Brain Abnormalities and Schizophrenia

The real etiology of schizophrenia is still a dream despite massive studies on the involvement of the brain. Studies of the brain through neuroimaging have revealed that frontal cortex, temporal lobe, and sub cortical structures are involved. Some of abnormalities in the brain of schizophrenic patients include enlarged ventricles, reduced volume of frontal cortex, temporal lobe cortex, and sub cortical structures like hippocampus and amygdala. These abnormalities have been persistently reported in schizophrenic patients and this shows that they are not functioning inadequately. Some of these abnormalities are present at the start and some even before the onset of psychosis and this is in support of neurodevelopment of theory of schizophrenia. The key neurotransmitter in schizophrenia is dopamine however, there are others such as serotonin and glutamate which are also thought to play a role. Schizophrenia is an inherited condition, although genetic research has not come up with a clear conclusion on this matter may be because of the complexity of genetic involvement. Despite the fact that brain abnormalities are still not very clear in schizophrenia, the evidence is continuously pilling and this is driving towards a complicated disease of the brain network that is affected by genetically mediated developmental abnormality.

Introduction
Neuropathologists have been involved in research on schizophrenia for about hundred years. Despite the length of the research, the neuropathogy of the disorder is still not clear. Although they have made some steps in their quest since the beginning when they believed that it was a functional psychosis without structural basis, the main cause of the chronic disorder is still illusive. With the technological advancement in science, researchers have come to a common finding in patients diagnosed with schizophrenia and the common finding is brain abnormalities. These discoveries have made the researchers to wonder if the cause of schizophrenia is brain abnormalities and how the abnormalities arise.

Despite recovery of some brain abnormalities in patients suffering from schizophrenia, most scientists maintained that some of the abnormalities realized are quite slight and some of them are not common in all schizophrenic patients and to occur exclusively in people with schizophrenia. Although these patients have structural pathologies in their brains, the developed abnormalities do not coincide with the disease duration. Some of the abnormalities realized remain the same throughout the development of the disease (Bhogal, 2002).

Understanding of the abnormalities of the brain in schizophrenia is among the challenges currently facing the medical community. The numerous symptoms associated with schizophrenia points at the involvement of various regions of the brain or even a widespread of network or system. Conventional approaches of neurological disorders such as lesion studies or post mortem examinations have defied efforts to understand the brain pathology in schizophrenia. Just like other fields of medicine, luck and destiny have help make major steps in discoveries like dopamine theory and anti psychotics which are used in the management of the disorder. Modern research in neuroscience such as neuroimaging has aided in improving the foundation knowledge of the disorder and has sustained the hope that complete understanding of the disorder will be realized in the future. In this paper, I am going to summarize the major brain abnormalities found in schizophrenia through neuroimaging (Haren, 2004).

Just like other complicated diseases, there are numerous theories on schizophrenia as compared to facts. The initially neurodevelopment theory points at abnormalities in fetal brain development as the cause of the failure of brain functions in early adulthood. A series of information such as increased rate of obstetric complications, minor physical abnormalities, neurologic mild signs, and slight behavioral abnormalities in children who later suffer from schizophrenia. This model is quite relevant to the development of schizophrenia in particular but also for other neuropsychiatric disorders (Bhogal, 2002). The major drawback of this model is that the prevalence of these signs in the non affected population is quite substantial therefore the positive predictive value in the development of schizophrenia is not convincing. The disease usually begins at adolescent or early childhood and early adulthood and this indicates brain maturational problem during that time or before the appearance of psychosis. Excessive synaptic or dendritic pruning during the time of onset of the disorder has been suggested as one of the potential mechanism explaining the onset of psychosis in adolescent or in early childhood, although the biology underlying this stage is still not very clear (Lawrie  Abukmeil, 1998).

Neurodegenerative model is based on active biologic processes that may be going on during the prodromal period or the usually prolonged period of untreated psychosis. Development of the disorder is also linked to environmental factors such as illicit drug use and psychosocial stress which are considered as potential secondary triggers which may be accompanying the beginning and the start of schizophrenia.

The initial researchers believed that schizophrenia is associated with brain pathology. Emergence of imaging techniques such as magnetic resonance imaging (MRI) and computed tomography scanning (CTS) have seriously contributed to the detailed study of the brain. Through computed tomography brain abnormalities such as enlarged ventricles and reduced total brain volume have been reported in schizophrenic individuals and these findings were later confirmed by magnetic resonance imaging (Bhogal, 2002).

Studies of the brain structures have also been made easy through improvement in segmentation techniques coupled with the use of MRI. These techniques can be used to identify grey from white matter and measuring of their volume. These also contributed to a more focused investigations of specific regions of the brain such as temporal, frontal lobes, and subcortical structures. Some of the consistent findings in these regions include alteration in structures such as hippocampus, amygdala, superior temporal gyrus, and platinum temporale (Lawrie  Abukmeil, 1998). Lateral temporal neocortical areas where primary auditory and auditory associations are located are the places of interest in schizophrenia since they are involved in thought processes. Most of the studies in the superior temporal gyrus in schizophrenic patients have always discovered reduced volumes of grey matter in the initial stages of the disorder together with those individuals who are genetically at risk of developing schizophrenia such as offspring of schizophrenic patients.

