Further examination of the candidate genes in chromosome 12p13 locus for late-onset Alzheimer disease

A broad region on chromosome 12p13 has been intensely investigated for novel genetic variants associated with Alzheimer disease (AD). We examined this region with 23 microsatellite markers using 124 North European (NE) families and 209 Caribbean Hispanic families with late-onset AD (FAD). Significant evidence for linkage was present in a 5-cM interval near 20 cM in both the NE FAD (LOD = 3.5) and the Caribbean Hispanic FAD (LOD = 2.2) datasets. We further investigated these families and an independent NE case–control dataset using 14 single nucleotide polymorphisms (SNPs). The initial screening of the region at ∼20 cM in the NE case–control dataset revealed significant association between AD and seven SNPs in several genes, with the strongest result for rs2532500 in TAPBPL (p = 0.006). For rs3741916 in GAPDH, the C allele, rather than the G allele as was observed by Li et al. (Proc Natl Acad Sci U S A 101(44):15688–15693, 2004), was the risk allele. When the two family datasets were examined, none of the SNPs were significant in NE families, but two SNPs were associated with AD in Caribbean Hispanics: rs740850 in NCAPD2 (p = 0.0097) and rs1060620 in GAPDH (p = 0.042). In a separate analysis combining the Caribbean Hispanic families and NE cases and controls, rs740850 was significant after correcting for multiple testing (empirical p = 0.0048). Subsequent haplotype analyses revealed that two haplotype sets—haplotype C-A at SNPs 6–7 within NCAPD2 in Caribbean Hispanics, and haplotypes containing C-A-T at SNPs 8–10 within GAPDH in Caribbean Hispanic family and NE case–control datasets—were associated with AD. Taken together, these SNPs may be in linkage disequilibrium with a pathogenic variant(s) on or near NCAPD2 and GAPDH. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Nitric oxide synthase genes and their interactions with environmental factors in Parkinson’s disease

Nitric oxide synthase (NOS) genes (NOS1, NOS2A, and NOS3) may create excess nitric oxide that contributes to neurodegeneration in Parkinson’s disease (PD). NOS genes might also interact with one another or with environmental factors in PD. Coding and tagging single nucleotide polymorphisms (SNPs) (27 NOS1, 18 NOS2A, and five NOS3 SNPs) were genotyped in families with PD (1,065 cases and 1,180 relative and other controls) and were tested for allelic associations with PD using the association in the presence of linkage test and the pedigree disequilibrium test (PDT), allelic associations with age-at-onset (AAO) using the quantitative transmission disequilibrium test, and interactions using the multifactor dimensionality reduction—PDT. Gene–environment interactions involving cigarette smoking, caffeine, nonsteroidal anti-inflammatory drugs, and pesticides were examined using generalized estimating equations in participants with environmental data available. Significant associations with PD were detected for the NOS1 SNPs rs3782218, rs11068447, rs7295972, rs2293052, rs12829185, rs1047735, rs3741475, and rs2682826 (range of p = 0.00083–0.046) and the NOS2A SNPs rs2072324, rs944725, rs12944039, rs2248814, rs2297516, rs1060826, and rs2255929 (range of p = 0.0000040–0.047) in earlier-onset families with sporadic PD, and some SNPs were also associated with earlier AAO. There was no compelling statistical evidence for gene–gene interactions. However, of the significantly associated SNPs, interactions were found between pesticides and the NOS1 SNPs rs12829185, rs1047735, and rs2682826 (range of p = 0.012–0.034) and between smoking and the NOS2A SNPs rs2248814 (p = 0.021) and rs1060826 (p = 0.013). These data implicate NOS1 and NOS2A as genetic risk factors for PD and demonstrate that their interactions with established environmental factors may modulate the environmental effects.     

