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Y Osher

Publications and source records attributed to Y Osher.

13 recordsLinked to original sources

Rorschach markers in offspring of manic-depressive patients.

BACKGROUND: Previously published data show large differences between euthymic Israeli adult bipolar patients and US normative data on several measures of psychological functioning as assessed with a sensitive projective measure (Rorschach Inkblot Test). The current study examines the Rorschach performance of healthy offspring of bipolar parents and compares them to matched normal controls. METHODS: 14 asymptomatic offspring of Israeli manic-depressive parents were matched for age, gender, and other demographic variables with 14 children of normal parents. All subjects were individually administered the Rorschach Inkblot Test, and protocols were scored blindly according to the Exner Comprehensive System. RESULTS: Offspring of bipolar parents, like bipolar patients themselves, show significantly increased incidence and severity of thought disorder (as defined by Exner), lower numbers of cognitively mediated affective responses, and fewer responses indicating conventional perceptions. LIMITATIONS AND CONCLUSIONS: Although the sample size is small, this study strengthens the possibility that these measures of psychological functioning may serve as markers for manic-depressive illness.

Adolescent↗

Association between tridimensional personality questionnaire (TPQ) traits and three functional polymorphisms: dopamine receptor D4 (DRD4), serotonin transporter promoter region (5-HTTLPR) and catechol O-methyltransferase (COMT).

Dopamine D4 receptor (DRD4), serotonin transporter promoter regulatory region (5-HTTLPR) and catechol O-methyltransferase (COMT) polymorphisms were examined for association with TPQ personality factors in 455 subjects. Significant interactions were observed by multivariate analysis, (COMT x 5-HTTLPR: Hotelling's Trace = 2.3, P = 0.02) and by subsequent univariate 3-way ANOVA when Novelty Seeking (NS) was the dependent variable: 5-HTTLPR x D4DR (F = 6.18, P = 0.03) and COMT x 5-HTTLPR (F = 4.42, P = 0.03). In the absence of the short 5-HTTLPR allele and in the presence of the high enzyme activity COMT val/val genotype, NS scores are higher in the presence of the DRD4 seven-repeat allele. The effect of these three polymorphisms on NS was also examined using a within-families design. Siblings who shared identical genotype groups for all three polymorphisms (COMT, DRD4 and 5-HTTLPR) had significantly correlated NS scores (intraclass coefficient = 0.39, F = 2.26, P = 0.008, n = 49) whereas sibs with dissimilar genotypes in at least one polymorphism showed no significant correlation for NS scores (intraclass coefficient = 0.177, F = 1.43, P = 0.09, n = 110). Similar interactions were also observed between these three polymorphisms and Novelty Seeking when the 150 independently recruited and non-related subjects were analyzed. The current results are consistent with two earlier reports in which we demonstrated an interaction between the 5-HTTLPR and DRD4 polymorphisms in 2-week-old neonates, in the same children assessed again at 2 months of age and in adults. Molecular Psychiatry (2000) 5, 96-100.

Adolescent↗

Association and linkage of anxiety-related traits with a functional polymorphism of the serotonin transporter gene regulatory region in Israeli sibling pairs.

A functional polymorphism in the regulatory region of the serotonin transporter gene (5-HTTLPR) has been reported to be both associated and linked to anxiety-related personality measures, although other studies have not replicated these findings. The current study examines both association and linkage of the gene to two major anxiety-related personality measures, the harm avoidance scale on the Tridimensional Personality Questionnaire and the neuroticism scale of the NEO-PI-R, in a sample of 148 Israeli subjects comprising 74 same-sex sibling pairs. We replicated the reported association between the short allele and higher scores on the TPQ harm avoidance scale (P = 0.03), including the subscale of shyness (P = 0.02), and also found association in the same direction between the short allele and the NEO-PI-R neuroticism subscales of anxiety (P = 0.03) and depression (P = 0.04). Sib-pair linkage analysis, using the regression method, further supported a role of the 5-HTTLPR in anxiety-related personality traits.

Adolescent↗

An interaction between the catechol O-methyltransferase and serotonin transporter promoter region polymorphisms contributes to tridimensional personality questionnaire persistence scores in normal subjects.

