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1.
Mol Psychiatry ; 8(5): 546-57, 2003 May.
Article in English | MEDLINE | ID: mdl-12808434

ABSTRACT

In a genome-wide linkage survey, we have previously shown evidence suggesting that the chromosome 22q12 region contains a susceptibility locus for bipolar disorder (BPD). Two independent family sets yielded lod scores suggestive of linkage at markers in this region near the gene G protein receptor kinase 3 (GRK3). GRK3 is an excellent candidate risk gene for BPD since GRK3 is expressed widely in the brain, and since GRKs play key roles in the homologous desensitization of G protein-coupled receptor signaling. We have also previously shown GRK3 expression to be induced by amphetamine in an animal model of mania using microarray-based expression profiling. To identify possible functional mutations in GRK3, we sequenced the putative promoter region, all 21 exons, and intronic sequence flanking each exon, in 14-22 individuals with BPD. We found six sequence variants in the 5'-UTR/promoter region, but no coding or obvious splice variants. Transmission disequilibrium analyses of one set of 153 families indicated that two of the 5'-UTR/promoter variants are associated with BPD in families of northern European Caucasian ancestry. A supportive trend towards association to one of these two variants (P-5) was then subsequently obtained in an independent sample of 237 families. In the combined sample, the P-5 variant had an estimated allele frequency of 3% in bipolar subjects, and displayed a transmission to non-transmission ratio of 26 : 7.7 (chi(2)=9.6, one-sided P value=0.0019). Altogether, these data support the hypothesis that a dysregulation in GRK3 expression alters signaling desensitization, and thereby predisposes to the development of BPD.


Subject(s)
Bipolar Disorder/genetics , Chromosomes, Human, Pair 22 , Linkage Disequilibrium , Polymorphism, Single Nucleotide , Protein Serine-Threonine Kinases/genetics , Animals , Base Sequence , G-Protein-Coupled Receptor Kinase 3 , Genome, Human , Humans , Mice , Molecular Sequence Data , Phenotype , Promoter Regions, Genetic/genetics
2.
Mol Psychiatry ; 8(5): 558-64, 2003 May.
Article in English | MEDLINE | ID: mdl-12808435

ABSTRACT

Bipolar (BP) disorder or manic depressive illness is a major psychiatric disorder for which numerous family, twin and adoption studies support a substantial genetic contribution. Recently, we reported the results of a genome-wide search for BP disorder susceptibility loci in 20 pedigrees. Suggestive evidence for linkage was found in this study at three markers on 13q, representing possibly two peaks separated by 18 cM. We have now collected a second set of 32 pedigrees segregating BP disorder and have tested for evidence of linkage to markers on human chromosome 13q. In this sample, we have replicated the linkage result in 13q32 at D13S154 (lod=2.29), the more proximal of the two original peaks. When all 52 pedigrees were combined, the multipoint maximum lod score peaked approximately 7 cM proximal to D13S154 (lod=3.40), with a second peak occurring between D13S225 and D13S796 (lod=2.58). There have been several other reports of significant linkage to both BP disorder and schizophrenia in this region of chromosome 13. These pedigrees provide additional evidence for at least one locus for BP disorder in 13q32, and are consistent with other reports of a possible genetic overlap between these disorders.


Subject(s)
Bipolar Disorder/genetics , Chromosomes, Human, Pair 13 , Genetic Linkage , Chromosome Mapping , Genetic Predisposition to Disease , Humans , Pedigree
3.
Mol Psychiatry ; 7(2): 165-73, 2002.
Article in English | MEDLINE | ID: mdl-11840309

ABSTRACT

The dopamine transporter gene (DAT) has been implicated in a variety of disorders, including bipolar disorder, attention-deficit hyperactivity disorder, cocaine-induced paranoia, Tourette's syndrome, and Parkinson's disease. As no clear functional polymorphism has been identified to date, studies rely on linkage disequilibrium (LD) to assess the possible genetic contribution of DAT to the various disorders. A better understanding of the complex structure of LD across the gene is thus critical for an accurate interpretation of the results of such studies, and may facilitate the mapping of the actual functional variants. In the process of characterizing the extent of variation within the DAT gene, we have identified a number of single nucleotide polymorphisms (SNPs) suitable for LD studies, 14 of which have been analyzed, along with a 3' repeat polymorphism, in a sample of 120 parent-proband triads. Calculations of pairwise LD between the SNPs in the parental haplotypes revealed a high degree of LD (P < 0.00001) in the 5' (distal promoter through intron 6) and 3' (exon 9 through exon 15) regions of DAT. This segmental LD pattern is maintained over approximately 27 kb and 20 kb in these two regions, respectively, with very little significant LD between them, possibly due to the presence of a recombination hotspot located near the middle of the gene. These analyses of the DAT gene thus reveal a complex structure resulting from both recombination and mutation, knowledge of which may be invaluable to the design of future studies.


