Shoulder joint synovial chondromatosis presenting as multiple axillary masses: A case report.

Synovial chondromatosis is a rare, benign, proliferative cartilaginous lesion arising from the synovial tissue, tenosynovium, or bursal lining. We describe the case of a patient who initially presented with multiple axillary masses. Breast ultrasound (US) was requested due to the concern of a breast tumor with axillary lymph node metastases. US study was helpful and provided adequate information to suggest the diagnosis.

Direct Injection LC-MS-MS Analysis of Opiates, Methamphetamine, Buprenorphine, Methadone and Their Metabolites in Oral Fluid from Substitution Therapy Patients.

A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was developed, validated and applied to simultaneous analysis of oral fluid samples for the following 10 analytes: methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), buprenorphine, norbuprenorphine, morphine, codeine, 6-acetylmorphine, 6-acetylcodeine, amphetamine, and methamphetamine. The oral fluid sample was briefly centrifuged and the supernatant was directly injected into the LC-MS-MS system operated under reverse-phase chromatography and electrospray ionization (ESI). Deuterated analogs of the analytes were adopted as the internal standards and found to be effective (except for buprenorphine) to compensate for potential matrix effects. Each analytical run took <10 min. Linearity range (r(2) > 0.99) established for buprenorphine and the other nine analytes were 5-100 and 1-100 ng/mL. Intra- and interday precision (% CV) ranges for the 10 analytes were 0.87-12.2% and 1.27-12.8%, while the corresponding accuracy (%) ranges were 91.8-113% and 91.9-111%. Limits of detection and quantitation established for these 10 analytes were in the ranges of 0.1-1.0 and 0.25-1.0 ng/mL (5 ng/mL for buprenorphine). The method was successfully applied to the analysis of 62 oral fluid specimens collected from patients participating in methadone and buprenorphine substitution therapy programs. Analytical results of methadone and buprenorphine were compared with data derived from GC-MS analysis and found to be compatible. Overall, the direct injection LC-MS-MS method performed well, permitting rapid analysis of oral fluid samples for simultaneous quantification of methadone, buprenorphine, opiate and amphetamine drug categories without extensive sample preparation steps.

Methadone concentrations in blood, plasma, and oral fluid determined by isotope-dilution gas chromatography-mass spectrometry.

Methadone (MTD) is widely used for detoxification of heroin addicts and also in pain management programs. Information about the distribution of methadone between blood, plasma, and alternative specimens, such as oral fluid (OF), is needed in clinical, forensic, and traffic medicine when analytical results are interpreted. We determined MTD and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) in blood, plasma, blood cells, and OF by gas chromatography-mass spectrometry (GC-MS) after adding deuterium-labeled internal standards. The analytical limits of quantitation for MTD and EDDP by this method were 20 and 3 ng/mL, respectively. The amounts of MTD and EDDP were higher in plasma (80.4 % and 76.5 %) compared with blood cells (19.6 % and 23.5 %) and we found that repeated washing of blood cells with phosphate-buffered saline increased the amounts in plasma (93.6 % and 88.6 %). Mean plasma/blood concentration ratios of MTD and EDDP in spiked samples (N = 5) were 1.27 and 1.21, respectively. In clinical samples from patients (N = 46), the concentrations of MTD in plasma and whole blood were highly correlated (r = 0.92, p < 0.001) and mean (median) plasma/blood distribution ratios were 1.43 (1.41). The correlations between MTD in OF and plasma (r = 0.46) and OF and blood (r = 0.52) were also statistically significant (p < 0.001) and the mean OF/plasma and OF/blood distribution ratios were 0.55 and 0.77, respectively. The MTD concentration in OF decreased as salivary pH increased (more basic). These results will prove useful in clinical and forensic medicine when MTD concentrations in alternative specimens are compared and contrasted.

Convergent evidence from mouse and human studies suggests the involvement of zinc finger protein 326 gene in antidepressant treatment response.

