Biomedical subjects

V Benegal

Publications and source records attributed to V Benegal.

6 recordsLinked to original sources

PubMed2006

Evidence of linkage and association on 18p11.2 for psychosis.

The genetic basis of bipolar disorder (BPD) and schizophrenia (SCZ) has been established through numerous clinical and molecular studies. Although often considered separate nosological entities, evidence now suggests that the two syndromes may share some genetic liability. Recent studies have used a composite phenotype (psychosis) that includes BPD, SCZ, psychosis not otherwise specified, and schizoaffective disorder, to identify shared susceptibility loci. Several chromosomal regions are reported to be shared between these syndromes (18p, 6q, 10p, 13q, 22q). As a part of our endeavor to scan these regions, we report a positive linkage and association finding at 18p11.2 for psychosis. Two-point linkage analysis performed on a series of 52 multiplex pedigrees with 23 polymorphic markers yielded a LOD score of 2.02 at D18S37. An independent set of 159 parent offspring trios was used to confirm this suggestive finding. The TDT analysis yielded support for association between the marker D18S453 and the disease allele (chi2 = 4.829, P < 0.028). This region has been implicated by several studies on BPD [Sjoholt et al. (2004); Mol Psychiatry 9(6):621-629; Washizuka et al. (2004); Biol Psychiatry 56(7):483-489; Pickard et al. (2005); Psychiatr Genet 15(1):37-44], SCZ [Kikuchi et al. (2003); J Med Dent Sci 50(3):225-229; Babovic-Vuksanovic et al. (2004); Am J Med Genet 124(3):318-322] and also as a shared region between the two diseases [Ishiguro et al. (2001); J Neural Transm 108(7):849-854; Reyes et al. (2002); Mol Psychiatry 7(4):337-339; Craddock et al. (2005); J Med Genet 42(3):193-204]. Our findings provide an independent validation of the above reports, and suggest the presence of susceptibility loci for psychoses in this region.

Chromosomes, Human, Pair 18↗

PubMed2001

Association of CAG repeat loci on chromosome 22 with schizophrenia and bipolar disorder.

Chromosome 22 has been implicated in schizophrenia and bipolar disorder in a number of linkage, association and cytogenetic studies. Recent evidence has also implicated CAG repeat tract expansion in these diseases. In order to explore the involvement of CAG repeats on chromosome 22 in these diseases, we have created an integrated map of all CAG repeats > or =5 on this chromosome together with microsatellite markers associated with these diseases using the recently completed nucleotide sequence of chromosome 22. Of the 52 CAG repeat loci identified in this manner, four of the longest repeat stretches in regions previously implicated by linkage analyses were chosen for further study. Three of the four repeat containing loci, were found in the coding region with the CAG repeats coding for glutamine and were expressed in the brain. All the loci studied showed varying degrees of polymorphism with one of the loci exhibiting two alleles of 7 and 8 CAG repeats. The 8-repeat allele at this locus was significantly overrepresented in both schizophrenia and bipolar patient groups when compared to ethnically matched controls, while alleles at the other three loci did not show any such difference. The repeat lies within a gene which shows homology to an androgen receptor related apoptosis protein in rat. We have also identified other candidate genes in the vicinity of this locus. Our results suggest that the repeats within this gene or other genes in the vicinity of this locus are likely to be implicated in bipolar disorder and schizophrenia.

Adult↗

PubMed2000

Association analysis of CAG repeats at the KCNN3 locus in Indian patients with bipolar disorder and schizophrenia.

Bipolar affective disorder and schizophrenia are severe behavioral disorders with a lifetime risk of approximately 1% in the population worldwide. There is evidence that these diseases may manifest the phenomenon of anticipation similar to that seen in diseases caused by trinucleotide repeat expansions. A recent report has implicated a potassium channel-coding gene, KCNN3, which contains a polymorphic CAG repeat in its coding region, in schizophrenia and bipolar disorder. We have tried to confirm these findings in Indian patients suffering from bipolar disorder and schizophrenia. No statistically significant evidence for the presence of an excess of longer alleles in the patient population, as compared to ethnically matched controls, was found. However, an analysis of the difference of allele sizes revealed a significantly greater number of patients with schizophrenia having differences of allele sizes > or = 5 when compared to normal controls. This finding may be of functional significance as the KCNN3 protein is thought to act as a tetramer, and a large difference in allele sizes would result in an asymmetric molecule with a different number of glutamine residues in each monomer. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:744-748, 2000.

Adult↗

PubMed1995

P300 amplitudes vary inversely with continuum of risk in first degree male relatives of alcoholics.

First degree relatives of alcoholics show significantly reduced P300 amplitudes. This phenomenon is though to be a vulnerability marker of alcoholism. Relatives of alcoholics with higher family loading and early onset alcoholism are at greater risk for developing alcoholism. The high risk population may comprise subtypes differentiated by family history and/or age at onset of alcoholism, with differing risks, measurable in terms of the expression of the vulnerability marker. Four groups of alcohol-naive sons/male siblings of alcoholics (n = 64) were studied. The groups were constructed on the permutation of two defining characteristics: high family loading (two or more first degree alcoholic relatives) and early onset alcohol dependence (before 25 years) in the relatives. Comparison of P300 amplitude in an auditory paradigm showed significant inter-group differences as well as progressive increase/normalization of amplitudes from the high loading-early onset group (HR1) to the low loading-late onset group (HR4), with the latter being indistinguishable from a separate group of (control) normals. There were no significant differences of P300 latency among the groups. We conclude that P300 amplitudes vary inversely with the presumed continuum of risk in those at high risk for developing alcoholism.

Adult↗

PubMed1993

Idiopathic catatonia: validity of the concept.

Although catatonic features can be seen in various psychiatric and organic disorders, some patients with catatonia cannot be fitted into existing classification systems. In the current study various sociodemographic and clinical variables were compared between patients who presented with catatonia only (idiopathic catatonia), or with catatonia as a symptom of an identifiable underlying functional disorder. Patients seen over one year (1988) were classified into idiopathic catatonia (n = 30) and according to diagnosis (n = 35; schizophrenia n = 19, depression n = 16). There was an excess of females in the idiopathic group and the illness was of a shorter duration. There were no other differences between the groups. All subjects showed good response to ECTs and required almost the same mean number of ECTs. No clusters were observed using the average method. The current study suggests that catatonic symptoms can occur in the absence of any other identifiable psychiatric syndrome, although they cannot be otherwise differentiated from other psychiatric syndromes in which catatonia can present.

Adult↗

PubMed1992

Is stupor by itself a catatonic symptom?

Many patients present with stupor or substupor without classical catatonic signs as described by Kahlbaum. The phenomenological literature is not clear as to whether stupor, when it presents alone, constitutes a separate syndrome or is a forme fruste of catatonia. All patients who presented with stupor, (a) partial or total mutism or (b) absent or decreased motor responses (n = 22), were compared with patients who also had classical catatonic signs such as negativism or waxy flexibility (n = 43) over a one-year period (1988), on sociodemographic and clinical variables. There were very few significant differences between the two groups (age, sex, diagnosis, duration of illness, number of ECTs required). The stupor group had a slight excess of patients with manic-depressive psychosis, depression and more frequently positive family histories of mental illness. The current study provides a tentative support to the hypothesis that stupor is a catatonic sign, and even when present alone can be considered to constitute a catatonic syndrome.

Adult↗