Monday, 11 March 2013

by whandie on 11:57 Leave a Comment

Glutamatergic theories of schizophrenia

Abstract Schizophrenia is a serious mental disorder that affects up to 1% of the population worldwide. Traditional models of schizophrenia have emphasized dopaminergic dysfunction. Over the last 20 years, however, limitations of the dopamine model have become increasingly apparent, necessitating development of alternative models. Glutamatergic models are based upon the observation that the psychotomimetic agents such as phencyclidine (PCP) and ketamine induce psychotic symptoms and neurocognitive disturbances similar to those of schizophrenia by blocking neurotransmission at N-methyl-D-aspartate (NMDA)-type glutamate receptors. Because glutamate/NMDA receptors are located throughout the brain, glutamatergic models predict widespread cortical dysfunction with particular involvement of NMDA receptors throughout the brain. Further, NMDA receptors are located on brain circuits that regulate dopamine release, suggesting that dopaminergic deficits in schizophrenia may also be secondary to underlying glutamatergic dysfunction. Agents that stimulate NMDA receptor-mediated neurotransmission, including glycine-site agonists and glycine transport inhibitors, have shown encouraging results in preclinical studies and are currently undergoing clinical development. Encouraging results have been observed as well with agents such as metabotropic 2/3 agonists that decrease resting glutamate levels, reversing potential disruption in firing patterns within prefrontal cortex and possibly other brain regions. Overall, these findings suggest that glutamatergic theories may lead to new conceptualizations and treatment approaches that would not be possible based upon dopaminergic models alone. 

Source: http://www.ncbi.nlm.nih.gov/pubmed/20686195
by whandie on 11:55 Leave a Comment

Developmental Theories of Schizophrenia

Developmental theories of schizophrenia say that something goes wrong when the brain is developing. Brain development, from the earliest stage of fetal development through the early years of life, is an extremely complicated process. Millions of neurons are formed, migrate to different regions of the forming brain, and specialize to perform different functions.

The “something” that goes wrong might be a viral infection, a hormonal imbalance, an error in genetic encoding, a nutritional stress, or something else. The common element in all developmental theories is that the causal event occurs during the brain’s development.

Symptoms of schizophrenia typically emerge in late adolescence or early adulthood. How could those symptoms be caused by developmental events that took place decades earlier? Developmental theories suggest an early disruption causes the brain structure to be disorganized. The start of puberty brings a number of neurological events, including the programmed death of many brain cells, and at that time the abnormalities become critical.

To support developmental theories, there are a number of risk factors for schizophrenia related to critical periods in fetal development, such as:

    Schizophrenia is more common in winter and spring births.
    Children whose mothers experienced famine during the first trimester are more likely to develop schizophrenia.
    Pregnancy and birth complications increase the risk of developing schizophrenia.

However, there is not yet enough evidence that the brains of adults with schizophrenia are disorganized in the ways that developmental theories predict. Also, these theories address the when of schizophrenia’s origin, but not the cause itself.

Source: http://schizophrenia.about.com/od/whatisschizophrenia/ss/WhatCauses_3.htm