Research Interests: Psychology, Personality, Polymorphism, Medicine, Molecular Psychiatry, and 12 moreAnxiety, Biological Sciences, Neuroticism, Serotonin Transporter, Big Five Personality Traits, Temperament, STEM (short form), ANXIETY, Harm Avoidance, Temperament and Character Inventory (TCI), Psychology and Cognitive Sciences, and Medical and Health Sciences
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... 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...
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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... 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.
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Additional file 1. Questionnaire: Information seeking in bipolar disorder.
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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... 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...
Research Interests: Psychology, Bipolar Disorder, Global Health, International Cooperation, Medicine, and 15 moreHumans, Female, Male, Cluster Analysis, Cohort, Mood Disorders, Aged, Middle Aged, Adult, Age of Onset, Cohort Studies, Psychology and Cognitive Sciences, GEE, european psychiatry, and Medical and Health Sciences
Research Interests: Bipolar Disorder, Medicine, Family history, Humans, Major Depressive Disorder, and 15 moreFemale, Male, Depressive Disorder, Clinical Sciences, Major Depression, Comprehensive, Adult, Analysis of Variance, Depressive Symptoms, Case Control Study, Bipolar Affective Disorder, Affective Disorder, Leisure Activities, Case Control Studies, and european psychiatry
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... 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.
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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,... 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.
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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... 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...
Research Interests: Geography, Depression, Bipolar Disorder, Global Health, Climate, and 15 moreAdolescent, Medicine, Humans, Affective Disorders, Female, Male, Depressive Disorder, Mood Disorders, Middle Aged, Adult, Retrospective Studies, Elsevier, Age of Onset, Psychology and Cognitive Sciences, and Medical and Health Sciences
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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... 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.
Research Interests: Genetics, Bipolar Disorder, Metabolism, Biology, Forecasting, and 15 moreLithium, Medicine, Israel, Norway, Humans, Female, Male, Jews, Gene, Aged, Middle Aged, Gen, Adult, alleles, and Gene frequency
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... 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.
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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... 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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Reports of toxic effects on the kidney of lithium treatment emerged very soon after lithium therapy was introduced. Lithium-induced nephrogenic diabetes insipidus is usually self-limiting or not clinically dangerous. Some reports of... more
Reports of toxic effects on the kidney of lithium treatment emerged very soon after lithium therapy was introduced. Lithium-induced nephrogenic diabetes insipidus is usually self-limiting or not clinically dangerous. Some reports of irreversible chronic kidney disease and renal failure were difficult to attribute to lithium treatment since chronic kidney disease and renal failure exist in the population at large. In recent years, large-scale epidemiological studies have convincingly shown that lithium treatment elevates the risk of chronic kidney disease and renal failure. Most patients do not experience renal side effects. The most common side effect of polyuria only weakly predicts increasing creatinine or reduced kidney function. Among those patients who do experience decrease in creatinine clearance, some may require continuation of lithium treatment even as their creatinine increases. Other patients may be able to switch to a different mood stabilizer medication, but kidney fun...
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Background: Bipolar disorder may be associated with a hypersensitive behavioral approach system and therefore to increased reward sensitivity. The objective of this study is to explore the interrelationships between bipolar disorder,... more
Background: Bipolar disorder may be associated with a hypersensitive behavioral approach system and therefore to increased reward sensitivity. The objective of this study is to explore the interrelationships between bipolar disorder, behavioral addictions, and personality/temperament traits in a group of euthymic outpatients with bipolar I disorder and in a group of comparison subjects. Methods: Fifty clinically stable patients and 50 comparison subjects matched for age, sex, and educational level were administered the Temperament and Character Inventory-140 and the Behavioral Addiction Scale. Results: The patient group scored significantly higher than comparison subjects for two benign behavioral addictions (music, shopping) as well as for smoking. Comparison subjects scored higher on two harmful behavioral addictions (drugs, alcohol). Novelty Seeking was positively correlated with harmful addictions, and Cooperativeness was negatively correlated with harmful addictions, in both gr...
Abstract Little is known about the effect of personality traits on learning. Thus the aim of this investigation was to better understand the role of depressive personality traits – primarily self-criticism and approach and inhibition... more
Abstract Little is known about the effect of personality traits on learning. Thus the aim of this investigation was to better understand the role of depressive personality traits – primarily self-criticism and approach and inhibition tendencies – in reward and punishment learning. In two studies (Study 1: N = 38; Study 2: N = 100), we used a probabilistic classification task in which participants needed to categorize ambiguous stimuli, and then received probabilistic feedback, according to their choice. In Study 2, we employed a variation of this task with difficult vs. easy contingencies. In both studies we examined the association between performance in the task and approach and avoidance personality traits (BIS/BAS, self-criticism and positive generalization) while controlling for depression and intelligence. Self-criticism and a tendency to generalize positive events were positively associated with reward, but not punishment, learning. As well, after exposure to difficult contingencies, participants had delayed punishment learning. In light of these results, we suggest that self-criticism might enhance monitoring of errors, which improves reward learning.
