Exploration of the influence of insecure attachment and parental maltreatment on the incidence and course of adult clinical depression.

BACKGROUND: Both childhood maltreatment and insecure attachment are known to be associated with depression in adulthood. The extent insecure attachment increases the risk of adult clinical depression over that of parental maltreatment among women in the general population is explored, using those at high risk because of their selection for parental maltreatment together with an unselected sample. METHODS: Semi-structured interviews and investigator-based measures are employed. RESULTS: Insecure attachment is highly associated with parental maltreatment with both contributing to the risk of depression, with attachment making a substantial independent contribution. Risk of depression did not vary by type of insecure attachment, but the core pathways of the dismissive and enmeshed involved the whole life course in terms of greater experience of a mother's physical abuse and their own anger as an adult, with both related to adult depression being more often provoked by a severely threatening event involving humiliation rather than loss. By contrast, depression of the insecure fearful and withdrawn was more closely associated with both current low self-esteem and an inadequately supportive core relationship. In terms of depression taking a chronic course, insecure attachment was again a key risk factor, but with this now closely linked with the early experience of a chaotic life style but with this involving only a modest number of women. CONCLUSIONS: Both insecure attachment and parental maltreatment contribute to an increased risk of depression with complex effects involving types of insecure attachment.

Functional polymorphism in the brain-derived neurotrophic factor gene interacts with stressful life events but not childhood maltreatment in the etiology of depression.

BACKGROUND: We test the hypothesis that the functional Val66Met polymorphism of BDNF interacts with recent life events to produce onset of new depressive episodes. We also explore the possibility that the Met allele of this polymorphism interacts with childhood maltreatment to increase the risk of chronic depression. METHODS: In a risk-enriched combined sample of unrelated women, childhood maltreatment and current life events were measured with the Childhood Experience of Care and Abuse, and Life Events and Difficulties Schedule interviews. Chronic episodes of depression (12 months or longer) during adulthood and onset of a major depressive episode during a 12-month follow-up were established with the Schedules for Clinical Assessment in Neuropsychiatry interview. RESULTS: Met alleles of BDNF moderated the relationship between recent life events and adult onsets of depression in a significant gene-environment interaction (interaction risk difference 0.216, 95% CI 0.090-0.342; P =.0008). BDNF did not significantly influence the effect of childhood maltreatment on chronic depression in the present sample. CONCLUSIONS: The Met allele of BDNF increases the risk of a new depressive episode following a severe life event. The BDNF and the serotonin transporter gene length polymorphism (5-HTTLPR) and BDNF may contribute to depression through distinct mechanisms involving interactions with childhood and adulthood adversity respectively, which may, in combination, be responsible for a substantial proportion of depression burden in the general population.

Serotonin transporter length polymorphism, childhood maltreatment, and chronic depression: a specific gene-environment interaction.

BACKGROUND: Key questions about the interaction between the serotonin transporter length polymorphism (5-HTTLPR) and stress in the etiology of depression remain unresolved. We test the hypotheses that the interaction is restricted to childhood maltreatment (as opposed to stressful events in adulthood), and leads to chronic depressive episodes (as opposed to any onset of depression), using gold-standard assessments of childhood maltreatment, severe life events, chronic depression, and new depressive onsets. METHOD: In a risk-enriched sample of 273 unrelated women, childhood maltreatment was retrospectively assessed with the Childhood Experience of Care and Abuse (CECA) interview and 5-HTTLPR was genotyped. A subset of 220 women was followed prospectively for 12 months with life events assessed with the Life Events and Difficulties (LEDS) interview. Any chronic episode of depression (12 months or longer) during adulthood and onset of a major depressive episode during a 12-month follow-up were established with the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) interview. RESULTS: The short alleles of 5-HTTLPR moderated the relationship between childhood maltreatment and chronic depression in adulthood, reflected in a significant gene-environment interaction (RD = 0.226, 95% CI: 0.076-0.376, P = .0032). 5-HTTLPR did not moderate the effects of either childhood maltreatment or severe life events on new depressive onsets. CONCLUSIONS: The short variant of the serotonin transporter gene specifically sensitizes to the effect of early-life experience of abuse or neglect on whether an adult depressive episode takes a chronic course. This interaction may be responsible for a substantial proportion of cases of chronic depression in the general population.

