Background Sunlight contains ultraviolet B (UVB) radiation that triggers the production of vitami... more Background Sunlight contains ultraviolet B (UVB) radiation that triggers the production of vitamin D by skin. Vitamin D has widespread effects on brain function in both developing and adult brains. However, many people live at latitudes (about > 40 N or S) that do not receive enough UVB in winter to produce vitamin D. This exploratory study investigated the association between the age of onset of bipolar I disorder and the threshold for UVB sufficient for vitamin D production in a large global sample. Methods Data for 6972 patients with bipolar I disorder were obtained at 75 collection sites in 41 countries in both hemispheres. The best model to assess the relation between the threshold for UVB sufficient for vitamin D production and age of onset included 1 or more months below the threshold, family history of mood disorders, and birth cohort. All coefficients estimated at P ≤ 0.001. Results The 6972 patients had an onset in 582 locations in 70 countries, with a mean age of onset...
Bipolar disorder is characterised by recurrent episodes of mania and depression. The major object... more Bipolar disorder is characterised by recurrent episodes of mania and depression. The major objective of long term treatment is to reduce the frequency of these episodes. Lithium is the most widely recommended drug for this purpose, having been shown in controlled clinical trials to be more effective than placebo in reducing the likelihood of relapse. Unfortunately, its effectiveness in clinical practice is less than that predicted from these trials. A major cause of relapse is noncompliance, largely due to intolerance to adverse effects such as perceived mental sluggishness, thirst, polyuria and weight gain. Regular monitoring of lithium plasma concentrations is required to ensure that the range of 0.5 to 0.9 mmol/L is not exceeded. Concentrations above this can lead to toxic symptoms, which if unchecked can cause brain damage and even death. The anticonvulsant drugs carbamazepine and valproic acid (sodium valproate) are potential alternatives to lithium. Patients who relapse frequently despite lithium may benefit from the addition of one of these agents, although formal clinical trial evidence of the efficacy of such combination treatment is lacking. Antipsychotics, administered as a depot formulation, can reduce the likelihood of relapse in patients with frequent manic episodes, especially if associated with poor compliance. Psychological treatment and patient education have been shown to improve outcome, and should be made more widely available to all patients with bipolar disorder.
Purpose:Two common approaches to identify subgroups of patients with bipolar disorder are cluster... more Purpose:Two common approaches to identify subgroups of patients with bipolar disorder are clustering methodology (mixture analysis) based on the age of onset, and a birth cohort analysis. This study investigates if a birth cohort effect will influence the results of clustering on the age of onset, using a large, international database.Methods:The database includes 4037 patients with a diagnosis of bipolar I disorder, previously collected at 36 collection sites in 23 countries. Generalized estimating equations (GEE) were used to adjust the data for country median age, and in some models, birth cohort. Model-based clustering (mixture analysis) was then performed on the age of onset data using the residuals. Clinical variables in subgroups were compared.Results:There was a strong birth cohort effect. Without adjusting for the birth cohort, three subgroups were found by clustering. After adjusting for the birth cohort or when considering only those born after 1959, two subgroups were fo...
Explicit memory has been tested extensively in young children. The results show that young childr... more Explicit memory has been tested extensively in young children. The results show that young children's explicit memory is weak and decays quickly but is in many ways similar to that of adults. However, most studies showed that young children's implicit memory is intact. This inconsistency has lead to a debate about the extent to which the memory of young children resembles that of healthy adults. When adults with impaired explicit memory and intact implicit memory are tested for semantic knowledge, they show better memory under errorless learning procedures. In contrast, healthy adults show better memory under errorful procedures. We tested these two procedures in 3- and 5-year-olds. 3-year-olds remembered less than 5-year-olds, but both groups showed similar errorful learning advantages, which persisted after 5 weeks. Our data show that while 3-year-old children's memory is weak, it is more similar to intact than to impaired explicit memory in adults.
