Schizophrenia: The Importance of Catching It Early

January 18, 2016 · Posted in Current Treatments, Diagnosis · Comment 


By the time psychosis appears in someone with schizophrenia, biological changes associated with the illness may have already been present for years. A 2015 article by R.S. Kahn and I.E. Sommer in the journal Molecular Psychiatry describes some of these abnormalities and how treatments might better target them.

One such change is in brain volume. At the time of diagnosis, schizophrenia patients have a lower intracranial volume on average than healthy people. Brain growth stops around age 13, suggesting that reduced brain growth in people with schizophrenia occurs before that age.

At diagnosis, patients with schizophrenia show decrements in both white and grey matter in the brain. Grey matter volume tends to decrease further in these patients over time, while white matter volume remains stable or can even increase.

Overproduction of dopamine in the striatum is another abnormality seen in the brains of schizophrenia patients at the time of diagnosis.

Possibly years before the dopamine abnormalities are observed, underfunctioning of the NMDA receptor and low-grade brain inflammation occur. These may be linked to cognitive impairment and negative symptoms of schizophrenia such as social withdrawal or apathy, suggesting that there is an at-risk period before psychosis appears when these symptoms can be identified and addressed. Psychosocial treatments such as individual, group, or family psychotherapy and omega-3 fatty acid supplementation have both been shown to decrease the rate of conversion from early symptoms to full-blown psychosis.

Using antipsychotic drugs to treat the dopamine abnormalities is generally successful in patients in their first episode of schizophrenia. Use of atypical antipsychotics is associated with less brain volume loss than use of the older typical antipsychotics. Treatments to correct the NMDA receptor abnormalities and brain inflammation, however, are only modestly effective. (Though there are data to support the effectiveness of the antioxidant n-acetylcysteine (NAC) on negative symptoms compared to placebo.) Kahn and Sommer suggest that applying treatments when cognitive and social function begin to be impaired (rather than waiting until psychosis appears) could make them more effective.

The authors also suggest that more postmortem brain analyses, neuroimaging studies, animal studies, and studies of treatments’ effects on brain abnormalities are all needed to clarify the causes of the early brain changes that occur in schizophrenia and identify ways of treating and preventing them.

Another Blocker of Glutamate Receptor Function with Rapid Antidepressant Effects

January 9, 2014 · Posted in Potential Treatments · Comment 


Certain drugs such as ketamine and memantine that work by blocking activity at the NMDA receptor for the excitatory neurotransmitter glutamate have antidepressant effects. D-cycloserine is a drug that has a related mechanism and is being studied as an antidepressant. At high doses the drug acts as an antagonist at the glycine site of the NMDA receptor, blocking glycine’s ability to facilitate glutamate transmission through the receptor.

Joshua Kantrowitz, a researcher at Columbia University, reported at a recent scientific meeting that the rapid-onset antidepressant effects of D-cycloserine could be maintained for eight weeks. Similar findings were published in the Archives of General Psychiatry in 2010 and were reported in another study by Uriel Heresco-Levy in a 2013 article in the Journal of Neuropsychopharmacology.

Glutamate is the major excitatory neurotransmitter in the brain and is important for the development of long-term memory. However, glutamate overactivity may contribute to depression. Decreasing this overactivity (with ketamine, memantine, or D-cycloserine) may produce antidepressant effects.