The coincidence of schizophrenia and Parkinsonism: some neurochemical implications

Abstract

SynopsisThe hypothesis has recently been advanced that increased activity of central dopaminergic mechanisms underlies the symptomatology of the schizophrenias. The evidence that dopaminergic transmission in the corpus striatum is impaired in Parkinson's disease suggests that observations on the relationship between Parkinson's disease and schizophrenia may illuminate the pathophysiology of the latter disease. Four cases are reported in which an illness with schizophrenic features developed in the setting of longstanding Parkinson's disease; attention is drawn to earlier reports of schizophrenic illnesses occurring as.postencephalitic sequelae in the presence of a parkinsonian syndrome. These observations appear to conflict with the view that increased dopamine release in the striatum is necessary for the expression of schizophrenic psychopathology, but do not exclude the possibility that increased transmission may occur at other dopaminergic sites in the brain, for example the nucleus accumbens, tuberculum olfactorium or cerebral cortex. Similarly the dopamine receptor blockade hypothesis of the therapeutic effects of neuroleptic drugs cannot be maintained with respect to an action in the striatum in view of the differences between the actions of thioridazine and chlorpromazine in this structure, but may be tenable for actions at extra-striatal sites.

Is negative schizophrenia a variant of parkinsonism?

“…In addition, the unusually high degree of basal ganglia involvement in diseases which resemble schizophrenia, supports the association of Parkinsonism with schizophrenia (Bowman & Lewis, 1980). The presence of psychotic symptoms in conjuction with Parkinsonism has been cited extensively in the past (Fairweather, 1947;Hollister & Glazener, 1961;Crow et al, 1976). More than 60 years ago McCown and Cook (1928) described the mental status of Parkinsonian patients as "extremely difficult to distinguish from ordinary cases of paraphrenia."…”

“…In addition to the neurochemical profile of negative schizophrenia, which overlaps with that of Parkinsonism, the co-occurrence of both disorders in the same patient suggests that they are interrelated (Crow et al, 1976;Friedman & Lannon, 1989). In addition, the unusually high degree of basal ganglia involvement in diseases which resemble schizophrenia, supports the association of Parkinsonism with schizophrenia (Bowman & Lewis, 1980).…”

“…Psychotic symptoms are particularly notable in patients with psutencephalitic Parkinsonism; during the acute illness some patients develop catatonic psychotic states, hallucinations, akinetic mutism, and amnesia (Howard & Lees, 1987). Crow et al, (1976) observed four cases in which an illness with schizophrenic features developed in the context of longstanding Parkinsonism and concluded that the "dopaminergic overactivity hypothesis of schizophrenia faces the difficulty that Parkinsonism and schizophrenia-like illnes can coexist." More recently, Friedman and Lannon (1989) described five patients with Parkinsonism who, during the course of the disease, suffered a severe psychotic illness that responded to clozapine.…”

Psychosis in Parkinson’s disease: ‘between a rock and a hard place’

“…Although several authors (Hale & Bellizzi, 1980;Crow & Johnstone, 1976) suggested that low potency neuroleptics might have a place in treating this group of patients, it became clear that all conventional neuroleptics led to an unacceptable worsening of motor symptoms (Murdock & Williamson, 1982;Scholz & Dichgans, 1985;Friedman et al, 1987;Wolk & Douglas, 1992;Greene et al, 1993). Even low doses of conventional drugs were found to be associated with a profound worsening of motor symptoms (Shaw et al, 1980).…”

“…Another problem in the interpretation of this literature is that some patients may have suffered from secondary Parkinsonian syndromes which are now recognized as being associated with psychosis; diffuse Lewy body disease, post-encephalitic parkinsonism and cerebro-vascular disease, for example. Reviewing this evidence, modern authors have concluded that psychosis in untreated Parkinson's disease (PD) is very rare (Crow & Johnstone, 1976;Cummings, 1992).…”