Characteristics and Treatment of Schizophrenia - Essay Example

Targeting the glutamatergic system for the improved treatment of schizophrenia Eugen Bleuler first coined the term "Schizophrenia" in the year 1908,in order to describe a type of mental disorder where the patient shows abnormal behavior in recognizing the reality. The union to two Greek words - Schizein and 'phren', formed the word. Here Schein means 'to split' and 'phren' means 'mind'. Characteristics of schizophrenia Patients with schizophrenia are know to show the following clinical signs - Hallucination - It is a condition when a person starts feeling some events (which are actually not present in reality) happening in his surroundings. The descriptions are usually vivid. These feelings happen in his conscious sense and without the effect of any drug. Delusions - it is a condition when a person repeatedly uses a self-made belief (which is actually a false one) in his daily life. Disorganization of speech - It is a condition when person shows inconsistency in his speech. Usually this develops due to thinking disorder. Affected person can speak very fast or can frequently change topics in between sentences or can say sentences with words but no meaning (word salad). Catatonic behavior - the condition shows abnormality in one's motor skill. It may be of hyperactive type or may show lesser or no activity. Avolition - the condition shows lack of interest in the affected person to approach to a definite aim in life or in daily activities. Anhedonia - it reflects the constant depression of mood. Here the affected person never gets a good mood to accept any interaction with any external stimuli. Alogia - this condition reflects lack of interest to state a descriptive answer to any question. Usually affected person uses few words or monosyllable in answering any question. Blunted affect - In this condition the affected person does not react in any emotional stimuli. These symptoms are known to appear singly in early stages of schizophrenia and in due course many symptoms develop. The last four symptoms are known as negative symptoms. Causes of schizophrenia Genetic reasons, prenatal exposure to infections, social life style and some times use of drugs can develop schizophrenia. Two types of genetic disorders can be assigned with schizophrenia. One is deletion or duplication of copy number variant (i.e. very small DNA sequences) from genes responsible for the development of brain and neural signaling (Walsh et al. 2008). The other is some complex interaction of some unspecific genes through linkage i.e. when some genes co-occur then only their expressions develop the disorder (Owen et al. 2005). Prenatal Early developments in neurological stages are considered to be most critical for the development of the disorder. Prenatal exposure to infection can be a major cause. Studies also have suggested that the pathology of development within uterus and development of the conditions are linked together (Brown, 2006). Social Socio-economic conditions can also become causes for schizophrenia. Generally these are racial discrimination, poverty, unemployment, poor living, experience of trauma in juvenile condition, relationship disorder in parents, etc (Mueser et al. 2004), (Selten et al. 2007). Drugs A huge number of Schizophrenics or similar type of patients remains under medication for a prolonged period. So, it is hard to analyze if use of drug causes schizophrenia or the use of drugs develops due to the disorder. A meta-analysis estimated that increase in the dose of cannabis could develop behavioral disorders like schizophrenia (Moore et al. 2007). Mechanism of schizophrenia Patho-physiological mechanism Many psychological researches have been conducted to determine the development of schizophrenia. Many psychological researches have been conducted to determine the development of schizophrenia. Schizophrenic conditions shows reduced thalamic neural number and volume of cortical gray matter. Reduction in cortical volume followed by early gestational irradiation is secondary to reduced thalamic neuronal number and consider as a model for understanding the pathology of schizophrenia. Neuro-chemistry of Schizophrenia 'PET' (Positron emission tomography) and 'f-MRI' (Functional magnetic resonance imaging) have revealed the differences between the brain of a normal person and a schizophrenic patient. These differences appeared in the frontal lobe, temporal lobe and hippocampus (a part of forebrain) of brain. Treatment of schizophrenia Schizophrenic patients are treated with courses of medicine, psychotherapy, social intervention (educating the family members) or by theSoteria model of therapy (Mosher, 1999). Animal model There are different animal models (monkey, rodent, mouse, rat) that have been used for discovery of different drugs or to determine the development of the abnormal condition. Pharmacological models are used for the first case; lesion model and neonat models are used for the later. Animals are not the appropriate substitute for humans. But they are used to work on any particular scheme. We would concentrate on pharmacologic model due to our context. This model is based on effect of alteration in neurotransmitter systems. These models are based on treatment of experimental animals with certain drugs that can induce symptoms of schizophrenia in man. Neurotransmitter It is a well known fact that nerve cells or neurons play an important role in coordination within organs, events or with environment. This coordination