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M Strober

Publications and source records attributed to M Strober.

At least 19 recordsLinked to original sources
PubMed2003

Candidate genes for anorexia nervosa in the 1p33-36 linkage region: serotonin 1D and delta opioid receptor loci exhibit significant association to anorexia nervosa.

Serotonergic and opioidergic neurotransmitter system alterations have been observed in people with eating disorders; the genes for the serotonin 1D receptor (HTR1D) and the opioid delta receptor (OPRD1) are found on chr1p36.3-34.3, a region identified by our group in a linkage analysis of anorexia nervosa (AN). These candidate genes were evaluated for sequence variation and for linkage and association of this sequence variation to AN in family and case : control data sets. Resequencing of the HTR1D locus and a portion of the OPRD1 locus identified novel SNPs and confirmed existing SNPs. Genotype assay development and genotyping of nine SNPs (four at HTR1D and five at OPRD1) was performed on 191 unrelated individuals fulfilling DSM-IV criteria (w/o amenorrhea criterion) for AN, 442 relatives of AN probands and 98 psychiatrically screened controls. Linkage analysis of these candidate gene SNPs with 33 microsatellite markers in families including relative pairs concordantly affected with restricting AN (N=37) substantially increased the evidence for linkage of this region to restricting AN to an NPL score of 3.91. Statistically significant genotypic, allelic, and haplotypic association to AN in the case : control design was observed at HTR1D and OPRD1 with effect sizes for individual SNPs of 2.63 (95% CI=1.21-5.75) for HTR1D and 1.61 (95% CI=1.11-2.44) for OPRD1. Using genotype data on parents and AN probands, three SNPs at HTR1D were found to exhibit significant transmission disequilibrium (P&<0.05). The combined statistical genetic evidence suggests that HTR1D and OPRD1 or linked genes may be involved in the etiology of AN.

Anorexia Nervosa↗
PubMed2002

Evidence for a susceptibility gene for anorexia nervosa on chromosome 1.

Eating disorders, such as anorexia nervosa (AN), have a significant genetic component. In the current study, a genomewide linkage analysis of 192 families with at least one affected relative pair with AN and related eating disorders, including bulimia nervosa, was performed, resulting in only modest evidence for linkage, with the highest nonparametric linkage (NPL) score, 1.80, at marker D4S2367 on chromosome 4. Since the reduction of sample heterogeneity would increase power to detect linkage, we performed linkage analysis in a subset (n=37) of families in which at least two affected relatives had diagnoses of restricting AN, a clinically defined subtype of AN characterized by severe limitation of food intake without the presence of binge-eating or purging behavior. When we limited the linkage analysis to this clinically more homogeneous subgroup, the highest multipoint NPL score observed was 3.03, at marker D1S3721 on chromosome 1p. The genotyping of additional markers in this region led to a peak multipoint NPL score of 3.45, thereby providing suggestive evidence for the presence of an AN-susceptibility locus on chromosome 1p.

Adult↗
PubMed2001

Males with anorexia nervosa: a controlled study of eating disorders in first-degree relatives.

OBJECTIVE: To compare lifetime rates of full and partial anorexia nervosa and bulimia nervosa in first-degree relatives of males with anorexia nervosa and in relatives of never-ill comparison subjects. METHODS: Rates of eating disorders were obtained for 747 relatives of 210 probands from personal structured clinical interviews and family history. Best-estimate diagnoses were determined blind to proband diagnosis and pedigree status. RESULTS: Full and partial syndromes of anorexia nervosa aggregated in female relatives of ill probands. For the full syndrome of anorexia nervosa, the crude relative risk was 20.3 among female relatives and for partial syndrome anorexia nervosa, the crude relative risk was 3.3. In contrast, bulimia nervosa was relatively uncommon among relatives of ill probands. CONCLUSION: Although anorexia nervosa in males is exceedingly rare, there is a pattern of familial aggregation that is highly similar to that observed in recent family studies of affected females. On the basis of these findings, there is no evidence that familial-genetic factors distinguish the occurrence of anorexia nervosa in the two sexes.

