Childhood maltreatment and the medical morbidity in bipolar disorder: a case–control study
Hosang et al. Int J Bipolar Disord
Childhood maltreatment and the medical morbidity in bipolar disorder: a case-control study
Georgina M. Hosang 0
Helen L. Fisher 2
Rudolf Uher 1
Sarah CohenW‑oods 3
Barbara Maughan 2
Peter McGuffin 2
Anne E. Farmer 2
0 Psychology Department , Goldsmiths , University of London , Lewisham Way, London SE14 6NW , UK
1 Department of Psychiatry, Dalhousie University , 5909 Veterans' Memorial Lane, Halifax, NS B3H 2E2 , Canada
2 MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London , De Crespigny Park, London SE5 8AF , UK
3 School of Psychology, Flinders University , GPO Box 2100, Adelaide, SA 5001 , Australia
Background: Childhood maltreatment (abuse and neglect) can have long‑ term deleterious consequences, including increased risk for medical and psychiatric illnesses, such as bipolar disorder in adulthood. Emerging evidence suggests that a history of childhood maltreatment is linked to the comorbidity between medical illnesses and mood disorders. However, existing studies on bipolar disorder have not yet explored the specific influence of child neglect and have not included comparisons with individuals without mood disorders (controls). This study aimed to extend the existing literature by examining the differential influence of child abuse and child neglect on medical morbidity in a sample of bipolar cases and controls. Methods: The study included 72 participants with bipolar disorder and 354 psychiatrically healthy controls (average age of both groups was 48 years), who completed the Childhood Trauma Questionnaire, and were interviewed regarding various medical disorders. Results: A history of any type of childhood maltreatment was significantly associated with a diagnosis of any medical illness (adjusted OR = 6.28, 95% confidence intervals 1.70-23.12, p = 0.006) and an increased number of medical illnesses (adjusted OR = 3.77, 95% confidence intervals 1.34-10.57, p = 0.012) among adults with bipolar disorder. Exposure to child abuse was more strongly associated with medical disorders than child neglect. No association between childhood maltreatment and medical morbidity was detected among controls. Conclusions: To summarise, individuals with bipolar disorder who reported experiencing maltreatment during childhood, especially abuse, were at increased risk of suffering from medical illnesses and warrant greater clinical attention.
Bipolar disorder; Childhood maltreatment; Medical illness; Physical health; Child abuse; Child neglect; Childhood adversity
Bipolar disorder is associated with substantial
morbidity and mortality
; for instance people
with bipolar disorder die up to 14 years younger than
the general population
(Chang et al. 2011)
mortality among individuals with this illness cannot be
explained by suicide alone
(Hoang et al. 2011)
been attributed to the high rates of medical illnesses in
(Crump et al. 2013)
. The rates of a myriad of
medical disorders (e.g. diabetes, stroke, thyroid disease
and cardiovascular disease) have been reported to be
significantly elevated among people with bipolar disorder
compared to the general population
(Forty et al. 2014;
Perron et al. 2009)
Little is known about the factors that are
associated with the high medical burden in bipolar
disorder, although the implications are huge for the
individual, their families and society as a whole. The
available evidence suggests that multiple factors are likely to
contribute to the medical morbidity in bipolar disorder
(and other serious mental illnesses), the factors which
have received the most attention include side effects of
psychotropic medications, unhealthy life style choices
and issues with health care provision for this group.
Various side effects are associated with psychotropic
medication, such as mood stabilisers and antipsychotics
which are commonly used to treat bipolar disorder, the
most pertinent to this context include weight gain and
. Such side effects
are risk factors for diabetes and cardiovascular disease
(Correll et al. 2015)
and thus may explain the high rates
of these illnesses in people with bipolar disorder.
Smoking, unhealthy diet and physical inactivity are lifestyle
choices and habits which are prevalent in people with
(Scott and Happell 2011)
but are also
known risk factors for physical illnesses, such as diabetes
and coronary heart disease, thus these lifestyle choices
may explain the comorbidity between these illnesses and
bipolar disorder (De Hert et al. 2011). A small but
growing body of research suggests that people with serious
mental illnesses are less likely to receive standard levels
(De Hert et al. 2011)
. For instance, low rates of
surgical interventions for coronary heart disease (e.g.
stenting) and screening for metabolic abnormalities
associated with diabetes are recorded for people with
mental illnesses including bipolar disorder
(De Hert et al.
. This is despite the fact that such illnesses are
highly prevalent in this population. A factor which has
received less attention in this context is the influence of
childhood adversity. Preliminary research suggests that
the experience of childhood maltreatment may
contribute to the medical morbidity observed in bipolar disorder
(Post et al. 2013)
, but these findings await replication and
Childhood maltreatment encompasses both abuse
(e.g. sexual, emotional and physical abuse) and neglect
(lack of provision for the individual’s needs by their
caregiver, including food, shelter and support)
(Norman et al.
. Childhood maltreatment can be considered a
plausible risk factor for the comorbidity between medical
illnesses and bipolar disorder based on two lines of
evidence. First, childhood maltreatment is associated with
lasting changes or abnormalities in a number of
biological systems or processes detected in adulthood
2013; Danese and Lewis 2016)
. For instance, increased
inflammatory cytokines are exhibited by maltreated
individuals both as children (Slopen et al. 2013) and adults
(Baumeister et al. 2016)
. Elevated inflammation has also
been implicated in bipolar disorder
(Leboyer et al. 2012)
and a series of medical illnesses, such as diabetes,
arthritis and certain cancers
could explain the comorbidity between the two
disorder groups. Moreover, there is evidence that people with
mood disorders and a history of childhood maltreatment
exhibit particularly pronounced elevation in
(Danese et al. 2008, 2011)
. For example,
maltreated individuals with depression have significantly
increased inflammation levels compared to those with
depression only, a history of childhood maltreatment
only and those without either (controls) (Danese et al.
Secondly, childhood maltreatment is associated with
an increased risk of medical illnesses
(Hosang et al. 2013;
Scott et al. 2011)
and bipolar disorder
(Fisher and Hosang
2010; Palmier-Claus et al. 2016)
in adulthood. The results
from several studies have gone further and shown that
childhood maltreatment is linked to the co-occurence of
medical illnesses and mood disorders (including bipolar
(Lu et al. 2008; McIntyre et al. 2012)
. To date
only one study has examined this relationship in bipolar
disorder specifically and found that childhood adversity
is significantly related to the diagnosis of medical
illnesses in adulthood, including diabetes, cardiovascular
disease and asthma (Post et al. 2013).
The limited available research in this area has not
explored the specific role of child neglect but has focused
on broadly defined childhood maltreatment
et al. 2012)
, or childhood adversity which includes child
abuse, parental psychopathology and violence in the
(Lu et al. 2008; Post et al. 2013)
. Exposure to child
neglect has been related to a number of medical illnesses,
such as cardiovascular disease, diabetes and
osteoarthritis in adulthood
(Norman et al. 2012; Scott et al. 2011)
and therefore is a crucial construct to consider in this
context. Furthermore, previous studies examining the
medical morbidity in bipolar disorder have not included
comparisons with control groups (Post et al. 2013), thus
it remains unclear whether the relationship between
child adversity (including childhood maltreatment) and
medical illnesses is specific to or greater among people
with bipolar disorder relative to the general population.
To address the methodological gaps in the literature,
the current study aimed to investigate the association
between a history of child maltreatment and the
diagnosis of medical illnesses in adulthood among people with
bipolar disorder compared to unaffected controls (those
without a personal or family history of a psychiatric
illness). The differential influence of child abuse and child
neglect on the diagnosis of medical illnesses was also
examined in this context. It is hypothesised that both
child abuse and neglect will be more significantly
associated with medical illnesses in the bipolar disorder group
compared to controls.
A total of 426 participants were included in this study,
354 (58% females, N = 205) of which were
psychiatrically healthy controls and 72 (78% females, N = 56)
were diagnosed with bipolar disorder (see Table 1). The
participants with bipolar disorder were aged between
29 and 72 years, with a mean of 48.4 years (SD = 9.43).
