Genetic Variation Throughout the Folate Metabolic Pathway Influences Negative Symptom Severity in Schizophrenia

Low serum folate levels previously have been associated with negative symptom risk in schizophrenia, as has the hypofunctional 677C>T variant of the MTHFR gene. This study examined whether other missense polymorphisms in folate-regulating enzymes, in concert with MTHFR, influence negative symptoms in schizophrenia, and whether total risk allele load interacts with serum folate status to further stratify negative symptom risk. Medicated outpatients with schizophrenia (n = 219), all of European origin and some included in a previous report, were rated with the Positive and Negative Syndrome Scale. A subset of 82 patients also underwent nonfasting serum folate testing. Patients were genotyped for the MTHFR 677C>T (rs1801133), MTHFR 1298A>C (rs1801131), MTR 2756A>G (rs1805087), MTRR 203A>G (rs1801394), FOLH1 484T>C (rs202676), RFC 80A>G (rs1051266), and COMT 675G>A (rs4680) polymorphisms. All genotypes were entered into a linear regression model to determine significant predictors of negative symptoms, and risk scores were calculated based on total risk allele dose. Four variants, MTHFR 677T, MTR 2756A, FOLH1 484C, and COMT 675A, emerged as significant independent predictors of negative symptom severity, accounting for significantly greater variance in negative symptoms than MTHFR 677C>T alone. Total allele dose across the 4 variants predicted negative symptom severity only among patients with low folate levels. These findings indicate that multiple genetic variants within the folate metabolic pathway contribute to negative symptoms of schizophrenia. A relationship between folate level and negative symptom severity among patients with greater genetic vulnerability is biologically plausible and suggests the utility of folate supplementation in these patients.     

Effects of antidepressant treatment on mice lacking brain‐derived neurotrophic factor expression through promoter IV

Brain‐derived neurotrophic factor (BDNF) is implicated in the pathophysiology of major depression; mice lacking BDNF expression through promoter IV (BDNF‐KIV) exhibit a depression‐like phenotype. We tested our hypothesis that deficits caused by promoter IV deficiency (depression‐like behavior, decreased levels of BDNF, and neurogenesis in the hippocampus) could be rescued by a 3‐week treatment with different types of antidepressants: fluoxetine, phenelzine, duloxetine, or imipramine. Each antidepressant reduced immobility time in the tail suspension test without affecting locomotor activity in the open field test in both BDNF‐KIV and control wild type mice, except that phenelzine increased locomotor activity in wild type mice and anxiety‐like behavior in BDNF‐KIV mice. The antidepressant treatments were insufficient to reverse decreased BDNF levels caused by promoter IV deficiency. No antidepressant treatment increased the hippocampal progenitors of either genotype, whereas phenelzine decreased the surviving progenitors in both genotypes. The antidepressant treatments differently affected the dendritic extension of hippocampal immature neurons: fluoxetine and imipramine increased extension in both genotypes, duloxetine increased it only in BDNF‐KIV mice, and phenelzine decreased it only in wild type mice. Interestingly, a saline‐only injection increased neurogenesis and dendrite extensions in both genotypes. Our results indicate that the behavioral effects in the tail suspension test by antidepressants do not require promoter IV‐driven BDNF expression and occur without a detectable increase in hippocampal BDNF levels and neurogenesis but may involve increased dendritic reorganisation of immature neurons. In conclusion, the antidepressant treatment demonstrated limited efficacy; it partially reversed the defective phenotypes caused by promoter IV deficiency but not hippocampal BDNF levels.     

