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Biomedical subjects

A B Goodman

Publications and source records attributed to A B Goodman.

At least 19 recordsLinked to original sources
PubMed2000

Meeting report; "Molecular neurobiological mechanisms in schizophrenia: seeking a synthesis," April 11-14, 1999.

A meeting on the molecular and neurobiological basis of schizophrenia was held April 11-14, 1999 at the Banbury Center of The Cold Spring Harbor Laboratory, Cold Spring Harbor, New York. This report is a summary of the predominant views of the participants, as perceived by the organizers. The purpose of this meeting was integrative-to bring together in a relaxed environment three dozen outstanding scientists in disparate underlying disciplines: psychiatry, psychology, genetics, neurobiology, biochemistry, molecular biology, and pharmacology. Brief talks emphasized concepts and questions rather than presentation of data. Exchanges of information and concepts provided an emerging synthesis of current and novel, even highly speculative, ideas. The reader is cautioned that the ideas, data supporting them, and data interpretations are not critiqued in this report. Nor is there much distinction made between speculations and findings that have more experimental support. The main questions and conclusions that emerged are presented in this report, which covers the following: 1) macrobiology (what schizophrenia is in terms of definition and improved diagnostics, genetics and environment, brain structure, development, and mind), 2) cell and molecular biology (defects of the expressed disease at both the membrane and nuclear levels, molecular defects of development, neuroreceptor genes and transcriptional control, and ligands), 3) therapies (current approaches, possible targets, and animal models), and 4) newer approaches (gene expression, early treatment and prevention strategies, and other problems). Two references per participant and abstracts (available from the organizers) served as a common basis.

Animals↗
PubMed1998

Three independent lines of evidence suggest retinoids as causal to schizophrenia.

Retinoid dysregulation may be an important factor in the etiology of schizophrenia. This hypothesis is supported by three independent lines of evidence that triangulate on retinoid involvement in schizophrenia: (i) congenital anomalies similar to those caused by retinoid dysfunction are found in schizophrenics and their relatives; (ii) those loci that have been suggestively linked to schizophrenia are also the loci of the genes of the retinoid cascade (convergent loci); and (iii) the transcriptional activation of the dopamine D2 receptor and numerous schizophrenia candidate genes is regulated by retinoic acid. These findings suggest a close causal relationship between retinoids and the underlying pathophysiological defects in schizophrenia. This leads to specific strategies for linkage analyses in schizophrenia. In view of the heterodimeric nature of the retinoid nuclear receptor transcription factors, e.g., retinoid X receptor beta at chromosome 6p21.3 and retinoic acid receptor beta at 3p24.3, two-locus linkage models incorporating genes of the retinoid cascade and their heterodimeric partners, e.g., peroxisome proliferator-activated receptor alpha at chromosome 22q12-q13 or nuclear-related receptor 1 at chromosome 2q22-q23, are proposed. New treatment modalities using retinoid analogs to alter the downstream expression of the dopamine receptors and other genes that are targets of retinoid regulation, and that are thought to be involved in schizophrenia, are suggested.

Animals↗
PubMed1996

Congenital anomalies in relatives of schizophrenic probands may indicate a retinoid pathology.

Retinoic acid, the morphogenic derivative of vitamin A, has been shown to alter patterns of neurulation and to regulate the expression of many genes involved in central nervous system development. Retinoid toxicity can result in craniofacial, limb, digit, heart and urogenital abnormalities. Hydrocephalus, due to increased ventricular size and/or decreased size of the hind- or forebrain, occurs frequently. Comparison of the frequency and type of congenital anomalies in extended pedigrees of 12 Ashkenazi probands with schizophrenia and seven normal Ashkenazi control probands indicates that relatives of the schizophrenic probands present a gamut of both minor and major congenital anomalies similar to, but less severe than, those caused by retinoid excess or deficiency, and at a frequency significantly greater than in control pedigrees. Within schizophrenic pedigrees, those diagnosed with schizophrenia spectrum illnesses are more likely to present such anomalies than are non-spectrum members. Retinoic acid receptors are present in all parts of the cranial region and delivery of retinoids is exquisitely controlled throughout embryonic and fetal development. Alterations in the functioning of the retinoid cascade may have profound implications for neurodevelopmental disorders like schizophrenia.