Subject(s)
Linkage Disequilibrium , Membrane Glycoproteins , Membrane Transport Proteins/genetics , Nerve Tissue Proteins , Dopamine Plasma Membrane Transport Proteins , Family Health , Genetic Variation , Haplotypes , Humans , Polymorphism, Single Nucleotide
4.
Am J Med Genet ; 105(2): 145-51, 2001 Mar 08.
Article in English | MEDLINE | ID: mdl-11304827

ABSTRACT

A role for the dopamine transporter (DAT) in bipolar disorder is implicated by several lines of pharmacological evidence, as well as suggestive evidence of linkage at this locus, which we have reported previously. In an attempt to identify functional mutations within DAT contributing a susceptibility to bipolar disorder, we have screened the entire coding region, as well as significant portions of the adjacent non-coding sequence. Though we have not found a definitive functional mutation, we have identified a number of single nucleotide polymorphisms (SNPs) that span the gene from the distal promoter through exon 15. Of the 39 SNPs that are suitable for linkage disequilibrium (LD) studies, 14 have been analyzed by allele-specific PCR in a sample of 50 parent-proband triads with bipolar disorder. A haplotyped marker comprised of five SNPs, spanning the region between exon 9 and exon 15, was constructed for each individual, and transmission/disequilibrium test (TDT) analysis revealed this haplotype to be in linkage disequilibrium with bipolar disorder (allele-wise TDT p = 0.001, genotype-wise TDT p = 0.0004). These data replicate our previous finding of linkage to markers within and near DAT in a largely different family set, and provide further evidence for a role of DAT in bipolar disorder. Published 2001 Wiley-Liss. Inc.


Subject(s)
Bipolar Disorder/genetics , Carrier Proteins/genetics , Linkage Disequilibrium , Membrane Glycoproteins , Membrane Transport Proteins , Nerve Tissue Proteins , Alleles , Dopamine Plasma Membrane Transport Proteins , Exons , Family Health , Female , Genetic Markers , Genetic Predisposition to Disease , Genotype , Haplotypes , Humans , Male , Polymerase Chain Reaction , Polymorphism, Single Nucleotide , Sequence Analysis, DNA
6.
Proc Natl Acad Sci U S A ; 98(2): 585-90, 2001 Jan 16.
Article in English | MEDLINE | ID: mdl-11149935

ABSTRACT

Bipolar disorder or manic depressive illness is a major psychiatric disorder that is characterized by fluctuation between two abnormal mood states. Mania is accompanied by symptoms of euphoria, irritability, or excitation, whereas depression is associated with low mood and decreased motivation and energy. The etiology is currently unknown; however, numerous family, twin, and adoption studies have argued for a substantial genetic contribution. We have conducted a genome survey of bipolar disorder using 443 microsatellite markers in a set of 20 families from the general North American population to identify possible susceptibility loci. A maximum logarithm of odds score of 3.8 was obtained at D22S278 on 22q. Positive scores were found spanning a region of nearly 32 centimorgans (cM) on 22q, with a possible secondary peak at D22S419. Six other chromosomal regions yielded suggestive evidence for linkage: 3p21, 3q27, 5p15, 10q, 13q31-q34, and 21q22. The regions on 22q, 13q, and 10q have been implicated in studies of schizophrenia, suggesting the possible presence of susceptibility genes common to both disorders.


Subject(s)
Bipolar Disorder/genetics , Chromosomes, Human, Pair 22/genetics , Genome, Human , Bipolar Disorder/classification , Bipolar Disorder/epidemiology , British Columbia/epidemiology , California/epidemiology , Chromosome Mapping , Chromosomes, Human, Pair 10/genetics , Chromosomes, Human, Pair 13/genetics , Chromosomes, Human, Pair 21/genetics , Chromosomes, Human, Pair 3/genetics , Chromosomes, Human, Pair 5/genetics , Female , Genetic Predisposition to Disease , Genotype , Humans , Lod Score , Male , Microsatellite Repeats , Polymerase Chain Reaction , Schizophrenia/epidemiology , Schizophrenia/genetics
7.
Can J Psychiatry ; 45(5): 471-5, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10900528