Mild traumatic brain injury and its sequelae: Characterisation of divided attention deficits

Deficits in divided attention occur after a mild traumatic brain injury (MTBI) but many extant tasks lack sensitivity for detecting subtle cognitive difficulties. We use the Test d'Attention Partagée Informatisé (TAPI), a novel dual-task paradigm, to investigate the impact of MTBI on the ability to divide attention between two stimuli sources. Individuals with MTBI (n = 37) were evaluated within the first week following head trauma and at three months post-injury. A healthy control (HC) group (n = 79) was also assessed. The primary outcome was reaction time and there were three different conditions that included visual target detection and auditory digit span tasks. Analyses utilised repeated measures ANOVA and ANCOVA models that adjusted for relevant variables including post-concussive and affective symptoms. Results indicated that at both baseline and follow-up, the MTBI group had significantly slower reaction time than the HC group. Also, both the MTBI and HC groups had slower reaction times as participants progressed through each of the more challenging TAPI conditions. This study supports the usefulness of this novel instrument and allows clinicians and researchers to assess for subtle divided attention deficits that may persist in those with MTBI even three months post-injury.     

Diffusion tensor imaging in brainstem tuberculoma

Integrity of descending white matter tracts can be evaluated by diffusion tensor imaging. In rim-enhancing intraparenchymal lesions, this technique can assist in the differentiation of demyelinating disease from tumor or abscess. Diffusion tensor imaging characteristics of tuberculoma have not been previously reported to our knowledge. A patient with headaches, dizziness, and mild left-sided weakness underwent MRI with diffusion tensor imaging. A large, rim-enhancing lesion within the pons was discovered, which subsequently was diagnosed as tuberculoma. Tractography maps prepared from diffusion tensor imaging data revealed predominantly displaced descending fiber tracts in the region of the rim-enhancing lesion. A few tracts adjacent to the lesion appeared truncated, and this abnormal finding correlated to the patient’s clinical deficit. The tractography characteristics of diffusion tensor imaging in this patient potentially are distinct from those seen with demyelinating lesions, which may show more extensive tract truncation. Together with the consonance of exam findings and tract truncation seen in this patient, tractography may prove useful in the diagnosis of suspected tuberculoma.     

Lambert-Eaton myasthenic syndrome in mixed small cell carcinoma and adenocarcinoma of extrapulmonary origin

A patient with typical Lambert–Eaton myasthenic syndrome (LEMS) has a clinical manifestation of proximal muscle weaknesses, a larger-than-100% incremental change in repetitive nerve stimulation on high-rate stimulation electrophysiological testing, and a paraneoplastic origin from small cell carcinoma of the lung. Here, we present a patient with an atypical myasthenic syndrome with an oculobulbar-predominant muscle involvement, a borderline incremental change in repetitive nerve stimulation at high frequencies, and a paraneoplastic origin from extrapulmonary mixed small cell carcinoma and adenocarcinoma. The purpose of this report is to emphasize the importance of painstaking scrutiny in the examination of a patient with a less-common presentation of LEMS.     

Exploring the relationships between the use of text message language and the literacy skills of dyslexic and normal students

It is apparent that individuals using text abbreviations as a written convention is a continuingly growing phenomenon. This special writing convention has been referred to as textism usage. However, there is surprisingly little research investigating the impacts of textism use on dyslexic children's cognitive abilities associated with literacy skills. Thus, the relation between textism use, phonological awareness, as well as morphological awareness is not yet clear. This issue is critical and urgent because no conclusive guidance is available for practitioners or educators to refine instructional strategies. Furthermore, given that prior researchers focus mainly on alphabetic language, little research draws attention on non-alphabetic language, in which morphological awareness seems rather significant than phonological awareness. In this study a total of 57 participants across six elementary schools in Taiwan were recruited and were formed into three groups. To effectively collect the textisms used by the participants, this study adopted Facebook as the tool to store the messages because of its high penetration rate of 51 percent in Taiwan. Findings of this study suggested that dyslexic children may get rid of the identification, which might encourage them shift their focuses from others’ judgment to selecting a proper textism. To use the textism appropriately requires the dyslexic children realize the meaning of the textism and memorize the spelling/writing convention. Consequently, the dyslexia group in this study performed as well as reading-age group in word recognition and meaning recognition. It seemed that dyslexic children preferred to use contraction, symbol, and combined word. These categories of textism are L–S (logography to semantics) in nature.