K S Jacob

Christian Medical College & Hospital, Ludhiana, Punjab, India

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Publications (150)491.56 Total impact

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    ABSTRACT: Background: Variable responses to clozapine in patients with schizophrenia are complex and poorly understood phenomena. The findings of pharmacogenetic studies on the use of this drug are poorly replicated. Effects of individual polymorphisms have rarely proved explanatory. One possible explanation may be multi-factorial involvement of genetic and environmental influences. Aim: To evaluate the role of possible second and third order genetic interactions (epistasis) between polymorphisms in CYP1A2 (*1F, *1D, *1E, *1C), HTR3A (rs1062613 and rs2276302), DRD4 (120-bp duplication) and COMT (Val158Met) genes in clinical response, serum levels and adverse effects of clozapine in patients with treatment-resistant schizophrenia (TRS). Methods: The model-based multidimensionality reduction (MB-MDR) method has recently been shown to be superior to traditional parametric regression methods in detecting higher order gene-gene interactions. We used this approach in a sample of 93 patients with TRS to explore the epistatic effects of the polymorphisms of interest on clinical phenotypes of clozapine. Data on genotypes and phenotypes of the patients that was available from a previous pharmacogenetic study was used for the analysis. Results: The MB-MDR analysis showed a significant interaction between Val158Met, CYP1A2*1D and rs1062613 polymorphisms and clinical response to clozapine (p=0.002). In addition, multiple significant second and third order interactions were observed with regard to the adverse effects of clozapine (p<0.05). No significant interactions were observed between the polymorphisms and serum levels of clozapine. All the reported interactions were found to be significant after 1000 permutations. Conclusion: Epistatic analysis showed significant associations of several polymorphisms with clinical phenotypes of clozapine that were not previously found on isolated analysis. This emphasizes the importance of epistatic analysis in pharmacogenetic studies of clozapine. Such an approach may be useful in predicting a patient’s response to clozapine therapy.
    World Congress of Psychiatric Genetics, Copenhagen, Denmark; 10/2014
  • P Thangadurai, K S Jacob
    Indian Journal of Psychological Medicine 10/2014; 36(4):351-4. DOI:10.4103/0253-7176.140698
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    ABSTRACT: Background: Genetic factors explaining phenotypes in psychiatric genetics were always characterised by significant heterogeneity and non-reproducibility. Even understanding genetic basis of highly heritable diseases such as schizophrenia, was challenging. Contribution of environmental factors in terms of its interaction with genetic factors were recently implicated in addressing the unexplained heterogeneity of schizophrenia genetics. Aims and Objectives: The present study explored the possible associations of polymorphisms in genes: DRD4 (120-bp duplication) and COMT (Val158Met), with clinical response to clozapine in patients with treatment resistant schizophrenia (TRS). We tried to identify the associations of gene-gene interaction( DRD4XCOMT) and gene-environmental interactions with clinical phenotypes of c!lozapine. Methodology: A cohort of 95 participants with diagnosis of TRS was studied. The patients, were genotyped for the polymorphisms of interest using polymerase chain reaction and restriction fragment polymorphism (RFLP) method. Clozapine response were defined a priori. Appropriate statistical analysis were employed. Results: The polymorphisms were not found to associate statistically with clozapine response when analysed individually. However, interestingly we found a statistically significant DRD4XCOMT interaction over clozapine response. We also found significant gene-environmental interactions over clozapine response. A logistic regression model (Response ~ (COMTXDRD4)+age+smoking habit + maximum dose of clozapine + Abnormal involuntary movements scale + Adden’s cognitive examination scale) that proved most explanatory was derived. ! Conclusion: Gene-gene interaction between DRD4 and COMT and their gene-environment interactions play a significant role in predicting clinical response to clozapine therapy. Future studies were suggested to replicate our findings before it could be translated to clinical practice.
