Clinical Usefulness of Loudness Dependence of Auditory Evoked Potentials (LDAEP) in Patients with Bipolar Disorder

While it has been reported previously that the loudness dependence of auditory evoked potentials (LDAEP) is a putative biological marker or a predictor of treatment response, there have been few studies of LDAEP in bipolar disorder. However, a recent study by Park and colleagues raised the possibility that the LDAEP could be useful as a biological marker of bipolar disorder. They found that the LDAEP was significantly higher in normal controls than in patients with either bipolar disorder or schizophrenia. Lee and colleagues also examined the LDAEP in bipolar disorder and normal controls, and found that it differed according to the bipolar phase, being significantly higher in cases of euthymic bipolar disorder, bipolar depression, and bipolar mania. With regard to treatment response, early clinical findings were that a higher LDAEP and a stronger intensity dependence of visual evoked potentials were related to a favorable response to lithium treatment. Juckel and colleagues recently demonstrated that the pretreatment LDAEP could be a predictor of successful prophylactic lithium treatment. The present article reviews the literature in order to determine whether the LDAEP can be used as a biological marker or a predictor of treatment response in patients with bipolar disorder and of manic switch or treatment resistance in patients with major depressive episode(s).     

Neurotrophic Tyrosine Kinase Receptor Type 2 (NTRK2) Gene Associated with Treatment Response to Mood Stabilizers in Patients with Bipolar I Disorder

There is increasing evidence supporting the relationship between bipolar disorder (BP) and neurotrophin. The present study investigated the relationship between neurotrophic tyrosine kinase receptor type 2 (NTRK2) gene polymorphisms and bipolar I disorder (BP I) susceptibility and treatment response to mood stabilizers (lithium or valproate). Two-hundred eighty-four patients who met the DSM-IV criteria for BP I and 295 matched healthy controls were enrolled into this study. TaqMan® SNP genotyping assays were applied to genotype three NTRK2 gene polymorphisms (rs2769605, rs1565445, rs1387923). Our study showed a significant allelic association between NTRK2 gene polymorphism rs2769605 and treatment response to mood stabilizers in BP I patients (t?=??2.53, P?=?0.01). However, no significant association between NTRK2 gene polymorphisms and BP I susceptibility was observed after correcting for multiple comparisons. The results suggest that the NTRK2 gene polymorphism likely plays an essential role in treatment response to mood stabilizers in Han Chinese BP I patients.     

Immunohistochemical Localization of Phosphorylated Glial Fibrillary Acidic Protein in the Prefrontal Cortex and Hippocampus from Patients with Schizophrenia, Bipolar Disorder, and Depression

Increasingly, abnormalities of glial cell function have been implicated in pathological studies of the major mental illnesses (schizophrenia, bipolar disorder, and major depression). In a recent proteomic study, four isoforms of astrocytic glial fibrillary acidic protein (GFAP) were decreased in one or more of these diseases. In the current study, we sought to determine the immunohistochemical localization of phosphorylated GFAP (pGFAP) in the prefrontal cortex and hippocampus and to describe possible disease-related changes in the distribution of pGFAP containing astrocytes. In the prefrontal cortex, interlaminar astrocytes in layer I and stellate astrocytes in layers II and VI were labeled. Labeled cells were also present adjacent to blood vessels in the gyral white matter and in underlying white matter generally. In the hippocampus, labeled cells were present in the polymorphic layer of the dentate gyrus. In the prefrontal cortex, schizophrenia and major depression were characterized by decreased labeling of astrocytes adjacent to blood vessels. There were no significant differences between the diagnostic groups in the other prefrontal layers or in the hippocampus. These results suggest that reduced numbers or functional regulation of pGFAP containing astrocytes occurs in schizophrenia and major depression. The mechanism by which this deficit occurs is not known, but it may adversely effect the regulation of neuronal metabolism, communication, and response to injury.     

