The median age (min-max) of the sample was 72 years (65–92). 38.4% of subjects in this study scored over the cutoff point on the CES-D either at recruitment or at one of the two follow-up examinations 23.5 % had been diagnosed with major depression during their life-time and 12.6% were taking anti-depressant medication at some point during the study. All subjects with diagnosed major depression scored over 16 on the CES-D and 27 subjects (2.9%) taking anti-depressant treatment did not meet either MINI or CES-D criteria for depression. These subjects were included as depressed on the assumption that a depressive episode had occurred but been effectively treated and thus was not detected by the MINI or CES-D. The period prevalence (over the four year observation period) of significant depressive symptomatology in this cohort is estimated at 41.3%. The socio-demographic and clinical characteristics of subjects with significant levels of depressive symptomatology are given in .
Relationship between sociodemographic variables, clinical charactristics and depression
Depressed subjects were observed to be more commonly female (odd ratio=2.92, 95% CI=2.21–3.86) older (odd ratio=1.60, 95% CI=1.11–2.31), to have medium-low education (odd ratio=2.07, 95% CI=1.44–2.96), to be divorced/separated (odd ratio=1.87, 95% CI=1.17–2.99) or widowed (odd ratio=2.15, 95% CI=1.56–2.96) and to have lower rates of hypertension (odd ratio=0.59, 95% CI=0.45–0.76). Experiencing recent adverse life events (in the year before and during follow-up) and before the onset of the depressive symptoms, showed a significant p trend. Subsequent analyses were thus adjusted for these competing causes of depression. No significant relationship was found between depression and dementia or other neurological disorders, disability, recent cardio- or cerebro-vascular disorder or 5-HTTLPR allele.
Previous research on child maltreatment and depression has principally highlighted personally threatening events (physical, sexual and verbal abuse; items 1 to 6, ) as being the most pathogenic (25
). In this older population we found exposure to at least one of these events significantly increased risk of late-life depression (odd ratio =2.28; 95%CI=1.53–3.41). Exposure to a major protective factor (maternal or paternal affection, availability of an adult friend; items 26 to 28, ) conversely decreased overall risk (odd ratio=0.54; 95%CI=0.28–1.01).
Relation between individual childhood events and late-life depression adjusting by age, gender, education, marital status, hypertension and recent life event
We also examined the effects of childhood events on the number of depressive episodes occurring during the study period. Exposure to at least one adverse childhood event significantly increased the risk of having one episode of depression with an odd ratio=1.72 (95% CI =1.04–2.86), and for two or more episodes with an odd ratio=2.89 (95% CI=1.83–4.57) (p-value for heterogeneity between these 2 odds-ratio was 0.05). The presence of at least one protective factors gave a risk of odd ratio=1.03 (95%CI=0.42–2.53) for one depressive episode, and a protective effect of odd ratio=0.34 (95% CI=0.17–0.69) for two or more episodes (p-value for heterogeneity was 0.02) (data not shown).
The relationship between late-life depression and individual childhood life-events were also examined using a logistic regression model. No significant sex interaction effects with individual childhood life-events and depressive symptomatology were observed so analyses were not gender stratified. shows that a significant risk was associated with excessive sharing of problems (odd ratio=1.53, 95% CI=1.04–2.27), poverty or financial difficulties (odd ratio=1.65, 95% CI=1.17–2.31), mental disorder experienced by the father (odd ratio=2.13, 95% CI=1.32–3.44) and mother (odd ratio=2.52, 95% CI=1.65–3.85), excessive punishment (odd ratio=2.77, 95% CI=1.41–5.46), verbal abuse by parents (odd ratio=2.90, 95% CI=1.57–5.38) humiliation and mental cruelty (odd ratio=4.31, 95% CI=1.87–9.93) and abuse by an adult outside the family (odd ratio=6.71; 95%CI=1.80–25.0). A protective effect was observed for maternal affection (odd ratio=0.45, 95% CI=0.29–0.70), and having the overall impression that parents had done their best (odd ratio=0.53; 95%CI=0.30–0.92)
The distribution of 5-HTTLPR did not deviate from Hardy-Weineberg equilibrium (χ2=0.06, Df=2, p=0.97). Interaction effects between 5-HTTLPR genotype and childhood events having a significant relationship with depressive symptomatology were examined adjusting by age, gender, education, marital status, hypertension and recent life events with stratification by genotype.
The risk of depression in relation to too frequent sharing of parental problems with children was increased in LL subjects (odd ratio=1.93, 95%, CI =0.95–3.90) and in SL subjects (odd ratio=2.00, 95%, CI =1.15–3.48) with a non-significant tendency for protection in SS subjects (odd ratio=0.30, 95%, CI= 0.08–1.19). A comparable pattern was observed for poverty or financial difficulties. We observed a tendency for an increased risk in LL subjects (odd ratio=1.51, 95%, CI =0.82–2.77) which was significant in SL subjects (odd ratio=2.54, 95%, CI =1.55–4.15). In the SS subjects, we found a non-significant tendency for reduced risk (odd ratio=0.64, 95%, CI =0.26–1.53).
Significant gene-event interactions were found for parents excessively sharing problems (Wald χ2=7.23, df =2, p=0.027) and for poverty or financial difficulties (Wald χ2=7.38, df =2, p=0.025) ().
Interaction between occurrence of specific childhood events and probability of late-life depression
As these results suggest a dominant effect of the L-carrying genotypes, we examined the effect of combining LL and LS subjects compared to SS subjects. The risk of depression with childhood poverty was significantly increased in LL/LS subjects (odd ratio=2.06, 95% CI=1.42–3.00) with a non-significant tendency to be reduced in SS subjects (odd ratio=0.64, 95% CI =0.26–1.53). The risk of depression in relation to too frequent sharing of parental problems with children was also increased in LL/LS subjects (odd ratio=1.94, 95%, CI =1.26–2.98) with a non-significant tendency to be reduced in SS subjects (odd ratio=0.30, 95%, CI= 0.08–1.19).
Finally, the life-time risk of subjects for major depressive episodes (MDE) was also ascertained from the MINI adjusting for age, education and gender only (life events and hypertension at the time of the episode being unknown). Significant risk factors were found to be in ascending order sharing of parental problems with children (odd ratio=1.68, 95% CI=1.11–2.54), maternal mental illness (odd ratio=1.69, 95% CI=1.11–2.59), verbal abuse from parents (odd ratio=1.94, 95% CI=1.07–3.55) poverty or financial difficulties (odd ratio=1.97, 95% CI=1.37–2.83), maternal affection (odd ratio=0.51, 95% CI=0.33–0.79), home conflict (odd ratio=2.09, 95% CI=1.43–3.05), physical and/or sexual abuse (odd ratio=2.72, 95% CI=1.04–7.08). Alcohol abuse by father, neglect and abuse by schoolmates are only significant risk factors for cases of early-onset depression (occurring before age 50; data not shown).