    International Conference on Schizophreni(ICONS) VI, Hyatt hotel, Chennai, TN, India; 08/2014
  • Sauradeep Sarkar, Mazda K Turel, Kuruthukulangara S Jacob, Ari G Chacko
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    ABSTRACT: Object T2-weighted intramedullary increased signal intensity (ISI) on MRI in patients with cervical spondylotic myelopathy (CSM) appears to represent a wide spectrum of pathological changes that determine reversibility of cord damage. Although sharp T2-weighted ISI on preoperative imaging may correlate with poorer surgical outcomes, there are limited data on how these changes progress following surgery. In this study, the authors characterized pre-and postoperative ISI changes in patients undergoing surgery for CSM and studied their postoperative evolution in an attempt to quantify their clinical significance. Methods The preoperative and postoperative MR images obtained in 56 patients who underwent oblique cervical corpectomy for CSM were reviewed, and the ISI was classified into 4 subtypes based on margins and intensity: Type 0 (none), Type 1 ("fuzzy"), Type 2 ("sharp"), and Type 3 ("mixed"). The locations of the ISI were further classified as focal if they represented single discrete lesions, multifocal if there were multiple lesions with intervening normal cord, and multisegmental if the lesions were continuous over more than 1 segment. The maximum craniocaudal length of the ISI was measured on each midsagittal MR image. The Nurick grade and Japanese Orthopaedic Association (JOA) score were used to assess clinical status. The mean duration of follow-up was 28 months. Results T2-weighted ISI changes were noted preoperatively in 54 patients (96%). Most preoperative ISI changes were Type 1 (41%) or Type 3 (34%), with a significant trend toward Type 2 (71%) changes at follow-up. Multi-segmental and Type 3 lesions tended to regress significantly after surgery (p = 0.000), reducing to Type 2 changes at follow-up. Clinical outcomes did not correlate with ISI subtype; however, there was a statistically significant trend toward improvement in postoperative Nurick Grade in patients with a > 50% regression in ISI size. In addition, patients with more than 18 months of follow-up showed significant regression in ISI size compared with patients imaged earlier. On logistic regression analysis, preoperative Nurick grade and duration of follow-up were the only significant predictors of postoperative improvement in functional status (OR 4.136, p = 0.003, 95% CI 1.623-10.539 and OR 6.402, p = 0.033, 95% CI 1.165-35.176, respectively). Conclusions There is a distinct group of patients with multisegmental Type 3 intramedullary changes who show remarkable radiological regression after surgery but demonstrate a residual sharp focal ISI at follow-up. A regression of the ISI by > 50% predicts better functional outcomes. Patients with a good preoperative functional status remain the most likely to show improvement, and the improvement continues to occur even at remote follow-up. The clinical relevance of the quality of the T2-weighted ISI changes in patients with CSM remains uncertain; however, postoperative regression of the ISI change is possibly a more important correlate of patient outcome than the quality of the ISI change alone.
    Journal of Neurosurgery Spine 07/2014; 21(4):1-9. DOI:10.3171/2014.6.SPINE13727 · 2.36 Impact Factor
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    ABSTRACT: Background. Sexual dysfunction, common in general medical practice, is under-recognized and inadequately managed resulting in significant morbidity and reduction in quality of life. We examined the nature, prevalence, clinical features and explanatory models of illness among men with sexual dysfunction in a general healthcare setting. Methods. We recruited 270 consecutive men attending a general health clinic. Participants were evaluated using a structured interview. The International Index of Erectile Function-5, the Chinese Index of Premature Ejaculation-5, Short Explanatory Model Interview and the Revised Clinical Interview Schedule were used to assess sexual dysfunction, explanatory models and psychiatric morbidity. Results. Premature ejaculation and erectile dysfunction were reported by 43.0% and 47.8% of men, respectively. The most common perceived causes were loss of semen due to masturbation and nocturnal emission. Popular treatments were herbal remedies and resources used were traditional healers. The factors associated with erectile dysfunction were diabetes mellitus, financial stress, past history of psychiatric treatment and common mental disorders such as depression and anxiety; those associated with premature ejaculation were common mental disorders, older age and financial debt. Sexual dysfunctions and concerns were under-diagnosed by physicians when compared to the research interview. Conclusion. There is a need to recognize sexual problems and effectively manage them in general medical settings. The need for sex education in schools and through the mass media, to remove sexual misconceptions, cannot be under-emphasized. Copyright 2014, NMJI.
    The National medical journal of India 07/2014; 27(4):198-201. · 0.91 Impact Factor
  • K S Jacob
    The National medical journal of India 07/2014; 27(4):189-91. · 0.91 Impact Factor
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    ABSTRACT: Background There is a dearth of information about the predictors of disability in schizophrenia from low and middle-income countries. This study attempted to investigate the impact of socio-demographic and clinical variables on disability in a cohort of first episode schizophrenia. Method Patients diagnosed to have DSM IV schizophrenia (n = 131) were assessed prospectively for psychopathology, functioning, insight and explanatory models of illness at baseline, 6, 12 and 60 months using standard instruments. Disability was assessed at 5 years. Multiple linear regression was employed to adjust for common confounders. Results We could follow up 95 (72.5%) patients. Sixty-five of these patients (68.4%) achieved remission. Disability scores at 5 years were associated negatively with episodic nature of illness at baseline, functional assessments at 6 and 12 months and return to pre-morbid level function. Disability correlated positively with psychopathology at 6 and 12 months and time spent in psychotic episodes. It was also associated with psychopathology, remission, insight and patient perspectives at the 5th year cross-sectional evaluation. While employment status at recruitment was not associated with disability, it was associated with unemployment at follow up. Conclusions Disability at 5 years was associated with illness variables- episodic nature of illness at baseline, psychopathology and functioning, duration in psychotic episode and return to pre-morbid function. Patient perspectives about their illness (insight and patient explanatory models) were only associated cross-sectionally at 60 months but not earlier and are more suggestive of a coping response rather than being predictive of outcome. The relationship between unemployment and disability suggests that they are products of the same disease process.
