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Biomedical subjects

K R Merikangas

Publications and source records attributed to K R Merikangas.

At least 37 records · Page 2Linked to original sources
PubMed1999

On a randomization procedure in linkage analysis.

Although much theoretical work has been undertaken to derive thresholds for statistical significance in genetic linkage studies, real data are often complicated by many factors, such as missing individuals or uninformative markers, which make the validity of these theoretical results questionable. Many simulation-based methods have been proposed in the literature to determine empirically the statistical significance of the observed test statistics. However, these methods either are not generally applicable to complex pedigree structures or are too time-consuming. In this article, we propose a computationally efficient simulation procedure that is applicable to arbitrary pedigree structures. This procedure can be combined with statistical tests, to assess the statistical significance for genetic linkage between a locus and a qualitative or quantitative trait. Furthermore, the genomewide significance level can be appropriately controlled when many linked markers are studied in a genomewide scan. Simulated data and a diabetes data set are analyzed to demonstrate the usefulness of this novel simulation method.

Computer Simulation↗
PubMed1999

Influence of parental concordance for psychiatric disorders on psychopathology in offspring.

OBJECTIVE: To examine the influence of parental mating types for substance abuse and anxiety/affective disorders on the risk of psychopathology among child and adolescent offspring. METHOD: Emotional and behavioral disorders were assessed in offspring, aged 7 to 17 years, of male and female parents who served as probands from a family study of comorbidity of substance abuse and anxiety disorders. RESULTS: The findings indicated that (1) patterns of psychopathology among offspring were similar for mothers and fathers; (2) spouse concordance for psychopathology was greater among parents with substance abuse than among those with anxiety, particularly among female substance abusers; (3) there was a direct relationship between the number of affected parents and the magnitude of psychopathology in children, particularly with respect to the anxiety disorders; and (4) by contrast, rates of conduct disorder were elevated only among offspring of dually affected parents, irrespective of the specific parental disorders. CONCLUSIONS: These findings underscore the importance of the contribution of both mothers and fathers, particularly those with concordance for psychiatric disorders, to the development of psychopathology in offspring.

Adolescent↗
PubMed1999

Psychosocial and clinical correlates of ADHD in a community sample of school-age children.

OBJECTIVE: To identify the psychosocial and clinical correlates of attention-deficit hyperactivity disorder (ADHD) in a community sample of children and to examine the validity of a subclinical form of ADHD. METHOD: The sample of 449 children (mean age 9.2 years, SD 1.78; 53.6% boys) participated in the second stage of a community survey. Of these, 359 (80%) screened positive at stage 1. On the basis of a structured diagnostic interview with a parent, children were classified into 1 of 3 mutually exclusive groups: ADHD (n = 89), subthreshold ADHD (n = 100), and non-ADHD (n = 260). RESULTS: As measured by the Children's Global Assessment Scale, the ADHD group was more impaired than the subthreshold group, which was more impaired than the non-ADHD group (p < .05 for each test). Children in the ADHD group were more likely to be male, to have mothers with a history of psychiatric treatment, to have fathers with a history of excessive alcohol use, and to live in low-income families with higher levels of family dysfunction (p < .05 for all variables). A model containing male gender, family dysfunction, and low income was most predictive of ADHD status (p < .01). ADHD was also associated with psychiatric comorbidity, especially disruptive behavior disorders. CONCLUSIONS: These results support a dimensional approach to ADHD. More severe forms of ADHD are associated with psychosocial adversity and psychiatric comorbidity.

Analysis of Variance↗
PubMed1998

Fear-potentiated startle in adolescent offspring of parents with anxiety disorders.

BACKGROUND: The startle reflex and its potentiation by aversive states was used as a possible vulnerability marker for anxiety disorders in adolescent offspring of parents with this condition. METHODS: The participants were 39 low-risk adolescents (16 male/23 female) with a parental history of no psychiatric disorder and 35 high-risk adolescents (18 male/17 female) with a parental history of anxiety disorders. The magnitude of startle was examined at baseline and during anticipation of an aversive stimulus (fear-potentiated startle). RESULTS: Startle was found to discriminate between children at high and low risk for anxiety disorders; however, different abnormalities for high-risk male and female subjects were observed. Startle levels, overall, were elevated among high-risk female subjects, whereas high-risk male subjects exhibited greater magnitude of startle potentiation during aversive anticipation. CONCLUSIONS: Startle reactivity may serve as a vulnerability marker for the development of anxiety disorders. With its basic grounding in animal and human behavioral research, startle may enhance our understanding of the underlying neurobiological bases of human anxiety states.

Adolescent↗
PubMed1998

Familial transmission of substance use disorders.

