Elizabeth S. Bowman

Patterns of dissociation in clinical and nonclinical samples

Research has consistently found elevated mean dissociation scores in particular diagnostic groups. In this study, we explored whether mean dissociation scores for different diagnostic groups resulted from uniform distributions of scores within the group or were a function of the proportion of highly dissociative patients that the diagnostic group contained. A total of 1566 subjects who were psychiatric patients, neurological patients, normal adolescents, or normal adult subjects completed the Dissociative Experience Scale (DES). An analysis of the percentage of subjects with high DES scores in each diagnostic group indicated that the diagnostic groups mean DES scores were a function of the proportion of subjects within the group who were high dissociators. The results contradict a continuum model of dissociation but are consistent with the existence of distinct dissociative types.

Multiple personality disorder. A clinical investigation of 50 cases.

To study the clinical phenomenology of multiple personality, 50 consecutive patients with DSM-III multiple personality disorder were assessed using clinical history, psychiatric interview, neurological examination, electroencephalogram, MMPI, intelligence testing, and a variety of psychiatric rating scales. Results revealed that patients with multiple personality are usually women who present with depression, suicide attempts, repeated amnesic episodes, and a history of childhood trauma, particularly sexual abuse. Also common were headaches, hysterical conversion, and sexual dysfunction. Intellectual level varied from borderline to superior. The MMPI reflected underlying character pathology in addition to depression and dissociation. Significant neurological or electroencephalographical abnormalities were infrequent. These data suggest that the etiology of multiple personality is strongly related to childhood trauma rather than to an underlying electrophysiological dysfunction.

Genomewide Linkage Analyses of Bipolar Disorder: A New Sample of 250 Pedigrees from the National Institute of Mental Health Genetics Initiative

We conducted genomewide linkage analyses on 1,152 individuals from 250 families segregating for bipolar disorder and related affective illnesses. These pedigrees were ascertained at 10 sites in the United States, through a proband with bipolar I affective disorder and a sibling with bipolar I or schizoaffective disorder, bipolar type. Uniform methods of ascertainment and assessment were used at all sites. A 9-cM screen was performed by use of 391 markers, with an average heterozygosity of 0.76. Multipoint, nonparametric linkage analyses were conducted in affected relative pairs. Additionally, simulation analyses were performed to determine genomewide significance levels for this study. Three hierarchical models of affection were analyzed. Significant evidence for linkage (genomewide P<.05) was found on chromosome 17q, with a peak maximum LOD score of 3.63, at the marker D17S928, and on chromosome 6q, with a peak maximum LOD score of 3.61, near the marker D6S1021. These loci met both standard and simulation-based criteria for genomewide significance. Suggestive evidence of linkage was observed in three other regions (genomewide P<.10), on chromosomes 2p, 3q, and 8q. This study, which is based on the largest linkage sample for bipolar disorder analyzed to date, indicates that several genes contribute to bipolar disorder.

Initial genomic scan of the NIMH genetics initiative bipolar pedigrees: Chromosomes 3, 5, 15, 16, 17, and 22

As part of the four-center NIMH Genetics Initiative on Bipolar Disorder we carried out a genomic scan of chromosomes 3, 5, 15, 16,17, and 22. Genotyping was performed on a set of 540 DNAs from 97 families, enriched for affected relative pairs and parents where available. We report here the results of the initial 74 markers that have been typed on this set of DNAs. The average distance between markers (theta) was 12.3 cM. Nonparametric analysis of excess allele sharing among affected sibling pairs used the SIBPAL program of the S.A.G.E. package to test three hierarchical models of affected status. D16S2619 gave some evidence of linkage to bipolar disorder, with P = 0.006 for Model II (in which bipolar 1, bipolar 2 and schizoaffective-bipolar type individuals are considered affected). Nearby markers also showed increased allele sharing. A second interesting region was toward the telomere of chromosome 5q, where D5S1456 and nearby markers showed increased allele sharing; for D5S1456, P = 0.05, 0.015 and 0.008 as the models of affected status become more broad. MOD score analysis also supported the possible presence of a susceptibility locus in this region of chromosome 5. A pair of adjacent markers on chromosome 3, D3S2405 and D3S3038, showed a modest increased allele sharing in the broad model. Several isolated markers had excess allele sharing at the P < 0.05 level under a single model. D15S217 showed a MOD score of 2.37 (P < 0.025). Multipoint analysis flagged the region of chromosome 22 around D22S533 as the most interesting. Thus, several regions showed modest evidence for linkage to bipolar disorder in this initial genomic scan of these chromosomes, including broad regions near previous reports of possible linkage.

