PubMed Health⌕ Search

Biomedical subjects

K Merikangas

Publications and source records attributed to K Merikangas.

At least 19 recordsLinked to original sources
PubMed2002

Genetic epidemiology: bringing genetics to the population--the NAPE Lecture 2001.

OBJECTIVE: To present an overview of the status of genetics of mental disorders and to describe the role of genetic epidemiology in the future of the implementation of the human genome initiative. METHOD: Reviews evidence on familial recurrence risk for major mental disorders and approaches to identify genes for complex disorders. RESULTS: The next decade will witness shifts in approaches of both epidemiology and genetics to address sources of complexity of the mental disorders. Descriptive genetic epidemiology will evolve into analytic genetic epidemiology by shifting the key questions from estimation of the magnitude of mental disorders to identification of risk and protective environmental factors that may be informative for both etiology and prevention. Genetics research will expand to population-based studies for complex disorders and will employ designs and methods that incorporate sources of complexity. CONCLUSION: In summary, the next era of human genetics will witness major shifts in approaches to identify the genes underlying mental disorders. The contributions of genetic epidemiology to translate advances in molecular genetics to public health are discussed.

Genetic Markers↗
PubMed2000

A frailty model of segregation analysis: understanding the familial transmission of alcoholism.

Coupled with environmental factors, genes contribute to numerous human diseases and traits. While there are many epidemiological methods to assess the familial clustering of traits, few are flexible enough to accommodate interactions between covariates and familial factors. In this paper, we propose and develop a frailty model that establishes an integrated framework to evaluate familial transmission of a disease by controlling for covariate effects and conveniently testing the interactions between covariates and familial factors. We also present a peeling algorithm that dramatically reduces the computational burden. This frailty model is employed to examine the familial transmission of major subtypes of alcoholism, namely, alcohol abuse and dependence. We conclude that alcohol dependence is strongly familial whereas alcohol abuse expresses a marginally significant pattern of familial transmission. Moreover, females manifest alcoholism at a lower threshold, and there is no sex-specific familial transmission of alcoholism after adjustment for the threshold effect.

Alcoholism↗
PubMed1997

The depressive spectrum: diagnostic classification and course.

The spectrum of depression is much wider than that reflected in the current diagnostic nomenclature. A large proportion of subjects with depression both in treatment and in the community fail to meet diagnostic criteria for either major depressive disorder (MDD) or dysthymia. Inclusion of subthreshold categories of depression dramatically improves the coverage of treated depression, particularly in community samples, and better enables the characterization of its longitudinal course. This paper investigates the application of diagnostic criteria for both threshold and subthreshold categories of depression in a prospective longitudinal community study of young adults from Zurich, Switzerland. We present the prevalence and treatment rates of each of the depressive subtypes, the degree of diagnostic overlap and the longitudinal stability of subthreshold and threshold categories of depression. The findings indicate that the prevalence rates of subthreshold categories of depression are quite high in the community, and that a substantial proportion of subthreshold depressives, particularly those with recurrent depression, receive treatment. There is a strong tendency for individuals to meet multiple depressive subtypes over time, with little stability of individual categories among those who continue to manifest depression over a 15-year period. The prospective longitudinal data reveal that major depression is both an antecedent to and sequela of subthreshold categories, providing evidence for the validity of the spectrum concept of depression. However, the need for a threshold for the symptom criteria is suggested by the lack of predictive value of minor depression and depressive symptoms only. These result suggest that both the current symptom threshold for a depressive syndrome and recurrence, but not the minimum duration of depressive episodes, are important components of the classification of depression.

Adolescent↗
PubMed1997

Strategies to identify genes for complex diseases.

Genes underlie numerous human diseases and traits. Although we have witnessed a great deal of success in identifying disease-susceptible genes, the task remains challenging for most of the complex diseases. This paper reviews evidence for the role of genetic factors in complex diseases including breast cancer, diabetes and multiple sclerosis. We then describe strategies that can potentially optimize our chance of success in identifying genes involved in complex diseases. Advances in molecular biology, particularly mapping of the human genome, statistical methods that provide more accurate models of complex patterns of inheritance, and basic medical science, which have increased our understanding of disease pathophysiology, will ultimately strengthen the ability of the current generation of genetic epidemiological studies to identify the genetic basis of complex human disorders.

Breast Neoplasms↗
PubMed1996

Eating pathology among women with alcoholism and/or anxiety disorders.

Two hundred one non-treatment seeking women with alcoholism, anxiety disorders, alcoholism and anxiety disorders, or neither alcoholism nor anxiety disorders were interviewed to assess core psychopathology associated with eating disorders using the Eating Disorders Examination and DSM-IIIR psychiatric diagnoses using the Schedule of Affective Disorders and Schizophrenia-Lifetime version. Alcoholic women had significantly higher mean scores on each of the Eating Disorders Examination subscales of Restraint, Overeating, Eating Concern, Shape Concern, and Weight Concern compared with nonalcoholic women. Women with anxiety disorders had significantly elevated scores on subscales of Overeating, Eating Concern, and Weight Concern compared with women without anxiety disorders. Women with both alcoholism and anxiety disorders had higher rates of bulimia nervosa and/or eating disorder NOS compared with women with either disorder alone. Implications of these findings are discussed in the context of the co-morbid association between alcoholism, eating disorders, and anxiety disorders.