MAG Gene Variation and Cortical Gray Matter Volume in First Episode Schizophrenia

Evidence implicating myelin related genes in the pathophysiology of schizophrenia is accumulating. Abnormalities of brain structure at the onset of psychosis may be related to variation in genes such as myelin associated glycoprotein (MAG). Subjects with first episode schizophrenia (n = 30) or schizoaffective disorder (n = 11), and healthy comparison subjects (n = 43) participated in an MRI scan. Two single nucleotide polymorphisms (rs720309, rs720308) in the MAG gene were genotyped. MAG genotype variation predicted cortical gray matter volume in first episode schizophrenia patients (p = 0.039), but not in controls (p = 0.827). Cortical gray matter, total gray matter, total white matter, and ventricular cerebrospinal fluid volumes did not differ between groups. Genetic variation in the MAG gene may predict cortical gray matter volume differences in patients in the first episode of schizophrenia or schizoaffective disorder.     

Association of Toll-like Receptor 2 Polymorphisms with National Institute of Health Stroke Scale Scores of Ischemic Stroke Patients

Toll-like receptor 2 (TLR2) has been shown to have an important role in the postischemic inflammatory response and to contribute to ischemic brain damage. In this study, we investigated whether coding region single nucleotide polymorphisms (SNPs) of the TLR2 gene were associated with ischemic stroke (IS) and with clinical phenotypes in IS patients. We genotyped two SNPs (rs3804099 [Asn199Asn] and rs3804100 [Ser450Ser]) using direct sequencing in 202 IS patients and 291 control subjects. No SNPs of the TLR2 gene were found to be associated with IS. However, in analysis of clinical phenotypes, we found that rs3804099 was associated with the National Institute of Health Stroke Scale (NIHSS) scores of IS patients in codominant (TC vs. TT, p = 0.0005; CC vs. TT, p = 0.0007) and dominant models (TC/CC vs. TT, p = 0.0001). Also, rs3804100 revealed significant association in codominant (TC vs. TT, p = 0.0002; CC vs. TT, p = 0.008) and dominant models (TC/CC vs. TT, p < 0.0001). In allele frequency analysis, we also found that the C alleles of rs3804099 and rs3804100 were associated with higher NIHSS scores (p = 0.0003 in rs3804099; p = 0.0001 in rs3804100). Our results suggest that TLR2 may be related to severe IS.     

Investigation of autism and GABA receptor subunit genes in multiple ethnic groups

Autism is a neurodevelopmental disorder of complex genetics, characterized by impairment in social interaction and communication, as well as repetitive behavior. Multiple lines of evidence, including alterations in levels of GABA and GABA receptors in autistic patients, indicate that the GABAergic system, which is responsible for synaptic inhibition in the adult brain, may be involved in autism. Previous studies in our lab indicated association of noncoding single nucleotide polymorphisms (SNPs) within a GABA receptor subunit gene on chromosome 4, GABRA4, and interaction between SNPs in GABRA4 and GABRB1 (also on chromosome 4), within Caucasian autism patients. Studies of genetic variation in African-American autism families are rare. Analysis of 557 Caucasian and an independent population of 54 African-American families with 35 SNPs within GABRB1 and GABRA4 strengthened the evidence for involvement of GABRA4 in autism risk in Caucasians (rs17599165, p=0.0015; rs1912960, p=0.0073; and rs17599416, p=0.0040) and gave evidence of significant association in African-Americans (rs2280073, p=0.0287 and rs16859788, p=0.0253). The GABRA4 and GABRB1 interaction was also confirmed in the Caucasian dataset (most significant pair, rs1912960 and rs2351299; p=0.004). Analysis of the subset of families with a positive history of seizure activity in at least one autism patient revealed no association to GABRA4; however, three SNPs within GABRB1 showed significant allelic association; rs2351299 (p=0.0163), rs4482737 (p=0.0339), and rs3832300 (p=0.0253). These results confirmed our earlier findings, indicating GABRA4 and GABRB1 as genes contributing to autism susceptibility, extending the effect to multiple ethnic groups and suggesting seizures as a stratifying phenotype.     

