Schizophrenia is a common illness. “Schizo”, Latin for “split” and “phrenic”, “mind” describes the split from reality experienced by the schizophrenic mind. The personality loses it unity and wholeness as a result of unorganized, incoherent thinking, shifting emotional moods and strange perceptions. It has approximately 1-% population prevalence in all cultures. Schizophrenia was once thought to be an artifact of Western civilization, but it is now known that this is not the case. It is likely a neurodevelopment brain disorder with both genetic and non-genetic causes, that best fits within the disease perspective.
As well as being common, schizophrenia is a serious, chronic, often disabling illness. It can begin at any age, but most commonly does so in adolescence or early adult life. With such unorganized and incoherent thoughts, disorganized schizophrenics have difficulty communicating and are confused. They often withdraw and regress to silly, childlike behavior. Schizophrenia starts early and is not fatal, but it is an enormous health care burden. Schizophrenic patients who were unresponsive to treatments ended up living out their lives in state hospitals, which are looked back upon as seen warehouses.
After schizophrenic patients go through the de-institutionalization they are likely to be found as street people or found in jails. Patients with schizophrenia often neglect their medical problems. Schizophrenia is currently defined clinically, on the basis both of cross-sectional symptoms and symptoms that occur over a long period of time. There is no reliable lab test for it, and no definitive post-mortem diagnosis. Their overall death rate is double expected. Frequently, when schizophrenic patients take their prescribed medication they take other medication that either compound or negate their prescribed medication effects.
There is currently no cure for the disorder, although medicines often help, especially with positive symptoms. Some positive symptoms include Form or disorganization of ideas and speech so that the listener cannot understand, or incoherence, Content, or bizarre and delusional ideas like the Government is tapping into my head and reading my thoughts. A lack of insight on their own problems of voices and delusions is another positive symptom of schizophrenia. Cognitive deficits in schizophrenia are especially marked for conceptual tasks and those requiring shifts of attention or cognitive set.
Schizophrenics do especially badly on abstract reasoning and problem-solving tests, and also do badly on tests of verbal memory and visual vigilance and attention. These cognitive deficits are also seen commonly in first degree relatives of patients with schizophrenia who themselves do not have schizophrenia, and may be a trait marker for the illness. Cognitive deficits are closely linked to negative symptoms of schizophrenia. Negative symptoms include avolition or self-neglect and apathy, alogia which is the poverty of speech and anhedonia defined as a lack of pleasure.
Their cognitive deficits are especially marked in certain areas of cognition. It used to be believed that schizophrenic cognitive problems were an artifact of patients being distracted during testing, or part of a generalized deficit due to reduced motivation and/or sedation by medications used to treat the illness. Carefully controlled studies have shown that these explanations are insufficient to explain the cognitive problems. The effectiveness of cognitive behavior therapy in schizophrenia has showed promise.
This is being demonstrated in an increasing number of studies, where patient s treated appear to show reductions in symptoms over and above control groups, or people receiving supportive care or routine treatment. One of the larger studies to date with 60 participants to evaluate a cognitive behavioral therapy program which was intended to reduce the distress and interference arising from the experience of psychotic symptoms. Also, to reduce the emotional disturbance and modify dysfunctional schemas, and encourage the patients to help regulate their own risk of relapse and social disability.
The program involved improvement of talking about coping strategies and developing new ones (e. g. activity scheduling, relaxation and skills training and encouraging clients to go shopping or socializing). Also, developing a shared model in collaboration with the client, discussing the nature of the symptoms and nature of their own illness. Modifying delusional beliefs and beliefs about hallucinations, by using gentle challenge and the possibility of alternative explanations, has showed tremendous promise for the cognitive-behavioral approach.
Links between clients experience of voices and events earlier in their lives were explored. Beliefs held with less conviction were explored first, before tackling those held with greater conviction. Modifying dysfunctional schemas, and re-examining evidence for clients dysfunctional beliefs about himself or herself. Another program which seems to work is having schizophrenics work on their management of social disability and relapse – discussing relapse signatures, issues of stigma and the kinds of events that triggered psychotic symptoms and how they might be avoided.
The authors conclude talking to patients about psychotic symptoms and their meaning to the individual is a skill that clinicians working in this area should develop. (Kinderman & Bentall, 1996) Kinderman and Bentall studies showed that perhaps delusions of persecution arise as a result of trying to maintain a positive self-image. Delusions may arise from the discrepancy between how individuals perceive themselves and how they would like to be perceived. Persecutory delusions are a kind of external causal attribution, which is evoked for negative events.
Thus, believing negative events are someone or something elses fault can have a positive function for the individual. Other reports on schizophrenia have suggested that paranoia is a form of camouflaged depression. When people with persecutory delusions are compared to normals or depressed people they do indeed show a strong tendency to attribute negative events to external causes. They tend to personalize – they blame other people when things go wrong. (Garety & Freeman, 1999) Schizophrenia is a uniquely human condition and a realistic model of schizophrenia is necessarily a complex one.
It has to consider neurodevelopmental and psychodevelopmental processes and also social learning. The neurobiology of schizophrenia, as it emerges from recent studies, accords well with the cognitive-neuropsychological dysfunctions that have been discussed. There seem to be two main neurobiological ‘dimensions’ of functional impairment and compensatory control. The first addresses deficits in cortical/subcortical cognitive processes; the second addresses impairments in the balance of lateralized functions (Levin, Yurgelun-Todd and Craft, 1989).
