Publications by authors named "Dhruva Ithal"

12 Publications

  • Page 1 of 1

Cross-diagnostic evaluation of minor physical anomalies in psychiatric disorders.

J Psychiatr Res 2021 Oct 20;142:54-62. Epub 2021 Jul 20.

Department of Psychiatry, National Institute for Mental Health and Neurosciences (NIMHANS), Bangalore, India. Electronic address:

Background: Minor physical anomalies (MPA) are markers of impaired neurodevelopment during the prenatal stage. Assessing MPA across psychiatric disorders may help understand their shared nature. In addition, MPA in family members would indicate a shared liability and endophenotype potential. We examined familial aggregation of MPA and their role as transdiagnostic and disorder-specific markers of 5 major psychiatric/neuropsychiatric conditions (schizophrenia, bipolar disorder, substance dependence, obsessive-compulsive disorder, and Alzheimer's dementia).

Methods: Modified Waldrop's MPA scale was applied on 1321 individuals from 439 transdiagnostic multiplex families and 125 healthy population controls (HC). Stage of fetal development (morphogenetic/phenogenetic)- and anatomical location (craniofacial/peripheral)-based sub-scores were calculated. Familiality and endophenotypic potential of MPA were analyzed with serial negative binomial mixed-effect regression. Cross-diagnostic differences and the effect of family history density (FHD) of each diagnosis on MPA were assessed. Mixed-effects Cox models estimated the influence of MPA on age-at-onset of illness (AAO).

Results: MPA were found to be heritable in families with psychiatric disorders, with a familiality of 0.52. MPA were higher in psychotic disorders after controlling for effects of sex and intrafamilial correlation. Morphogenetic variant MPA was noted to be lower in dementia in comparison to HC. FHD of schizophrenia and bipolar disorder predicted higher, and that of dementia and substance dependence predicted lower MPA. MPA brought forward the AAO [HR:1.07 (1.03-1.11)], and this was more apparent in psychotic disorders.

Conclusion: MPA are transmissible in families, are specifically related to the risk of developing psychoses, and predict an earlier age at onset. Neurodevelopmentally informed classification of MPA has the potential to enhance the etiopathogenic and translational understanding of psychiatric disorders.
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http://dx.doi.org/10.1016/j.jpsychires.2021.07.028DOI Listing
October 2021

Association study of Val66Met gene polymorphism with bipolar disorder and lithium treatment response in Indian population.

J Psychopharmacol 2021 Jul 27:2698811211032609. Epub 2021 Jul 27.

Molecular Genetics Laboratory, Department of Psychiatry, National Institute of Mental Health and Neuro Sciences, Bengaluru, Karnataka, India.

Background: The association of the Val66Met (rs6265) polymorphism in the brain-derived neurotrophic factor () gene with bipolar disorder (BD) and response to lithium treatment has been suggested, though inconsistently. The considerable diversity of allele frequency across different populations contributes to this. There is no data from South Asia till date. Hence, we examined the association of this polymorphism in BD cases from India, and its association with lithium treatment response.

Methods: BD patients ( = 301) were recruited from the clinical services of National Institute of Mental Health and Neurosciences (NIMHANS), India. Lithium treatment response for 190 BD subjects was assessed using Alda scale by NIMH life charts. Patients with total score ⩾7 were defined as lithium responders ( = 115) and patients with score <7 were defined as lithium non-responders ( = 75). Healthy controls ( = 484) with no lifetime history of neuropsychiatric illness or a family history of mental illness were recruited as control set. Genotyping was performed by TaqMan genotyping assay.

Results: Genotype and allele frequency of Val66Met SNP was significantly different (χ2 = 7.78,  = 0.02) in cases compared to controls, and the Val(G) allele was more frequent (χ2 = 7.08,  = 0.008) in BD patients. However, no significant difference is noted in genotype or allele frequencies of this polymorphism between the lithium responders and non-responders.

Conclusions: The Val(G) allele of Val66Met polymorphism is associated with risk of BD in this sample, but it is not related to response to lithium.
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http://dx.doi.org/10.1177/02698811211032609DOI Listing
July 2021

Are There Familial Patterns of Symptom Dimensions in Obsessive-Compulsive Disorder?

Front Psychiatry 2021 20;12:651196. Epub 2021 Apr 20.

Accelerator Program for Discovery in Brain Disorders Using Stem Cells, National Institute of Mental Health & Neuro Sciences (NIMHANS), Bangalore, India.