OBJECTIVES: The forced swim test (FST) is a commonly used model to predict antidepressant efficacy. Uncovering the genetic basis of the model may unravel the mechanism of antidepressant treatment. METHODS: FVB/NJ (FVB) and C57BL/6J (B6) were first identified as the response and non-response strains to fluoxetine (a serotonin-specific reuptake inhibitor antidepressant) treatment in the mouse FST. Simple-interval (SIM) and composite-interval (CIM) mappings were applied to map the quantitative trait loci (QTLs) of the anti-immobility effect of fluoxetine in FST (FST(FLX)) in 865 male B6×FVB-F2 mice. The brain mRNA expressions of the gene with the maximum QTL-linkage signal for FST(FLX) after the FST were compared between B6 and FVB mice and also compared between fluoxetine and saline treatment. The association of the variants in the human homologue of the mouse FST(FLX)-QTL gene with major depressive disorder (MDD) and antidepressant response were investigated in 1080 human subjects (MDD/control = 582/498). RESULTS: One linkage signal for FST(FLX)-QTL was detected at an intronic SNP (rs6215396) of the mouse Zfp326 gene (maximal CIM-LOD = 9.36). The Zfp326 mRNA expression in the FVB thalamus was significantly down-regulated by fluoxetine in the FST, and the higher FVB-to-B6 Zfp326 mRNA expressions in the frontal cortex, striatum and hypothalamus diminished after fluoxetine treatment. Two coding-synonymous SNPs (rs2816881 and rs10922744) in the human homologue of Zfp326, ZNF326, were significantly associated with the 8-week antidepressant treatment response in the MDD patients (Bonferroni-corrected p = 0.004-0.028). CONCLUSIONS: The findings suggest the involvement of the Zfp326 and ZNF326 genes in antidepressant treatment response.

The influence of apolipoprotein E Epsilon4 polymorphism on qEEG profiles in healthy young females: a resting EEG study.

The epsilon4 allele of the Apolipoprotein E (ApoE) gene has been linked to various neurological conditions and the aging process in the elderly. However, evidence has suggested that the influence of ApoE epsilon4 may commence in early life. This study examined the modulatory effects of ApoE epsilon4 on regional neural activity as well as inter-regional neural interactions in a young population aged 19-21. Blood samples and resting state eyes-closed EEG signals were collected from 265 healthy females, and stratified into two groups: epsilon4 carriers and non-carriers. The values of the log-transformed mean power of 18 electrodes and the mutual information of 20 channel pairs across delta, theta, alpha and beta frequencies were analyzed. Our connectivity analysis was based on information theory, which combined Morlet wavelet transform and mutual information calculation. Between-group statistics were performed by independent t-test. We notice a consistent trend across the brain, in which ApoE epsilon4 carriers possess lower regional power at the alpha band. The epsilon4 allele is also associated with lower regional power at the theta frequency in the left frontal and posterior brain regions. Functional connectivity analyses reveal a right-lateralized network that differentiates epsilon4 carriers and non-carriers, with lower connectivity strengths for the former. Our tonic EEG analyses complement those of previous reports in that the ApoE epsilon4 allele has a negative impact on regional neural synchronization and inter-regional neural interaction.

The influence of dopamine receptor d4 polymorphism on resting EEG in healthy young females.

The polymorphism of variable number of tandem repeat (VNTR) in dopamine receptor D4 (DRD4) gene exon III has been linked to various neuro-psychiatric conditions with disinhibition/impulsivity as one of the core features. This study examined the modulatory effects of long-allele variant of DRD4 VNTR on the regional neural activity as well as inter-regional neural interactions in a young female population. Blood sample and resting state eyes-closed EEG signals were collected in 233 healthy females, stratified into two groups by polymerase chain reaction: long-allele carriers (>4- repeat) and non-carriers (<=4-repeat/<=4-repeat). The values of mean power of 18 electrodes and mutual information of 38 channel pairs across theta, alpha, and beta frequencies were analyzed. Our connectivity analysis was based on information theory, which combined Morlet wavelet transform and mutual information calculation. Between-group differences of regional power and connectivity strength were quantified by independent t-test, while between-group differences in global trends were examined by non-parametric analyses. We noticed that DRD4 VNTR long-allele was associated with decreased global connectivity strength (from non-parametric analysis), especially over bi-frontal, biparietal and right fronto-parietal and right fronto-temporal connections (from independent t-tests). The between-group differences in regional power were not robust. Our findings fit with the networks of response inhibition, providing evidence bridging DRD4 long-allele and disinhibition/impulsivity in neuropsychiatric disorders. We suggest future DRD4 studies of imaging genetics incorporate connectivity analysis to unveil its impact on cerebral network.

An exploratory study of religious involvement as a moderator between anxiety, depressive symptoms and quality of life outcomes of older adults.

