Study of Monozygotic Twins Discordant for Schizophrenia

Stabenau, James R.

doi:10.1001/archpsyc.1969.01740140017002

Cited by 16 publications

(2 citation statements)

References 32 publications

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“…Takahashi (1953) [28] confirmed this finding and recommended further investigations on OXPHOS in the brain tissue of schizophrenics. In line with those findings was the report by Stabenau et al (1969) [29], who observed in a biochemical study of discordant monozygotic twin pairs that lactate production and the lactate-pyruvate ratios were higher in the affected twins than in the unaffected co-twins. More recently, Prabakaran et al (2004) [30], in a large-scale functional genomics study, suggested a state of intermittent or chronic hypoxic stress and MD in the brains of patients with SCZ.…”

Section: Resultssupporting

confidence: 83%

Paradox of schizophrenia genetics: is a paradigm shift occurring?

Doi

Hoshi

Itokawa

et al. 2012

Behavioral and Brain Functions

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BackgroundGenetic research of schizophrenia (SCZ) based on the nuclear genome model (NGM) has been one of the most active areas in psychiatry for the past two decades. Although this effort is ongoing, the current situation of the molecular genetics of SCZ seems disappointing or rather perplexing. Furthermore, a prominent discrepancy between persistence of the disease at a relatively high prevalence and a low reproductive fitness of patients creates a paradox. Heterozygote advantage works to sustain the frequency of a putative susceptibility gene in the mitochondrial genome model (MGM) but not in the NGM.MethodsWe deduced a criterion that every nuclear susceptibility gene for SCZ should fulfill for the persistence of the disease under general assumptions of the multifactorial threshold model. SCZ-associated variants listed in the top 45 in the SZGene Database (the version of the 23rd December, 2011) were selected, and the distribution of the genes that could meet or do not meet the criterion was surveyed.Results19 SCZ-associated variants that do not meet the criterion are located outside the regions where the SCZ-associated variants that could meet the criterion are located. Since a SCZ-associated variant that does not meet the criterion cannot be a susceptibility gene, but instead must be a protective gene, it should be linked to a susceptibility gene in the NGM, which is contrary to these results. On the other hand, every protective gene on any chromosome can be associated with SCZ in the MGM. Based on the MGM we propose a new hypothesis that assumes brain-specific antioxidant defenses in which trans-synaptic activations of dopamine- and N-methyl-d-aspartate-receptors are involved. Most of the ten predictions of this hypothesis seem to accord with the major epidemiological facts and the results of association studies to date.ConclusionThe central paradox of SCZ genetics and the results of association studies to date argue against the NGM, and in its place the MGM is emerging as a viable option to account for genomic and pathophysiological research findings involving SCZ.

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Section: Resultssupporting

confidence: 83%

Paradox of schizophrenia genetics: is a paradigm shift occurring?

Doi

Hoshi

Itokawa

et al. 2012

Behavioral and Brain Functions

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“…Patients were rated on 4 different sets of diagnostic criteria for 'schizophrenia' (Astrachan et al 1972;Carpenter et al 1973;NIMH, 1964;Shakow, 1969;Stabenau et al 1969). In 40 of the 48 cases, all 4 diagnostic criteria agreed on a diagnosis of schizophrenia; in 6 cases, 3 of the 4 criteria were in agreement.…”

Section: Diagnosismentioning

confidence: 99%

Does a plasma level of chlorpromazine help?

Putten¹,

May²,

Jenden³

1981

Psychol. Med.

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SynopsisForty-eight newly admitted schizophrenic patients were treated with a fixed, conservative (6·6 mg/kg) dose of chlorpromazine (CPZ) for 28 days. CPZ plasma levels were measured by a gas chromatography mass spectrometry method (GCMS) using 2H6-chlorpromazine as an internal standard. At the end of the fixed-dose period, ‘responders’ had the same plasma levels as ‘non-responders’, suggesting that lack of response is primarily a matter of the illness' sensitivity to CPZ, not to a plasma level below some therapeutic window. After the fixed-dose period, the dosage of CPZ was increased in the ‘non-responders’ by physician's choice. Improvement occurred over a wide range of 10–225 picomoles (3–72 ng)/ml. Above 300 picomoles (95 ng/ml) 4 inaccessible patients eventually became much worse, suggesting psychotoxicity. It is in the inaccessible patient whose illness is only minimally, or not at all, sensitive to CPZ that a plasma level might be especially useful.Interpretation of plasma levels is complicated by the speed of response: some initial non-responders improved by the 56th day of treatment on very conservative plasma levels.

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