Ying He

Shorter telomere length in peripheral blood leukocytes is associated with childhood autism

Telomeres are protective chromosomal structures that play a key role in preserving genomic stability. Epidemiologic studies have shown that the abnormal telomere length in leukocytes is associated with some mental disorders and age-related diseases. However, the association between leukocyte telomere length and autism has not been investigated. Here we investigated the possible association between relative telomere length (RTL) in peripheral blood leukocytes and childhood autism by using an established real-time polymerase chain reaction method. We observed significantly shorter RTL in patients with childhood autism than in controls (p = 0.006). Individuals with shorter RTL had a significantly increased presence of childhood autism compared with those who had long RTL. In patients, we found that family training interventions have a significant effect on telomere length (P = 0.012), but no correlations between RTL and clinical features (paternal age, maternal age, age of onset, illness of duration, CARS score and ABC score) were observed in this study. These results provided the first evidence that shorter leukocytes telomere length is significantly associated with childhood autism. The molecular mechanism underlying telomere length may be implicated in the development of autism.

Association of telomere length and mitochondrial DNA copy number with risperidone treatment response in first-episode antipsychotic-naive schizophrenia.

Accumulating evidence indicates a putative association of telomere length and mitochondrial function with antipsychotics response in schizophrenia (SCZ). However, pharmacological findings were limited and no previous work has assessed this in a prospective longitudinal study. This study assessed telomere length and mitochondrial DNA copy number in first-episode antipsychotic-naïve SCZ patients with 8-week risperidone treatment to evaluate the association between these biomarkers and clinical treatment response. We recruited 137 first-episode antipsychotic-naive SCZ patients (and 144 controls) at baseline and 89 patients completed the 8-week follow-up. Patients, completed follow-up, were divided into Responders (Nu2009=u200946) and Non-Responders (Nu2009=u200943) according to the percentage of symptoms improvement. Linear regression analyses show that SCZ patients had significantly lower mtDNA copy number (βu2009=u2009−0.108, pu2009=u20090.002), and no alteration of telomere length when compared with healthy controls. In addition, compared with Non-Responders, Responders had significantly lower mtDNA copy number (βu2009=u2009−0.178, pu2009=u20090.001), and longer telomere length (βu2009=u20090.111, pu2009=u20090.071) before the 8-week treatment. After treatment, Responders persisted lower mtDNA copy number comparing with No-Responders (partial η2u2009=u20090.125, pu2009=u20090.001). These findings suggest that telomere length and mtDNA copy number may hold the potential to serve as predictors of antipsychotic response of SCZ patients.

Elevated mitochondrial DNA copy number in peripheral blood cells is associated with childhood autism

BackgroundSeveral lines of evidence indicate mitochondrial impairment in the pathophysiology of autism. As one of the most common biomarkers for mitochondrial dysfunction, mitochondrial DNA (mtDNA) copy number has also been linked to autism, but the relationship between mtDNA copy number and autism was still obscured. In this study, we performed a case–control study to investigate whether mtDNA copy number in peripheral blood cells is related to patients with autism.MethodsRelative mtDNA copy number in peripheral blood cells was measured by using real-time polymerase chain reaction method. The participants in this study included 78 patients with childhood autism and 83 typically developing children.ResultsWe observed children with autism had significantly elevated relative mtDNA copy number than healthy controls (Betau2009=u2009−0.173, Pu2009=u20090.0003). However, there were no significant correlations between mtDNA copy number and clinical features (paternal age, maternal age, age of onset, illness of duration, CARS score and ABC score) in childhood autism.ConclusionWe show that elevated mtDNA copy number in peripheral blood is associated with autism, indicating that there may be mitochondrial dysfunction in children with autism.