Genes in the serotonin pathway are associated with bipolar affective disorder in a Han Chinese population

Serotonin plays an important role in mood regulation, but the involvement of serotonin pathway genes in the development of bipolar I disorder (BP-I), a mood disorder, is not clear. We selected 21 singlenucleotide polymorphisms (SNPs) within the HTR2A gene, 8 within the SLC6A4 gene and 23 within the TPH2 gene for genotyping using the GoldenGate genotyping assay. A total of 375 patients with BP-I and 475 normal controls were recruited. Two out of 21 SNPs (rs1475196 and rs9567747) in the HTR2A gene and 1/23 SNPs (rs17110566) in the TPH2 gene were significantly associated with BP-I, both genotype-wise and allele-wise. Furthermore, a specific haplotype in the HTR2A gene showed a significant association with BP-I. Our results indicate that the HTR2A and TPH2 genes in the serotonin pathway play important roles in susceptibility to BP-I.     

Association Between DARPP-32 Gene Polymorphism and Personality Traits in Healthy Chinese-Han Subjects

The 32-kDa dopamine- and cAMP-regulated phosphoprotein (DARPP-32) is a key signaling factor in several neurotransmitter pathways (including dopamine and serotonin) that impact personality traits. Therefore, different DARPP-32 alleles may influence the biological determination of distinct personality types. We established an association between the DARPP-32 gene polymorphisms (rs12601930C/T, rs879606A/G, and rs3764352A/G) and personality traits as measured by the Tridimensional Personality Questionnaire in 502 healthy Chinese-Han subjects. Of the three polymorphic sites examined, rs12601930C/T was associated with novelty seeking (χ ² = 13.06, P = 0.001), while both rs879606A/G and rs3764352A/G were associated with harm avoidance (rs879606: χ ² = 7.74, P = 0.021; rs3764352: χ ² = 8.53, P = 0.014). There was no significant association between reward dependence scores and DARPP-32 gene polymorphisms. Our results suggest that polymorphisms in the DARPP-32 gene are involved in the biological mechanisms that confer the traits of novelty seeking and harm avoidance.     

The Age at Motor Symptoms Onset in <Emphasis Type="Italic">LRRK2</Emphasis>-Associated Parkinson's Disease is Affected by a Variation in the <Emphasis Type="Italic">MAPT</Emphasis> Locus: A Possible Interaction

The current paradigm on Parkinson's disease (PD) pathogenesis and course suggests the involvement of multiple genes and the interaction between them. Recently, it was reported that a variation (rs2435207) in the MAPT gene region influenced the age of motor symptoms onset (AO) in 44 PD patients from 19 families, carriers of leucine-rich repeat kinase 2 (LRRK2) mutations, all of European and North American origin. To examine whether genetic factors within the MAPT locus exert a similar effect on AO in a different population of LRRK2-associated PD patients, 99 unrelated Ashkenazi patients with the LRRK2 p.G2019S mutation were analyzed. Three SNPs in the MAPT region were studied, rs393152, rs2435207, and rs11079727; the latter is located in the first intron of MAPT. Among carriers of the single LRRK2 p.G2019S mutation that did not carry a founder Ashkenazi GBA mutation too (n = 84), the AO in minor rs11079727 A allele carriers (C/A genotype) was significantly older (62.5 ± 10.6 years) compared to the AO (55.7 ± 11.6) among carriers of the C/C genotype (p = 0.025). Our results further support a possible interaction between genetic factors in the MAPT region and the LRRK2 gene, which influence the clinical course of PD patients.     

Age-at-onset linkage analysis in Caribbean Hispanics with familial late-onset Alzheimer’s disease

