Correction: Odegaard et al. Distinct Synaptic Vesicle Proteomic Signatures Associated with Pre- and Post-Natal Oxycodone-Exposure. Cells 2022, 11, 1740.

In the original publication [...].

Methylome-wide and meQTL analysis helps to distinguish treatment response from non-response and pathogenesis markers in schizophrenia.

Schizophrenia is a complex condition with entwined genetic and epigenetic risk factors, posing a challenge to disentangle the intermixed pathological and therapeutic epigenetic signatures. To resolve this, we performed 850K methylome-wide and 700K genome-wide studies on the same set of schizophrenia patients by stratifying them into responders, non-responders, and drug-naïve patients. The key genes that signified the response were followed up using real-time gene expression studies to understand the effect of antipsychotics at the gene transcription level. The study primarily implicates hypermethylation in therapeutic response and hypomethylation in the drug-non-responsive state. Several differentially methylated sites and regions colocalized with the schizophrenia genome-wide association study (GWAS) risk genes and variants, supporting the convoluted gene-environment association. Gene ontology and protein-protein interaction (PPI) network analyses revealed distinct patterns that differentiated the treatment response from drug resistance. The study highlights the strong involvement of several processes related to nervous system development, cell adhesion, and signaling in the antipsychotic response. The ability of antipsychotic medications to alter the pathology by modulating gene expression or methylation patterns is evident from the general increase in the gene expression of response markers and histone modifiers and the decrease in class II human leukocyte antigen (HLA) genes following treatment with varying concentrations of medications like clozapine, olanzapine, risperidone, and haloperidol. The study indicates a directional overlap of methylation markers between pathogenesis and therapeutic response, thereby suggesting a careful distinction of methylation markers of pathogenesis from treatment response. In addition, there is a need to understand the trade-off between genetic and epigenetic observations. It is suggested that methylomic changes brought about by drugs need careful evaluation for their positive effects on pathogenesis, course of disease progression, symptom severity, side effects, and refractoriness.

A Review of Radiation-Induced Alterations of Multi-Omic Profiles, Radiation Injury Biomarkers, and Countermeasures.

Increasing utilization of nuclear power enhances the risks associated with industrial accidents, occupational hazards, and the threat of nuclear terrorism. Exposure to ionizing radiation interferes with genomic stability and gene expression resulting in the disruption of normal metabolic processes in cells and organs by inducing complex biological responses. Exposure to high-dose radiation causes acute radiation syndrome, which leads to hematopoietic, gastrointestinal, cerebrovascular, and many other organ-specific injuries. Altered genomic variations, gene expression, metabolite concentrations, and microbiota profiles in blood plasma or tissue samples reflect the whole-body radiation injuries. Hence, multi-omic profiles obtained from high-resolution omics platforms offer a holistic approach for identifying reliable biomarkers to predict the radiation injury of organs and tissues resulting from radiation exposures. In this review, we performed a literature search to systematically catalog the radiation-induced alterations from multi-omic studies and radiation countermeasures. We covered radiation-induced changes in the genomic, transcriptomic, proteomic, metabolomic, lipidomic, and microbiome profiles. Furthermore, we have covered promising multi-omic biomarkers, FDA-approved countermeasure drugs, and other radiation countermeasures that include radioprotectors and radiomitigators. This review presents an overview of radiation-induced alterations of multi-omics profiles and biomarkers, and associated radiation countermeasures.

Co-Transcriptomic Analysis of the Maize-Western Corn Rootworm Interaction.

The Western corn rootworm (WCR; Diabrotica virgifera virgifera) is an economically important belowground pest of maize. Belowground feeding by WCR is damaging because it weakens the roots system, diminishes nutrient uptake, and creates entry points for fungal and bacterial pathogens and increases lodging, all of which can significantly suppress maize yields. Previously, it was demonstrated that belowground herbivory can trigger plant defense responses in the roots and the shoots, thereby impacting intraplant communication. Although several aspects of maize-WCR interactions have been reported, co-transcriptomic remodeling in the plant and insect are yet to be explored. We used a maize genotype, Mp708, that is resistant to a large guild of herbivore pests to study the underlying plant defense signaling network between below and aboveground tissues. We also evaluated WCR compensatory transcriptome responses. Using RNA-seq, we profiled the transcriptome of roots and leaves that interacted with WCR infestation up to 5 days post infestation (dpi). Our results suggest that Mp708 shoots and roots had elevated constitutive and WCR-feeding induced expression of genes related to jasmonic acid and ethylene pathways, respectively, before and after WCR feeding for 1 and 5 days. Similarly, extended feeding by WCR for 5 days in Mp708 roots suppressed many genes involved in the benzoxazinoid pathway, which is a major group of indole-derived secondary metabolites that provides resistance to several insect pests in maize. Furthermore, extended feeding by WCR on Mp708 roots revealed several genes that were downregulated in WCR, which include genes related to proteolysis, neuropeptide signaling pathway, defense response, drug catabolic process, and hormone metabolic process. These findings indicate a dynamic transcriptomic dialog between WCR and WCR-infested maize plants.