Adolescent↗
PubMed1996

Co-occurrence and contransmission of affective disorders and alcoholism in families.

The analysis of patterns of co-occurrence and cotransmission of affective disorders and alcoholism in families may provide clues for understanding the excess comorbidity between these conditions in clinical settings and in the general population. This paper reports the results of a family study of the relatives of patients with bipolar disorder, unipolar depression and alcoholism, and combinations thereof. Excess comorbidity between affective disorders and alcoholism was observed in all groups of relatives. However, the sharing of familial aetiological components was not a major contributor to the excess comorbidity between affective disorders and alcoholism. Unipolar depression and alcoholism segregated independently in families, whereas a modest correlation between familial components of alcoholism and bipolar disorder was observed.

Adolescent↗
PubMed1995

Cognitive impairment and depression in the oldest old in a German and in U.S. communities.

Data on cognitive impairment in the oldest old is reported comparing two different samples, one in Munich, Germany, and the other in the United States (Epidemiologic Catchment Area [ECA] study). In both studies the Mini Mental State Examination (MMSE) was used for assessing cognitive impairment. The Munich sample consisted of 402 and the ECA sample of 827 very old people aged 85 years and above. The results indicate that approximately 40% of each sample scored below 24 points in the MMSE indicating at least mild cognitive impairment. Severe cognitive impairment was found in 13.4% of the Munich and in 14.6% of the American sample. The prevalence of major depression was 1.4% in Munich and 2.0% in the ECA study, and dysthymia was found in 5.1% in the Munich and in 2.0% in the ECA sample aged 85 years and above. Persons living in institutions in both studies more frequently showed signs of cognitive impairment than those living in private households. The ECA sample, but not the Munich sample, showed a significantly higher prevalence of cognitive impairment for females and for the oldest age cohort above 90 years of age. Major depression was more frequent in Munich in persons living in institutions and in the ECA study among the oldest age cohort above 90 years of age. Dysthymia in both studies did not show any association with sociodemographic factors. Most of the excess comorbidity (cognitive impairment and depression) was observed among subjects with mild (and not with severe) cognitive impairment.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1994

Neurasthenia in a longitudinal cohort study of young adults.

This study examines the concept of neurasthenia in a longitudinal cohort of young adults selected from a community sample of the canton of Zurich, Switzerland. The major focus is on the validity of the case definition of neurasthenia. Close approximations of the proposed descriptive and research definitions of the ICD-10 are employed as well as the concept of 'irritable weakness' as described in 1831 by Kraus (1926-1932). The prevalence of neurasthenia defined according to the ICD-10 criteria was: 1% across 10 years and 0.9% in 1988 for a duration criterion of > or = 3 months; and 8.1% across 10 years and 12% in 1988 for a duration criterion of > or = 1 month. The duration criterion of > or = 3 months appeared to be excessively restrictive to represent individuals with neurasthenia in the community. Subjects with 1 month episodes of neurasthenia exhibited sufficient differences from controls and similarities to subjects with anxiety or depressive disorders to justify a 1 month duration criterion for neurasthenia in community samples. The clinical significance of neurasthenia was indicated by the magnitude of subjective distress, and occupational and social impairment reported by the majority of the cases. Prospective assessment of the longitudinal course of neurasthenia revealed that approximately 50% of the cases continued to exhibit this disorder at follow-up. Our findings suggest that neurasthenia is equally likely to represent an early manifestation of affective illness as it is a consequence in those neurasthenic subjects who exhibited comorbid affective disorders. The magnitude, chronicity, impairment, longitudinal stability and distinction from anxiety and depression associated with this condition in the general population, suggest that neurasthenia is an important diagnostic entity for which additional validation studies should be undertaken.

Adult↗
PubMed1994

Comorbidity of migraine and major affective disorders.

Two epidemiologic studies of young adults from the Detroit metropolitan area and from Zurich, Switzerland, focused on the relationship between migraine and affective disorders, such as major depression, dysthymia, bipolar disorder, and cyclothymia. Through application of current definitions of migraine and psychiatric disorders in structured diagnostic interviews, data have been obtained that strongly support clinical observations on migraine-major depression comorbidity. The findings to support a link between migraine and bipolar disorder are less consistent. Physicians caring for patients with migraine or affective disorders should maintain diagnostic vigilance for comorbid disease and, when present, should consider comorbidity in planning treatment interventions.

Adult↗
PubMed1993

Measuring the time course of anticipatory anxiety using the fear-potentiated startle reflex.

