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Francine M. Benes, MD, PhD; John Walsh, MA; Sujoy Bhattacharyya, MS; Archna Sheth; Sabina Berretta, MD

Arch Gen Psychiatry. 2003;60:359-364.

Background  Apoptosis is thought to play a role in neuronal pathology in schizophrenia and bipolar disorder.

Methods  To test this hypothesis, the Klenow method for in situ end-labeling of single-stranded DNA breaks was applied to anterior cingulate cortex from 18 healthy controls, 18 schizophrenic subjects, and 10 bipolar subjects.

Results  An unexpected reduction (71%) in Klenow-positive nuclei was found in schizophrenic but not in bipolar cortexes.

Conclusions  To our knowledge to date, this is the first demonstration that there is much less DNA fragmentation in individuals with schizophrenia than in healthy controls and bipolar subjects, which raises a key question as to whether this alteration represents an adaptive or nonadaptive change in the regulation of intracellular signaling and mitochondrial oxidative pathways associated with apoptosis.

From the Laboratories for Structural Neuroscience, McLean Hospital, Belmont, Mass, and the Program in Neuroscience and Department of Psychiatry, Harvard Medical School, Boston, Mass.

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