Contribution from MHC-Mediated Risk in Schizophrenia Can Reflect a More Ethnic-Specific Genetic and Comorbid Background.

The immune system seems to play a significant role in the development of schizophrenia. This becomes more evident with the emerging role of MHC complex and cytokines in schizophrenia. In the recent past, several GWAS have implied that the 6p21 region was associated with schizophrenia. However, the majority of these studies were performed in European populations. Considering tremendous variations in this region and the probability of South Indian populations being quite different from the European gene-pool from an immunogenetic point, the present study was initiated to screen SNPs in the 2.28 MB region, spanning the extended MHC locus, in 492 cases and controls from a South Indian population. We found a very strong association of rs3815087 with schizophrenia at both allelic and genotypic levels with a 7.3-fold increased risk in the recessive model. Interestingly, the association of none of the earlier reported GWAS hits, such as rs3130375, rs3131296, rs9272219, or rs3130297 were found to be replicable in our study population. rs3815087 lies in the 5'UTR region of the psoriasis susceptibility 1 candidate 1 (PSORS1C1) gene, which further suggests that inflammatory processes might be an important common pathogenic pathway leading to both schizophrenia and psoriasis. The study hints at ethnic specific gene-environment interaction in determining the critical threshold for disease initiation and progression.

Distinct Synaptic Vesicle Proteomic Signatures Associated with Pre- and Post-Natal Oxycodone-Exposure.

The current opioid crisis, which has ravaged all segments of society, continues to pose a rising public health concern. Importantly, dependency on prescription opioids such as oxycodone (oxy) during and after pregnancy can significantly impact the overall brain development of the exposed offspring, especially at the synapse. A significant knowledge gap that remains is identifying distinct synaptic signatures associated with these exposed offspring. Accordingly, the overall goal of this current study was to identify distinct synaptic vesicle (SV) proteins as signatures for offspring exposed to oxy in utero (IUO) and postnatally (PNO). Using a preclinical animal model that imitates oxycodone exposure in utero (IUO) and postnatally (PNO), we used a quantitative mass spectrometry-based proteomics platform to examine changes in the synaptic vesicle proteome on post-natal day 14 (P14) IUO and PNO offspring. We identified MEGF8, associated with carpenter syndrome, to be downregulated in the IUO offspring while LAMTOR4, associated with the regulator complex involved in lysosomal signaling and trafficking, was found to be upregulated in the PNO groups, respectively. Their respective differential expression was further validated by Western blot. In summary, our current study shows exposure to oxy in utero and postnatally can impact the SV proteome in the exposed offspring and the identification of these distinct SV signatures could further pave the way to further elucidate their downstream mechanisms including developing them as potential therapeutic targets.

Decoding the Synaptic Proteome with Long-Term Exposure to Midazolam during Early Development.

The intensive use of anesthetic and sedative agents in the neonatal intensive care unit (NICU) has raised controversial concerns about the potential neurodevelopmental risks. This study focused on midazolam (MDZ), a common benzodiazepine regularly used as a sedative on neonates in the NICU. Mounting evidence suggests a single exposure to MDZ during the neonatal period leads to learning disturbances. However, a knowledge gap that remains is how long-term exposure to MDZ during very early stages of life impacts synaptic alterations. Using a preclinical rodent model system, we mimicked a dose-escalation regimen on postnatal day 3 (P3) pups until day 21. Next, purified synaptosomes from P21 control and MDZ animals were subjected to quantitative mass-spectrometry-based proteomics, to identify potential proteomic signatures. Further analysis by ClueGO identified enrichment of proteins associated with actin-binding and protein depolymerization process. One potential hit identified was alpha adducin (ADD1), belonging to the family of cytoskeleton proteins, which was upregulated in the MDZ group and whose expression was further validated by Western blot. In summary, this study sheds new information on the long-term exposure of MDZ during the early stages of development impacts synaptic function, which could subsequently perturb neurobehavioral outcomes at later stages of life.