Adolescent↗
PubMed2001

The evolving genetic foundations of eating disorders.

Data described earlier are clear in establishing a role for genes in the development of eating abnormalities. Estimates from the most rigorous studies suggest that more than 50% of the variance in eating disorders and disordered eating behaviors can be accounted for by genetic effects. These high estimates indicate a need for studies identifying the specific genes contributing to this large proportion of variance. Twin and family studies suggest that several heritable characteristics that are commonly comorbid with AN and BN may share genetic transmission with these disorders, including anxiety disorders or traits, body weight, and possibly major depression. Moreover, some developmental research suggests that the genes involved in ovarian hormones or the genes that these steroids affect also may be genetically linked to eating abnormalities. Molecular genetic research of these disorders is in its infant stages. However, promising areas for future research have already been identified (e.g., 5-HT2A receptor gene, UCP-2/UCP-3 gene, and estrogen receptor beta gene), and several large-scale linkage and association studies are underway. These studies likely will provide invaluable information regarding the appropriate phenotypes to be included in genetic studies and the genes with the most influence on the development of these disorders.

Anorexia Nervosa↗
PubMed2001

Decreased anterior cingulate myo-inositol/creatine spectroscopy resonance with lithium treatment in children with bipolar disorder.

This project was designed to compare differences in brain proton spectra between children and adolescents with bipolar disorder (BPD) and gender and age-matched normal controls, and to measure changes in myo-inositol levels following lithium therapy, utilizing in vivo proton magnetic resonance spectroscopy (1H MRS). A single voxel (2x2x2 cm3) was placed in brain anterior cingulate cortex for acquisition of the 1H spectra at baseline and after acute (7 days) lithium administration in 11 children (mean age 11.4 years) diagnosed with BPD, and in 11 normal controls. Acute lithium treatment was associated with a significant reduction in the myo-inositol/creatine ratio. This decrement was also significant in lithium-responders when analyzed separate from non-responders. Compared to normal controls, BPD subjects showed a trend towards a higher myo-inositol/creatine during the manic phase. These preliminary data provide evidence that a significant reduction in anterior cingulate myo-inositol magnetic resonance may occur after lithium treatment, especially among responders. Follow-up studies involving a larger sample may allow us to confirm whether changes in myo-inositol associated with acute lithium therapy persist in long-term clinical response of patients with and without lithium compliance.

Adolescent↗
PubMed2001

Efficacy of paroxetine in the treatment of adolescent major depression: a randomized, controlled trial.

OBJECTIVE: To compare paroxetine with placebo and imipramine with placebo for the treatment of adolescent depression. METHOD: After a 7- to 14-day screening period, 275 adolescents with major depression began 8 weeks of double-blind paroxetine (20-40 mg), imipramine (gradual upward titration to 200-300 mg), or placebo. The two primary outcome measures were endpoint response (Hamilton Rating Scale for Depression [HAM-D] score < or = 8 or > or = 50% reduction in baseline HAM-D) and change from baseline HAM-D score. Other depression-related variables were (1) HAM-D depressed mood item; (2) depression item of the Schedule for Affective Disorders and Schizophrenia for Adolescents-Lifetime version (K-SADS-L); (3) Clinical Global Impression (CGI) improvement scores of 1 or 2; (4) nine-item depression subscale of K-SADS-L; and (5) mean CGI improvement scores. RESULTS: Paroxetine demonstrated significantly greater improvement compared with placebo in HAM-D total score < or = 8, HAM-D depressed mood item, K-SADS-L depressed mood item, and CGI score of 1 or 2. The response to imipramine was not significantly different from placebo for any measure. Neither paroxetine nor imipramine differed significantly from placebo on parent- or self-rating measures. Withdrawal rates for adverse effects were 9.7% and 6.9% for paroxetine and placebo, respectively. Of 31.5% of subjects stopping imipramine therapy because of adverse effects, nearly one third did so because of adverse cardiovascular effects. CONCLUSIONS: Paroxetine is generally well tolerated and effective for major depression in adolescents.