The P3 Event-Related Potential is a Biomarker for the Efficacy of Vagus Nerve Stimulation in Patients with Epilepsy

Currently, the mechanism of action of vagus nerve stimulation (VNS) is not fully understood, and it is unclear which factors determine a patient’s response to treatment. Recent preclinical experiments indicate that activation of the locus coeruleus noradrenergic system is critical for the antiepileptic effect of VNS. This study aims to evaluate the effect of VNS on noradrenergic signaling in the human brain through a noninvasive marker of locus coeruleus noradrenergic activity: the P3 component of the event-related potential. We investigated whether VNS differentially modulates the P3 component in VNS responders versus VNS nonresponders. For this purpose, we recruited 20 patients with refractory epilepsy who had been treated with VNS for at least 18 months. Patients were divided into 2 groups with regard to their reduction in mean monthly seizure frequency: 10 responders (>50 %) and 10 nonresponders (≤50 %). Two stimulation conditions were compared: VNS OFF and VNS ON. In each condition, the P3 component was measured during an auditory oddball paradigm. VNS induced a significant increase of the P3 amplitude at the parietal midline electrode, in VNS responders only. In addition, logistic regression analysis showed that the increase of P3 amplitude can be used as a noninvasive indicator for VNS responders. These results support the hypothesis that activation of the locus coeruleus noradrenergic system is associated with the antiepileptic effect of VNS. Modulation of the P3 amplitude should be further investigated as a noninvasive biomarker for the therapeutic efficacy of VNS in patients with refractory epilepsy.     

The Quality of Life in Bipolar Disorder (QoL.BD) Scale: Validation of a French Cross-Cultural Adaptation

Objective:The goal of this study was to validate the French version of the Quality of Life in Bipolar Disorder (QoL.BD) scale, a condition-specific measure for bipolar disorder (BD).Method:The QoL.BD scale was translated into French in accordance with the recommendations for transcultural adaptation. It was administered to 125 participants with BD living in Quebec, Canada. Construct validity was evaluated through correlations with other measures of self-reported quality of life (QoL), functioning, and symptoms. Factorial structure was examined through an exploratory factor analysis.Results:Internal reliability and test–retest reliability standards were met. Correlations in expected directions with other QoL, functioning, and depressive symptom scales supported convergent validity. The item loadings structure of the French QoL.BD largely replicated the original English version, with some modifications.Conclusion:The French version of the QoL.BD (full and brief) is comparable in its psychometric properties to the English version. It is a valid and sound measure for the evaluation of the QoL of French-speaking patients with BD.     

Evidence for taurine as an inhibitory neurotransmitter in cerebellar stellate interneurons: selective antagonism by TAG (6-aminomethyl-3-methyl-4H, 1, 2, 4-benzothiadiazine-1, 1-dioxide)

Using a novel amino acid antagonist, TAG (6-aminomethyl-3-methyl-4H, 1, 2, 4-benzothiadiazine-1, 1-dioxide), intradendritic electrophysiological investigations were carried out to obtain evidence for taurine as a neurotransmitter in the cerebellum. The hyperpolarizing action of taurine on Purkinje cell dendrites in guinea pig cerebellar slices was selectively antagonized by TAG (200 μM), while the actions of GABA, glycine and β-alanine were virtually unaffected. TAG shifted the log dose-response curve of the taurine action to the right in parallel, indicating a competitive antagonism. A hyperpolarizing synaptic potential which was evoked by electrical stimulation of the upper region of the cerebellar molecular layer and recorded from a Purkinje cell dendrite. was reversed to a depolarizing one at a membrane potential of -70 mV. The hyperpolarization induced by exogenously applied taurine was also reversed at the same potential. Moreover, TAG (200 μM) completely and reversibly blocked the synaptic potential. These results suggest that taurine may be an inhibitory neurotransmitter in stellate neuronal synapses on Purkinje cell dendrites.     