Depression and the serotonin transporter 5-HTTLPR polymorphism: a review and a hypothesis concerning gene-environment interaction.

Studies of the interaction of the serotonin transporter genotype and environment upon adult depression (G x E) have suggested a role for both childhood maltreatment and stressful life events. This paper deals with two main issues. First, do both contribute? Evidence that G x E with childhood maltreatment plays a role is much stronger than that for G x E with life events occurring close to onset, although that for G x E with life events occurring over a 5-year period before the presence of the recorded depression is stronger. However, non-genetic research shows that life events occurring so long before onset as 5 years have little or no relationship with adult depression once childhood maltreatment is taken into account, suggesting they serve as a marker for childhood maltreatment rather than making a direct contribution to G x E. Second, genetic research has dealt only with the presence of depression and taking account of course may radically change ideas about the point at which G x E occurs. Two findings from non-genetic research concerning childhood maltreatment are relevant. Childhood maltreatment is associated with a particularly high risk of an adult onset of depression taking a chronic course (i.e. lasting 12 months or more). Moreover such maltreatment makes a substantial direct contribution - i.e. its link with course is independent of all other childhood and adult risk factors. This is consistent with early changes in brain function associated with the polymorphism in the context of childhood maltreatment explaining the link of such maltreatment with adult chronic episodes. It also follows that restricting analysis to such episodes would increase current estimates of G x E.

Parental maltreatment and proximal risk factors using the Childhood Experience of Care & Abuse (CECA) instrument: a life-course study of adult chronic depression - 5.

BACKGROUND: This is the final paper of a series concerning parental maltreatment and chronic depression in women. It extends the scope of the analysis to take account of proximal risk factors, present within at most six months of an onset. It deals with the contribution of factors influencing onset of a depressive episode as well as those related to whether this takes a chronic course. Once a two-stage model dealing with both sets of risk factors has been developed we explore how far distal factors (more than at least one year earlier) influence each stage. METHODS: Three studies are employed. All take account of parental maltreatment. Two prospective studies deal with proximal risk factors, and a retrospective one with distal and proximal factors. RESULTS: For the first stage of the model concerning onset the influence of parental maltreatment and its correlated risk factors (e.g. conduct problems) are almost entirely mediated by proximal factors (e.g. quality of core relationships). However, for the second stage concerning course parental maltreatment makes a direct contribution that is independent of all other risk factors. LIMITATIONS: The retrospective nature of some of the data may introduce bias (But see the second paper in the present series [Brown, G.W., Craig, T.K.J., Harris, T.O., Handley, R.V., Harvey, A.L., 2007b. Validity of retrospective measures of early maltreatment and depressive episodes using the Childhood Experience of Care & Abuse (CECA) instrument - a life-course study of adult chronic depression - 2. J. Affect. Dis., 103, 217-224]). Only females have been considered. CONCLUSIONS: The influence of parental maltreatment on the onset of adult depression is largely indirect and the mechanisms involved are reasonably clear. However, the mechanisms involved in the substantial direct contribution of maltreatment to course are as yet unclear. Some interplay of maltreatment and early brain development is one of a number of interesting possibilities.

Parental maltreatment and adulthood cohabiting partnerships: a life-course study of adult chronic depression--4.

