Inverse relationship between serum high density lipoprotein and negative syndrome in antipsychotic-naive schizophrenia

Background: Recent literature suggests a role for apolipoprotein L (apoL) aberrations in the pathogenesis of schizophrenia. ApoL is almost exclusively associated with apolipoprotein A-I in high-density lipoproteins (HDLs). The objective of this study was to examine the correlation between symptom scores and serum HDL in antipsychotic-naive schizophrenia patients. Methods: In this cross-sectional study, 60 antipsychotic-naive schizophrenia patients were systematically examined for their symptom scores, with good inter-rater reliability. Concurrently, an overnight fasting serum lipid profile from these patients was assessed. Results: Serum HDL had a significant inverse correlation with a total negative syndrome score (ρ=−0.43; p=0.001). Conclusions: The study observation supports the potential role for HDL abnormalities in the genesis of negative symptoms in schizophrenia. Clin Chem Lab Med 2010;48:95–8.Peer Reviewe

Emotion Processing Deficit in Euthymic Bipolar Disorder: A Potential Endophenotype

Background: Emotion processing deficits have been described in patients with bipolar disorder (BD) and are considered one of the core cognitive abnormalities in BD with endophenotype potential. However, the literature on specific impairments in emotion processing cognitive strategies (directive/cortical/higher versus intuitive/limbic/lower) in euthymic adult BD patients and healthy first-degree relatives/high-risk (HR) subjects in comparison with healthy controls (HCs) is sparse. Methods: We examined facial emotion recognition deficits (FERD) in BD (N = 30), HR (N = 21), and HC (N = 30) matched for age (years), years of education, and sex using computer-administered face emotions–Matching And Labeling Task (eMALT). Results: The three groups were significantly different based on labeling accuracy scores for fear and anger (FA) (P \u3c 0.001) and sad and disgust (SD) (P \u3c 0.001). On post-hoc analysis, HR subjects exhibited a significant deficit in the labeling accuracy of FA facial emotions (P \u3c 0.001) compared to HC. The BD group was found to have significant differences in all FA (P = 0.004) and SD (P = 0.003) emotion matching as well as FA (P = 0.001) and SD (P \u3c 0.001) emotion labeling accuracy scores. Conclusions: BD in remission exhibits FERD in general, whereas specific labeling deficits of fear and anger emotions, indicating impaired directive higher order aspect of emotion processing, were demonstrated in HR subjects. This appears to be a potential endophenotype. These deficits could underlie the pathogenesis in BD, with possible frontolimbic circuitry impairment. They may have potential implications in functional recovery and prognosis of BD

Toxoplasma Antibody Titers in Mania: A Cross Sectional Study

Background: Recent studies have found a role of infectious agents, especially Toxoplasma gondii, in pathology of bipolar disorder - mania. Aim and Objectives: This study was conducted with the aim to find the prevalence of toxoplasma antibody titers in Indian patients with mania and to assess its specificity towards the clinical profile. Material and Methods: Thirty-four patients having mania were recruited who were psychotropic naïve/free, along with 74 healthy controls. Psychopathology was assessed using structured assessment scales. Serum concentration of Toxoplasma IgG was measured using Diesse Enzywell Toxoplasma IgG immunoassay kit. Results: Mann–Whitney U test revealed that the toxoplasma antibody levels were significantly higher in the mania group than healthy controls (U = 766.5, z = 3.25, p = 0.001). Spearman correlation analyses did not reveal any significant correlation between toxoplasma antibody levels and age at onset (ñ = 0.19, p = 0.26) or YMRS scores (ñ = 0.15, p = 0.39). Discussion: The herein reported association could have potential implications in better understanding the pathophysiology of mania and its treatment. This is the first study to evaluate the association between toxoplasma titers and mania in India with only a few studies done elsewhere in the world

Inferior parietal lobule volume and schneiderian first-rank symptoms in Antipsychotic-Naive schizophrenia: A 3-Tesla MRI study

Background: As per Frith′s neuro-cognitive model, inferior parietal lobule (IPL) is implicated in the pathogenesis of Schneiderian first-rank symptoms (FRS) in schizophrenia. The specific role of IPL structural abnormalities in the pathogenesis of FRS is yet to be ascertained. Materials and Methods: Using 3-tesla MRI scanner, this first-time study examined antipsychotic-naοve schizophrenia patients ( n = 28) (patients with FRS [FRS +]: N = 14, M: F = 7:7; and patients without FRS [FRS-]: N = 14, M: F = 7:7) in comparison with sex-, handedness-, education- and socioeconomic status-matched healthy controls ( n = 14, M: F = 7:7). The volume of IPL was measured using a three-dimensional, interactive, semi-automated analysis, with good inter-rater reliability. Results: FRS + patients showed significant volume deficit in right IPL in comparison with healthy controls (F = 4.0; P=.028) after controlling for the potential confounding effects of age, sex and intracranial volume. Conclusions: Right IPL volume deficit in FRS+patients adds further support to the Frith′s model of FRS in schizophrenia

Relationship between Brain-Derived Neurotrophic Factor and Schneiderian First Rank Symptoms in Antipsychotic-Naïve Schizophrenia