Prefrontal cortex and hippocampus, but also subcortical nuclei, are the brain structures that are now considered involved in schizophrenia. The prefrontal cortex elicits responses guided by internalized knowledge. This includes concepts and plans (cognitive schemata), held in representational memory. The hippocampus is primarily known for its role in memory maintenance and retrieval, but it seems essential for providing the brain with its ‘sense’ of context as well. This structure is needed to temporarily bind together distributed sites in the neocortex that together represent the correct contextual framework.
In accordance with the cooperative relationship between prefrontal cortex and hippocampus, as well as with their functional role in schizophrenic cognitive dysfunction, Corrigan and Green found a strong and selective correlation between prefrontal physiological activation and (reduced) hippocampal volume in schizophrenic subjects. Patterson (1987) has suggested that the thalamus may be involved in the re-creation of prior experience in parallel with current stimulus input in order to achieve an understanding of the current context.
The thalamic nuclei are supposed to be set in motion by frontal cortex and in turn to activate specific patterns of cortical columns, which represent perceptual schemata. Similarly, corticostriatal loops are supposed to be involved in the production of integrated output. Hemisphere imbalance, in the sense of a relative dysfunction of the (parallel, holistic) right hemisphere, and a compensatory overactivation of the (analytic, sequential) left hemisphere, is probably a reflection of the basic impairments and secondary adaptive strategies.
This imbalance corresponds with the cognitive fragmentation versus cognitive control mechanisms described. Researchers have come up with a few hypotheses on what makes a person Schizophrenic. The hypotheses include the Dopamine Hypothesis, the NMDA Receptor Hypothesis, the Single-Carbon Hypothesis, and the Membrane Hypothesis. The Dopamine Hypothesis is the notion that dopamine may be involved in schizophrenia derives from the therapeutic usefulness of drugs that block certain dopamine receptors in treating the disorder.
Because dopamine blockers are so often effective, it has been proposed that an over activity of dopamine neurotransmission in cortical and limbic areas of the brain may cause schizophrenia. Drugs with selectivity for the D4 dopamine receptor (such as clozapine or olanzapine) can be particularly effective, and so this receptor subtype may play a critical role; in fact, elevated levels of D4 receptor binding have been found post-autopsy in the brains of persons who had schizophrenia. Dopamine is further shown by the fact that a schizophrenia-like psychosis can be induced by abusing amphetamines, which act on dopamine pathways.
The NMDA Receptor Hypothesis is another hypothesis researchers have come up with about what causes schizophrenia. NMDA receptors respond to the excitatory neurotransmitter glutamate as known to and are important for normal memory and cognition. Because drugs affecting NMDA receptors (such as ketamine or phencyclidine (PCP)) can cause schizophrenia-like hallucinations and because neuroleptic drugs, including clozapine, can inhibit their occurrence, it has been suggested that NMDA receptor dysfunction may cause schizophrenia.
Recent studies have shown therapeutic benefit from drugs acting on NMDA receptors, such as glycine and D-cycloserine. The Single-Carbon Hypothesis is a possible suggestion for schizophrenia but conclusions so far have been misleading. Researchers have often linked disturbances of the single-carbon folate pathway to schizophrenia. This metabolic pathway provides carbon groups for a variety of biochemical reactions in the brain, including the synthesis of purine and pyrimidine nucleotides and the methyl-donating amino acid methionine.
A number of studies have shown that methionine metabolism is impaired in most schizophrenic persons, and other work has demonstrated enzyme deficits in the folate pathway in some schizophrenic persons. These observations are clear, but their relationship to neuronal transmission has remained elusive. The Membrane Hypothesis suggests people may suffer from Schizophrenia because there is a problem when transmitting signals to the cell membrane. Nerves are largely composed of phospholipid membranes, and phospholipid metabolism is critical to normal brain function.
Neurotransmitter receptors, such as dopamine and NMDA receptors function within the membranes of nerve cells. So, disturbances of the membrane structure could readily affect how neurons transmit messages across nerve synapses. Studies have demonstrated that a deficit in the level of highly unsaturated fatty acids is associated with schizophrenia, as is decreased activity of the enzyme phospholipase A2, which breaks down membrane phospholipids. These observations suggest that impairment in the transmission of signals across cell membranes may be responsible for schizophrenia.
Recently researchers have discovered a signaling pathway that combines elements of all four of these theories. The research found that dopamine can stimulate the methylation of membrane phospholipids via the activation of the D4 dopamine receptor. Furthermore, we found that the D4 receptor is complexed to NMDA receptors, suggesting that the methylation of phospholipids could regulate NMDA receptor activity. Only in man and primates does the D4 receptor possesses a repeat structural feature, facilitating its complexation with synaptic NMDA receptors.
This finding suggests that schizophrenia may result from impairment in the ability of D4 dopamine receptors to modulate NMDA receptors at nerve synapses via phospholipid methylation. This modulation may be important for the normal attention and cognitive abilities of man. Certainly more research is necessary to follow-up on the clues provided by these results. There is reason to hope, though, that new findings will not only make the cause of schizophrenia clearer, but will also lead to more effective treatments.