AIMS: The aims of this study were to examine the relationships among religion, religious involvement, anxiety, depressive symptoms and quality of life in older adults with psychological problems and whether religious involvement moderated anxiety and depressive symptoms on the outcome of quality of life. Evidence for the mechanism through which religious involvement exerts its moderated effect on anxiety and depressive symptoms was provided. BACKGROUND: Older adults suffering from stress may consequently have anxiety or depressive symptoms and their quality of life is also influenced. The meanings of religious involvement are well documented but less is known about moderating characteristics that determine which older adults with psychological problems are most likely to benefit. DESIGN: A correlational, cross-sectional study. METHODS: The study was conducted in 2007-2008 with a purposive sample of 115 older adults who were 60 years of age or older at a psychiatric centre in Taiwan. Three reliable and valid questionnaires and a demographic sheet were administered. RESULTS: Approximately 75% of older adults had mild to severe anxiety; 76·5% had depressive symptoms; and 67·8% of participants who had depressive symptoms also had comorbid anxiety. Findings indicated that there was a significant moderating effect for religious involvement on the quality of life outcome. Religious involvement significantly moderated anxiety and depressive symptoms on quality of life. Moreover, religious participants had a better quality of life and had lower anxiety and depressive symptoms than non-religious participants. CONCLUSION: Testing for moderating effects provides important information regarding the benefits of religious involvement. The current study reveals that religious participants have lower levels of depressive symptoms and anxiety and better quality of life than non-religious ones. Religious involvement plays a role in buffering the relationship between psychological problems and quality of life. RELEVANCE TO CLINICAL PRACTICE: Nurses can encourage individuals with health problems to participate in religious involvement, which may help individuals to experience a feeling of support and enhance their quality of life.

The implication of functional connectivity strength in predicting treatment response of major depressive disorder: a resting EEG study.

Predicting treatment response in major depressive disorder (MDD) has been an important clinical issue given that the initial intent-to-treat response rate is only 50 to 60%. This study was designed to examine whether functional connectivity strengths of resting EEG could be potential biomarkers in predicting treatment response at 8 weeks of treatment. Resting state 3-min eyes-closed EEG activity was recorded at baseline and compared in 108 depressed patients. All patients were being treated with selective serotonin-reuptake inhibitors. Baseline coherence and power series correlation were compared between responders and non-responders evaluated at the 8th week by Hamilton Depression Rating Scale. Pearson correlation and receiver operating characteristic (ROC) analyses were applied to evaluate the performance of connectivity strengths in predicting/classifying treatment responses. The connectivity strengths of right fronto-temporal network at delta/theta frequencies differentiated responders and non-responders at the 8th week of treatment, such that the stronger the connectivity strengths, the poorer the treatment response. ROC analyses supported the value of these measures in classifying responders/non-responders. Our results suggest that fronto-temporal connectivity strengths could be potential biomarkers to differentiate responders and slow responders or non-responders in MDD.

Do resting brain dynamics predict oddball evoked-potential?

BACKGROUND: The oddball paradigm is widely applied to the investigation of cognitive function in neuroscience and in neuropsychiatry. Whether cortical oscillation in the resting state can predict the elicited oddball event-related potential (ERP) is still not clear. This study explored the relationship between resting electroencephalography (EEG) and oddball ERPs. The regional powers of 18 electrodes across delta, theta, alpha and beta frequencies were correlated with the amplitude and latency of N1, P2, N2 and P3 components of oddball ERPs. A multivariate analysis based on partial least squares (PLS) was applied to further examine the spatial pattern revealed by multiple correlations. RESULTS: Higher synchronization in the resting state, especially at the alpha spectrum, is associated with higher neural responsiveness and faster neural propagation, as indicated by the higher amplitude change of N1/N2 and shorter latency of P2. None of the resting quantitative EEG indices predict P3 latency and amplitude. The PLS analysis confirms that the resting cortical dynamics which explains N1/N2 amplitude and P2 latency does not show regional specificity, indicating a global property of the brain. CONCLUSIONS: This study differs from previous approaches by relating dynamics in the resting state to neural responsiveness in the activation state. Our analyses suggest that the neural characteristics carried by resting brain dynamics modulate the earlier/automatic stage of target detection.

Clustering heart rate dynamics is associated with ß-adrenergic receptor polymorphisms: analysis by information-based similarity index.