BACKGROUND: There is increasing evidence that substance use disorders are familial and that genetic factors explain a substantial degree of their familial aggregation. To perform a controlled family study of probands with several different predominant drugs of abuse, including opioids, cocaine, cannabis, and/or alcohol. METHODS: The subjects for the present study included 231 probands with dependence on opioids, cocaine, cannabis, and/or alcohol and 61 control probands, and their 1267 adult first-degree relatives. Diagnostic estimates were based on semistructured diagnostic interviews and/or structured family history interviews regarding each proband, spouse, and adult first-degree relative. The interview data were reviewed blindly and independently by clinicians with extensive experience in the evaluation and treatment of substance use disorders. RESULTS: There was an 8-fold increased risk of drug disorders among the relatives of probands with drug disorders across a wide range of specific substances, including opioids, cocaine, cannabis, and alcohol, which is largely independent from the familial aggregation of both alcoholism and antisocial personality disorder. There was also evidence of specificity of familial aggregation of the predominant drug of abuse. CONCLUSIONS: Elevation in risk of this magnitude places a family history of drug disorder as one of the most potent risk factors for the development of drug disorders. These results suggest that there may be risk factors that are specific to particular classes of drugs as well as risk factors that underlie substance disorders in general.

Adult↗
PubMed1998

A controlled family study of anorexia nervosa and bulimia nervosa: psychiatric disorders in first-degree relatives and effects of proband comorbidity.

BACKGROUND: We used contemporary family-epidemiological methods to examine patterns of comorbidity and familial aggregation of psychiatric disorders for anorexia and bulimia nervosa. METHODS: Direct interviews and blind best-estimate diagnostic procedures were used with diagnostically "pure" groups of probands with eating disorders and a matched control group. Lifetime prevalence rates of eating disorders, mood disorders, substance use disorders, anxiety disorders, and selected personality disorders were determined in female probands with restricting anorexia nervosa (n=26) or bulimia nervosa (n=47), control women (n=44), and first-degree biological relatives (n=460). RESULTS: Relatives of anorexic and bulimic probands had increased risk of clinically subthreshold forms of an eating disorder, major depressive disorder, and obsessive-compulsive disorder. Familial aggregation of major depressive disorder and obsessive-compulsive disorder was independent of that of anorexia nervosa and bulimia nervosa. These relatives also had increased risk of other anxiety disorders, but the mode of familial transmission was not clear-cut. The risk of substance dependence was elevated among relatives of bulimic probands compared with relatives of anorexic probands, and familial aggregation was independent of that of bulimia nervosa. The risk of obsessive-compulsive personality disorder was elevated only among relatives of anorexic probands, and there was evidence that these 2 disorders may have shared familial risk factors. CONCLUSIONS: There may be a common familial vulnerability for anorexia nervosa and bulimia nervosa. Major depressive disorder, obsessive-compulsive disorder, and substance dependence are not likely to share a common cause with eating disorders. However, obsessional personality traits may be a specific familial risk factor for anorexia nervosa.

Adolescent↗
PubMed1998

Psychopathology and temperament in parents and offspring: results of a family study.

BACKGROUND: Although research on the association between temperament and psychopathology has received renewed interest, few investigations have addressed the issues of psychiatric comorbidity or the role of temperament across the life span. The present investigation employed a family study/high-risk design to examine the specificity of associations between temperamental traits and psychiatric disorders in both children and adults. METHODS: The sample was composed of 244 probands and 82 children (ages 7-17) from the Yale Family Study of Comorbidity of Substance Abuse and Anxiety. Psychiatric disorders were assessed using structured diagnostic interviews administered by clinicians, and temperament was measured using the Dimensions of Temperament Survey. RESULTS: In both adults and children, anxiety and depression were generally associated with low scores on adaptability and approach/withdrawal, while externalizing or substance use disorders were associated with low attention scores and higher activity. However, psychiatric comorbidity was associated with the manifestation of both clusters of temperamental traits and far greater impairment and clinical severity. Some temperamental characteristics in children also demonstrated specificity of association with parental psychiatric disorder. LIMITATIONS: This investigation was limited to the analysis of cross-sectional data and was unable to separate genetic from other familial risk factors. CONCLUSIONS: The results suggest that temperament remains associated with psychopathology across the life span and may reflect diverse familial influences. Clinical intervention and prevention efforts may benefit from focusing on individuals at higher risk for psychiatric disorder through parental psychopathology or the expression of temperament problems in childhood.

Adolescent↗
PubMed1998

Co-morbidity and familial aggregation of alcoholism and anxiety disorders.