Journal of Neuroscience, Psychology, and Economics, 2018
The present research investigates the ways in which the time preferences of young adults are infl... more The present research investigates the ways in which the time preferences of young adults are influenced by the level of their executive cognitive abilities and by situational changes in these abilities. Within the framework of this study, young adults were asked to respond to a questionnaire dealing with their time preferences in light of changing amounts and delay durations. Some were asked to do a Stroop task beforehand, whereas others performed a similar but simpler task. This research assumes that because the Stroop task requires that the individual reach a decision while overcoming an automatic tendency and an ingrained habit, his or her self-control resources are depleted. As such, when an individual is filling out the questionnaire dealing with time preferences after a Stroop task, his or her ability to avoid automatic tendencies is depleted, making it difficult for him/her to reject the receipt of money in the present. The study found that, in general, individuals having good executive cognitive abilities, namely, those who got the highest scores on the Stroop task, were characterized by a lower rate of subjective discounting. In addition, the research showed a marked difference between those individuals who had experienced depletion and those who had not, in that the depleted individuals tended to demand higher discount rates for having postponed the payment. This means that the depletion of executive-ability resources caused a behavior similar to that of those having the lowest executive abilities. This outcome may attest to the fact that a depletion in the available level of executive abilities in an individual reduces the ability of that individual to overcome his or her natural tendency to prefer the present, thus influencing his or her intertemporal choices.
The onset of bipolar disorder is influenced by the interaction of genetic and environmental facto... more The onset of bipolar disorder is influenced by the interaction of genetic and environmental factors. We previously found that a large increase in sunlight in springtime was associated with a lower age of onset. This study extends this analysis with more collection sites at diverse locations, and includes family history and polarity of first episode. Data from 4037 patients with bipolar I disorder were collected at 36 collection sites in 23 countries at latitudes spanning 3.2 north (N) to 63.4 N and 38.2 south (S) of the equator. The age of onset of the first episode, onset location, family history of mood disorders, and polarity of first episode were obtained retrospectively, from patient records and/or direct interview. Solar insolation data were obtained for the onset locations. There was a large, significant inverse relationship between maximum monthly increase in solar insolation and age of onset, controlling for the country median age and the birth cohort. The effect was reduce...
Long-term treatment with lithium salts has been established as an effective prophylactic therapy ... more 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.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2004
The chromosome 8p region is of interest in human behavioral genetics since it harbors a susceptib... more The chromosome 8p region is of interest in human behavioral genetics since it harbors a susceptibility region not only for schizophrenia but also for anxiety-related personality traits such as harm avoidance and neuroticism. Towards verifying our preliminary linkage finding of a QTL for TPQ harm avoidance at chromosome 8p, we have now genotyped altogether 24 micro-satellite markers in 377 families. Using three methods (maximum likelihood binomial or MLB, MERLIN, and an associated one parameter model), we observed significant results (P values from 0.002 to 0.0004) for linkage to harm avoidance in this region. A peak multipoint LOD score of 2.76 (P value 0.0002) was obtained with the MLB method. The region-wide empirical P value was 0.002 [0.001-0.0046]. Although, the peak position varied somewhat according to the method (D8S1048 for MLB, D8S1463 for the two other methods), for three methods D8S1810 ( approximately 60 cM) is within 1-2 cM of the peak for harm avoidance. This marker is of particular interest since it is proximate (<0.5 cM) of the core haplotype that in several recent studies show significant association with schizophrenia near neuroregulin 1. Although association studies with microsatellite markers need to be interpreted cautiously, using the Haplotype Trend Regression test one marker, D8S499 ( approximately 60 cM), showed an empirical P value of 2 x 10(-5) for allele 3, which confers a decreased harm avoidance score. Altogether, the current linkage and association results suggest the possibility that the same locus near the neuroregulin 1 gene on chromosome 8p confers risk for both an anxiety-related personality trait as well as schizophrenia. We hypothesize that this common genetic factor may contribute to emotional liability during early development, which constitutes a predisposing factor for major psychosis.
INTRODUCTION Simple logic would suggest that there should be some endophenotype for bipolar disor... more INTRODUCTION Simple logic would suggest that there should be some endophenotype for bipolar disorder. Possible endophenotypes could include specific variations in personality. Bagby and Ryder summarized the work up to that point by noting that the related personality traits of high neuroticism and harm avoidance seem to be associated with bipolar disorder as well as with unipolar depression, whereas higher novelty seeking may be associated only with bipolar patients. As these parameters are all very sensitive to the affective state, it is critical to examine the literature that pertains specifically to euthymic patients in order to evaluate the extent to which this signifies underlying personality (trait), and not primarily clinical status (state). Several important studies have been published since the Bagby and Ryder paper, which we review here. We restrict our current review to empirical studies which employed both adequate samples of euthymic (to minimize the state/trait dilemma...
