News and Commentary Archive

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


The Center for Law, Brain & Behavior puts the most accurate and actionable neuroscience in the hands of judges, lawyers, policymakers and journalists—people who shape the standards and practices of our legal system and affect its impact on people’s lives. We work to make the legal system more effective and more just for all those affected by the law.

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



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.


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.


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]).


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.

Specificity of Incident Diagnostic Outcomes in Patients at Clinical High Risk for Psychosis

By Jadon R. WebbJean AddingtonDiana O. PerkinsCarrie E. BeardenKristin S. CadenheadTyrone D. CannonBarbara A. CornblattRobert K. HeinssenLarry J. SeidmanSarah I. TarboxMing T. TsuangElaine F. WalkerThomas H. McGlashan, and Scott W. Woods | Schizophrenia Bulletin | September 2015


It is not well established whether the incident outcomes of the clinical high-risk (CHR) syndrome for psychosis are diagnostically specific for psychosis or whether CHR patients also are at elevated risk for a variety of nonpsychotic disorders. We collected 2 samples (NAPLS-1, PREDICT) that contained CHR patients and a control group who responded to CHR recruitment efforts but did not meet CHR criteria on interview (help-seeking comparison patients [HSC]). Incident diagnostic outcomes were defined as the occurrence of a SIPS-defined psychosis or a structured interview diagnosis from 1 of 3 nonpsychotic Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) groups (anxiety, bipolar, or nonbipolar mood disorder), when no diagnosis in that group was present at baseline. Logistic regression revealed that the CHR vs HSC effect did not vary significantly across study for any emergent diagnostic outcome; data from the 2 studies were therefore combined. CHR (n = 271) vs HSC (n = 171) emergent outcomes were: psychosis 19.6% vs 1.8%, bipolar disorders 1.1% vs 1.2%, nonbipolar mood disorders 4.4% vs 5.3%, and anxiety disorders 5.2% vs 5.3%. The main effect of CHR vs HSC was statistically significant (OR = 13.8, 95% CI 4.2–45.0, df = 1, P < .001) for emergent psychosis but not for any emergent nonpsychotic disorder. Sensitivity analyses confirmed these findings. Within the CHR group emergent psychosis was significantly more likely than each nonpsychotic DSM-IV emergent disorder, and within the HSC group emergent psychosis was significantly less likely than most emergent nonpsychotic disorders. The CHR syndrome is specific as a marker for research on predictors and mechanisms of developing psychosis.

Read the full article here.

Association of Thalamic Dysconnectivity and Conversion to Psychosis in Youth and Young Adults at Elevated Clinical Risk

By Jadon R. WebbJean AddingtonDiana O. PerkinsCarrie E. BeardenKristin S. CadenheadTyrone D. CannonBarbara A. CornblattRobert K. HeinssenLarry J. SeidmanSarah I. TarboxMing T. TsuangElaine F. WalkerThomas H. McGlashanand Scott W. Woods | JAMA Psychiatry | August 12, 2015



Severe neuropsychiatric conditions, such as schizophrenia, affect distributed neural computations. One candidate system profoundly altered in chronic schizophrenia involves the thalamocortical networks. It is widely acknowledged that schizophrenia is a neurodevelopmental disorder that likely affects the brain before onset of clinical symptoms. However, no investigation has tested whether thalamocortical connectivity is altered in individuals at risk for psychosis or whether this pattern is more severe in individuals who later develop full-blown illness.


To determine whether baseline thalamocortical connectivity differs between individuals at clinical high risk for psychosis and healthy controls, whether this pattern is more severe in those who later convert to full-blown illness, and whether magnitude of thalamocortical dysconnectivity is associated with baseline prodromal symptom severity.

Design, Setting, and Participants

In this multicenter, 2-year follow-up, case-control study, we examined 397 participants aged 12-35 years of age (243 individuals at clinical high risk of psychosis, of whom 21 converted to full-blown illness, and 154 healthy controls). The baseline scan dates were January 15, 2010, to April 30, 2012.

Main Outcomes and Measures

Whole-brain thalamic functional connectivity maps were generated using individuals’ anatomically defined thalamic seeds, measured using resting-state functional connectivity magnetic resonance imaging.