BACKGROUND: Genetic polymorphisms in the gene encoding the ß-adrenergic receptors (ß-AR) have a pivotal role in the functions of the autonomic nervous system. Using heart rate variability (HRV) as an indicator of autonomic function, we present a bottom-up genotype-phenotype analysis to investigate the association between ß-AR gene polymorphisms and heart rate dynamics. METHODS: A total of 221 healthy Han Chinese adults (59 males and 162 females, aged 33.6 ± 10.8 years, range 19 to 63 years) were recruited and genotyped for three common ß-AR polymorphisms: ß(1)-AR Ser49Gly, ß(2)-AR Arg16Gly and ß(2)-AR Gln27Glu. Each subject underwent two hours of electrocardiogram monitoring at rest. We applied an information-based similarity (IBS) index to measure the pairwise dissimilarity of heart rate dynamics among study subjects. RESULTS: With the aid of agglomerative hierarchical cluster analysis, we categorized subjects into major clusters, which were found to have significantly different distributions of ß(2)-AR Arg16Gly genotype. Furthermore, the non-randomness index, a nonlinear HRV measure derived from the IBS method, was significantly lower in Arg16 homozygotes than in Gly16 carriers. The non-randomness index was negatively correlated with parasympathetic-related HRV variables and positively correlated with those HRV indices reflecting a sympathovagal shift toward sympathetic activity. CONCLUSIONS: We demonstrate a bottom-up categorization approach combining the IBS method and hierarchical cluster analysis to detect subgroups of subjects with HRV phenotypes associated with ß-AR polymorphisms. Our results provide evidence that ß(2)-AR polymorphisms are significantly associated with the acceleration/deceleration pattern of heart rate oscillation, reflecting the underlying mode of autonomic nervous system control.

The influence of serotonin transporter polymorphisms on cortical activity: a resting EEG study.

BACKGROUND: The serotonin transporter gene (5-HTT) is a key regulator of serotonergic neurotransmission and has been linked to various psychiatric disorders. Among the genetic variants, polymorphisms in the 5-HTT gene-linked polymorphic region (5-HTTLPR) and variable-number-of-tandem-repeat in the second intron (5-HTTVNTR) have functional consequences. However, their genetic impact on cortical oscillation remains unclear. This study examined the modulatory effects of 5-HTTLPR (L-allele carriers vs. non-carriers) and 5-HTTVNTR (10-repeat allele carriers vs. non-carriers) polymorphism on regional neural activity in a young female population. METHODS: Blood samples and resting state eyes-closed electroencephalography (EEG) signals were collected from 195 healthy women and stratified into 2 sets of comparisons of 2 groups each: L-allele carriers (N=91) vs. non-carriers for 5-HTTLPR and 10-repeat allele carriers (N=25) vs. non-carriers for 5-HTTVNTR. The mean power of 18 electrodes across theta, alpha, beta, gamma, gamma1, and gamma2 frequencies was analyzed. Between-group statistics were performed by an independent t-test, and global trends of regional power were quantified by non-parametric analyses. RESULTS: Among 5-HTTVNTR genotypes, 10-repeat allele carriers showed significantly low regional power at gamma frequencies across the brain. We noticed a consistent global trend that carriers with low transcription efficiency of 5-HTT possessed low regional powers, regardless of frequency bands. The non-parametric analyses confirmed this observation, with P values of 3.071×10-8 and 1.459×10-12 for 5-HTTLPR and 5-HTTVNTR, respectively. CONCLUSIONS AND LIMITATIONS: Our analyses showed that genotypes with low 5-HTT activity are associated with less local neural synchronization during relaxation. The implication with respect to genetic vulnerability of 5-HTT across a broad range of psychiatric disorders is discussed. Given the low frequency of 10-repeat allele of 5-HTTVNTR in our research sample, the possibility of false positive findings should also be considered.

Cortical mechanisms of the symptomatology in major depressive disorder: a resting EEG study.

