Papers by Bhaskar Kolachana
R script used for analyses. This file contains R code used to identify CNV genotypes and to perfo... more R script used for analyses. This file contains R code used to identify CNV genotypes and to perform association analyses with haploid genotypes. (R 4Â kb)
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Selon cette invention, il a ete decouvert qu'un polymorphisme met66val dans le gene du facteu... more Selon cette invention, il a ete decouvert qu'un polymorphisme met66val dans le gene du facteur neurotrophique derive du cerveau (BDNF) est associe a la fonction hippocampique et a la memoire verbale ainsi qu'au risque de troubles neuropsychiatriques tels que la schizophrenie.
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Biological Psychiatry
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American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Schizophrenia has been hypothesized to be a human‐specific condition, but experimental approaches... more Schizophrenia has been hypothesized to be a human‐specific condition, but experimental approaches to testing this idea have been limited. Because Neanderthals, our closest evolutionary relatives, interbred with modern humans prior to their disappearance from the fossil record, leaving a residual echo that survives in our DNA today, we leveraged new discoveries about ancient hominid DNA to explore this hypothesis in living people in three converging ways. First, in four independent case–control datasets totaling 9,362 individuals, individuals with schizophrenia had less Neanderthal‐derived genetic variation than controls (p = .044). Second, in 49 unmedicated inpatients with schizophrenia, having more Neanderthal admixture predicted less severe positive symptoms (p = .046). Finally, using 18F‐fluorodopa PET scanning in 172 healthy individuals, having greater Neanderthal introgression was significantly associated with lower dopamine synthesis capacity in the striatum and pons (p's < 2 × 10−5), which is fundamentally important in the pathophysiology and treatment of psychosis. These results may help to elucidate the evolutionary history of a devastating neuropsychiatric disease by supporting the notion of schizophrenia as a human‐specific condition. Additionally, the relationship between Neanderthal admixture and dopamine function suggests a potential mechanism whereby Neanderthal admixture may have affected our gene pool to alter schizophrenia risk and/or course.
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Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
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Biological Psychiatry
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Biological Psychiatry
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Biological Psychiatry
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BMC medical genetics, Jan 4, 2018
Williams syndrome ([WS], 7q11.23 hemideletion) and 7q11.23 duplication syndrome (Dup7) show contr... more Williams syndrome ([WS], 7q11.23 hemideletion) and 7q11.23 duplication syndrome (Dup7) show contrasting syndromic symptoms. However, within each group there is considerable interindividual variability in the degree to which these phenotypes are expressed. Though software exists to identify areas of copy number variation (CNV) from commonly-available SNP-chip data, this software does not provide non-diploid genotypes in CNV regions. Here, we describe a method for identifying haploid and triploid genotypes in CNV regions, and then, as a proof-of-concept for applying this information to explain clinical variability, we test for genotype-phenotype associations. Blood samples for 25 individuals with WS and 13 individuals with Dup7 were genotyped with Illumina-HumanOmni5M SNP-chips. PennCNV and in-house code were used to make genotype calls for each SNP in the 7q11.23 locus. We tested for association between the presence of aortic arteriopathy and genotypes of the remaining (haploid in WS...
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Schizophrenia Bulletin
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NeuroImage
&NA; Adaptive learning impairments are common in cognitive and behavioral disorders, but the ... more &NA; Adaptive learning impairments are common in cognitive and behavioral disorders, but the neurogenetic mechanisms supporting human affective learning are poorly understood. We designed a higher‐order contextual learning task in which healthy participants genotyped for the Val66Met polymorphism of the brain derived neurotropic factor gene (BDNF) were required to choose the member of a picture pair most congruent with the emotion in a previously‐viewed facial expression video in order to produce an advantageous monetary outcome. Functional magnetic resonance imaging (fMRI) identified frontolimbic blood oxygenation level dependent (BOLD) reactivity that was associated with BDNF Val66Met genotype during all three phases of the learning task: aversive and reward‐predictive learning, contextually‐challenging decision‐making, and choice‐related monetary loss‐avoidance and gain outcomes. Relative to Val homozygotes, Met carriers showed attenuated ventromedial prefrontal response to predictive affective cues, dorsolateral prefrontal signaling that depended on decision difficulty, and enhanced ventromedial prefrontal reactivity that was specific to loss‐avoidance. These findings indicate that the BDNF Val66Met polymorphism is associated with functional tuning of behaviorally‐relevant frontolimbic circuitry, particularly involving the ventromedial prefrontal cortex, during higher‐order learning. HighlightsfMRI BOLD identifies a genetic signature for adaptive learning.BDNF Val66Met genotype tuned prefrontal BOLD signals were context specific.BDNF mediated vMPFC BOLD was predominant for predictive affective and outcome.cues.BDNF influenced DLPFC activity during decision‐making was affected by load.Magnitude of vMPFC response to outcomes correlated with performance.
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Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
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Molecular Psychiatry, 2007
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Cerebral cortex (New York, N.Y. : 1991), Mar 21, 2016
Brain-derived neurotrophic factor (BDNF) is an important modulator of constitutive stress respons... more Brain-derived neurotrophic factor (BDNF) is an important modulator of constitutive stress responses mediated by limbic frontotemporal circuits, and its gene contains a functional polymorphism (Val(66)Met) that may influence trait stress sensitivity. Reports of an association of this polymorphism with anxiety-related personality traits have been controversial and without clear neurophysiological support. We, therefore, determined the relationship between resting regional cerebral blood flow (rCBF) and a well-validated measure of anxiety-related personality, the TPQ Harm Avoidance (HA) scale, as a function ofBDNFVal(66)Met genotype. Sixty-four healthy participants of European ancestry underwent resting H2 (15)O positron emission tomography scans. For each genotype group separately, we first determined the relationship between participants' HA scores and their resting rCBF values in each voxel across the entire brain, and then directly compared these HA-rCBF relationships between V...
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The Journal of Neuroscience, May 16, 2012
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Neuropsychopharmacology, 2016
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Translational Psychiatry, 2015
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European Journal of Neuroscience, 2015
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Nature, Jan 14, 1998
The effects of early brain damage are often, but not always, milder than the effects of comparabl... more The effects of early brain damage are often, but not always, milder than the effects of comparable damage in adults, depending on the age at which injury occurred, the region of the brain damaged, and the brain functions involved. Studies of the impact of early brain damage have generally focused on functions primarily associated with the neural structures injured, even though the development and function of distant but interconnected neural systems might also show effects. Here we examine the regulation of striatal dopamine by the dorsolateral prefrontal cortex, in adult monkeys that had had either neonatal or adult lesions of the medial-temporal lobe and in normal animals. We use microdialysis to measure the dopamine response in the caudate nucleus after the infusion of amphetamine into the dorsolateral prefrontal cortex. Normal animals and those with adult lesions showed a reduction in dopamine overflow; in contrast, monkeys with neonatal lesions showed increased dopamine release...
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Papers by Bhaskar Kolachana