Schizophrenia

Drugs that are effective in treating the most disturbing forms of psychotic illness, such as schizophrenia and manic depression, are called antipsychotics. Antipsychotic medication helps the person with the disorder function as well as possible in their life, while at the same time increasing their feelings of subjective well-being. Antispsychotics are usually recommended as the initial treatment for the symptoms of schizophrenia, after which clinicians tend to use a combination of medication and psychological therapy to manage the disorder. All antipsychotics work by reducing dopaminergic transmission, i.e. reducing the action of the neurotransmitter dopamine in areas of the brain associated with the symptoms of schizophrenia.

Typical Antipsychotics - developed in the 1950s. Basic mechanism of these drugs is to reduce the effects of dopamine and so reduce the symptoms of schizophrenia. Typical Antipsychotics are dopamine antagonists in that they bind to but do not stimulate dopamine receptors, thus blocking their action. By reducing stimlutation of the dopamine system in the mesolimbic pathway, antipsychotic drugs such as chlorpromazine eliminate the hallucinations and delusions experienced by people with schizophrenia. Hallucinations and delusions usually diminish within a few days of beginning medication, although other symptoms may take several weeks before a significant improvement is noted. Kapur et al estimate that between 60% and 75% of D2 receptors in the mesolimbic pathway must be blocked for these drugs to be effective. Unfortunately, in order to do this, a similar number of D2 receptors in other areas of the brain must also be blocked, leading to undesirable side effects.

Atypical Antipsychotics - so called because of the three main differences to first generation. They carry a lower risk of extrapyramidal side effects, have a beneficial effect on negative symptoms and cognitive impairment, and are suitable for treatment-resistant patients. As with typical antipsychotics, these drugs also act on the dopamine system by blocking D2 receptors. However, they only temporarily occupy them and then rapidly dissociate to allow normal dopamine transmission. It is this characteristic of atypical antipsychotics that is thought to be responsible for the lower levels of extrapyramidal side effects found with these drugs compared to conventional antipsychotics. Because atypical antipsychotics such as clozapine have very little effect on the dopamine systems that control movement, they tend not to cause the movement problems found with the typical antipsychotics. Rapid dissociation is one feature of atypical antipsychotics that distinguish them from typical antipsychotics, but there are others.

Support for the effectiveness of antipsychotics comes from studies that have compared relapse rates for antipsychotics and placebos. Leucht et al carried out a meta-analysis of 65 studies, published between 1959 and 2011, and involving nearly 6,000 patients. Some of these patients were taken off their antipsychotic medication and given a placebo instead. The remaining patients remained on their regular antipsychotic. Within 12 months, 64% of those patients who had been given the placebo relapsed, compared to 27% of those who stayed on the antipsychotic drug. This study clearly demonstrates the superiority of antipsychotic drugs compared to placebo in preventing relapse, although their use must be weighed against their side effects.

Typical antipsychotics drugs can sometimes produce movement problems for the patient. These are called extrapyramidal effects because antipsychotic drugs appear to impact on the extrapyramidal area of the brain, which helps control motor activity. The most common are the Parkinsonian and related symptoms, so called because they resemble the features of the neurological disorder Parkinson's disease. More than half of the patients taking typical antipsychotics experience these symptoms. When people take antipsychotic drugs for an extended period, a second type of extrapyramidal effect can occur - tardive dyskinesia, i.e. involuntary movements of the tongue, face and jaw. These side effects can be so distressing for the patient that other drugs have to be given to control them, or the patient may stop taking their antipsychotic medication completely.

The problems associated with antipsychotic medication raise significant ethical issues relating to their use. Recently in the US, a large out-of-court settlement was awarded to a tardive dyskinesia sufferer on the basis of Article 3 of the Human Rights Act 1988, which states that 'no one shall be subjected to inhuman or degrading treatment or punishment'. This suggests that if side effects, deaths and psychosocial consequences were taken into account, a cost-benefit analysis of typical antipsychotics would most probably be negative.

Atypical antipsychotics are claimed to have a number of advantages when compared to typical antipsychotics. A key advantage of atypical antipsychotics is that patients experience fewer side effects. Atypical antipsychotics, particularly newly developed drugs, such as olanzapine and quetiapine, are less likely to produce the extrapyramidal effects commonly found with typical antipsychotics. As a result, patients are more likely to continue with their medication, which in turn means they are more likely to see a reduction in their symptoms.

The introduction of atypical antispsychotics led to claims of the superiority of these drugs over the older 'typical antipsychotics. Crossley et al carried out a meta-analysis of 15 studies to examine the efficacy and side effects of atypical versus typical antipsychotics in the early-phase treatment of schizophrenia. They found no significant differences between atypical and typical drugs in terms of their effect on symptoms but did note differences in the type of side effects experienced. Patients on atypical antipsychotics gained more weight than those on typicals, whereas those on typicals experienced more extrapyramidal side effects. They concluded there was no evidence for differences in efficacy between atypical and typical antipsychotics, but there was a clear difference in the side-effect profile.

Ross and Read argue that when people are prescribed antipsychotic medication, it reinforces the view that there is 'something wrong with them'. This prevents the individual from thinking about possible stressors that might be contributing to their condition. In turn this reduces their motivation to look for possible solutions that might alleviate these stressors and reduce their suffering. Read concludes that as human misery is largely inflicted by other people then the best solutions are usually human - rather than chemical or electrical - interventions.

