Mohammed T. Abou-Saleh

384 PRINCIPLES AND PRACTICE OF GERIATRIC PSYCHIATRYof the disorder, with up to half of the environmental contributionto the variance having reflected measurement error, leading to adilution of the previous reported genetic contributions 77 . About60% of the genetic effect contributed was indirect, mediated bypast history of depression, neuroticism, life events and childhoodadversity. Two coping strategies, turning to others and problemsolving, which had been negatively correlated with levels ofdepression, were also found to have substantial heritability 78 . Therelationship between genetic liability, stressful life events anddepression was explored in detail, and evidence provided tosupport a gene–environment interaction in which genetic factorsdetermined sensitivity to serious life events 79 .Data on older subjects is relatively lacking. Two studies fromThe Netherlands examined cross-sectional relationships betweendepression and the exposures of a family history of mental illness,and a personal past history of depression. In the Amstel study,based on a large population sample of 2540 subjects aged 65+,there was a positive association between a family history ofmental problems and a diagnosis of GMS–AGECAT depression80 . This association was modified by both cognitive status andpersonal past psychiatric history. The strongest association wasseen in the group with a past psychiatric history and no cognitiveimpairment. However, only 22% of depressed subjects reported afamily history of mental health problems, suggesting a modestpopulation-attributable fraction. Van Ojen 13 also reported that,while depression was twice as common in those with a psychiatrichistory with an onset before the age of 65, the prevalence of thisexposure decreased linearly with increasing age 13 . Only 22% ofcurrently depressed subjects reported a previous episode ofpsychiatric illness with an onset before age 65. While failure ofrecall and ‘‘telescoping’’ of ages of onset might have accounted forthese findings, the reduction in the prevalence of past history withincreasing age was consistent with predictions based upon theknown excess mortality among those so affected. The LASAstudy, based on a national Dutch sample of over 3000 subjectsaged 65+, used two definitions of depressive disorder, majordepression diagnosed using DIS, and minor depression defined asthose scoring 16 or more on the Center for EpidemiologicalStudies Depression Scale. A family history of depression wasassociated with neither outcome. A past history of psychiatricdisorder was strongly associated with major depression, with anodds ratio (OR) of 90.8 (39.1–211.1) and a population-attributablefraction (PAF) of 74%, but much more weakly associatedwith minor depression; OR 4.1 (2.3–7.3) PAF 7%.COGNITIVE DECLINEAn inverse association between depression scores and cognitivetest scores has been reported in four cross-sectional surveys46,71,81,82 with one negative report 42 . These cross-sectionalstudies did not permit further analysis of direction of causality.However, at least one study has suggested that low mood may bea risk factor for subsequent decline in cognitive ability 83 . Abiological basis for this association has been suggested; the failure,seen in chronically depressed subjects, of fast-feedback mechanismsto shut off the cortisol stress response may lead to highconcentrations of neurotoxic metabolites, causing specific damageto hippocampal regions essential to new learning and memoryrecall tasks 84 . Alternatively, microvascular lesions leading tocognitive decline may also cause late-life depression throughcritical subcortical damage to frontotemporal cortical projectionsnecessary for the maintenance of mood and motivation. MRIevidence suggests that first onsets of late-life depression may beassociated with characteristic deep white matter lesions 85 . Thefinding from the Amstel study, that the associations between lifeevents and depression and living alone and depression were notapparent in those with cognitive impairment, would be consistentwith a hypothesis of an alternative pathway to late-life depressionmediated through cerebral deterioration 86 . There may be a moreprosaic explanation for a prospective association betweencognitive decline and depression. Cognitive impairment, likeother health impairments, may lead to depression to the extent towhich it causes disability and handicap.CONCLUSIONThe factors most consistently implicated in these studies aresimilar to those observed in younger adults: constitutional orgenetic vulnerability, e.g. a family history or past history ofpsychiatric disorder; current vulnerability, e.g. lack of socialsupport, recent stress, as in life events, and current adversity, as inlow socioeconomic class, poor housing or low income. However,some factors may be particularly salient for late-life depression,either because, as in the case of disablement or bereavement, theyare a much more common exposure among the older population,or because they may impact differently upon those who areexposed, depending on their age. There is already evidence tosuggest that disablement associated with declining health in olderage may be a prime determinant of the prevalence, incidence andmaintenance of late-life depression.In younger adult populations, depression is a substantiallyheritable disorder in which both direct genetic effects and geneticeffects mediated through childhood adversity, neurotic personality,coping styles, propensity for life events and sensitivity to lifeevents can be discerned. Evidence from genetically sensitivedesigns in older populations is lacking, but circumstantialevidence suggests that the selective early death of those with anearly first onset and multiple episodes of depression, who perhapshave a higher genetic loading for the disorder, may mean that theheritability of depression in late life is lower than in youngerpopulations. The finding that the large majority of older depressedsubjects are experiencing a first onset of the disorder raises thepossibility of aetiological dissimilarity between early adult andlate-life depression. There is a clear case for focusing in ourinvestigations on those aspects of physical health status, cognitionand social milieu that change most acutely in late-life and bestdistinguish the life experience of older and younger adults.REFERENCES1. Beekman AT, Penninx BW, Deeg DJ et al. Depression and physicalhealth in later life: results from the Longitudinal Aging StudyAmsterdam (LASA). J Affect Disord 1997; 46: 219–31.2. Chen R, Copeland JR, Wei L. A meta-analysis of epidemiologicalstudies in depression of older people in the People’s Republic of China.Int J Geriatr Psychiat 1999; 14(10): F21–30.3. Weissman MM, Leaf PJ, Tischler GL et al. Affective disorders in fiveUnited States communities [published erratum appears in Psychol Med1988 Aug; 18(3): following 792]. 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