The time course of the facilitation of the acoustic startle reflex induced by anticipation of electric shocks was measured in 20 normal volunteers. Shocks could be administered during the last 10 s of 45-s threat conditions but not during 50-s no-threat conditions, each condition being signaled by a different light. Consistent with previous data, overall eyeblink startle levels were higher during the threat than during the no-threat conditions. However, the magnitude of this fear-potentiated startle effect became progressively larger in the threat condition the longer the light was on and then abruptly decreased with the onset of the light signaling the no-threat condition. These effects of the threat of shock on startle were interpreted in terms of anticipatory anxiety. Other interpretations, such as changes in selective or generalized attention, were also discussed. This paradigm provides a method to assess the time course of anticipatory anxiety in humans.

Acoustic Stimulation↗
PubMed1991

No association between an allele at the D2 dopamine receptor gene (DRD2) and alcoholism.

OBJECTIVE: --We attempted to replicate a positive allelic association between the A1 allele of DRD2 (the D2 dopamine receptor locus) and alcoholism that has been reported. DESIGN: --We compared allele frequencies at the previously described Taq I restriction fragment length polymorphism system of DRD2 in alcoholics and random population controls. SUBJECTS: --The alcoholic subjects were 44 unrelated white individuals, diagnosed by direct structured interview to have alcohol dependence (by the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, criteria). The subjects in our random population control group (N = 68) were also white. RESULTS: --For the control group, allele frequencies at DRD2 were 0.20 (A1) and 0.80 (A2). For the alcoholic group overall, allele frequencies were 0.23 (A1) and 0.77 (A2). There were no significant differences in allele frequencies at the DRD2 locus between alcoholics and controls. The allele frequencies in both groups agreed closely with those observed in most previously described control populations. Subtyping the alcoholic group according to presence or absence of family history of alcoholism, presence or absence of antisocial personality disorder, age of onset, presence or absence of physical withdrawal symptoms, or recent alcohol consumption (as a measure of severity) did not in any case reveal significant differences in allele frequencies. CONCLUSION: --We were not able to replicate the results previously reported. We conclude that our data do not support an allelic association between the A1 allele at DRD2 and alcoholism.

Adult↗
PubMed1991

Psychiatric disorders in relatives of probands with opiate addiction.

Previous research has documented high rates of major depression and antisocial personality in opiate addicts. This study was designed to investigate the relationship of dual diagnosis in opiate-addicted probands to family history of psychiatric disorders and substance use disorders in biological relatives. Psychiatric disorders and substance use disorders were evaluated using direct interview and family history in a sample of 877 first-degree relatives of 201 opiate addicts and 360 relatives of 82 normal controls. Results indicate that (1) compared with relatives of normal subjects, opiate addicts' relatives had substantially higher rates of alcoholism, drug abuse, depression, and antisocial personality; (2) relatives of depressed opiate-addicted probands had elevated rates of major depression and anxiety disorders but not of other disorders, suggesting the validity of subtyping opiate addicts by the presence or absence of major depression; and (3) in contrast, relatives of antisocial opiate addicts had rates of disorders that were not significantly different from those of relatives of opiate addicts without antisocial personality. Implications of these findings for the classification and treatment of substance abuse are discussed.

Adult↗
PubMed1991

Gender differences in the specificity of alcoholism transmission among the relatives of opioid addicts.

Gender differences in the specificity of drug versus alcohol transmission were examined among 201 opioid addicts and their 877 first-degree relatives using direct interviews and a structured family history method based on the Schedule for Affective Disorders and Schizophrenia Research Diagnostic Criteria. A strong association of parental alcoholism with alcoholism among the proband addicts was found, suggesting some specificity for drug versus alcohol abuse. We also found that among the 477 siblings, those with alcoholism alone did not have parents with drug abuse and those parents with drug abuse did not have children with alcoholism alone. Rates of parental alcoholism were higher in alcoholic female than in alcoholic male probands, suggesting greater female "loading" was needed in order to become alcoholic. This increased loading in women was also found among the siblings, but alcoholic parents appeared to transmit a nonspecific tendency for either drug or alcohol abuse to their female children. Thus, it may take a greater "dose" of parental transmission for a woman to become a substance abuser, and transmission of alcoholism may be specific in men, but not in women.

Adult↗
PubMed1991

Fear-potentiated startle in humans: effects of anticipatory anxiety on the acoustic blink reflex.

The effects of fear/anticipatory anxiety on the acoustic startle reflex were investigated in humans using a paradigm involving anticipation of electric shocks. The eyeblink component of the startle reflex, elicited by an abrupt auditory stimulus, was measured in 9 normal volunteers during either the anticipation of electric shocks (anticipatory anxiety) or periods in which no shocks were anticipated (safe period). The eyeblink was consistently higher in amplitude, and shorter in latency, during periods when the subjects anticipated shocks, compared to the safe periods. This effect could not be attributed solely to a reduction in habituation and was statistically significant before the subjects actually received any shock (a single 30 mA stimulation on the median nerve). These results indicate that anticipatory anxiety can be measured objectively in humans using the fear-potentiated startle reflex in a paradigm not actually requiring any shock. Because a great deal is known about the neuroanatomical and pharmacological mechanisms of fear-potentiated startle in laboratory animals, this test procedure may be especially useful in humans to investigate the neurobiological substrates of anxiety disorders and their pharmacological treatments.

Acoustic Stimulation↗