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Patrick F Sullivan

Publications and source records attributed to Patrick F Sullivan.

At least 37 records · Page 2Linked to original sources
PubMed2006

A joint genomewide linkage analysis of symptoms of alcohol dependence and conduct disorder.

BACKGROUND: A large linkage peak for alcohol dependence (AD) was detected on chromosome 4q in the Irish Affected Sib Pair Study of Alcohol Dependence (IASPSAD). Are the susceptibility genes underlying this peak specific for AD or do they increase risk for externalizing disorders more generally? Can we, in the IASPSAD, replicate prior evidence for linkage to conduct disorder (CD)? METHODS: The 733 all possible sibling pairs in IASPSAD were typed for 1,020 short-tandem-repeat genetic markers. Univariate and bivariate linkage analyses were conducted by the program sequential oligogenic linkage analysis routines (SOLAR), for both the raw and the transformed number of symptoms of AD (ADsx) and number of symptoms of CD (CDsx). In the bivariate analyses, specificity was assessed by the ratio of the variance accounted for in ADsx and CDsx by the quantitative trait locus. RESULTS: In the univariate linkage analyses, no evidence for linkage to CDsx was found under the 4q peak for ADsx and the largest peaks for CDsx were seen on chromosomes 1q (LOD=3.16) and 14p (LOD=2.36). In the bivariate linkage analysis, the 4q peak had high specificity for AD (AD/CD ratio of 39.9). Several smaller peaks, on chromosomes 1, 7, and 10, had moderate specificity for CD but also impacted on risk for AD, with AD/CD ratios of 0.18 to 0.32. CONCLUSIONS: Genes under the 4q linkage peak for AD in the IASPSAD impact specifically on risk for AD rather than more broadly on risk for externalizing syndromes. Suggestive linkages were found in several locations for CD, 2 of which broadly replicate prior findings. The bivariate analyses identified genomic locations containing susceptibility loci that impacted on risk for both CDsx and ADsx.

Alcohol-Related Disorders↗
PubMed2006

Six months of treatment for depression: outcome and predictors of the course of illness.

OBJECTIVE: The goals of this study were to determine the course of illness in a cohort of depressed patients undergoing treatment for 6 months and whether there are clinically useful predictors of their course of illness. METHOD: A cohort of 175 depressed outpatients undergoing drug treatment were followed prospectively for 6 months. Patients were initially randomly assigned to fluoxetine or nortriptyline. Those who responded were encouraged to continue taking their drugs for the 6 months. Those who did not were switched to other drugs or drug combinations. RESULTS: Of the 175 patients, 101 (58%) had a good outcome (achieved recovery and remained well), 54 (31%) had a fluctuating outcome (achieved recovery or remission but suffered a relapse or recurrence), and 20 (11%) had a poor outcome (remained depressed for the 6 months). Factors predicting good outcome included early response and a low level of schizoid personality disorder symptoms, and variables predicting poor outcome included a high score for harm avoidance and the absence of an early response. CONCLUSIONS: Depression is a recurring and chronic disorder. Personality factors such as a high harm avoidance score and schizoid traits were associated with a worse outcome, but demographic features, depression characteristics, depression subtypes, and comorbidity were not. Early response was strongly associated with the course of illness, but none of these features added significantly to the clinicians' ability to predict outcome.

Adult↗
PubMed2006

Empirical evaluation of the genetic similarity of samples from twin registries in Australia and the Netherlands using 359 STRP markers.

One way to achieve the large sample sizes required for genetic studies of complex traits is to combine samples collected by different groups. It is not often clear, however, whether this practice is reasonable from a genetic perspective. To assess the comparability of samples from the Australian and the Netherlands twin studies, we estimated Fst (the proportion of total genetic variability attributable to genetic differences between cohorts) based on 359 short tandem repeat polymorphisms in 1068 individuals. Fst was estimated to be 0.30% between the Australian and the Netherlands cohorts, a smaller value than between many European groups. We conclude that it is reasonable to combine the Australian and the Netherlands samples for joint genetic analyses.

Australia↗
PubMed2005

Combined linkage and association analyses of the 124-bp allele of marker D2S2944 with anxiety, depression, neuroticism and major depression.