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Background Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with... more
Background Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries. Methods Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun’s electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries). Results This analysis confirmed the results of the exploratory study with the same best model and slightly...
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The world population is aging and the number of older adults with bipolar disorder is increasing. Digital technologies are viewed as a framework to improve care of older adults with bipolar disorder. This analysis quantifies Internet use... more
The world population is aging and the number of older adults with bipolar disorder is increasing. Digital technologies are viewed as a framework to improve care of older adults with bipolar disorder. This analysis quantifies Internet use by older adults with bipolar disorder as part of a larger survey project about information seeking. A paper-based survey about information seeking by patients with bipolar disorder was developed and translated into 12 languages. The survey was anonymous and completed between March 2014 and January 2016 by 1222 patients in 17 countries. All patients were diagnosed by a psychiatrist. General estimating equations were used to account for correlated data. Overall, 47% of older adults (age 60 years or older) used the Internet versus 87% of younger adults (less than 60 years). More education and having symptoms that interfered with regular activities increased the odds of using the Internet, while being age 60 years or older decreased the odds. Data from ...
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Peer support is an established component of recovery from bipolar disorder, and online support groups may offer opportunities to expand the use of peer support at the patient's convenience. Prior research in bipolar disorder has... more
Peer support is an established component of recovery from bipolar disorder, and online support groups may offer opportunities to expand the use of peer support at the patient's convenience. Prior research in bipolar disorder has reported value from online support groups. To understand the use of online support groups by patients with bipolar disorder as part of a larger project about information seeking. The results are based on a one-time, paper-based anonymous survey about information seeking by patients with bipolar disorder, which was translated into 12 languages. The survey was completed between March 2014 and January 2016 and included questions on the use of online support groups. All patients were diagnosed by a psychiatrist. Analysis included descriptive statistics and general estimating equations to account for correlated data. The survey was completed by 1222 patients in 17 countries. The patients used the Internet at a percentage similar to the general public. Of the ...
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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,... 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, while others performed a similar, but simpler task. This research assumes that, since the Stroop task requires that the individual reach a decision while overcoming an automatic tendency and an ingrained habit, this depletes his/her self-control resources. As such, when an individual is filling-out the questionnaire dealing with time preferences after a Stroop task, his/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, those 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 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/her natural tendency to prefer the present, thus influencing his/her intertemporal choices.
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Information seeking is an important coping mechanism for dealing with chronic illness. Despite a growing number of mental health websites, there is little understanding of how patients with bipolar disorder use the Internet to seek... more
Information seeking is an important coping mechanism for dealing with chronic illness. Despite a growing number of mental health websites, there is little understanding of how patients with bipolar disorder use the Internet to seek information. A 39 question, paper-based, anonymous survey, translated into 12 languages, was completed by 1222 patients in 17 countries as a convenience sample between March 2014 and January 2016. All patients had a diagnosis of bipolar disorder from a psychiatrist. Data were analyzed using descriptive statistics and generalized estimating equations to account for correlated data. 976 (81 % of 1212 valid responses) of the patients used the Internet, and of these 750 (77 %) looked for information on bipolar disorder. When looking online for information, 89 % used a computer rather than a smartphone, and 79 % started with a general search engine. The primary reasons for searching were drug side effects (51 %), to learn anonymously (43 %), and for help copin...
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There is considerable international interest in online education of patients with bipolar disorder, yet little understanding of how patients use the Internet and other sources to seek information. 1171 patients with a diagnosis of bipolar... more
There is considerable international interest in online education of patients with bipolar disorder, yet little understanding of how patients use the Internet and other sources to seek information. 1171 patients with a diagnosis of bipolar disorder in 17 countries completed a paper-based, anonymous survey. 81% of the patients used the Internet, a percentage similar to the general public. Older age, less education, and challenges in country telecommunications infrastructure and demographics decreased the odds of using the Internet. About 78% of the Internet users looked online for information on bipolar disorder or 63% of the total sample. More years of education in relation to the country mean, and feeling very confident about managing life decreased the odds of seeking information on bipolar disorder online, while having attended support groups increased the odds. Patients who looked online for information on bipolar disorder consulted medical professionals plus a mean of 2.3 other information sources such as books, physician handouts, and others with bipolar disorder. Patients not using the Internet consulted medical professionals plus a mean of 1.6 other information sources. The percentage of patients with bipolar disorder who use the Internet is about the same as the general public. Other information sources remain important.
