What is schizophrenia?
Schizophrenia is a type of mental illness characterized by delusional thinking,
hallucinations, and a lack of normal emotional response. The schizophrenic typically
experiences social isolation as a result of these characteristics, and drug therapy is
almost always necessary to quell the devastating effects of the disease.
Schizophrenia typically strikes its victims during their teens and twenties, often
leads to total disability, and in 10-15% of its victims, ends in death by suicide.
Schizophrenia afflicts almost 1% of the world's population, including at least 2 million
Americans. The World Health Organization (WHO) ranks schizophrenia high among all
medical conditions (psychiatric and non-psychiatric alike) in terms of overall disease
burden to the individual, his or her family, and society.
Symptoms of schizophrenia
Persons with schizophrenia typically show a decreased ability to think clearly, and
they experience hallucinations and delusions. The schizophrenic may see, feel and hear
the hallucinations as very real events. Many times the individual may experience delusions,
including "paranoid delusions", in which he feels that he is being conspired against, and
"broadcasting", in which the affected person believes that his own thoughts can be heard
by other people. Often, the schizophrenic will hear voices that may tell him how to
behave or they may constantly warn him of danger. These voices may contribute to the
person's overall withdrawl from society, many times isolating him from family and
friends.
The schizophrenic may also express a lack of emotion or appear apathetic and withdrawn.
These "flat" or "blunted" emotional responses are typical symptoms of schizophrenic
behavior.
Drug treatment for schizophrenia
Almost 50 years ago the first "modern" antipsychotic drug, chlorpromazine (ThorazineR),
was introduced for the treatment of schizophrenia. Over the next two decades at least a
dozen more antipsychotic drugs were introduced. While these drugs offered unprecedented
hope and diminished suffering for countless mentally ill people (and substantially
contributed to the "deinstitutionalization" of mentally ill people from long-term
hospitalization in the 1960's and 70's), the "neuroleptic" drugs had serious limitations.
First, their effectiveness was limited to the "positive symptoms" of schizophrenia, such
as hallucinations, delusions, and grossly disorganized thinking. The "negative symptoms"
of schizophrenia, such as social withdrawal, paucity of thought, diminished motivation and
energy, and blunted emotional expression, were relatively untouched by these treatments.
Second, the neuroleptics caused serious neurological side effects, sometimes permanently,
in people on these drugs. All of the drugs are thought to exert their effects through an
ability to block post-synaptic dopamine receptors.
In 1990 the first "atypical" antipsychotic drug, clozapine, was introduced for the
treatment of schizophrenia. It was considered atypical for several reasons, including a
different pharmacodynamic profile (significant affinity for serotonin as well as dopamine
receptors), a different side effect profile (minimal propensity for causing neurological
side effects, although at the expense of more weight gain and other metabolic consequences),
and the ability to alleviate, albeit modestly, negative symptoms. This drug was followed
by four more "new generation" antipsychotics over the next decade, including risperidone
(RisperdalR, 1994), olanzapine (ZyprexaR, 1996), quetiapine (SeroquelR, 1998), and
ziprasidone (GeodonR, 2001). While each drug varies somewhat in its properties, all have
pharmacodynamic and side effect profiles and negative symptom efficacy that differ from
the older neuroleptic drugs.
The new generation antipsychotic drugs represented a major advance in the treatment of
schizophrenia. Many people who did not respond to the older drugs or could not tolerate
the neurological side effects have had remarkable success with the newer drugs. Many
people's lives have improved immeasurably or have even been saved altogether thanks to
these drugs. However, clinicians have had little evidence to guide drug selection for a
given patient. Basic questions about which drug to use, and in what circumstances, are
yet to be answered.
Schizophrenia research at the WKNI
An ambitious group of scientists and clinicians at Wallace-Kettering Neuroscience
Institute (WKNI) at Kettering Medical Center and Wright State University School of Medicine
in Dayton, Ohio, Mt. Sinai Medical Center in New York City, and the University of California
at Irvine have banded together to delve into the nature of schizophrenia. The study entitled,
"Evaluation of the Distribution of 18F-FDG and 18F-Fallypride Using PET in Schizophrenic
and Normal Subjects" has the goal of increased understanding of the brain "circuitry" of
schizophrenia. The first subjects to participate in the study arrived in November. Drawing
from as far away as central Kentucky, we have engaged ill and normal "control" subjects alike
in what we believe will be a landmark investigation into the brain the possible root causes
of schizophrenia.
Using the rich variety of brain imaging resources found at WKNI and the cadre of scientists
that support these technologies, we hope to reveal new information about the interaction
between several areas of the brain thought to be involved in schizophrenia, including the
striatum, prefrontal cortex, and thalamus.
The WKNI is the only facility in the Dayton area that can perform Positron Emission
Tomography (PET), and is one of the only centers in the world able to produce a PET
radioisotope known as fallypride, a dopamine receptor ligand with several advantages
(superior dopamine receptor affinity and specificity) over its predecessors
(Figure 1).
WKNI also possesses a full array of state of the art
Magnetic Resonance Imaging (MRI) research tools, including functional MRI (fMRI) and Diffusion Tensor
Imaging (DTI), able to demonstrate brain activation patterns during specific tasks or
mental states, and white matter tract architecture, respectively. By obtaining this
battery of imaging studies, as well as comprehensive psychiatric and neurocognitive
information, on never-medicated people with schizophrenia and normal "control" subjects,
we hope to better characterize disease-related brain abnormalities than has previously
been possible.
This enthusiastic collaboration between psychiatrists (Dr. Buchsbaum and Lehrer), nuclear
medicine clinicians and scientists (Drs. Mantil, Mukherjee, Christian, Satter, and Shi),
MRI physicists (Drs. Ezzeddine and Adineh), and a neuropsychologist (Dr. Finton), supported
by our absolutely indispensable research coordinator/assistant team (Candi Lee, R.N., and
Aaron Murray, B.S.) offers a rich opportunity to create an enduring schizophrenia
research effort at Kettering.
The WKNI and Kettering Medical Center have been invited to join two dozen of America's
leading university based psychiatric research centers to participate in a major study of
antipsychotic drugs. This drug company funded double-blind study will compare the
effectiveness of three new generation antipsychotic drugs in about 400 people suffering
their first episode of schizophrenia.
Over the next two years we expect to complete both of these studies. We anticipate that
we will have enough data to receive National Institute of Mental Health (NIMH) support to
continue our investigations into the nature of schizophrenia, and contribute to the
development of safer, more effective treatments.
A salute to our donor
We wish to thank Mr. Oscar Boonshoft for his generous support of our work. We are
extremely gratified that his gift has led to a range of scientific investigations that will
hopefully become self-perpetuating and self-supporting. The WKNI may then take its place
among those institutions that will someday unlock the awful secrets of schizophrenia.
Author: Douglas Lehrer, M.D.
Schizophrenia Links
Current Schizophrenia Research
CAFE Study
(Comparison of Atypicals for First Episode)
NARSAD
(National Alliance for Research on Schizophrenia and Depression)
Schizophrenia.com