Misconstrued Notions and Misplaced Interventions: An Assessment of State Policy on Domestic Work in India.

Given the informal employment relationship that marks the paid domestic work sector, this paper examines the important state interventions in India which follow the ILO convention on domestic work. The understanding that the sector is homogenous and thus could be regulated or managed through uniform intervention, whether legal or otherwise, has prevailed. This was even when existing studies have demonstrated the existence of segmented labour markets with varying employer, work and worker identities. The extension of the Minimum Wages Act to domestic workers, the draft National Policy on Domestic Work, and the Domestic Workers Sector Skill Council (DWSSC) set up under the National Skill Development Council of the Ministry of Skill Development & Entrepreneurship of Government of India, are examined in the paper in detail. The paper highlights how various state interventions have outlined the sector, the work, the workers and their everyday experiences and negotiations in terms of extending or framing these interventions. Examining the assumptions and objectives that have defined the formation of Domestic Workers Sector Skill Development council and its functioning, the paper argues that the attempt to corporatize the sector is a classic case of how the state tends to ignore the specificities that feature the sector leading to its poor impact.

A compiled dataset of molecular pathways associated with fusion genes identified in pediatric cancers.

Fusion genes can serve as actionable biomarkers for diagnosis, prognosis or therapeutic stratification in the clinic. Pathways associated with fusion genes identified in different pediatric cancers are compiled in this article. Fusion genes reported in each cancer were collected using the PubMed search option with the keywords 'fusion transcript', 'fusion gene,' 'chromosomal translocation,' or 'DNA translocation' along with the corresponding pediatric cancer type. Research articles that identified fusion genes using conventional Fluorescence in situ hybridization (FISH) or quantitative real-time polymerase chain reaction (RT-PCR) methods or high-throughput RNA or DNA sequencing were included. The collected fusion gene data were compiled for each cancer and analyzed to identify their functions related to cancer and associated pathways using Ingenuity Pathway Analysis (IPA) and ClueGO software programs. Similarities in associated pathways across different cancers were also analyzed using IPA to identify commonly affected genes and pathways. This value-added and functionally annotated dataset will be an excellent resource for pediatric cancer researchers and clinicians interested in exploring fusion genes in different cancers. This article is a companion article to 'Fusion genes as biomarkers in pediatric cancers: A review of the current state and applicability in diagnostics and personalized therapy'[1].

ChimeRScope: a novel alignment-free algorithm for fusion transcript prediction using paired-end RNA-Seq data.

The RNA-Seq technology has revolutionized transcriptome characterization not only by accurately quantifying gene expression, but also by the identification of novel transcripts like chimeric fusion transcripts. The 'fusion' or 'chimeric' transcripts have improved the diagnosis and prognosis of several tumors, and have led to the development of novel therapeutic regimen. The fusion transcript detection is currently accomplished by several software packages, primarily relying on sequence alignment algorithms. The alignment of sequencing reads from fusion transcript loci in cancer genomes can be highly challenging due to the incorrect mapping induced by genomic alterations, thereby limiting the performance of alignment-based fusion transcript detection methods. Here, we developed a novel alignment-free method, ChimeRScope that accurately predicts fusion transcripts based on the gene fingerprint (as k-mers) profiles of the RNA-Seq paired-end reads. Results on published datasets and in-house cancer cell line datasets followed by experimental validations demonstrate that ChimeRScope consistently outperforms other popular methods irrespective of the read lengths and sequencing depth. More importantly, results on our in-house datasets show that ChimeRScope is a better tool that is capable of identifying novel fusion transcripts with potential oncogenic functions. ChimeRScope is accessible as a standalone software at (https://github.com/ChimeRScope/ChimeRScope/wiki) or via the Galaxy web-interface at (https://galaxy.unmc.edu/).

The genomewide transcriptional response underlying the pea aphid wing polyphenism.

