Schizophrenia positive symptoms

Neuroleptics or antipsychotics suppress the positive symptoms of schizophrenia such as combativeness, hallucinations and formal thought disorder. Some also alleviate the negative symptoms such as affective blunting, withdrawal and seclusiveness. Neuroleptics also produce a state of apathy and emotional indifference. Most neuroleptics block dopamine D2-receptors but some, like clozapine, also block dopamine D4-receptors or serotonin 5-hydroxytryptamine2A-receptors. 

Initiation of behaviour Mesolimbic pathway to nucleus accumbens from VTA (AIO) Mesocortical pathways to prefrontal cortex from VTA (AIO) Animals Increases locomotor activity and intracranial self-stimulation Humans Hallucinations, psychoses (reward, reinforcement) Animals Decreases activity and self-stimulation Humans Reduces positive symptoms of schizophrenia D2 ... 

On this evidence one can confidently equate EPS with neuroleptic DA receptor (D2) antagonism in the striatum and possibly a reduction in the positive symptoms of schizophrenia through similar action in the limbic system (nucleus accumbens). 

It appears that an ideal neuroleptic may need to reduce DA activity in the mesolimbic system (nucleus accumbens) to counter the positive symptoms of schizophrenia, increase it in the prefrontal cortex to overcome negative symptoms and have little or possibly no effect on it in the striatum so EPSs do not arise (Fig. 17.9). No wonder we still await the ideal drug. 

For approximately 20% to 30% of people with schizophrenia, drug treatment is ineffective. A standard definition of treatment resistance includes patients who have persistent positive symptoms despite treatment with at least two different antipsychotics given at adequate doses (at least 600 chlorpro-mazine equivalents) for an adequate duration (4 to 6 weeks). In addition, patients must have a moderately severe illness as defined by rating instruments, and have a persistence of illness for at least 5 years.40 These patients are often highly symptomatic and require extensive periods of hospital care. 

Schizophrenia is characterized by three partially independent symptom clusters. These symptom clusters are designated positive symptoms, negative symptoms and cognitive impairments [1], The positive symptoms are the most dramatic and are manifestations of psychosis. 

The positive symptoms are the most responsive to antipsychotic medications, such as chlorpromazine or halo-peridol. Initially, these drugs were thought to be specific for schizophrenia. However, psychosis is not unique to schizophrenia, and frequently occurs in bipolar disorder and in severe major depressive disorder in which paranoid delusions and auditory hallucinations are not uncommon (see Ch. 55). Furthermore, in spite of early hopes based on the efficacy of antipsychotic drugs in treating the positive symptoms, few patients are restored to their previous level of function with the typical antipsychotic medications [2]. 

The typical antipsychotic drugs, which for 50 years have been the mainstay of treatment of schizophrenia, as well as of psychosis that occurs secondary to bipolar disorder and major depressive disorder, affect primarily the positive symptoms[10]. The behavioral symptoms, such as agitation or profound withdrawal, that accompany psychosis, respond to the antipsychotic drugs within a period of hours to days after the initiation of treatment. The cognitive aspects of psychosis, such as the delusions and hallucinations, however, tend to resolve more slowly. In fact, for many patients the hallucinations and delusions may persist but lose their emotional salience and intrusiveness. The positive symptoms tend to wax and wane over time, are exacerbated by stress, and generally become less prominent as the patient becomes older. 

One of the most prominent positive symptoms in schizophrenia is the auditory hallucinations that are perceived as distinct voices emanating from outside the individual. Regional cerebral-blood-flow studies in patients experiencing auditory hallucinations reveal activation of the associational auditory cortex during the episodes of hallucinations, but not in their absence. One theory holds that auditory hallucinations occur as a consequence of the inability of individuals with schizophrenia to monitor effectively their inner speech. fMRI studies suggest that... 

Controlled clinical investigations with careful titration of doses in normal subjects demonstrate that ketamine produces negative symptoms, such as withdrawal and the subtle cognitive impairments associated with schizophrenia [25]. As is the case for schizophrenia, these symptoms occur without clouding of consciousness or frank dementia. Positive symptoms with auditory hallucinations and fully... 

