News and Commentary Archive

Explore recent scientific discoveries and news as well as CLBB events, commentary, and press.

Mission

The speed of technology in neuroscience as it impacts ethical and just decisions in the legal system needs to be understood by lawyers, judges, public policy makers, and the general public. The Massachusetts General Hospital Center for Law, Brain, and Behavior is an academic and professional resource for the education, research, and understanding of neuroscience and the law. Read more

Reciprocal White Matter Alterations Due to 16p11.2 Chromosomal Deletions Versus Duplications

By Yi Shin Chang, Julia P. Owen, Nicholas J. Pojman, Tony Thieu, Polina Bukshpun, Mari L.J. Wakahiro, Elysa J. Marco, Jeffrey I. Berman, John E. Spiro, Wendy K. Chung, Randy L. Buckner, Timothy P.L. Roberts, Srikantan S. Nagarajan, Elliott H. Sherr, and Pratik Mukherjee | Human Brain Mapping | May 24, 2016

Abstract:

Copy number variants at the 16p11.2 chromosomal locus are associated with several neuropsychiatric disorders, including autism, schizophrenia, bipolar disorder, attention-deficit hyperactivity disorder, and speech and language disorders. A gene dosage dependence has been suggested, with 16p11.2 deletion carriers demonstrating higher body mass index and head circumference, and 16p11.2 duplication carriers demonstrating lower body mass index and head circumference. Here, we use diffusion tensor imaging to elucidate this reciprocal relationship in white matter organization, showing widespread increases of fractional anisotropy throughout the supratentorial white matter in pediatric deletion carriers and, in contrast, extensive decreases of white matter fractional anisotropy in pediatric and adult duplication carriers. We find associations of these white matter alterations with cognitive and behavioral impairments. We further demonstrate the value of imaging metrics for characterizing the copy number variant phenotype by employing linear discriminant analysis to predict the gene dosage status of the study subjects. These results show an effect of 16p11.2 gene dosage on white matter microstructure, and further suggest that opposite changes in diffusion tensor imaging metrics can lead to similar cognitive and behavioral deficits. Given the large effect sizes found in this study, our results support the view that specific genetic variations are more strongly associated with specific brain alterations than are shared neuropsychiatric diagnoses.

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Multimodal Analysis of Cortical Chemoarchitecture and Macroscale fMRI Resting-State Functional Connectivity

By Martijn P. van den Heuvel, Lianne H. Scholtens, Elise Turk, Dante Mantini, Wim Vanduffel, and Lisa Feldman Barrett | Human Brain Mapping | May 21, 2016

Abstract:

The cerebral cortex is well known to display a large variation in excitatory and inhibitory chemoarchitecture, but the effect of this variation on global scale functional neural communication and synchronization patterns remains less well understood. Here, we provide evidence of the chemoarchitecture of cortical regions to be associated with large-scale region-to-region resting-state functional connectivity. We assessed the excitatory versus inhibitory chemoarchitecture of cortical areas as an ExIn ratio between receptor density mappings of excitatory (AMPA, M1) and inhibitory (GABAA, M2) receptors, computed on the basis of data collated from pioneering studies of autoradiography mappings as present in literature of the human (2 datasets) and macaque (1 dataset) cortex. Cortical variation in ExIn ratio significantly correlated with total level of functional connectivity as derived from resting-state functional connectivity recordings of cortical areas across all three datasets (human I: P = 0.0004; human II: P = 0.0008; macaque: P = 0.0007), suggesting cortical areas with an overall more excitatory character to show higher levels of intrinsic functional connectivity during resting-state. Our findings are indicative of the microscale chemoarchitecture of cortical regions to be related to resting-state fMRI connectivity patterns at the global system’s level of connectome organization.

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Migraine Photophobia Originating in Cone-Driven Retinal Pathways

By , , , , , , , , , , , and 

Abstract:

Migraine headache is uniquely exacerbated by light. Using psychophysical assessments in patients with normal eyesight we found that green light exacerbates migraine headache significantly less than white, blue, amber or red lights. To delineate mechanisms, we used electroretinography and visual evoked potential recording in patients, and multi-unit recording of dura- and light-sensitive thalamic neurons in rats to show that green activates cone-driven retinal pathways to a lesser extent than white, blue and red; that thalamic neurons are most responsive to blue and least responsive to green; and that cortical responses to green are significantly smaller than those generated by blue, amber and red lights. These findings suggest that patients’ experience with colour and migraine photophobia could originate in cone-driven retinal pathways, fine-tuned in relay thalamic neurons outside the main visual pathway, and preserved by the cortex. Additionally, the findings provide substrate for the soothing effects of green light.