Background Sunlight contains ultraviolet B (UVB) radiation that triggers the production of vitami... more Background Sunlight contains ultraviolet B (UVB) radiation that triggers the production of vitamin D by skin. Vitamin D has widespread effects on brain function in both developing and adult brains. However, many people live at latitudes (about > 40 N or S) that do not receive enough UVB in winter to produce vitamin D. This exploratory study investigated the association between the age of onset of bipolar I disorder and the threshold for UVB sufficient for vitamin D production in a large global sample. Methods Data for 6972 patients with bipolar I disorder were obtained at 75 collection sites in 41 countries in both hemispheres. The best model to assess the relation between the threshold for UVB sufficient for vitamin D production and age of onset included 1 or more months below the threshold, family history of mood disorders, and birth cohort. All coefficients estimated at P ≤ 0.001. Results The 6972 patients had an onset in 582 locations in 70 countries, with a mean age of onset...
Bipolar disorder is characterised by recurrent episodes of mania and depression. The major object... more Bipolar disorder is characterised by recurrent episodes of mania and depression. The major objective of long term treatment is to reduce the frequency of these episodes. Lithium is the most widely recommended drug for this purpose, having been shown in controlled clinical trials to be more effective than placebo in reducing the likelihood of relapse. Unfortunately, its effectiveness in clinical practice is less than that predicted from these trials. A major cause of relapse is noncompliance, largely due to intolerance to adverse effects such as perceived mental sluggishness, thirst, polyuria and weight gain. Regular monitoring of lithium plasma concentrations is required to ensure that the range of 0.5 to 0.9 mmol/L is not exceeded. Concentrations above this can lead to toxic symptoms, which if unchecked can cause brain damage and even death. The anticonvulsant drugs carbamazepine and valproic acid (sodium valproate) are potential alternatives to lithium. Patients who relapse frequently despite lithium may benefit from the addition of one of these agents, although formal clinical trial evidence of the efficacy of such combination treatment is lacking. Antipsychotics, administered as a depot formulation, can reduce the likelihood of relapse in patients with frequent manic episodes, especially if associated with poor compliance. Psychological treatment and patient education have been shown to improve outcome, and should be made more widely available to all patients with bipolar disorder.
Purpose:Two common approaches to identify subgroups of patients with bipolar disorder are cluster... more Purpose:Two common approaches to identify subgroups of patients with bipolar disorder are clustering methodology (mixture analysis) based on the age of onset, and a birth cohort analysis. This study investigates if a birth cohort effect will influence the results of clustering on the age of onset, using a large, international database.Methods:The database includes 4037 patients with a diagnosis of bipolar I disorder, previously collected at 36 collection sites in 23 countries. Generalized estimating equations (GEE) were used to adjust the data for country median age, and in some models, birth cohort. Model-based clustering (mixture analysis) was then performed on the age of onset data using the residuals. Clinical variables in subgroups were compared.Results:There was a strong birth cohort effect. Without adjusting for the birth cohort, three subgroups were found by clustering. After adjusting for the birth cohort or when considering only those born after 1959, two subgroups were fo...
Explicit memory has been tested extensively in young children. The results show that young childr... more Explicit memory has been tested extensively in young children. The results show that young children's explicit memory is weak and decays quickly but is in many ways similar to that of adults. However, most studies showed that young children's implicit memory is intact. This inconsistency has lead to a debate about the extent to which the memory of young children resembles that of healthy adults. When adults with impaired explicit memory and intact implicit memory are tested for semantic knowledge, they show better memory under errorless learning procedures. In contrast, healthy adults show better memory under errorful procedures. We tested these two procedures in 3- and 5-year-olds. 3-year-olds remembered less than 5-year-olds, but both groups showed similar errorful learning advantages, which persisted after 5 weeks. Our data show that while 3-year-old children's memory is weak, it is more similar to intact than to impaired explicit memory in adults.