Adolescent↗
PubMed2000

A search for susceptibility loci for anorexia nervosa: methods and sample description.

BACKGROUND: Eating disorders have not traditionally been viewed as heritable illnesses; however, recent family and twin studies lend credence to the potential role of genetic transmission. The Price Foundation funded an international, multisite study to identify genetic factors contributing to the pathogenesis of anorexia nervosa (AN) by recruiting affective relative pairs. This article is an overview of study methods and the clinical characteristics of the sample. METHODS: All probands met modified DSM-IV criteria for AN; all affected first, second, and third degree relatives met DSM-IV criteria for AN, bulimia nervosa (BN), or eating disorder not otherwise specified (NOS). Probands and affected relatives were assessed diagnostically with the Structured Interview for Anorexia and Bulimia. DNA was collected from probands, affected relatives and a subset of their biological parents. RESULTS: Assessments were obtained from 196 probands and 237 affected relatives, over 98% of whom are of Caucasian ancestry. Overall, there were 229 relative pairs who were informative for linkage analysis. Of the proband-relative pairs, 63% were AN-AN, 20% were AN-BN, and 16% were AN-NOS. For family-based association analyses, DNA has been collected from both biological parents of 159 eating-disordered subjects. Few significant differences in demographic characteristics were found between proband and relative groups. CONCLUSIONS: The present study represents the first large-scale molecular genetic investigation of AN. Our successful recruitment of over 500 subjects, consisting of affected probands, affected relatives, and their biological parents, will provide the basis to investigate genetic transmission of eating disorders via a genome scan and assessment of candidate genes.

Adult↗
PubMed2000

Personality traits among currently eating disordered, recovered and never ill first-degree female relatives of bulimic and control women.

BACKGROUND: A combined family study and recovered study design was utilized to examine several hypothesized relationships between personality and bulimia nervosa (BN). METHODS: We studied 47 women with a lifetime history of DSM-III-R BN (31 currently ill and 16 recovered), 44 matched control women (CW) with no history of an eating disorder (ED), and their first-degree female relatives (N = 89 and N = 100, respectively), some of whom had current or previous EDs. RESULTS: BN probands' relatives with no ED history had significantly elevated levels of perfectionism, ineffectiveness, and interpersonal distrust compared to CW probands' relatives with no ED history. In contrast, diminished interoceptive awareness, heightened stress reactivity and perfectionistic doubting of actions were found among the previously eating disordered relatives of bulimic probands compared to their never ill relatives. Finally, a sense of alienation and emotional responsivity to the environment were elevated among currently ill compared to recovered bulimic probands. CONCLUSIONS: The fact that perfectionism, ineffectiveness and interpersonal distrust are transmitted independently of an ED in relatives suggests that they may be of potential aetiological relevance for BN. In contrast, diminished interoceptive awareness, heightened stress reactivity and perfectionistic doubting of actions are more likely consequent to, or exacerbated by, previously having experienced the illness. Finally, a sense of alienation and emotional responsivity to the environment are more likely to be associated with currently having BN.

Adolescent↗
PubMed2000

Temperament and character in women with anorexia nervosa.

The present study examined temperament differences among anorexia nervosa (AN) subtypes and community controls, as well as the effect of body weight on personality traits in women with AN. Temperament and Character Inventory (TCI) scores were compared between 146 women with restrictor-type AN (RAN), 117 women with purging-type AN (PAN), 60 women with binge/purge-type AN (BAN), and 827 community control women (CW) obtained from an archival normative database. Women with AN scored significantly higher on harm avoidance and significantly lower on cooperativeness than CW. Subtype analyses revealed that women with RAN and PAN reported the lowest novelty seeking, RAN women the highest persistence and self-directedness, and PAN women the highest harm avoidance. Body mass index had a nominal effect on subgroup differences, suggesting that personality disturbances are independent of body weight. Findings suggest that certain facets of temperament differ markedly between women with AN, regardless of diagnostic subtype, and controls. More subtle temperament and character differences that were independent of body weight emerged that distinguish among subtypes of AN.

