Video - Louis Wain's Progression into Schizophrenia

A few people requested that the video of Louis Wain's drawings be posted up so below should be the same video I showed while presenting.

Integration of Hypotheses

The cause and origin of schizophrenia remains poorly understood, involving genetic and epigenetic mechanisms, as well as environmental contributions. Additionally, immune modifications have been widely reported in schizophrenic patients, involving both the unspecific and specific pathways of the immune system, and signifying that infectious/autoimmune processes play an important role in the etiopathogenesis of the disorder. Cytokines, in particular, are thought to play a critical role in infectious and inflammatory processes, mediating the cross-talk between the brain and the immune system. In this perspective, even though mixed results have been reported, it seems that schizophrenia is associated with an imbalance in inflammatory cytokines. Alterations in the inflammatory and immune systems, moreover, seem to be already present in the early stages of schizophrenia and connected to the neurodevelopmental hypothesis of the disorder, identifying its roots in brain development abnormalities that do not manifest themselves until adolescence or early adulthood.  At the same time, neuropathological and longitudinal studies in schizophrenia also support a neurodegenerative hypothesis and, more recently, a novel mixed hypothesis, integrating neurodevelopmental and neurodegenerative models, has been put forward.  

References:

http://brain.oxfordjournals.org/content/122/4/593.full

http://www.nature.com/mp/journal/v6/n6/full/4000956a.html

Developmental Disorder

Despite numerous well conducted studies associating congenital or neonatal infections to schizophrenia, the infection hypothesis remains compelling but has yet to be proven. Perhaps most annoying to both critics and proposers of the infection hypotheses is the differentiality between studies performed and the failure to identify a specific infection as being consistently associated with all or most cases of the disease.

The developmental theories of schizophrenia say that basically something goes wrong when the brain is developing. Brain development, from the beginning stage of fetal development through the early years of life, is an incredibly complicated process. During this time, millions upon millions of neurons are formed, travel to different regions of the forming brain, and specialize to perform different functions.

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

 

Symptoms of schizophrenia usually emerge in late adolescence or early adulthood. Developmental theories suggest an early mutation or interruption causes the brain structure to be disordered. 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.

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

          
           Mothers who experienced famine during the first trimester are more likely to have children that develop schizophrenia.

                Pregnancy and birth complications increase the risk of developing schizophrenia.

Although the studies are compelling and risk factors point to developmental theories, there is not yet enough evidence that the brains of adults with schizophrenia are disorganized in the ways that developmental theories suggest. Also, these theories address the When of schizophrenia’s origin, but not the cause itself.

References:

http://apt.rcpsych.org/content/13/5/384.full

http://mentalhealth.about.com/od/schizophrenia/a/sz2.htm

Insanity Virus

Before reading the following information, I suggest clearing your mind of any prior knowledge of the cause of schizophrenia in order to begin judging Dr. Torrey’s analysis without bias.

Research recently conducted by Dr. Fuller Torrey and members of his staff at the Stanley Medical Research Institute proposes that the disorder, which has always been regarded as a psychiatric condition, may not be a mental illness at all. Rather, Torrey’s research claims that schizophrenia is, in fact, caused by a virus.

This theory suggested by Torrey is known as "the insanity virus" and while the theory is accredited to Dr. Torrey alone, there are many psychiatrists and medical researchers that support the idea of this virus. The insanity virus theory suggests that there is a virus ingrained in human DNA. The insanity virus is not contagious. Actually, it is something that we are all born with. Torrey claims that certain environmental conditions, like stress or immune response, can somehow activate the virus, leading to inflammation in the brain, delusions, and other psychotic symptoms.

  Increased inflammation in patients as schizophrenia worsens

Torrey began conducting research on schizophrenia and bipolar disorder after his younger sister was diagnosed as being schizophrenia. Many doctors and therapists 30-40 years ago believed that the disease was attributed to bad parenting or the result of abuse. Later, a genetic link was recognized, but doctors still do not have the answer as to why some people with a genetic predisposition for disorders on the same spectrum go on to develop schizophrenia while others do not.

In his preliminary research, Torrey began to notice similar patterns of inflammation in the brain of people diagnosed with schizophrenia. Inflammation is commonly attributed to illness, infection, or heightened immune response. Following this, Torrey began studying over 100 volunteers. His theory states that an infection or illness can trigger the insanity virus, leading to the development of schizophrenic symptoms that last for longer periods of time.