Participants with bipolar disorder were enrolled in the
BADGE (gene-environment interplay in bipolar
affective disorder) study
(see Hosang et al. 2012)
recruited by re-contacting bipolar cases from the
Bipolar affective disorder case–control study (BaCCs)
Gaysina et al. 2009; Hosang et al. 2017)
recruitment for BACCs was mainly via psychiatric
outpatient clinics with the rest enlisted through media
advertisement and self-help groups in the UK. All
participants with bipolar disorder met DSM-IV criteria
for bipolar I or bipolar II disorder ascertained via the
schedules for clinical assessment in neuropsychiatry
interview (see “Measures” section), and were Caucasian
to control for population stratification since they were
originally recruited from a genetic association study
(see Gaysina et al. 2009). Participants were excluded if
their bipolar episodes only occurred in relation to
substance misuse or a physical disorder or if they had a
personal or family history of schizophrenia. Participants
with bipolar disorder were not experiencing a mood
Significant p values are italicised
N number of participants, SD standard deviations, % percentage, P probability due to chance
a These figures are not the sum of the derived variables as some participants report experiencing more than one type of maltreatment
b Childhood maltreatment was considered present if any type of child abuse or neglect were rated as moderate or severe
c Child abuse was considered present if any form of child abuse was rated as moderate or severe
d Child neglect was considered present if physical or emotional neglect was rated as moderate or severe
episode at either of their assessments for the BaCCs and
The controls were a sub-sample of a case–control
genetic association study on unipolar depression that
provided information on their experience of
maltreatment during childhood
(see Fisher et al. 2013)
controls were aged between 24 and 68 years with a mean
of 47.7 years (SD = 9.15). They were recruited through
UK general medical practices and excluded if they had a
personal or family history (among first degree relatives)
of any psychiatric disorder. Given that participants were
drawn from genetic association studies they were
Caucasian to control for population stratification. All
participants were aged 18 years or over and provided written
informed consent after the nature of the study and
procedures were fully explained. All studies received ethical
approval from either King’s College Hospital or the Joint
from South London and Maudsley and Institute of
Psychiatry Research Ethics Committees. All procedures
contributing to this work were conducted in accordance with
the Declaration of Helsinki in 1975 (revised in 2008), and
the ethical standards of the national and institutional
committees on human experimentation.
Bipolar disorder diagnosis
The Schedules for Clinical Assessment in
Neuropsychiatry (SCAN), Version 2.1 interview
(Wing et al. 1990)
used to ascertain a lifetime DSM-IV diagnosis of bipolar
disorder. The presence and severity of the
psychopathology items were rated for the worst depressive and manic
History of childhood maltreatment
All participants completed the 28-item Childhood
Trauma Questionnaire (CTQ)
(Bernstein et al. 2003)
which was used to record the experience of five types
of childhood maltreatment (i.e. physical abuse, sexual
abuse, emotional abuse, physical neglect and emotional
neglect). A total of 5 items were used to measure each
type of maltreatment, which were rated on a 5-point
Likert scale ranging from 1 (never true) to 5 (very often
true). The cut-offs for moderate to severe levels of each
type of maltreatment were employed in this study in
accordance with the manual
(Bernstein et al. 2003)
five types of childhood maltreatment rated as moderate
or severe were categorised into abuse (i.e. sexual,
emotional and/or physical abuse) and neglect (emotional
and/or physical neglect). Good psychometric properties
have been reported for this instrument, for instance there
is high concordance between CTQ scores and therapists’
ratings of childhood maltreatment
(Bernstein et al. 2003)
Moreover, good test–retest reliability has been found
using this instrument in a sample of people with bipolar
(Shannon et al. 2016)
All participants completed a self-report questionnaire to
determine the lifetime presence of various medical
(Farmer et al. 2008; Forty et al. 2014)
were asked whether they had been formally diagnosed
with any of the following illnesses: heart problems (i.e.
stroke, angina and heart attack), asthma, diabetes (I and
II), arthritis (i.e. osteoarthritis, rheumatoid arthritis and
other types of arthritis), hypertension, epilepsy or
convulsions, osteoporosis, multiple sclerosis, emphysema or
chronic bronchitis, or post herpetic neuralgia. Trained
research assistants administered the questionnaire to all
participants, which involved confirming that a formal
diagnosis of the illness was provided by a medical
professional (e.g. General Practitioner or medical consultant).
Good concordance between the self-report of medical
illnesses using this interview and practitioner ratings have
been found (Farmer et al. 2008).
Group differences were tested using Chi-square (χ2) tests,
one-way ANOVAs and independent sample t tests. The
Fisher’s exact test was conducted if a χ2 test could not be
used (e.g. expected values were less than 5).
Case–control differences concerned with the association between
childhood maltreatment and medical illnesses were
examined using two approaches. First, using logistic
regression models when at least one medical disorder
was examined and second, ordinal logistic regression
models when the number of medical illnesses was the
focus (none, 1 and 2 or more illnesses). Gender and age
were entered as covariates, along with child
maltreatment, bipolar disorder status, as well as the interaction
between childhood maltreatment and bipolar disorder
status. Three parallel models (for each approach) were
undertaken to investigate the effect of any type of
childhood maltreatment, child abuse and child neglect. Given
the relatively small bipolar disorder sample size and
uneven distribution of some variables, we estimated the
variance in the regression models with non-parametric
bootstrap with replacement (1000 replications) to obtain
empirical standard error estimates without making
distributional assumptions. All statistical tests were
performed in STATA version 14.0; the conventional level of
significance, p < 0.05, was used in this study.