Adult↗
PubMed2000

Anorexia and bulimia nervosa.

Anorexia nervosa (AN) and bulimia nervosa (BN) are disorders characterized by abnormal patterns of weight regulation and eating behavior and by disturbances in attitudes and perceptions toward weight and body shape. Etiologic research has indicated substantial genetic influence on these disorders, suggesting significant biological contributions to their development. Obsessional, perfectionistic, and anxious personality styles may be premorbid traits that contribute to this pathogenesis. Studies of neuroendocrine, neuropeptide, and neurotransmitter functioning in patients with AN and BN indicate that disturbances of these systems may contribute to the maintenance as well as the etiology of these sometimes fatal disorders. The efficacy of psychological treatments and pharmacotherapy has been more clearly established for BN than for AN.

Anorexia↗
PubMed2000

Perfectionism in anorexia nervosa: variation by clinical subtype, obsessionality, and pathological eating behavior.

OBJECTIVE: The purpose of this study was to examine the role of perfectionism as a phenotypic trait in anorexia nervosa and its relevance across clinical subtypes of this illness. METHOD: The Multidimensional Perfectionism Scale and the perfectionism subscale of the Eating Disorder Inventory were administered to 322 women with a history of anorexia nervosa who were participating in an international, multicenter genetic study of anorexia nervosa. All participants were additionally interviewed with the Yale-Brown Obsessive Compulsive Scale and the Yale-Brown-Cornell Eating Disorder Scale. Mean differences on dependent measures among women with anorexia nervosa and comparison subjects were examined by using generalized estimating equations. RESULTS: Persons who had had anorexia nervosa had significantly higher total scores on the Multidimensional Perfectionism Scale than did the healthy comparison subjects. In addition, scores of the anorexia subjects on the Eating Disorder Inventory-2 perfectionism subscale exceeded Eating Disorder Inventory-2 normative data. For the anorexia nervosa participants, the total score on the Multidimensional Perfectionism Scale and the Eating Disorder Inventory-2 perfectionism subscale score were highly correlated. Total score on the Multidimensional Perfectionism Scale was also significantly related to the total score and the motivation-for-change subscale score of the Yale-Brown-Cornell Eating Disorder Scale. CONCLUSIONS: These data show that perfectionism is a robust, discriminating characteristic of anorexia nervosa. Perfectionism is likely to be one of a cluster of phenotypic trait variables associated with a genetic diathesis for anorexia nervosa.

Adolescent↗
PubMed2000

Controlled family study of anorexia nervosa and bulimia nervosa: evidence of shared liability and transmission of partial syndromes.

OBJECTIVE: Lifetime rates of full and partial anorexia nervosa and bulimia nervosa were determined in first-degree relatives of diagnostically pure proband groups and relatives of matched, never-ill comparison subjects. METHOD: Rates of each eating disorder were obtained for 1,831 relatives of 504 probands on the basis of personal structured clinical interviews and family history. Best-estimate diagnoses based on all available information were rendered without knowledge of proband status and pedigree identity. Only definite and probable diagnoses were considered. RESULTS: Whereas anorexia nervosa was rare in families of the comparison subjects, full and partial syndromes of anorexia nervosa aggregated in female relatives of both anorexic and bulimic probands. For the full syndrome of anorexia nervosa, the relative risks were 11.3 and 12.3 in female relatives of anorexic and bulimic probands, respectively. Bulimia nervosa was more common than anorexia nervosa in female relatives of comparison subjects, but it, too, aggregated in the families of ill probands; the corresponding relative risks for bulimia nervosa were 4.2 and 4.4 for female relatives of anorexic and bulimic probands, respectively. When partial syndromes of anorexia nervosa and bulimia nervosa were considered, relative risks fell by one-half in each group of ill probands. CONCLUSIONS: Both anorexia nervosa and bulimia nervosa are familial. Their cross-transmission in families suggests a common, or shared, familial diathesis. The additional observation that familial aggregation and cross-transmission extend to milder phenotypes suggests the validity of their inclusion in a continuum of familial liability.

