The association between parental MDD and child diagnosis is moderated by grandparental MDD status. The rates of psychopathology are highest in grandchildren of parents and grandparents with a moderately to severely impairing depression. Anxiety disorders are the early sign of psychopathology in the young grandchildren. Early interventions in the offspring of 2 generations affected with moderately to severely impairing MDD seem warranted. This familial group may be the target for neuroimaging, genetic, and other biological studies.

The utility of the Center for Epidemiologic Studies Depression Scale for Children (CES-DC), a modified version of the Center for Epidemiologic Studies Depression Scale, was explored in a sample of children, adolescents, and young adults at high or low risk for depression according to their parents' diagnosis. Proband parents were participants in the Yale Family Study of Major Depression who had children between the ages of 6 and 23 years. Diagnostic and self-report information on offspring was collected over two waves, spaced 2 years apart, from 1982 to 1986. Support was obtained for the reliability and validity of the CES-DC as a measure of depressive symptoms, especially for girls and for children and adolescents aged 12-18 years. Children with major depressive disorder or dysthymia, as defined by the Diagnostic and Statistical Manual of Mental Disorders, Third Edition (DSM-III), had elevated scores in comparison with all other respondents. The CES-DC lacked diagnostic specificity; children with a range of current DSM-III diagnoses had elevated scores on the measure. A cutoff point of 15 and above for screening children and adolescents for current major depressive disorder or dysthymia may be optimal. Depressed respondents scoring below this cutoff point (false negatives) showed better social adjustment than true positives; nondepressed respondents scoring above this cutoff point (false positives) showed worse adjustment than true negatives. Factor analysis was used to construct an abbreviated, four-item version of the scale. The abbreviated scale was shown to be useful as a screen.

No abstract

The offspring of depressed parents remain at high risk for depression, morbidity, and mortality that persists into their middle years. While adolescence is the major period of onset for major depression in both risk groups, it is the offspring with family history who go on to have recurrences and a poor outcome as they mature. In the era of personalized medicine, until a more biologically based understanding of individual risk is found, a simple family history assessment of major depression as part of clinical care can be a predictor of individuals at long-term risk.

The brain disturbances that place a person at risk for developing depression are unknown. We imaged the brains of 131 individuals, ages 6 to 54 years, who were biological descendants (children or grandchildren) of individuals identified as having either moderate to severe, recurrent, and functionally debilitating depression or as having no lifetime history of depression. We compared cortical thickness across high-and low-risk groups, detecting large expanses of cortical thinning across the lateral surface of the right cerebral hemisphere in persons at high risk. Thinning correlated with measures of current symptom severity, inattention, and visual memory for social and emotional stimuli. Mediator analyses indicated that cortical thickness mediated the associations of familial risk with inattention, visual memory, and clinical symptoms. These findings suggest that cortical thinning in the right hemisphere produces disturbances in arousal, attention, and memory for social stimuli, which in turn may increase the risk of developing depressive illness. is a highly familial illness (1).It is the leading cause of disability worldwide for persons 15 to 44 years of age (2), and it is associated with increased mortality resulting from cardiovascular disorder (3), poor personal care (4), and suicide (5). Genetic and environmental factors and their interactions are important in its pathogenesis (6), but the abnormalities of brain structure and function that mediate these effects have not yet been identified. Brain-imaging studies have suggested the involvement of the limbic system and related frontal cortices in persons suffering from MDD, although findings from those studies have been inconsistent and have had relatively small effect sizes. Moreover, studies reporting abnormalities in brain structure and function in already-affected individuals have been unable to discern whether those abnormalities represent the causes of depressive illness, the compensatory neural responses that help to promote recovery or the attenuation of symptoms, the epiphenomenal effects of chronic illness or stress, or the effects of prior or ongoing treatment.To address these limitations of prior neurobiological studies of already-affected individuals, we undertook a study of brain structure in individuals who are at high familial risk for developing MDD. These individuals belonged to a 3-generation cohort in which the first 2 generations have been followed for more than 20 years. The first generation (G1) comprised 2 groups of adults: 1 group that was clinically ascertained during treatment of moderate to severe, recurrent, and functionally debilitating MDD; and a control group composed of a sample of matched adults, ascertained from the same community, who had no discernible lifetime history of depression. The second generation (G2) comprised the biological offspring of the first generation, and the third generation (G3) comprised the offspring of the second generation. Longitudinal assessments in this sample (7) and in similar 2-generation stu...