During the past year, we have analyzed the data from the latest wave of this prospective cohort study that now covers a total observation period of 30 years for this cohort of young adults who have been followed since the age of 18. The major topic that we have addressed this year is the prevalence and stability of headache subtypes, and their prevalence, impact, and stability. The paper was recently accepted for publication in the British Medical Journal (Merikangas et al., in press). Our findings reveal that: (1) the cumulative one-year prevalence of migraine without aura with repeated interviews over a 30-year period is very high (36%), whereas that of migraine with aura is far less prevalent, (3% across 23 years of follow- up);(2) about 30% of those with migraine continue to experience only migraine over 30 years of follow-up; (3) the longitudinal specificity of headache subtypes is fairly low, with a high prevalence of co-occurrence across headache subtypes and little prospective stability of the specific pure types of headache;and (4) there is a gradient of clinical severity across headache subtypes moving from migraine with aura to migraine without aura, tension-type headache, and unclassified headaches. We also examined the impact of psychiatric comorbidity in migraine, tension-type and other headaches. The findings highlight the importance of prospective follow-up of people with headache. One of the most important findings from this study was the substantial magnitude of overlap between the predominant headache subtypes that occurred at each interview. Nearly all of those with migraine with aura at one or more interviews also experienced migraine without aura (84%) at another interview;and nearly half of those with migraine without aura or with tension-type headache also suffered from the other headache subtype longitudinally. We also examined the association between migraine and other psychiatric disorders, and found that migraine and other headache subtypes were substantially comorbid with mood and anxiety disorders. Comorbid migraine was associated with the highest levels of consulting a physician, treatment-seeking, medication use, distress and impairment. This study provides valuable insight on the association between specific headache subtypes and psychiatric conditions, as well as the differential impact of these subtypes on the affected individual using prospective data from a population-based sample. Understanding the specificity of these associations will aid in our efforts to more accurately detect at-risk individuals, inform the development of more targeted prevention and treatment efforts, and help refine studies examining the etiology of these conditions. Analyses led by our colleagues in Zurich assessed the association between smoking and mood disorders and the association between smoking and its traditional risk factors, comparing those who started smoking in adolescence with those who started smoking in early adulthood (Ajdacic-Gross et al., 2011). It was found that adolescent onset of smoking was associated strongly with later major depression, dysthymia or bipolar disorders and, furthermore, with parental smoking, extroverted personality and discipline problems, and rebelliousness in youth. However, only depression and dysthymia were associated with adult onset smoking and other risk factors associated with smoking were not so associated in this group. These results suggest that more specific study designs are needed to shed more light on adult onset of smoking. The interplay between two subclinical psychosis symptoms dimensions, and one depression symptom dimension, was investigated using this unique longitudinal data (Rossler et al., 2011). To summarize, the main driving force within the dynamics between symptoms of psychosis and depression is the schizotypal symptoms subscale, which represents social and interpersonal deficiencies, ideas of reference, suspiciousness, paranoid ideation, and finally, odd behavior. It exercises a strong effect on the depression symptoms, and a moderate effect on the schizophrenia nuclear symptoms subscale. Depression has partly a mediator function in this dynamic. Our findings suggest strongly that schizotypal symptoms preferably convey depression symptoms, which for their part can convey schizophrenia nuclear symptoms. Finally we examined smoking prevalence in association with mental disorders to include not only psychiatric disorders but also subthreshold disorders in the analysis. The association between smoking and mental disorders turned out to be clearly stronger if subthreshold mental disorders were appropriately considered in the analyses. Constructing appropriate reference groups is as crucial for the analysis of mental disorders and their outcomes as constructing adequate diagnostic groups. Public Health Impact: This study highlights the importance of prospective research in studying the developmental course and consequences of headache syndromes. The findings have important implications for health policy, clinical care, classification and etiologic studies of migraine and other headaches. First, our findings clearly demonstrate the high prevalence and magnitude of disability associated with these headache syndromes across young to middle adulthood in the general population. Second, clinical evaluation and treatment of headache necessarily relies on retrospective recall that has been shown to be highly unreliable. A person-based rather than headache-based approach would provide a more valid depiction of headache for both treatment and etiologic studies. Clinicians should attempt to obtain maximal information on the past history including ancillary information where possible rather than relying on the current clinical presentation in treatment decision-making. Third, the high frequency of longitudinal cross-over of the predominant headache subtype may indicate that the distinction between discrete headache subtypes in the ICHD-2 may not provide an accurate representation of the manifestations of headache in general population samples. The lifetime heterogeneity of expression of headache subtypes is an important impediment to etiologic research such as genetic studies that relies upon lifetime categorical classification of affected status. Similar to the emerging trend in the classification of mood disorders, our data provide evidence for a spectrum of expression of headache characterized by the core symptoms independent of recurrence, duration and severity. Etiologic research may benefit from a more descriptive empirical approach that captures the protean manifestations of headache across lifes developmental stages. Future Plans: During the next year, we plan to conduct additional analyses of the 30 year follow up data on sleep patterns and disorders, stability of depression subtypes, particularly atypical depression, and persistent fatigue/ neurasthenia. In addition, we are beginning to investigate the stability of symptoms and subtypes of migraine to identify phenotypes that should be investigated in our genetic studies of migraine.

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Angst, J; Paksarian, D; Cui, L et al. (2015) The epidemiology of common mental disorders from age 20 to 50: results from the prospective Zurich cohort Study. Epidemiol Psychiatr Sci :1-9
Merikangas, Kathleen R; Cui, Lihong; Richardson, Amanda Kalaydjian et al. (2011) Magnitude, impact, and stability of primary headache subtypes: 30 year prospective Swiss cohort study. BMJ 343:d5076
Rössler, Wulf; Angst, Jules; Gamma, Alex et al. (2011) Reappraisal of the interplay between psychosis and depression symptoms in the pathogenesis of psychotic syndromes: results from a twenty-year prospective community study. Eur Arch Psychiatry Clin Neurosci 261:11-9
Landolt, Karin; Ajdacic-Gross, Vladeta; Angst, Jules et al. (2010) Smoking and psychiatric disorders: have subthreshold disorders been overlooked? Nicotine Tob Res 12:516-20
Ajdacic-Gross, Vladeta; Landolt, Karin; Angst, Jules et al. (2009) Adult versus adolescent onset of smoking: how are mood disorders and other risk factors involved? Addiction 104:1411-9