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

Alterations of Lateral Temporal Cortical Gray Matter and Facial Memory as Vulnerability Indicators for Schizophrenia: An MRI Study in Youth at Familial High-Risk for Schizophrenia

By Benjamin K. Brent, Isabelle M. Rosso, Heidi W. Thermenos, Daphne J. Holt, Stephen V. Faraone, Nikos Makris, Ming T. Tsuang, and Larry J. Seidman | Schizophrenia Research | November 24, 2015

Abstract:

Background

Structural alterations of the lateral temporal cortex (LTC) in association with memory impairments have been reported in schizophrenia. This study investigated whether alterations of LTC structure were linked with impaired facial and/or verbal memory in young first-degree relatives of people with schizophrenia and, thus, may be indicators of vulnerability to the illness.

Methods

Subjects included 27 non-psychotic, first-degree relatives of schizophrenia patients, and 48 healthy controls, between the ages of 13 and 28. Participants underwent high-resolution magnetic resonance imaging (MRI) at 1.5 Tesla. The LTC was parcellated into superior temporal gyrus, middle temporal gyrus, inferior temporal gyrus, and temporal pole. Total cerebral and LTC volumes were measured using semi-automated morphometry. The Wechsler Memory Scale — Third Edition and the Children’s Memory Scale — Third Edition assessed facial and verbal memory. General linear models tested for associations among LTC subregion volumes, familial risk and memory.

Results

Compared with controls, relatives had significantly smaller bilateral middle temporal gyri. Moreover, right middle temporal gyral volume showed a significant positive association with delayed facial memory in relatives.

Conclusion

These results support the hypothesis that smaller middle temporal gyri are related to the genetic liability to schizophrenia and may be linked with reduced facial memory in persons at genetic risk for the illness. The findings add to the growing evidence that children at risk for schizophrenia on the basis of positive family history have cortical and subcortical structural brain abnormalities well before psychotic illness occurs.

Read the full article here.

Early Auditory Processing Evoked Potentials (N100) Show a Continuum of Blunting from Clinical High Risk to Psychosis in a Pediatric Sample

By Joseph Gonzalez-Heydrich, Michelle Bosquet Enlow, Eugene D’Angelo, Larry J. Seidman, Sarah Gumlak, April Kim, Kristen A. Woodberry, Ashley Rober, Sahil Tembulkar, Kelsey Graber, Kyle O’Donnell, Hesham M. Hamoda, Kara Kimball, Alexander Rotenberg, Lindsay M. Oberman, Alvaro Pascual-Leone, Matcheri S. Keshavan, and Frank H. Duffy | Schizophrenia Research | November 6, 2015

Abstract:

Background

The N100 is a negative deflection in the surface EEG approximately 100 ms after an auditory signal. It has been shown to be reduced in individuals with schizophrenia and those at clinical high risk (CHR). N100 blunting may index neural network dysfunction underlying psychotic symptoms. This phenomenon has received little attention in pediatric populations.

Method

This cross-sectional study compared the N100 response measured via the average EEG response at the left medial frontal position FC1 to 150 sinusoidal tones in participants ages 5 to 17 years with a CHR syndrome (n = 29), a psychotic disorder (n = 22), or healthy controls (n = 17).

Results

Linear regression analyses that considered potential covariates (age, gender, handedness, family mental health history, medication usage) revealed decreasing N100 amplitude with increasing severity of psychotic symptomatology from healthy to CHR to psychotic level.

Conclusions

Longitudinal assessment of the N100 in CHR children who do and do not develop psychosis will inform whether it predicts transition to psychosis and if its response to treatment predicts symptom change.

Read the entire study here.

Sexual Dimorphic Abnormalities in White Matter Geometry Common to Schizophrenia and Non-Psychotic High-Risk Subjects: Evidence for a Neurodevelopmental Risk Marker?

By Peter Savadjiev, Larry J. Seidman, Heidi Thermenos, Matcheri Keshavan, Susan Whitfield-Gabrieli, Tim J. Crow and Marek Kubicki | Human Brain Mapping | October 15, 2015

Abstract:

The characterization of neurodevelopmental aspects of brain alterations require neuroimaging methods that reflect correlates of neurodevelopment, while being robust to other progressive pathological processes. Newly developed neuroimaging methods for measuring geometrical features of the white matter fall exactly into this category. Our recent work shows that such features, measured in the anterior corpus callosum in diffusion MRI data, correlate with psychosis symptoms in patients with adolescent onset schizophrenia and subside a reversal of normal sexual dimorphism. Here, we test the hypothesis that similar developmental deviations will also be present in nonpsychotic subjects at familial high risk (FHR) for schizophrenia, due to genetic predispositions. Demonstrating such changes would provide a strong indication of neurodevelopmental deviation extant before, and independent of pathological changes occurring after disease onset. We examined the macrostructural geometry of corpus callosum white matter in diffusion MRI data of 35 non-psychotic subjects with genetic (familial) risk for schizophrenia, and 26 control subjects, both male and female. We report a reversal of normal sexual dimorphism in callosal white matter geometry consistent with recent results in adolescent onset schizophrenia. This pattern may be indicative of an error in neurogenesis and a possible trait marker of schizophrenia.