The aim of the study was to identify chromosomal regions that may harbor putative genetic variants influencing age at onset in familial late-onset Alzheimer’s disease (LOAD). Data from a genome-wide scan that included genotyping of APOE were analyzed in 1,161 individuals from 209 families of Caribbean Hispanic ancestry with a mean age at onset of 73.3 years multiply affected by LOAD. Two-point and multipoint analyses were conducted using variance component methods using 376 microsatellite markers with an average intermarker distance of 9.3 cM. Family-based test of association was also conducted for the same set of markers. Age at onset of symptoms among affected individuals was used as the quantitative trait. Our results showed that the presence of APOE-ɛ4 lowered the age at onset by 3 years. Several candidate loci were identified. Using linkage analysis strategy, the highest logarithm of odds (LOD) scores were obtained using a conservative definition of LOAD at 5q15 (LOD = 3.1), 17q25.1 (LOD = 2.94), 14q32.12 (LOD = 2.36), and 7q36.3 (LOD = 2.29) in a model that adjusted for APOE-ɛ4 and other covariates. Both linkage and family-based association identified 17p13 as a candidate region. Family-based association analysis showed markers at 12q13 (p = 0.00002), 13q33 (p = 0.00043), and 14q23 (p = 0.00046) to be significantly associated with age at onset. The current study supports the hypothesis that there are additional genetic loci that could influence age at onset of late onset Alzheimer’s disease. The novel loci at 5q15, 17q25.1, 13q33, and 17p13 and the previously reported loci at 7q36.3, 12q13, 14q23, and 14q32 need further investigation. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. Joseph H. Lee, Sandra Barral, Rong Cheng, and Inara Chacon contributed equally to this work.     

Serotonin 1A receptor gene,schizophrenia and bipolar disorder: An association study and meta-analysis

Several investigations have reported associations between serotonin 1A (5-HT1A) receptor and major psychiatric disorders, such as schizophrenia and bipolar disorder (BP), making the 5-HT1A receptor gene (HTR1A) a good candidate gene for the pathophysiology of schizophrenia and BP. To evaluate the association between HTR1A and schizophrenia and BP, we conducted a case-control study of Japanese population samples with two single- nucleotide polymorphisms (SNPs), including rs6295 (C-1019G) in HTR1A. In addition, we conducted a meta-analysis of rs6295, which has been examined in other studies. Using one functional single- nucleotide polymorphism (SNP; rs6295) and one tagging SNP (rs878567), we conducted a genetic association analysis of case-control samples (857 schizophrenic patients, 1028 BP patients and 1810 controls) in the Japanese population. Two association studies for schizophrenia and three association studies for BP, including this study, met our criteria for the meta-analysis of rs6295. We found an association between HTR1A and Japanese BP in a haplotype-wise analysis, the significance of which remained after Bonferroni correction. In addition, we detected an association between rs6295 and BP in the meta-analysis (fixed model: P(Z) = 0.000400). However, we did not detect an association between HTR1A and schizophrenia in the allele/genotype-wise, haplotype-wise or meta-analysis. HTR1A may play an important role in the pathophysiology of BP, but not schizophrenia in the Japanese population. In the meta-analysis, rs6295 in HTR1A was associated with BP patients.     

A fMRI Study of Verbal Working Memory, Cardiac Output, and Ejection Fraction in Elderly Patients with Cardiovascular Disease

Cardiovascular disease (CVD) is associated with cognitive deficits even in the absence of stroke. We examined the relationship between cardiac performance, as measured by cardiac output (CO) and ejection fraction (EF), and brain activity during a verbal working memory (VWM) task in elderly CVD patients who tend to be at increased risk for vascular cognitive impairments. Seventeen patients were recruited from a cohort participating in an ongoing prospective study examining the effects of CVD on cognitive function in the elderly. Participants were diagnosed with CVD (age 68 ± 8) and completed a 2-back VWM task in a 1.5T fMRI paradigm. CO and EF were calculated from echocardiogram measures. Task-related activation was averaged in a priori regions of interest. The relationship between CO, EF, and 2-back-related activity was modeled using partial correlations (two-tailed p < .05) controlling for age and 2-back accuracy. All participants were globally cognitively intact as indicated by Mini-Mental Status Exam and Dementia Rating Scale scores. Mean accuracy on the 2-back was 78 ± 9% while reaction time averaged 1,027 ± 192 ms. Mean CO and EF values showed a large range (CO: 3.55 to 6.31; EF: 0.36 to 0.76) but average values were within the normal range. After controlling for age and 2-back accuracy, lower EF was related to decrease in left insula activity (r = 0.61, p = 0.03). There were trends for EF to be related to accuracy (r = 0.47, p = 0.09) and reaction time (r = −0.48, p = 0.09). CO was also related to insula activity (r = 0.60, p = 0.04) and activity in the supplementary motor area activity (r = 0.66, p = 0.01). Cardiac performance was related to decreased efficiency in task related brain areas and tended to be related to performance on a VWM task in elderly patients with CVD. Results have implications for a line of investigation indicating that cardiac and systemic vascular indices could be used as proxy measures to examine mechanisms of cerebrovascular dysfunction in the elderly.     

Efficacy of a Brief Image-Based Multiple-Behavior Intervention for College Students

Background  Epidemiologic data indicate most adolescents and adults experience multiple, simultaneous risk behaviors. Purpose  The purpose of this study is to examine the efficacy of a brief image-based multiple-behavior intervention (MBI) for college students. Methods  A total of 303 college students were randomly assigned to: (1) a brief MBI or (2) a standard care control, with a 3-month postintervention follow-up. Results  Omnibus treatment by time multivariate analysis of variance interactions were significant for three of six behavior groupings, with improvements for college students receiving the brief MBI on alcohol consumption behaviors, F(6, 261) = 2.73, p = 0.01, marijuana-use behaviors, F(4, 278) = 3.18, p = 0.01, and health-related quality of life, F(5, 277) = 2.80, p = 0.02, but not cigarette use, exercise, and nutrition behaviors. Participants receiving the brief MBI also got more sleep, F(1, 281) = 9.49, p = 0.00, than those in the standard care control. Conclusions  A brief image-based multiple-behavior intervention may be useful in influencing a number of critical health habits and health-related quality-of-life indicators of college students.     

Effects of Mindfulness-Based Stress Reduction Intervention on Psychological Well-being and Quality of Life: Is Increased Mindfulness Indeed the Mechanism?

Background  Although several studies have reported positive effects of mindfulness-based stress reduction (MBSR) intervention on psychological well-being, it is not known whether these effects are attributable to a change in mindfulness. Purpose  The aim of this study is to compare the effects of MBSR to a waiting-list control condition in a randomized controlled trial while examining potentially mediating effects of mindfulness. Methods  Forty women and 20 men from the community with symptoms of distress (mean age 43.6 years, SD = 10.1) were randomized into a group receiving MBSR or a waiting-list control group. Before and after the intervention period, questionnaires were completed on psychological well-being, quality of life, and mindfulness. Results  Repeated measures multiple analysis of variance (MANCOVAs) showed that, compared with the control group, the intervention resulted in significantly stronger reductions of perceived stress (p = 0.016) and vital exhaustion (p = 0.001) and stronger elevations of positive affect (p = 0.006), quality of life (p = .009), as well as mindfulness (p = 0.001). When mindfulness was included as a covariate in the MANCOVA, the group effects on perceived stress and quality of life were reduced to nonsignificance. Conclusion  Increased mindfulness may, at least partially, mediate the positive effects of mindfulness-based stress reduction intervention.     

Comparing Psychosocial Predictors of Physical Activity Adoption and Maintenance

Background   Most health behavior models do not distinguish between determinants of behavior adoption and maintenance. Purpose   This study compared psychosocial predictors of physical activity (PA) adoption and predictors of PA maintenance among 205 initially sedentary adults enrolled in a home-based PA promotion trial. Methods   Psychosocial variables were measured at 6 months (at which point 107 participants remained inactive and 98 participants adopted regular PA) and used to predict 12-month PA status (an indicator of PA adoption among those inactive at 6 months and an indicator of PA maintenance among those active at 6 months). Results   Six-month PA status moderated the relationships between 6-month measures of home access to PA equipment (p = .049), self-efficacy (p = .086), and perceived satisfaction (p = .062) and 12-month PA status. Simple effects analyses revealed that home access to PA equipment was predictive of PA adoption (OR = 1.73; 95% CI: 1.05, 2.85), but not PA maintenance (OR = 0.88; 95% CI: 0.58, 1.35), whereas self-efficacy and perceived satisfaction were predictive of PA maintenance (OR = 2.65; 95% CI: 1.55, 4.52; OR = 1.95; 95% CI: 0.93, 4.06), but not PA adoption (OR = 1.50; 95% CI: 0.87, 2.57; OR = 0.82, CI: 0.44, 1.52). Conclusion   Results suggest that these psychosocial variables may operate differently in predicting PA adoption versus maintenance.     