A central issue in psychiatric genetics is whether positive findings replicate. Zubenko et al. (2002b, Mol. Psychiatry 7:460-467) reported an association of the 124-bp allele of D2S2944 with recurrent early-onset major depression for females. We tested for association of this allele to continuous measures of anxiety, depression and neuroticism in a Dutch sample of 347 males and 448 females, and to DSM-IV major depression in a subsample of 210 males and 295 females. The association of the 124-bp allele to depression in females was not replicated, but there were significant associations (not significant after correction for multiple testing) with anxiety and anxious depression in males. However, the association occurred in the absence of evidence for linkage in this region on chromosome 2.

Anxiety↗
PubMed2005

Epidemiology of cancer-related fatigue in the Swedish twin registry.

BACKGROUND: Estimates of the prevalence of cancer-related fatigue (CRF) are wide, and data suggest that fatigue is more prevalent among cancer patients than among the general population. However, most studies examining the prevalence of CRF have been hospital-based or clinic-based studies, which often are subject to bias. METHODS: Point prevalence and prevalence odds ratios of fatigue were estimated using data from a large, population-based cohort that was screened for fatigue and linked with national registry-based data about cancer. Prevalence odds ratios and 95% confidence intervals were calculated using logistic regression with general estimating equations. RESULTS: Approximately 23% of cancer registrants reported abnormal fatigue in the previous 6 months, 19% reported abnormal fatigue that lasted for at least 1 month, 14% reported abnormal fatigue that lasted at least 6 months, and 11% reported abnormal fatigue that lasted at least 6 months and caused significant functional impairment. Individuals who were listed in the cancer registry within the last 5 years were more likely to report experiencing fatigue than individuals who were not listed. There was an elevated prevalence of fatigue among those who were registered with carcinomas of the lung, uterine cervix, colon-rectum, ovaries, and prostate. Both women and men who were listed recently in the cancer registry were more likely to experience any level of fatigue than the comparison group. However, a greater proportion of women experienced fatigue relative to men. CONCLUSIONS: A greater proportion of individuals who were listed in a national cancer registry reported experiencing fatigue compared with individuals in the general population.

Cohort Studies↗
PubMed2005

MAOA haplotypes associated with thrombocyte-MAO activity.

BACKGROUND: The aim was to ascertain whether thrombocyte MAO (trbc-MAO) activity and depressed state are genetically associated with the MAO locus on chromosome X (Xp11.3 - 11.4). We performed novel sequencing of the MAO locus and validated genetic variants found in public databases prior to constructing haplotypes of the MAO locus in a Swedish sample (N = 573 individuals). RESULTS: Our results reveal a profound SNP desert in the MAOB gene. Both the MAOA and MAOB genes segregate as two distinct LD blocks. We found a significant association between two MAOA gene haplotypes and reduced trbc-MAO activity, but no association with depressed state. CONCLUSION: The MAO locus seems to have an effect on trbc-MAO activity in the study population. The findings suggest incomplete X-chromosome inactivation at this locus. It is plausible that a gene-dosage effect can provide some insight into the greater prevalence of depressed state in females than males.

Blood Platelets↗
PubMed2005

A genome scan of neuroticism in nicotine dependent smokers.

Neuroticism is a personality factor that has consistently been demonstrated to be associated with anxiety, depression, and other "internalizing" disorders. We analyzed a genome scan for neuroticism on a sample of 129 sib-pair families (113 with a single sibling pair, 18 with multiple sibling pairs) containing a total of 201 possible sibling pairs, ascertained for concordance on nicotine dependence. Using Merlin-Regress, we replicated peaks for neuroticism described by prior studies, on chromosomes 1 and 11 with LOD scores of 2.52 and 1.97 (P-value of 0.003 and 0.0108) respectively, and have some evidence for a novel finding on chromosome 12 with a LOD of 2.85 (P-value of 0.0014).

Adult↗
PubMed2005

The prevalence of self-reported chronic fatigue in a U.S. twin registry.