BACKGROUND: This fourth paper of a series of five concerning depression in women considers: i. why parental maltreatment increases risk of highly aversive ('very poor') partnerships, and ii. how far these relationships explain the link of such maltreatment with adult chronic depression. METHODS: Data was collected retrospectively by semi-structured interviews and only women living at some point with a partner included. RESULTS: Parental maltreatment was indirectly linked to chronic depression via highly aversive partnerships. This was partly mediated by childhood conduct problems. However, a broader range of behaviour in late adolescence and early adulthood such as early risky sexual behaviour among those without conduct problems was also involved. In addition parental maltreatment was directly linked to chronic depression, judged by a substantial remaining association when other risk factors were controlled. Highly aversive partnerships were less common by the late 20s while this was matched by an increase of 'very poor' circumstances among those no longer living with a partner. This increase often involved lone motherhood, an established risk factor for chronic depression. LIMITATIONS: These findings should be seen as tentative given the retrospective nature of many of the measures (But see the second paper in the present series [Brown, G.W., Craig, T.K.J., Harris, T.O., Handley, R.V., & Harvey, A.L. (2007b). Validity of retrospective measures of early maltreatment and depressive episodes using CECA (Childhood Experience of Care & Abuse)--A life-course study of adult chronic depression--2. J. Affect. Disord., 103, 217-224]. Only women were studied. CONCLUSIONS: Parental maltreatment relates indirectly to adult chronic episodes of depression with highly aversive partnerships playing an important mediating role. Parental maltreatment also has a direct link. While these results are broadly consistent with earlier research a more complete understanding of the mechanisms acting across the life-course requires an assessment of a wider range of factors around the time of an onset of depression. This is the task of our next and final paper.

Validity of retrospective measures of early maltreatment and depressive episodes using the Childhood Experience of Care and Abuse (CECA) instrument -- A life-course study of adult chronic depression - 2.

BACKGROUND: A previous paper, using data collected retrospectively from sister pairs, reported substantial associations of adult depressive episodes lasting at least 12 months with childhood maltreatment [Brown, G.W., Craig, T.K.J., Harris, T.O. Handley, R.V. & Harvey, A.L. 2007a-this issue. Development of a retrospective interview measure of parental maltreatment using the Childhood Experience of Care & Abuse (CECA) instrument - a life-course study of adult chronic depression - 1. J. Affect. Disord. doi:10.1016/j.jad.2007.05.022]. Risk was far less when depressive episodes of any duration were considered. This paper considers how much scientific weight can be placed on these findings in the light of doubt often expressed about retrospective collection of childhood and adult data. METHODS: The retrospectively gathered material was obtained from adult sister pairs within 5 years of age, comprising a high-risk series (n = 118) where the first sister was selected as likely to have experienced childhood abuse or neglect, and a comparison series (n = 80) where she was selected at random. Current age ranged between early 20s and 50s. Data was collected by semi-structured interviews, using investigator-based ratings covering a wide range of parental behaviour and childhood behaviour. RESULTS: A series of analyses failed to reveal evidence of significant bias in the collection of material about adult depression or parental maltreatment. There was, however, some evidence of under reporting. LIMITATIONS: Conclusions from such analyses can only be judged in terms of degree of plausibility. CONCLUSIONS: Nothing emerged to suggest the presence of significant bias in the aetiological findings of our earlier paper. There is evidence of some underreporting of both early adverse experience and adult depressive episodes, but this is unlikely to threaten the conclusions drawn about the link of parental maltreatment with adult chronic depressive episodes.

Development of a retrospective interview measure of parental maltreatment using the Childhood Experience of Care and Abuse (CECA) instrument -- A life-course study of adult chronic depression - 1.

BACKGROUND: Childhood maltreatment among women is related to risk of adult depression and particularly an episode taking a chronic course. This paper explores the aspects of parental behaviour involved. METHODS: An expanded version of CECA (Childhood Experiences of Care and Abuse), a retrospective interview-based instrument covering neglect as well as various forms of abuse is used to develop a new index of parental maltreatment. Data are derived from an enquiry of sister pairs between early 20s and 50s, comprising a high-risk series (n=118) where the first sister was selected as likely to have experienced childhood abuse or neglect, and a comparison series (n=80) where she was selected at random. RESULTS: Adverse maternal behaviour emerges as of critical importance for the link with adult chronic depression. Maternal lack of affection ('neglect') and maternal rejection ('emotional abuse') form the core of an index of parental maltreatment, and it is concluded that persistent rejection, particularly from a mother, appears to be the core experience of importance. The findings of behavioural genetics that the experience of siblings of parents in ordinary families often differs have been found to hold for the more extreme behaviour involved in maltreatment. Difference between siblings in risk of later chronic depression is entirely related to such experience. LIMITATIONS: The study is based on retrospective questioning of adult women. Our next paper considers the possible threats to validity involved [Brown, G.W., Craig, T.K.J., Harris, T.O., Handley, R.V., Harvey, A.L., 2007a. Validity of retrospective measures of early maltreatment and depressive episodes using CECA (Childhood Experience of Care and Abuse) - a life-course study of adult chronic depression - 2. J. Affect. Disord. doi:10.1016/j.jad.2007.06.003]. CONCLUSIONS: Parental maltreatment emerges as a critical determinant of later chronic depressive episodes among adult women.