ABSTRACT

Shoplifting behaviours were examined in an eating disorder group (EDG, n = 48), a psychiatric control group (PCG, n = 46), and an undergraduate control group (UCG, n = 82). They were examined in relation to self-esteem, depression, and eating disorder symptomatology. The 3 groups did not differ in overall history of shoplifting, but EDG women were more likely to have shoplifted in the past 6 months (current shoplifting) and to have shoplifted often than were women from the PCG or UCG. Across all 3 groups, current shoplifting was associated with low self-esteem, elevated depression, and purging behaviours at the time of the assessment. The implications of these findings with regard to the relationship between shoplifting and eating disorder symptomatology will be addressed.


Subject(s)
Depressive Disorder/psychology , Feeding and Eating Disorders/psychology , Theft/statistics & numerical data , Adolescent , Adult , Female , Humans , Middle Aged , Self Concept , Surveys and Questionnaires
8.
J Affect Disord ; 59(3): 183-92, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10854635

ABSTRACT

BACKGROUND: Numerous genetic mechanisms and modes of transmission underlying bipolar affective disorder (BPAD) have been postulated. Recently, the discovery of genomic imprinting and mitochondrial transmission of illness in humans has stimulated study of parent-of-origin effects in the transmission of BPAD. METHODS: We examined a large sample of families from an associated linkage study to search for a possible parent-of-origin effect. Selecting for unilineal families with at least one offspring and/or parent diagnosed with BPAD after structured interview, we conducted three analyses: (1) the rates of illness among mothers and fathers of offspring affected with BPAD; (2) the observed frequency of transmission and rates of illness among maternal and paternal lineages; and (3) the rates of affective illness among offspring of parents affected with BPAD. RESULTS: Our results indicate no significant differences in the rates of illness among mothers and fathers of offspring affected with BPAD. Also, the frequency of transmission and rates of illness among maternal and paternal lineages did not differ significantly. However, the rate of BPAD among the offspring of fathers affected with BPAD was significantly higher than for mothers with the illness. LIMITATIONS: Substantially more women than men, and maternal than paternal relatives were studied - introducing possible gender biases. CONCLUSIONS: These results suggest a possible paternal parent-of-origin effect.


Subject(s)
Bipolar Disorder/genetics , Fathers , Mothers , Penetrance , Bipolar Disorder/diagnosis , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/genetics , Female , Genetic Linkage/genetics , Genetic Testing , Humans , Male
12.
Biol Psychiatry ; 45(11): 1419-25, 1999 Jun 01.
Article in English | MEDLINE | ID: mdl-10356623

ABSTRACT

BACKGROUND: Olfactory identification performance has been investigated in several psychiatric populations, with deficits most commonly reported in patients with schizophrenia. In this study, olfactory identification performance was investigated in a more homogenous group of treatment-refractory patients with schizophrenia (T-RS) and in two additional psychiatric groups who demonstrate some similarities to the patients with schizophrenia in terms of symptomotology and medication regime. METHODS: The olfactory identification performance of 16 T-RS patients was assessed using the University of Pennsylvania Smell Identification Test (UPSIT) and compared to that of 16 normal control subjects and two other psychiatric patient groups: 19 affective disorder patients requiring maintenance antipsychotic medication and 20 affective disorder patients not receiving antipsychotic medication. RESULTS: The olfactory identification performance of T-RS patients was significantly lower than that of normal controls but not significantly different from either affective disorder group. The olfactory identification performance of affective disorder patients receiving antipsychotic medication was significantly lower than that of affective disorder patients not receiving antipsychotic medication. DISCUSSION: Results are discussed in the context of a possible link between psychotic symptomotology and olfactory identification performance.


Subject(s)
Mood Disorders/physiopathology , Perceptual Disorders/complications , Psychotic Disorders/physiopathology , Schizophrenia/physiopathology , Smell/physiology , Adult , Aged , Analysis of Variance , Antipsychotic Agents/pharmacology , Case-Control Studies , Drug Resistance , Female , Humans , Male , Middle Aged , Mood Disorders/classification , Mood Disorders/complications , Mood Disorders/drug therapy , Psychotic Disorders/complications , Psychotic Disorders/drug therapy , Regression Analysis , Schizophrenia/complications , Schizophrenia/drug therapy
13.
Int J Eat Disord ; 24(3): 285-98, 1998 Nov.
Article in English | MEDLINE | ID: mdl-9741039