OBJECTIVE: To investigate the prevalence and correlates of various definitions of self-reported lifetime fatiguing illness in a U.S. twin registry. METHODS: Data from 4591 female and male twins from the population-based Mid-Atlantic Twin Registry were available for this study. Variables representing different definitions of lifetime fatiguing illness and personal characteristics were obtained through questionnaires. Odds ratios and 95% confidence intervals were calculated as measures of association between fatigue and gender. Kaplan-Meier curves were produced to examine the age at onset for lifetime fatiguing illnesses. RESULTS: Prevalences for different definitions of self-reported lifetime fatigue ranged from 36.7% for any fatigue to 2.7% for chronic fatigue syndrome-like illness. Females were two to three times more likely to report fatigue than males. Gender differences increased as fatigue definitions grew more restrictive. Ages at onset of chronic fatiguing illness were significantly earlier and the number of ancillary symptoms was greater for females than males. People with lifetime fatigue had significantly more compromised functional status than people without lifetime fatigue. CONCLUSION: The prevalence of self-reported lifetime fatiguing illness varied widely depending upon how it was defined. Given the debilitating consequences of fatiguing illnesses, the reasons for the female predominance and the earlier onset in women should receive increased research priority.

Adult↗
PubMed2005

The epidemiology of chronic fatigue in the Swedish Twin Registry.

BACKGROUND: Chronic fatigue syndrome (CFS) remains an idiopathic and controversial entity. METHOD: We screened 31405 individual members of the Swedish Twin Registry (aged 42-64 years) for the symptoms of fatiguing illness via a telephone questionnaire. We refined self-reported symptoms via data from several national registries and from physician review of all available medical records in order to approximate closely the dominant case definition of CFS. FINDINGS: The 6-month prevalence of CFS-like illness was 2.36% (95% CI 2.19-2.53) and was markedly higher in women than men, odds ratio 3.92 (95% CI 3.24-4.72) with no significant association with age or years of education. There was a highly significant association with occupation that disappeared after accounting for gender. INTERPRETATION: CFS-like illness may be more common that previously acknowledged. There is a marked increase in risk by gender. Previous reports that CFS is more prevalent in individuals in certain occupational categories were not confirmed and may have been due to confounding by gender.

Adult↗
PubMed2005

Chronic fatigue in a population sample: definitions and heterogeneity.

BACKGROUND: Numerous nosological decisions are made when moving from the common human symptom of unusual fatigue to the rare chronic fatigue syndrome (CFS). These decisions have infrequently been subjected to rigorous evaluation. METHOD: We obtained telephone interview data on fatiguing symptoms from 31406 individuals twins in the Swedish Twin Registry aged 42-64 years; 5330 subjects who endorsed fatigue and possessed no exclusionary condition formed the analytic group. We evaluated the definition and classification of CFS-like illness using graphical methods, regression models, and latent class analysis. RESULTS: Our results raise fundamental questions about the 1994 Centers for Disease Control criteria as (1) there was no empirical support for the requirement of four of eight cardinal CFS symptoms; (2) these eight symptoms were not equivalent in their capacity to predict fatigue; and (3) no combination of symptoms was markedly more heritable. Critically, latent class analysis identified a syndrome strongly resembling CFS-like illness. CONCLUSIONS: Our data are consistent with the 'existence' of CFS-like illness although the dominant nosological approach captures population-level variation poorly. We suggest that studying a more parsimonious case definition - impairing chronic fatigue not due to a known cause - would represent a way forward.

Adult↗
PubMed2005

Twin analyses of chronic fatigue in a Swedish national sample.

BACKGROUND: Chronic fatigue has infrequently been studied in twins. Data from twin studies can inform clinical and research approaches to the management and etiology of human complex traits. METHOD: The authors obtained telephone interview data on current chronic fatigue from 31406 individuals twins in the Swedish Twin Registry (aged 42-64 years, 75.68% response rate), from both members of 12407 pairs and from one member of 6592 pairs. Of the complete pairs, 3269 pairs were monozygotic, 9010 pairs dizygotic, and 128 pairs of unknown zygosity. Structural equation twin modeling was used to estimate the latent genetic architecture of varying definitions of fatiguing illness. RESULTS: Estimates of additive genetic effects, shared environmental effects, and individual-specific environmental effects were similar in males and females. No definition of current fatiguing illness (ranging from any fatigue to CFS-like illness) was strikingly distinctive. Individual-specific effects were the predominant source of variation, followed by modest genetic influences. We could not exclude a small but conceptually important contribution of shared environmental effects. CONCLUSIONS: Current fatiguing illness appears to be a complex trait resulting from both environmental and genetic sources of variation without pronounced differences by gender.

Adult↗
PubMed2005

The use of race variables in genetic studies of complex traits and the goal of reducing health disparities: a transdisciplinary perspective.

