A Twin Study of Depression and Migraine: Evidence for a Shared Genetic Vulnerability

Schur, Ellen A.; Noonan, Carolyn; Buchwald, Dedra; Goldberg, Jack; Afari, Niloofar

doi:10.1111/j.1526-4610.2009.01425.x

Cited by 72 publications

(75 citation statements)

References 49 publications

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“…SEM has been used in other fields, such as genetic epidemiology and psychology, 19,20 but remains very rarely used in medical research. Path analysis is an appropriate method to assess the causal contribution of one variable to another.…”

Section: Discussionmentioning

confidence: 99%

Pathways Leading to Atherosclerosis

et al. 2011

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Abstract-Several risk factors of cardiovascular diseases have been studied using direct association measures. Because the incidence of obesity and cardiovascular diseases is rising, it is important to correctly model these risk factors involved in development of cardiovascular diseases. Until now, statistical methods lacked to achieve this goal because of complex interrelationships involved. Structural Equation Modeling (SEM) is an advanced statistical technique that enables solving this issue. The aims of this study were to investigate whether SEM could unravel pathways involved in cardiovascular diseases and to visualize these pathways in a model. In 322 healthy participants of the PROGRAM (PROgramming factors for GRowth And Metabolism) study, 18 to 24 years of age, we explored pathways leading to atherosclerosis measured by carotid intima-media thickness. Using SEM, we were able to model these pathways for males and females using body fat percentage, serum lipid levels, and blood pressure. We are the first to present a model of complex direct and indirect effects of fat mass leading to atherosclerosis using SEM. Both male and female path-model had an excellent fit. Fat mass had a significant effect on carotid intima-media thickness through various pathways, with the largest effect size on carotid intima-media thickness via blood pressure. SEM showed that the pathways differed between males and females, with a larger effect of serum lipids on carotid intima-media thickness in males. In conclusion, SEM is suitable in identifying models to unravel potential causal pathways in complex origins of diseases. We present a model involving several pathways, showing that fat mass has an influence on risk factors for atherosclerosis, already at 21 years of age. 1 These statistics explain the increasing interest of clinical researchers to determine risk factors for CVD. Atherosclerosis is an important etiologic element of CVD, and although causes of atherosclerosis have been explored previously, it remained difficult to investigate several atherosclerosis risk factors simultaneously. Cohort studies have been used to determine associations between risk factors of atherosclerosis. 2,3 However, these studies did not take into account indirect effects of risk factors because only direct effects between 2 variables were analyzed. Thus, such studies lacked to provide a statistical method that could unravel the pathways simultaneously in one path analysis.Structural Equation Modeling (SEM) is an advanced statistical technique that enables solving these issues. SEM has been applied in several research fields but is still rarely used in clinical research, despite its ability to identify, test, and estimate pathways in a non-hypothesis-driven manner. 4 We hypothesized that SEM is a suitable method to unravel multidirectional associations and potential causal pathways in complex origins of diseases such as CVD. This approach, in which the interdependency of risk factors is unraveled simultaneously, is innovative in this field. Our ...

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Section: Discussionmentioning

confidence: 99%

Pathways Leading to Atherosclerosis

et al. 2011

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“…Anxiety symptoms and ADHD symptoms also show substantial genetic correlations (0.45-0.58) (Michelini et al, 2015). In addition, shared genetic factors have been found between MDD and non-psychiatric disorders including obesity and migraine headache (Afari et al, 2010;Ligthart et al, 2010;Schur et al, 2009). Molecular genetic studies have recently extended the study of cross-disorder effects to the level of DNA variation.…”

Section: Cross-phenotype Genetics Of Stress-related Disordersmentioning

confidence: 99%

The Genetics of Stress-Related Disorders: PTSD, Depression, and Anxiety Disorders

Smoller

2015

Neuropsychopharmacol

378

243

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Research into the causes of psychopathology has largely focused on two broad etiologic factors: genetic vulnerability and environmental stressors. An important role for familial/heritable factors in the etiology of a broad range of psychiatric disorders was established well before the modern era of genomic research. This review focuses on the genetic basis of three disorder categories-posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and the anxiety disorders-for which environmental stressors and stress responses are understood to be central to pathogenesis. Each of these disorders aggregates in families and is moderately heritable. More recently, molecular genetic approaches, including genome-wide studies of genetic variation, have been applied to identify specific risk variants. In this review, I summarize evidence for genetic contributions to PTSD, MDD, and the anxiety disorders including genetic epidemiology, the role of common genetic variation, the role of rare and structural variation, and the role of gene-environment interaction. Available data suggest that stress-related disorders are highly complex and polygenic and, despite substantial progress in other areas of psychiatric genetics, few risk loci have been identified for these disorders. Progress in this area will likely require analysis of much larger sample sizes than have been reported to date. The phenotypic complexity and genetic overlap among these disorders present further challenges. The review concludes with a discussion of prospects for clinical translation of genetic findings and future directions for research.

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“…Alternatively, the relationship may not be causal with other factors explaining the association, such as trauma/stress leading to both disorders, or common genetic predispositional factors resulting in high co-occurrence. For example, one study estimated that 20% of the variance in migraine and depression could be explained by shared genetics (Schur, Noonan, Buchwald, Goldberg, & Afari, 2009). These explanations are not mutually exclusive, and it seems plausible that a combination of factors is likely to explain comorbidity.…”

mentioning

confidence: 98%

Cognitive behavior therapy for comorbid migraine and/or tension-type headache and major depressive disorder: An exploratory randomized controlled trial

Martin

Aiello

Gilson

et al. 2015

Behaviour Research and Therapy

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Numerous studies have demonstrated comorbidity between migraine and tension-type headache on the one hand, and depression on the other. Presence of depression is a negative prognostic indicator for behavioral treatment of headaches. Despite the recognised comorbidity, there is a limited research literature evaluating interventions designed for comorbid headaches and depression. Sixty six participants (49 female, 17 male) suffering from migraine and/or tension-type headache and major depressive disorder were randomly allocated to a Routine Primary Care control group or a Cognitive Behavior Therapy group that also received routine primary care. The treatment program involved 12 weekly 50-min sessions administered by clinical psychologists. Participants in the treatment group improved significantly more than participants in the control group from pre-to post-treatment on measures of headaches, depression, anxiety, and quality of life. Improvements achieved with treatment were maintained at four month follow-up. Comorbid anxiety disorders were not a predictor of response to treatment, and the only significant predictor was gender (men improved more than women). The new integrated treatment program appears promising and worthy of further investigation.

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A Twin Study of Depression and Migraine: Evidence for a Shared Genetic Vulnerability

Cited by 72 publications

References 49 publications

Pathways Leading to Atherosclerosis

Pathways Leading to Atherosclerosis

The Genetics of Stress-Related Disorders: PTSD, Depression, and Anxiety Disorders

Cognitive behavior therapy for comorbid migraine and/or tension-type headache and major depressive disorder: An exploratory randomized controlled trial

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