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Creatine plays a pivotal role in brain energy homeostasis and has been tried in the treatment of neurologic, neuromuscular, and atherosclerotic disease with a paucity of side effects. Creatine monohydrate supplementation may enhance... more
Creatine plays a pivotal role in brain energy homeostasis and has been tried in the treatment of neurologic, neuromuscular, and atherosclerotic disease with a paucity of side effects. Creatine monohydrate supplementation may enhance cognitive functions in healthy subjects. Several independent lines of evidence suggest the possible involvement of altered cerebral energy metabolism in schizophrenia. Creatine effects on brain energy metabolism and its possible cognitive-enhancing properties raise the possibility of developing a new therapeutic strategy in schizophrenia by focusing on treating metabolic hypoactive brain areas including frontal regions. Twelve schizophrenia patients (DSM-IV criteria) were enrolled into a treatment study with creatine or placebo, and each treatment was administered for 3 months (dosage, 3-5 grams per day) in a randomized, double-blind crossover design. Ten patients completed the study, which was conducted from November 2004 through February 2006. Rating scales included the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions (CGI) scale, scales for the assessment of side effects, and a cognitive battery. Creatine treatment was not superior to placebo in improving the scores of PANSS, CGI, or the neurocognitive measures administered. Side effects of creatine treatment were few. Three months of creatine administration failed to detect any efficacy in treating symptoms of schizophrenia, but further research is suggested. ClinicalTrials.gov identifier NCT00140192.
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Patients with bipolar disorder are characterized by an unusually high divorce rate. As such, the purpose of the present study was to uncover information relating specifically to the impact of bipolar disorder on patients and spouses... more
Patients with bipolar disorder are characterized by an unusually high divorce rate. As such, the purpose of the present study was to uncover information relating specifically to the impact of bipolar disorder on patients and spouses individually, and on the marital relationship from the perspectives of both patients and spouses. Eleven patients with bipolar disorder and ten spouses were interviewed separately about the impact of bipolar disorder on their lives and on their marital relationship. Data were analyzed using the grounded theory method. The impact of bipolar disorder for spouses included self-sacrifice, caregiving burden, emotional impact, and a sense of personal evolution. The impact of bipolar disorder on patients included an emotional impact, responsibility for self-care, and struggling socially and developmentally. When comparing patient and spouse perspectives on the impact of the disorder, neither the patient nor the spouse was able to accurately assess the impact of the disorder on their partner's lives. The impact of bipolar disorder on the relationship included volatility in the relationship, strengthening the relationship, weakening the relationship, and family planning. The research indicated that patients and partners alike struggle with the tremendous impact of bipolar disorder on their lives and on their relationships. Given the high rates of divorce and volatility in these relationships, healthcare professionals can provide (or refer to) emotional and practical support both to patients and spouses on their own, and as a couple in their clinics.
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We review three studies of omega-3 fatty acids in the treatment of depression that were carried out by our research group at the Beer Sheva Mental Health Center. The first study examined eicosapentaenoic acid (EPA) versus placebo as an... more
We review three studies of omega-3 fatty acids in the treatment of depression that were carried out by our research group at the Beer Sheva Mental Health Center. The first study examined eicosapentaenoic acid (EPA) versus placebo as an adjunct to antidepressant treatment in 20 unipolar patients with recurrent major depression. The second study used omega-3 fatty acids in childhood major depression; 28 children aged 6-12 were randomized to omega-3 fatty acids or placebo as pharmacologic monotherapy. The third study was an open-label add-on trial of EPA in bipolar depression. Twelve bipolar outpatients with depressive symptoms were treated with 1.5-2.0 g/day of EPA for up to 6 months. In the adult unipolar depression study, highly significant benefits were found by week 3 of EPA treatment compared with placebo. In the child study, an analysis of variance (ANOVA) showed highly significant effects of omega-3 on each of the three rating scales. In the bipolar depression study, 8 of the 10 patients who completed at least 1 month of follow-up achieved a 50% or greater reduction in Hamilton depression (Ham-D) scores within 1 month. No significant side effects were reported in any of the studies. Omega-3 fatty acids were shown to be more effective than placebo for depression in both adults and children in small controlled studies and in an open study of bipolar depression. (This review discusses three studies, all from our group, completed before the clinical trial registry was initiated.)