Leukocyte Mitochondrial DNA Copy Number in Blood Is Not Associated with Major Depressive Disorder in Young Adults

Background Major depressive disorder (MDD) is the leading cause of disability worldwide, and has significant genetic predisposition. Mitochondria may have a role in MDD and so mitochondrial DNA (mtDNA) has been suggested as a possible biomarker for this disease. We aimed to test whether the mtDNA copy number of peripheral blood leukocytes is related to MDD in young adults. Methods A case-control study was conducted with 210 MDD patients and 217 healthy controls (HC). The mtDNA copy number was measured by quantitative polymerase chain reaction (qPCR) method. Depression severity was assessed by the Hamilton-17 Depression Rating Scale (HDRS-17). Results We found no significant differences in mtDNA copy number between MDD patients and HC, though the power analysis showed that our sample size has enough power to detect the difference. There were also no significant correlations between mtDNA copy number and the clinical characteristics (such as age, age of onset, episodes, Hamilton Depression Rating Scale (HDRS) score and Global Assessment of Function Scale (GAF) score) in MDD patients. Conclusion Our study suggests that leukocyte mtDNA copy number is unlikely to contribute to MDD, but it doesn’t mean that we can exclude the possibility of involvement of mitochondria in the disease. Further studies are required to elucidate whether mtDNA can be a biomarker of MDD.

A Review of the Functional and Anatomical Default Mode Network in Schizophrenia

Schizophrenia is a severe mental disorder characterized by impaired perception, delusions, thought disorder, abnormal emotion regulation, altered motor function, and impaired drive. The default mode network (DMN), since it was first proposed in 2001, has become a central research theme in neuropsychiatric disorders, including schizophrenia. In this review, first we define the DMN and describe its functional activity, functional and anatomical connectivity, heritability, and inverse correlation with the task positive network. Second, we review empirical studies of the anatomical and functional DMN, and anti-correlation between DMN and the task positive network in schizophrenia. Finally, we review preliminary evidence about the relationship between antipsychotic medications and regulation of the DMN, review the role of DMN as a treatment biomarker for this disease, and consider the DMN effects of individualized therapies for schizophrenia.

N-Acetylaspartate Reduction in the Medial Prefrontal Cortex Following 8 weeks of Risperidone Treatment in First-Episode Drug-Naive Schizophrenia Patients

It is unclear whether N-acetylaspartate (NAA) depletions documented in schizophrenia patients might be due to the disease progression or medications. Here we investigated longitudinal NAA changes in drug-naïve first-episode patients (FEP) who are relatively free from chronicity. Forty-two drug-naïve FEP and 38 controls were enrolled in this study to explore the effect of 8-week risperidone monotherapy on NAA. All spectra were obtained from the medial prefrontal cortex (MPFC) on a 3.0u2005T MRI and analyzed with LCModel. At baseline, patients presented no significant differences in NAA (P = 0.084) or NAA/Cr + Pcr (P = 0.500) compared to controls; NAA levels were negatively correlated with PANSS total scores (P = 0.001) and WCST-PE (P = 0.041). After treatment, patients demonstrated significant reductions of NAA (P < 0.001) and NAA/Cr + Pcr (P < 0.001), and significant improvement in PANSS-P (P < 0.001) and PANSS-G (P < 0.001) symptoms. We detected no significant correlations between NAA alterations and PANSS-P (P = 0.679) or PANSS-G (P = 0.668) symptom changes; nor did NAA/Cr + Pcr changes with alterations in PANSS-P (P = 0.677) and PANSS-G (P = 0.616). This is the first evidence that short-term risperidone treatment induces an acute reduction of MPFC NAA during the early phase of schizophrenia, which may be a previously unavailable biomarker to indicate risperidone with a similar pharmacological mechanism, although the functional significance is still unclear.

Association between childhood trauma and accelerated telomere erosion in adulthood: A meta-analytic study

BACKGROUNDnChildhood trauma has long-term sequelae on health status and contributes to numbers of somatic and mental disorders in later life. Findings from experimental studies in animals suggest that telomere erosion may be a mediator of this relationship. However, results from human studies are heterogeneous. To address these inconsistencies, we performed a meta-analysis regarding the association between childhood trauma and telomere length in adulthood.nnnMETHODnArticles were identified by systematically searching the Medline, EMBASE and Web of Science databases. Twenty four studies, which include twenty six sample sets and 30,919 participants, met the inclusion criteria for meta-analyses.nnnRESULTSnThis meta-analyses revealed that individuals experienced childhood trauma have accelerated telomere erosion in adulthood, with a small effect size (rxa0=xa0-0.05, 95% CIxa0=xa0-0.08-0.03, pxa0<xa00.001). Subgroup analyses by type of childhood trauma revealed a trend in difference between groups (Qxa0=xa05.24, pxa0=xa00.07). Analyses for individual trauma types revealed a significant association between childhood separation and telomere erosion (rxa0=xa0-0.09, pxa0<xa00.001), but not for physical abuse, sexual abuse and loss of a parent.nnnCONCLUSIONnThis meta-analysis demonstrated a significant association between childhood trauma and accelerated telomere erosion in adulthood, and further revealed that different trauma types have various impacts on telomere. Additional research on the mechanism that links the individual types of childhood trauma with telomere is needed in the future.