Read the full paper here.

Severity of Thought Disorder Predicts Psychosis in Persons at Clinical High-Risk

By Diana O. Perkins, Clark D. Jeffries, Barbara A. Cornblatt, Scott W. Woods, Jean Addington, Carrie E. Bearden, Kristin S. Cadenhead, Tyrone D. Cannon, Robert Heinssen, Daniel H. Mathalon, Larry J. Seidman, Ming T. Tsuang, Elaine F. Walker, and Thomas H. McGlashan | Schizophrenia Research | October 2, 2015

Abstract:

Background

Improving predictive accuracy is of paramount importance for early detection and prevention of psychosis. We sought a symptom severity classifier that would improve psychosis risk prediction.

Methods

Subjects were from two cohorts of the North American Prodrome Longitudinal Study. All subjects met Criteria of Psychosis-Risk States. In Cohort-1 (n = 296) we developed a classifier that included those items of the Scale of Psychosis-Risk Symptoms that best distinguished subjects who converted to psychosis from nonconverters, with performance initially validated by randomization tests in Cohort-1. Cohort-2 (n = 592) served as an independent test set.

Results

We derived 2-Item and 4-Item subscales. Both included unusual thought content and suspiciousness; the latter added reduced ideational richness and difficulties with focus/concentration. The Concordance Index (C-Index), a measure of discrimination, was similar for each subscale across cohorts (4-Item subscale Cohort-2: 0.71, 95% CI = [0.64, 0.77], Cohort-1: 0.74, 95% CI = [0.69, 0.80]; 2-Item subscale Cohort-2: 0.68, 95% CI = [0.3, 0.76], Cohort-1: 0.72, 95% CI = [0.66–0.79]). The 4-Item performed better than the 2-Item subscale in 742/1000 random selections of 80% subsets of Cohort-2 subjects (p-value = 1.3E−55). Subscale calibration between cohorts was proportional (higher scores/lower survival), but absolute conversion risk predicted from Cohort-1 was higher than that observed in Cohort-2, reflecting the cohorts’ differences in 2-year conversion rates (Cohort-2: 0.16, 95% CI = [0.13, 0.19]; Cohort-1: 0.30, 95% CI = [0.24, 0.36]).

Conclusion

Severity of unusual thought content, suspiciousness, reduced ideational richness, and difficulty with focus/concentration informed psychosis risk prediction. Scales based on these symptoms may have utility in research and, assuming further validation, eventual clinical applications.

Read the full article here.

Gating Deficit Heritability and Correlation With Increased Clinical Severity in Schizophrenia Patients With Positive Family History

By Tiffany A. Greenwood, Gregory A. Light, Neal R. Swerdlow, Monica E. Calkins, Michael F. Green, Raquel E. Gur, Ruben C. Gur, Laura C. Lazzeroni, Keith H. Nuechterlein, Ann Olincy, Allen D. Radant, Larry J. Seidman, Larry J. Siever, Jeremy M. Silverman, William S. Stone, Catherine A. Sugar, Debby W. Tsuang, Ming T. Tsuang, Bruce I. Turetsky, Robert Freedman, and David L. Braff | The American Journal of Psychiatry | August 10, 2015

Abstract:

Method:

A total of 296 nuclear families consisting of a schizophrenia proband, at least one unaffected sibling, and both parents underwent a comprehensive endophenotype and clinical characterization. The Family Interview for Genetic Studies was administered to all participants and used to obtain convergent psychiatric symptom information for additional first-degree relatives. Among the families, 97 were multiply affected, and 96 were singletons.

Results:

Both PPI and P50 gating displayed substantially increased heritability in the 97 multiply affected families (47% and 36%, respectively) compared with estimates derived from the entire sample of 296 families (29% and 20%, respectively). However, no evidence for heritability was observed for either measure in the 96 singleton families. Schizophrenia probands derived from the multiply affected families also displayed a significantly increased severity of clinical symptoms compared with those from singleton families.

Conclusions: