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DEPRESSION AND ANXIETY 26 : 711–717 (2009)
CHILDHOOD NEGLECT AND ABUSE AS PREDICTORS OF
ANTIDEPRESSANT RESPONSE IN ADULT DEPRESSION
Jeanette M. Johnstone, M.A.,1Ã Suzanne E. Luty, M.B. Ch.B. Ph.D. F.R.A.N.Z.C.P.,1
Janet D. Carter, Ph.D. Dip. Clin. Psych. M.N.Z.C.C.P.,2 Roger T. Mulder, M.B. Ch.B. Ph.D. F.R.A.N.Z.C.P.,1
Christopher M.A. Frampton, Ph.D.,1 and Peter R. Joyce, M.D. Ph.D. D.Sc. F.R.S.N.Z. F.R.A.N.Z.C.P.1
Background: Childhood neglect and abuse are recognized as risk factors fordepression, but are not often studied as predictors of treatment response indepression. Methods: Clinically depressed outpatients (n 5 195) were askedabout childhood experiences before beginning a randomized antidepressant trialwith either fluoxetine or nortriptyline. Three treatment outcomes weremeasured: Adequate trial, six-week response and two months sustainedrecovery. Results: Patients reporting low paternal care (paternal neglect), asmeasured by the Parental Bonding Instrument (PBI), were less likely tocomplete an adequate six-week trial of medication. Patients who reported highmaternal protection (maternal overprotection) on the PBI had poorer treatmentresponse in the short-term at six weeks, and longer term, for two months ofsustained recovery. However, abuse, whether sexual, physical, or psychological innature, did not predict treatment response. Conclusions: The experience ofhaving a neglectful father or an overprotective mother was more predictiveof response to treatment for depression than abuse, suggesting that the quality ofongoing intra-familial relationships has a greater impact on treatmentoutcomes for depression than experiences of discrete abuse in childhood.
Depression and Anxiety 26:711–717, 2009.
Key words: depression; Parental Bonding Instrument (PBI); childhoodadversity; treatment predictors; abuse; neglect
Childhood adversity, whether abuse or neglect, has
1Department of Psychological Medicine, University of Otago,
been associated with the development of depression in
adult life.[1–5] Abuse can take various forms including
2Department of Psychology, University of Canterbury,
physical, verbal, psychological, or sexual. All forms of
abuse have been strongly implicated in predisposingchild victims to adult psychopathology.[6,7] Even the
Contract grant sponsors: Health Research Council of New
oft-downplayed experience of being called names as a
Zealand; Lottery Health; Eli Lilly; University of Otago; MentalHealth Division of Canterbury Health.
child, when perpetrated by one’s parents, has been
found to contribute to higher levels of depressive
Correspondence to: Jeanette M. Johnstone, Department of
symptoms in adulthood. In two retrospective studies
Psychological Medicine, University of Otago, Christchurch, PO
involving more than 25,000 adult members of a large
Box 4345, Christchurch 8140, New Zealand.
health maintenance organization, adverse childhood
experiences were found to increase risk for depressive
Received for publication 2 March 2009; Revised 7 May 2009;
One well-documented approach to measuring child-
hood experiences is the Parental Bonding Instrument
(PBI) developed by Parker et al. Created more than
25 years ago, this self-report tool has been used around
the world with community and clinical samples; in
Childhood neglect and abuse were assessed using the PBI and
Australia, Japan,[13,14] the Netherlands, New
structured interview questions. The PBI is a series of 25 self-report
Zealand,[3,16] the United States, and throughout
questions, which ask the respondent to rate separately the level of
Europe. The PBI asks the respondent to reflect on
care and protection provided by his or her mother and father or
the level of perceived care and protection received from
caregiver in the first 16 years of life. Responses are coded 0–3: very
one’s mother and father before age 17. Parker’s early
unlike, moderately unlike, moderately like and very like, with scores
work, which has been supported by others, sug-
ranging from 0 to 36 on the care scale; 0–39 on the protection scale.
gested that the combination of low care (neglect) and
High care scores indicate the respondent experienced a caring and
high protection (overprotection) was a determinant in
affectionate relationship with that parent or caregiver; lower scores, arejecting or cold attitude. High protection scores indicate the
adult depression.[18–20] More often though, neglect or
experience of an overprotective relationship with that parent; lower
abuse by either parent has been identified as a common
scores indicate the respondent felt able to differentiate from that
antecedent for adult depression.[5,12,17,21–23]
parent. The PBI has a high degree of reliability and validity.
Despite the substantial evidence for links between
The abuse measure came from a structured nurse-administered
childhood abuse and neglect with adult depression, a
interview, which assessed the presence, frequency, and type of abuse
small amount of literature examines these adverse
the individual may have experienced before age 16. Six question
childhood experiences as predictors of treatment
categories asked about a range of experiences including psychologi-
response. In one notable study, Nemeroff et al.
cal, physical, or sexual abuse or threat. Responses were collapsed into
treated 681 chronically depressed patients with an
three frequencies: 0 (not occurring), 1 (occurring 1–3 times), or 2
antidepressant (nefazodone), Cognitive Behavioural
(occurring four or more times). Total abuse scores ranged from 0 (noabuse) to 12 (repeated abuse in all six categories). For analytical
Analysis System of Psychotherapy or a combination
purposes, the abuse score was then classified into four categories
of both. Results showed that those reporting childhood
according to frequency reported: ‘‘none’’ for a 0 score, ‘‘mild’’ if r2,
adversity responded better to psychotherapy by itself
‘‘moderate’’ if r4, and ‘‘severe’’ if 44. The CSA measure was derived
than to an antidepressant alone, and the combination of
from the same interview as the abuse measure but included only those
the two treatments was only marginally better than
questions relating to sexual abuse. The three CSA categories were
psychotherapy alone. Further examination of these data
defined as: noncontact sexual abuse, such as exposure or being forced
revealed that the likelihood of achieving remission
to watch sexual activity, contact sexual abuse such as unwanted sexual
from depressive symptoms was two times higher with
touching or attempted intercourse, and sexual intercourse or rape. In
psychotherapy for those with an adverse childhood
reporting the CSA variable, ‘‘none’’ was recorded if the patient
history, suggesting that psychotherapy may be an
reported no sexual abuse. ‘‘Severe’’ was defined as any sexual abuseinvolving intercourse or more than three reports of contact sexual
essential element of treatment for those patients
abuse. ‘‘Some’’ was defined by three or fewer incidents of contact
reporting adverse childhood experiences. Other studies
sexual abuse or any report of noncontact sexual abuse.
support the notion that childhood adversity is asso-ciated with decreased response to pharmacotherapy
intervention for adult depression and dysthymia.
Given the established risk between experiencing
Following the baseline assessment, patients were randomly
adversity in childhood and developing depression in
assigned to treatment with either fluoxetine or nortriptyline. Theywere seen at least weekly for 20–40 min, depending on clinical need.
adulthood, we hypothesized that neglect, particularly
Sessions were focused on patient support and education and were
from one’s mother; overprotection and childhood
designed to optimize treatment response rather than offer formal
sexual abuse (CSA) would result in poorer outcomes
psychotherapy. Patients randomized to fluoxetine initially received
20 mg per day for three weeks, after which time the clinician couldadjust the dose up to a maximum of 80 mg. At six weeks, the meanfluoxetine dose of the sample was 28.1 mg per day, with a range of
10–80 mg. Patients taking nortriptyline initially received 25 mg forone night, 50 mg for one night, then 75 mg. Blood levels were taken
after one week and dosing adjustments made based on clinicalresponse, side effects, and individual levels. At six weeks, the mean
Depressed patients (111 females and 84 males) were recruited from
nortriptyline dose was 93.5 mg per day, with a range of 50–175 mg.
various outpatient sources. After receiving study information,
All patients who improved were encouraged to continue taking the
patients gave written consent and were screened over the telephone
medication for the six months. Further details regarding clinical
by a research nurse, then seen for an initial assessment with a
characteristics of the patients, dosing, monitoring, and follow-up care
psychiatrist or senior psychiatric registrar. Eligible patients were free
from any medication aside from oral contraceptives and occasionalhypnotics for a minimum of two weeks before study participation.
Exclusion criteria for the study included schizophrenia, a history ofmania, but not hypomania, severe alcohol and/or drug dependence,
Depression severity was assessed with the clinician-rated
or severe antisocial personality disorder, which may interfere with
Montgomery–A˚sberg Depression Rating Scale (MADRS), at
study compliance. Patients with a current major medical illness were
also excluded. After assessment, patients were randomly assigned to
Three treatment outcomes were assessed. The first measure,
either fluoxetine or nortriptyline. The study was approved by the
adequate trial, recorded whether or not the patient took an adequate
Canterbury Ethics Committee, New Zealand.
dose of the initially prescribed medication to which they had been
Research Article: Abuse and Neglect as Treatment Predictors
randomized for a majority of the first six weeks of treatment. Second
TABLE 1. Sample characteristics, pre- and post-
was the patient’s percentage improvement on the MADRS after six
treatment of 195 depressed outpatients presenting for
weeks, based on the change from baseline and represented a patient’s
response in the short-term. Finally, looking longer term, two monthssustained recovery measured whether or not the patient sustained a
‘‘much improved’’ or ‘‘very much improved’’ score on the Clinical
Global Impression scale for a minimum of two months, based on
the consensus assessments of both the treating psychiatrist and the
All data analyses were performed using the Statistical Package for
the Social Sciences (SPSS, V.15, 2006). For categorical outcome
variables, logistic regression was used plus a two-way, between groups
Analysis of Variance for known interaction effects. For the
continuous outcome variable, univariate Pearson’s correlations were
used, followed by multiple regressions for multivariate analyses.
The descriptive characteristics, pretreatment mea-
sures, treatment, and three outcomes examined for the
195 depressed outpatients in the sample are presented
in Table 1. The mean age was 32 years (711) with
37%o25 years old. Of the depressed patients, 57%
were female; 62% had recurrent depression, while 64%
had chronic depression, defined as lasting more than
two years. Lifetime rates of comorbid diagnoses are
Of the 195 patients, 10 did not rate their mother on
the PBI, while 21 did not rate their father. As such, the
maternal rating total was 185 and the paternal rating
total was 174. The mean maternal care score was 21.5
(79.3); paternal care, 17.9 (79.6). The mean maternal
protection score was 16.1 (78.4); paternal protection
14.7 (78.1). The mean PBI scores of this sample are
comparable to other depressed clinical and community
samples, which show a pattern of lower care and higher
protection scores, in contrast to never-depressed
community norms. For example, the mean maternal
care score in this study is nearly one standard deviationless than local community norms.[3,35]
When abuse is broadly defined to include physical,
psychological, or sexual experiences, more than half of the
the only one associated with failing to complete an
sample (62%) reported abuse (58% of men and 63% of
adequate six-week trial of medication.
women). When abuse was defined specifically as sexual,
In previous analyses, drug and gender influenced
18% reported CSA (8% of men and 26% of women).
completion of an adequate trial, with more patients
More than three quarters of the sample (79%)
randomized to nortriptyline failing to complete than
completed an adequate trial of medication. The mean
those assigned to fluoxetine. Furthermore, women
percentage improvement on the MADRS after six
were less likely to complete if prescribed nortriptyline;
weeks was 60.3% (731.5%). Two months of sustained
men less likely to complete if taking fluoxetine. Given
recovery was achieved by 47% of the sample.
these previously known effects, drug and gender wereincluded as covariates along with the childhoodvariables, in a multivariate analysis. The multivariate
analyses showed that low paternal care was still
associated with failure to complete an adequate trial
Table 2 shows that of the six childhood neglect and
(OR 5 1.07, 95% CI: 1.00, 1.14). Once again, this was
abuse variables, low paternal care (paternal neglect) is
the only significant childhood predictor (P 5.036).
TABLE 2. Univariate logistic regression of baseline
To illustrate this relationship, of those reporting high
variables with an adequate trial of medicationa
maternal protection (scores of 416), the meanimprovement was just 52%, compared with 67%
improvement in those who did not report high
TABLE 4. Univariate logistic regression of baseline
variables with two months sustained recovery in those
who completed an adequate trial of medicationa
cPsychological, physical, or sexual abuse or threat dichotomized into
‘‘none,’’ ‘‘mild,’’ ‘‘moderate,’’ or ‘‘severe.’’
dChildhood Sexual Abuse dichotomized into ‘‘none,’’ ‘‘some,’’
TABLE 3. Univariate Pearson’s correlation of baselinevariables with percentage improvementa
PREDICTORS OF TWO MONTHSSUSTAINED RECOVERY
Table 4 shows that high maternal protection
(maternal overprotection) was the only childhood
variable associated with fewer participants achieving
two months sustained recovery in those who completed
Previous data have shown an interaction effect
between age and drug, with patients under the age of25 less likely to achieve two months of sustained
aBased on the patient’s change from baseline on Montgomery-A˚sberg
recovery when taking nortriptyline compared with
Depression Rating Scale after six weeks of treatment.
fluoxetine. Even when including these covariatesalong with all the childhood variables in multivariate
It should be noted that the scales for parental care
analyses, maternal overprotection was the only child-
(0–36) and protection (0–39) are quite different to the
hood variable, which predicted fewer patients achieving
abuse scale (0–3). Thus, odds ratios and their
two months sustained recovery. There was a little
confidence intervals cannot be compared across these
difference between the univariate (OR 5 0.93; 95% CI:
childhood variables. To illustrate the effect of low
0.89, 0.97; Po.001) and multivariate (OR 5 0.90, 95%
paternal care on completion of an adequate trial, for
those with paternal care scores r17, nearly 30% did
To illustrate the relationship between maternal
not complete an adequate trial of medication, while
protection and two months sustained recovery, of those
only 11% failed to complete an adequate trial with
who reported maternal overprotection (scores416),
only 39% achieved two months sustained recovery incomparison to 61% of those who did not reportmaternal overprotection.
Table 3 shows that maternal protection was inversely
correlated with the percentage improvement in symp-
The aim of this study was to examine whether
toms of depression after six weeks of treatment.
adverse childhood experiences predicted response to
As previous analyses have shown that patients under
antidepressant medication in adult outpatients. Three
the age of 25 randomized to nortriptyline had poorer
key findings emerged. The first notable finding was
outcomes at six weeks, these interaction effects were
that low paternal care (paternal neglect) was associated
included as covariates, along with the childhood
with not completing a six week trial of medication. The
variables, in multiple regression analyses. Results
second finding was that in both the short and longer
showed that high maternal protection remained sig-
term, high maternal protection (maternal overprotec-
nificant in predicting a reduced improvement in
tion) was associated with poorer response. The third
symptoms of depression after six weeks of treatment.
finding was that the presence of abuse, whether defined
Research Article: Abuse and Neglect as Treatment Predictors
broadly or specifically as sexual abuse, did not predict
adulthood. This speculation finds some support in
response to any of the treatment outcomes. These
Parker’s early examination of maternal overprotec-
three findings, initially observed in univariate analyses,
tion. In his study, a mother who was rated by her
remained significant in multivariate analyses, which
child as being overprotective rated herself ‘‘as having a
included all the childhood variables as well as potential
more external locus of control,’’ (p. 307) or perceiving
confounding variables such as age, drug, and gender.
that the environment and external factors have the
Our first finding, that paternal neglect predicted
greatest impact on what happens in her life. An external
failure to complete an adequate trial of medication, has
locus of control may operate in parallel with reduced
not been reported. Researchers examining adequate
expectations for treatment. Patients with lower
trial or ‘‘dropout,’ as it is often defined, suggest patient
expectations of improvement with treatment do less
characteristics are the primary predictors of attrition.
well than those who have higher expectations.[44,47]
General patient characteristics implicated include
Patients who have limited experience thinking for
comorbidities, age, race, and education level. Tedlow
themselves may not readily form positive opinions
et al. comparing dropouts and completers in a
about their treatment, thus reducing its efficacy.
fluoxetine-only trial, noted that dropouts had higher
Our third finding, that abuse did not predict
rates of histrionic or narcissistic personality disorder
treatment outcomes in this pharmacotherapy trial, runs
than completers, and higher anxiety levels. Higher
counter to our initial hypothesis. Research suggests
rates of anxiety in dropouts have also been found by
strong evidence for the epidemiological role of child-
Arnow. Younger patients, subjects with less educa-
hood abuse in the development of adult depression but
tion and those belonging to an ethnic minority, are also
a weaker connection between childhood abuse and
more likely to drop out.[37,38] One study examined
poorer response to treatment. A few studies have found
childhood experiences in relation to dropout, but in the
childhood trauma associated with treatment-resistant
context of bulimic women. Those who dropped out
depression and dysthymia, while another study
rated their families as very poor at showing emotional
found differential response to psychotherapy vs.