ABSTRACT

OBJECTIVES: To determine the psychometric properties of the Shape- and Weight-Based Self-Esteem (SAWBS) Inventory in women with eating disorders, and to compare SAWBS scores in women who have eating disorders with women from psychiatric and normal control groups. METHOD: Women with eating disorders (n = 48), women with other psychiatric disorders (n = 44), and undergraduate control women (n = 82) completed the SAWBS Inventory and measures of depression, self-esteem, and eating disorder symptomatology. Twenty women from the eating disorder group completed the SAWBS Inventory a second time 1 week later. RESULTS: Similar to previous work in undergraduate samples, SAWBS scores were stable over 1 week, and demonstrated concurrent and discriminant validity in women with eating disorders. In between-group comparisons, SAWBS scores were higher among women with eating disorders than in either control group, even after controlling for age, socioeconomic status, body mass index, and self-esteem. A differing relationship between depression and SAWBS emerged as a function of group; SAWBS scores differed significantly among depressed, but not nondepressed women from the three groups. CONCLUSION: The psychometric properties of the SAWBS Inventory were established in women with eating disorders. As expected, SAWBS scores were higher in women with eating disorders than in the control groups. Clinical implications of these findings are discussed.


Subject(s)
Body Weight , Feeding and Eating Disorders/psychology , Self Concept , Adult , Female , Humans , Personality Inventory , Reproducibility of Results
14.
J Clin Psychopharmacol ; 18(4): 268-73, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9690691

ABSTRACT

Ipsapirone, an azapirone with 5-hydroxytryptamine (5-HT1A) partial agonist activity, has been shown in preliminary studies to be effective in the treatment of major depressive disorder. This 8-week, randomized, double-blind study compared the efficacy, safety, and tolerability of three fixed doses of controlled-release ipsapirone (10-, 30-, and 50-mg dose once daily) with placebo in 410 patients with moderate to severe major depression (Hamilton Rating Scale for Depression [HAM-D] score > or = 20). The 10-mg ipsapirone treatment arm was discontinued early in the study. A total of 390 patients were eligible for evaluation in the intent-to-treat sample. The primary efficacy variable was the change in HAM-D total score from baseline to visit 8. There was no significant difference in efficacy in the two treatment groups versus the placebo group. The overall treatment response, defined as a 50% decrease in the HAM-D total score from baseline, was 43% with ipsapirone 50 mg given once daily, 34% with ipsapirone 30 mg given once daily, and 35% with placebo. In subanalyses, ipsapirone 50 mg given once daily was superior to placebo according to the HAM-D Core Depression (mood, guilt, interest, psychomotor activity) subtotal (p = 0.0453) and Melancholic item (p = 0.0225). Ipsapirone 30 mg given once daily was superior to placebo only in patients with moderate depression (baseline HAM-D total score < or = 25; p = 0.0100). The most common adverse effect in all groups was headache. The only dose-dependent adverse effects were dizziness and nausea.


Subject(s)
Depressive Disorder, Major/drug therapy , Pyrimidines/administration & dosage , Serotonin Receptor Agonists/administration & dosage , Adolescent , Adult , Aged , Ambulatory Care , Canada , Delayed-Action Preparations , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/psychology , Dose-Response Relationship, Drug , Double-Blind Method , Drug Administration Schedule , Female , Humans , Male , Middle Aged , Personality Inventory , Pyrimidines/adverse effects , Serotonin Receptor Agonists/adverse effects , Treatment Outcome
15.
Am J Med Genet ; 74(2): 121-8, 1997 Apr 18.
Article in English | MEDLINE | ID: mdl-9129709

ABSTRACT

Velo-cardio-facial syndrome (VCFS) is a congenital anomaly characterized by multiple dysmorphisms, cleft palate, cardiac anomalies, and learning disabilities, that results from a microdeletion of chromosome 22q11. An increased prevalence of psychiatric illness has been observed, with both schizophrenia and bipolar disorder commonly being diagnosed. For these reasons, the VCFS region is an interesting candidate region for bipolar disorder. We examined this region in 17 bipolar families from three populations: 13 families from the general North American population (University of California, San Diego/University of British Columbia, UCSD/UBC), three larger families from New York, and a portion of Old Order Amish pedigree 110. Three microsatellite markers spanning 13 cM around the VCFS region were genotyped in all the families. A maximum lod score of 2.51 was obtained in the UCSD/UBC families under a dominant model at D22S303. In the combined family set, maximum lod scores of 1.68 and 1.28 were obtained at this marker under dominant and recessive models, respectively. Four additional markers were subsequently typed in selected positive families, and yielded positive lods at 6 of 7 markers spanning 18 cM in this region. Nonparametric, multipoint analyses using the affected pedigree member (APM) method also yielded suggestive evidence for linkage in both the UCSD/UBC family set (P = 0.0024) and in the combined families (P = 0.017). Affected sibpair analyses were similarly positive in the UCSD/UBC families (P = 0.017), and in the combined families (P = 0.004). These results are suggestive of a possible locus for bipolar disorder near the VCFS region on chromosome 22.


