Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, Denmark Hill, London
Department of Psychological Medicine, University of Wales College of Medicine, Cardiff
Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, Denmark Hill, London
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Correspondence: Dr Anne Farmer, Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, London
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ABSTRACT |
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Aims To examine the familiality of life events and depression and whether there may be a common familial factor influencing vulnerability to depression and the experiencing of life events.
Method In a sib-pair design, 108 probands with depression and their siblings were compared with 105 healthy controls and their siblings for psychopathology and life events.
Results The lifetime relative risk of depressive disorder in the siblings of depressed subjects as compared with siblings of controls was 9.74, although these groups did not differ in the life events measures. Several categories of events showed significant sibling correlations, but this was due to the same event affecting both members of the pair.
Conclusions Although depressive disorder was strongly familial, the familial effects on life events were largely explained by shared experiences. There was no evidence for a common factor influencing both depression and life events.
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INTRODUCTION |
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The CCDS researchers suggested that at least part of the association between life events and depression results from familial factors that influence both, such as personality attributes leading to risk-taking behaviour or having high levels of threat perception. In the Cardiff Depression Study, we aimed to investigate this matter further by using a sib-pair design to compare psychopathology, life events, measures of personality and attributional and cognitive style. In this paper we report the findings on co-familiality of depression and life events.
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METHOD |
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In addition, probands with depression were recruited from two general practices in Cardiff. One of the psychiatrists (S.S) obtained listings from each practice of all patients currently receiving repeat prescriptions for antidepressant medication. All such patients were then approached personally (by phone or by calling at their home) in order to assess their willingness to participate and to assess whether they fulfilled the inclusion criteria. Where possible, the sibling nearest in age to the depressed proband was studied; where this was not possible, the sibling next in age was invited to participate.
An age- and gender-matched sample of control subjects was recruited from two sources: firstly from patients attending orthopaedic and dental out-patient clinics, and secondly from employees of the University Hospital of Wales Trust, who were invited to participate via a request in their wage or salary slips. Orthopaedic and dental out-patient clinic attenders were initially screened with the 30-item General Health Questionnaire (GHQ; Goldberg, 1978). Those who scored below the caseness threshold (i.e. less than 11) on this questionnaire were personally approached by one of the research psychologists (T.H. or K.R.). Those respondents who had no history of depression and who had a sibling who was willing to be studied were recruited as control probands. Similarly, Trust employees who responded to our request were interviewed by telephone by T.H. or K.R. in order to establish whether they had ever been treated for depression and whether they had a sibling who was willing to be studied. As with the depressed siblings, where possible their siblings nearest in age were recruited; otherwise, the sibling next in age was invited to participate.
Interviews and self-rating questionnaires
All subjects were interviewed personally. In the majority of cases the
interview was face to face but 20 depressed (18.5%) and 35 control siblings
(33.3%) were interviewed by telephone. Interviewers used the Schedules for the
Clinical assessment of Neuro-psychiatry (version 2) (SCAN;
Wing et al, 1990) and
the Life Events and Difficulties Schedule (LEDS;
Brown & Harris, 1978). By
careful enquiry at interview, supplemented by examination of the case records
where available, the date of onset of illness was agreed with the probands
with depression. Where the proband was chronically ill and onset of the
illness could not be determined (a few cases only), events were rated for the
12 months prior to interview. In order that life events would be recorded for
the same period across sibling pairs, events and difficulties of depressed
probands for siblings were recorded for 12 months before the proband's illness
onset, unless the sibling was also currently ill, in which case the date of
illness onset was determined in the same way as for the depressed probands.
For control probands and their siblings, enquiry was made for the 12 months
before interview date.
Events and difficulties were recorded according to the LEDS instruction manual and panel-rated in the standard way for contextual severity on a four-point scale and for independence. All subjects also completed self-report questionnaires in order to evaluate risk-taking behaviour and threat perception.
Proband and sibling characteristics
Initially, 119 depressed probands and their siblings and 148 control
probands and their siblings were recruited. Information was incomplete for one
or both members of the pairs in 11 of the depressed group and 22 of the
control group. Hence, complete information was obtained for 108 probands with
depression (38 males and 70 females) and their siblings (33 males and 75
females), and for 126 control probands (44 males and 82 females) and their
siblings (50 males and 76 females). Because there was a significant age
difference between the proband with depression and the control proband which
could potentially confound the findings for both life events and depressive
symptoms, the 21 youngest control pairs were omitted from the data set for the
present analyses. Hence, the final analyses were carried out on 108 depressed
proband-and-sibling pairs and 105 control proband-and-sibling pairs (control
probands: 27 male and 78 females, control siblings: 42 males and 63
females).
Statistical analyses
SPSS Version 8 for Windows (SPSS Inc,
1998) was used to create a database and to undertake the
statistical analyses.
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RESULTS |
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Twenty-four (23%) of the control probands were recruited via out-patient clinics (all but one came from orthopaedic clinics), while 81 (77%) responded to the request for volunteers. It is possible that control probands recruited via the orthopaedic clinics were more hazard-probe than respondents recruited from other sources. However, those recruited from these clinics reported no more life events than those recruited from elsewhere (Mann-Whitney U-test: z=-0.41, NS).
