Negative psychotic symptoms

The conventional antipsychotics have little effect on the negative psychotic symptoms such as autism, stupor and emotional withdrawal. The so-called atypical antipsychotics, or second-generation antipsychotics, like the heterocyclic compound risperidone, the benzamide sulpiride and several diben-zepines of which clozapine is the best known, have a broader spectrum which means that they also have an effect on the negative psychotic symptoms. Most share a common attribute of working on serotonin receptors as well as dopamine receptors. They have a low risk of extrapyramidal side effects. 

Psychotic Disorders glycine improves negative psychotic symptoms... 

There are data to confirm and reject the association of the Cys23Ser S-HT and the Gly22Ser 5-HTj receptor variants, characterized in vitro by reduced agonist potency, with phenotypes such as intractable suicidal ideation (98), ADHD (100), alcohol dependence, and schizophrenia (98,99,109-116). While the -1348 A/G polymorphism of the S-HT receptor has been associated with the negative symptoms of schizophrenia, other studies of eating disorders appear to be equivocal. A body of evidence is available, however, that S-HT variants may be associated with psychotic symptoms in Alzheimer s patients (94,100,117,118). 

Abnormalities of the glutamate system have also been documented in neuropsychiatric disorders. For example, compounds such as PCP and ketamine, which block the NMDA receptor, can induce psychotic symptoms. By contrast, compounds such as d-cycloserine or glycine, which increase NMDA receptor function via the glycine binding site, can decrease psychotic and/or negative symptoms in schizophrenia (Farber et ah, 1999 Goff et ah, 1999, Fleresco-Levy et ah, 1999). 

Glutamate was initially implicated in schizophrenia by studies of the behavioral effects of N-methyl-D-aspartate (NMDA) receptor antagonists (e.g., PCP, ketamine), which produce psychotic symptoms and cognitive dysfunction in healthy subjects and exacerbate psychotic, negative, and cognitive symptoms in patients with schizophrenia. Studies show that acute administration of NMDA antagonists causes NMDA receptor dysfunction, resulting in decreased inhibition of subcortical dopamine neurons and consequent increased mesolimbic dopamine release. Chronic administration produces decreased release, or hypoactivity, of dopamine in the prefrontal cortex (Davis and Lieberman, 2000). 

Psychotic symptoms must be distinguished from obsessions with poor or variable insight and overvalued ideation. Other positive or negative symptoms of a psychotic disorder may be present and the nature of the obsessions is often atypical and associated with a de-... 

A basic ethical issue in several areas of psychiatric research is whether participants are able to provide informed consent, particularly for protocols entailing medication washout and/or placebo treatment. The majority of psychiatric patients who are asked to participate in clinical trials have adequate capacity to provide consent. Thus, in a study specifically designed to examine the capacity of schizophrenic patients to give informed consent, cognitive dysfunction and negative symptoms (apathy and avolition). but not psychotic symptoms (hallucinations, delusions), were found to be associated with impaired decisional capacity (Moser et al., 2002). These features are probably not unique to schizophrenia but are likely to apply to many other forms of illness. 

Delusions are false beliefs that the patient maintains in the face of incontrovertible, contradictory evidence. The schizophrenic patient usually has no insight that these beliefs are not real, but rather maintains a firm conviction in them. Schizophrenia is characterized by a variety of delusions, of which the persecutory type predominates. Other delusions often involve bizarre bodily changes. In contrast to delusional disorder, these delusions are not as well formed and occur in the context of other psychotic symptoms (e.g., hallucinations, negative symptoms). 

Schizophrenia is a complex neuropsychiatric disorder with a prevalence of nearly 1% of the world population. Clinically, schizophrenia is characterized by chronic psychotic symptoms and psychosocial impairment. At least two core syndromes of schizophrenia, the positive and the negative, are recognized (Liddle, 1987). Those in whom positive symptoms predominate have hallucinations, delusions, and paranoid ideation. Those with negative symptoms have apathy and anledonia. Besides impairment in the cognitive domain, individuals with schizophrenia show a deficit in emotion processing, as indicated by a markedly reduced ability to perceive, process, and express facial emotions (Aleman et al., 1999). 

Recently, a relationship between ketamine-induced psychotic symptoms and NMDA receptor occupancy was reported (Stone et al., 2008). NMDA receptor binding in middle inferior frontal cortex showed a significant correlation with BPRS negative subscale, suggesting that ketamine may induce negative symptoms through direct inhibition of the NMDA receptor within this region. 

Ketamine and PCP are use-dependent noncompetitive antagonists of the NMDA receptor that bind to the intrachannel site of the receptor and prevent calcium ion flux (Javitt and Zukin, 1991) in humans they cause a syndrome that is clinically indistinguishable from schizophrenia and that involves not only positive (psychotic) symptoms, but also, negative symptoms (blunted affect, avolition), thought... 

In a 28-year-old woman with psychotic symptoms resistant to monotherapy with clozapine or ziprasidone, the combination produced marked improvement in both positive and negative symptoms along with a reduction in adverse effects body weight fell, blood pressure, pulse, and the electrocardiogram remained normal, and valproic acid, which had been introduced for epileptic seizures during clozapine monotherapy, was successfully withdrawn (23). 

We can consider the positive and negative symptoms listed earlier as target symptoms for antipsychotic medication treatment. Antipsychotic medications are now considered an important, if not essential, component in the treatment of schizophrenia. The focus of treatment is not only the resolution of psychotic symptoms but also relapse prevention. Unfortunately, schizophrenia is a disorder in whidi relapse is extremely common. It is estimated that following a psychotic episode and subsequent recovery, 70 percent of patients will relapse within a year if treated with either placebo or no medication at all. With continued antipsychotic treatment the relapse rate can drop to 30 to 40 percent. Studies have shown that low-dose and intermittent treatment are associated with poorer outcome, as measured by number of hospitalizations (Carpenter et al. 1990 Kane 1990). 

The antipsychotic medications tend to be effective in the treatment of psychotic symptoms, regardless of the disorder. They can be effective in substance-induced delusional disorders, delirium, schizophrenia, mania, delusional disorder, and so on. Standard antipsychotics tend to be much more effective for positive symptoms but do little to improve negative symptoms. The newer, atypical antipsychotics are more effective for negative symptoms although clearly not a panacea since they are successful in only about 30 percent of cases. 

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