The use of racial variables in genetic studies has become a matter of intense public debate, with implications for research design and translation into practice. Using research on smoking as a springboard, the authors examine the history of racial categories, current research practices, and arguments for and against using race variables in genetic analyses. The authors argue that the sociopolitical constructs appropriate for monitoring health disparities are not appropriate for use in genetic studies investigating the etiology of complex diseases. More powerful methods for addressing population structure exist, and race variables are unacceptable as gross proxies for numerous social/environmental factors that disproportionately affect minority populations. The authors conclude with recommendations for genetic researchers and policymakers, aimed at facilitating better science and producing new knowledge useful for reducing health disparities.

Health Status↗
PubMed2005

The types of regular cigarette smokers: a latent class analysis.

The present study sought to refine cigarette smoking exposure by examining whether individuals with a history of regular cigarette smoking could be classified into meaningful subgroups based on their smoking habits, nicotine dependence, and quit attempts. Data were obtained from 3,025 male and female twins aged 22-59 years who participated in two longitudinal studies based on the Virginia Twin Registry. Latent class analysis was used to identify the number and nature of subgroups of smokers reporting similar smoking habits based on 18 characteristics. Estimates of prevalence for different classes of smoking were obtained along with expected frequencies of endorsements for each smoking behavior by class. Distributions of demographic characteristics, psychopathology, and personality were examined as external validators. The results demonstrated considerable heterogeneity and revealed eight classes of smokers who differed in their degree of nicotine dependence, cessation attempts, and ability to quit smoking. Smoking classes ranged from individuals who were all former smokers with low nicotine dependence who attempted to quit once and were successful, to individuals who were all current smokers with little desire to quit, to individuals with high nicotine dependence with multiple quit attempts, only a subset of which were successful. Estimates of prevalence for each class were 9%-20%. Our findings support the idea that regular cigarette smokers are highly heterogeneous and highlight the need for smoking exposure refinement in future studies. Acknowledging the complexity of cigarette smoking and classifying smokers into more specific subgroups based on their smoking behavior in future studies will enable more accurate evaluation of disease etiology and risk and could lead to more appropriate smoking cessation interventions.

Adult↗
PubMed2005

Mania in the Swedish Twin Registry: criterion validity and prevalence.

BACKGROUND: In population surveys, the assessment of mania is commonly done by trained lay interviewers using structured diagnostic instruments: the validity of this approach has been questioned. We examined the criterion validity and prevalence of lifetime mania in a survey of Swedish twins conducted with interview methodology usually applied in psychiatric epidemiology. METHODS: 41 838 individuals in the Swedish Twin Registry were evaluated via a telephone interview that included the eight DSM-IV mania items, and these data were merged with inpatient hospitalization discharge diagnoses from two comprehensive national registries (the criterion). An algorithm with eight cut-points was used to diagnose lifetime mania, and compared by a receiver operator characteristic curve to the criterion. The algorithm requiring at least four positive items resembling a DSM-IV diagnosis. RESULTS: History of hospitalization for a psychiatric condition that included a manic episode was present for 0.7% of all living twins, and predicted non-response to the survey (OR = 0.5; 95% CI = 0.4-0.6). The incidence rate for first hospitalization was 2.1/10 000 year(-1). For > or =1 symptom (first cut-point), the prevalence, sensitivity and specificity were 3.6%, 39.0% and 96.6%; for > or = 4 symptoms (DSM-IV-like cut-point) 2.6%, 36.5% and 97.6%; and for eight symptoms 0.3%, 18.0% and 99.8%. Positive predictive values were, respectively, 5.5%, 7.0% and 29.8%. CONCLUSIONS: The performance of the telephone screening for mania by lay interviewers in terms of positive predictive power was not satisfactory; despite a high specificity, the false positive rate was high. The low population prevalence of mania, non-response bias, criterion choice and inherent limitations of the interviewing method are among the explanations. Assessment of a lifetime manic episode based on lay interviewer screening may yield misleading data.

Bipolar Disorder↗
PubMed2005

The Irish Affected Sib Pair Study of Alcohol Dependence: study methodology and validation of diagnosis by interview and family history.

