Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

The sex difference in age of onset in schizophrenia is paradoxical in the sense that the brain is developing faster in females but onsets are earlier in males. Therefore if schizophrenia, as widely believed, is a disorder of development, the difference is in the wrong direction. Here we attempt to resolve the paradox with the hypothesis that psychosis is an anomaly of development of cerebral asymmetry and the following assumptions: (1) asymmetry (the torque) confers directionality on the 'language circuit'--failure to develop asymmetry leads to the risk of reverse transmission, a putative mechanism of psychotic symptoms; (2) the corpus callosum goes on developing in an antero-posterior direction into the third and fourth decades of life; (3) a sex difference in structure and development of the corpus callosum (with some anterior components greater in males and posterior components greater in females) reflects stronger, faster lateralization in females; (4) because of the inverse relationship between asymmetry and interhemispheric connections, females, by developing faster, avoid the misconnectivity phenomena in the frontal lobes that males, developing more slowly, may encounter at a younger age with particular risk of negative symptoms.

Original publication




Journal article


Int Rev Psychiatry

Publication Date





449 - 457


Age of Onset, Brain, Cerebral Cortex, Corpus Callosum, Female, Functional Laterality, Humans, Male, Postmortem Changes, Psychotic Disorders, Sex Characteristics, Torque, Treatment Outcome