Fewer probands with depression than control probands were able to recruit
their nearest-age sibling (2=4.90, d.f.=1,
P=0.03).
Depression ratings
The data from the SCAN interviews were scored using the CATEGO-5 program
(Wing et al, 1990).
The CATEGO-5 program produces ICD-10 operational definitions for unipolar
depression as well as an Index of Definition severity rating. All depression
probands fulfilled one of the following ICD-10 categories: F32.1 (moderate
depressive episode), F32.2 (severe depressive episode without psychotic
symptoms), F33.1 (recurrent depressive disorder - current episode moderate) or
F33.2 (recurrent depressive disorder - current episode severe without
psychotic symptoms). All depressed probands had Index of Definition levels of
5 or 6, which confirmed that all reached caseness levels of
illness severity. Thirty-six probands with depression (33.3%) were
experiencing a first episode of depression, while 72 (66.7%) were having a
recurrent episode. The mean age of probands with depression experiencing their
first episode of illness was 37.8 years, compared with 40.3 years for those
experiencing a recurrent episode, although these differences were not
statistically significant (Mann-Whitney U-test. z=1.12,
NS).
Table 2 shows the prevalence
of CATEGO-5-derived ICD-10-defined unipolar depression in the siblings. Nine
(7.4%) of probands with depression reported being treated for an episode of
depression at the time of interview; all of these siblings were classified as
cases by CATEGO-5. Twenty (18.5%) of the siblings of depressed
probands (17 female and three males) who had reported being treated for
depression in the past were also classified as lifetime ever
cases according to CATEGO-5, as were two (1.9%) (both females) of the siblings
of control probands =9.7 (95% CI 2.34-40.01). This difference was
highly significant (
2=15.87, d.f.=1, P <
0.001).
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Life events ratings
Number of contextual life events
The mean numbers of severe (threat contextually rated as 1 or 2 on the
LEDS) life events for all four groups are for three and 12 months are shown in
Table 3. Probands with
depression experienced very significantly more such events for both time
frames than the other three groups (three months Kruskal-Wallis
2=30.05, d.f.=3, P < 0.001, 12 months:
Kruskal-Wallis
2=21.59, d.f.=3, P < 0.001).
Siblings of probands with depression had only a modestly elevated frequency of
events compared with siblings of control probands; the difference was not
significant at either three or 12 months (Mann-Whitney U-test:
z=-0.67 and z=-0.82 respectively).
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Severe independent and possibly independent events
There were significant differences in the mean number of severe independent
or possibly independent life events (Table
4) between depressed and control probands at three months
(Mann-Whitney U-test: z=1.88, P=0.03) but not at 12
months (Mann-Whitney U-test: z=-0.92). Again, although the
siblings of probands with depression had more frequent events than control
siblings, the differences at three months (Mann-Whitney U-test:
z=-0.22) and 12 months (Mann-Whitney U-test:
z=-0.91) were not significant. Probands with depression who were
having their first episode of illness had significantly more independent and
possibly independent severe events than probands who had experienced a
previous episode (three months, Mann-Whitney U-test:
z=-3.40, P < 0.001; 12 months Mann-Whitney
U-test: z=-3.05, P=0.001).
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For comparison with the CCDS, severe life events that were judged to be
independent or possibly independent were dichotomised into whether one or more
such events were present or absent over a three month and a 12-month period.
The results are shown in Table
5. There were no significant differences across the four groups
(three months: 2=4.73, d.f.=3). In particular, and by contrast
with the CCDS, there was no significant difference at three months in the
proportion siblings of probands with depression who had experienced events in
this category between probands with depression and control siblings
(
2=0.004, d.f.=2). Also by contrast with the CCDS, there was
an association between recent life events and current depression in the
relatives of probands with depression. Of siblings of probands with depression
rated as current cases of depression, 37.5% had experienced one or more
independent or possibly independent severe events in the three months before
interview, compared with 7% of probands with depression rated as non-cases
(Yates
2=4.9, d.f.=1, P=0.013, one-tailed).
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Familiality of life events
There were significant correlations within the total sample of 213 sibling
pairs for the number of life events reported for three months (Pearson
r=0.20, P < 0.005) and 12 months (r=0.22,
P < 0.001). However, these correlations were partly explained by
shared events that impinged on both members of the pairs. The partial
correlations controlling for shared events were r=0.16
(P=0.012) at three months and r=0.13 at 12 months
(P=0.036). In keeping with the CCDS finding that events rated as
independent may nevertheless be familial, there was evidence of familiality
for severe independent events over 12 months in the total sample of 213 pairs
(Spearman =0.32, P < 0.001). However, this was not confined
to the probands with depression and their siblings (
=0.33, P
< 0.001), and the correlation was only slightly lower (
=0.31,
P < 0.001) in control probands and their siblings. There was also
a modest correlation for severe independent events over three months in the
total sample (
=0.19, P < 0.005). However, when shared events
were controlled for, both the three-month and 12-month correlations for the
total sample reduced to
=0.06, which was not significant.
