Cross-cultural study of a biochemical abnormality in paranoid schizophrenia

Jeste, Dilip V.; Doongaji, D. R.; Panjwani, Dilkhush; Datta, Manali; Potkin, Steven G.; Karoum, Farouk; Thatte, Shobha; Sheth, Ashit; Apte, Jayant S.; Wyatt, Richard Jed

doi:10.1016/0165-1781(81)90082-2

Cited by 23 publications

(4 citation statements)

References 28 publications

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“…The reduced synthesis may lead to altered dopamine function, a well‐known mechanism proposed for SZ genesis [Snyder, 1973; Seeman et al, 1976; Carlsson, 1988]. HPA may also increase Phe catabolism through alternative pathways, such as increased synthesis of phenylethylamine (PEA), a putative psychotogenic compound [Jeste et al, 1981]. This hypothesis has been investigated extensively previously, albeit with conflicting results [O'Reilly and Davis, 1994].…”

Section: Discussionmentioning

confidence: 99%

Convergent patterns of association between phenylalanine hydroxylase variants and schizophrenia in four independent samples

Talkowski¹,

McClain²,

Allen³

et al. 2008

American J of Med Genetics Pt B

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Recessive mutations in the Phenylalanine hydroxylase (PAH) gene predispose to phenylketonuria (PKU) in conjunction with dietary exposure to phenylalanine. Previous studies have suggested PAH variations could confer risk for schizophrenia, but comprehensive follow-up has not been reported. We analyzed 15 common PAH “tag” SNPs and 3 exonic variations that are rare in Caucasians but common in African-Americans among four independent samples (total n = 5,414). The samples included two US Caucasian cohorts (260 trios, 230 independent cases, 474 controls), Bulgarian families (659 trios), and an African-American sample (464 families, 401 controls). Analyses of both US Caucasian samples revealed associations with five SNPs; most notably the common allele (G) of rs1522305 from case-control analyses (z = 2.99, p = 0.006). This SNP was independently replicated in the Bulgarian cohort (z = 2.39, p = 0.015). A non-significant trend was also observed among African-American families (z = 1.39, p = 0.165), and combined analyses of all four samples were significant (rs1522305: χ2 = 23.28, 8 d.f., p = 0.003). These results for this SNP met our a priori criteria for statistical significance, namely an association that was robust to multiple testing correction in one sample, a replicated risk allele in multiple samples, and combined analyses that were nominally significant. Case-control results in African-Americans detected an association with L321L (p = 0.047, OR = 1.46). Our analyses suggest several associations at PAH, with consistent evidence for rs1522305. Further analyses, including additional variations and environmental influences such as phenylalanine exposure are warranted.

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Section: Discussionmentioning

confidence: 99%

Convergent patterns of association between phenylalanine hydroxylase variants and schizophrenia in four independent samples

Talkowski¹,

McClain²,

Allen³

et al. 2008

American J of Med Genetics Pt B

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“…In a later study, Jeste et al (1981) noted higher levels of urinary phenylethylamine, a metabolite of phenylalanine in paranoid schizophrenic patients compared to controls and other patients. Other studies have shown similar results, reviewed by O'Reilly and Davis (1994).…”

Section: Introductionmentioning

confidence: 94%

The association between risk factors for tardive dyskinesia and phenylalanine‐induced abnormal movements in schizophrenia

Schultz

Ellingrod

Fleming

et al. 2001

Human Psychopharmacology

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We examined whether an oral challenge dose of the amino acid phenylalanine (a dopamine precursor) exacerbates the abnormal movements of tardive dyskinesia (TD). We also examined age, gender, treatment duration, and baseline movement severity in relation to phenylalanine-induced changes in movements. Lastly, we assessed the influence of fasting amino acid levels on phenylalanine-induced movements. In a placebo-controlled fashion, the abnormal involuntary movement scale (AIMS) was obtained on 25 patients before and after a phenylalanine challenge drink. A general linear model determined the relative effects of age, gender, treatment duration, and fasting amino acid levels on the magnitude of induced movements. Age and treatment duration did not affect phenylalanine-induced movements. Lower fasting levels of phenylalanine were associated with greater movements after controlling for age, F = 11.89, p < 0.003. The severity of abnormal movements at baseline also predicted response to phenylalanine, F = 8.62, p = 0.0079. Brain amino acid and neurotransmitter pools are influenced by changes in dietary protein, which may have implications in the development and prevention of movement disorders. This study suggests that fasting amino acid levels may predict differences in vulnerability to movements during an influx of neurotransmitter precursors, perhaps due to long-term compensatory changes in receptor sensitivity. Copyright 2001 John Wiley & Sons, Ltd.

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“…Elevated unmetabolized biogenic amines could then cross the blood-brain barrier to cause behavioral symptoms. With this reasoning in mind, it is interesting that four out of six studies have found evidence of elevated phenylethylamine (PEA) levels in the urine of some schizophrenics (Wyatt et al 1980;Jeste et al 1981). PEA structurally resembles amphetamine and is known to induce a hyperactivity syndrome in animals which resembles the effects of dopaminergic drugs (Potkin et al 1979).…”

Section: Monoamine Oxidase (Mao) and Catechol-o-methyl Transferase (C...mentioning

confidence: 99%

The Dopamine Hypothesis: An Overview of Studies With Schizophrenic Patients

Haracz

1982

Schizophrenia Bulletin

132

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For the past decade, the dopamine hypothesis of schizophrenia has been the predominant biochemical theory of schizophrenia. Despite the extensive study of tissue samples obtained from schizophrenics, indirect pharmacological evidence still provides the major support for the hypothesis. Direct support is either uncompelling or has not been widely replicated. The dopamine hypothesis is limited in theoretical scope and in the range of schizophrenic patients to which it applies. No comprehensive biological scheme has yet been proposed to draw together the genetic, environmental, and clinical features of schizophrenia. Recent refinements of the dopamine hypothesis may aid in the delineation of biologically homogeneous subgroups. Positive symptoms (e.g., hallucinations, delusions) and negative symptomatology (e.g., affective flattening, social withdrawal) may result from different pathophysiological processes. Schizophrenia research might benefit from an increased attention to neurophysiological adaptations.

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Cross-cultural study of a biochemical abnormality in paranoid schizophrenia

Cited by 23 publications

References 28 publications

Convergent patterns of association between phenylalanine hydroxylase variants and schizophrenia in four independent samples

Convergent patterns of association between phenylalanine hydroxylase variants and schizophrenia in four independent samples

The association between risk factors for tardive dyskinesia and phenylalanine‐induced abnormal movements in schizophrenia

The Dopamine Hypothesis: An Overview of Studies With Schizophrenic Patients

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