A treatment trial with an analog of thyrotropin-releasing hormone (DN-1417) in schizophrenia

Mizuki, Yasushi; Nishikori, S.; Kajimura, Naofumi; Imaizumi, Junichi; Yamada, Masakazu; Inanaga, Kazutoyo

doi:10.1016/0006-3223(85)90204-5

Cited by 8 publications

(2 citation statements)

References 13 publications

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“…It also demonstrates neuroprotective effects3637, and may be involved in chronic neuronal hyperexcitability associated with kindling36. More controversial reports have suggested that TRH administration may be of therapeutic benefit for patients afflicted with schizophrenia3839. Trhr1 knockout mice have central hypothyroidism and mild hyperglycemia but exhibit normal growth and development as well as normal body weight and food intake40.…”

Section: Discussionmentioning

confidence: 99%

Candidate Genes for Inherited Autism Susceptibility in the Lebanese Population

Kourtian

Soueid

Makhoul

et al. 2017

Sci Rep

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Autism spectrum disorder (ASD) is characterized by ritualistic-repetitive behaviors and impaired verbal/non-verbal communication. Many ASD susceptibility genes implicated in neuronal pathways/brain development have been identified. The Lebanese population is ideal for uncovering recessive genes because of shared ancestry and a high rate of consanguineous marriages. Aims here are to analyze for published ASD genes and uncover novel inherited ASD susceptibility genes specific to the Lebanese. We recruited 36 ASD families (ASD: 37, unaffected parents: 36, unaffected siblings: 33) and 100 unaffected Lebanese controls. Cytogenetics 2.7 M Microarrays/CytoScan™ HD arrays allowed mapping of homozygous regions of the genome. The CNTNAP2 gene was screened by Sanger sequencing. Homozygosity mapping uncovered DPP4, TRHR, and MLF1 as novel candidate susceptibility genes for ASD in the Lebanese. Sequencing of hot spot exons in CNTNAP2 led to discovery of a 5 bp insertion in 23/37 ASD patients. This mutation was present in unaffected family members and unaffected Lebanese controls. Although a slight increase in number was observed in ASD patients and family members compared to controls, there were no significant differences in allele frequencies between affecteds and controls (C/TTCTG: γ2 value = 0.014; p = 0.904). The CNTNAP2 polymorphism identified in this population, hence, is not linked to the ASD phenotype.

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Section: Discussionmentioning

confidence: 99%

Candidate Genes for Inherited Autism Susceptibility in the Lebanese Population

Kourtian

Soueid

Makhoul

et al. 2017

Sci Rep

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“…schizophrenia (Bigelow et al, 1975;Brambilla et al, 1986;Campbell, 1975;Clark et al, 1975;Drayson, 1974;Hollister et al, 1975;Inanaga et al, 1978;Lindstrom et al, 1977;Mizuki et al, 1985;Prange et al, 1979; Wilson et al, 1973). While conflicting results have been reported, the trend across all studies is that the majority of schizophrenic patients demonstrate some improvement in memory and disordered thought after administration of TRH or TRH analogs.…”

Section: Introductionmentioning

confidence: 99%

Alterations in TRH receptors in temporal lobe of schizophrenics: A quantitative autoradiographic study

Lexow

Joyce

Kim

et al. 1994

Synapse

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We utilized quantitative autoradiography to determine the distribution of receptors for thyrotropin-releasing hormone (TRH) throughout the human temporal lobe and to examine the distribution of these receptors in discrete subregions of the temporal lobe from patients diagnosed premortem with schizophrenia. When compared to non-neurologic controls, schizophrenic patients demonstrated an increase of 51% in the concentration of TRH receptors in the molecular layer of the dentate gyrus. Within nuclei of the schizophrenic amygdala, marked decreases were found in the central (44%), medial (38%), cortical (36%), accessory cortical (52%), lateral (54%), and medial basal (22%) nuclei. We also examined postmortem brain samples from patients with Huntington's disease, amyotrophic lateral sclerosis, and Alzheimer's disease for alterations in the distribution of TRH receptors. No significant differences from non-neuropsychiatric controls were noted within the hippocampus in any of these disease states; however, slight alterations were noted in the central and medial basal amygdala in Huntington's disease and in the cortical amygdala in Alzheimer's disease. These disease-specific findings suggest that TRH may play a role in the neurochemical dysfunction of schizophrenia.

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Novel approaches to the pharmacotherapy of schizophrenia

Meltzer

1986

Drug Development Research

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Meltzer, H.Y.: Novel approaches to the pharmacotherapy of schizophrenia. Drug Dev.Res. 9:23-40, 1986. Numerous attempts to extend the pharmacotherapy of schizophrenia beyond conventional neuroleptics are reviewed. Clozapine and melperone are atypical neuroleptics that produce few extrapyramidal side effects during acute usage and possibly less tardive dyskinesia with prolonged use. Decreasing dopamingeric activity with a tyrosine hydroxylase inhibitor or dopamine autoreceptor agonists may also be of value. Neuroleptics that block voltage-sensitive calcium channels or calcium channel blockers per se have been advocated for treatment of negative symptoms or the deficit state. Among other possible clinical approaches reviewed are: beta adrenergic blockers, clonidine, tryptophan, 5-hydroxytryptophan, fenfluramine, GABA drugs, including high dose benzodiazepines, lithium, carbamazepine, opioid agonists and antagonists, gamma-endorphins, TRH analogs and vasopressin. Most studies indicate these agents produce inconsistent or slight-to-modest benefits, either in comparison with standard neuroleptic drugs or in addition to neuroleptics, in groups of schizophrenic patients, including some double blind placebo-controlled trials. Those individuals who do respond sometimes, but not always, fail to relapse when the experimental drug is discontinued or fail to respond to it in subsequent trials. Consistent with the presumed heterogeneity of schizophrenia, there is some evidence supporting non-neuroleptic drug treatment for specific schizophrenic subtypes. The various stages of this usually life-long disorder, together with the possible mutability of the underlying etiological factors over time, requires the utmost care in clinical trials.

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A treatment trial with an analog of thyrotropin-releasing hormone (DN-1417) in schizophrenia

Cited by 8 publications

References 13 publications

Candidate Genes for Inherited Autism Susceptibility in the Lebanese Population

Candidate Genes for Inherited Autism Susceptibility in the Lebanese Population

Alterations in TRH receptors in temporal lobe of schizophrenics: A quantitative autoradiographic study

Novel approaches to the pharmacotherapy of schizophrenia

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