mechanisms.

     

Single-Session Behavioral Interventions for Sexual Risk Reduction: A Meta-Analysis

Background

Evidence-based, single-session STI/HIV interventions to reduce sexual risk taking are potentially effective options for implementation in resource-limited settings and may solve problems associated with poor participant retention.

Purpose

The purpose of the study is to estimate the efficacy of single-session, behavioral interventions in reducing unprotected sex or increasing condom use.

Methods

Data sources were searched through April 2013 producing 67 single-session interventions (52 unique reports; N?=?20,039) that included outcomes on condom use and/or unprotected sex.

Results

Overall, participants in single-session interventions reduced sexual risk taking relative to control groups (d ₊ ?=?0.19, 95 % CI?=?0.11, 0.27). Within-group effects of the interventions were larger than the between-groups effects when compared to controls.

Conclusions

Brief, targeted single-session sexual risk reduction interventions demonstrate a small but significant effect and should be prioritized.

     

The Perceived and Built Environment Surrounding Urban Schools and Physical Activity Among Adolescent Girls

Background

Neighborhood perceived/built environment and physical activity (PA) associations have been examined for adolescents around homes, but not surrounding schools.

Purpose

The purpose of this paper is to examine if positive perceptions/built environment in neighborhoods surrounding schools predict PA among low-income, urban adolescent girls.

Methods

Measures include: minutes in moderate-vigorous PA (MVPA, ankle accelerometry), perceptions of the school environment (questionnaire), built environment (neighborhood audit). Analyses include multi-level models.

Results

Two hundred twenty-four sixth and seventh grade girls [mean(sd) age?=?12.1(0.7)?years] from 12 schools serving low-income, primarily African American communities; mean MVPA 35.4 min (mean days assessed?=?5.8). Girls in schools with more positive perceptions of the neighborhood environment surrounding the school were less active (β?=?7.2, p?=?0.043). Having “places to go within walking distance” (perceptions) and number of food stores near school (built environment) positively relate to MVPA (β?=?5.5, p?=?0.042 and β?=?0.59, p?=?0.047).

Conclusions

Among neighborhoods surrounding urban schools, positive perceptions do not predict PA; accessibility, via both perceived and built environment, support PA.

     

Adult normative values for the PATA Rate Test

Background

During neurological evaluation, dysarthria is not rated using quantitative measures, but rather using a qualitative approach.

Objective

Aim of our study was to validate and acquire normative values for the PATA Rate Task (PRT), a quantitative test used to measure the severity of dysarthria.

Methods

For the PRT probands are invited to repeat the syllables “PA-TA” as quickly as possible during a 10-s interval. The score consists in the number of correct repetition of both syllables.

Results

We enrolled 232 healthy controls (118 males, 114 females), mean and standard deviation of the PRT was 28.84?±?6.6 (range 14–52). The PRT showed good inter-rater reliability (R?=?0.783; p?<?0.001), as well as test–retest reliability (R?=?0.927; p?<?0.001), and intra-rater reliability (R?=?0.888; p?<?0.001). Higher age correlated with lower scores (R?=?? 0.368; p?<?0.001).

Conclusions

The PRT showed good reliability and could be easily added to the evaluation of movement disorders where a speech evaluation is essential.

     

Association study in the 5q31-32 linkage region for schizophrenia using pooled DNA genotyping

Background

Several linkage studies suggest that chromosome 5q31-32 might contain risk loci for schizophrenia (SZ). We wanted to identify susceptibility genes for schizophrenia within this region.

Methods

We saturated the interval between markers D5S666 and D5S436 with 90 polymorphic microsatellite markers and genotyped two sets of DNA pools consisting of 300 SZ patients of Bulgarian origin and their 600 parents. Positive associations were followed-up with SNP genotyping.

Results

Nominally significant evidence for association (p < 0.05) was found for seven markers (D5S0023i, IL9, RH60252, 5Q3133_33, D5S2017, D5S1481, D5S0711i) which were then individually genotyped in the trios. The predicted associations were confirmed for two of the markers: D5S2017, localised in the SPRY4-FGF1 locus (p = 0.004) and IL9, localized within the IL9 gene (p = 0.014). Fine mapping was performed using single nucleotide polymorphisms (SNPs) around D5S2017 and IL9. In each region four SNPs were chosen and individually genotyped in our full sample of 615 SZ trios. Two SNPs showed significant evidence for association: rs7715300 (p = 0.001) and rs6897690 (p = 0.032). Rs7715300 is localised between the TGFBI and SMAD5 genes and rs6897690 is within the SPRY4 gene.

Conclusion

Our screening of 5q31-32 implicates three potential candidate genes for SZ: SMAD5, TGFBI and SPRY4.

