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Annotation

Lee H, Dvorak D, Kao HY, Duffy ÁM, Scharfman HE, Fenton AA. Early cognitive experience prevents adult deficits in a neurodevelopmental schizophrenia model. Neuron . 2012 Aug 23 ; 75(4):714-24. PubMed Abstract

Comments on Paper and Primary News
Primary News: Is Early Cognitive Training Key to Minimizing Schizophrenia Impact?

Comment by:  Til Wykes
Submitted 24 August 2012 Posted 24 August 2012

The notion that cognitive remediation is effective in producing cognitive and functional gains in established schizophrenia (Wykes et al., 2011), and produces other gains such as changes identified in brain imaging (e.g., Wykes et al., 2002) is unsurprising. But the paper on remediation in adolescent rats by Lee and colleagues provides results that the authors do consider surprising, and could lead to further extensions of cognitive remediation to those who are "at risk" for disorders such as schizophrenia. This is because of the procognitive effects of providing training in youthful rats.

Procognitive effects of experience-based training are not, however, surprising. The authors quote research showing that there are functional changes with training—the one that springs to my mind is London taxi drivers whose hippocampi are larger following their "training" for The Knowledge—an all-roads-in-London test. So why are the authors surprised? Perhaps it is because the results...  Read more


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Primary News: Is Early Cognitive Training Key to Minimizing Schizophrenia Impact?

Comment by:  Angus MacDonald, SRF Advisor
Submitted 24 August 2012 Posted 24 August 2012

In their new Neuron article, Lee and colleagues from Andre Fenton’s group at NYU report that spatial cognitive control deficits in a rat model of schizophrenia can be prevented through a ratish analogue of cognitive remediation therapy during adolescence. The importance of early intervention has been one of the hottest debates in applied schizophrenia research; the current findings suggest a basic mechanism in support of such efforts.

What is remarkable about the Fenton study is how small a training “dosage” was required to lead to markedly different adult performance. Two days of training about five weeks after birth led to marked changes in the rats’ capacity to use spatial cognitive control eight to nine weeks after birth.

Rats were sacrificed at the end of the experiment, allowing the researchers to examine the extent to which the initial lesion had affected brain development. The initial lesions dramatically altered hippocampal development. Despite this, lesioned rats who received training did not show any observable difference in brain morphology in adulthood...  Read more


View all comments by Angus MacDonald

Primary News: Is Early Cognitive Training Key to Minimizing Schizophrenia Impact?

Comment by:  Patrick McGorry, SRF Advisor
Submitted 27 August 2012 Posted 27 August 2012

I am always a little skeptical of animal models of psychosis or schizophrenia, which are pretty high-order disturbances and seem very specific to humans. If this model has some validity, the preventive therapy in humans would be more akin to cognitive remediation therapy rather than cognitive therapy per se, which has more CBT links or connotations.

View all comments by Patrick McGorry


Primary News: Is Early Cognitive Training Key to Minimizing Schizophrenia Impact?

Comment by:  Barbara K. Lipska
Submitted 27 August 2012 Posted 27 August 2012

Lee et al. report exciting new data in support of the neurodevelopmental hypothesis of schizophrenia and the plausibility of the early intervention that might prevent the emergence of schizophrenia symptoms. Lee and colleagues used a neonatal ventral hippocampal lesion in rats as a model of schizophrenia.

First, using the active place avoidance task with carefully designed control tasks, they showed that the animals with neonatal lesions are cognitively impaired as adults, consistent with the results of the previous studies (see Tseng et al., 2009, for review). Next, they examined whether training of the lesioned animals in adolescence would prevent the emergence of these abnormalities. They exposed the animals to a series of cognitive tests and found that, indeed, the neonatally lesioned rats that acquired additional training as adolescents showed improved cognition in adulthood. Moreover, specific measures of neural function were also improved. The authors recorded local field potentials in the hippocampi and found that the...  Read more


View all comments by Barbara K. Lipska

Comment by:  Patricio O'Donnell, SRF Advisor
Submitted 4 September 2012 Posted 5 September 2012
  I recommend this paper

Can cognitive training restore function in a developmentally compromised neural circuit? This is a critical question that may open the door to novel preventive strategies for disorders with a developmental component but adult onset, such as schizophrenia. Lee et al. used rats with a neonatal ventral hippocampal lesion to test whether cognitive experience could prevent the emergence of typical schizophrenia-related deficits in adulthood in this model. The study is elegant, the data quite convincing, and the implications are vast. This is indeed a perfect example of what the field of schizophrenia research needs: the use of animal models as tools to test specific hypotheses.

Animal models of schizophrenia have been around for quite some time, and new ones keep being proposed. The data obtained from pharmacological, developmental, environmental, and genetic models over the past decade have been critical for shaping current thoughts about possible pathophysiological scenarios. But the field is still caught in the trap of trying to think of models as reproducing the disease,...  Read more


View all comments by Patricio O'Donnell
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