Neurodevelopmental aberrations influenced by neurotrophic factors are among the important paradigms to understand schizophrenia pathogenesis. Among various neurotrophic factors, Brain-Derived Neurotrophic Factor (BDNF) is strongly implicated by previous research studies. Evaluating co-morbidity free, antipsychotic-naïve schizophrenia patients for BDNF levels and examining the correlates of this factor with symptoms might facilitate elucidation of its pathogenetic role without confounds of potential influencing factors. In this study, 59 co-morbidity free, antipsychotic-naïve schizophrenia patients were compared with 60 healthy controls for serum BDNF levels. In addition, the relationship between Schneiderian First Rank Symptoms (FRS) and BDNF level in patients was examined. As a group, schizophrenia patients (28.8 ± 11.7 ng/mL) had significantly lower serum BDNF than healthy controls (34.9 ± 8.2 ng/mL) after controlling for the potential confounding effects of age and sex (F = 7.8; p = 0.006). Further analyses revealed FRS status to have significant effect on plasma BDNF after controlling for the potential confounding effects of age and sex (F = 4.5; p = 0.01). Follow-up post hoc analyses revealed FRS(+) patients to have significant deficit in plasma BDNF level in comparison with healthy controls (p = 0.002); however, FRS(−) patients did not differ from healthy controls (p = 0.38). Our study observations add further support to the role for BDNF in schizophrenia pathogenesis and suggest a potential novel link between deficient BDNF and FRS

Neural Effects of Transcranial Direct Current Stimulation in Schizophrenia: A Case Study Using Functional Near-Infrared Spectroscopy

Schizophrenia is a severe neuropsychiatric disorder characterized by delusions, hallucinations, behavioral symptoms, and cognitive deficits. Roughly, 70%-80% of schizophrenia patients experience auditory verbal hallucinations (AVHs), with 25%-30% demonstrating resistance to conventional antipsychotic medications. Studies suggest a promising role for add-on transcranial direct current stimulation (tDCS) in the treatment of medication-refractory AVHs. The mechanisms through which tDCS could be therapeutic in such cases are unclear, but possibly involve neuroplastic effects. In recent years, functional near-infrared spectroscopy (fNIRS) has been used successfully to study tDCS-induced neuroplastic changes. In a double-blind, sham-controlled design, we applied fNIRS to measure task-dependent cerebral blood flow (CBF) changes as a surrogate outcome of single session tDCS-induced effects on neuroplasticity in a schizophrenia patient with persistent auditory hallucinations. The observations are discussed in this case report

Predicting Individual Survival Distributions Using ECG: A Deep Learning Approach Utilizing Features Extracted by a Learned Diagnostic Model

In the field of healthcare, individual survival prediction is important for personalized treatment planning. This study presents machine learning algorithms for predicting Individual Survival Distributions (ISD) using electrocardiography (ECG) data in two different formats. The models, which predict time until death, are developed and evaluated on a large, population-based cohort from Alberta, Canada. Our results demonstrate that models trained on raw ECG waveforms significantly outperform those trained on traditional ECG measurements in several metrics, including concordance index, hinge L1 loss, margin L1 loss, and margin truncated L1 loss. Additionally, the integration of predicted probabilities from wide-range diagnostic tasks not only enhances our ISD models' performance but also makes them significantly superior to other models across all evaluation metrics in individual survival prediction tasks. This innovative approach highlights the potential to leverage insights from diagnostic models for prognostic tasks, such as individual survival prediction. These findings could have far-reaching implications for the development of personalized treatment plans and open new avenues for future research in survival prediction using ECGs

Learning Structure Activity Relationship (SAR) of the Wittig Reaction from Genetically-Encoded Substrates

The Wittig reaction can be used for late stage functionalization of proteins and peptides to ligate glycans, pharmacophores, and many other functionalities. In this manuscript, we modified 160,000 N-terminal glyoxaldehyde peptides displayed on phage with the Wittig reaction by biotin labeled ylide under conditions that functionalize only 1% of the library population. Deep-sequencing of the biotinylated and input populations estimated the rate of conversion for each sequence. This “deep conversion” (DC) from deep sequencing correlates with rate constants measured by HPLC. Peptide sequences with fast and slow reactivity highlighted a critical role of primary backbone amides (N-H) in accelerating the rate of the aqueous Wittig reaction. Experimental measurement of reaction rates and density functional theory (DFT) computation of the transition state geometries corroborated this relationship. We also collected deep-sequencing data to build structure activity relationship (SAR) models that can predict DC value of the Wittig reaction. By using this data, we trained two classifier models based on Gradient Boosted trees. These classifiers achieved area under the ROC (Receiver Operating Characteristic) Curve (ROC AUC) of 81.2 ± 0.4 and 73.7 ± 0.8 (90–92% accuracy) in determining whether a sequence belonged to the top 5% or the bottom 5% in terms of its reactivity. We have deployed our learned models as a publicly available web app: http://44.226.164.95/ We anticipate that phage-displayed peptides and related mRNA or DNA-displayed substrates can be employed in a similar fashion to study the substrate scope and mechanisms of many other chemical reactions

The impact of HLA-G 3\u27 UTR variants and sHLA-G on risk and clinical correlates of schizophrenia

The Major Histocompatibility Complex (MHC)/Human Leukocyte Antigen (HLA) is known to influence the pathogenesis of several complex human diseases resulting from gene-environmental interactions. Recently, it has emerged as one of the risk determinants of schizophrenia. The HLA-G protein (a non-classical MHC class I molecule), encoded by the HLA-G gene, is shown to play important role in embryonic development. Importantly, its genetic variations and aberrant expression have been implicated in pregnancy complications like preeclampsia, inflammation, and autoimmunity. Converging evidence implicates these phenomena as risk mechanisms of schizophrenia. However, the functional implications of HLA-G in schizophrenia are yet to be empirically examined. The impact of two functional polymorphisms [14bp Insertion/Deletion (INDEL) and +3187 A>G] and soluble HLA-G (sHLA-G) levels on schizophrenia risk was evaluated. In this exploratory study, the Ins/Ins genotype of 14bp INDEL was found to confer a strong risk for schizophrenia. Further, low levels of sHLA-G were shown to have a significant impact on Clinical Global Impression (CGI) severity in people with schizophrenia