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Biomedical subjects

M M Weissman

Publications and source records attributed to M M Weissman.

At least 19 recordsLinked to original sources

Rates of lifetime suicide attempt and rates of lifetime major depression in different ethnic groups in the United States.

OBJECTIVE: Rates of major depression and suicide vary across ethnic groups within the US. This also may be true of suicide attempts. METHOD: Data on lifetime suicidal behavior and major depression among Mexican American, Cuban American, and Puerto Rican adults who participated in the Hispanic Health and Nutrition Epidemiologic Survey were pooled with Epidemiological Catchment Area Study data for Blacks, Whites and Hispanics. RESULTS: Rates of major depression ranged from 9.3 (Puerto Ricans) to 3.24% (Cuban Americans). Puerto Ricans and whites had the highest rates of depression. Similarly, suicide attempt rates ranged from 9.1% for Puerto Ricans to 1.9% for Cuban Americans. Puerto Ricans had higher suicide attempt rates compared with other groups. CONCLUSION: This study underscores that there are differences between Hispanic ethnic groups. The impact of the migration process, socioeconomic status, and acculturation may underlie differences in major depression and suicide attempt rates across ethnic groups.

Adult↗

Premorbid polysomnographic signs in depressed adolescents: a reanalysis of EEG sleep after longitudinal follow-up in adulthood.

BACKGROUND: This is a report of a clinical follow-up study (10-15 years later as young adults) of adolescent major depressives and normal control subjects. Polysomnographic data were obtained during the original study period when the subjects were adolescent (time 1). With clinical follow-up (time 2) assessments in hand, our objective was to ascertain whether there were any premorbid polysomnographic signs associated with depression during adolescence. METHODS: Based upon initial (during adolescence) and follow-up clinical assessments (as adults), new subject groupings were generated: depression-free normal subjects and original normal subjects who experienced a depressive episode during the follow-up period (latent depressives). Suicidality and recurrence of depression were also examined. Multivariate analysis of covariance was used to analyze group differences in sleep measures and logistic regression for predicting three outcomes: lifetime depression, lifetime suicidality, and recurrence. RESULTS: Comparison of the depression-free normal subjects, the latent depressives, and the original major depressives revealed significant differences for sleep latency and sleep period time. Comparing all lifetime depressives (original major depressives and the latent depressives) to depression-free normal subjects revealed significantly more stages 3 and 4 combined (ST34) sleep and greater sleep period times among the depressives. An analysis involving the presence or absence of suicidality revealed no overall significant differences between the groups. Comparison of the lifetime depressives grouped by nonrecurrent and recurrent depressive course to the depression-free normal subjects revealed significant difference for sleep period time. Using logistic regression, we found that a longer sleep latency and sleep period time significantly predicted lifetime depression. Gender, ST34 sleep, and an interaction term for ST34 sleep and REM latency significantly predicted lifetime suicidality. CONCLUSIONS: There was evidence of premorbid sleep abnormalities during adolescence. A general pattern of sleep disruption around sleep onset and during the first 100 min of the sleep period and overall sleep was evident among the major and lifetime depressives, involving sleep latency (initial insomnia), sleep period time (hypersomnia), REM latency, and slow-wave sleep. This adds to the body of literature that highlights the importance of the first 100 min of the sleep period in depression.

Adolescent↗

Phenotype definitions: some hidden issues in psychiatry.

Three hidden problems in phenotype definition in psychiatric genetic studies are described. 1. Data on physical conditions in family members are not routinely collected in genetic studies of psychiatric disorders. These data may reveal cosegregation with psychiatric disorders which can be included in genetic analysis when defining the phenotype. Data on physical conditions can be obtained by a combination of medical checklists, medical history, and medical records. 2. Detailed clinical narrative summaries should be prepared on family members even if the narratives are not part of the diagnostic data included in centralized cell repositories for future distribution to qualified genetic investigators. Means for retaining the narratives for future use, while protecting patient confidentiality, should be sought. The narratives include detailed information on the context, severity, and sequence of the symptoms and can provide phenotype descriptions for reconsideration of diagnosis in the future. 3. The selection of early onset psychiatric disorders for genetic studies does not automatically mean that affected children should be included in genetic studies for some psychiatric disorders. Screening for genetic studies among child psychiatric patients and inclusion of children as affected in pedigrees should proceed with caution until more data are available from longitudinal studies on the continuity between childhood and adult psychiatric disorders.

