News and Commentary Archive

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

Mission

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.

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

Abstract: 

Importance

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.

Objectives

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.

Results

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.

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

Abstract:

Background:
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.

Methods:
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.

Results:
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).

Conclusions:
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.

CLBB leads in special issue on “Neuropsychiatry”

CLBB faculty and staff are significant contributors to an in-press special issue of Current Opinion in Neurobiology on Neuropsychiatry. CLBB faculty and psychiatric genetics pioneer Steven Hyman, along with Raquel Gur, is co-editor of this special issue. The also issue includes a paper co-authored by Justin Baker, CLBB associate director, on the use of fMRI in understanding the neurodevelopment of psychosis.

View the issue in-press, and stay tuned for its publication in February 2015.

Cortical Thinning, Functional Connectivity, and Mood-Related Impulsivity in Schizophrenia: Relationship to Aggressive Attitudes and Behavior

By MJ Hoptman, D Antonius, CJ Mauro, EM Parker & DC Javitt | American Journal of Psychiatry | July 2014

Abstract:

Objective: Aggression in schizophrenia is a major societal issue, leading to physical harm, stigmatization, patient distress, and higher health care costs. Impulsivity is associated with aggression in schizophrenia, but it is multidetermined. The subconstruct of urgency is likely to play an important role in this aggression, with positive urgency referring to rash action in the context of positive emotion, and negative urgency referring to rash action in the context of negative emotion.

Method: The authors examined urgency and its neural correlates in 33 patients with schizophrenia or schizoaffective disorder and 31 healthy comparison subjects. Urgency was measured using the Urgency, Premeditation, Perseverance, and Sensation-Seeking scale. Aggressive attitudes were measured using the Buss-Perry Aggression Questionnaire. Continue reading »

A Schizophrenic on Death Row

The Florida Supreme Court decided on Wednesday that the state can proceed with the execution next week of a 64-year-old inmate named John Ferguson. His lawyers immediately said that they will ask the United States Supreme Court to stay the execution and to review the case on grounds that Mr. Ferguson is mentally incompetent and that executing him would violate his constitutional rights as defined by the court in two earlier decisions.

The court must review the case. At issue are not only Mr. Ferguson’s life but also two differing interpretations of what constitutes competence: one Florida’s, the other the Supreme Court’s.

Mr. Ferguson believes that he is the Prince of God and that he is facing execution not for murders he committed but because of a conspiracy against him for being the prince. He believes that he cannot be killed and that he has “inner ears” so he can hear God whisper instructions. All of this is consistent with his being a paranoid schizophrenic, as he was diagnosed 40 years ago and many times since, including earlier this month. …

Source: The New York Times, Oct. 17, 2012.

[Read full editorial at NYTimes.com]