The schizophrenia susceptibility gene ZNF804A confers risk of major mood disorders

Objectives: Genome-wide association studies (GWAS) followed by independent replications suggest that ZNF804A is a risk gene for schizophrenia (SCZ), considering the substantial genetic overlap between SCZ and major mood disorders (e.g., bipolar disorder (BPD) and major depressive disorder (MDD)).

Methods: We collected the data of two ZNF804A single-nucleotide polymorphisms (SNPs rs1344706 and rs7597593) from European and Asian populations to perform systematic meta-analyses with major mood disorders in a total of 65,240 subjects.

Results: Meta-analysis showed that rs1344706 and rs7597593 were both associated with major mood disorders as well as diagnosis of either BPD or MDD, although neither of the analyses achieved a genome-wide level of statistical significance.

Conclusions: Our data provide evidence for the genetic involvement of ZNF804A SNPs in the susceptibility of major mood disorders, but further replication analyses in larger samples are necessary.     

Increased serum midkine levels in autism spectrum disorder patients

Background: Midkine (MK) is a heparin binding growth factor and is involved in neurogenesis, neural development and neuroprotection. Additionally, MK may contribute to cancer development and pathogenesis of neurodegenerative disorders and schizophrenia. Considering these effects of MK, this study researched whether MK is involved in autism spectrum disorders (ASD) pathogenesis.

Methods: We evaluated serum MK levels of 38 patients with ASD and 32 healthy control group. MK levels were measured with ELISA, while ASD severity was assessed with Childhood Autism Rating Scale.

Results: Our data showed that the serum MK concentration in ASD patients (mean ± SD, 11.51 ± 8.53 pg/ml) is significantly higher than healthy controls (mean ± SD, 6.19 ± 3.94 pg/ml) (p = 0.007).

Conclusions: According to these results, MK may play a role in ASD pathogenesis.     

Self-reported sense of presence and responses to social stimuli by adolescents with autism spectrum disorder in a collaborative virtual reality environment

Background Collaborative virtual environments (CVEs) have the potential to support sociocommunicative interactions for people with autism spectrum disorder (ASD), but little is known about the sense of presence participants feel in CVEs or how CVEs can be used to assess skills.

Method Ten children with ASD and 10 typically developing (TD) children (aged 12–16 years) judged greeting behaviours of a human avatar and static facial expressions in a virtual gallery.

Results There were no differences in presence reported by the two groups. The ASD group was less sensitive to a negative greeting from the human avatar than the TD group, and impaired in recognising static facial expressions.

Conclusions Self-reported measures of presence are valuable for informing which kinds of tasks, and technology may provide more authentic contexts in which to identify and support social competence in participants with ASD.     

An examination of interactions among children with autism and their typically developing peers

Objective: To determine whether pre-school children with Autism Spectrum Disorders (ASD) interact differently with their peers with ASD compared to their typically developing (TD) peers, across three activities (free play, structured group time and semi-structured play) in an early intervention setting.

Methods: We completed a series of non-experimental case studies involving 13 children with ASD and two TD peers.

Results: We found trends, but no uniform differences, in the frequency or quality of means by which the children with ASD interacted with one another versus with their TD peers across the three contexts. The children with ASD interacted with both peer types more frequently during the semi-structured and structured activities, than during free play.

Conclusions: The children with ASD showed no clear bias towards one peer type over the other. Semi-structured activities may be the best context in which to facilitate peer interactions involving children with ASD in early intervention settings.     

Impact of CRP gene and additional gene–smoking interaction on ischemic stroke in a Chinese Han population

Aims: To investigate the association of C-reactive protein (CRP) gene single nucleotide polymorphisms (SNPs), additional gene–gene, and gene–smoking interaction with ischemic stroke (IS) risk.

Methods: Logistic regression is performed to investigate association between SNPs within CRP gene and IS risk. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene–gene and gene–smoking interaction, cross-validation consistency, the testing balanced accuracy and the sign test were calculated.

Results: Logistic analysis showed that three SNPs were all associated with decreased IS risk in additive and dominant models. The IS risks were lower in carriers of homozygous mutant of rs2794521 polymorphism and heterozygous of rs3093059 and rs1205 than those with wild-type homozygotes genotype, OR (95%CI) were 0.62 (0.40–0.90), 0.68 (0.50–0.96) and 0.65 (0.46–0.97), respectively. GMDR analysis suggested a significant two-locus model (P = 0.0010) involving rs2794521 and rs3093059. We also found a significant two-locus model (P = 0.0010) involving rs2794521 and smoking. Participants with rs2794521-AG or GG and rs3093059-AG or GG genotype have the lowest IS risk, compared to participants with rs2794521-AA and rs3093059-AA genotype, OR (95%CI) was 0.4 2 (0.233–0.61). In addition, non-smokers with rs2794521-AG or GG genotype have the lowest IS risk, compared to smokers with rs2794521-AA genotype, OR (95%CI) was 0.47 (0.23–0.76).