Adult↗

Panic and suicidal ideation in primary care.

The objective of this article is to examine the relationship between panic attacks, panic disorder, and suicidal ideation among primary care patients. A probability sample of 1,007 primary care attenders from a large urban university practice was assessed for current mental disorders and suicidal ideation (past 2 week prevalence) with the PRIME-MD Patient Health Questionnaire. Controlling for major depression, substance use disorders, and sociodemographic variables simultaneously, patients with either panic attacks or panic disorder had significantly increased risks of suicidal ideation. Suicidal ideation was highly associated with major depression and comorbid panic disorder (OR = 15.4) or panic attacks (OR = 7.9). There is need for detection and possible treatment of patients with panic attacks or disorder in primary care, especially among those with co-occurring major depression.

Adult↗

No association or linkage between polymorphisms in the genes encoding cholecystokinin and the cholecystokinin B receptor and panic disorder.

Growing animal data implicate cholecystokinin in the regulation of anxiety, while human clinical research confirms the role of cholecystokinin in the provocation of panic attacks. Antipanic medications suppress the ability of cholecystokinin to induce panic attacks, and may alter the expression of the cholecystokinin gene. Thus, there is increased interest in understanding the molecular genetic component of these observations. Recent association studies using persons with panic disorder described some association between polymorphisms in the genes encoding cholecystokinin and the cholecystokinin B-receptor and panic disorder. In this study, we used a family-based design, employing 596 individuals in 70 panic disorder pedigrees, as well as 77 haplotype relative risk 'triads'. Subjects were genotyped for two polymorphisms: the polymorphic microsatellite marker in the CCK-BR locus using PCR-based genotyping and at a single nucleotide polymorphism in the CCK promoter using a fluorescence polarization detection assay, and the data were analyzed for genetic association and linkage. Employing a variety of diagnostic and genetic models, linkage analysis produced no significant lod scores at either locus. Family-based tests of association, the haplotype-based haplotype relative risk statistic and the transmission disequilibrium test, were likewise non-significant. The results reported here provide little support for the role of these polymorphisms in panic disorder.

Cholecystokinin↗

Ethnic and sex differences in suicide rates relative to major depression in the United States.

OBJECTIVE: Suicide rates differ between ethnic groups in the United States. Since suicide is commonly associated with a mood disorder, the authors compared suicide rates relative to depression rates in five ethnic groups in the United States. METHOD: Rates of major depression were generated from the Epidemiologic Catchment Area study and the Hispanic Health and Nutrition Epidemiologic Survey. Sociodemographic effects were determined by examining depression rates for respondents who were separated or divorced, earning low incomes, or not working for pay. The survey data were analyzed with age and sex standardization to generate 1-year prevalence rates of major depression. The depression rates of the different ethnic groups were compared and were examined in relation to suicide rates. RESULTS: The 1-year prevalence rates of major depression were 3.6% for whites, 3.5% for blacks, 2.8% for Mexican Americans, 2.5% for Cuban Americans, and 6.9% for Puerto Ricans. Compared to the rate for whites, the rate of depression was significantly higher in Puerto Ricans and significantly lower in Mexican Americans. Relative to the depression rates, the annual suicide rates were higher for males than for females. Mexican American and Puerto Rican males had lower relative suicide rates than white males. CONCLUSIONS: Identifying reasons for differences in suicide rates relative to depression among ethnic groups and between males and females may suggest interventions to reduce suicide rates. Some possibilities are that depression differs in form or severity or that unidentified factors protect against suicide in different subgroups.

Adult↗

A comparison of three scales for assessing social functioning in primary care.