Torrey began treating many schizophrenic patients with antibiotics and anti-viral medications, and his studies have had astounding results. Each time that immune response is diminished through the use of these kinds of drugs, symptoms in schizophrenic patients began to improve, and inflammation declined. The theory of the insanity virus has still not thoroughly been proven. There is substantial criticism from other researchers in the field, and there is considerable research left to do.

References:

http://www.nature.com/mp/journal/v6/n6/full/4000956a.html

http://www.npr.org/templates/story/story.php?storyId=106151437

Neuropathology

It is believed by some that schizophrenia is a mental illness caused by a chemical imbalance of Dopamine and Seratonin; neurotransmitters that are significant in their ability to function as both excitatory and inhibitory. This, based on my research, has not shown to be the case. Rather than a simple chemical imbalance, there have been studies to show resemblances in all if not most of the brains of those diagnosed with schizophrenia. Tests showed that blood flow was lower in frontal regions in afflicted people when compared to non-afflicted people. This condition has become known as hypofrontality. Other studies illustrate that people with schizophrenia often show reduced activation in frontal regions of the brain during tasks known to normally activate them.

Some studies have found the hippocampus and amygdala to be reduced in volume. Also, components of the limbic system, which is involved in the control of mood and emotion, and regions of the Superior Temporal Gyrus (STG), which is a large contributor in language function, have been notably smaller. The Heschl's Gyrus (which contains the primary auditory cortex), and the Planum Temporale are diminished. The severity of symptoms such as auditory hallucinations has been found to be dependent upon the sizes of these language areas.

Another area of the brain that has been found to be severely affected is the prefrontal cortex. The prefrontal cortex is associated with memory, which would explain the disordered thought processes found in schizophrenics. All of these abnormalities in brain function and structure size have pointed to the fact that all, if not most, people with the illness have increased ventricular space. Enlargement of the lateral cerebral ventricles is one of the earliest reported structural brain imaging abnormalities found in schizophrenia, as well as one of the most stable findings in morphometric investigations. However, it is unclear whether ventricular changes are related to focal or diffuse volume reduction of brain parenchyma. Previous studies have implicated preferential enlargement of certain parts of the ventricular system, such as the temporal horn or body of the ventricles. This might suggest that ventricular enlargement in these patients is related to specific shrinkage of gray matter or white matter structures, rather than diffuse brain atrophy. Structures implicated in schizophrenia such as the thalamus, hippocampus, or corpus callosum are located adjacent to or near the ventricles and show structural alteration in schizophrenia.

References:

http://brain.oxfordjournals.org/content/122/4/593.full

http://www.nature.com/mp/journal/v6/n6/full/4000956a.html

Introducing...Schizo

Schizophrenia is a chronic, complex, and disabling brain disorder that effects people throughout the world. Those with schizophrenia tend to have difficulty acting normal in social situations, experiencing normal emotional responses, thinking clearly, and being able to tell the difference between what is real and what is not real.

 

 

People with Schizophrenia find it hard to determine what is real and what is not


 

Over 2.1 million people in America have been diagnosed with schizophrenia not counting undocumented immigrants. The number of people with this complex illness is increasing at an alarming rate with an estimated 100,000 - 200,000 diagnosed each year.

 

 

 

Schizophrenia effects those diagnosed as well as those surrounding the person(s) diagnosed. Self - harm and harm to others is a factor when determining the functionality of one with schizophrenia. People with schizophrenia are diagnosed with one of five subtypes at a time. While no case is typical, a person may experience signs of multiple subtypes of schizophrenia and be diagnosed with several of these subtypes throughout the course of their life. These five subtypes are; Paranoid, Disorganized, Catatonic, Undifferentiated, & Residual.

 

 

 

 

Schizophrenia used to be thought of only as a psychological issue and did not have very many treatment options until the 1950s with the development of the first dopamine antagonist used as an antipsychotic, Chlorpromazine. Since the development of this drug, there have been leaps in the advancement regarding treatments and knowledge of schizophrenia.

Synthesis Structure of the antipsychotic dopamine antagonist Chlorpromazine (right)

One of these advancements is the fact that researchers are getting closerand closer to finding the cause of schizophrenia by looking more into the difference of their brian function compared to those without schizophrenia. There have also been studies done determining the genetic differentiation of the disorder showing that it may be hereditary. Although it may increase the chances of person(s) to develope schizophrenia if there are blood- related relatives diagnosed with the disorder, it is not purely genetic.

Many treatments for schizophrenia are available but there has yet to be a cure.