Double Bind Theory - Gregory Bateson et al suggest that children who frequently receive contradictory messages from their parents are more likely to develop schizophrenia. For example, if a mother tells her son that she loves him, yet at the same time turns her head away in disgust, the child receives two conflicting messages about their relationship on different communicative levels, one of affection on the verbal, and one of animosity on the non-verbal level. These interactions prevent the development of an internally coherent construction of reality, and in the long run this manifests itself as schizophrenic symptoms. These ideas were echoed in the work of psychiatrist R.D. Laing, who argued that what we call schizophrenia  is actually a reasonable response to an insane world.

Expressed Emotion - Another family variable associated with schizophrenia is a negative emotional climate or, more generally, a high degree of expressed emotions. Expressed emotion is a family communication style in which members of the family of a psychiatric patient talk about that patient in a critical or hostile manner or in a way that indicates emotional over-involvement or over-concern with the patient or their behaviour. A patient returning to a family with high EE is about four times more likely to relapse than a patient whose family is low in EE. This suggests that people with schizophrenia  have a lower tolerance for intense environmental stimuli, particularly intense emotional comments and interactions with family members. 

The importance of family relationships in schizophrenia was demonstrated in an adoption study by Tienari et al. In this study, adopted children who had schizophrenic biological parents were more likely to become ill themselves than were children with non-schizophrenic biological parents. However, this difference emerged only in situations where the adopted family itself was rated as disturbed. This suggests that the illness only manifests itself under appropriate environmental conditions, therefore genetic vulnerability alone is not sufficient.

There is some evidence to support this particular account of how family relationships lead to schizophrenia. For example, Berger found that schizophrenics reported a higher recall of double bind statements by their mothers than non-schizophrenics. However, other studies are less supportive. Liem measured patterns of parental communication in families with a schizophrenic child and found no difference when compared to normal families. Despite these inconsistencies in research support, Gibney claims that the real value of double bind theory is that it led to the development of family therapy. If interactions could be problematic and pathology producing, then they might also be organised more constructively and so become health producing.

Not all patients who live in high EE families relapse, and not all patients who live in low EE homes avoid relapse. Research has found individual differences in stress response to high EE-like behaviours. Altorfer et al found that one-quarter of the patients they studied showed no physiological responses to stressful comments from their relatives. Vulnerability to the influences of high EE-may also be psychologically based. Lebell et al. claims that how patients appraise the behaviour of their relatives is important. In cases where high EE behaviours are not perceived as being negative or stressful, patients can do well regardless of how the family environment is objectively rated. This shows that not all patients are equally vulnerable to high levels of expressed emotion within the family environment.

Compared to normal controls, research has found evidence of dysfunctional thought processing in people with schizophrenia.

Cognitive explanations of delusions - During the formation of delusions, the patient's interpretations of their experiences are controlled by inadequate information processing. A critical characteristic of delusional thinking is the degree to which the individual perceives him or herself as the central component in events and so jumps to conclusions about external events. This is manifested in the patient's tendency to relate irrelevant events to themselves and consequently arrive at false conclusions. Muffled voices are interpreted as people criticising them, and flashes of light are a signal from God. Delusions in schizophrenia are relatively impervious to reality testing, in that patients are unwilling or unable to consider that they may be wrong.

Cognitive explanations of hallucinations - Hallucinating individuals focus excessive attention on auditory stimuli and so have a higher expectancy for the occurence of a voice than normal individuals. Aleman suggests that hallucination-prone individuals find it difficult to distinguish between imagery and sensory-based perception. For these individuals, the inner representation of an idea can override the actual sensory stimulus and produce an auditory image that is every bit as real as the transmission of actual sound. Hallucinating patients with schizophrenia are significantly more likely to misattribute the source of a self-generated auditory experience to an external source than are non-hallucinating patients with schizophrenia. These errors are not corrected by disconfirming evidence because patients with schizophrenia do not go through the same processes of reality testing that others would do.

Sarin and Wallin found supporting evidence for the claim that the positive symptoms of schizophrenia have their origins in faulty cognition. For example, delusional patients were found to show various biases in their information processing, such as jumping to conclusions and lack of reality testing. Likewise, schizophrenic individuals with hallucinations were found to have impaired self-monitoring and also tended to experience their own thoughts as voices. A consequence of this is that a therapist can use this information when he or she chooses techniques for the treatment of patients.

The claim that the symptoms of schizophrenia have their origin in faulty cognition is reinforced by the success of cognitive-based therapies for schizophrenia. The effectiveness of cognitive behavioural therapy for psychosis was demonstrated in the National Institute for Health and Care Excellence review of treatments for schizophrenia. This review found consistent evidence that, when compared with treatment by antipsychotic medication, cognitive behavioural therapy was more effective in reducing symptom severity and improving levels of social functioning. This supports the view that faulty cognitions have an important causal influence in the development of schizophrenia.

A problem with the cognitive model of schizophrenia is that it deals adequately with one aspect of the disorder but fails to explain, or ignores, other aspects. Howes and Murray addressed this problem with an integrated model of schizophrenia. Early vulnerability factors, together with exposure to significant social stressors, sensitises the dopamine system, causing it to increase the release of dopamine. Biased cognitive processing of this increased dopamine activity results in paranoia and hallucinations and eventually the development of a psychosis. By putting the impact of life events at the centre of the process leading to schizophrenia, this model fits in with more recent research showing that exposure to significant social stressors is associated with a considerable increase in risk of developing this disorder.