OBJECTIVE: Assessment of functional status is increasingly important in clinical trials and outcome research. Although several scales for assessing functioning are widely used, they vary in coverage, and direct comparisons among them are rare. Comparative information is useful in guiding selection of appropriate scales for research applications. METHOD: Results from three scales that measure functioning-the Medical Outcomes Study 36-item Short-Form Health Survey, the Social Adjustment Scale Self-Report, and the Social Adaptation Self-Evaluation Scale-were compared in a consecutively selected sample of 211 patients coming to primary care. Patients also received psychiatric assessments. RESULTS: All three scales were acceptable to patients, showed few significant correlations with demographic variables, and were able to differentiate psychiatrically ill and well patients. Correlations among scales, even among scale items that assessed similar domains of functioning, were modest. CONCLUSIONS: Although all three scales are presumed to assess functional status, their item content and coverage differ. Selection of a scale requires a review of the scale items and consideration of research priorities and the characteristics of the study group. If functional status is a critical outcome measure, use of more than one scale may be necessary.

Adult↗

The association between childhood depression and adulthood body mass index.

OBJECTIVE: Stress in childhood relates to both childhood depression and elevated adult body mass index (BMI), a measure of relative overweight. However, there are limited data on the association between major depression in childhood and BMI in adulthood. The current study examines this association. METHOD: Children 6 to 17 years old with major depression (n = 90) or no psychiatric disorder (n = 87) were identified at Columbia Presbyterian Medical Center and followed up 10 to 15 years later. Psychiatric status at intake and follow-up was assessed via standardized psychiatric interviews. BMI during adulthood was recorded so that the association between depression and BMI could be considered over time. RESULTS: Participants with childhood major depression had a BMI of 26.1 +/- 5.2 as adults, compared with a BMI of 24.2 +/- 4.1 in healthy comparisons (t(175) = 2.7). This association could not be explained by a number of potentially confounding factors, including age, gender, cigarette or alcohol use, social class, and pregnancy or medication history. Although poverty during adulthood also predicted adult BMI, both the association between poverty and adult BMI (t(152) = 2.9), as well as between childhood depression and adult BMI (t(152) = 2.2) were significant in a multivariate model. Finally, duration of depression between childhood and adulthood also emerged as a predictor of adult BMI. CONCLUSIONS: Depression during childhood is positively associated with BMI during adulthood. This association cannot be explained by various potential confounding variables and may develop over time as children pass into their adult years.body mass index, depression, children, adolescents.

Adolescent↗

Drawbacks of GENEHUNTER for larger pedigrees: application to panic disorder.

Large pedigrees can pose a problem for GENEHUNTER linkage analysis software. Differences in two-point and multipoint lodscores were observed when comparing GENEHUNTER to other linkage software. Careful consideration must be given when selecting linkage analysis programs. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:781-783, 2000.

Chromosome Mapping↗

Investigation of dopamine receptor (DRD4) and dopamine transporter (DAT) polymorphisms for genetic linkage or association to panic disorder.

Clinical and animal studies suggest a role for the neurotransmitter dopamine in anxiety states. In humans, one such condition is panic disorder, which is typified by recurrent panic attacks accompanied by anticipatory anxiety. Family, segregation, and twin studies imply a genetic component to the pathophysiology of panic disorder. In this study, we examined the genes for the D4 dopamine receptor (DRD4) and the dopamine transporter (DAT) using three common sequence polymorphisms. Two of these polymorphisms were in DRD4, a 12 base-pair insertion/deletion in exon 1 and a 48 base-pair repeat in exon 3, and the third was a 40 base-pair repeat in the 3' untranslated region of DAT. We employed a family-based design, using 622 individuals in 70 families, as well as 82 haplotype relative risk "trios". Subjects were genotyped at the polymorphic loci, and the data were analyzed for genetic association and linkage. There were no significant differences in allele frequencies or occurrence of genotypes within the triads for any of the three polymorphisms. No significant linkage between the DRD4 or DAT polymorphisms and panic disorder was observed in the multiplex families, using a variety of simulations for dominant and recessive models of inheritance. However, LOD scores of approximately 1.1 and 1.05 were observed for the DAT and DRD4 exon 1 loci, respectively. The results reported here provide little support for the role of these polymorphisms in panic disorder.

Alleles↗

Nocturnal growth hormone secretion studies in adolescents with or without major depression re-examined: integration of adult clinical follow-up data.

