TY - JOUR

T1 - Risk. Impact of having a first-degree relative with affective disorder

T2 - a 7-year follow-up study

AU - Vinberg, Maj

PY - 2016/10

Y1 - 2016/10

N2 - This study investigated a high-risk sample in order to elucidate risk factors for affective disorder. Healthy monozygotic (MZ) and dizygotic (DZ) twins with and without a co-twin with a history of affective disorder were identified through nationwide registers. Two risk groups were identified: the high-risk group comprised twins at risk of developing affective disorder (DZ or MZ twin; index co-twin affected); the low risk group (control group) comprised twins at low risk of developing affective disorder (DZ or MZ twin; index co-twin not affected). At baseline 234 participants were divided into groups according to their risk for affective disorder; they were followed up at 6-month intervals with posted questionnaires assessing depression. After a mean follow-up period of 7 years, the participants were invited to participate in an individual interview. A total of 36 participants (31 high-risk twins and 5 low-risk twins) developed a psychiatric disorder during the 7-year follow-up period: 24 developed mood disorder (67%), 7 anxiety disorder (19%) and 5 (14%) substance abuse, schizophrenia or personality disorder. The results showed that familial risk, impaired stress tolerance and discrete cognitive dysfunction seem to be core predictors of affective illness. It is possible to identify a cluster of prodromal symptoms encompassing subclinical anxiety and depressive symptoms, higher neuroticism and cognitive problems. The cognitive problems may further be related to the cross-sectional finding that high-risk twins had lower hippocampal volumes. Further, 2 genetic polymorphisms: the 5-HTTLPR and the brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms were not directly associated with familial risk for affective disorder and did not predict illness onset. Similarly, salivary cortisol levels and whole-blood BDNF levels did not predict subsequent illness. The more complex 2-way interactions between 5-HTTLPR and life events suggested that high-risk individuals and individuals carrying the short s allele are exposed to more stressors and that this seems to contribute to an overall enhanced risk and thus accelerate the onset of illness. Low-risk individuals seem to experience fewer life events and may exhibit resilience to their adverse psychological effects. Overall, having a 1st-degree relative with affective disorder matters. This thesis demonstrates that high-risk studies are informative, allowing observation and investigation of the pathological processes that occur prior to the onset of illness. There is a lack of prospective intervention studies assessing psychopathology in well-defined, high-risk samples and it is obvious that future research must transcend diagnostic boundaries in order to have an impact on prevention. Furthermore, there is a need to move beyond the notion of ''magic bullets'', instead developing an integrated paradigm encompassing clusters of biomarkers related to behavioural measures of developmental psychopathology. Finally, as most psychiatric treatment developed to date target end-state disorders, the identification of high-risk individuals and mapping of individual risk profiles should be a priority in order to facilitate early treatment and prevention.

AB - This study investigated a high-risk sample in order to elucidate risk factors for affective disorder. Healthy monozygotic (MZ) and dizygotic (DZ) twins with and without a co-twin with a history of affective disorder were identified through nationwide registers. Two risk groups were identified: the high-risk group comprised twins at risk of developing affective disorder (DZ or MZ twin; index co-twin affected); the low risk group (control group) comprised twins at low risk of developing affective disorder (DZ or MZ twin; index co-twin not affected). At baseline 234 participants were divided into groups according to their risk for affective disorder; they were followed up at 6-month intervals with posted questionnaires assessing depression. After a mean follow-up period of 7 years, the participants were invited to participate in an individual interview. A total of 36 participants (31 high-risk twins and 5 low-risk twins) developed a psychiatric disorder during the 7-year follow-up period: 24 developed mood disorder (67%), 7 anxiety disorder (19%) and 5 (14%) substance abuse, schizophrenia or personality disorder. The results showed that familial risk, impaired stress tolerance and discrete cognitive dysfunction seem to be core predictors of affective illness. It is possible to identify a cluster of prodromal symptoms encompassing subclinical anxiety and depressive symptoms, higher neuroticism and cognitive problems. The cognitive problems may further be related to the cross-sectional finding that high-risk twins had lower hippocampal volumes. Further, 2 genetic polymorphisms: the 5-HTTLPR and the brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms were not directly associated with familial risk for affective disorder and did not predict illness onset. Similarly, salivary cortisol levels and whole-blood BDNF levels did not predict subsequent illness. The more complex 2-way interactions between 5-HTTLPR and life events suggested that high-risk individuals and individuals carrying the short s allele are exposed to more stressors and that this seems to contribute to an overall enhanced risk and thus accelerate the onset of illness. Low-risk individuals seem to experience fewer life events and may exhibit resilience to their adverse psychological effects. Overall, having a 1st-degree relative with affective disorder matters. This thesis demonstrates that high-risk studies are informative, allowing observation and investigation of the pathological processes that occur prior to the onset of illness. There is a lack of prospective intervention studies assessing psychopathology in well-defined, high-risk samples and it is obvious that future research must transcend diagnostic boundaries in order to have an impact on prevention. Furthermore, there is a need to move beyond the notion of ''magic bullets'', instead developing an integrated paradigm encompassing clusters of biomarkers related to behavioural measures of developmental psychopathology. Finally, as most psychiatric treatment developed to date target end-state disorders, the identification of high-risk individuals and mapping of individual risk profiles should be a priority in order to facilitate early treatment and prevention.

KW - Adult

KW - Cross-Sectional Studies

KW - Denmark

KW - Family

KW - Female

KW - Follow-Up Studies

KW - Genetic Predisposition to Disease

KW - Humans

KW - Incidence

KW - Male

KW - Middle Aged

KW - Mood Disorders

KW - Pedigree

KW - Prospective Studies

KW - Registries

KW - Risk Assessment

KW - Risk Factors

KW - Time Factors

KW - Journal Article

KW - Multicenter Study

M3 - Journal article

C2 - 27697135

VL - 63

JO - Danish Medical Journal

JF - Danish Medical Journal

SN - 2245-1919

IS - 10

M1 - B5298

ER -