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Genome-Wide Association Studies of Posttraumatic Stress Disorder in 2 Cohorts of US Army Soldiers

By Murray B. Stein, Chia-Yen Chen, Robert J. Ursano, Tianxi Cai, Joel Gelernter, Steven G. Heeringa, Sonia Jain, Kevin P. Jensen, Adam X. Maihofer, Colter Mitchell, Caroline M. Nievergelt, Matthew K. Nock, Benjamin M. Neale, Renato Polimanti, Stephan Ripke, Xiaoying Sun, Michael L. Thomas, Qian Wang, Erin B. Ware, Susan Borja, Ronald C. Kessler, and Jordan W. Smoller | JAMA Psychiatry | May 11, 2016

Abstract:

Importance —  Posttraumatic stress disorder (PTSD) is a prevalent, serious public health concern, particularly in the military. The identification of genetic risk factors for PTSD may provide important insights into the biological foundation of vulnerability and comorbidity.

Objective —  To discover genetic loci associated with the lifetime risk for PTSD in 2 cohorts from the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS).

Design, Setting, and Participants —  Two coordinated genome-wide association studies of mental health in the US military contributed participants. The New Soldier Study (NSS) included 3167 unique patients with PTSD and 4607 trauma-exposed control individuals; the Pre/Post Deployment Study (PPDS) included 947 unique patients with PTSD and 4969 trauma-exposed controls. The NSS data were collected from February 1, 2011, to November 30, 2012; the PDDS data, from January 9 to April 30, 2012. The primary analysis compared lifetime DSM-IV PTSD cases with trauma-exposed controls without lifetime PTSD. Data were analyzed from March 18 to December 27, 2015.

Main Outcomes and Measures —  Association analyses for PTSD used logistic regression models within each of 3 ancestral groups (European, African, and Latino American) by study, followed by meta-analysis. Heritability and genetic correlation and pleiotropy with other psychiatric and immune-related disorders were estimated.

Results —  The NSS population was 80.7% male (6277 of 7774 participants; mean [SD] age, 20.9 [3.3] years); the PPDS population, 94.4% male (5583 of 5916 participants; mean [SD] age, 26.5 [6.0] years). A genome-wide significant locus was found in ANKRD55 on chromosome 5 (rs159572; odds ratio [OR], 1.62; 95% CI, 1.37-1.92; P = 2.34 × 10−8) and persisted after adjustment for cumulative trauma exposure (adjusted OR, 1.64; 95% CI, 1.39-1.95; P = 1.18 × 10−8) in the African American samples from the NSS. A genome-wide significant locus was also found in or near ZNF626 on chromosome 19 (rs11085374; OR, 0.77; 95% CI, 0.70-0.85; P = 4.59 × 10−8) in the European American samples from the NSS. Similar results were not found for either single-nucleotide polymorphism in the corresponding ancestry group from the PPDS sample, in other ancestral groups, or in transancestral meta-analyses. Single-nucleotide polymorphism–based heritability was nonsignificant, and no significant genetic correlations were observed between PTSD and 6 mental disorders or 9 immune-related disorders. Significant evidence of pleiotropy was observed between PTSD and rheumatoid arthritis and, to a lesser extent, psoriasis.

Conclusions and Relevance —  In the largest genome-wide association study of PTSD to date, involving a US military sample, limited evidence of association for specific loci was found. Further efforts are needed to replicate the genome-wide significant association with ANKRD55—associated in prior research with several autoimmune and inflammatory disorders—and to clarify the nature of the genetic overlap observed between PTSD and rheumatoid arthritis and psoriasis.

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Traumatic Brain Injury in Individuals at Clinical High Risk for Psychosis

By Stephanie Deighton, Lisa Buchy, Kristin S. Cadenhead, Tyrone D. Cannon, Barbara A. Cornblatt, Thomas H. McGlashan, Diana O. Perkins, Larry J. Seidman, Ming T. Tsuang, Elaine F. Walker, Scott W. Woods, Carrie E. Bearden, Daniel Mathalon, and Jean Addington | Schizophrenia Research | May 7, 2016

Abstract:

Background

Recent research suggests that a traumatic brain injury (TBI) can significantly increase the risk of later development of psychosis. However, it is unknown whether people at clinical high risk (CHR) of psychosis have experienced TBI at higher rates, compared to otherwise healthy individuals. This study evaluated the prevalence of mild TBI, whether it was related to past trauma and the relationship of mild TBI to later transition to psychosis.

Methods

Seven-hundred forty-seven CHR and 278 healthy controls (HC) were assessed on past history of mild TBI, age at first and last injury, severity of worst injury and number of injuries using the Traumatic Brain Injury Interview. Attenuated psychotic symptoms were assessed with the Scale of Psychosis-risk Symptoms. IQ was estimated using the Wechsler Abbreviated Scale of Intelligence and past trauma and bullying were recorded using the Childhood Trauma and Abuse Scale.

Results

CHR participants experienced a mild TBI more often than the HC group. CHR participants who had experienced a mild TBI reported greater total trauma and bullying scores than those who had not, and those who experienced a mild TBI and later made the transition to psychosis were significantly younger at the age at first and most recent injury than those who did not.

Conclusion

A history of mild TBI is more frequently observed in CHR individuals than in HC. Inclusion or study of CHR youth with more severe TBI may provide additional insights on the relationship between TBI and later transition to psychosis in CHR individuals.

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