environmental events associated with schizophrenia, such as
maternal virus infection and malnutrition as well as exposure
to stress and early adversity, inluence the expression of these
genes, resulting in abnormal brain development and patho-
logical behaviour in experimental animals.
Schizophrenia has therefore been reconceptualised as a
disease of abnormal neural development caused by the inter-
action of many genes and adverse early events.
Insulin Resistance
About 10 years ago researchers at The University of Cambridge
discovered abnormal expression of genes responsible for the
proper breakdown and utilisation of glucose in the prefrontal
cortex of patients with schizophrenia. This brain region is
involved in higher cognitive functions that are abnormal in
schizophrenia, such as attention, planning and executive control
of other brain areas. Other groups conirmed that these enzyme
proteins are abnormally low in this brain region. They also
identiied changes in the structure and function of the mito-
chondria, the “power stations” that fuel all of the processes
required for proper communication between nerve cells. These
discoveries have given rise to the hypothesis that abnormal
glucose and energy metabolism may contribute to the devel-
opment of schizophrenia.
This wasn’t surprising. Maudsley, the famous 19th century
British psychiatrist, had already observed that patients suffering
from “insanity”, as well as their irst-degree relatives, showed a
disproportionately higher rate of diabetes mellitus. This was
the irst hint that glucose and energy metabolism might be
abnormal in schizophrenia.
Before the discovery of modern antipsychotic agents, psychi-
atrists at the beginning of the 20th century employed insulinMAY 2016|| 15Terence Mendoza/adobe