Persistence (RD2) is a subscale of the reward dependence trait, one of the three major personality factors assessed by the Tridimensional Personality Questionnaire (TPQ). Subjects with high RD2 scores are characterized as industrious, hard-working, ambitious, perfectionistic. TPQ scores were examined in 577 normal subjects inventoried for two common genetic polymorphisms, the catechol O-methyltransferase (COMT) valine to methionine (val to met) amino acid substitution that determines high and low enzyme activity, and the serotonin transporter promoter region 44 bp deletion (5-HTTLPR) linked in some studies to harm avoidance or neuroticism. When TPQ RD2 scores are grouped by COMT and 5-HTTLPR polymorphisms and analyzed by two-way ANOVA, significant main effects for COMT (F = 2. 98, p = 0.05) and 5-HTTLPR (F = 4.27, p = 0.04) and a significant interaction COMT x 5-HTTLPR (F = 6.18, p = 0.002) are observed. In the presence of COMT homozygosity (val/val or met/met genotypes), the presence of the short 5-HTTLPR allele raises RD2 scores. The effect of these two polymorphisms on RD2 was also examined using a within-families design. Siblings in our data set who shared identical genotypes had significantly correlated RD2 scores (intraclass coefficient = 0.34, F = 2.03, p = 0.002, n = 67), whereas sibs with dissimilar genotypes in at least one polymorphism showed no significant correlation for RD2 scores (intraclass coefficient = 0.105, F = 1.23, p = 0.16, n = 92).

Adolescent↗

Predominant polarity of bipolar patients in Israel.

Studies in European and American populations have suggested that the course of bipolar illness is most often characterised by a predominance of depressions over manias. The current chart review study suggests that among manic-depressive patients in Southern Israel, a predominately manic course of illness is more common. Unlike some previous studies, no sex differences were noted in type of illness course. Possible explanations for the main finding, including climate-related factors, are discussed.

Adult↗

Low persistence in euthymic manic-depressive patients: a replication.

BACKGROUND: A previous study which compared euthymic Israeli bipolars in a public hospital clinic to US normative data suggested that low Persistence scores on the Tridimensional Personality Questionnaire (TPQ) may be a temperament marker for manic-depressive illness. The current study attempts to replicate that finding. METHODS: A new sample of 25 euthymic Israeli bipolars in private treatment was compared to Israeli normal controls matched for gender and ethnic background. All subjects completed Hebrew versions of the TPQ. RESULTS: Patients scored lower than controls on the Novelty Seeking and Persistence Scales. LIMITATIONS AND CONCLUSIONS: Though sample and effect size are both small, the finding of low Persistence is consistent with that of the earlier study.

Affect↗

The polymorphic inositol polyphosphate 1-phosphatase gene as a candidate for pharmacogenetic prediction of lithium-responsive manic-depressive illness.

Long-term treatment with lithium salts has been established as an effective prophylactic therapy in manic-depressive (bipolar) illness. Many patients, however, display a lack of (or partial) treatment response. We recently proposed that pharmacogenetic factors may influence and determine the therapeutic efficacy of lithium in bipolar disorder. The lithium-blockable enzyme inositol polyphosphate 1-phosphatase in the phospholipase C signaling pathway is a putative target for the mood-stabilizing effects of lithium. In the present study, we searched for DNA variations in the human INPP1 gene encoding the inositol polyphosphate 1-phosphatase enzyme. We report the existence of four common polymorphisms in the coding region of the gene. The DNA alterations were all single base substitutions, of which one (A682G) predicted an amino acid change (Thr228Ala), whereas the remaining three (G153T, G348A and C973A) were silent, In a Norwegian pilot sample the frequencies of the four single base substitutions were not significantly different between lithium-treated bipolar patients and healthy control individuals. When subdivided with respect to drug response, however, the C973A transversion was present in six out of nine lithium responders (67%) versus one out of nine non-responders (11%) In contrast, the C973A polymorphism was equally common among lithium responders and non-responders in an independent sample of bipolar patients from Israel. Future studies are therefore need to determine whether allelic variants of the INPP1 gene are associated with a favourable efficacy of lithium in manic-depressive illness.

Adult↗

5-HT2C (HTR2C) serotonin receptor gene polymorphism associated with the human personality trait of reward dependence: interaction with dopamine D4 receptor (D4DR) and dopamine D3 receptor (D3DR) polymorphisms.