Other structures of the brain which have also been reported to be abnormally small in schizophrenic patients include medial temporal structures such as hippocampus, amygdala, and parahippocampus gyri. These structures are also reported to be altered in other psychiatric disorders like mood disorders and post traumatic stress disorder (Lawrie  Abukmeil, 1998). Injuries sustained at the time of birth such as anoxia may be associated to hippocampus reduction and this is possibly due to neurodevelopmental abnormality. The finding is also common among concordant twins who had birth injuries. Medial temporal volume reductions have been discovered in people who are genetically at risk of developing schizophrenia. Reductions in the grey matter in the temporal regions of the brain have also been observed in people who are classified as having prodromal features of schizophrenia who have later on developed psychotic symptoms during the follow up (Haren, 2004).

The highly developed region of the brain in man is the frontal lobe. It is involved in the modulations of higher brain functions such as planning, attention, and working memory. Behavioral and cognitive deficits like lack of motivation, defects in executive functions, Wisconsin card score sorting test and spatial working memory points at frontal lobe functional abnormalities in schizophrenic patients (Lawrie, 1999). Decreased blood flow to the frontal lobe is a common finding in schizophrenia. Despite the fact that this finding is not consisted, it can also be attributed to the complex nature of the region, it has been observed though quite slight.

Basal ganglia which contain caudate, putamen, and globus pallidus are involved in information processing in the cortical and subcortical networks involved in integration of cognition, emotion, and motor function. These structures have been reported to be enlarged in patients using the conventional antipsychotics and this can lead to a conclusion that dopamine blockades causes an increase in volume of the above structures. Psychosis patients who have not used any antipsychotics are reported to have a smaller caudate volume which implies that caudate may be involved in the development of psychoses.

Thalamus acts as the regulatory board for sensory signals and has reciprocal connections to the frontal lobe. It has been suggested that the connections between these two structures are associated with schizophrenia. Thalamus is a bit difficult to measure using MRI, although the findings are inconsistent, smaller thalamus have always been reported in schizophrenic patients. Other anatomic abnormalities in schizophrenia include corpus callosum which is altered both in shape and structure therefore disruption in the integration between the hemispheres. In most humans, brain functions are lateralized with the left cerebrum being dominantly involved in language. There are proposals that developmental abnormalities of language, peculiar functions of the human beings, and its lateralization which is genetically mediated may be one of the causes of schizophrenia (Bhogal, 2002).Temporal lobe findings of smaller superior temporal gyrus and hippocampus have been reported to be in the left cerebrum and loss of normal asymmetry of the left superior temporal gyrus being a bit larger that the right has been reported in patients suffering from schizophrenia (Staal et. al, 2000). In the meta analysis study of laterality in schizophrenia, the researchers who were involved in this study concluded that there is a strong proof for decreased cerebral lateralization in schizophrenia more so in the language cortex. 

We can therefore summarize that structural imaging studies have discovered evidence of extensive anatomic alterations in the brain regions of schizophrenic patients. The regions highly altered in these patients include those mediating higher mental functions like thought, cognition, effect, and language both early in the illness and those at risks of developing the disorder like children born to schizophrenic patients (Haren, 2004).

Synapses and susceptibility genes
Neuroimaging studies are in support of the possibility of neurodevelopmental abnormality in schizophrenia, neuronal, molecular, and neurochemical mechanisms underlying these brain abnormalities are not conclusive. High profile neuropathologic studies have revealed losses in synapse density and relatively normal or elevated neuronal numbers in schizophrenia, which indicates that the main defect may be synapse integrity. This discovery has elicited search for genes that may be associated with synapse integrity by the use of DNA microarray techniques. Post mortem findings on the patients with schizophrenia revealed under expression of a family of synapse related genes (Bhogal, 2002).

Genetic factors are the main factors listed as being associated with schizophrenia, however the exact genes involved in susceptibility is still a puzzle. Although the initial studies on finding these genes was not successful, current studies have implicated several genes in the development of schizophrenia and some of the genes include dysbindin-1, neuregulin-1, d-amino acid oxidase, its activator DAOA, and the regulator of G protein signaling 4. Recent proposals indicated that synapses, especially glutamatergic ones might be the site of initial abnormalities in schizophrenia with downstream disruption of neural circuitry and subsequent effect on other neurotransmitters (Lawrie, 1999).

Conclusions
It has become clear that the early scientists were right in their suspicion that the brain is involved in schizophrenia. This evidence cannot be disputed despite the fact that there is no comprehensive information on the etiology and pathophysiology of the disorder. The brain abnormalities in schizophrenia appear to be distributed in extensive areas supporting the fact that schizophrenia is a disorder associated with brain connections. We are still very far from understanding some of the major neuropsychiatric disorders such as Alzheimers disease. The molecular, physiologic, and neurochemical mechanisms underlying schizophrenia continues to evade our findings. Recent research on the disorder acts as the foundations for future fundamental discoveries on the nature of schizophrenia.

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