Abnormalities, Multiple↗
PubMed1995

Chromosomal locations and modes of action of genes of the retinoid (vitamin A) system support their involvement in the etiology of schizophrenia.

Vitamin A (retinoid), an essential nutrient for fetal and subsequent mammalian development, is involved in gene expression, cell differentiation, proliferation, migration, and death. Retinoic acid (RA) the morphogenic derivative of vitamin A is highly teratogenic. In humans retinoid excess or deficit can result in brain anomalies and psychosis. This review discusses chromosomal loci of genes that control the retinoid cascade in relation to some candidate genes in schizophrenia. The paper relates the knowledge about the transport, delivery, and action of retinoids to what is presently known about the pathology of schizophrenia, with particular reference to the dopamine hypothesis, neurotransmitters, the glutamate hypothesis, retinitis pigmentosa, dermatologic disorders, and craniofacial anomalies.

Chromosome Aberrations↗
PubMed1994

Elevated risks for amyotrophic lateral sclerosis and blood disorders in Ashkenazi schizophrenic pedigrees suggest new candidate genes in schizophrenia.

Among relatives of Ashkenazi schizophrenic probands the rate of amyotrophic lateral sclerosis was 3/1,000, compared to expected population rates of approximately 2/100,000. Relative risk of bleeding disorders, including hematologic cancers, was increased more than three-fold compared to controls. Co-occurrence of motor neuron disease and blood dyscrasias, accompanied by psychosis, has long been recognized. A virally mediated autoimmune pathogenesis has been proposed. However, the familial co-occurrence of these three disease entities raises the possibility that the disease constellation be considered as a manifestation of a common underlying genetic defect. Such expansion of the spectrum of affectation might enhance the power of both candidate gene and linkage studies. Based on these findings the loci suggested as candidate regions in schizophrenia include a potential hot spot on chromosome 21q21-q22, involving the superoxide dismutase and amyloid precursor protein genes. Alternatively, genes on other chromosomes involved in the expression, transcription, or regulation of these genes, or associated with the illnesses of high frequency in these pedigrees are suggested. Candidates include the choroid plexus transport protein, transthyretin at 18q11.2-q12.1; the t(14;18)(q22;21) characterizing B-cell lymphoma-2, the most common form of hematologic cancer; and the 14q24 locus of early onset Alzheimer's disease, c-Fos, transforming growth factor beta 3, and heat shock protein A2. Expression of hematologic cancers and the suggested candidate genes are known to involve retinoid pathways, and retinoid disregulation has been proposed as a cause of schizophrenia.

Age Factors↗
PubMed1994

A family history study of schizophrenia spectrum disorders suggests new candidate genes in schizophrenia and autism.

To limit genetic heterogeneity, this study focused on the widely extended pedigrees of Ashkenazi Jewish schizophrenic and autistic probands, to determine if similar causal mechanisms might obtain for both conditions. At least two previous epidemiological studies have demonstrated increased risk for schizophrenia in Ashkenazi Jews. The hypothesis posed is that increased prevalence of various rare autosomal recessive diseases among the Ashkenazim might contribute to the increased vulnerability to schizophrenia and to autism in this large genetic isolate. Rates of amyotrophic lateral sclerosis (ALS) and bleeding disorders were significantly increased among relatives of schizophrenic and autistic probands, compared to relatives of normal probands. These results suggest new candidate loci in schizophrenia and autism, particularly the chromosome 15q23-24 locus of the hexosaminidase A gene, causing various GM2 gangliosidoses, and the 21q22.1-q22.2 loci of the antioxidant, superoxide dismutase gene, and a cytokine receptor gene.

Adult↗
PubMed1994

Medical conditions in Ashkenazi schizophrenic pedigrees.