Phenotypic plasticity is a key life history strategy used by many plants and animals living in heterogeneous environments. A multitude of studies have investigated the costs and limits of plasticity, as well as the conditions under which it evolves. Much less well understood are the molecular genetic mechanisms that enable an organism to sense its environment and respond in a plastic manner. The pea aphid wing polyphenism is a compelling laboratory model to study these mechanisms. In this polyphenism, environmental stressors like high density cause asexual, viviparous adult female aphids to change the development of their embryos from wingless to winged morphs. The life history trade-offs between the two morphs have been intensively studied, but the molecular mechanisms underlying this process remain largely unknown. We therefore performed a genomewide study of the maternal transcriptome at two time points with and without a crowding stress to discover the maternal molecular changes that lead to the development of winged vs. wingless offspring. We observed significant transcriptional changes in genes associated with odorant binding, neurotransmitter transport, hormonal activity and chromatin remodelling in the maternal transcriptome. We also found that titres of serotonin, dopamine and octopamine were higher in solitary compared to crowded aphids. We use these results to posit a model for how maternal signals inform a developing embryo to be winged or wingless. Our findings add significant insights into the identity of the molecular mechanisms that underlie environmentally induced morph determination and suggest a possible role for biogenic amine regulation in polyphenisms generally.

Pro-inflammatory cytokines and their epistatic interactions in genetic susceptibility to schizophrenia.

BACKGROUND: In schizophrenia, genetic background may provide a substrate for intrinsic maldevelopment of the brain through environmental influences, by recruiting neurotrophic factors and cytokines, to trigger the changes that lead to impaired neuronal functions. Cytokines being the key regulators of immune/inflammatory reactions are also known to influence the dopaminergic, noradrenergic, and serotonergic neurotransmission. Therefore, functional polymorphisms in cytokine genes may result in imbalances in the pro- and anti-inflammatory cytokine production. METHODS: We screened polymorphisms in pro- and anti-inflammatory cytokine genes using a case-control association study in a South Indian population. The role of allele, genotype, haplotype, and diplotypes of these cytokine genes and their epistatic interactions were assessed in contributing to the risk of developing schizophrenia. Meta-analysis for the reported associations was also monitored for global significance. RESULTS: The pro-inflammatory cytokine gene polymorphisms in IL1Ars1800587, IL6rs1800796, TNFArs361525, and IFNGrs2069718 were associated with schizophrenia. The study also provides significant evidence for strong epistatic interactions among pro-inflammatory cytokine genes IL6 and IFNG in the development of schizophrenia. In silico analysis suggested that associated risk variants were indicative of altered transcriptional activity with higher production of IL1α, IL-6, TNF-α, and IFN-ɤ cytokines. Meta-analysis indicated heterogeneity among study population while IL1Ars1800587 was found to be globally significant. CONCLUSIONS: It is important to identify the nature of inflammatory response that can be amplified by the environment, to influence either Th1 response or Th2 response. The associated functional variants in the study are involved with increased expression resulting in higher production of the pro-inflammatory cytokines IL-1α, IL-6, TNF-α, and IFN-γ. The interaction of immunological stressors with these high producer alleles of pro-inflammatory cytokines may suggest that even a lower threshold may be sufficient to induce a resultant chronic effect on the psycho-social and environmental stressors that may result in the development and pathogenesis of schizophrenia. Understanding environmental factors that influence the expression of these pro-inflammatory cytokine genes or their interaction can possibly help in dissecting the phenotypic variation and therapeutic response to antipsychotics in schizophrenia.

Antipsychotic drug dosage and therapeutic response in schizophrenia is influenced by ABCB1 genotypes: a study from a south Indian perspective.

AIM: The conventional practice of using trial and error mode to select antipsychotic drugs in treatment of schizophrenia can result in symptom exacerbations, relapse and severe side effects, resulting in higher costs of treatment. P-glycoprotein (ABCB1) is known to regulate the concentration of antipsychotic drugs in the brain. Variable expressivity based on polymorphism in the gene ABCB1 may reflect on the drug response and its relationship to dosage. MATERIALS & METHODS: All antipsychotic dosages administered to patients were converted to common chlorpromazine equivalents. Response to antipsychotics was based on 50% cutoff in Brief Psychiatric Rating Scale ratings after 1-year of follow-up. Using a case-control study design, ABCB1 polymorphisms were screened in 192 individuals grouped into responders and nonresponders. RESULTS: A strong allelic, genotypic and haplotypic association, was observed, which was predictive of good response to antipsychotics. Individuals carrying the favorable homozygous genotypes of rs1045642 and rs2032582 displayed better response with increased dosage while those carrying risk genotype manifested refractoriness on increased dosage. CONCLUSION: The study suggests that a priori knowledge of ABCB1 genotypes can provide a significant input into evaluating the patient's response to medication, and minimizing redundant dosing and refractoriness.