     

Perceived Housing Discrimination and Self-Reported Health: How Do Neighborhood Features Matter?

Background

While the association between perceived discrimination and health has been investigated, little is known about whether and how neighborhood characteristics moderate this association.

Purpose

We situate discrimination in the housing context and use relative deprivation and social capital perspectives to fill the knowledge gap.

Methods

We applied multilevel logistic modeling to 9,842 adults in 830 neighborhoods in Philadelphia to examine three hypotheses.

Results

First, the detrimental effect of discrimination on self-reported health was underestimated without considering neighborhood features as moderators. The estimated coefficient (β) increased from approximately 0.02 to 1.84 or higher. Second, the negative association between discrimination and self-reported health was enhanced when individuals with discrimination experience lived in neighborhoods with higher housing values (β?=?0.42). Third, the adverse association of discrimination with self-reported health was attenuated when people reporting discrimination resided in neighborhoods marked by higher income inequality (β?=??4.34) and higher concentrations of single-parent households with children (β?=??0.03) and minorities (β?=??0.01).

Conclusions

We not only confirmed the moderating roles of neighborhood characteristics, but also suggested that the relative deprivation and social capital perspectives could be used to understand how perceived housing discrimination affects self-reported health via neighborhood factors.

     

Onset of bladder and motor symptoms in multiple system atrophy: differences according to phenotype

Purpose

To compare the order of presentation of bladder and motor symptoms between multiple system atrophy phenotypes.

Methods

Medical records were retrospectively reviewed in 144 patients.

Results

Bladder symptoms occurred either before or within 12 months after onset of motor symptoms in significantly more patients with the cerebellar phenotype than the parkinsonian phenotype (80 vs. 53%, p = 0.003); similar results were observed for urinary incontinence (79 vs. 45%, p = 0.001).

Conclusions

Urinary dysfunction is more likely to appear either before or shortly after motor symptoms in the cerebellar phenotype than in the parkinsonian phenotype.

     

Bone mineral density in pediatric patients with meningomyelocele

Purpose

The aim of this study was to determine the bone mineral density (BMD) and the factors leading to reduction in BMD in children diagnosed with meningomyelocele.

Methods

A total of 31 patients with meningomyelocele (mean (SD) age, 8.5 (3.9) years; 51.6 % were females) and 22 healthy children were included. BMD of femoral neck and spinal L1–L4 levels and markers for bone metabolism were recorded.

Results

BMD of femoral neck (p?=?0.001) and spinal L1–L4 (p?=?0.01), serum calcium (p?=?0.031), and urinary deoxypyridinoline (p?=?0.015) levels were significantly lower in patients than in controls. Mobilization was significantly reduced in lumbar (p?=?0.001) and thoracic (p?=?0.002) level meningomyelocele compared to controls, while a significant positive correlation was noted between BMD of spinal L1–L4 and mobility (r?=?0.58, p?=?0.015).

Conclusions

Our findings suggest a decrease in BMD in meningomyelocele patients being associated with osteoporosis rather than nutritional and hormonal factors and the negative impact of higher levels of lesion on the mobility.

     

A novel SNP in <Emphasis Type="Italic">COMT</Emphasis> is associated with alcohol dependence but not opiate or nicotine dependence: a case control study

Background

It is well established that COMT is a strong candidate gene for substance use disorder and schizophrenia. Recently we identified two SNPs in COMT (rs4680 and rs165774) that are associated with schizophrenia in an Australian cohort. Individuals with schizophrenia were more than twice as likely to carry the GG genotype compared to the AA genotype for both the rs165774 and rs4680 SNPs. Association of both rs4680 and rs165774 with substance dependence, a common comorbidity of schizophrenia has not been investigated.

Methods

To determine whether COMT is important in substance dependence, rs165774 and rs4680 were genotyped and haplotyped in patients with nicotine, alcohol and opiate dependence.

Results

The rs165774 SNP was associated with alcohol dependence. However, it was not associated with nicotine or opiate dependence. Individuals with alcohol dependence were more than twice as likely to carry the GG or AG genotypes compared to the AA genotype, indicating a dominant mode of inheritance. The rs4680 SNP showed a weak association with alcohol dependence at the allele level that did not reach significance at the genotype level but it was not associated with nicotine or opiate dependence. Analysis of rs165774/rs4680 haplotypes also revealed association with alcohol dependence with the G/G haplotype being almost 1.5 times more common in alcohol-dependent cases.

Conclusions

Our study provides further support for the importance of the COMT in alcohol dependence in addition to schizophrenia. It is possible that the rs165774 SNP, in combination with rs4680, results in a common molecular variant of COMT that contributes to schizophrenia and alcohol dependence susceptibility. This is potentially important for future studies of comorbidity. As our participant numbers are limited our observations should be viewed with caution until they are independently replicated.