We recently reported an association between the long repeat allele of the dopamine D4 exon III receptor polymorphism and a human personality dimension, novelty seeking, as measured by the tridimensional personality questionnaire (TPQ), a personality instrument designed by Cloninger to reflect heritable facets of human temperament. The D4 receptor polymorphism (D4DR) accounts for only a small percent of the variance for this trait, suggesting that additional genes influence both novelty seeking as well as the other temperaments that are inventoried by the Cloninger TPQ. In the current investigation, we examined, in the original cohort of 120 normal volunteers, two additional coding region polymorphisms, a glycine to serine substitution in the dopamine D3 receptor (D3DR) and a cysteine to serine substitution in the 5-HT2C serotonin receptor (HTR2C). Three-way analysis of variance (TPQ score grouped by D4DR, D3DR and 5-HT2C) demonstrated that reward dependence and persistence scores were significantly reduced by the presence of the less common 5-HT2Cser polymorphism. The effect of the serine substitution in this X-linked serotonin receptor polymorphism on reward dependence was also observed when male and female subject groups were separately analyzed. There was also a significant interaction between the two dopamine receptor polymorphisms and the serotonin polymorphism on reward dependence. In particular, the effect of the 5-HT2C polymorphism on reward dependence was markedly accentuated in individuals who had the long version of the D4DR exon III repeat polymorphism. When present in the same individual, the 5-HT2C and dopamine receptor polymorphisms account for 30% of the observed variance for persistence (RD2) and 13% of the variance for reward dependence scores (RD134). However, the number of subjects with both less common D4DR and 5-HT2C polymorphisms is small, underscoring the importance of verifying this interaction in a larger cohort.

Adult↗

No association between the serotonin transporter gene regulatory region polymorphism and the Tridimensional Personality Questionnaire (TPQ) temperament of harm avoidance.

A functional polymorphism in the upstream regulatory region of the serotonin transporter gene has been recently reported to be associated with anxiety-related traits assessed by the NEO-PI-R. Individuals both hetero- and homozygous for the short form of a highly repetitive regulatory element in this gene have significantly higher neuroticism scores. We have attempted to replicate these findings in a normal cohort of 120 individuals, whom we have previously examined for association between personality dimensions and other serotonergic and dopaminergic receptor polymorphisms. The Tridimensional Personality Questionnaire (TPQ) was used to assess personality dimensions in this cohort. No association was observed in the present study between individuals grouped by the long and short form of the transporter gene and any of the personality dimensions measured by the TPQ including Harm Avoidance, which incorporates many aspects of anxiety and is correlated with NEO-PI-R Neuroticism.

Adult↗

TPQ in euthymic manic-depressive patients.

Researchers using various psychological measures and instruments have concluded that the personality of remitted bipolars and normal controls are essentially similar. We recently suggested that specific personality traits might be genetic markers for manic-depressive illness. The Tridimensional Personality Questionnaire (TPQ) is a personality questionnaire with heritable subscales and hypothesized anchoring in neurochemistry. We studied the personality of euthymic bipolar manic depressive patients using the TPQ. Subjects were volunteers from the out-patient Lithium Clinic. TPQs were individually administered to 50 euthymic bipolar patients. Persistence is significantly reduced, and harm avoidance and reward dependence significantly increased, compared with U.S. norms. These traits may be part of the genetic diathesis for manic-depressive illness.

Adult↗

Social adjustment and self-esteem in remitted patients with unipolar and bipolar affective disorder: a case-control study.

To evaluate social adjustment and self-esteem in patients with unipolar (UP) and bipolar (BP) affective disorder and to examine demographic and clinical correlates of these variables, outpatients with UP and BP disorder in remission for at least 12 months were consecutively recruited and individually matched to control subjects with no personal or family history of psychiatric illness (UP-control matched pairs, n = 23; BP-control matched pairs, n = 27). Subjects completed the Rosenberg Self-Esteem scale (SES) and the self-report version of the Social Adjustment Scale (SAS). UP patients reported significantly worse overall social adjustment than their matched controls (P = .009), specifically in the area of social and leisure activities (P = .0003) and poorer self-esteem (P = .02). When separated by gender, only the female UP group manifested significant findings on the SAS. BP patients reported poorer self-esteem than their controls (P = .04), but were not significantly different on the SAS. Although the patients were not clinically depressed, a worse social adjustment was significantly associated with a higher score on the Hamilton Depression Scale (HAM-D) in both groups. In the UP group, this association was absent when the analysis was limited to patients receiving antidepressant pharmacotherapy. The findings indicate that (1) UP patients, particularly women, experience substantial difficulties in social adjustment, primarily in social and leisure activities, even during stable clinical remission, and (2) in both UP and BP patients, adjustment problems are related to depressive symptoms even though these are minimal in severity.

Adult↗