Obsessive-compulsive disorder (OCD) is a heterogeneous illness, and emerging evidence suggests that different symptom dimensions may have distinct underlying neurobiological mechanisms. We aimed to look for familial patterns in the occurrence of these symptom dimensions in a sample of families with at least two individuals affected with OCD. Data from 153 families (total number of individuals diagnosed with DSM-5 OCD = 330) recruited as part of the Accelerator Program for Discovery in Brain Disorders using Stem Cells (ADBS) was used for the current analysis. Multidimensional Item Response Theory (IRT) was used to extract dimensional scores from the Yale-Brown Obsessive-Compulsive Scale (YBOCS) checklist data. Using linear mixed-effects regression models, intra-class correlation coefficients (ICC), for each symptom dimension, and within each relationship type were estimated. IRT yielded a four-factor solution with Factor 1 (Sexual/Religious/Aggressive), Factor 2 (Doubts/Checking), Factor 3 (Symmetry/Arranging), and Factor 4 (Contamination/Washing). All except for Factor 1 were found to have significant ICCs, highest for Factor 3 (0.41) followed by Factor 4 (0.29) and then Factor 2 (0.27). Sex-concordant dyads were found to have higher ICC values than discordant ones, for all the symptom dimensions. No major differences in the ICC values between parent-offspring and sib-pairs were seen. Our findings indicate that there is a high concordance of OCD symptom dimensions within multiplex families. Symptom dimensions of OCD might thus have significant heritability. In view of this, future genetic and neurobiological studies in OCD should include symptom dimensions as a key parameter in their analyses.
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http://dx.doi.org/10.3389/fpsyt.2021.651196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093508PMC
April 2021

Exome hits demystified: The next frontier.

Asian J Psychiatr 2021 May 2;59:102640. Epub 2021 Apr 2.

Department of Psychiatry, National Institute of Mental Health and Neuro Sciences, Bengaluru, Karnataka, India.

Severe mental illnesses such as schizophrenia and bipolar disorder have complex inheritance patterns, involving both common and rare variants. Whole exome sequencing is a promising approach to find out the rare genetic variants. We had previously reported several rare variants in multiplex families with severe mental illnesses. The current article tries to summarise the biological processes and pattern of expression of genes harbouring the aforementioned variants, linking them to known clinical manifestations through a methodical narrative review. Of the 28 genes considered for this review from 7 families with multiple affected individuals, 6 genes are implicated in various neuropsychiatric manifestations including some variations in the brain morphology assessed by magnetic resonance imaging. Another 15 genes, though associated with neuropsychiatric manifestations, did not have established brain morphological changes whereas the remaining 7 genes did not have any previously recorded neuropsychiatric manifestations at all. Wnt/b-catenin signaling pathway was associated with 6 of these genes and PI3K/AKT, calcium signaling, ERK, RhoA and notch signaling pathways had at least 2 gene associations. We present a comprehensive review of biological and clinical knowledge about the genes previously reported in multiplex families with severe mental illness. A 'disease in dish approach' can be helpful to further explore the fundamental mechanisms.
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http://dx.doi.org/10.1016/j.ajp.2021.102640DOI Listing
May 2021

Resting State Functional Connectivity of Brain With Electroconvulsive Therapy in Depression: Meta-Analysis to Understand Its Mechanisms.

Front Hum Neurosci 2020 21;14:616054. Epub 2021 Jan 21.

ECT Services, Noninvasive Brain Stimulation (NIBS) Team, Department of Psychiatry, Bengaluru, India.

Electroconvulsive therapy (ECT) is a commonly used brain stimulation treatment for treatment-resistant or severe depression. This study was planned to find the effects of ECT on brain connectivity by conducting a systematic review and coordinate-based meta-analysis of the studies performing resting state fMRI (rsfMRI) in patients with depression receiving ECT. We systematically searched the databases published up to July 31, 2020, for studies in patients having depression that compared resting-state functional connectivity (rsFC) before and after a course of pulse wave ECT. Meta-analysis was performed using the activation likelihood estimation method after extracting details about coordinates, voxel size, and method for correction of multiple comparisons corresponding to the significant clusters and the respective rsFC analysis measure with its method of extraction. Among 41 articles selected for full-text review, 31 articles were included in the systematic review. Among them, 13 articles were included in the meta-analysis, and a total of 73 foci of 21 experiments were examined using activation likelihood estimation in 10 sets. Using the cluster-level interference method, one voxel-wise analysis with the measure of amplitude of low frequency fluctuations and one seed-voxel analysis with the right hippocampus showed a significant reduction ( < 0.0001) in the left cingulate gyrus (dorsal anterior cingulate cortex) and a significant increase ( < 0.0001) in the right hippocampus with the right parahippocampal gyrus, respectively. Another analysis with the studies implementing network-wise (posterior default mode network: dorsomedial prefrontal cortex) resting state functional connectivity showed a significant increase ( < 0.001) in bilateral posterior cingulate cortex. There was considerable variability as well as a few key deficits in the preprocessing and analysis of the neuroimages and the reporting of results in the included studies. Due to lesser studies, we could not do further analysis to address the neuroimaging variability and subject-related differences. The brain regions noted in this meta-analysis are reasonably specific and distinguished, and they had significant changes in resting state functional connectivity after a course of ECT for depression. More studies with better neuroimaging standards should be conducted in the future to confirm these results in different subgroups of depression and with varied aspects of ECT.
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http://dx.doi.org/10.3389/fnhum.2020.616054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859100PMC
January 2021

Estimating the familial risk of psychiatric illnesses: A review of family history scores.