Using baseline magnetic resonance images, we identified thalamocortical dysconnectivity in the 243 individuals at clinical high risk for psychosis, which was particularly pronounced in the 21 participants who converted to full-blown illness. The pattern involved widespread hypoconnectivity between the thalamus and prefrontal and cerebellar areas, which was more prominent in those who converted to full-blown illness (t173 = 3.77, P < .001, Hedge g = 0.88). Conversely, there was marked thalamic hyperconnectivity with sensory motor areas, again most pronounced in those who converted to full-blown illness (t173 = 2.85, P < .001, Hedge g = 0.66). Both patterns were significantly correlated with concurrent prodromal symptom severity (r = 0.27, P < 3.6 × 10−8, Spearman ρ = 0.27, P < 4.75 × 10−5, 2-tailed).

Conclusions and Relevance

Thalamic dysconnectivity, resembling that seen in schizophrenia, was evident in individuals at clinical high risk for psychosis and more prominently in those who later converted to psychosis. Dysconnectivity correlated with symptom severity, supporting the idea that thalamic connectivity may have prognostic implications for risk of conversion to full-blown illness.

Read the full study here.

The Impact of Premorbid Adjustment, Neurocognition, and Depression on Social and Role Functioning in Patients in an Early Psychosis Treatment Program

By Kyle S. Minor, Michelle Friedman-Yakoobian, Y. Jude Leung, Eric C. Meyer, Suzanna V. Zimmet, Brina Caplan, Thomas Monteleone, Caitlin Bryant, Margaret Guyer, Matcheri S. Keshavan, and Larry J. Seidman | Australian and New Zealand Journal of Psychiatry | August 2015



Functional impairments are debilitating concomitants of psychotic disorders and are present early in the illness course and, commonly, prior to psychosis onset. The factors affecting social and role functioning in early psychosis (EP) following treatment are unclear. We evaluated whether six months of participation in the PREPR, Boston, EP treatment program, part of a public-academic community mental health center, was related to improvements in social and role functioning and whether premorbid adjustment in adolescence, baseline neurocognition, and depression symptoms predicted functional improvement.


The Global Functioning Social and Role scales, MATRICS neurocognitive battery, and Calgary Depression Scale were assessed at baseline and six months during naturalistic treatment, while premorbid adjustment was measured at baseline. All participants were psychotic disorder patients in PREPR (n = 46 with social functioning and 47 with role functioning measures at both time points).


Large improvements were observed in role functioning (d = 0.84) and medium to large improvements were observed in social functioning (d = 0.70). Models consisting of adolescent premorbid adjustment and change in depression symptoms predicted social and role functioning change, whereas neuropsychological functioning did not.


Substantial improvements in social and role functioning were observed among this sample participating in a recovery-based EP program. The impact of clinical factors on social and role functioning was highlighted. Further studies of premorbid adjustment in adolescence and the treatment of depression in EP programs in controlled treatment trials are needed to confirm these findings.

Read the full paper here.

Factor structure and heritability of endophenotypes in schizophrenia: Findings from the Consortium on the Genetics of Schizophrenia

Larry Seidman et al | Schizophrenia Research | February 11, 2015


Although many endophenotypes for schizophrenia have been studied individually, few studies have examined the extent to which common neurocognitive and neurophysiological measures reflect shared versus unique endophenotypic factors. It may be possible to distill individual endophenotypes into composite measures that reflect dissociable, genetically informative elements.

The first phase of the Consortium on the Genetics of Schizophrenia (COGS-1) is a multisite family study that collected neurocognitive and neurophysiological data between 2003 and 2008. For these analyses, participants included schizophrenia probands (n = 83), their nonpsychotic siblings (n = 151), and community comparison subjects (n = 209) with complete data on a battery of 12 neurocognitive tests (assessing domains of working memory, declarative memory, vigilance, spatial ability, abstract reasoning, facial emotion processing, and motor speed) and 3 neurophysiological tasks reflecting inhibitory processing (P50 gating, prepulse inhibition and antisaccade tasks). Factor analyses were conducted on the measures for each subject group and across the entire sample. Heritability analyses of factors were performed using SOLAR.

Analyses yielded 5 distinct factors: 1) Episodic Memory, 2) Working Memory, 3) Perceptual Vigilance, 4) Visual Abstraction, and 5) Inhibitory Processing. Neurophysiological measures had low associations with these factors. The factor structure of endophenotypes was largely comparable across probands, siblings and controls. Significant heritability estimates for the factors ranged from 22% (Episodic Memory) to 39% (Visual Abstraction).

Neurocognitive measures reflect a meaningful amount of shared variance whereas the neurophysiological measures reflect largely unique contributions as endophenotypes for schizophrenia. Composite endophenotype measures may inform our neurobiological and genetic understanding of schizophrenia.

Read the full paper here.