Conclusions: We found that rs2794521, rs3093059, and rs1205 were associated with decreased IS risk; we also found that gene–gene interaction between rs2794521 and rs3093059, and gene–environment interaction between rs2794521 and smoking were associated with decreased IS risk.     

Sonographic assessment of optic nerve and ophthalmic vessels in patients with idiopathic intracranial hypertension

Background: Early diagnosis and proper monitoring of intracranial pressure (ICP) in idiopathic intracranial hypertension (IIH) could reduce morbidity.

Objectives: The objective was to explore and monitor reflection of raised ICP in IIH on optic nerve sheath diameter (ONSD), papillary height and ophthalmic vessels hemodynamics, using transorbital sonography (TOS).

Methods: The study included 24 IIH patients and 30 controls. Patients were compared to controls (phase I) then reassessed twice; 1 week and 4 weeks later (phase II). Both groups underwent clinical evaluation and TOS to measure ONSD, papillary elevation, and color Doppler indices of the ophthalmic vessels. Patients underwent lumbar puncture (LP) to measure cerebrospinal fluid (CSF) pressure.

Results: ONSD was significantly higher in patients compared to controls (p < 0.001). The cut-off value was 6.2 mm. Papillary elevation (p = 0.006) and ONSD (p = 0.006) were significantly reduced 4 weeks following LP. Baseline color Doppler indices of the ophthalmic vessels were comparable between both groups and the changes observed during the follow-up visits in the patients were insignificant.

Conclusion: Reflected ICP changes on ONSD and papilla, measured by TOS, could be a valuable noninvasive additional tool to diagnose and monitor IIH patients. IIH insignificantly influences ophthalmic vessels hemodynamics.

Abbreviation BMI: Body mass index. CSF: Cerebrospinal fluid. EDV: End diastolic velocity. ICP: Intracranial pressure. IH:intracranial hypertension. IIH: Idiopathic intracranial hypertension. LP: Lumbar puncture. MI: Mechanical index. MRI: Magnetic resonance imaging. MRV: Magnetic resonance venography. OA: Ophthalmic artery OND: Optic nerve diameter. ONSD: Optic nerve sheath diameter. OV: Ophthalmic vein. PIs: Pulsatility indices. PSV: Peak systolic velocity. ROC: Receiver operator characteristic. TOS: Trans-orbital sonography.     

Nerve root anomalies detected intra-operatively technical nuances towards achieving a successful surgical outcome: our experience of three case reports at a tertiary level centre

Objective: Analysis of three case reports of nerve root anomalies detected intra-operatively and its implications.

Design: Data collected during one year prospective non-randomised study using hospital records.

Setting: Single tertiary care centre.

Subjects: 3 patients in one year period.     

Possible error in the Danish version of the WHO Quality of Life (WHOQOL-BREF) Questionnaire

Background: The WHOQOL-BREF is widely used to measure quality of life.

Aims: The goal of the present study was to use the questionnaire in a doctoral study.

Methods: We studied all the instructions provided by the WHO.

Results: In the Danish version of the WHOQOL-BREF there is a discrepancy between the negatively phrased question 9 and both the syntax file and the verbal instructions for coding the data provided by the WHO.

Conclusions: This is a notification of possible error interpretations in projects that use the questionnaire. This could be corrected by manual correction in the coding process or by changing the negatively phrased question 9.     

Parental report on socio-communicative behaviours in children with 22q11.2 deletion syndrome

Background Children with 22q11.2 deletion syndrome (22q11.2DS) are reported to have socio-communicative impairments. Although many of these children are diagnosed with intellectual disability (ID) and/or autism spectrum disorder (ASD), these populations are seldom used as control groups. Hence, information regarding syndrome-specific socio-communicative challenges is lacking.

Method Parental concerns regarding everyday communication were investigated by means of the Children’s Communication Checklist-2-NL (Geurts, 2007). Twenty children with 22q11.2DS (chronological age: 6 years–13 years 3 months) were compared to 21 children with idiopathic ID and 23 children with idiopathic ID and comorbid ASD. All groups were matched for fluid intelligence (Gf), chronological age, and core language scores.

