Neurochemical Function in Schizophrenia: A Case Study

This research project addresses the topic of schizophrenia. Because of the vast amount of information available regarding schizophrenia, this paper will only focus on a few aspects of the disease. In particular the symptoms, brain abnormalities, hypotheses, and treatment strategies associated with brain abnormalities in schizophrenia will be presented. These emphases were chosen because they are of particular interest to the researcher. The intent ofthis paper is to discover what brain abnormalities, both physiological and chemical, are associated with schizophrenia. The intent is also to discuss treatment strategies and assess how this information may apply to a case study. Neurochemical Function in Schizophrenia 3 Neurochemical Function in Schizophrenia: A Case Study Schizophrenia is a multi-faceted disease. It would be an immense task to attempt to capture all the intricacies of the disorder in one research project. Therefore, this document is biased in a way, because only certain topics relating to schizophrenia will be addressed. The purpose of this paper is discover what brain abnormalities, both physiological and chemical, are associated with schizophrenia. Also, this paper intends to discuss various treatment options, relative to their impact on brain neurophysiology. The information gathered will be applied to a case study. While this study is not an exhaustive treatment on the topic of schizophrenia, hopefully it will prove useful in allowing the reader to catch a glimpse of the complexity of schizophrenia. History and Background It was Emil Kraepelin who led the way in placing schizophrenia in a distinct category separate from related disorders such as Alzheimer's and manic depression. In his early writings, Kraepelin dubbed schizophrenia 'dementia praecox' and stressed the chronic nature of the disease. Bleuler disagreed with Kraepelin's emphasis on the persistence ofthe disorder, and shortly after the turn of the twentieth century he renamed it to the commonly recognized name it bears today: schizophrenia. In renaming the disorder, Bleuler sought to underscore the disintegration of thinking and personality that typifies schizophrenia (Andreasen, 1995). Schizophrenia is an unforgiving disorder, leaving most sufferers unable to completely return to pre-diagnosis functional levels. As yet, there is no cure for the disease, and a great majority of patients must receive ongoing therapy, usually psychoparmaceuticals, for the rest of their lives. Even if all preventative measures are taken after the diagnosis in confirmed, the Neurochemical Function in Schizophrenia 4 person may suffer a relapse and require treatment more intense than maintenance treatment, or even hospitalization. Approximately 62 million people worldwide suffer from schizophrenia. In US hospitals, schizophrenics are occupying about 25% of all beds and comprise 40% of long-term care days (Pickar, 1995). According to 1980 estimates, schizophrenia costs about $11.1 billion in terms of medical care and maintenance. Sadly enough, schizophrenia usually arises in the late adolescent to early adulthood stages of life, when opportunities seem boundless, and life is yet to be fully experienced. The victim struggles with loss of identity, independence, and mental functioning abilities. In light of this, it is no wonder that 10% of schizophrenics terminate their existence by committing suicide (Andreasen, 1995). Symptoms A wide array of symptoms characterize schizophrenia. Hallucinations, delusions, avolition, affective blunting serve as a few examples of the symptoms displayed in this disorder. A sampling of symptoms is present in all patients, but no single symptom is present in all. Schizophrenia is termed a polythetic disorder because it lacks a unifying characteristic. Because of this complexity, symptoms have been classified into two distinct categories, positive and negative symptoms, in order to simplify the diagnosis of the type of schizophrenia prevalent in the patient (Andreasen, 1995). Positive Positive symptoms usually designate the presence of a trait that would normally be absent. According to Mattson, Berk, and Lucas (1997) "positive symptoms include delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness, and hostility"(p. 490). Those who predominately express positive symptoms have an increased Neurochemical Function in Schizophrenia 5 success rate in responding to treatment (Andreasen, 1995). While complete restoration to a prediagnosis state may not be possible, typically treatment offers more hope than if negative symptoms were predominately present. Negative Negative symptoms tend to indicate the lack of a certain feature that should be present under normal functioning. Typically, negative symptoms are less responsive to treatment than positive symptoms, and disable patients from returning to daily activities such as work or school (Andreasen, 1995). Negative symptoms