Multiple genes contribute to risk for schizophrenia and appear to function in pathways related to transmission of signals in the brain and immunity, according to an international study led by Virginia Commonwealth University School of Pharmacy researchers.
By better understanding the molecular and biological mechanisms involved with schizophrenia, scientists hope to use this new genetic information to one day develop and design drugs that are more efficacious and have fewer side effects.
In a study published online in the April issue of JAMA Psychiatry, the JAMA Network journal, researchers used a comprehensive and unique approach to robustly identify genes and biological processes conferring risk for schizophrenia.
The researchers first used 21,953 subjects to examine over a million genetic markers. They then systematically collected results from other kinds of biological schizophrenia studies and combined all these results using a novel data integration approach.
The most promising genetic markers were tested again in a large collection of families with schizophrenia patients, a design that avoids pitfalls that have plagued genetic studies of schizophrenia in the past. The genes they identified after this comprehensive approach were found to have involvement in brain function, nerve cell development and immune response.
“Now that we have genes that are robustly associated with schizophrenia, we can begin to design much more specific experiments to understand how disruption of these genes may affect brain development and function,” said principal investigator Edwin van den Oord, Ph.D., professor and director of the Center for Biomarker Research and Personalized Medicine in the Department of Pharmacotherapy and Outcomes Science at the VCU School of Pharmacy.
“Also, some of these genes provide excellent targets for the development of new drugs,” he said.
One specific laboratory experiment currently underway at VCU to better understand the function of one of these genes, TCF4, is being led by Joseph McClay, Ph.D., a co-author on the study and assistant professor and laboratory director in the VCU Center for Biomarker Research and Personalized Medicine. TCF4 works by switching on other genes in the brain. McClay and colleagues are conducting a National Institutes of Health-funded study to determine all genes that are under the control of TCF4. By mapping the entire network, they aim to better understand how disruptions to TCF4 increase risk for schizophrenia.
“Our results also suggest that the novel data integration approach used in this study is a promising tool that potentially can be of great value in studies of a large variety of complex genetic disorders,” said lead author Karolina A. Aberg, Ph.D., research assistant professor and laboratory co-director of the Center for Biomarker Research and Personalized Medicine in the VCU School of Pharmacy.
Letter written by Emma Hauck to her husband while in a psychiatric hospital. The words ‘sweetheart come’ (‘Herzensschatzi komm’), are written over and over filling the surface of the paper. Circa 1909.
Raymond Depardon - San Clemente Psychiatric Hospital (1980)
ELECTROCONVULSIVE THERAPY (shock therapy) ECT
ECT has a higher success rate or severe depression than any other form of treatment. It is particularly useful for people who suffer from psychotic depressions or intractable mania, people who cannot take antidepressants due to problems of health or lack of response & pregnant women who suffer from depression or mania. A patient who is very intent on suicide, & who would not wait 3 weeks for an antidepressant to work, would be a good candidate for ECT because it works more rapidly. In fact, suicide attempts are relatively rare after ECT.
ECT is usually given 3 times a week. A patient may require as few as 3 or 4 treatments or as many as 12 to 15. Once the family & patient consider that the patient is more or less back to his normal level of functioning, it is usual for the patient to have 1 or 2 additional treatments in order to prevent relapse. Today the method is painless, & with modifications in technique it bears little relationship to the unmodified treatments of the 1940s.
The patient is put to sleep with a very short-acting barbiturate, & then the drug succinycholine is administered to temporarily paralyze the muscles so they do not contract during the treatment & cause fractures. An electrode is placed above the temple of the nondominant side of the brain, & a second in the middle of the forehead (this is called unilateral ECT); or one electrode is placed above each temple (this is called bilateral ECT). A very small current is passed through the brain, activating it & producing a seizure. Because the patient is anesthetized & his body is totally relaxed by the succinycholine, he sleeps peacefully while an electroencephalogram (EEG) monitors the seizure activity & an electrocardiogram (EKG) monitors the heart rhythm. The current is applied for one second or less, & the patient breathes pure oxygen through a mask. The duration of a clincally effective siezure ranges from 30 seconds to sometimes longer than a minute, & the patient wakes up 10 to 15 minutes later. Upon awakening, a patient may experience a brief period of confusion, headache or muscle stiffness, but these symptoms typically ease in a matter of 20 to 60 minutes. During the few seconds following the ECT stimulus there may be temporary drop in blood pressure. This may be followed by a marked increase in heart rate, which may then lead to a rise in blood pressure. Heart rhythm disturbances, not unusual during the period of time, generally subside without complications. A patient with a history of high blood pressure or other cardiovascular problems should have a cardiology consultation first.
Because as many as 20 to 50 percent of the people who respond well to a course of ECT relapse within 6 months, a maintenance treatment of antidepressants, lithium or ECT at monthly or 6 week intervals might be advisable.
Short-term memory loss has always been a concern to patients who receive ECT, but several studies conclude that patients who received unilateral ECT performed better on attention/memory tests than those who received bilateral ECT. However, there is a question as to whether unilateral is as effective. Experts agree that changes in memory function do occur & persist for a few days following treatment, but that patients return to normal within a month. A 1985 NIMH Consensus Conference concluded that while some memory loss is frequent after ECT, it is estimated that one-half of 1 percent of ECT patients suffer severe loss. Memory problems usually clear within 7 months of treatment, although there may be a persistent memory deficit for the period immediately surrounding the treatment.