Results Neglect or inadequate use of context information was more prevalent in children with 22q11.2DS than in children with idiopathic ID. Nonverbal communication seemed less impaired than in children with idiopathic ID + ASD.

Conclusion Pragmatic language skills and developmental trajectories in children with 22q11.2DS merit further investigation.     

Do depressive symptoms predict mortality in older people?

Context: Depressive symptoms are common in older persons, and may predict mortality.

Objectives: To determine: (1) If depressive symptoms predict mortality; (2) If there is a gradient in this effect; and (3) Which depressive factors predict mortality.

Population: In 1991–1992, 1751 community-dwelling older persons, sampled from a population-based registry, were interviewed.

Measures: The Center for Epidemiologic Studies – Depression (CES-D), age, gender, the Modified Mini-Mental State Examination, self-rated health, and functional status.

Outcome measure: Time to death.

Analysis: Those scoring 16+ on the CES-D were considered depressed. To determine if a gradient was present, the CES-D was treated as a continuous variable. Four depressive factors from the CES-D (depressed affect, positive affect, somatic, and interpersonal) were analyzed. Cox regression models were constructed.

Results: The mortality in those with depressive symptoms was higher in those without depressive symptoms (Hazard Ratio of 1.71, p < 0.001, Log rank test). In multivariable models, this association was no longer significant after accounting for self-rated health and functional status. There was a gradient in risk of mortality across the range of the CES-D. Somatic factors, depressed affect, and positive affect were all associated with mortality in bivariate analyses, but not in multivariable models adjusting for functional status. Interpersonal factors were not associated with mortality.

Conclusions: Depressive symptoms predict mortality in older persons.     

Parentification of adult siblings of individuals with autism spectrum disorder: Distress,sibling relationship attitudes,and the role of social support

Background Typically developing (TD) siblings of individuals with autism spectrum disorder (ASD) often fulfil caregiving roles as children or adults (i.e., parentification, which can be either parent-focused or sibling-focused).

Method This study examines how parentification interacts with social support when predicting distress and sibling relationship attitudes in 60 TD adult siblings of individuals with ASD.

Results Perceived social support served as a moderator. Specifically, TD adult siblings who experienced high parent-focused parentification during childhood and low current social support were most likely to report high distress. TD siblings who reported low sibling-focused parentification during childhood and low current social support were most likely to report less positive attitudes about their relationships with their siblings with ASD.

Conclusions Current findings suggest that perceived social support may serve as a potential point of intervention for reducing distress and improving sibling relationship attitudes among adult TD siblings of those with ASD.     

Identification of 5-hydroxytryptamine receptor gene polymorphisms modulating hyperprolactinaemia in antipsychotic drug-treated patients with schizophrenia

Objectives: Hyperprolactinaemia (HPRL) is a classical side effect of antipsychotic drugs primarily attributed to blockade of dopamine D2 subtype receptors in the pituitary gland. Although dopamine is considered the primary factor inhibiting prolactin release, the activity of prolactin-producing lactotrophs is also regulated by the secretagogues thyrotrophin releasing hormone, vasoactive intestinal polypeptide and serotonin (5-hydroxytryptamine; 5-HT).

Methods: We describe the association between HPRL and a set of 29 SNPs from 5-HT receptor genes HTR1A, HTR1B, HTR2A, HTR2C, HTR3A, HTR3B and HTR6 in a population of 446 Caucasians (221 males/225 females) with a clinical diagnosis of schizophrenia (according to ICD-10: F20) who were treated with classical and/or atypical antipsychotic drugs.

Results: None of the studied autosomal markers were found to be associated with HPRL. However, a significant association was established between various HTR2C polymorphisms and HPRL.

Conclusions: This study revealed an association between HPRL and X-chromosome haplotypes comprised of the rs569959 and rs17326429 polymorphisms.     

Effects of Hesel-coil deep transcranial magnetic stimulation for depression – a systematic review

Background: One third of the depressed patients are not improved by antidepressant drugs and psychological treatments, and there is a need for additional treatments. Repetitive transcranial magnetic stimulation (rTMS) is being developed towards an alternative in treatment-resistant depression. Deep transcranial stimulation (dTMS) with the Hesel-coil (H-coil) is a further development of rTMS aiming to enhance the effect by getting the magnetic pulses to penetrate deeper into the brain.

Aims: This report aims to assess the evidence-base for dTMS for depression. The report also includes an assessment of the ethical and economic aspects involved.

Methods: A systematic review of the effects of H-coil dTMS on depression was conducted and the scientific support was evaluated using GRADE (Grading of Recommendations Assessment, Development and Evaluation).

Results: Only one controlled study was identified. In the sham-controlled randomized study, 212 participants with major depression that had not responded to antidepressant medication were enrolled. A two-point superiority in Hamilton Depression Rating Scale was observed in the dTMS arm vs the sham-arm at 4 weeks, but the difference was not statistically significant. No serious adverse events were reported apart from rare cases of epileptic seizures.

Conclusions: The existing scientific support for H-coil dTMS therapy for depression is insufficient. The clinical implication is that the use of dTMS in depression should be restricted to the framework of clinical trials pending further studies. Fortunately, additional studies are underway and the evidence base should presumably improve over the next several years.     

Typically developing adolescents’ experience of growing up with a brother with an autism spectrum disorder

Background Researchers studying siblings of people with an autism spectrum disorder (ASD) suggest that growing up with an individual with disability has positive and negative effects.

Method Qualitative content analysis of semistructured interviews with 14 typically developing (TD) adolescents with a brother with an ASD and their mothers was used to explore the experience of growing up with a sibling with an ASD and identify differences in the relationship with, and attitude toward, the brother.

Results TD siblings expressed mixed feelings about their brother, a precocious sense of responsibility, concern about the future, friendship difficulties, and troubles and the desire to talk about their experience. Most adolescents integrated their positive and negative feelings; however, 3 adolescents displayed rejection, denial, or a sense of persecution.

Conclusions Qualitative research into the experiences of adolescent siblings of people with an ASD should be used to develop support programs to help adolescents manage their relationship with a sibling with a disability.     

Psychometric testing of a Swedish version of the Apathy Evaluation Scale

Background: Apathy, a prevalent and clinically relevant symptom in neurodegenerative disease, is often evaluated by the instrument Apathy Evaluation Scale (AES). However, this instrument has not been translated into Swedish, halting clinical and research efforts. Furthermore, previous studies lack analyses of some basic properties, such as the legitimacy of a total score, or have analysed dimensionality by questionable methods.

Aim: To translate and psychometrically evaluate a Swedish version of the AES.

Method: The AES was translated, and its psychometric properties were tested in the Swedish BioFINDER study, including cognitively well elderly, and subjects with mild cognitive or parkinsonian symptoms. Psychometric analyses were conducted according to classical test theory (CTT) and aimed to resemble those performed in the English original study by Marin et al. in 1991. Dimensionality was additionally analysed on a matrix of polychoric correlations and parallel analyses.

Results: Data indicate that the Swedish AES performs satisfactorily regarding data completeness, scaling assumptions, targeting, and reliability. Principal component analyses (with parallel analysis) of polychoric correlation matrices identified a single component. Convergent and discriminative validity correlations accorded with a priori expectations.

Conclusions: The study provides initial support that this Swedish AES performs similarly to the English original, and exhibits acceptable psychometric properties according to CTT, including supported unidimensionality, and may be adopted for use in clinical and research settings.     

A metacognitive training pilot study for adolescents with autism spectrum disorder: Lessons learned from the preliminary stages of intervention development

Background Cognitive differences, including deficits in self-awareness, are common in high-functioning individuals with autism spectrum disorder (ASD) and represent a fruitful target for intervention. The current project presents the preliminary research undertaken in the development of metacognitive training (MCT), an intervention designed to increase knowledge about personal strengths and challenges in adolescents with ASD.

Method Two groups of 4 adolescents with ASD completed MCT, as well as measures to assess satisfaction and adverse effects. Visual inspection and thematic analysis were used to interpret the data.

Results Overall, both participants and their parents rated MCT favourably; the youth most enjoyed the interactive activities, whereas parents appreciated the opportunity for socialising and psychoeducation. There were no systematic changes on quantitative measures of adverse effects (i.e. self-esteem or depression).

Conclusion Although the results suggest further investigation of MCT may be warranted, certain modifications to the MCT protocol and research methodology are needed.     

Association of TNF-α rs1799964 and IL-1β rs16944 polymorphisms with multiple system atrophy in Chinese Han population

Background: Recent evidence suggested that several single nucleotide polymorphisms (SNPs) of inflammation-related genes (TNF-α rs1799964, IL-1α rs1800587, IL-1β rs16944, IL-8 rs4073, ICAM-1 rs5498) were associated with multiple system atrophy (MSA). Herein, we conducted this case-control study to evaluate the possible correlation between the five SNPs related to inflammation and MSA in Chinese Han population.

