Insanity, then, is inordinate or irregular, or impaired action of the mind, of the instincts, sentiments, intellectual, or perceptive powers, depending upon and produced by an organic change in the brain.

---W.A.F. Browne, MD, 18371

Schizophrenia is considered a disease of the brain, a physical disorder that, thanks to modern technology, is able to be visualized. Schizophrenia, along with other diseases of the brain, such as Parkinson's, Alzheimer's, and multiple sclerosis, are all brain diseases which alter both functionality and structure of the brain. Schizophrenia has been called a cruel disease, one that impairs life greatly in a degenerative fashion, altering emotions and various abilities greatly. This unfortunate disease is quite common, effecting about one to two percent of the World's population. About two to four percent of the population suffer from less severe yet still debilitating and disturbing schizophrenic-like symptoms. An estimated sixty five billion a dollars per year is spent on this disorder in the United States.(2) It is estimated that over two million Americans suffer from schizophrenia in their lifetime..

There is a definite biological basis for this disease, although it is not totally understood. For a long time schizophrenia was a mystery to doctors and scientists. Virtually any patient with a psychological disorder used to be placed under the expansive umbrella that defined the disease. Poor parenting was a misleading, early excuse for the troubles caused by what is now known to be substantially based in genetics. The most current idea of origin is that this disorder occurs during the crucial beginning months of life, those spent within the womb. Neither social nor psychological factors have been ruled out, but the primary cause of schizophrenia is thought to be a mix of environmental and mostly hereditary factors. .(3) Schizophrenia is often present in familial clusters. Monozygotic twins have an even slightly higher concordance rate. It has been found through studies that adoptive parents do not have any effect upon children in relation to developing the disease, which is also another strong biological marker. The risk factor of children with parents suffering from the disease rises from one percent to twelve percent . Another finding that backs up the biological basis claim is that lower levels of platelet monomania oxidase B are found in people suffering from chronic schizophrenia. Higher levels in the cerebral spinal fluid of these monoamine metabolites, HVA, and 5HIAA are found in people with a family history of schizophrenia as opposed to people without the genetic predisposition afflicted with the disease. .(4) These varying levels result in varying biochemical changes that are predetermined and passed through families.

Environmental factors are still unclear in relation to this complicated disease. Clinical psychologist Meggin Hollister from the University of Pennsylvania researched the Rh factor, a blood protein. She found that a fetus with a differing Rh factor than its mother is more prone to developing the disorder. This difference is a condition that allows the immune system of the mother to attack that of the child, which can cause substantial damage. Higher possibilities of the disease has also been linked to influenza, hypoxia, and endocrine problems during pregnancy. Evidence to support the idea that damage occurs early in development is present in post-mortem brains of some schizophrenics in one study. Histological changes with out the proliferation of glial cells, gliosis, suggests that schizophrenic damage occurs very early in development. .(5) This damage is thought to become apparent later in life, which explains for the late teens to twenties age of onset. Two other ideas that have been brought up are a genetically triggered cell death, apoptosis and a stress related glucocorticoid-mediated cell toxicity. These have not been fully researched and are quite new.

Schizophrenia is a complex disease which lacks central characteristics. It is thought to almost be considered a compilation of multiple related disorders. Schizophrenia has such a wide range of symptoms stemming from different parts of the brain that it is not really possible to localize it to one section or another. The general idea is that it is a disorder of neural circuits and neurotransmitter systems, that is brought on by multiple factors that result in the common, devastating mental illness. Basically schizophrenia is considered a disorder generally characterized by bizarre, disoriented thoughts, delusions, hallucinations, and motor capabilities, that occurs for at least six months and significantly impairs social, physical, and emotional functioning. The varying symptoms of schizophrenia include positive symptoms: disorganized speech, delusions, hallucinations, disorganized, and negative symptoms: abnormal movements, alogia, loss of ability to experience pleasure, and memory, attention, and executive functioning deficits. Unlike Alzheimer's Disease, schizophrenia does not include mental deterioration to the extent of full dementia. Also unlike the most common forms of dementia, there are no visible neuropathological markers such as Lewy Bodies, tangles, or plaques. Once again, this points to the evidence that schizophrenia must be a problem within the development and maturation processes of the brain, such as formation of neurites, synaptogenesis, and neuronal pruning. .(6) Modern technology and post-mortem examination reveals many structural abnormalities in the brain of the schizophrenic. Enlarged ventricles, filled with CSF fluid, are thought to cause the compression, shrinkage, and inadequate development of the brain. It is thought that the larger the ventricle swelling, the more serious the mental devastation. Behavioral functioning involves a section of the brain in the third ventrical and near the left temporal lobe. This area consistently reveals the most drastic abnormalities. The basal ganglia, limbic regions, hippocampus, and cortex are also structures involved with this common disorder and found to be marginally smaller. .(7)