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DISCUSSION |
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Differences between the Cardiff and Camberwell studies
Using the same design might be expected to amplify differences between the
relatives of depressed subjects and control relatives with respect to
threatening life events. In fact, we failed to find any convincing evidence of
higher rates of life events in the siblings of probands with depression than
in the control siblings. It is unlikely that this finding could be explained
by lack of power. The CCDS results, where 70 of 244 relatives of probands with
depression experienced severe events over a three-month period compared with
21 of 289 controls gave an odds ratio of 5.13 (95% CI 3.04-8.66). We estimate
that our power to detect such an odds ratio at =0.05 is over 99%, and
that even if the true odds ratio were only 3.04 the power would still be
approximately 80%.
How then can we explain the differences between the present study and the CCDS? One possibility is that they result from the proband with depression samples in the two studies differing in terms of their symptom pattern or severity. The Cardiff study included probands ascertained via general practice and, by contrast with the CCDS (Bebbington et al, 1988), did not include any subjects with an Index of Definition greater than six or any who had psychotic or melancholic subtypes of unipolar depression. However, this fact seems unlikely to explain the differences in the frequency of life events in relatives, because life events are associated with broadly defined depression (Brown & Harris, 1978) and as much with mild neurotic forms as with more severe endogenous types (Bebbington et al, 1988). An alternative reason is that in restricting ourselves to a study of siblings we have introduced a bias. For example, we were successful in recruiting the nearest-age sibling less often in the depression sample than in the control sample. The siblings of probands with depression were also more likely to be cohabiting in a stable relationship.
There is therefore a possibility that, by contact with a study including all first-degree relatives our sib-pair design tended to preferentially recruit stable, socially compliant individuals. Even so, this did not prevent us from finding a large difference in depression between the two sibling samples, and would therefore not seem to offer a convincing explanation of the failure to detect differences in life events.
A more likely explanation of differences between the two studies is that the CCDS focused on probands with clearly defined recent onsets of depression, whereas the Cardiff study did not. Hence, although the Cardiff depression probands showed a high number of recent severe life events, this number was not large enough to produce a significant excess compared with controls when life events were dichotomised into present or absent over a three-month period. The CCDS depressed-proband sample showed a much higher rate of adverse experiences, with a provoking agent occurring in almost half of the sample (Bebbington et al, 1988). The possibility arises that a study such as the CCDS focusing on onset cases and finding a strong association between depression and threatening events in probands tends to identify a coincident period of turmoil affecting other members of the family. In the CCDS an attempt was made to control for this by excluding proband-related events from the family analysis. However, the time course of life events in the CCDS (McGuffin et al, 1988b) would support a family turmoil explanation, because the excess of events occurred mainly in the three-month period before interview.
Another methodological difference between the Cardiff and Camberwell studies is the time period used for rating events in the siblings of probands with depression, which was determined by the timing of illness onset in the depressed probands in the Cardiff Study. Comparable time frames were selected in the depressed proband-sibling pairs in order to allow the familiality of events to be assessed. Hence, enquiry regarding life events was some distance back in time for some of the probands with depression and their siblings. Recall failure could have led to lower rates of events being reported in these respondents and could account for the non-significant difference between the groups for independent events present or absent over three and 12 months.
Familiality of life events and comparison with other studies
The present study found evidence of familiality of life events across the
whole sample, as reflected in significant positive correlations for total
number of events and for severe independent events. In keeping with recent
twin studies which have sought to identify events that impinge upon both
members of a pair (Kendler et al,
1993; Thapar & McGuffin,
1996), we rated events according to whether they were shared by
the probands and their siblings. When we controlled for shared events the
partial correlations for total number of events were reduced, while for severe
independent events the partial correlations were not significantly different
from zero, indicating that the entire familial effect was explained by events
being shared.
Limitations of the present study
One of the main limitations of the Cardiff study was that there was not a
strictly systematic method of ascertainment of the probands. It was not
possible to have separate interviewers carry out the LEDS and SCAN interviews
or even to ensure that siblings were assessed blind to proband diagnosis.
Although such lack of blindness could have resulted in an exaggerated familial
effect on the diagnosis of depression, this effect might in part have been
counter-balanced by the fact that we were able to interview nearest-age
siblings less often among siblings of depressed probands than among control
siblings. This is unlikely to account completely for the lack of an excess of
adverse events in that sample - and again, lack of blindness might have been
expected to bias in favour of finding such an effect.
In conclusion, we did not replicate the most striking finding of the CCDS - that severe events judged to be independent or possibly independent of the subjects' actions are familial - once we allowed for events that impinge on both members of sibling pairs. Our present findings therefore provide no support for the hypothesis that there is a causal factor in common between depressive disorder and severe life events.
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Clinical Implications and Limitations |
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LIMITATIONS
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REFERENCES |
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Received for publication February 26, 1999. Revision received June 29, 1999. Accepted for publication June 30, 1999.