Adolescent↗
PubMed1999

New directions in treatment research of anorexia and bulimia nervosa.

Although considerable progress has been made in the understanding and treatment of anorexia and bulimia nervosa, a substantial proportion of people with these disorders have a limited response to treatment. Treatment strategies used in eating disorders have tended to be adopted from therapies that were devised to treat other psychiatric illnesses. Recent studies suggest that eating disorders are independently transmitted familial liabilities with a unique pathophysiology. These new findings raise the possibility that an improved understanding of the pathogenesis of eating disorders will generate more specific and effective psychotherapies and pharmacologic interventions.

Anorexia Nervosa↗
PubMed1999

Atypical anorexia nervosa: separation from typical cases in course and outcome in a long-term prospective study.

OBJECTIVE: To assess differences in long-term course and outcome between typical and atypical cases of anorexia nervosa. METHOD: A naturalistic, longitudinal prospective design was used to assess recovery, relapse, and onset of binge eating over 10 to 15 years in patients ascertained through a university-based specialty treatment program. Atypical anorexia nervosa was distinguished from the diagnostically prototypic form of the disorder based on the continuous absence of morbid fear of weight gain and body size distortion during the inpatient phase of treatment. Patients were assessed semiannually for 5 years then annually thereafter until the final visit. RESULTS: Compared to pure cases of anorexia nervosa, atypical cases were less likely to drop weight after discharge, recovered more rapidly, and had lower cumulative risk for developing binge eating. CONCLUSION: It has been argued recently that weight phobia and body image disturbance should not be viewed as critical to the diagnosis of anorexia nervosa. This study shows that the absence of these particular symptoms in patients presenting with malnutrition secondary to extreme dietary restriction predicts a less malignant course and outcome compared to typical cases of anorexia nervosa. These course differences suggest that the division of patients into typical versus atypical diagnostic subtypes may be nosologically valid and clinically useful.

Adult↗
PubMed1999

Familial aggregation of eating disorders: results from a controlled family study of bulimia nervosa.

OBJECTIVE: While familial aggregation of bulimia nervosa (BN) is known to occur, the extent to which aggregation of a broader spectrum of eating disorders (ED) occurs in the families of individuals with BN is less certain. METHOD: Direct interviews and blind best-estimate diagnostic procedures were used to assess lifetime histories of EDs among first-degree relatives (n = 177) of probands with BN (n = 47) and first-degree relatives (n = 190) of non-ED control probands (n = 44). RESULTS: Forty-three percent of sisters and 26% of mothers of BN probands had a lifetime ED diagnosis, with eating disorder not otherwise specified (ED-NOS) diagnoses being most common. These rates were significantly higher than among sisters (5%) and mothers (5%) of controls. Few male relatives of either cohort had an ED. CONCLUSIONS: Diagnostic assessment using contemporary family-epidemiology methodology revealed very strong familial aggregation of a broad spectrum of EDs among female relatives of women with BN.

Bulimia↗
PubMed1999

No effect of adjunctive fluoxetine on eating behavior or weight phobia during the inpatient treatment of anorexia nervosa: an historical case-control study.

A six-week open label clinical trial investigated the response to fluoxetine in adolescents hospitalized for treatment of anorexia nervosa. Patients were drawn from consecutive admissions to a specialty treatment service and received fluxoetine as an add-on to their multidisciplinary treatment regimen beginning three weeks to one month postintake. Global clinical severity ratings of eating behavior and weight phobia were obtained at baseline and then at biweekly intervals. These ratings were compared to those obtained from matched historical case-controls who received an identical course of inpatient therapy but without adjunctive pharmacotherapy. Analyses failed to show any beneficial or detrimental effect of fluoxetine on these clinical measures. We conclude that fluoxetine has no robust additive or synergistic therapeutic benefit when measured against the effects of intensive, multidisciplinary inpatient therapy.

Adolescent↗