concern for each other. Perhaps this finding is
pharmacotherapy, with those patients reporting child-
important in understanding why those reporting a
hood adversity responding better to psychother-
neglectful father dropped out of treatment. Psychody-
apy.[24,25] Given that abuse by itself did not predict
namic theory posits that supportive, caring parental
any of the treatment responses, perhaps it is the quality
attachment is a foundation for forming and maintain-
of ongoing intra-familial relationships that has a
ing social relationships in adulthood, a concept
greater impact on treatment than experiences of
supported by research.[41–43] Carrying this notion
discrete abuse in childhood, a hypothesis supported
beyond social constructs, the professional relationship
between patient and psychiatrist may be negatively
In summary, a significant body of research links
influenced by the patient’s experience of a neglectful
various forms of childhood neglect and abuse to the
father, to the extent that the patient is not sufficiently
development of adult depression. This study indicates
trusting the psychiatrist to take the prescribed medica-
that those who reported having a neglectful father were
less likely to take an adequate dose of the initially
In both the short-term (percentage improvement at
prescribed antidepressant medication for the six-week
six weeks), and longer term (two months sustained
trial. Additionally, those who reported an overprotec-
recovery), maternal overprotection predicted a poorer
tive mother had a poorer response to treatment in both
response. While maternal overprotection has been
short and longer term. Finally, abuse, whether physical,
implicated in the development of adult depression,
sexual, or psychological in nature, did not predict
no previous research was found regarding the specific
treatment response to antidepressant medication.
role of maternal overprotection in predicting treatment
Findings may inform clinicians’ decisions with respect
outcomes. Three patient characteristics shown to
to prescribing antidepressants to patients who report
predict poorer outcomes in pharmacotherapy trials
specific types of childhood adversity.
levels,[44,45] minority ethnicity, and concurrent anxietyissues. Other predictors of poor outcome included
Acknowledgments. The principal author thanks
living alone and poorer functioning and quality of
Dr. Virginia McIntosh for her invaluable input; thanks
also to Robyn Abbott and Isobel Stevens for their early
Speculating on the role of maternal overprotection as
work on this study, and to the local psychiatrists who
a predictor of poor treatment outcomes, perhaps this
finding suggests the importance of developing an
Role of funding source: This research was funded by
independent sense of self in childhood, as an over-
a grant from the Health Research Council of
protective mother is one who does not encourage her
New Zealand, a grant from Lottery Health, and an
child to think and act independently of her. Children
unrestricted grant from Eli Lilly (New Zealand). These
discouraged from independent thought and behavior
sponsors had no further role in study design; in the
are less likely to develop these skills for use in
collection of analysis and interpretation of data; in the
writing of the report; and in the decision to submit the
14. Sato T, Sakado K, Uehara T, et al. Dysfunctional parenting as a
paper for publication. The Clinical Research Unit of
risk factor to lifetime depression in a sample of employed
the Department of Psychological Medicine, Christch-
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Carter the supervisor, Mulder the study investigator
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IMPORTANT INFORMATION ABOUT TAKING YOUR TRANSPLANT DRUGS After an organ transplant you need to take medication such as ciclosporin or tacrolimus to help prevent you from rejecting that organ. How you take your medication is very important. Below are some key things to remember. For further details or if you have any questions, ask your transplant nurse, doctor or phar
Prof. Dr. Uta Meyding-Lamadé Schriftenverzeichnis 1. U. Meyding-Lamadé, B. Bassa, C. Jacobi, B. Kress, C. Schranz, Abstract: A Stroke Therapy in the 21st Century: A Case Report Brunei Darussalam Journal of Health . 2012, 5: 13-19 in press 2. Kunze U, Meyding-Lamadé U , ISW TBE. Tick-born encephalitis: the impact of epidemiology, changing lifestyle, and environmental factor