BACKGROUND: This study examined the patterns of familial aggregation and co-morbidity of alcoholism and anxiety disorders in the relatives of 165 probands selected for alcoholism and/or anxiety disorders compared to those of 61 unaffected controls. METHODS: Probands were either selected from treatment settings or at random from the community. DSM-III-R diagnoses were obtained for all probands and their 1053 first-degree relatives, based on direct interview or family history information. RESULTS: The findings indicate that: (1) alcoholism was associated with anxiety disorders in the relatives, particularly among females; (2) both alcoholism and anxiety disorders were highly familial; (3) the familial aggregation of alcoholism was attributable to alcohol dependence rather than to alcohol abuse, particularly among male relatives; and (4) the the pattern of co-aggregation of alcohol dependence and anxiety disorders in families differed according to the subtype of anxiety disorder; there was evidence of a partly shared diathesis underlying panic and alcoholism, whereas social phobia and alcoholism tended to aggregate independently. CONCLUSIONS: The finding that the onset of social phobia tended to precede that of alcoholism, when taken together with the independence of familial aggregation of social phobia and alcoholism support a self-medication hypothesis as the explanation for the co-occurrence of social phobia and alcoholism. In contrast, the lack of a systematic pattern in the order of onset of panic and alcoholism among subjects with both disorders as well as evidence for shared underlying familial risk factors suggests that co-morbidity between panic disorder and alcoholism is not a consequence of self-medication of panic symptoms. The results of this study emphasize the importance of examining co-morbid disorders and subtypes thereof in identifying sources of heterogeneity in the pathogenesis of alcoholism.

Alcoholism↗
PubMed1998

Multiple jeopardy: risk and protective factors among addicted mothers' offspring.

Objectives of this study were to ascertain risk and protective factors in the adjustment of 78 school-age and teenage offspring of opioid- and cocaine-abusing mothers. Using a multimethod, multiinformant approach, child outcomes were operationalized via lifetime psychiatric diagnoses and everyday social competence (each based on both mother and child reports), and dimensional assessments of symptoms (mother report). Risk/protective factors examined included the child sociodemographic attributes of gender, age, and ethnicity, aspects of maternal psychopathology, and both mother's and children's cognitive functioning. Results revealed that greater child maladjustment was linked with increasing age, Caucasian (as opposed to African American) ethnicity, severity of maternal psychiatric disturbance, higher maternal cognitive abilities (among African Americans) and lower child cognitive abilities (among Caucasians). Limitations of the study are discussed, as are implications of findings for future research.

Adaptation, Psychological↗
PubMed1998

Psychopathology among offspring of parents with substance abuse and/or anxiety disorders: a high-risk study.

This paper reports the results of a high-risk study of children under age 18 of parents who served as probands in a family study of comorbidity of substance abuse and anxiety disorders. There was a strong degree of specificity of familial aggregation of both the anxiety disorders and substance disorders. Rates of conduct disorder and depression were elevated among offspring of all affected parents. Inclusion of co-parent disorders in the evaluation of familial transmission in the present study strengthened the findings regarding the specificity of transmission of the anxiety disorders and the links between both parental substance abuse and antisocial personality with child conduct disorder.

Adolescent↗
PubMed1997

Darkness facilitates the acoustic startle reflex in humans.

The effects of darkness on startle reactivity and prepulse inhibition were investigated in two studies with 25 subjects participating in each study. Acoustic startle stimuli that were or were not preceded by an acoustic prepulse were delivered in alternating periods of complete darkness or light. In both studies, darkness significantly increased the magnitude of startle but did not affect prepulse inhibition (PPI). The PPI results suggest that darkness did not increase attention to the auditory modality, so that the startle facilitation in the dark probably did not result from an attentional process. The increased startle in the dark was significantly correlated with the intensity of subjects' fear of the dark as children based on retrospective rating scales. It is hypothesized that the startle facilitation in the dark results from a change in affect rather than from a change in attention.

Acoustic Stimulation↗
PubMed1997

Association between migraine and stroke in a large-scale epidemiological study of the United States.

OBJECTIVE: To examine the association between stroke and migraine in an epidemiological study. DATA SOURCES AND DESIGN: The National Health and Nutrition Examination Survey baseline and first follow-up data were used to investigate cross-sectional and longitudinal associations between headache/migraine and stroke. SETTING: Study participants from a national probability sample of the civilian noninstitutionalized population of the United States. MAIN OUTCOME MEASURE: Self-reported physician diagnosis of stroke. RESULTS: After controlling for established risk factors for stroke (hypertension, diabetes, heart disease, and gender), both migraine and severe nonspecific headache were associated with a significantly increased risk for stroke reported at follow-up. The risk for stroke associated with migraine decreased as the age at stroke increased. CONCLUSIONS: Our results strengthen previous evidence regarding a nonrandom association of both headache and migraine with stroke, particularly among young women. To our knowledge, this is the first systematic examination in a large-scale prospective epidemiological study of men and women with sufficient statistical power to test the association between migraine and stroke in women. Severe headache and migraine should be considered as risk factors for the development of stroke, particularly in the absence of other well-established stroke risk factors. Further investigation is required to identify the putative mechanisms underlying comorbidity of migraine and stroke.