Despite their importance in psychiatry, the neuroleptics are by no means cure-alls. Even patients that respond extremely well to neuroleptics remain disturbed. Specifically, though their florid hallucinations and delusions, the positive symptoms of schizophrenia, are alleviated, patients remain emotionally detached from the environment. This wallflower syndrome and related symptoms are commonly designated the negative symptoms of schizophrenia and often are the most disabling ones. The first glimmer of effective treatment of such negative symptoms came with the drug clozapine. 

The term psychotomimetic was coined to compare the effects of hallucinogens to the symptoms of schizophrenia and other psychotic conditions. However, the effects produced by hallucinogens and mental illness are qualitatively different. While drug-induced hallucinations tend to be more visual, auditory hallucinations are most common in schizophrenia. The hallucinogenic drugs discussed here may induce positive symptoms (e.g., hallucinations), but do not induce the negative symptoms (e.g., cognitive deficits, social withdrawal) of schizophrenia. 

There are two general classes of clinical characteristics of schizophrenia. First, there are the positive symptoms that include auditory hallucinations (voices) and delusions, often paranoid. Second, there are the negative symptoms these include disorganization, loss of will, inability to pay attention, social withdrawal, and flattening of affect. The relative roles of positive and negative symptoms for a particular victim vary over time. The positive symptoms may predominate for a period to be followed by one in which the negative symptoms are more prominent. About 10% of people with schizophrenia commit suicide. 

The characteristic symptoms of schizophrenia have historically been conceptually divided into positive and negative symptoms. At least two of these symptoms must be present for a month during the so-called active phase of illness. One can conceptualize the positive symptoms as the presence of abnormal beliefs or behaviors, whereas, in contrast, negative symptoms are a deficit or absence of normal behaviors. 

Negative Symptoms. Although the odd nature of positive symptoms draws the most attention, the negative symptoms are perhaps the most disabling. These hinder a schizophrenia patient s desire and ability to maintain relationships or hold employment. The negative symptoms include poor motivation (avolition), a bland expressionless face (flattened affect), minimal speech (alogia), and social withdrawal. 

Leading up to the first break, most individuals with schizophrenia go through a prodromal phase of illness. This prodrome is a departure from the patient s usual behavior, but patients seldom seek treatment during this phase. The prodromal symptoms are usually limited to negative symptoms of apathy or social isolation or to lesser variants of the positive symptoms taking the form of eccentric beliefs or a... 

Chlorpromazine (Thorazine). The first of the modem antipsychotics was developed in the early 1950s, not as an antipsychotic but as an antihistamine that could be used during surgery to minimize the amount of anesthesia needed. It was hoped that this would lessen the danger of shock (dangerously low blood pressure) during surgery. It was actually quite successful, but it was soon found to have other benefits. Of key importance, it could relieve the positive symptoms of schizophrenia. In the years to follow, this led to the production of other similar antipsychotics collectively known as the typical antipsychotics. 

In admittedly oversimplified terms, it is believed that hyperactivity of dopamine neurons in the mesolimbic pathway contribute to the positive symptoms of schizophrenia. All the typical antipsychotics are believed to work by reducing the activity of the mesolimbic dopamine pathway. More specifically, they do this by blocking dopamine receptors on the nerve cells. Over a period of 1-3 weeks, the dopamineblocking effect of the typical antipsychotic begins to relieve the positive symptoms of schizophrenia. 

The second revolution began in the past 10 years with the arrival of the atypical antipsychotics. Although the atypicals are no panacea for schizophrenia, they represent an advance in at least three areas. First, they lessen the burden of antipsychotic side effects and therefore frequently increase adherence dramatically. Second, the atypicals may treat all of the schizophrenia symptom clusters (positive, negative, mood, cognitive), whereas the typical antipsychotics chiefly treat the positive symptoms. Third, atypical antipsychotics sometimes benefit patients whose schizophrenia is unresponsive to typical antipsychotics. 

The goals of treatment during the acute phase of illness are to reduce the positive symptoms of schizophrenia and to plan for extended treatment during the maintenance phase. Reducing the positive symptoms quickly is important for at least two reasons. First, the erratic behavior of an acutely psychotic patient can take a tremendous toll, risking arrest, loss of job, suicide, and the alienation of friends and family. Second, there is some evidence that psychosis itself is harmful to the brain. In other words, it may be that the longer the patient is actively psychotic, the worse the prognosis becomes. 

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