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Biomedical subjects

L E DeLisi

Publications and source records attributed to L E DeLisi.

At least 19 recordsLinked to original sources
PubMed2001

Speech disorder in schizophrenia: review of the literature and exploration of its relation to the uniquely human capacity for language.

The language capacity of modern humans is thought by some to be clearly distinct from that of nonhuman primates (Bickerton 1990). Crow (1997, 1998a) has proposed that a disturbance in the uniquely human aspects of language is central to the genetic etiology of schizophrenia. A review of the literature on language disorder in schizophrenia provides evidence for widespread deficits in comprehension, production, attention, and cerebral lateralization of language. We focused here on those anomalies that are uniquely human aspects of language. Bickerton's five distinctly human language devices were examined in patients with schizophrenia and their families by using a structured scoring format on oral soliloquies. The chronic patients showed reduced use of clausal embedding and used fewer words than first episode patients or well family members. The amount of sentence complexity was found to be familial and to cosegregate with schizophrenia within families. These data are consistent with previous literature and additionally show a familial component to these measures, thus suggesting that deficits in specifically human aspects of language may be related to the genetics of schizophrenia.

Adult↗
PubMed2001

Systematic screening for mutations in the glycine receptor alpha2 subunit gene (GLRA2) in patients with schizophrenia and other psychiatric diseases.

The glycine receptor, which is a member of the ligand-gated ion channel superfamily, mediates synaptic inhibition in the spinal cord and other brain regions. This superfamily has been implicated in the pathogenesis of schizophrenia and other psychiatric diseases. The complete coding sequence and splice junctions of the GLRA2 gene were scanned by DOVAM-S, a form of SSCP analysis with sufficient redundancy to detect virtually all mutations. Those analyses were performed in 113 patients with schizophrenia, and in pilot studies of patients with bipolar illness, alcoholism, puerperal psychosis, autism, and attention-deficit hyperactivity disorder (533 kb total scanned sequences). We detected three sequence changes in the coding region, all resulting in silent mutations: C894T in exon 5, C1134T in exon 7, and C1476T in exon 9. These do not alter the structure or the expression of the protein. It is unlikely that mutations in the coding region and splice junction of GLRA2 gene are associated with schizophrenia and other psychiatric diseases.

Alcoholism↗
PubMed2001

Clinical characteristics of schizophrenia in multiply affected Spanish origin families from Costa Rica.

Sixty-six families from Costa Rica with multiply ill sets of siblings were examined in detailed clinical evaluations and compared with 59 similarly evaluated families from the USA. Eighty-six unrelated Costa Rican individuals with a schizophrenia spectrum diagnosis and no other ill siblings were an additional comparison group. This study was undertaken to examine whether schizophrenia in Costa Rica has similar clinical and demographic characteristics to that in the USA, whether a homogeneous population such as that in Costa Rica might harbor a specific definable subtype, and whether singletons have similar or differing characteristics from individuals in multiplex families. Overall, schizophrenia in Costa Rica is similar to that in any other geographic location. The same symptoms, sex ratio and age of onset characteristics predominate. However, there was significantly less prevalence of affective symptoms (depression and mania) and drug abuse among the Costa Rican multiplex families by comparison with those from the USA. The families with only one ill member from Costa Rica had significantly more alcohol abuse than the multiply affected families. Within multiplex families (both USA and Costa Rica), age of onset was found to have a familial component. Family sibship size was significantly greater in Costa Rica than the USA for the generation with illness studied. However, these siblings had overall fewer children. In Costa Rica, the male but not the female siblings with schizophrenia had reduced fecundity compared with their well siblings. These families from Costa Rica will be used in further molecular genetic studies to determine whether the illness etiology can be traced to one or more specific genetic linkages.

Analysis of Variance↗
PubMed2000

No evidence for a parent-of-origin effect detected in the pattern of inheritance of schizophrenia.

BACKGROUND: Schizophrenia is a complex genetic disorder with no clear pattern of inheritance. Epigenetic modification of genes may thus play a role in its transmission. METHODS: In our study, 439 families with at least two ill siblings with schizophrenia (208 with unilineal transmission) were examined for evidence of a parent-of-origin effect (e.g., evidence of parental imprinting on the familial transmission of schizophrenia). RESULTS: No significant difference in the prevalence of maternal compared with paternal transmission was found. In addition, affected male subjects did not differ from affected female subjects in the proportion of their offspring diagnosed with schizophrenia. CONCLUSIONS: Although the transmission of schizophrenia may be influenced by epigenetic events, our study fails to find evidence that one epigenetic mechanism, a parent-of-origin imprinting effect, determines whether an individual expresses the illness.

Adult↗
PubMed2000

A geometric morphometric assessment of change in midline brain structural shape following a first episode of schizophrenia.