BACKGROUND: Early sleep is associated with an increased secretion of human growth hormone (GH) through muscarinic inhibition of somatostatin, a GH suppressant. A clinical follow-up was performed approximately 1 decade after depressed and psychiatrically "normal" control adolescents, who were now young adults, had undergone baseline serial GH measurements over a 24-hour period on the third night of sleep polysomnography studies. METHODS: The study population consisted of 77 young adults who had received a diagnosis of adolescent major depressive disorder and had participated in the adolescent sleep and neuroendocrine studies. Alternatively, the young adult subjects were assessed as normal adolescent control subjects free of any psychiatric diagnosis. Blood samples had been collected for GH every 20 min during the 24-hour period coinciding with the third consecutive night of sleep electroencephalography. Subjects, now in young adulthood, were relocated and blindly reinterviewed using the Schedule for Affective Disorders and Schizophrenia (lifetime version). The original adolescent nocturnal GH data were analyzed in light of the information obtained regarding clinical course into adulthood. RESULTS: A substantial proportion of the nominally normal control group developed at least one episode of major depression or dysthymia during the follow-up period. "Latent" depressive subjects differed from depression-free control subjects by having exhibited a significantly more rapid increase of adolescent nocturnal GH secretion following sleep onset. Of the subjects who had experienced at least one lifetime major depressive episode during the follow-up, the subgroup who would go on to make suicide attempts secreted significantly greater amounts of GH during the first 4 hours of sleep. Adults with lifetime depression exhibited significantly reduced levels of GH in the 100 min preceding sleep onset during adolescence. CONCLUSIONS: Assignment of subjects based on longitudinal clinical follow-up into adulthood revealed that the sleep-related GH secretion paradigm has predictive value for future depressive episodes and future suicide attempts. Dysfunction of complex sleep-onset mechanisms may be a premorbid marker of depression and suicidal behavior.

Adolescent↗

Potential panic disorder syndrome: clinical and genetic linkage evidence.

This paper reports evidence for a possible "chromosome 13 syndrome," which includes panic disorder, kidney or bladder problems, serious headaches, thyroid problems (usually hypothyroid), and/or mitral valve prolapse (MVP). In the course of a genetic linkage study of panic disorder, we noted these medical conditions in individual family members. (We were blind to family relationships and marker data.) We hypothesized that there may exist a subgroup of panic families with these medical conditions, which for simplicity we called it the "syndrome." Subsequently we reclassified the families as with or without the "syndrome" and extended the phenotype for analysis to include the above medical conditions. All these classifications were also done before the analysis and blind to marker data. We then examined our linkage results, looking for significant differences between families with and without the "syndrome" (using several definitions of the "syndrome")-i.e., testing for genetic heterogeneity. When the families with and without bladder/kidney problems were separated from each other, one marker-D13S779 (ATA26D07)-yielded a lod score of over 3 in the families with bladder/kidney problems. This lod score went up to 4.2 in these families when we diagnosed any individual with any one of the "syndrome" conditions as affected. These results were statistically significant even after applying an extremely overconservative Bonferroni correction for multiple tests. We present these results in order to alert other investigators working on panic disorder, for replication. If replicated, one may hypothesize that a candidate gene for the syndrome should be expressed in CNS, kidney, gut, thyroid, etc. We also noted that two independent studies report recent linkage findings between schizophrenia and the same region on chromosome 13. No connection between schizophrenia and panic disorder has ever been reported. Finally, we suggest that genetic studies of psychiatric disorders might prove more fruitful if phenotypes were expanded to include possible manifestations of the disorder in medical (non-mental) symptoms. Am. J. Med. Genet.(Neuropsychiatr. Genet.) 96:24-35, 2000.

Genetic Linkage↗

Selecting early onset MDD probands for genetic studies: results from a longitudinal high-risk study.