Subject(s)
Abnormalities, Multiple/genetics , Bipolar Disorder/genetics , Genetic Linkage , Genotype , Humans , Pedigree , Syndrome
16.
Biol Psychiatry ; 41(6): 737-42, 1997 Mar 15.
Article in English | MEDLINE | ID: mdl-9066998

ABSTRACT

Some hypotheses suggest that lithium produces its therapeutic effect by reducing sensitivity to light at the level of the retina. In humans, acute administration of lithium is associated with a reduction in retinal light sensitivity. To determine whether similar retinal light sensitivity changes occur with chronic use, we studied 24 euthymic bipolar patients on chronic lithium treatment and 21 age- and sex-matched normal comparison subjects using electroretinography (ERG) and electro-oculography (EOG). No significant differences were found in ERG b-wave amplitudes or implicit times, or in EOG ratios, between the two groups. We conclude that chronic lithium use is not associated with differences in retinal light sensitivity when bipolar patients are compared to normal comparison subjects, and that there is no evidence for retinal toxicity with long-term lithium treatment.


Subject(s)
Antimanic Agents/adverse effects , Lithium/adverse effects , Retina/drug effects , Adult , Antimanic Agents/blood , Antimanic Agents/therapeutic use , Bipolar Disorder/drug therapy , Bipolar Disorder/physiopathology , Electrophysiology , Electroretinography/drug effects , Female , Humans , Lithium/blood , Lithium/therapeutic use , Male , Middle Aged , Psychiatric Status Rating Scales , Pupil/drug effects
17.
Am J Med Genet ; 67(6): 533-40, 1996 Nov 22.
Article in English | MEDLINE | ID: mdl-8950410

ABSTRACT

The dopamine transporter (DAT) plays a key role in the regulation of dopaminergic neurotransmission by mediating the active reuptake of synaptic dopamine. It is an important candidate gene for bipolar disorder because of data implicating dopamine abnormalities in mania, and because it is the site of action of amphetamine, which has activating and psychotogenic properties. DAT has recently been cloned by its homology to a family of transporters, and mapped to chromosome 5p15.3. We tested DAT for linkage to bipolar disorder in a collection of 21 families from the general North American population (University of California, San Diego/University of British Columbia [UCSD/UBC] families), three Icelandic pedigrees, and Old Order Amish pedigree 110. We examined three markers at DAT, including a 5' TaqI RFLP (HDAT-TaqI), a highly polymorphic variable number of tandem repeats marker (VNTR) (HDAT-VNTR1), and a 3' 40-bp repeat marker (HDAT-PCR1), as well as two nearby microsatellite markers, D5S392 and D5S406. A maximum lod score of 2.38 was obtained at D5S392 in one of the UCSD/UBC families under an autosomal-dominant model. A lod score of 1.09 was also obtained under the same dominant model in the Amish at HDAT-PCR1. In the combined set of families, a maximum lod score of 1.76 was obtained under an autosomal-recessive model at HDAT-TaqI. Positive results were also obtained at several markers, using three nonparametric methods in the UCSD/UBC family set: the affected pedigree member method (P = 0.001), an affected sib pair method (ESPA, P = 0.0008), and the transmission disequilibrium test (P = 0.024). These results suggest the presence of a susceptibility locus for bipolar disorder near the DAT locus on chromosome 5.