Presenting the diagnosis of pseudoseizure.

Simultaneous video-EEG monitoring has allowed pseudoseizures to be effectively diagnosed. Discussing the results of the monitoring with the patient is the 1st step in treatment. We outline a protocol for presenting the diagnosis of pseudoseizure with the goal of conveying to the patient the importance of knowing the nonepileptic nature of the spells and the need for psychiatric follow-up. The protocol also allows elicitation of a sexual abuse history and the use of suggestion to aid in controlling the pseudoseizures.

Genomic Survey of Bipolar Illness in the NIMH Genetics Initiative Pedigrees: A Preliminary Report

NIMH Genetics Initiative Bipolar Group: John I. Nurnberger, Jr.* (Chair), J. Raymond DePaulo,Elliot S. Gershon, Theodore Reich, Mary C. Blehar, and collaborators from Indiana University(Howard J. Edenberg, Tatiana Foroud, Marvin Miller, Elizabeth Bowman, Aimee Mayeda, N. LeelaRau, Carrie Smiley, and P. Michael Conneally), Johns Hopkins University (Francis Mc-Mahon, Deborah Meyers, Sylvia Simpson, Melvin McInnis, and O. Colin Stine), NIMH IntramuralResearch Program (Sevilla Detera-Wadleigh, Lynn Goldin, Juliet Guroff, Elizabeth Max-well, Diane Kazuba, Pablo V. Gejman, Judith Badner, and Alan Sanders), and WashingtonUniversity of St. Louis (John Rice, Laura Bierut, and Alison Goate).Four sites collaborated with the NIMH todevelop a resource for the genetic study ofbipolar (BP) illness. Common methods of as-certainment and assessment were devel-oped in 1989. A series of families with a bi-polar I (BPI) proband and at least one BPIor schizoaffective, bipolar type (SA/BP)first-degree relative has been studied. Wenow report initial data from a genomic sur-vey with an average intermarker interval of10 cM on 540 subjects from 97 families. Thisis the largest commonly ascertained and as-sessed linkage sample for bipolar illness re-ported to date; it includes 232 subjects withBPI, 32 SA/BP, 72 bipolar II (BPII), and 88unipolar, recurrent (UPR). Nonparametricmethods of analysis were employed, with allsites using affected sib pair analysis. Thestrongest findings thus far appear to be onchromosomes 1, 6, 7, 10, 16, and 22. Supporthas also been found for some previously re-ported linkages, including 21q and possiblyXq26. All these areas (as well as others) willbe followed up with additional markers andfurther analyses. No locus tested thus farmeets stringent criteria for an initial find-ing of significant linkage. Am. J. Med. Genet.74:227–237, 1997.

Family-based association of FKBP5 in bipolar disorder.

The FKBP5 gene product forms part of a complex with the glucocorticoid receptor and can modulate cortisol-binding affinity. Variations in the gene have been associated with increased recurrence of depression and with rapid response to antidepressant treatment. We sought to determine whether common FKBP5 variants confer risk for bipolar disorder. We genotyped seven tag single-nucleotide polymorphisms (SNPs) in FKBP5, plus two SNPs previously associated with illness, in 317 families with 554 bipolar offspring, derived primarily from two studies. Single marker and haplotypic analyses were carried out with FBAT and EATDT employing the standard bipolar phenotype. Association analyses were also conducted using 11 disease-related variables as covariates. Under an additive genetic model, rs4713902 showed significant overtransmission of the major allele (P=0.0001), which was consistent across the two sample sets (P=0.004 and 0.006). rs7757037 showed evidence of association that was strongest under the dominant model (P=0.001). This result was consistent across the two datasets (P=0.017 and 0.019). The dominant model yielded modest evidence for association (P<0.05) for three additional markers. Covariate-based analyses suggested that genetic variation within FKBP5 may influence attempted suicide and number of depressive episodes in bipolar subjects. Our results are consistent with the well-established relationship between the hypothalamic–pituitary–adrenal (HPA) axis, which mediates the stress response through regulation of cortisol, and mood disorders. Ongoing whole-genome association studies in bipolar disorder and major depression should further clarify the role of FKBP5 and other HPA genes in these illnesses.