There was no significant age difference between
the controls and participants with bipolar disorder
(t(393) = 0.60, p = NS), but there was a significantly
higher proportion of females in the bipolar group relative
to the controls (χ2(1) = 9.34, p = 0.002). The percentage
of participants reporting each medical illness and
different types of childhood maltreatment are presented in
Table 1. The most commonly reported medical illnesses
in the sample were arthritis, asthma and hypertension.
The relatively low number of participants that recorded
being diagnosed with each medical illness prevented the
examination of associations between specific disorders
and childhood maltreatment. Thus the remaining
analyses focused on either the diagnosis of at least one or the
number of (none, 1 and 2 or more) medical illnesses.
There were no gender differences in the diagnosis of at
least one (χ2(1) = 0.08, p = NS) or the number of
medical disorders (χ2(1) = 0.29, p = NS). Those individuals
that reported receiving a diagnosis of at least one
medical disorder were significantly older than those without
a diagnosis (t(393) = 4.05, p < 0.001). A similar pattern
was observed when the number of medical illnesses
were examined (F(2, 392) = 9.92, p < 0.001): participants
that reported 1 (mean age = 49.73 years, SD = 8.14) or
at least 2 (mean age = 52.54 years, SD = 9.54) medical
disorders were significantly older than the individuals
that recorded none (mean age = 46.53 years, SD = 9.19)
according to a Tukey post hoc test (p = 0.009, p < 0.001,
Significantly more participants with bipolar disorder
reported being diagnosed with at least one medical
illness compared to controls (χ2(1) = 26.61, p < 0.001) and
they also reported to have significantly more medical
illnesses relative to controls (χ2(2) = 49.88, p < 0.001). The
rates of all types of childhood maltreatment were
significantly greater among the bipolar group compared to the
controls (see Table 1). A moderate correlation between
child abuse and neglect was detected in the entire sample
(Pearson’s r(426) = 0.33, p < 0.001).
Logistic regression models were conducted to explore
the interaction between bipolar disorder status and the
history of childhood maltreatment on the diagnosis of at
least one medical illness, and ordinal logistic regression
models were undertaken to examine the number of
medical disorders (gender and age were included as
covariates in the analyses), the results of which are presented
in Table 2. Bipolar disorder status significantly interacted
with both the exposure to any type of childhood
maltreatment and child abuse on the diagnosis of at least one and
the increased number of medical illnesses (see Table 2).
The results remained significant for child abuse even when
the effects of child neglect were controlled for (at least one
medical illness: adjusted OR = 5.90, 95% confidence
intervals (CI) 1.31–26.62, p = 0.021; number of medical
disorders: adjusted OR = 4.85, 95% CI 1.30–18.06, p = 0.019).
Although exposure to child neglect was associated with
higher odds of having a medical illness with bipolar
disorder, the results failed to reach conventional levels of
significance (at least one medical illness: adjusted OR = 4.32,
95% CI 0.96–19.47, p = 0.057; number of medical
disorders: adjusted OR = 3.30, 95% CI 0.89–12.22, p = 0.075).
Further examination of the interactions showed that
exposure to any type of childhood maltreatment, child
abuse and child neglect were significantly associated with
higher odds of having at least one and a greater number
of medical illnesses in the bipolar group but not for the
controls (see Table 3). The percentage of bipolar cases
and controls with medical illnesses by each type of
childhood maltreatment is visually presented in Fig. 1. Given
that there were a restricted number of participants that
reported experiencing each type of child abuse (i.e.
sexual, physical and emotional) and neglect (i.e. emotional
and physical), analyses examining their individual and
interactional effects were not possible.
This study found a significant relationship between
childhood maltreatment and medical illnesses in adulthood
among individuals with bipolar disorder but not in
unaffected controls. When the analyses were stratified by the
type of childhood maltreatment the results were
strongest for child abuse rather than child neglect. This is the
first study to explore child neglect in this context using
both controls and participants with bipolar disorder. Our
findings are consistent with previous studies that have
focused on mood disorders
(Lu et al. 2008; McIntyre et al.
and bipolar disorder specifically (Post et al. 2013).
