Defining the Role of Specific Limbic Circuitry in the Pathophysiology of Schizophrenia and Bipolar Disorder

  • Francine M. Benes
  • Sabina Berretta
Part of the Neurobiological Foundation of Aberrant Behaviors book series (NFAB, volume 4)


A core component of all corticolimbic circuitry is the GABAergic interneuron. Recent postmortem studies have provided consistent evidence that a defect of GABAergic neurotransmission probably plays a role in both schizophrenia and bipolar disorder. Based on the regional and subregional distribution of changes in GABA cells in layer II of the anterior cingulate regions and sectors CA3 and CA2 of the hippocampal formation, it has been postulated that the basolateral nucleus of the amygdala (BLa), a region that projects preferentially to both of these latter sites, may contribute to these abnormalities by sending an increased flow of excitatory activity. In support of this hypothesis, a “partial” rodent model in which the GABAA antagonist picrotoxin is injected into the BLa has demonstrated changes in the GABA system that are remarkably similar to those seen in schizophrenia and bipolar disorder. In the years to come, the combined use of studies in rodent, primate and human brain will be useful in identifying how specific phenotypic changes in subclasses of interneurons may have been induced in schizophrenia and bipolar disorder. Such information will undoubtedly provide important new insights into how the integration of GABAergic interneurons with other intrinsic and extrinsic transmitter systems may be altered in neuropsychiatric disease.


Anterior Cingulate Cortex GABAA Receptor Hippocampal Formation Stratum Oriens Basolateral Nucleus 
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  • Francine M. Benes
  • Sabina Berretta

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