BACKGROUND: Diagnosis and treatment rely on symptom criteria in modern psychiatry. However, the cortical mechanisms of symptomatology in major depressive disorder (MDD) are still not clear. This study examined neural correlates of symptom clusters of MDD by electroencephalography (EEG). METHODS: Resting state eye-closed EEG signals were recorded in 196 depressive patients. Quantitative EEG (qEEG) of regional power, coherence and power series correlation across delta, theta, alpha and beta frequencies were used to correlate with overall depression severity evaluated by the Hamilton Depression Rating Scale (HDRS). Further, statistical comparisons between patients with high vs. low qEEG indices (median-split) were undertaken regarding symptom severity of core depression, sleep, activity, psychic anxiety, somatic anxiety, and delusion. RESULTS: None of the qEEG indices significantly correlated with overall depression severity or differentiated symptom severity of core depression, sleep, activity and psychic anxiety. A higher symptom severity of somatic anxiety was associated with higher regional power over widespread cortical regions and lower strengths at bi-temporal, temporo-parietal and fronto-parietal connections. A higher symptom severity of delusion was associated with higher regional power in the frontal and temporal regions, and lower strengths at inter-hemispheric (frontal, temporal and parietal) and fronto-temporo-parietal connections. LIMITATIONS: Our EEG recording with sampling rate of 128Hz and 20 electrodes may provide restricted spatial and temporal precision. CONCLUSIONS: Our results suggest that cortical mechanisms play important roles in the symptom manifestation of cognitive distortion (sub-score of delusion) and somatic anxiety in MDD. Our findings further imply that psychic anxiety and somatic anxiety are distinct entities.

Reduced physiologic complexity is associated with poor sleep in patients with major depression and primary insomnia.

BACKGROUND: Depression is known to be associated with altered cardiovascular variability and increased cardiovascular comorbidity, yet it is unknown whether altered cardiac autonomic function in depression is associated with insomnia, a common symptom comorbid with depression. This study aimed to investigate the long-term diurnal profile of autonomic function as measured by heart rate variability (HRV) in both major depression and primary insomnia patients. METHOD: A total of 52 non-medicated patients with major depression, 47 non-medicated patients with primary insomnia, and 88 matched controls without insomnia were recruited. Each subject was assessed by means of sleep and mood questionnaires and underwent twenty-four-hour ambulatory electrocardiogram monitoring. Standard HRV analysis and a well-validated complexity measure, multiscale entropy, were applied to comprehensively assess the diurnal profiles of autonomic function and physiologic complexity in our study sample. RESULTS: Compared with the controls, the patients with major depression and those with primary insomnia exhibited significant reductions in parasympathetic-related HRV indices, and this association was mainly driven by the presence of poor sleep. Both groups of patients also exhibited significant reductions in physiologic complexity during the sleep period as compared with the healthy controls. Alterations in HRV indices were correlated with perceived sleep questionnaire scores but not with depression scales. CONCLUSIONS: Our findings suggest a pivotal role of sleep disturbance in regulating cardiovascular variability in major depression and primary insomnia patients. These findings could highlight the importance of treating insomnia as an independent disease rather than a symptom.

The effects of catechol-O-methyl-transferase polymorphism Val158Met on functional connectivity in healthy young females: a resting EEG study.

The catechol-O-methyl-transferase (COMT) gene has been linked to a wide spectrum of human phenotypes, including cognition, affective response, pain sensitivity, anxiety and psychosis. This study examined the modulatory effects of COMT Val158Met on neural interactions, indicated by connectivity strengths. Blood samples and resting state eyes-closed EEG signals were collected in 254 healthy young females. The COMT Val158Met polymorphism was decoded into 3 groups: Val/Val, Val/Met and Met/Met. The values of mutual information of 20 frontal-related channel pairs across delta, theta, alpha and beta frequencies were analyzed based on the time-frequency mutual information method. Our one-way ANOVA analyses revealed that the significant connection-frequency pairs were relatively left lateralized (P<0.01) and included F7-T3 and F7-C3 at delta frequency, and F3-F4, F7-T3, F7-C3, F7-P3, F3-C3, F3-F7 and F4-F8 at theta frequency. The F-test at F7-T3 and F7-C3 theta surpassed the statistical threshold of P<0.003 (after Bonferroni correction). For all the above connection-frequency pairs, there was a dose-dependent trend in the connectivity strengths of the alleles as follows: Val/Val>Val/Met>Met/Met. Our analyses complemented previous literature regarding neural modulation by the COMT Val158Met polymorphism. The implication to the pathogenesis in schizophrenia was also discussed. Further studies are needed to clarify whether there is gender difference on this gene-brain interaction.

Evidence of involvement of the human Par-4 (PAWR) gene in major depressive disorder.