Molecular imaging of striatal dopamine transporters in major depression—A meta-analysis

BACKGROUNDnIncreasing studies have revealed the dopamine transporter (DAT) availability altered in striatum associated with major depression. However, the results remain inconsistent.nnnMETHODSnTo assess the alteration of striatal DAT availability in major depression, we performed a meta-analysis based on 12 case-control molecular imaging studies, including a total of 209 depressed patients and 314 healthy controls. Hedges׳ g and corresponding 95% confidence intervals (CIs) for striatal DAT availability in major depression compared with controls were estimated.nnnRESULTSnOur meta-analysis revealed no evidence for the alteration of striatal DAT availability in major depression (Hedges׳ g=0.09, CI 95% from -0.43 to 0.61, P=0.73). Meta-regression analyses suggested that there were no moderating effects for age, gender, year of publication, sample size, medication exposures and severity of depression on the hedges׳g values for striatal DAT availability.nnnLIMITATIONSnThe results should be treated with caution because of the significant heterogeneity and the potential interference of confounding factors in this meta-analysis.nnnCONCLUSIONSnOur results showed no altered striatal DAT availability in major depression and indicated that striatal DAT may not implicated in the pathophysiology of major depression.

Whole-genome sequencing of monozygotic twins discordant for schizophrenia indicates multiple genetic risk factors for schizophrenia

Schizophrenia is a common disorder with a high heritability, but its genetic architecture is still elusive. We implemented whole-genome sequencing (WGS) analysis of 8 families with monozygotic (MZ) twin pairs discordant for schizophrenia to assess potential association of de novo mutations (DNMs) or inherited variants with susceptibility to schizophrenia. Eight non-synonymous DNMs (including one splicing site) were identified and shared by twins, which were either located in previously reported schizophrenia risk genes (p.V24689I mutation in TTN, p.S2506T mutation in GCN1L1, IVS3+1Gxa0>xa0T in DOCK1) or had a benign to damaging effect according to in silico prediction analysis. By searching the inherited rare damaging or loss-of-function (LOF) variants and common susceptible alleles from three classes of schizophrenia candidate genes, we were able to distill genetic alterations in several schizophrenia risk genes, including GAD1, PLXNA2, RELN and FEZ1. Four inherited copy number variations (CNVs; including a large deletion at 16p13.11) implicated for schizophrenia were identified in four families, respectively. Most of families carried both missense DNMs and inherited risk variants, which might suggest that DNMs, inherited rare damaging variants and common risk alleles together conferred to schizophrenia susceptibility. Our results support that schizophrenia is caused by a combination of multiple genetic factors, with each DNM/variant showing a relatively small effect size.

Short-term Effects of Risperidone Monotherapy on Spontaneous Brain Activity in First-episode Treatment-naïve Schizophrenia Patients: A Longitudinal fMRI Study.

It is unclear whether abnormal spontaneous neural activation patterns found in chronic schizophrenia patients (CSP) are part of the pathogenesis of disease, consequences of chronic illness, or effects of antipsychotic treatment. We performed a longitudinal resting-state functional magnetic resonance imaging (fMRI) study in 42 treatment-naïve first-episode schizophrenia patients (FESP) at baseline and then after 8-weeks of risperidone monotherapy, and compared the findings to 38 healthy volunteers. Spontaneous brain activity was quantified using the fractional amplitude of low-frequency fluctuations (fALFF) and regional homogeneity (ReHo) and compared between patients and controls. Pretreatment, patients exhibited higher fALFF in left caudate compared with controls. After treatment, patients had elevated fALFF in bilateral putamen and right caudate, and increased ReHo in right caudate and left putamen. Greater increase of fALFF in the left putamen correlated with less improvement in positive symptoms. Thus, abnormalities of spontaneous neural activity in chronic schizophrenia is at least partly due to a medication effect. The observed post-treatment increase in striatal intrinsic activity may reflect counter-therapeutic functional adaptation to dopamine D2 receptor occupancy required for medication effects on psychosis.