include "poverty of thought and speech, blunted affect, decreased motor activity, apathy and avolition, and diminished interpersonal interactions. Other symptoms such as poor rapport, difficulty in abstract thinking, lack of spontaneity and flow of conversation, and stereotyped thinking have been included" (Mattson et al., 1997, p. 490). Findings indicate that many manifestations of negative symptoms may be due to depression (Beck & Rector, 2000). Brain Abnormalities While the symptoms offer themselves to classification, the causes of schizophrenia do not. There are a variety of factors that may work together to induce psychosis. Below is a closer look at the brain abnormalities that are associated with schizophrenia. Over 15 years of computed tomography indicate that people diagnosed with schizophrenia have brain abnormalities. These include an "upward shift in the distribution of ventricular size and dilation of the cortical sulci" (Waddington, 1993, p. 533). MRI studies point to an increase in ventricular volume with some increases in cortical sulcal volume and loss of gray matter. The 3-D MRI brain images indicate a reduced amount of gray matter in the anterior Neurochemical Function in Schizophrenia 6 hippocampus, parahippocampal gyrus, and the superior temporal gyrus in the left hemisphere (Waddington, 1993). Using positron emission tomography (PET) to estimate regional cerebral blood flow has provided important information on the sites of abnormal neuronal activity and metabolism in the brain. Typically, schizophrenic patients demonstrate frontal hypometabolism. MR spectroscopy findings also indicate frontal lobe dysfunction (Waddington, 1993). Currently there are two view being used to link the clinical view of schizophrenia with its underlying brain mechanisms. One view states that specific symptoms or closely related symptoms are concentrated in a specific brain region. This view tends to look at schizophrenia as a disease like multiple sclerosis, which has lesions at various sites in the brain. The second view emphasizes a problem at the level of the wiring in the brain and states that symptoms are a result of this incorrect wiring. The focus of this view is that one single misconnection can trigger a variety of symptoms because of the complex feedback mechanisms that function in the brain (Andreasen, 1995). The first iew is related with positive symptoms at the temporal and limbic regions of the brain. Magnetic resonance (MR) studies show that a decrease in size of the superior temporal gyrus is associated with auditory hallucinations. MR has also indicated that a smaller planum temporale is linked with thought disorder. Both of these findings support the first view. PET scans have also provided support for this view by revealing that abnormalities in these brain regions are related to psychotic manifestations. Both PET and MR have provided evidence of frontal lobe dysfunction associated with negative symptoms. The main problem faced with this view is that the brain must be dissected and then pieced together one region at a time (Andreasen, 1995). Neurochemical Function in Schizophrenia 7 Applying the second view is still in the beginning stages. Several circuits have been proposed, most of which deal with pathways that link the prefrontal cortex and the subcortical regions such as the basal ganglia and thalamus. One model that is achieving increasing acceptance locates deficits in the circuitry that gates or filters the information perceived by the brain and forwards the relevant or socially and biologically important information to heteromodal cortex for further prioritization and decisions about action or behavior (Andreasen, 1995). If this circuit were defective, the individual would be besieged with information, therefore causing hallucinations, delusions, strange behavior, and a variety of negative symptoms. Studies that indicate a lack of information processing in schizophrenia provide support for this model. Neuropathological studies demonstrating abnormalities in the thalamus also supply evidence for this model (Andreasen, 1995). Development of Dopamine Theory In order to take a closer look at the role the brain plays in schizophrenia, it is necessary to look at the neurochemistry involved. It was not until the almost half way into the twentieth century that experimental evidence linked mental disorders with neurochemical abnormalities in the brain. Studies indicated that the endogenous monoamines such as dopamine, noradrenaline, and serotonin were involved with schizophrenia pathology. Later, numerous studies revealed that antipsychotic drugs block the transmission of monoamines (Sed vall & Farde, 1995). New technology emerged during the 1970s allowing for a closer examination of neurotransmitter activity at the level of neuroreceptors. Isotopically labeled drugs demonstrated that these drugs were indeed binding the dopamine receptors, the use of positron emission Neurochemical Function in Sch