UNLABELLED: QBJECTIVES: The aim of the study was to examine the associations between genetic variations in the human PAWR gene and major depressive disorder (MDD) as well as the response to antidepressant treatment. METHODS: Six-hundred and two patients with MDD and 543 controls were included in the study; among the MDD patients, 268 were followed-up for a further 8 weeks in order to assess their response to treatment with selective serotonin reuptake inhibitors (SSRIs). Six polymorphisms (rs17005769, rs4842318, rs7305141, rs2307223, rs8176874 and rs2307220) of the PAWR gene were investigated with regard to their association with MDD and antidepressant treatment efficacy. RESULTS: One polymorphism, rs8176874, was in genotypic (uncorrected P=0.005) and allelic (uncorrected P=0.0015) association with MDD. Several haplotypes spanning rs7305141-rs2307223-rs8176874 were also significantly associated with MDD after correction for multiple testing (corrected P<0.05). However, neither single-marker nor haplotype-based analyses suggested an association between the studied markers and SSRI treatment response. CONCLUSIONS: Genetic variations in the PAWR gene are related to susceptibility to MDD but not to SSRI treatment response.

Cortical and subcortical abnormalities in late-onset depression with history of suicide attempts investigated with MRI and voxel-based morphometry.

Late-onset major depression is thought to have a biological (vascular) basis, which could be a result of brain structure change. Vascular lesions can affect both the gray matter (GM) and white matter (WM), while most previous studies addressed WM abnormality. This study explored the disease- and symptom (history of suicide attempt) -related GM morphometry in elderly male patients with late-onset depression. A total of 70 patients with depression admitted to our geriatric psychiatric ward were investigated, and 26 age-matched males were recruited as controls. We used T1-weighted magnetic resonance imaging (MRI) to obtain cerebral structural information and adopted voxel-based morphometry (VBM) to investigate brain volume change related to disease (depression vs control) and symptom (depression with history of suicide attempt vs depression without history of suicide attempt). Late-onset depression was associated with smaller volumes in several regions of GM (insula and the posterior cingulate region) and WM (subcallosal cingulate cortex, floor of lateral ventricles, parahippocampal region, insula, and the cerebellum). Compared with nonsuicidal counterpart, suicidal depression was associated with decreased GM and WM volume in the frontal, parietal, and temporal regions, and the insula, lentiform nucleus, midbrain, and the cerebellum. Marked regional volume reduction was noticed at dorsal medial prefrontal cortex. Our results demonstrate that the development of suicidal behaviors in major depression is related to widespread but discrete volume reduction in several cortical and subcortical structures, fitting with the hypothesis that decreased cerebral volume in certain regions renders biological susceptibility to attempt suicide during depressive states.

Risk factors of isolated antibody against core antigen of hepatitis B virus: association with HIV infection and age but not hepatitis C virus infection.

BACKGROUND: Isolated antibody to hepatitis B core antigen (anti-HBc) is defined as seropositivity for anti-HBc in the absence of hepatitis B surface antigen (HBsAg) and antibody to HBsAg (anti-HBs). It is commonly found in HIV-infected persons or hepatitis C virus (HCV)-infected persons, but the risk factors for isolated anti-HBc remain uncertain, especially in regions that are hyperendemic for hepatitis B virus (HBV) infection. METHODS: This cross-sectional study included a cohort of 955 nonhemophiliac, HIV-infected patients, diagnosed between 1988 and 2009, and 643 HIV-uninfected injection drug users (IDUs) attending the methadone clinic between August 2007 and May 2009, with available HBV serological data. The medical records were reviewed to identify the risk factors associated with seropositivity of isolated anti-HBc. RESULTS: The overall seroprevalence of isolated anti-HBc was 12.1% (193 of 1598), in which occult HBV infection accounted for 1.6% (3 of 185) and the majority (91.2 %, 176 of 193) had low titers of anti-HBs (3.6 +/- 2.9 IU/L). Subjects with isolated anti-HBc were significantly older (40.7 +/- 9.3 versus 36.9 +/- 8.0, respectively, P < 0.0001). There was a significantly increasing trend in the prevalence of isolated anti-HBc with age, from 4.0% in those younger than 30 years to 22.5% after 50 years of age (test for trend, P < 0.0001). A significantly higher prevalence of isolated anti-HBc was observed in HIV-infected subjects [14.0% (134 of 955) versus 9.2% (59 of 643), adjusted odds ratio, 1.64; P < 0.01], but not in those with HCV infection (P = 0.18). CONCLUSIONS: Isolated anti-HBc seropositivity was significantly associated with HIV infection, and older age. HCV infection was not associated with isolated anti-HBc in a country hyperendemic with HBV infection, even in populations with a high prevalence of HCV infection. The majority was not attributable to occult HBV infection, but rather, low level of anti-HBs, suggesting that HBV vaccination may not be required.