Association of progesterone receptor with migraine-associated vertigo

While migraine has been demonstrated to be familial and have genetic contributions, genome-wide linkage analyses and candidate gene studies have highlighted that migraine is genetically complex. Despite substantial efforts, no consistent replication of linkage or association has been reported for common migraine syndromes. Among the candidate genes tested for association with migraine by several groups were female sex hormone genes based on the observation of a much higher incidence of migraine in females. Migraine-associated vertigo (MAV) is a migraine syndrome also much more common in females than males. Because MAV is less common in the general population than migraine or migraine with aura, it may be a better migraine syndrome to detect susceptibility alleles. In this study, we tested the association of two female hormonal genes, progesterone receptor (PGR) and estrogen receptor (ESR1), which were previously reported to be associated with migraine in women. We typed 150 MAV subjects and 145 genomic matched control subjects. One SNP (rs1042838) within PGR, which is in high linkage disequilibrium with the functional PROGINS variant, was significantly associated with MAV (p = 0.0007). Two SNPs (rs2228480 and rs1801132) within ESR1 demonstrated no significant association. No synergistic effect between ESR1 variants and PGR variants was identified.     

<Emphasis Type="Italic">PEMT</Emphasis> G523A (V175M) Is Associated with Sporadic Alzheimer's Disease in a Chinese Population

There is evidence that increased concentrations of circulating homocysteine are associated with Alzheimer's disease (AD). Phosphatidylethanolamine N-methyltransferase (PEMT) is an important catalyst involved in the production of homocysteine. We investigated the association of a functional single nucleotide polymorphism (rs7946) in PEMT with sporadic AD risk in a Han Chinese population that included 386 AD patients and 366 controls. PEMT G523A was genotyped by either sequencing or PCR-restriction fragment length polymorphism analysis. The plasma homocysteine concentrations of 210 subjects were determined by high-performance liquid chromatography. Significant higher frequency of the A allele was detected in AD cases than in controls (A vs. G, p = 0.007, OR = 1.482, 95% CI 1.114–1.972). After adjusting for gender, age/age at onset, and APOE ε4 status, logistic analysis showed rs7946 was associated with AD in a dominant model (AA + GA vs. GG, p = 0.007, OR = 1.596, 95% CI 1.138–2.240). When stratified by APOE ε4 status or gender, the significant difference was only observed in the APOE ε4 non-carriers and in the female subjects, respectively. We did not find a relationship of this polymorphism with plasma homocysteine levels. These results suggested that PEMT G523A is associated with AD and that the A allele is an APOE ε4-independent risk factor for AD among Han Chinese women.     

Circulating B7-H3(CD276) Elevations in Cerebrospinal Fluid and Plasma of Children with Bacterial Meningitis