Methods and Patients: We recruited 154 sporadic patients with MSA and 223 health controls in this study. All subjects were genotyped for the five SNPs using polymerase chain reaction amplification and Sanger sequencing.

Results: TNF-α rs1799964, genotype distribution and minor allele frequency (MAF) showed significant differences between patients and controls, which might illustrate the minor allele C may increase the risk for MSA (genotype, P = 0.006, OR = 1.245, 95% CI = [1.066–1.455]; allele, P = 0.001, OR = 1.887, 95% CI = [1.303–2.733]). For rs16944, patients carrying AA genotype showed a nearly 5-year early age at onset (AAO) than GG genotype (50.52 ± 7.45 years vs. 54.90 ± 7.21 years, P = 0.037). No differences were found in genotype distribution and MAF of the five SNPs between patients with MSA with predominant cerebellar ataxia (MSA-C) and with predominant Parkinsonism (MSA-P).

Conclusion: Our study suggests that rs1799964 of TNF-α may act as a risk factor for MSA and the IL-1β rs16944 might be a genetic factor that modifies the AAO in MSA. Moreover, the exact mechanism of neuroinflammatory response in MSA deserves further exploration.     

Internal decompression for spinal stenosis (IDSS) for decompression and use of interlaminar dynamic device (CoflexTM) for stabilization in the surgical management of degenerative lumbar canal stenosis with or without mild segmental instability: our initial results

Introduction: Internal decompression of spinal stenosis (IDSS) and Posterior dynamic stabilization (PDS) form a bridge between decompression laminectomy alone and rigid fusion, by attempting to sustain beneficial effects of decompression and stabilization in an attempt to prevent bad effects of relentless degeneration.

Objective: To evaluate the clinical outcome in operated patient of posterior dynamic stabilization.

Design: Data were collected over 1 year in prospective, nonrandomized follow-up study using outcome scales.

Setting: Single surgeon, tertiary care centre in Mumbai, India.

Described here is the operative technique of posterior dynamic stabilization using CoFlex^TM and clinical outcome of 67 consecutive patients using Visual Analogue Scale and Oswestry Disability Score.     

Integrating mental health in primary healthcare in low-income countries: changing the future for people with mental disorders

Background: Untreated mental disorders are a huge challenge for healthcare systems worldwide. Treatment possibilities are particularly scarce in low-income countries (LICs). WHO estimates that up to 85% of all people with a mental disorder in LICs do not have access to evidence-based treatment.

Aims: This paper seeks to explore the rationale behind the WHO recommendations for improving mental health services in LICs. At the core of these recommendations is an integration of mental health services into existing primary healthcare. This article presents available research supporting this approach. Furthermore, it highlights challenges needing special attention and opportunities demanding additional research to guide a comprehensive restructuring of a healthcare system.

Methods: A literature review of WHO documents and searches on PubMed for relevant supporting literature.

Results: Research from LICs that investigate mental health interventions is scarce. The evidence that does exist favours integration into primary healthcare. There is evidence that collaborative- and stepped-care interventions can provide viable treatment options for patients.

Conclusion: Integration of mental health services into primary healthcare seems like a viable solution to ensure that treatment becomes more available, even though the evidence is limited. Locally conducted research is needed to guide the development of sustainable evidence-based mental health treatment, involving relevant healthcare providers, with optimal task-sharing and possibilities for referral of complex cases. Furthermore, to achieve this, comprehensive political will and investments are necessary pre-requisites.     

Meaningful outcomes for enhancing quality of life for individuals with autism spectrum disorder

Background Autism spectrum disorder (ASD) is a developmental disorder that continues across the lifespan, but little research exists to examine interventions from both child and adult perspectives. The researchers in this study considered the perspectives of individuals with ASD and caregivers of children with ASD to determine interventions and outcomes perceived as meaningful for both children and adults.

Methods Grounded theory methodology was used to guide data collection and analysis. Participants included 5 parents of children with ASD and 5 adults with ASD. Data were collected through interviews.

Results A central theme of Intervention priorities for quality of life was supported. Individual themes identified from parents focused on future planning, community involvement, and scheduling and planning. Individual themes identified from the adults focused on misconceptions. Both groups shared the themes of acceptance; financial challenges; support, resources, and advocacy; skills learned; and socially and functionally based interventions.

Conclusion Results support interventions and resources for individuals with ASD focused on meaningful outcomes, including acceptance, community involvement, social success, independent living, and vocational/financial stability.