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Research Interests: Genetics, Personality, Polymorphism, Adolescent, Molecular Psychiatry, and 21 moreIsrael, Anxiety, Biological Sciences, Humans, Neurotic Disorders, Female, Serotonin Transporter, Male, Jews, Membrane transport proteins, Genetic linkage analysis, Aged, Middle Aged, Questionnaires, Adult, Nuclear Family, ANXIETY, Exploratory Behavior, Harm Avoidance, Linkage Analysis, and Personality Trait
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ABSTRACT
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Environmental conditions early in life may imprint the circadian system and influence response to environmental signals later in life. We previously determined that a large springtime increase in solar insolation at the onset location was... more
Environmental conditions early in life may imprint the circadian system and influence response to environmental signals later in life. We previously determined that a large springtime increase in solar insolation at the onset location was associated with a younger age of onset of bipolar disorder, especially with a family history of mood disorders. This study investigated whether the hours of daylight at the birth location affected this association. Data collected previously at 36 collection sites from 23 countries were available for 3896 patients with bipolar I disorder, born between latitudes of 1.4 N and 70.7 N, and 1.2 S and 41.3 S. Hours of daylight variables for the birth location were added to a base model to assess the relation between the age of onset and solar insolation. More hours of daylight at the birth location during early life was associated with an older age of onset, suggesting reduced vulnerability to the future circadian challenge of the springtime increase in solar insolation at the onset location. Addition of the minimum of the average monthly hours of daylight during the first 3 months of life improved the base model, with a significant positive relationship to age of onset. Coefficients for all other variables remained stable, significant and consistent with the base model. Light exposure during early life may have important consequences for those who are susceptible to bipolar disorder, especially at latitudes with little natural light in winter. This study indirectly supports the concept that early life exposure to light may affect the long term adaptability to respond to a circadian challenge later in life.
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While neuropsychological impairment in bipolar disorder is well documented, the effect size of this impairment is rarely compared directly to that in other clinically familiar cognitive disorders. This study compares neuropsychological... more
While neuropsychological impairment in bipolar disorder is well documented, the effect size of this impairment is rarely compared directly to that in other clinically familiar cognitive disorders. This study compares neuropsychological functioning of euthymic bipolar patients to those with mild cognitive impairment (MCI) as well as healthy controls. Following evaluation during regular follow-up in a mood disorders clinic, 58 euthymic adult bipolar subjects were administered a validated and fully computerized cognitive assessment (Mindstreams; NeuroTrax Corp., N.Y., USA). Study data were compared to existing data for MCI and cognitively healthy individuals tested with the same assessment. Final analyses were based on 51 bipolar patients, 162 MCI patients and 495 healthy comparison subjects. Significant (p < 0.001) group effects were found for every parameter. Post hoc analysis revealed that the bipolar and MCI groups showed statistically equivalent functioning in memory, executive function, verbal function, and information processing speed. In the domains of visual-spatial processing, attention, and motor skills, the MCI group outperformed the bipolar group. In every domain, the healthy control group outperformed both the bipolar and the MCI groups. The cognitive function of euthymic bipolar patients and those diagnosed with MCI was found to be similar in most but not all domains. Both groups performed significantly less well than the comparison group of healthy subjects. It may be helpful for clinicians to conceptualize the overall level of cognitive impairment in bipolar patients as similar to that in MCI.
Research Interests: Psychology, Psychotherapy, Bipolar Disorder, Attention, Mild Cognitive Impairment, and 20 moreAdolescent, Executive Function, Information Processing, Humans, Effect size, Female, Male, Young Adult, Cognitive Assessment, Aged, Middle Aged, Cognitive impairment, Adult, Cognitive Function, Memory Disorders, Healthy Subjects, Mood Disorder, Motor Skills, Psychomotor Performance, and Neuropsychological Tests
Research Interests: Animal Behavior, Schizophrenia, Bipolar Disorder, Aging, Adolescent, and 20 moreCerebrospinal Fluid, Humans, HPLC, Mice, Animals, Male, Statistical Significance, Animal Model, MTHFR, Spatial Learning, Risk factors, Homocysteine, Middle Aged, Cognitive impairment, Adult, Sex Factors, Age Factors, Risk Factors, Morris water maze, and Vascular Disease
The Hebrew Tridimensional Personality Questionnaire was administered to over a thousand individuals in the community, 16–78 years of age. Factor analysis was run first on individual items, and then on the 12 sub-scales described by... more
The Hebrew Tridimensional Personality Questionnaire was administered to over a thousand individuals in the community, 16–78 years of age. Factor analysis was run first on individual items, and then on the 12 sub-scales described by [Cloninger, CR, Pryzbeck, TR, & Svrakic, DM (1991). The TPQ: US normative data. Psychological Reports, 69, 1047–1051)]. The factor analyses were restricted to four orthogonal factors in order to attempt confirmation of the corrected four-factor solution [Stallings, MC, Hewitt, JK, Cloninger, RC, Heath, AC, & ...