The objective of this study was to analyze the clinical significance of cerebrospinal fluid (CSF) and plasma concentrations of B7-H3, tumor necrosis factor-alpha (TNF-α), gamma interferon (IFN-γ), and interleukin-17 (IL-17) in bacterial and aseptic meningitis in children. The participants were six children with bacterial meningitis, 16 with aseptic meningitis, and 12 control subjects. All participants were between 2 months and 12 years of age on admission. Cytokines determination was performed by enzyme-linked immunosorbent assay technique. CSF and plasma-circulating B7-H3 were significantly higher in the bacterial meningitis group as compared with the aseptic group (p = 0.001) and the control group (p = 0.000 and p = 0.001 respectively). However, CSF and plasma-circulating B7-H3 in aseptic meningitis were not significantly higher than control group (p = 0.071 and p = 0.72 respectively).CSF and plasma-circulating TNF-α were significantly higher in the bacterial meningitis group as compared with the aseptic group (p = 0.004 and p < 0.0001 respectively) and control group (p = 0.004 and p < 0.0001 respectively). Similarly, we did not observe significant elevated TNF-α levels in CSF and plasma in aseptic group compared with control group (p = 0.03 and p = 0.12 respectively). IFN-γ levels in CSF and plasma were undetectable in control group, and we did not find statistical significances in both of CSF and plasma between the elevated IFN-γ level in bacterial meningitis group and aseptic meningitis group(p = 0.055 and p = 0.095 respectively) CSF and plasma levels of IL-17 were undetectable in all subjects. There were correlations between B7-H3 and TNF-α, IFN-γ (r = 0.875, p = 0.000; r = −0.693, p = 0.000, respectively) in CSF in meningitis subjects. In plasma, levels of B7-H3 in bacterial meningitis on admission correlated positively with TNF-α (r = 0.968, p = 0.002), and white blood cell counts (r = 0.973, p = 0.001). Detectable CSF levels of B7-H3, TNF-α, and IFN-γ on admission were not associated significantly with any of CSF characteristics. Additionally, CSF and plasma levels of B7-H3 decreased remarkably after treatment. Altogether, our data indicated that circulating B7-H3 and TNF-α levels in the CSF and plasma were useful markers for distinguishing bacterial from aseptic meningitis, and Circulating B7-H3 was demonstrated to be useful in evaluating the intensity of the infectious inflammatory process in the central nervous system in children. An erratum to this article can be found at     

Can Psychological Factors Account for a Lack of Nocturnal Blood Pressure Dipping?

Background  In healthy individuals, blood pressure (BP) decreases, or “dips”, during sleep. Ethnicity and high daytime blood pressure level are known markers of nondipping status. The literature on psychological markers of nondipping is scant but suggests that anger/hostility and chronic stress may be contributors to nondipping. Purpose  We have investigated this phenomenon in drug-free hypertensives who participated in a clinical trial and supplied extensive demographic, psychological, and biological risk factor data after medication washout prior to any treatment. Method  Sixty-two patients were available for analysis (n = 30 nondippers). While most studies focus only on systolic BP nondipping, we explicitly studied both systolic and diastolic BP dipping as outcomes given that both have prognostic value. Results  Hierarchical multiple regression revealed that predictor variables in total accounted for 38% of variance in systolic blood pressure dipping and 44% of variance in diastolic blood pressure dipping. A significant positive predictor was alcohol consumption (β = 0.37, t = 2.8, p = 0.007) for systolic BP and β = 0.43, t = 3.7, p = 0.001 for diastolic BP), and an anger diffusion preference was also a positive predictor (β = 0.42, t = 2.7, p = 0.01) for systolic BP dipping. No measure of trait negative affect reached significance as a predictor for systolic or diastolic BP dipping. Conclusion  These findings suggest that for a better understanding of the nondipping phenomenon, behavioral risk factors are important, and anger response styles may also be worthy of further study. Furthermore, anger coping preferences may be as important, or even more so, than levels of negative affect.     

HTR2A is Associated with SSRI Response in Major Depressive Disorder in a Japanese Cohort

Several recent investigations reported that the serotonin 2A receptor gene (HTR2A) was associated with selective serotonin reuptake inhibitors (SSRIs) in major depressive disorder. There have also been two reported association analyses of HTR2A with SSRI response in Japanese MDD patients, but the results were rather inconsistent and both studies had the problem of small sample sizes. Therefore, we conducted a replication association study using a sample larger than those in the two original Japanese studies (265 MDD patients), and found that four SNPs, two functional SNPs (-A1438G: rs6311 and T102C: rs6313) and two SNPs (rs7997012 and rs1928040) in HTR2A, were associated with the therapeutic response to SSRIs. HTR2A was associated with the therapeutic response SSRIs in Japanese MDD patients in a haplotype-wise analysis (P _{all markers} = 0.0136), and a significant association between rs1928040 in HTR2A and SSRI response was detected in MDD (P _{allele-wise analysis} = 0.0252). However, this significance disappeared after Bonferroni correction (P _{allele-wise analysis} = 0.101). In conclusion, we suggest that HTR2A may play an important role in the pathophysiology of the therapeutic response to SSRIs in Japanese MDD patients. However, it will be important to replicate and confirm these findings in other independent studies using large samples.