Neuropsychological Features of Patients with Spinocerebellar Ataxia (SCA) Types 1, 2, 3, and 6

A subtype-specific impairment of cognitive functions in spinocerebellar ataxia (SCA) patients is still debated. Thirty-two SCA patients (SCA1, 6; SC2, 3; SCA3, 15; SCA6, 8) and 14 matched healthy controls underwent neuropsychological evaluation testing attention, executive functions, episodic and semantic memory, and motor coordination. Severity of ataxia was assessed with the Scale for the Assessment and Rating of Ataxia (SARA), nonataxia symptoms with the Inventory of Non-Ataxia Symptoms. Depressive symptoms were evaluated with the Beck Depression Inventory. The SARA scores of our SCA patients (range 1–19.5) indicated an overall moderate ataxia, most pronounced in SCA6 and SCA1. Mean number of nonataxia symptoms (range 0–2.2) were most distinct in SCA1 and nearly absent in SCA6. SCA1 performed poorer than controls in 33% of all cognitive test parameters, followed by SCA2, SCA3, and SCA6 patients (17%). SCA 1–3 patients presented mainly attentional and executive dysfunctions while semantic and episodic memory functions were preserved. Attentional and executive functions were partly correlated with ataxia severity and fine motor coordination. All patients exhibited mildly depressed mood. Motor and dominant hand functions were more predictive for depressed mood than cognitive measures or overall ataxia. Besides motor impairments in all patients, SCA patients with extracerebellar pathology (SCA 1–3) were characterized by poor frontal attentional and executive dysfunction while mild cognitive impairments in predominantly cerebellar SCA6 patients appeared to reflect mainly cerebellar dysfunction. Regarding the everyday relevance of symptoms, (dominant) motor hand functioning emerged as a marker for the patient’s mood.     

癫痫患者外周血清中β淀粉样蛋白与IL-8、TNF-α水平的改变

目的 观察癫痫患者外周血β淀粉样蛋白（Aβ1-28）、肿瘤坏死因子（TNF-α）和白细胞介素8（IL-8）水平变化，以探讨是否与癫痫的发病存在相关性。方法收集36例癫痫患者和40例正常人血清，应用放射免疫分析法分别检测31例癫痫患者血清Aβ1-28、24例患者血清IL-8和13例患者血清TNF-α的水平变化，应用SPSS及Origin统计软件进行数据分析。结果癫痫患者血清Aβ1-28和IL-8水平明显增高（P=0．05），癫痫组患者血清TNF-α水平较正常对照组水平增高．但差异无显著性（P〉0．05）。癫痫组部分患者血清IL-8水平同TNF-α水平进行相关性分析．结果二者呈正相关。结论血清Aβ1-28、IL-8水平与癫痫发病可能存在相关性．而血清TNF-α水平与癫痫发病的相关性则不明显．在癫痫患者外周血中IL-8和TNF-α可能存在协同作用。     

Type 3 (chronic) GM1 gangliosidosis presenting as infanto-choreo-athetotic dementia, without epilepsy, in three sisters

Three sisters (ages 27, 24, and 17 years) presented with slowly progressing dystonic dementia and spastic tetraparesis with infantile onset. CSF, bone marrow, and conjunctival cells showed storage vacuoles. Biochemical analysis revealed increased urinary oligosaccharide excretion and decreased activity of acid beta-D-galactosidase and beta-D-fucosidase in serum, leukocytes, and cultured fibroblasts. The parents' enzyme values were in the heterozygous range. This is the only case in the literature of severe dementia associated with the clinical symptoms of type 3 GM1 gangliosidosis. The clinical heterogeneity of GM1 gangliosidosis and the significance of the combination of beta-D-galactosidase and beta-D-fucosidase defects in this syndrome are discussed.     