BACKGROUND: Previous reports indicate that brain structural abnormalities may be progressive in some patients with schizophrenia. Our study was designed to determine deviations in the shape of midline brain structures at the time of onset of symptoms of schizophrenia and 3-5 years later. METHODS: Eleven landmarks were located on the midsagittal magnetic resonance imagery brain scans of 55 patients with schizophrenia and 22 nonpsychiatric control individuals. Geometric morphometric methods were used for the extraction of shape variables from landmark coordinates. Permutation tests were used to test the effects of gender, diagnosis, time elapsed since illness onset, and age on brain shape. RESULTS: The diagnosis-by-time interaction and the effect of gender were significantly different from zero (p<.027 and p <.039, respectively). The effect of time was significant in patients (p <.002), but not in control subjects. Some anatomical abnormalities in mean patient brain morphology seem to be present both at the time of diagnosis and at follow-up. These are similar to anomalies reported by previous geometric morphometrics studies. CONCLUSIONS: Some previously identified brain abnormalities are detectable at the time of first hospitalization. The rapid change in midline brain morphology in patients with schizophrenia during the subsequent 3-5 years is consistent with either a neurodegenerative disease process or an effect of treatment with psychiatric drugs. There is a sexual dimorphism in brain morphology that might be reduced by schizophrenia.

Adult↗
PubMed2000

Failure to establish linkage on the X chromosome in 301 families with schizophrenia or schizoaffective disorder.

The hypothesis that a gene for susceptibility to psychosis (specifically in the X-Y homologous class) is located on the sex chromosomes has been proposed. Such a gene would account for the excess of sex chromosome anomalous males and females in populations of patients with psychosis, a tendency towards concordance by sex within families, and sex differences associated with psychosis and its underlying brain pathology. In earlier studies we observed small positive LOD scores in Xp11, and in a more recent and larger cohort of 178 sibling pairs, a peak multipoint nonparametric LOD score of 1. 55 at the locus DXS8032 in Xq21. The present study with a new set of markers extended the cohort to 301 ill sibling pairs and their parents. Despite the increase in sample size, the LOD score did not increase. A peak NPL of 1.55 was observed at the locus DXS1068 in proximal Xp, a region remote from the previous report. Separating families into those who were more likely to have X chromosome inheritance (maternal with no male to male transmission) did not yield stronger findings. In spite of the evidence that psychosis is related to a sex-dependent dimension of cerebral asymmetry, it is concluded that no consistent linkage of schizophrenia to the X chromosome can be demonstrated. In the context of the general failure of replication of linkage in psychosis, the possibility that the genetic predisposition to psychosis is contributed to by epigenetic modification rather than variations in the nucleotide sequence has to be considered.

Chromosome Mapping↗
PubMed2000

Investigation of a candidate gene for schizophrenia on Xq13 previously associated with mental retardation and hypothyroidism.

Weak support for linkage of schizophrenia to proximal Xq has previously been reported. In addition, an increased prevalence of thyroid disorder has been noted in families of individuals with schizophrenia. Recently, a gene mapped to Xq13 termed HOPA has been found to be associated with mental retardation, hypothyroidism, and depression and to function as a coactivator for the thyroid receptor. We therefore examined the HOPA gene in a group of 111 probands from a larger cohort of multiplex families with schizophrenia, several of whom (n = 53) also had a family history of hypothyroidism. Four males and two females were found with an alteration in exon 42 of the HOPA gene compared with 8/492 males and 18/471 females (942 X chromosomes) compared with consecutively screened newborns (chi(2) = 3.92, P < 0.05). However, when available family members of each of the probands with an exon 42 variation were subsequently screened, the mutation did not segregate with schizophrenia in three of five families, although all 6 probands with an exon 42 variation did have hypothyroidism in either themselves (n = 3) or their mothers (n = 3) (P < 0.008). These findings replicate prior findings demonstrating an association between HOPA polymorphisms and hypothyroidism. In addition, the increased frequency of HOPA variants in this population may also provide a genetic basis for the familial association of thyroid disease and schizophrenia.

Amino Acid Sequence↗
PubMed2000

Lack of evidence for linkage to chromosomes 13 and 8 for schizophrenia and schizoaffective disorder.

A previous report [Blouin et al., 1998: Nat Genet 20:70-73] suggesting linkage to chromosomes 13q32 and 8p21 in families with schizophrenia led us to investigate these regions in a large set of 301 multiplex families with schizophrenia. Multipoint analyses failed to reveal evidence for linkage to any portion of chromosome 13, while only a weakly positive score was present on 8p using the identical marker reported in the earlier report. Failure to confirm the Blouin et al claims in a substantially larger cohort adds emphasis to the inconsistency of the findings concerning linkage in schizophrenia. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:235-239, 2000.