Adult↗
PubMed1997

Psychiatric disorders in women with bulimia nervosa and their first-degree relatives: effects of comorbid substance dependence.

OBJECTIVE: Women with bulimia nervosa (BN) and comorbid substance dependence often display impulsive behaviors. We assessed Axis I and II psychiatric diagnoses in their first-degree relatives in order to understand the etiological factors that may contribute to this subtype of BN. METHOD: We used contemporary family-epidemiological methodology to compare the lifetime prevalence of psychiatric disorders among 47 women with BN and 44 non-eating-disordered community control women, and their first-degree relatives (177 and 190, respectively). BN probands were stratified by the presence (n = 20) or absence (n = 27) of a lifetime history of alcohol and/or drug dependence. RESULTS: Social phobia, conduct disorder, and clusters B and C personality disorders were significantly more prevalent among BN probands with substance dependence than among BN probands without substance dependence or control women probands. Substance use disorders, social phobia, panic disorder, and cluster B personality disorders were significantly more prevalent among the relatives of BN probands with substance dependence than the relatives of the other two groups. DISCUSSION: Women with BN and substance dependence have problems with social anxiety, antisocial behavior, and a variety of personality disturbances, and come from families where there are problems with substance use disorders, anxiety, impulsivity, and affective instability. These data raise the possibility that a familial vulnerability for impulsivity and affective instability may contribute to the development of substance dependence in a subgroup of women with BN.

Adult↗
PubMed1997

Comorbidity of migraine and psychiatric disorders.

This article reviews the evidence for comorbidity of migraine with psychiatric disorders, particularly the affective and anxiety disorders. Studies of the association between migraine and depression in both clinical and community studies have provided consistent evidence regarding a substantial degree of comorbidity between these disorders, regardless of the index disorder for which the subject sought treatment in the clinical settings. Methodologic issues, possible mechanisms, and implications of comorbidity for clinical practice and future research are discussed.

Anxiety↗
PubMed1997

Startle modulation in children at risk for anxiety disorders and/or alcoholism.

OBJECTIVE: To examine the startle reflex as a possible vulnerability marker among offspring of parents with anxiety disorders and/or alcoholism. METHOD: The subjects were 66 male and female offspring (aged 10 to 17 years) of proband who participated in a family study of comorbidity of alcoholism and anxiety disorders. Testing consisted of examining the startle reflex and its modulation by prepulse stimuli (prepulse facilitation and prepulse inhibition). RESULTS: Different components of the startle discriminated among children of parents with anxiety disorders, children of alcoholics, and children of normal controls. Specifically startle magnitude was elevated in children with a parental history of an anxiety disorder, whereas startle habituation and prepulse inhibition were impaired in children with a parental history of alcoholism. CONCLUSION: These findings suggest that individual differences in the startle reflex may serve as a vulnerability marker for the development of anxiety disorders and alcohol problems.

Adolescent↗
PubMed1997

Subthreshold syndromes of depression and anxiety in the community.

Nearly 50% of individuals in the community meet threshold or subthreshold diagnostic criteria for depression or anxiety, with depression being far more common. Co-occurrence of anxiety and depression is common, as the majority of individuals who experience anxiety also manifest threshold- or subthreshold-level depression. In the current study, addition of subthreshold categories improved the coverage of treated cases in the community by nearly a third; 61% of subjects were diagnosed according to threshold criteria while 89% were diagnosed according to subthreshold categories. These results suggest that inclusion of subthreshold-level syndromes enhances the validity of diagnostic systems by increasing the proportion of treated cases that meet diagnostic criteria and by providing a more accurate representation of milder syndromes of depression and anxiety.

Adult↗
PubMed1996

Genetics of migraine and other headache.

Recent progress in the genetics of migraine and other headache syndromes occurred in three major areas during the past year: systematic family studies of migraine, large-scale population-based twin studies, and linkage and association studies of familial hemiplegic migraine. Studies of linkage between familial hemiplegic migraine and marker 19p13 in 13 extended families have found a total of seven families with linkage to this region. Three large scale population-based twin studies of headache have revealed that approximately one-half of the variation in migraine could be attributable to additive genes, with the remainder primarily caused by unshared rather than shared environmental factors between twins. Migraine is clearly a complex disease characterized by high population prevalence, an inconclusive mode of transmission, and a lack of clear evidence for phenotypic validity. Increasing knowledge from family and twin studies using contemporary diagnostic methods will help to clarify the factors contributing to the heterogeneity of this condition.

Headache↗