    Asian Journal of Psychiatry 06/2014; DOI:10.1016/j.ajp.2014.01.003
  • K.S. Jacob
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    ABSTRACT: While the traditional view within psychiatry is that insight is independent of psychopathology and predicts the course and outcome of psychosis, recent data from India argues that insight is secondary to interaction between progression of illness on one hand and local culture and social environment on the other. The findings suggest that “insight” is an Explanatory Model (EM) and may reflect attempts at coping with the devastating effects of mental disorders. Most societies are pluralistic and offer multiple, divergent and contradictory explanations for illnesses. These beliefs systems interact with the trajectory of the person's illness to produce a unique personal understanding, often based on a set of complex and contradictory EMs. Like all EMs, insight provides meaning to explain and overcome challenges including disabling symptoms, persistent deficits, impaired social relations and difficult livelihood issues. The persistence of distress, impairment, disability and handicap, despite regular and optimal treatment, call for explanations, which go beyond the simplistic concept of disease. People tend to choose EMs, which are non-stigmatizing and which seem to help explain and rationalize their individual concerns. The frequent presence of multiple and often contradictory EMs, held simultaneously, suggest that they are pragmatic responses at coping. The results advocate a non-judgmental approach and broad based assessment of EMs of illness and their comparison with culturally appropriate beliefs, attributions and actions. The biomedical model of illness should be presented without dismissing patient beliefs or belittling local cultural explanations for illness. Clinical practice demands a negotiation of shared model of care and treatment plan between patient and physician perspectives. The diversity of patients, problems, beliefs and cultures mandates the need to educate, match, negotiate and integrate psychiatric and psychological frameworks and interventions. It calls for multifaceted and nuanced understanding of “insight” and explanatory models of illness.
    Asian Journal of Psychiatry 06/2014; DOI:10.1016/j.ajp.2014.06.001
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    ABSTRACT: Early detection of residual disease may benefit management strategies in patients undergoing transsphenoidal surgery for acromegaly. This requires establishing objective thresholds for early postoperative growth hormone (GH) assays, and incorporating these parameters into a scale for outcome prediction. We analyzed a database containing the records of 86 patients who had undergone gross total transsphenoidal resection of GH-secreting pituitary adenomas. Early postoperative biochemical testing included a morning fasting basal GH assay on the first postoperative day (POD1) and a second GH assay following suppression with 100 g of oral glucose on the seventh postoperative day (POD7). Remission was defined as a normal IGF-1 with either a GH nadir <0.4 ng/ml following suppression with oral glucose or a basal fasting GH <1 ng/ml on follow-up dated >3 months after surgery. Receiver operator characteristic (ROC) curves identified optimal thresholds for all biochemical parameters. Logistic regression analysis assessed the statistical significance of factors associated with cure. A point system was developed, employing regression coefficients obtained from the multivariate statistical model to quantify the impact of each predictor on cure. Remission was achieved in 34.6 % of patients and was associated with smaller, non-invasive tumors with lower preoperative, POD1 and POD7 GH levels. Optimal thresholds obtained from the ROC analysis suggested that lower POD1 and POD7 GH values provided good sensitivity and specificity for cure, despite modest predictive values. The model with the best ability to predict outcome included size, POD1 GH and POD7 GH levels, with a score of ≥95 demonstrating high specificity for prediction of remission. Early postoperative GH assays are highly sensitivity and specific. The scoring system that we propose provided excellent predictive value and requires further validation in larger cohorts and in different populations. The model may help guide the intensity of follow-up and enable early identification of residual disease.