Genome-wide scan and conditional analysis in bipolar disorder: Evidence for genomic interaction in the National Institute of Mental Health genetics initiative bipolar pedigrees

BACKGROUND In 1989 the National Institute of Mental Health began a collaborative effort to identify genes for bipolar disorder. The first 97 pedigrees showed evidence of linkage to chromosomes 1, 6, 7, 10, 16, and 22 (Nurnberger et al 1997). An additional 56 bipolar families have been genotyped, and the combined sample of 153 pedigrees studied. METHODS Three hierarchical affection status models were analyzed with 513 simple sequence repeat markers; 298 were common across all pedigrees. The primary analysis was a nonparametric genome-wide scan. We performed conditional analyses based on epistasis or heterogeneity for five regions. RESULTS One region, on 16p13, was significant at the genome-wide p <.05 level. Four additional chromosomal regions (20p12, 11p15, 6q24, and 10p12) showed nominally significant linkage findings (p </=.01). Conditional analysis assuming epistasis identified a significant increase in linkage at four regions. Families linked to 6q24 showed a significant increase in nonparametric logarithms of the odds (NPL) scores at 5q11 and 7q21. Epistasis also was observed between 20p12 and 13q21, and 16p13 and 9q21. CONCLUSIONS The findings are presented in rank order of nominal significance. Several of these regions have been previously implicated in independent studies of either bipolar disorder or schizophrenia. The strongest finding is at 16p13 at D16S748 with an NPL of 3.3, there is evidence of epistasis between this locus and 9q21. Application of conditional analyses is potentially useful in larger sample collections to identify susceptibility genes of modest influence that may not be identified in a genome-wide scan aimed to identify single gene effects.

Suggestive evidence of a locus on chromosome 10p using the NIMH genetics initiative bipolar affective disorder pedigrees

As part of a four-center NIMH Genetics Initiative on Bipolar Disorder, a genome screen using 365 markers was performed on 540 DNAs from 97 families, enriched for affected relative pairs. This is the largest uniformly ascertained and assessed linkage sample for this disease, and includes 232 subjects diagnosed with bipolar I (BPI), 32 with schizo-affective, bipolar type (SABP), 72 with bipolar II (BPII), and 88 with unipolar recurrent depression (UPR). A hierarchical set of definitions of affected status was examined. Under Model I, affected individuals were those with a diagnosis of BPI or SABP, Model II included as affected those fitting Model I plus BPII, and Model III included those fitting Model II plus UPR. This data set was previously analyzed using primarily affected sib pair methods. We report the results of nonparametric linkage analyses of the extended pedigree structure using the program Genehunter Plus. The strongest finding was a lod score of 2.5 obtained on chromosome 10 near the marker D10S1423 with diagnosis as defined under Model II. This region has been previously implicated in genome-wide studies of schizophrenia and bipolar disorder. Other chromosomal regions with lod scores over 1.50 for at least one Model Included chromosomes 8 (Model III), 16 (Model III), and 20 (Model I). Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:18-23, 2000

Multiple personality in adolescence: relationship to incestual experiences.

Children who are physically and/or sexually abused may develop multiple personality. Dissociation provides an effective way to cope with the strong affects evoked by abuse and is a predictable defense for young children whose natural development involves fluid role changes as part of fantasy life. This paper presents a case of multiple personality in an adolescent and discusses the relationship between abuse and dissociation in children. Guidelines are offered for treatment of an adolescent multiple personality.