Child-specific and family-wide risk factors using the retrospective Childhood Experience of Care & Abuse (CECA) instrument: a life-course study of adult chronic depression - 3.

BACKGROUND: An earlier paper [Brown, G.W., Craig, T.K.J., Harris, T.O., Handley, R.V., Harvey, A.L., 2007a-this issue. Development of a retrospective interview measure of parental maltreatment using the Childhood Experience of Care & Abuse (CECA) instrument - a life-course study of adult chronic depression - 1. J. Affect. Disord. doi:10.1016/j.jad.2007.05.022] documented an association between parental maltreatment and risk of adult chronic depression. This paper explores the contribution of other child-specific factors (e.g. conduct problems) and family-wide factors (e.g. parental discord). METHODS: Data are derived from an enquiry of 198 women largely comprising of adult sister pairs. Data was collected by semi-structured interviews covering a wide range of parental behaviour and childhood behaviour. RESULTS: Parental maltreatment emerged as channelling the effect of family-wide factors on risk of adult chronic depression, but with a child's conduct problems and shame-withdrawal partly mediating this link. A child's depression before 17, although correlated with parental maltreatment, did not appear to play a significant role in adult depression. This core model is supplemented by analyses exploring the mechanisms involved. A mother's rejection/physical abuse and her depression via her lax control, for example, account for the link of parental maltreatment with conduct problems. Also 'rebelliousness' of a child relates to the chances of her low affection moving to rejection. "Rebelliousness" also appears to play a role in why the paired sisters so often had a different experience of maltreatment. LIMITATIONS: The data is collected retrospectively - but see [Brown, G.W., Craig, T.K.J., Harris, T.O., Handley, R.V., Harvey, A.L., 2007b-this issue. Validity of retrospective measures of early maltreatment and depressive episodes using the Childhood Experience of Care and Abuse (CECA) instrument - A life-course study of adult chronic depression - 2. J. Affect. Disord. doi:10.1016/j.jad.2007.06.003]. CONCLUSIONS: Child-specific factors play a major role in the origins of adult chronic depressive episodes. This, however, is fully consistent with an equally significant contribution from family-wide factors. The crucial point is that the link of the latter with such depression appears to be indirect and mediated very largely by parental maltreatment.

Antidepressants, social adversity and outcome of depression in general practice.

BACKGROUND: The role of current social risk factors in moderating the impact of antidepressant medication has not previously been explored. METHOD: In a RCT of SSRIs of general practice patients with mild to moderate depression (HDRS 12-19) two social indices of aversive experience were developed on the basis of prior research. First, the Life Events and Difficulties Schedule (LEDS) was used twice to document: i) recent stressful experience prior to baseline, and ii) after baseline and before follow up at 12 weeks both stressful and positive experiences, taking account of 'fresh start' and 'difficulty-reduction' events. Second, an index of unemployment-entrapment at baseline was developed for the current project. The HDRS was used to measure outcome as a continuous score and as a cut-point representing improvement below score 8. RESULTS: Each social index (LEDS and Unemployment-entrapment) was associated with a lower chance of remission at 12 weeks and each was required to model remission along with treatment arm. However there was no interaction: the degree of increased remission for those randomised to SSRIs plus supportive care compared to that for those with supportive care alone was the same regardless of social context. LIMITATIONS: Dating of remission was not as thorough as in previous work with the LEDS. Detailed examination of positive experiences suggested the large majority were not the result of remitting symptoms, but it is impossible to rule this out altogether. CONCLUSIONS: Remission rates among patients in aversive social contexts are consistently much lower irrespective of treatment. There is thus a need to evaluate the efficacy of alternative more socially focussed interventions for depressive conditions likely to take a chronic course in general practice.