Stratified familialism: the care regime in India through the lens of childcare.

This article explores the political and social economy of care in India through a focus on childcare practices, from the viewpoint of the care giver ­ a perspective frequently ignored or touched on only generally in earlier discussions on development or social policy. It is argued that the care regime is an ad hoc summation of informal, stratified practices. It is shaped by the institutional context, in particular the economic and social inequalities of work and livelihoods, as well as trends and absences in state economic and social policy. Central to the dynamics of care practices in India is the ideology of gendered familialism in public discourse and policy, which reiterates care as a familial and female responsibility and works to devalue and diminish the dimensions of care. By delineating the range of institutions through which everyday childcare practices are organized, this contribution draws out the differentiations and actualities of stratified familialism and care. At one end of the spectrum are those who have the possibility to retain familial carers at home and supplement them with paid and other institutional carers; at the other are those who are neither able to retain family members at home nor fill the care gap through formal institutions.

Association of single nucleotide gene polymorphism at interleukin-1beta +3954, -511, and -31 in chronic periodontitis and aggressive periodontitis in Dravidian ethnicity.

BACKGROUND: Interleukin (IL)-1beta gene polymorphisms are considered a potential risk factor for periodontal disease. The aim of this study is to identify the association of IL-1beta gene polymorphisms with chronic periodontitis and aggressive periodontitis in a Malayalam-speaking Dravidian population from South India. METHODS: The case-control study consisted of 43 patients with chronic periodontitis and 54 patients with aggressive periodontitis as cases, and the control group consisted of 101 healthy subjects. All subjects were genotyped for IL-1beta +3954, -511, and -31 loci by polymerase chain reaction amplification followed by restriction enzyme digestion and gel electrophoresis. Genotype, allele, and haplotype analyses were done. RESULTS: Analyses for allele and genotypes showed a high frequency of the C allele and CC genotype for single nucleotide polymorphism IL-1beta +3954 in the group with chronic periodontitis and no difference for patients with aggressive periodontitis compared to controls (P <0.05). Haplotype analysis showed that IL-1beta -31 and -511 were in strong linkage disequilibrium in all groups. The IL-1beta -31 allele T was in linkage with allele T of IL-1beta +3954 in the control group. CONCLUSIONS: In the Malayalam-speaking Dravidian population, allele C of IL-1beta +3954 appeared to be an important risk factor for chronic periodontitis. The IL-1beta -31 allele T was in linkage with allele T of IL-1beta +3954 in the control group. No gene polymorphisms were found in patients with aggressive periodontitis. More studies with a larger sample size involving the entire cluster of the IL-1beta gene are necessary to determine the exact role of IL-1beta gene polymorphisms in periodontal disease.

Evidence of association of serotonin transporter gene polymorphisms with schizophrenia in a South Indian population.

Serotonin (5-hydroxytryptamine (5-HT)) transporter (SLC6A4) is known to influence mood, emotion, cognition and efficacy of antidepressants, particularly that of selective serotonin reuptake inhibitors. Atypical antipsychotics exert their effects partially through serotinergic systems, and hence, variation in 5-HT uptake may affect antipsychotic action mediated through the serotinergic system. Therefore, investigating the role of SLC6A4 as a risk factor for developing schizophrenia and treatment response had been a point of concern for many investigators, but with variable outcome. In this study, we examined the genetic roles of five polymorphisms of SLC6A4, including those of the widely studied 44 base pair variable number of tandem repeat (VNTR) in the promoter region of SLC6A4 (the serotonin transporter gene-linked polymorphic region: 5HTTLPR) and a VNTR polymorphism (STin2) in the second intron, in schizophrenia and its influence on the severity of symptoms in a South Indian population from Kerala, comprising 586 individuals. We detected significant allelic and genotypic associations with rs2066713 (both allelic and genotypic P-value <0.001), 5HTTLPR (allelic P-value=0.008 and genotypic P-value=0.03) and STin2 polymorphisms (allelic P-value=0.001 and genotypic P-value=0.002). A haplotype linking these three risk alleles, 5HTTLPR/S-rs2066713/C-STin2/12-repeat (P-value=0.0059), was also significantly associated with disease in our population. Patients with STin2 12-repeat homozygotes showed a greater severity of blunted effect symptom. These results suggest a strong role of SLC6A4 in schizophrenia, possibly with a specific behavioral endophenotype in a South Indian population.