    Acta Neurochirurgica 04/2014; 156(7). DOI:10.1007/s00701-014-2098-5 · 1.79 Impact Factor
  • Indian Journal of Psychiatry 01/2014; 56(1):1-2. DOI:10.4103/0019-5545.124706
  • K S Jacob
    The National medical journal of India 01/2014; 27(1):35-8. · 0.91 Impact Factor
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    ABSTRACT: Background. We examined the nature, prevalence and explanatory models of sexual concerns and dysfunction among women in rural Tamil Nadu. Methods. Married women between 18 and 65 years of age, from randomly selected villages in Kaniyambadi block, Vellore district, Tamil Nadu, were chosen by stratified sampling technique. Sexual functioning was assessed using the Female Sexual Function Index (FSFI). The modified Short Explanatory Model Interview (SEMI) was used to assess beliefs about sexual concerns and the General Health Questionnaire-12 (GHQ-12) was used to screen for common mental disorders. Sociodemographic variables and other risk factors were also assessed. Results. Most of the women (277; 98.2%) contacted agreed to participate in the study. The prevalence of sexual dysfunction, based on the cut-off score on the FSFI, was 64.3%. However, only a minority of women considered it a problem (4.7%), expressed dissatisfaction (5.8%) or sought medical help (2.5%). The most common explanatory models offered for sexual problems included an unhappy marriage,stress and physical problems. Factors associated with lower FSFI included older age, illiteracy, as well as medical illness and sexual and marital factors such as menopause, poor quality of marital relationship, history of physical abuse and lack of privacy. Conclusion. The diagnosis of female sexual dysfunction needs to be nuanced and based on the broader personal and social context. Our findings argue that there is a need to use models that employ personal, local and contextual standards in assessing complex behaviours such as sexual function. Copyright 2014, NMJI.
    The National medical journal of India 01/2014; 27(1):4-8. · 0.91 Impact Factor
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    ABSTRACT: and aims: There is a dearth of data on the predictors of insight in schizophrenia. This study attempted to assess the predictors of insight in a cohort of first-episode schizophrenia followed up over 5 years. Patients diagnosed to have Diagnostic and statistical manual of mental disorders (4th ed.; DSM-IV) schizophrenia (n = 131) were assessed prospectively for insight, psychopathology and explanatory models of illness over a 5-year period using standard instruments. Multiple linear regression and generalized estimating equations (GEE) were employed to assess predictors of insight. We could follow up 95 (72.5%) patients, 5 years after recruitment. A total of 65 of these patients interviewed at 60 months (68.4%) achieved remission. Cross-sectional evaluations suggest a relationship between insight, psychosis rating and explanatory models of illness with good insight and medical models associated with good outcome. However, baseline and early illness data do not predict insight scores at 5 years. Serial longitudinal assessment of insight is negatively associated with Brief Psychiatric Rating Scale (BPRS) scores and positively associated with the number of nonmedical explanatory models of illness held by patients. These findings argue that insight and explanatory models of illness are secondary to psychopathology, course and outcome. They are dependent on the trajectory of the person's illness, are not independent of the condition and call for multifaceted understanding of the issues.
    International Journal of Social Psychiatry 10/2013; 60(6). DOI:10.1177/0020764013504561 · 1.15 Impact Factor
  • K S Jacob
    The National medical journal of India 09/2013; 26(5):307-8. · 0.91 Impact Factor
  • K S Jacob
    The National medical journal of India 09/2013; 26(5):255-7. · 0.91 Impact Factor
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    European Spine Journal 07/2013; 22(9). DOI:10.1007/s00586-013-2912-4 · 2.47 Impact Factor
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    ABSTRACT: The relative contributions of psychiatric morbidity and psychosocial stress to suicide, and the efficacy of mental health systems in reducing population suicide rates, are currently unclear. This study, therefore, aimed to investigate whether national suicide rates are associated with their corresponding mental health system indicators. Relevant data were retrieved from the following sources: the World Health Organization, the United Nations Statistics Division and the Central Intelligence Agency World Fact book. Suicide rates of 191 countries were compared with their mental health system indicators using an ecological study design and multivariate non-parametric robust regression models. Significant positive correlations between suicide rates and mental health system indicators (p<0.001) were documented. After adjusting for the effects of major macroeconomic indices using multivariate analyses, numbers of psychiatrists (p=0.006) and mental health beds (p<0.001) were significantly positively associated with population suicide rates. Countries with better psychiatric services experience higher suicide rates. Although these associations should be interpreted with caution, as the issues are complex, we suggest that population-based public health strategies may have greater impact on national suicide rates than curative mental health services for individuals.