Subject(s)
Bipolar Disorder/genetics , Carrier Proteins/genetics , Chromosomes, Human, Pair 5 , Dopamine/metabolism , Membrane Glycoproteins/genetics , Membrane Transport Proteins , Nerve Tissue Proteins/genetics , Dopamine Plasma Membrane Transport Proteins , Genotype , Humans , Polymorphism, Restriction Fragment Length
18.
Am J Med Genet ; 67(4): 347-53, 1996 Jul 26.
Article in English | MEDLINE | ID: mdl-8837701

ABSTRACT

The clinical concept of "double depression," i.e., the superimposition of a major depressive disorder in a patient with dysthymic disorder, implies that there are at least some differences between dysthymia, major depression, and double depression. However, the relationship between these two syndromes remains unclear. The present study uses genetic methodology to explore any possible relationship between minor depression, double depression, and major depression. From 1988-1990, all consecutive unrelated inpatients and outpatients (index cases) presenting to a university-based mood disorders service had detailed family histories taken, using modification of the "family history method." Diagnoses for index cases and their first-degree relatives were made according to Research Diagnostic Criteria. For all index cases with a diagnosis of minor or intermittent depression, and minor/intermittent depression plus either single or recurrent depression ("double depression"), morbidity risks for mood disorders were calculated for first-degree relatives (parents, siblings, and children) using the maximum likelihood approach. Results showed no significant differences in morbidity risk calculations to first-degree relatives of index cases with minor/intermittent depression, major depression, or double depression. The data from this genetic perspective suggest that single depression, recurrent depression, minor depression, and double depression are indistinguishable.


Subject(s)
Depression/classification , Depression/genetics , Depressive Disorder/classification , Depressive Disorder/genetics , Depression/epidemiology , Depressive Disorder/epidemiology , Female , Humans , Male , Morbidity , Nuclear Family , Pedigree , Recurrence , Retrospective Studies , Risk Factors , Sex Characteristics
19.
Am J Med Genet ; 67(2): 215-7, 1996 Apr 09.
Article in English | MEDLINE | ID: mdl-8723051

ABSTRACT

The serotonin transporter (HTT) is an important candidate gene for the genetic transmission of bipolar disorder. It is the site of action of many antidepressants, and plays a key role in the regulation of serotonin neurotransmission. Many studies of affectively ill patients have found abnormalities in serotonin metabolism, and dysregulation of the transporter itself. The human serotonin transporter has been recently cloned and mapped to chromosome 17. We have identified a PstI RFLP at the HTT locus, and here report our examination of this polymorphism for possible linkage to bipolar disorder. Eighteen families were examined from three populations: the Old Order Amish, Iceland, and the general North American population. In addition to HTT, three other microsatellite markers were examined, which span an interval known to contain HTT. Linkage analyses were conducted under both dominant and recessive models, as well as both narrow (bipolar only) and broad (bipolar + recurrent unipolar) diagnostic models. Linkage could be excluded to HTT under all models examined. Linkage to the interval spanned by the microsatellites was similarly excluded under the dominant models. In two individual families, maximum lod scores of 1.02 and 0.84 were obtained at D17S798 and HTT, respectively. However, these data overall do not support the presence of a susceptibility locus for bipolar disorder near the serotonin transporter.


Subject(s)
Bipolar Disorder/genetics , Carrier Proteins/genetics , Genetic Linkage , Membrane Glycoproteins/genetics , Membrane Transport Proteins , Nerve Tissue Proteins , Serotonin/metabolism , Humans , Microsatellite Repeats , Serotonin Plasma Membrane Transport Proteins
20.
Neurology ; 46(3): 628-32, 1996 Mar.
Article in English | MEDLINE | ID: mdl-8618657

ABSTRACT

The objective of the present study were (1) to ascertain the lifetime risk of a depression in a representative group of multiple sclerosis (MS) patients, (2) to assess the morbidity risks for depression among first-degree relatives of these MS patients, and (3) to compare these familial risks for first-degree relatives of MS patients with those for first-degree relatives of a primary depression population, i.e., depression but no MS. We psychiatrically evaluated 221 MS patients (index cases) using a structured clinical interview for the DSM-III-R and calculated the rate and lifetime risk of depression for these index cases using the product limit estimate of survival function. We obtained psychiatric histories for all first-degree relatives of index cases, and we calculated morbidity risks for depression for these relatives using the maximum likelihood approach and compared the risks using the likelihood ratio tests. Index cases had a 50.3% lifetime risk of depression. Morbidity risks for depression among first-degree relatives of index cases were decidedly lower when compared with morbidity risks among first-degree relatives of the reference population. Although there appears to be a very high rate of depression among MS patients, the data for their first-degree relatives do not support a clear genetic basis for this depression, or at least the same genetic basis that probably operates within families when depression occurs in the absence of MS.


Subject(s)
Depression/etiology , Depression/genetics , Multiple Sclerosis/genetics , Multiple Sclerosis/psychology , Adolescent , Adult , Aged , Child , Depression/diagnosis , Depression/epidemiology , Female , Humans , Interview, Psychological , Male , Middle Aged , Morbidity , Risk Factors
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