Role of endothelial nitric oxide synthase gene polymorphisms in predicting aneurysmal subarachnoid hemorrhage in South Indian patients.

Endothelial nitric oxide synthase (eNOS) gene polymorphisms have been implicated as predisposing genetic factors that can predict aneurysmal subarachnoid hemorrhage (aSAH), but with controversial results from different populations. Using a case-control study design, we tested the hypothesis whether variants in eNOS gene can increase risk of aSAH among South Indian patients, either independently, or by interacting with other risk factors of the disease. We enrolled 122 patients, along with 224 ethnically matched controls. We screened the intron-4 27-bp VNTR, the promoter T-786C and the exon-7 G894T SNPs in the eNOS gene. We found marked interethnic differences in the genotype distribution of eNOS variants when comparing the South Indian population with the reported frequencies from Caucasian and Japanese populations. Genotype distributions in control and patient populations were found to be in Hardy-Weinberg equilibrium. In patients, the allele, genotype and estimated haplotype frequencies did not differ significantly from the controls. Multiple logistic regression indicated hypertension and smoking as risk factors for the disease, however the risk alleles did not have any interaction with these risk factors. Although the eNOS polymorphisms were not found to be a likely risk factor for aSAH, the role of factors such as ethnicity, gender, smoking and hypertension should be evaluated cautiously to understand the genotype to phenotype conversion.

Universal protocol for generating 100bp size standard for endless usage

Developing countries are facing severe bottlenecks in the technological advancement in biotechnology, due to restrictions imposed by patent protected products and protocols. This calls for designing of simple and cost-effective alternatives for the indispensable products like DNA molecular weight markers. We demonstrate a novel, rapid and cost-effective method of making in-house 100bp ladder for routine use. In our method we use a single forward primer and five reverse primers designed on the backbone sequence of a commonly used vector template. These primers are used at a universal annealing temperature to amplify ten DNA fragments of accurate size ranging from 100bp to 1000bp. Our PCR-based method can provide size standards for an endless usage.

The XVth World Congress of Psychiatric Genetics, October 7-11, 2007: Rapporteur summaries of oral presentations.

The World Congress of Psychiatric Genetics (WCPG) has become an annual event since the early 1990's sponsored by the International Society of Psychiatric Genetics (ISPG). Each year the latest published and unpublished findings are aired for discussion by representatives of the majority of research programs on this topic world-wide. The 2007 congress was held in New York City and attracted over 1000 researchers. The topics emphasized included results from whole genome association studies, the significance of copy number variation and the important contributions of epigenetic events to psychiatric disorders. There were over 20 oral sessions devoted to these and other topics of interest. Young investigator recipients of travel awards served as rapporteurs to summarize sessions and these summaries follow.

Association of dopamine receptor polymorphisms with schizophrenia and antipsychotic response in a South Indian population.

BACKGROUND: Alterations in the dopamine transmission and receptor density are hypothesized in the pathophysiology of schizophrenia but ethnic disparities are reported to exist in disease association and therapeutic response to psychotropic medication. Antipsychotics have higher binding affinity to D2 subtype of dopamine receptor. DRD2 Cys311, TaqIB1 and TaqIA1 variants are considered to have either reduced affinity for dopamine and hypo-dopaminergic activity. METHODS: We examined the role of Taq1B, Taq1D, S311C, H313H and Taq1A polymorphisms of DRD2 gene in schizophrenia and antipsychotic treatment response in 213 patients and 196 controls from a homogenous South Indian population. A more detailed genotype phenotype association analysis was carried out to understand the disease in terms of its socio-cultural factors. RESULTS: H313HTT genotype was found to be associated with schizophrenia (P = 0.004) while TaqIB1B1 genotype was significantly associated with higher psychopathology score. When treatment response was considered H313HCC, TaqIA2A2 and Taq1D1D1 had higher mean improvement scores. TaqID1D1 and H313HTT genotype were found to be significantly higher in responders than in nonresponder group. Distinct shift in the LD patterns of responder and non-responder group was observed. Certain symptoms were characteristic of our patient population. Following medication the scores and presentation of these symptoms tend to vary in the responder and non-responder groups. CONCLUSION: Based on genotype phenotype correlations it can be suggested that certain polymorphisms can be defined for their critical functions in disease and their role in treatment response in South Indian population. The present study suggests that in addition to ethnic bias, socio-cultural factors should also be considered while evaluating genotype phenotype correlations, in association and treatment response to complex disorders like schizophrenia.