Positive symptoms in schizophrenia

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... 

Most often reduces positive symptoms in schizophrenia but does not eliminate them... 

Low doses of sulpiride may be more effective at reducing negative symptoms than positive symptoms in schizophrenia high doses may be equally effective at reducing both symptom dimensions... 

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. 

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. 

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 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. 

Underactivity of dopamine in mesocortical pathways, specifically those projecting to the frontal lobes, may account for the negative symptoms of schizophrenia (e.g., anergia, apathy, lack of spontaneity) (Davis et al. 1991 Goff and Evins 1998). In addition, this underactivity in the frontal lobes may serve to disinhibit mesolimbic dopamine activity via a corticolimbic feedback loop. Overactivity of mesolimbic dopamine is the result, which manifests as the positive symptoms of schizophrenia (e.g., hallucinations, delusions). 

Sellwood, W., Haddock, G., Tarrier, N., Yusupoff, L. Advances in the psychological management of positive symptoms of schizophrenia. Int. Rev. Psvchiatrv 6, 201-215, 1994. 

Negative symptoms in schizophrenia can be either primary or secondary (Fig. 10—3). Primary negative symptoms are considered to be those that are core to primary deficits of schizophrenia itself. Other core deficits of schizophrenia that may manifest themselves as negative symptoms may be those associated with or thought to be secondary to the positive symptoms of psychosis. Other negative symptoms are considered to be secondary to extrapyramidal symptoms (EPS), especially those... 

FIGURE 10—3. Negative symptoms in schizophrenia can either be a primary deficit of the illness (1° deficit) or secondary to depression (2° to dep), secondary to extrapyramidal symptoms (2° to EPS), secondary to environmental deprivation, or even secondary to positive symptoms (2° to pos sxs) in schizophrenia. 

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