Recent studies have found high rates of familial aggregation of major depression (MDD) in relatives of depressed children coming for treatment, leading investigators to suggest that probands for genetic studies of MDD should be selected from samples of depressed children being brought for treatment. Implicit in this recommendation is the assumption that childhood and adult depression are similar disorders. This assumption in turn implies that children with prepubertal or adolescent onset depression are at high risk for having recurrent episodes of MDD that continue into adulthood. The data supporting this latter hypothesis, however, is limited and contradictory. In this article we report results from a high-risk longitudinal family study in which we explored the recurrence and continuity into adulthood of prepubertal or adolescent onset MDD in offspring who were at high or low risk for MDD, by virtue of their parental depression status. One hundred eighteen offspring from 55 families in which one or more parents had MDD and 50 offspring from 21 families in which neither parent had MDD were followed for more than 10 years (all offspring were 20 years or older at the end of follow-up time) and blindly reassessed using a semistructured diagnostic instrument. Offspring with childhood/adolescent onset MDD were at significantly greater risk for recurrence in adulthood (after age 25) as compared with offspring without an onset of childhood/adolescent MDD, if they had a history of parental MDD. In contrast, among offspring without a history of parental MDD, those with childhood/adolescent onset MDD were at no greater risk for continuing to have MDD in adulthood (after age 25) than those without childhood/adolescent onset MDD. Moreover, there was a trend for offspring with childhood/adolescent onset MDD to be at greater risk for recurrence after age 25 if they had a history of parental MDD, as compared with offspring without a history of parental MDD (60 vs. 18%). We conclude that childhood/adolescent onset MDD is a heterogeneous disorder, with family history of MDD appearing to define a subtype of childhood/adolescent onset MDD that is recurrent and continues into adulthood. Our findings suggest that caution should be exercised in selecting depressed children and adolescents brought for treatment as probands in genetic studies of early onset MDD. A conservative strategy would be to select only those depressed children and adolescents with a family history of MDD and reassess the treated sample as they mature, ensuring that they go on to have MDD in adulthood. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:93-101, 2000

Adolescent↗

Brief screening for family psychiatric history: the family history screen.

BACKGROUND: Brief screens to collect lifetime family psychiatric history are useful in clinical practice and for identifying potential families for genetic studies. METHODS: The Family History Screen (FHS) collects information on 15 psychiatric disorders and suicidal behavior in informants and their first-degree relatives. Since each question is posed only once about all family members as a group, the administrative time is 5 to 20 minutes, depending on family size and illness. Data on the validity against best-estimate (BE) diagnosis based on independent and blind direct interviews on 289 probands and 305 relatives and test-retest reliability across 15 months in 417 subjects are presented. RESULTS: Agreement between FHS and BE diagnosis for proband and relative self-report had median sensitivity (SEN) of 67.6 and 71.1 respectively; median specificity (SPC) was 87.6 and 89.4, respectively. Marked decrease in SEN occurred when a single informant (the proband) reported on a relative (median, 37.5); however, median SPC was 95.8. Use of more than 1 informant substantially improved SEN (median, 68.2), with a modest reduction in SPC (median, 86.8). Test-retest reliability across 15 months resulted in a median kappa of 0.56. CONCLUSIONS: The FHS is a promising brief screen for collecting lifetime psychiatric history on an informant and/or first-degree relatives. Its validity is best demonstrated for major depression, anxiety disorders, substance dependence (alcohol and drug dependence), and suicide attempts. It is not a substitute for more lengthy family history if more detail on diagnosis is required.

Adolescent↗

The epidemiology and cross-national presentation of obsessive-compulsive disorder.

One of the challenges facing modern psychiatry is to determine to what extent the diagnostic categories clinicians have represent valid constructs. Epidemiologic studies are helpful in this regard when their findings are consistent across various cultural or geographic settings or with those of clinical studies. The cross-national epidemiologic data on OCD reviewed in this article are remarkable for their consistency in rates, age at onset, and comorbidity across diverse countries, a fact which lends additional support to the validity of the diagnosis of OCD. The variability in symptom presentation across national sites suggests that cultural factors may affect the symptom expression; however, why the rates of OCD and other psychiatric disorders are so much lower in Taiwan than in other sites, including another Asian site, is unclear. Epidemiologic studies of adolescents and of adults have shown similar prevalence of OCD and substantial comorbidity with major depression and other anxiety disorders. Studies of adolescent populations indicate that OCD symptoms are fairly common among adolescents but not necessarily predictive of developing the full disorder within 1 year of follow-up. Family studies have suggested an association between OCD and TS and other CMT disorders. Clinical studies have suggested an association between Sydenham's chorea and OCD. These various studies provide a growing body of knowledge regarding the nature of OCD. Together with evidence of the substantial demand on mental health services by those afflicted with OCD, the epidemiologic data make a compelling case for additional efforts to improve the understanding and treatment of this troubling disorder.

Adolescent↗