Asian J Psychiatr 2021 Feb 10;56:102551. Epub 2021 Jan 10.

Department of Psychiatry, National Institute of Mental Health and Neuro Sciences (NIMHANS), Bengaluru.

A history of psychiatric illnesses in family members of those diagnosed to have an illness has been of significant interest both in research and in clinical practice. Almost all of the major psychiatric illnesses have a familial component to them, perhaps influenced by genetics and a shared environment or their combination. Systematic attempts have been made to quantify these familial risks, as obtained from family history (FH) of psychiatric illnesses. The methods range from a simple dichotomous or count scores to those quantifying as weighted risks such as the Family history density (FHD) measures. This article reviews the available literature on such FH methods and discusses their advantages and limitations. Validation studies have shown that FHD measures may be preferred over dichotomous measures as indicators of familial risk. However, the FHD method has certain limitations, like mostly relying on categorical diagnosis and ignoring other familial risk factors. By critically analysing various existing density measures based on 'ideal characteristics', we suggest a modified version of FHD that would benefit psychiatric research.
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http://dx.doi.org/10.1016/j.ajp.2021.102551DOI Listing
February 2021

Psychiatric symptoms and syndromes transcending diagnostic boundaries in Indian multiplex families: The cohort of ADBS study.

Psychiatry Res 2021 02 16;296:113647. Epub 2020 Dec 16.

Department of Psychiatry, National Institute of Mental Health And Neuro Sciences (NIMHANS), Bengaluru, India. Electronic address:

Syndromes of schizophrenia, bipolar disorder, obsessive-compulsive disorder, substance use disorders and Alzheimer's dementia are highly heritable. About 10-20% of subjects have another affected first degree relative (FDR), and thus represent a 'greater' genetic susceptibility. We screened 3583 families to identify 481 families with multiple affected members, assessed 1406 individuals in person, and collected information systematically about other relatives. Within the selected families, a third of all FDRs were affected with serious mental illness. Although similar diagnoses aggregated within families, 62% of the families also had members with other syndromes. Moreover, 15% of affected individuals met criteria for co-occurrence of two or more syndromes, across their lifetime. Using dimensional assessments, we detected a range of symptom clusters in both affected and unaffected individuals, and across diagnostic categories. Our findings suggest that in multiplex families, there is considerable heterogeneity of clinical syndromes, as well as sub-threshold symptoms. These families would help provide an opportunity for further research using both genetic analyses and biomarkers.
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http://dx.doi.org/10.1016/j.psychres.2020.113647DOI Listing
February 2021

Comparable effects of 0.5 ms and 1.5 ms pulse-widths on cardiovascular response in schizophrenia patients receiving electroconvulsive therapy.

J Psychiatr Res 2021 01 16;132:195-197. Epub 2020 Oct 16.

Senior Professor, Department of Psychiatry, National Institute of Mental Health and Neuro Sciences, Bangalore, India. Electronic address:

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http://dx.doi.org/10.1016/j.jpsychires.2020.10.013DOI Listing
January 2021

The 2019 Schizophrenia International Research Society Conference, 10-14 April, Orlando, Florida: A summary of topics and trends.

Psychiatry Res 2020 02 9;284:112672. Epub 2019 Nov 9.

Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.

The Schizophrenia International Research Society (SIRS) recently held its first North American congress, which took place in Orlando, Florida from 10-14 April 2019. The overall theme of this year's congress was United in Progress - with the aim of cultivating a collaborative effort towards advancing the field of schizophrenia research. Student travel awardees provided reports of the oral sessions and concurrent symposia that took place during the congress. A collection of these reports is summarized and presented below and highlights the main themes and topics that emerged during the congress. In summary, the congress covered a broad range of topics relevant to the field of psychiatry today.
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http://dx.doi.org/10.1016/j.psychres.2019.112672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232873PMC
February 2020

Is tapentadol a potential Trojan horse in the postdextropropoxyphene era in India?

Indian J Pharmacol 2018 Jan-Feb;50(1):44-46

Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India.

Tapentadol is a centrally acting opioid analgesic which has partial opioid agonistic and norepinephrine reuptake inhibitor action similar to its nearest congener and tramadol though with a relatively higher μ-affinity. It has abuse potential, is a scheduled drug, yet currently is not known to be an opioid widely misused in India. However, under the current drug abuse legislation in India, where common prescription opioids such as dextropropoxyphene have been banned, tapentadol may take the center stage of pharmaceutical opioid abuse in the near future. We present a series of two cases where the opioid use started with codeine, dextropropoxyphene, and buprenorphine but moved on to tapentadol and tramadol due to ease of access and cost. These cases highlight the potential of tapentadol in replacing dextropropoxyphene as the widespread prescription opioid of abuse and also emphasize the current controversies regarding opioid control policies in India.
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http://dx.doi.org/10.4103/ijp.IJP_21_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5954633PMC
October 2018
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