is mediated by neurotransmitters. These are chemical substances used to transfer signals from neuron to neuron. They actually relay the nerve signals, also can amplify them. There are different types of neurotransmitter present in living animals. The major groups are acetylcholine, monoamine, purine, amino acid etc. There are four major neurotransmitter system associated with schizophrenia. These are serotoninergic system, -aminobutyric acid (GABA) system, glutamatergic systems and dopamine system. Serotoninergic system Indoleamine and phenethylamine type of drugs develops symptoms of schizophrenia by affecting the serotoninergic (5-HT) system or through 5-HT receptors. In schizophrenic condition PFC disappears from 5-HT, receptors increase and a neuroendocrine response (blunted) occurs to it. But the evidences for the primary abnormalities in schizophrenia are little. This data were mainly obtained from rat model (Marcotte et al. 2008, p.398). -aminobutyric acid (GABA) system The neurons that are present in the middle layer of pre frontal cortex of brain receive a direct synaptic input and put an inhibitory control over excitatory output of layer III pyramidal neurons. It thus develops schizophrenic symptoms in adolescence stage. In animal models, if the animal is injected with -aminobutyric acid into medial PFC then the GABA receptor antagonist picrotoxin reduces PPI (PPI is a test of preattentional sensory-motor gating, which is impaired in schizophrenia) in rats (Marcotte et al. 2008, p.398). Glutamatergic systems Glutamate is an amino acid, which acts as an exicitatory neurotransmitter. It is present in central nervous system. This glutamatergic system is very important for formation of memory and processing of information. It has been clinically proved that some drugs like phencyclidine and ketamine reduce the glutamate function, which lead to schizophrenic symptoms (positive and negative). The complexity of the structure of glutamate receptor is a drawback for researchers. Most worked glutamate receptors are N-methyl-D-aspartate (NMDA) receptor, alpha-amino-3-hydroxy-5-methyl-4-isoxazopropionic (AMPA) receptor and Metabotropic glutatmate receptors. Dopamine system Absence of proper functioning in Dopamine (DA) neurotransmission is a prominent cause of schizophrenia. Hyperactivity of mesolimbic dopaminergic neurone produces symptoms like psychosis. It also can develop negative symptoms by the hypodopaminergic activity of mesocortical DA neurons (Marcotte et al. 2008, p.398). Evidences in Glutamatergic system 1. It is proved that in mice model if the glutamatergic neurotransmission is suppressed then a huge change in behavioural is produced. It suggests that less activity in the corticostriatal glutamatergic/aspartergic pathway may be an important patho-physiological cause in schizophrenia. So, glutamatergic agonists may be beneficial in the treatment of this disease (Carlsson et al. 1990). 2. Both preclinical and clinical studies have indicated that dysfunction ofglutamatergic neurotransmission can play an important role inthe development of negative symptoms and cognitive impairments associated with schizophrenia (Goff et al. 2001). 3. Investigation in postmortem brain samples from schizophrenics has proved that overabundant glutamatergic innervations are found in orbital frontal cortex in schizophrenia. The investigation also proved that schizophrenia has a tendency to involve left-sided abnormalities in the relationship between temporal glutamatergic and dopaminergic projections to amygdala (Deakin et al. 1989). 4. In a study the NMDA receptor-ion channel complex was marked with [3H]MK-801 binding in postmortem brain samples from the frontal cortex, putamen, hippocampus and amygdala of schizophrenic patients and controls. The study revealed that in schizophrenia [3H]MK-801 binding levels were increased in all regions of brain under investigation. It shows a direct relationship between glutamatergic system and the disorder (Kornhuber et al. 1989). 5. Experiments on mice have shown an alteration in the development of PFC circuitry in neonatal's ventral hippocampus. It produces behavioral and cellular changes similar to schizophrenia. This neonatal hippocampal disconnection model represents the importance of Glutamatergic systems (Lipska, 2003), (Marcotte et al. 2008, p.398 - 399). 6. In human model it is observed that the direct and chronic perturbation of NRG1/erbB4 signaling lead to the hypofunction of glutamatergic synapse. It also causes abnormal development in circuitry. Supporting this view, a decrease in markers for excitatory synapses has been reported in the brain of schizophrenia patients(Li et al. 2007). 7. Some highly modified glutamate receptors (like mGluR2 and mGluR5) have been discovered. Highly selective positive allosteric modulators (PAMs) of mGluR2 and mGluR5 has also been discovered.. These mGlu receptor-selective PAMs have properties that can show robust effects in animal models confirming the relation between Glutamatergic system and schizophrenia (Conn et al. 2009). All the above mentioned studies showed that previously dopamine system was considered to be effective in schizophrenia. But this concept has been substituted by emerging hypothesis of activities of Glutamatergic system. Though all researcher have not been able to properly establish the exact role of Glutamatergic system. The relation of Glutamatergic system in schizophrenia is well established. References: Brown, A.S. (2006). 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