Schizophrenia and Brain Morphometry - Essay Example

? SCHIZOPHRENIA Institute SCHIZOPHRENIA Schizophrenia is a chronic mental disorder, characterized by psychosis and impaired cognition. The underlying pathology has long been the subject of investigations to identify the brain abnormality. Several studies were conducted before it was finally concluded that disturbance in the ratio of brain’s gray and white matter in different areas is the culprit. Wexler et al (2009) conducted a study to analyze the deviation in cognition from normal levels. The deviation from normal in schizophrenics was found to be more than one standard deviation. These patients were called neuropsychological impaired (NPI). 20 to 25 % of schizophrenics were however found to have levels of cognition close to normal, this group of patients was named as neuropsychological near normal (NPNN) . This difference in levels of cognition in various patients led to more research into other underlying pathologic pathways responsible for severe cognitive impairment in NPI patients but was apparently working fine in patients on NPNN category. Brain morphometry was used to analyze differences. Both groups were tested against each other on the basis of four tests to asses the attention and working memory (verbal and nonverbal) and were confirmed by California verbal learning test and degraded stimulus continuous performance test. The standard deviation within 0.5 was the cut off for near normal cognition whereas 1 standard deviation below normal rendered the patient cognitively impaired. They gray matter was found to be smaller in both the groups along with larger third ventricle. An additional pathology found in NPI was that along with the gray matter, their white matter was also decreased in volume. The lateral ventricle cavity was also enlarged. Whitford et al (2007) further investigated the white matter abnormalities in schizophrenics and also studied whether the degenerative changes are progressive. T1 weighted magnetic resonance images (MRI) of 41 first- episode schizophrenics were compared against those of 47 normal comparable people for baseline volume of white matter using voxel-based morphometry in statistical parametric mapping- 2 (SPM2). The schizophrenics had decreased volume of white matter in frontal and temporal lobes. However there was an increase in white matter at frontoparietal junctions on both sides. The longitudinal changes at follow up after 2 to 3 years were compared using tensor based morphometry which showed decreased white matter bilaterally in middle and inferior temporal cortices of schizophrenics. The neural connection abnormalities were attributed to this progressive loss of white matter. The structural brain abnormalities at the time of first psychotic episode were studied by Fannon et al (2000) whose research involved 37 patients going through their first episode of psychosis. T1 weighted steady brain scans of 1.5 mm contiguous sections were obtained and volumetric brain measurements were taken. The patients were found to have structural deviations and there was generalized reduction in brain volume, along with enlarged third and lateral ventricles. Cortical and temporal gray matter was found to be decreased. Schizophrenia is a chronic progressive mental disorder. It is associated with cognitive impairment and worsening interpersonal skills. The attacks are accompanied by hallucinations and delusions. Person feels that he is hearing different sorts of voices and has false beliefs and perceptions. There is extreme emotional instability and the patient may suffer from depression or social isolation. Cognitive decline involves memory impairment, decreased ability to pay attention and difficulty in functional execution of activities. The abnormalities are attributed to abnormal distribution and ratios of gray and white matter in the brain. Apart from that, increase in size of ventricular cavities as well as generalized reduction in brain volume also adds to affect the typical schizophrenic picture. The result is alterations in various brain functions owing to gray matter misdistribution and disturbance in neural connections due to white matter abnormalities. Since it is the white matter forms the neural pathways in the brain, any lesions in white matter or changes in its volume and distribution in different areas of brain can impair the neural circuits and cause abnormalities in communication and cognition. Early investigations in the brains of schizophrenics to look for the abnormalities was undertaken by Fanon et al who studied neuropsychological function in the schizophrenics going through the first attack of psychosis. These patients had deficits in various areas like verbal learning, execution of a task, delayed recall and speed. The patients were found to have reduced number of synaptic connections, smaller neuron size with increased neuron density and a generalized decrease in gray matter. The gray matter deficits were dispersed throughout the brain and not localized. Thus the episodes of psychosis were attributed to more complex interactions between neural connections and regional brain abnormalities. The cognitive defects affect almost all parts of the brain, especially attention and verbal memory and cause alterations in information in memory. The result of these defects is manifested as decrease in performance. Schizophrenia is a disease that affects various pathways and thus may affect different individuals in different ways and to variable degrees in severity. Many patients were found to have significantly less gray matter and large lateral ventricle cavity, and yet have near normal cognition. On the other hand, the patients with impaired cognition had major abnormalities in white matter. Thus it is the loss of white matter that causes cognitive impairment in schizophrenics. The cortical-cerebellar-thalamic-cortical circuit is traversed by the band of white matter and deficits in this circuit impair the neurocognitive response. The changes in volume of white matter over the years and progression of psychotic symptoms are correlated. The progression of the disease is associated with a significant decrease in white matter in the frontal lobe. Progressive decline in mental health in schizophrenics is attributed to these dying neuronal circuits and abnormal axonal myelination causing dysfunctional neuronal communication. There has been extensive research in the pathophysiology of schizophrenia and attempts are being made to pinpoint the deficits in exact loci in the brain so as to affect the progression of disease by target specific treatment therapy. Further research is needed to correlate the level of cognitive impairment and specific deficits in gray and white matter and follow up with neuropsychological tests to identify the underlying pathology (Wexler et al 2009). It is important to identify the disease early in its course and diagnose the underlying abnormality during the initial episodes so as to guide the management according to the site of origin of disturbance and put the patient on appropriate therapy. This also saves the patient from long term usage of neuroleptic drugs (Whitford et al 2007). There is a need of further research for the development of instruments to adequately measure the psychosocial function and to standardize the cut off scores. Psychosocial function can be assessed using surveys and focus groups. The behavior patterns can then be compared to the standard normal population. There should be longitudinal and prospective studies, along with clinical trials and follow up record to keep a track of recovery and the improvement in the condition of patients, and further aid the data for future research. Since schizophrenia is a disorder that involves multiple neural pathways, its presentations are varied and so it should be taken into research as a heterogeneous group of disorders rather than a single unit. Thus interventions at treatment, recovery and rehabilitation should focus all aspects of the disease, including personality disorder, impaired cognition and failing memory, and social as well as personal turmoil that the patient goes through during the course of psychosis (Liberman 2000) References: 1. Fannon, D., Chitnis, X., Doku, V., Tennakoon, L., O'Ceallaigh, S., Soni, W., Sumich, A., ... Sharma, T. (January 01, 2000). Features of structural brain abnormality detected in first-episode psychosis. The American Journal of Psychiatry, 157, 11, 1829-34. 2. Liberman, R. P. (November 01, 2002). Future directions for research studies and clinical work on recovery from schizophrenia: questions with some answers. International Review of Psychiatry, 14, 4, 337-342. 3. Wexler, B. E., Zhu, H., Bell, M. D., Nicholls, S. S., Fulbright, R. K., Gore, J. C., Colibazzi, T., ... Peterson, B. S. (January 01, 2009). Neuropsychological Near Normality and Brain Structure Abnormality in Schizophrenia. The American Journal of Psychiatry, 166, 2, 189. 4. Whitford, T. J., Grieve, S. M., Farrow, T. F. D., Gomes, L., Brennan, J., Harris, A. W. F., Gordon, E., ... Williams, L. M. (January 01, 2007). Volumetric White Matter Abnormalities in First-Episode Schizophrenia: A Longitudinal, Tensor-Based Morphometry Study. The American Journal of Psychiatry, 164, 7, 1082. Read More