Family Study of Affective and Anxiety Spectrum Disorders
Family Study of Affective and Anxiety Spectrum Disorders
This study will examine how depression, anxiety, and migraine run in families. It will help
 in defining the risk factors for physical, mental, and health problems-as well as define ways
 that those problems may be prevented and treated.

 A broad range of ages among family members will be included to evaluate the patterns of how
 these disorders are expressed throughout people's lives. Children of all ages will be
 included, and those ages 8 to 17 will be interviewed directly.

 Assessments will be collected through criteria of the Diagnostic and Statistical Manual of
 Mental Disorders IV as well as the spectrum, or range, of mood disorders and co-existing
 conditions. A member of the study team will visit the participants at home or will do an
 interview by telephone. Participation will take approximately 3 to 4 hours. Children will
 complete questionnaires given by the research team as well as questionnaires that they will
 do by themselves. The questions will pertain to the children's health, including physical and
 mental health and medical history, social relationships, problems, skills, and ways of
 dealing with important or stressful issues in their lives. These questionnaires will take up
 to 1 hour to complete.

 Health history gathered from adult participants will pertain to height, weight, exercise, and
 general function. Women will be asked about the use of oral contraceptives, estrogen, and
 progesterone. In addition, there will be questionnaires on personality and temperamental
 traits, that is, behavior and impulsiveness. Questions will also involve social intuition,
 family and other environmental factors, general functioning, and basic demographics such as
 ethnicity, race, socioeconomic status, marital status, education level, and employment
 history.

 Families enrolled in this phase of the research will be invited to participate in the next
 phase. There would be follow-up to evaluate the development of mood disorders, subtypes, and
 syndromes across the lifespan.
Objective:

 The chief goal of this study is to identify the endophenotypes of the spectrum of mood
 disorders using the methods of genetic epidemiology, developmental psychopathology and
 clinical psychiatry/psychology. The major research questions focus on the specificity of
 familial transmission of the mood disorder spectrum (i.e., symptoms, symptom clusters,
 subtypes) and the role of comorbidity with anxiety disorders and migraine syndromes in
 defining subtypes of mood disorders.

 Study Population:

 We propose to recruit 800 probands with bipolar I, bipolar II, major depression, panic/GAD,
 phobias, migraine, and unaffected controls, ascertained through both psychiatric and
 non-psychiatric clinical settings and systematic community samples, in order to enhance
 generalizability to the population. Approximately 2750 first-degree adult relatives and
 spouses, 350 child offspring (ages 7-17) will comprise the family study component.

 Design:

 This study employs a retrospective cohort family study for the association between mood and
 other mental and physical disorders in probands and their relatives. Probands and relatives
 will be evaluated using structured diagnostic interviews and standardized diagnostic criteria
 followed by clinical validation interviews and diagnostic consensus procedures. Assessment
 instruments will collect information on the DSM-IV criteria as well as the spectrum of mood
 disorders and comorbid conditions. In addition, DNA will also be collected from participants.
 A subset of families also complete electronic diaries and measures of light exposure and
 activity in this protocol, and will be invited to participate in another protocol to undergo
 more comprehensive evaluation of clinical, laboratory, and other functional domans to
 identify biologic markers and endophentypes for mood and related disorders. Data from the two
 protocols will be linked. A subset of families will also be followed forward over time.

 Outcome Measures:

 The primary outcome measure is the familial aggregation of mood disorder subtypes and their
 co-aggregation with migraine and anxiety disorders with diagnoses based on clinical review of
 the diagnostic interviews, family history information and clinical evaluation of study
 participants when relevant using traditional family study measures of association. Secondary
 outcomes include associations between mood disorders with the data collected from laboratory,
 biological, and functional assessments that have been collected as part of the clinical study
 and their familial correlations. Moving forward, these data will be collected as part of a
 new protocol and linked with the interview and mobile assessment data collected in this
 protocol.
-  Since this study is based on systematic recruitment from the local community and other
 non-clinical settings such as screening protocols from volunteers, there are no
 specific diagnostic inclusion and exclusion criteria. However, the study targets
 individuals with mood spectrum conditions and migraine. Criteria for the specific
 subgroups of mood and anxiety disorders are presented in Table 1. Individuals who do
 not meet criteria are classified as controls.

 INCLUSION CRITERIA:

 1. the ability to comprehend the interview, and

 2. probands must agree to contact at least two relatives (contacting relatives is not
 required in cases where the participant is enrolled in just the mobile technologies
 assessments (EMA and Actigraphy).

 EXCLUSION CRITERIA:

 The only exclusion criteria include impaired ability to comprehend the interview or
 inability to read.

 SPECIFIC INCLUSION AND EXCLUSION CRITERIA BY PROBAND GROUP:

 GENERAL INCLUSION CRITERIA:

 The only inclusion criteria for the study are that the person be English-speaking and
 ability to read and comprehend the interview.

 BIPOLAR I INCLUSION CRITERIA:

 Lifetime history of DSM-IV Bipolar I or Manic Episode.

 BIPOLAR II INCLUSION CRITERIA:

 Lifetime history of DSM-IV Bipolar II with duration of hypomania reduced to 2 or more
 days (according to RDC)

 MAJOR DEPRESSION INCLUSION CRITERIA:

 Lifetime history of at least 2 episodes of DSM-IV Major Depression

 PANIC/GAD INCLUSION CRITERIA:

 Lifetime history of DSM-IV diagnosis for Panic Disorder or GAD

 PHOBIAS INCLUSION CRITERIA:

 Lifetime history of DSM-IV diagnosis for social anxiety disorder, agoraphobia, or
 specific phobias (greater than or equal to 3)

 MIGRAINE INCLUSION CRITERIA:

 Lifetime history of IHS migraine with or without Aura

 GENERAL EXCLUSION CRITERIA:

 The only exclusion criteria include impaired ability to comprehend the interview or
 inability to read.