    International Journal of Law and Psychiatry 07/2013; 36(5-6). DOI:10.1016/j.ijlp.2013.06.004 · 1.19 Impact Factor
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    ABSTRACT: PURPOSE: To determine whether motion preservation following oblique cervical corpectomy (OCC) for cervical spondylotic myelopathy (CSM) persists with serial follow-up. METHODS: We included 28 patients with preoperative and at least two serial follow-up neutral and dynamic cervical spine radiographs who underwent OCC for CSM. Patients with an ossified posterior longitudinal ligament (OPLL) were excluded. Changes in sagittal curvature, segmental and whole spine range of motion (ROM) were measured. Nathan's system graded anterior osteophyte formation. Neurological function was measured by Nurick's grade and modified Japanese Orthopedic Association (JOA) scores. RESULTS: The majority (23 patients) had a single or 2-level corpectomy. The average duration of follow-up was 45 months. The Nurick's grade and the JOA scores showed statistically significant improvements after surgery (p < 0.001). 17 % of patients with preoperative lordotic spines had a loss of lordosis at last follow-up, but with no clinical worsening. 77 % of the whole spine ROM and 62 % of segmental ROM was preserved at last follow-up. The whole spine and segmental ROM decreased by 11.2° and 10.9°, respectively (p ≤ 0.001). Patients with a greater range of segmental movement preoperatively had a statistically greater range of movement at follow-up. The analysis of serial radiographs indicated that the range of movement of the whole spine and the range of movement at the segmental spine levels significantly reduced during the follow-up period. Nathan's grade showed increase in osteophytosis in more than two-thirds of the patients (p ≤ 0.01). The whole spine range of movement at follow-up significantly correlated with Nathan's grade. CONCLUSIONS: Although the OCC preserves segmental and whole spine ROM, serial measurements show a progressive decrease in ROM albeit without clinical worsening. The reduction in this ROM is probably related to degenerative ossification of spinal ligaments.
    European Spine Journal 03/2013; 22(7). DOI:10.1007/s00586-013-2724-6 · 2.47 Impact Factor
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    ABSTRACT: AIM: We examinted the attitude, knowledge and perceived barriers to evidence-based practice of radiology (EBPR) among residents in radiology. STUDY DESIGN AND SETTING: We used the McColl questionnaire (1) and the BARRIERS scale (2) to assess the issues among radiology trainees attending an annual refresher course. Ninety six residents from 32 medical colleges from Southern India attended the course. RESULTS: Eighty (83.3%) residents, 55 male and 25 female of age range 24-34 years, consented and returned the questionnaire. The majority of the participants had a positive attitude towards EBPR. However, 45% were unaware of sources for evidence based literature although many had access to Medline (45%) and the internet (80%). The majority (70%) were aware of the common technical terms (e.g. odds ratio, absolute and relative risk) but other complex details (e.g. meta-analysis, clinical effectiveness, confidence interval, publication bias and number needed to treat) were poorly understood. Though majority of residents (59%) were currently following guidelines and protocols laid by colleagues within their departments, 70% of residents were interested in learning the skills of EBPR and were willing to appraise primary literature or systematic reviews by themselves. Insufficient time on the job to implement new ideas (70.1%); relevant literature is not being complied in one place (68.9%); not being able to understand statistical methods (68.5%) were considered to be the major barriers to EBPR. Training in critical appraisal significantly influence usage of bibliographic databases (p<0.0001). Attitude of collegues (p=0.006) influenced attitude of the trainees towards EBPR. Those with higher knowledge scores (p=0.02) and a greater awareness of sources for seeking evidence based literature (p=0.05) held stronger beliefs that EBPR significantly improved patient care. CONCLUSIONS: The large knowledge gap related to EBPR suggests the need to incorporate structured training into the core-curriculum of training programmes in radiology.
    European journal of radiology 02/2013; DOI:10.1016/j.ejrad.2013.01.026 · 2.65 Impact Factor

Publication Stats

2k Citations
491.56 Total Impact Points


  • 2006–2014
    • Christian Medical College & Hospital
      Ludhiana, Punjab, India
  • 1999–2014
    • Christian Medical College Vellore
      • • Department of Psychiatry
      • • Department of Neurosurgery
      Velluru, Tamil Nādu, India
  • 2013
    • Aarhus University
      • Department of Biomedicine
      Århus, Central Jutland, Denmark
  • 2012
    • JSS Medical College, Mysore
      • Department of Psychiatry
      Mahisūr, Karnātaka, India
  • 2009–2010
    • King's College London
      • Department of Health Service and Population Research
      London, ENG, United Kingdom
    • PSG Institute of Medical Sciences & Research
      • Department of Psychiatry
      Koyambattūr, Tamil Nādu, India
  • 2007
    • University of Pittsburgh
      Pittsburgh, Pennsylvania, United States
  • 2004
    • Christian Hospital
      Saint Louis, Michigan, United States