The RS685012 Polymorphism of ACCN2, the Human Ortholog of Murine Acid-Sensing Ion Channel (ASIC1) Gene,is Highly Represented in Patients with Panic Disorder

Panic disorder (PD) is a disabling anxiety disorder that is characterized by unexpected, recurrent panic attacks, associated with fear of dying and worrying about possible future attacks or other behavioral changes as a consequence of the attacks. The acid-sensing ion channels (ASICs) are a family of proton-sensing channels expressed throughout the nervous system. Their activity is linked to a variety of behaviors including fear, anxiety, pain, depression, learning, and memory. The human analog of ASIC1a is the amiloride-sensitive cation channel 2 (ACCN2). Adenosine A2A receptors are suggested to play an important role in different brain circuits and pathways involved in anxiety reactions. In this work we aimed to evaluate the distribution of ACCN2 rs685012 and ADORA2A rs2298383 polymorphisms in PD patients compared with healthy subjects. We found no association between ADORA2A polymorphism and PD. Instead, the C mutated allele for ACCN2 rs685012 polymorphism was significantly more frequent in patients than in controls. On the contrary, the TT homozygous wild-type genotype and also the ACCN2 TT/ADORA2A CT diplotype were significantly more represented in controls. These results are suggestive for a role of ACCN2 rs685012 polymorphism in PD development in Caucasian people.     

Evidence That Corticotropin-Releasing Hormone Acts as a Growth Hormone-Releasing Factor in a Primitive Teleost, the European Eel (Anguilla anguilla)

The inhibitory control of growth hormone (GH) release by somatostatin (SRIH) has been conserved throughout vertebrate evolution. In contrast, the neuropeptides involved in the stimulatory control of GH vary according to species and/or physiological situations. We investigated the direct pituitary regulation of GH release in a primitive teleost, the European eel (Anguilla anguilla L.) at the juvenile stage. Short-term serum-free primary cultures of dispersed pituitary cells were used, and GH release was measured by an homologous radioimmunoassay. Whereas growth hormone-releasing hormone (GHRH), gonadotropin-releasing hormone (GnRH), thyrotropin-releasing hormone (TRH), neuropeptide Y (NPY) and cholecystokinin (CCK) failed to induce any change in GH release, corticotropin-releasing hormone (CRH) dose-dependently stimulated GH release with a significant effect at 1 nM and a maximal effect (> or =400% of controls at 24 h) at 100 nM. In agreement with our previous studies, PACAP also stimulated GH release but its maximal effect was lower than that of CRH. Proopiomelanocortin (POMC)-peptides, corticotropin (ACTH), melanotropin (alpha-MSH), beta-endorphin) had no effect on GH release, at any dose tested (0.1-1000 nM), indicating that the stimulatory effect of CRH on GH release by somatotrophs was not mediated by CRH-induced release of POMC-peptides from corticotrophs and melanotrophs. The CRH antagonist, alpha-helical CRH(9-41), significantly inhibited the stimulatory effect of CRH on GH release, suggesting the implication of specific CRH receptors related to mammalian ones. The stimulatory effect of CRH on GH release was reduced after 24 h of incubation, indicating a desensitization. In contrast, no desensitization to the inhibitory effect of SRIH was observed. SRIH inhibited CRH action in a dose-dependent manner. The effect of SRIH was overriding, 1 nM SRIH being able to abolish the effect of 1000 nM CRH. In conclusion, in the eel, CRH stimulates GH release directly at the pituitary cell level. GH and cortisol secretions could interact in controlling several physiological functions such as metabolism and ion exchange. This study suggests that CRH may have played an important early role in vertebrates co-ordinating the activation of various endocrine axes involved in metamorphosis, osmoregulation, stress and fasting. The stimulatory role of CRH on GH release may have been partially conserved during evolution, as it is found in some human physio-pathological situations such as stress, fasting and depression.     

Genetic Analysis of UGT1A1 Polymorphisms Using Preserved Dried Umbilical Cord for Assessing the Potential of Neonatal Jaundice as a Risk Factor for Autism Spectrum Disorder in Children

Journal of Autism and Developmental Disorders - Neonatal jaundice has been suggested as a perinatal risk factor for autism spectrum disorder (ASD). We examined UGT1A1 polymorphisms to assess the...