Journal of Neuroscience, Psychology, and Economics, 2018
The present research investigates the ways in which the time preferences of young adults are infl... more The present research investigates the ways in which the time preferences of young adults are influenced by the level of their executive cognitive abilities and by situational changes in these abilities. Within the framework of this study, young adults were asked to respond to a questionnaire dealing with their time preferences in light of changing amounts and delay durations. Some were asked to do a Stroop task beforehand, whereas others performed a similar but simpler task. This research assumes that because the Stroop task requires that the individual reach a decision while overcoming an automatic tendency and an ingrained habit, his or her self-control resources are depleted. As such, when an individual is filling out the questionnaire dealing with time preferences after a Stroop task, his or her ability to avoid automatic tendencies is depleted, making it difficult for him/her to reject the receipt of money in the present. The study found that, in general, individuals having good executive cognitive abilities, namely, those who got the highest scores on the Stroop task, were characterized by a lower rate of subjective discounting. In addition, the research showed a marked difference between those individuals who had experienced depletion and those who had not, in that the depleted individuals tended to demand higher discount rates for having postponed the payment. This means that the depletion of executive-ability resources caused a behavior similar to that of those having the lowest executive abilities. This outcome may attest to the fact that a depletion in the available level of executive abilities in an individual reduces the ability of that individual to overcome his or her natural tendency to prefer the present, thus influencing his or her intertemporal choices.
The onset of bipolar disorder is influenced by the interaction of genetic and environmental facto... more The onset of bipolar disorder is influenced by the interaction of genetic and environmental factors. We previously found that a large increase in sunlight in springtime was associated with a lower age of onset. This study extends this analysis with more collection sites at diverse locations, and includes family history and polarity of first episode. Data from 4037 patients with bipolar I disorder were collected at 36 collection sites in 23 countries at latitudes spanning 3.2 north (N) to 63.4 N and 38.2 south (S) of the equator. The age of onset of the first episode, onset location, family history of mood disorders, and polarity of first episode were obtained retrospectively, from patient records and/or direct interview. Solar insolation data were obtained for the onset locations. There was a large, significant inverse relationship between maximum monthly increase in solar insolation and age of onset, controlling for the country median age and the birth cohort. The effect was reduce...
Long-term treatment with lithium salts has been established as an effective prophylactic therapy ... more 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.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2004
The chromosome 8p region is of interest in human behavioral genetics since it harbors a susceptib... more The chromosome 8p region is of interest in human behavioral genetics since it harbors a susceptibility region not only for schizophrenia but also for anxiety-related personality traits such as harm avoidance and neuroticism. Towards verifying our preliminary linkage finding of a QTL for TPQ harm avoidance at chromosome 8p, we have now genotyped altogether 24 micro-satellite markers in 377 families. Using three methods (maximum likelihood binomial or MLB, MERLIN, and an associated one parameter model), we observed significant results (P values from 0.002 to 0.0004) for linkage to harm avoidance in this region. A peak multipoint LOD score of 2.76 (P value 0.0002) was obtained with the MLB method. The region-wide empirical P value was 0.002 [0.001-0.0046]. Although, the peak position varied somewhat according to the method (D8S1048 for MLB, D8S1463 for the two other methods), for three methods D8S1810 ( approximately 60 cM) is within 1-2 cM of the peak for harm avoidance. This marker is of particular interest since it is proximate (<0.5 cM) of the core haplotype that in several recent studies show significant association with schizophrenia near neuroregulin 1. Although association studies with microsatellite markers need to be interpreted cautiously, using the Haplotype Trend Regression test one marker, D8S499 ( approximately 60 cM), showed an empirical P value of 2 x 10(-5) for allele 3, which confers a decreased harm avoidance score. Altogether, the current linkage and association results suggest the possibility that the same locus near the neuroregulin 1 gene on chromosome 8p confers risk for both an anxiety-related personality trait as well as schizophrenia. We hypothesize that this common genetic factor may contribute to emotional liability during early development, which constitutes a predisposing factor for major psychosis.
INTRODUCTION Simple logic would suggest that there should be some endophenotype for bipolar disor... more INTRODUCTION Simple logic would suggest that there should be some endophenotype for bipolar disorder. Possible endophenotypes could include specific variations in personality. Bagby and Ryder summarized the work up to that point by noting that the related personality traits of high neuroticism and harm avoidance seem to be associated with bipolar disorder as well as with unipolar depression, whereas higher novelty seeking may be associated only with bipolar patients. As these parameters are all very sensitive to the affective state, it is critical to examine the literature that pertains specifically to euthymic patients in order to evaluate the extent to which this signifies underlying personality (trait), and not primarily clinical status (state). Several important studies have been published since the Bagby and Ryder paper, which we review here. We restrict our current review to empirical studies which employed both adequate samples of euthymic (to minimize the state/trait dilemma...
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Papers by Yamima Osher