Chromosomes, Human, Pair 13↗
PubMed2000

Critical overview of current approaches to genetic mechanisms in schizophrenia research.

A genetic etiology to schizophrenia was recognized a century ago by E. Kraepelin [Ein Lehrbuch fur studirende und aerzte, Vol II. Leipzig, Verlagvon, Barth (1899)], yet no clear inherited pattern or mechanism has been established. In the last decade, a new wave of molecular genetic studies of families with schizophrenia has yielded unconvincing evidence for the involvement of multiple putative loci. The task of the next century will be to use genomics to define the true nature of deviant brain growth and development throughout the lifetime of an individual that could result in the perceptual disturbances characterized as schizophrenia.

Humans↗
PubMed2000

Seymour S. Kety MD: the man and his accomplishments. Summary of a symposium in his honor at the VIIIth World Congress of Psychiatric Genetics, Versailles, France, 30 August 2000.

Seymour S. Kety was a physician and neuroscientist of great distinction. His impact on both the dynamics and imaging of cerebral blood flow and metabolism, as well as the nature-nurture controversy about the etiology of schizophrenia, led to his receiving the Lasker Award in 1999. He died at the age of 84 in the year 2000, leaving medical research, and psychiatric genetics in particular, a bountiful legacy of rich science, thoughtful critiques and prophesies about hypotheses from the past and well into the future. Reviewed in this paper is a tribute to his work as presented during the VIIIth World Congress of Psychiatric Genetics in Versailles, France, August 2000.

Cerebrovascular Circulation↗
PubMed2000

Lack of association between duration of untreated illness and severity of cognitive and structural brain deficits at the first episode of schizophrenia.

OBJECTIVE: The purpose of the study was to determine whether the duration of illness before antipsychotic drug treatment for schizophrenia was associated with the severity of cognitive deficits and volumetric brain structure anomalies observed in some patients with a first episode of schizophrenia. METHOD: Duration of psychotic symptoms and of other symptoms marking a behavioral change was estimated from structured interviews with 50 patients who had a first episode of schizophrenia and their family members. Interviews were conducted within a month of the patients' hospitalization. Duration of untreated psychotic symptoms and of behavioral change was correlated with neuropsychological summary scores from a comprehensive cognitive battery and with measurements of lateral ventricular, temporal lobe, and cerebral hemispheric volumes. RESULTS: No significant correlations were observed between measures of untreated illness and the severity of either cognitive or structural brain deficits at baseline. CONCLUSIONS: The duration of untreated symptoms of schizophrenia, for which an association with an uncontrolled toxic brain process has been proposed, is unlikely to explain why first-episode patients with schizophrenia have widespread deficits in cognitive functioning and have detectable ventricular enlargement and some loss of cortical mass.

Adult↗
PubMed1999

Anticipation in schizophrenia: a review and reconsideration.

There have been several reports on anticipation and schizophrenia, and the purpose of the present article is to review the literature and present data from an ongoing family study of schizophrenia. The published data find on average a 10-year difference in the age of onset between the parental and offspring generation in family sets that have been ascertained for a genetic linkage study. The biases inherent in such studies include the biases of ascertainment that were described by Penrose [1948]. Several investigators have searched for evidence of enlarged triplet repeats, and some find evidence consistent with expanded triplet repeats, whereas others do not. In any event the phenomenon of anticipation in schizophrenia appears to be consistently found and an explanation is needed. Data are presented from pairwise analyses using intergenerational pairs from 61 pedigrees with schizophrenia showing evidence of anticipation as well as the fertility bias. Anticipation was found in aunt:niece/nephew pairs (14.5 years) but not in uncle:niece/nephew pairs (0.5 years). The sex difference in age of onset was accentuated in uncles versus aunts (8.5 years), present in parents (4.5 years), but absent in the proband generation. Therefore, there appears to be an interaction within families between age of onset and sex that deserves further investigation. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:686-693, 1999.

Adolescent↗
PubMed1999

Defining the course of brain structural change and plasticity in schizophrenia.

Recent evidence from controlled CT and MRI longitudinal studies suggests that some cerebral ventricular enlargement and hemispheric volumetric reductions (e.g. cerebral atrophy) may have a progressive component in patients with schizophrenia. These studies vary in cohort composition, stage of illness examined, duration of follow-up interval, imaging techniques used, and specific brain regions with findings. They also conflict with earlier evidence suggesting that schizophrenia is a neurodevelopmental disorder with brain pathological deviance occurring prior to the illness onset. The newer brain imaging reports may be detecting subtle brain plasticity that results from a continuing cortical disruptive process, may be epi-phenomena caused by scanning and image analysis artifacts or may possibly reflect systemic physiological fluctuations. Future longitudinal studies of subjects at all stages of illness using a variety of new technologies are needed to clarify these findings.

Atrophy↗