Structural abnormalities are accompanied by biochemical difficulties. Dopamine, which regulates behavioral functioning, is thought to be present in excess in the schizophrenic brain. The "dopamine hypothesis" attempts to explain the presence of the positive symptoms in the disorder due to overactivity of the dopaminergic neurons, most likely occurring in the mesolimbic pathway, projecting from the ventral tegmental area to the nucleus acumbens and the amygdala. .(8) Antipsychotic drugs block the transmission of dopamine and are used to improve the condition of people afflicted with schizophrenia. Recent research attempts to introduce another major neurotransmitter, serotonin, into the picture. More advanced antipsychotics, atypical neuroleptics, which interfere with both dopamine and serotonin have been introduced. .(9) Low levels of glutamate, found in CSF, have also been found in people with schizophrenia. Glutamate is also involved in the regulation of the dopaminergic system. .(10)

Drug therapy was introduced in the 1950s, mostly replacing the common treatment of electro-convulsive shock therapy. The chronically disordered thinking and emotional withdrawal, often associated with auditory hallucinations and paranoid delusions can be greatly helped with the drug therapy. There are two classifications of antipsychotics, neuroleptics and atypical neuroleptics. The neuroleptics are experimental and clinical antagonists of the D2 dopamine receptor. They flood the system with dopamine, effecting positively the metabolism of other neurotransmitters. These drugs include: Haldol, Thorazine, and Prolixin. The downfall to these drugs are the extrapyramidal side effects that are often reach a level more bothersome than the actual schizophrenic disturbances. These side effects include dry mouth, drowsiness, constipation, stiff muscles, decreased libido, tremors, slurred speech, and possible increased likelihood of seizures. Tardive Dyskinesia is the most serious side effect. It consists of involuntary facial tics and spastic, abnormal movement of other parts of the body. The condition arises usually in older people, who have been taking antipsychotics for an extended period of time. This condition slowly disappears upon discontinuation of the drug. .(11) Atypical neuroleptics are more popular due to the fact that they basically create the same therapeutic effect without the extrapyramidal side effects. Examples of atypical neuroleptics include Clozaril, Risperdal, and Zyprexa. .(12)

There is no cure for this common, debilitating disease, only treatments that continue to improve with modern research. Schizophrenia is a difficult disease that many chose to hide, which simply adds to the societal stigma that only causes more pain to those that suffer from it and their friends and family.

WWW Sources

2) a href= http://www.powerpak.com/ce/PsychDisorders/lesson.htm

3) http://www.schizophrenia.com/ami/diagnosis/nbd%20intro.html

4) http://www.powerpak.com/ce/PsychDisorders/lesson.htm

5) http://www.schizophrenia.com,/newsletter/1296/1296usnews.htm

6) http://www.nejm.org/content/1999/0340/0008/0645.asp

7) http://www.powerpak.com/ce/PsychDisorders/lesson.htm

8) Goodman&Gilman's CD-Rom The Pharmacological Basis of Therapeutics, 9th edition

9) http://www.schizophrenia.com/newsletter/buckets/hypo.html

10) http://www.powerpak.com/ce/PsychDisorders/lesson.htm

11) http://www.schizophrenia.com/newsletter/buckets/intro.html

12) Goodman&Gilman's CD-Rom The Pharmacological Basis of Therapeutics, 9th edition

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