BDNF Val66Met polymorphism alters sympathovagal balance in healthy subjects.

A common polymorphism of the brain-derived neurotrophic factor (BDNF) gene (Val66Met) has been implicated in anxiety, which is associated with lower vagal activity. We hypothesize that the BDNF Val66Met polymorphism may have a modulatory effect on the cardiac sympathovagal balance. A total of 211 healthy Chinese-Han adults (58 male, 153 female, aged 33.3 +/- 10.3 years) were recruited with three BDNF genotypes: Val/Val (47, 22.3%), Val/Met (108, 51.2%), and Met/Met (56, 26.5%). Autonomic function was assessed via an analysis of heart rate variability. Reductions in high-frequency power, an index for parasympathetic activity, and increases in the low-frequency/high-frequency ratio, an index for sympathovagal balance, were found in subjects bearing the Met/Met genotype as compared to the Val/Val group. These results suggest that an altered sympathovagal balance with relatively decreased parasympathetic activity is associated with the Met/Met genotype, suggesting a potential role for the studied BDNF polymorphism in modulating cardiac autonomic functions.

Support for the involvement of the KCNK2 gene in major depressive disorder and response to antidepressant treatment.

OBJECTIVE: The aim of this study was to examine the associations between genetic variations in the human KCNK2 gene and major depressive disorder (MDD) and response to antidepressant treatment. METHOD: Four hundred and forty-nine patients with MDD and 421 normal controls were included in the study; among the MDD patients, 158 were further followed-up for 8 weeks to assess their response to antidepressant treatment. Five polymorphisms (rs12131478, rs6667764, rs10494994, rs11583745 and rs6686529) of the KCNK2 gene were investigated in terms of their association with MDD and antidepressant treatment efficacy. RESULTS: The genotype frequency of rs6686529 differed significantly between the MDD patients and controls (uncorrected P = 0.00052) and remained statistically significant after correction for multiple comparisons. Individuals with homozygous genotypes (CC or GG) showed greater susceptibility to MDD than those with heterozygous genotypes, indicating a possible heterosis effect of the polymorphism on MDD. In addition, this polymorphism also affected the efficacy of antidepressant treatment: the CC carriers had a greater probability of achieving remission after 8 weeks of treatment than the G-allele carriers [odds ratio = 2.55 (95% confidence interval = 1.11-5.88)]. CONCLUSION: Our findings are in line with those of animal studies, and show that KCNK2 is related to the susceptibility to MDD, and involved in antidepressant treatment response. However, the finding of heterosis association of rs6686529 and MDD may be mechanistic, and further replication studies will be essential.

Haplotype analysis of single nucleotide polymorphisms in the vascular endothelial growth factor (VEGFA) gene and antidepressant treatment response in major depressive disorder.

Vascular endothelial growth factor (VEGF) has been implicated in neurotrophy and neurogenesis, which play a pivotal role in brain development and may be involved in antidepressant therapeutic mechanisms. Recent animal studies demonstrate that VEGF levels are increased by several antidepressants, including selective serotonin reuptake inhibitors, and that VEGF signalling is required for antidepressant-induced behavioural response. We hypothesized that common genetic variants in the VEGF gene (official gene name: VEGFA) may be associated with the therapeutic response to antidepressants in major depressive disorders (MDD). Seven VEGFA polymorphisms were genotyped in 351 patients with MDD who were treated with selective serotonin reuptake inhibitor (fluoxetine or citalopram) antidepressants and who were were studied in a therapeutic evaluation for at least 4 weeks. Of the 351 patients, 158 completed an 8-week therapeutic evaluation. No significant association with either 4-week or 8-week antidepressant therapeutic effect was shown in the alleles and genotypes of single loci, or haplotypes from two blocks constructed from these polymorphisms. Our findings suggested that VEGFA genetic variants do not play a major role in the response to selective serotonin reuptake inhibitors.