     

Low prevalence of lipid metabolism abnormalities in <Emphasis Type="Italic">APOE</Emphasis> ε2-genotype and male patients 60 years or older with schizophrenia

Background

Schizophrenia is a serious mental disorder largely manageable with atypical antipsychotics; however, these drugs have been associated with glucose/lipid metabolism issues such as diabetes and hyperlipidaemia. Apolipoprotein E (APOE) is the most abundant apolipoprotein, and APOE genotypes have been correlated with lipid metabolism phenotypes in an age-dependent manner. Studies examining the relationship between the APOE genotype and lipid abnormalities in patients with schizophrenia have been inconclusive, but primarily focused on adult patient populations. Therefore, we explored the correlations between the APOE genotype and glucose/lipid metabolism indicators and abnormalities in hospitalized patients 60 years or older with schizophrenia with a history of long-term antipsychotics use.

Methods

We assessed APOE genotype, age, weight, height, blood glucose, triglycerides, cholesterol, high-density lipoprotein, and low-density lipoprotein in a total of 294 patients. APOE genotypes were divided into three groups: APOE ε2 (ε2/ε2 and ε2/ε3), APOE ε3 (ε3/ε3), and APOE ε4 (ε3/ε4 and ε4/ε4), and comparisons were conducted among these groups or according to ε2 carrier status.

Results

APOE ε3/ε3 was the most common genotype (68.3%) and at least one ε3 allele was present in 81.8% of patients. There were no differences in antipsychotics type or dose according to the APOE genotype, but serum cholesterol values varied near significantly (P?=?0.052) and low-density lipoprotein values varied significantly according to genotype (P?<?0.05, lowest in the APOE ε2 genotype). Men had lower cholesterol and low-density lipoprotein levels (P?<?0.05) than women. Compared to patients administered typical antipsychotics, those administered atypical antipsychotics had higher triglyceride, cholesterol, and low-density lipoprotein levels (P?<?0.05). Stepwise linear regressions showed that cholesterol and low-density lipoprotein levels were influenced by sex, the APOE ε2 genotype, and atypical antipsychotics use.

Conclusions

In the context of atypical antipsychotics use, carriers of the APOE ε2-genotype and male patients with schizophrenia 60 years or older may be less likely to develop a lipid metabolism abnormality.

     

Family-based association study of the BDNF,COMT and serotonin transporter genes and DSM-IV bipolar-I disorder in children

Background

Over the past decade pediatric bipolar disorder has gained recognition as a potentially more severe and heritable form of the disorder. In this report we test for association with genes coding brain-derived neurotrophic factor (BDNF), the serotonin transporter (SLC6A4), and catechol-O-methyltransferase (COMT).

Methods

Bipolar-I affected offspring triads (N = 173) were drawn from 522 individuals with 2 parents in 332 nuclear families recruited for genetic studies of pediatric psychopathology at the Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD at Massachusetts General Hospital.

Results

We failed to identify an association with the val66 allele in BDNF (OR = 1.23, p = 0.36), the COMT-l allele (OR = 1.27, p = 0.1), or the HTTLPR short allele (OR = 0.87, p = 0.38).

Conclusion

Our study suggests that the markers examined thus far in COMT and SLC6A4 are not associated with pediatric bipolar disorder and that if the val66met marker in BDNF is associated with pediatric bipolar disorder the magnitude of the association is much smaller than first reported.

     

Mutations in <Emphasis Type="Italic">dock1</Emphasis> disrupt early Schwann cell development

Background

In the peripheral nervous system (PNS), specialized glial cells called Schwann cells produce myelin, a lipid-rich insulating sheath that surrounds axons and promotes rapid action potential propagation. During development, Schwann cells must undergo extensive cytoskeletal rearrangements in order to become mature, myelinating Schwann cells. The intracellular mechanisms that drive Schwann cell development, myelination, and accompanying cell shape changes are poorly understood.

Methods

Through a forward genetic screen in zebrafish, we identified a mutation in the atypical guanine nucleotide exchange factor, dock1, that results in decreased myelination of peripheral axons. Rescue experiments and complementation tests with newly engineered alleles confirmed that mutations in dock1 cause defects in myelination of the PNS. Whole mount in situ hybridization, transmission electron microscopy, and live imaging were used to fully define mutant phenotypes.

Results

We show that Schwann cells in dock1 mutants can appropriately migrate and are not decreased in number, but exhibit delayed radial sorting and decreased myelination during early stages of development.

Conclusions

Together, our results demonstrate that mutations in dock1 result in defects in Schwann cell development and myelination. Specifically, loss of dock1 delays radial sorting and myelination of peripheral axons in zebrafish.