To limit the genetic heterogeneity of schizophrenia, this study focused on the widely extended pedigrees of Ashkenazi Jewish schizophrenia probands. The hypothesis posed is that the increased prevalence among the Ashkenazim of the rare lysosomal enzyme disorders, Tay Sachs disease (TDS), caused by low levels of hexosaminidase A, and Gaucher's disease (GD), caused by low levels of glucocerebrosidase, might contribute to the demonstrated increased vulnerability to schizophrenia in this ethnic group. Signs and symptoms characterizing the candidate illnesses were systematically queried by the family history method. Rates and relative risks for symptoms characterizing these disorders and for several nonautosomal illnesses associated with TSD and/or GD (i.e., amyotrophic lateral sclerosis and Hodgkin's disease, leukemia and lymphoma) are significantly elevated in the schizophrenia pedigrees, compared to controls. The conditions with elevated rates and risks have been associated with chromosomal regions 1q21 and 15q23-q24. These areas are suggested as candidate regions for future targeted deoxyribonucleic acid (DNA) research in schizophrenia.

Adolescent↗
PubMed1989

Inpatients of Taipei City Psychiatric Center, Zhenjiang Psychiatric Hospital and New York State Mental Hospital, Rockland Psychiatric Center: comparison of the diagnostic distribution and sex ratios.

Description among Zhenjiang Psychiatric Hospital (ZPH) Taipei City Psychiatric Center (TCPC), and New York State Psychiatric Hospital, Rockland Psychiatric Center (RPC) admission cohorts during the identical year indicates that the RPC cohort demonstrates different frequencies of major psychiatric illness than the ZPH and TCPC cohorts which are remarkably similar. Schizophrenia is more prevalent among RPC public admissions than ZPH and TCPC. Mania exceeds depression in ZPH and TCPC samples while depression exceeds mania in RPC. Females predominate among ZPH and TCPC admissions, in contrast to male predominance in RPC. Wherease alcoholism is almost non-existant among ZPH and TCPC admissions, over half the RPC sample had a diagnosis of substance abuse.

Alcoholism↗
PubMed1986

Distribution of treated mental illness in the neighborhoods of Jerusalem.

The authors compared the rates of treated mental illness among ethnically advantaged Ashkenazic Jews and ethnically disadvantaged Sephardic Jews in four areas of Jerusalem defined by socioeconomic status. They found that the rates of illness were higher in areas of lower socioeconomic status, that the Ashkenazim had higher rates of illness than the Sephardim in the areas of lower status, and that there was a comparatively high rate of illness among the Ashkenazim in the very religious Jewish neighborhoods. They interpret these findings on the basis of the theories of social causation and social selection, including genetic transmission.

Health Status↗
PubMed1986

Elderly schizophrenic inpatients in the wake of deinstitutionalization.

The authors investigated the factors relating to the observation that in a large state hospital, there is an age-related increase in the ratio of patients with a DSM-II diagnosis of paranoid schizophrenia to those with a diagnosis of nonparanoid schizophrenia. Elderly inpatients (N = 1,518) treated over a 5-year period were studied and the hypotheses of proportionately greater numbers with late onset of paranoid conditions, longer lengths of stay for recently admitted paranoid patients, and changing diagnosis over time were tested and rejected. The data suggest that the buildup among the elderly of those diagnosed under DSM-II to have paranoid conditions is due to patients admitted well before age 54. The authors discuss the reasons for the poor prognosis of this group.

Age Factors↗
PubMed1985

Clinical correlates of readmission in a schizophrenic cohort.

A study of a cohort of 223 schizophrenic patients from a single catchment area followed up for two years after discharge from inpatient status revealed a significant association between the presence of two of 38 clinical problem categories (social withdrawal and drug abuse) and subsequent readmission. In addition, patients without social withdrawal who were readmitted showed a significantly greater use of aftercare services than those not readmitted, while, among those with social withdrawal, male patients were significantly more likely to be readmitted than female patients. Neither prior hospitalization nor the presence of affective symptoms were significantly associated with readmission. Clinical and research implications of these findings are discussed.

Follow-Up Studies↗