BACKGROUND: This article is the first report of the Irish Affected Sib Pair Study of Alcohol Dependence, whose goal is to detect the genomic location of susceptibility loci for alcohol dependence (AD). This article describes phenotypic characteristics of the probands, siblings, and parents included in the sample and examines agreement among different sources of diagnostic information, including the validity of family history (FH) assessment. METHODS: Structured diagnostic interviews were conducted with 1414 individuals from 591 families ascertained in Ireland. AD was assessed among 1201 probands and affected siblings with use of the Semi-Structured Assessment for the Genetics of Alcoholism and among 213 parents with use of a modified version of the Structured Clinical Interview for DSM. Probands and siblings were also assessed for drinking history, comorbid disorders, and other clinical characteristics. FH reports based on FH-Research Diagnostic Criteria were obtained for 1113 of these individuals as well as for 3652 first-degree relatives who were not interviewed. RESULTS: Sample characteristics confirm the severity of AD among the affected individuals. Agreement between FH ratings and diagnoses based on direct interviews was high for both parent-offspring and sibling-sibling comparisons (e.g., positive and negative predictive values > 80% for a range of cutoffs). Agreement among individuals about their family members was also high for a single item (1 month or more of drinking problems, tetrachoric r = 0.86-0.98), the total number of DSM-IV AD symptoms (polychoric r = 0.86-0.96), and classifications based on a range of cutoffs (kappa = 0.75-0.80). Use of multiple informants improved classification accuracy only slightly (6-10%). CONCLUSIONS: The authors successfully collected data for a large sample of affected sibling pairs for molecular genetic analysis of AD. Individuals with AD were able to provide accurate evaluations of alcoholism symptoms in their parents and adult siblings. A single screening item performed nearly as well as the full scale. Collecting information from multiple informants may not be cost effective for the gain in predictive accuracy. FH information collected from affected informants can be a valuable source of diagnostic information for family studies of alcoholism.

Adult↗
PubMed2005

Familial clustering of major depression and anxiety disorders in Australian and Dutch twins and siblings.

The aim of this study was to investigate familial influences and their dependence on sex for panic disorder and/or agoraphobia, social phobia, generalized anxiety disorder and major depression. Data from Australian (N = 2287) and Dutch (N = 1185) twins and siblings who were selected for a linkage study and participated in clinical interviews to obtain lifetime Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) diagnoses were used. In a liability model, tetrachoric correlations were estimated in sibling pairs and sex differences between sibling correlations were tested. For each diagnosis, the sibling correlations could be constrained to be equal across the Australian and Dutch samples. With the exception of panic disorder and/or agoraphobia, all sibling correlations were the same for brother, sister and opposite-sex sibling pairs and were around .20. For panic disorder and/or agoraphobia, the correlation was .23 in brother and sister pairs, but absent in opposite-sex sibling pairs. From these results it can be concluded that upper heritability estimates, based on twice the correlations in the sibling pairs, vary between 36% (major depression) and 50% (social phobia). Furthermore, different genetic risk factors appear to contribute to the vulnerability for panic disorder and/or agoraphobia in men and women. No other sex differences were found.

Adult↗
PubMed2004

Warming chambers stimulate early season growth of an arctic sedge: results of a minirhizotron field study.

We examined the effects of passive open-top warming chambers on Eriophorum vaginatum production near Toolik Lake, Alaska, USA. During the 2002 growing season, chamber warming was consistent with the magnitude and seasonality observed in recent decades throughout northwestern North America. Leaf-growth rates were higher in late May and early June; maximum growth rates in each leaf cohort occurred earlier and peak biomass was observed 20 days earlier within the chambers. Consequently, plants within the chambers maintained more live leaf biomass during the period of highest photosynthetically active radiation. Annual leaf production within the chambers (21+/-2 mg tiller) was not significantly different than under ambient conditions (17+/-2 mg tiller) (P=0.2256) despite higher early-season growth rates. Root growth began earlier; growth rates were higher in late May and early June, and maximum growth rates occurred earlier within the chambers. Therefore, plants within the chambers maintained greater root biomass during what earlier studies have identified as a period of relatively high nutrient availability. Annual root production within the chambers (191+/-42 g m-2) was not significantly different than under ambient conditions (119+/-48 g m-2) (P=0.1979), although there was a trend toward higher production within the chambers. The tendency toward higher root production within the chambers is consistent with previous laboratory experiments and with the predictions of biomass allocation theory.

Alaska↗