For instance, broadly defined childhood adversity, which
includes child abuse (verbal, physical and sexual) and
parental psychiatric diagnosis, but not child neglect, was
found to be significantly associated with the overall
number of medical illnesses in a sample of over 900 people
with bipolar disorder
(Post et al. 2013)
adversity was also found to be significantly associated with
specific medical illnesses in this group including
arthritis, asthma, hyper- and hypo-tension
(Post et al. 2013)
However the results from the present investigation add
to this literature by showing that the relationship between
childhood maltreatment and medical illnesses is
especially pertinent to bipolar disorder compared to controls.
Although the relationship between childhood
maltreatment and medical illnesses in adulthood has been
established in the general population
(Scott et al. 2011)
relationship maybe particularly relevant to bipolar disorder
for two reasons. First, high rates of childhood
maltreatment have been found among people with bipolar disorder
(Fisher and Hosang 2010; Palmier-Claus et al. 2016)
Childhood maltreatment has also been associated with a worse
clinical course among people with bipolar disorder, such
as, earlier age of onset and more mood episodes
(AgnewBlais and Danese 2016)
. Such clinical course characteristics
have also been linked to the medical morbidity in bipolar
Magalhães et al. 2012
). Bringing together these
lines of research it is possible that childhood maltreatment
may lead to an unfavourable clinical course in bipolar
disorder that in turn contributes to the high medical burden
observed in this illness. Although the exact mechanism
that underpins this relationship is unclear, it has been
postulated that it may reflect shared biological vulnerabilities,
such as disruption in inflammation and oxidative systems
Magalhães et al. 2012
). Alternatively, the more severe
clinical course associated with childhood maltreatment
(Agnew-Blais and Danese 2016)
is likely to increase the
need for medication treatment. The side effects of mood
stabilisers and antipsychotics, include weight gain and
are linked to various
medical conditions, such as diabetes
potentially explaining the link between childhood
maltreatment and physical illnesses in bipolar disorder but may
Panel a At least one medical illness
Bipolar cases (one medical illness)
Controls (one medical illness)
Bipolar cases (two or more medical illnesses)
Controls (two or more medical illnesses)
Any type of childhood maltreatment
Type of childhood maltreatment
Panel b Number of medical illnesses
Child abuse Child Neglect Any type of childhood maltreatment
Type of childhood maltreatment
Fig. 1 Percentage of participants with medical illnesses by type of childhood maltreatment experienced. The y‑axis presents the percentage of
participants with medical illnesses by the different types of childhood maltreatment groups (child abuse, child neglect and any type of childhood
maltreatment) for bipolar cases and controls. a The diagnosis of at least one medical illness and b the number of medical illnesses (one and two or
have also attenuated the results here. Although in the
current study all of the participants with bipolar disorder were
on long-term medication regimens for their psychiatric
illness; therefore this confounding effect is unlikely here, but
more research is needed to clarify this issue.
Second, the biological sequelae of childhood
maltreatment, such as increased inflammation levels
et al. 2016)
are also evident in bipolar disorder
et al. 2012)
and various medical illnesses, particularly
autoimmune diseases, such as arthritis and type I
. Research indicates that
elevated inflammation is particularly pronounced among
maltreated individuals with mood disorders even when
compared to those who have a history of child abuse
(Danese et al. 2008, 2011)
, thus potentially
increasing the risk of such medical illnesses. For
example, the results from one study found that inflammation
levels were significantly higher among those with a
history of childhood maltreatment and depression relative
to those with depression only, childhood maltreatment
only and controls (without either) (Danese et al. 2011).
The biological consequences of childhood maltreatment
in bipolar disorder warrants further research attention to
better understand the possible mechanisms that underlie
its high medical burden.
The results from the current investigation provide a
novel contribution to the field by helping to show
differential relationships between child abuse, child neglect
and medical illnesses in bipolar disorder. Previous
studies examined these adversities under one overarching
construct of childhood maltreatment or did not explore
the impact of child neglect separately
(Lu et al. 2008;
McIntyre et al. 2012; Post et al. 2013)
. The results of the
present study suggest that the effect of child abuse on
medical illnesses is not only significant but may also be
stronger than that of child neglect in bipolar disorder.
This is consistent with the results of previous studies
which have shown that child abuse is associated with a
list of medical disorders whereas neglect is linked to only
a limited number of illnesses
(Scott et al. 2011; Norman
et al. 2012)
. It is possible that unhealthy lifestyles may
explain the stronger association between the
experience of child abuse and medical disorders compared to
child neglect. For example, smoking is a major risk
factor for a series of medical disorders
(Ezzati et al. 2002)
and has been significantly associated with child abuse but
not child neglect
(Norman et al. 2012)
. The exact
mechanisms behind the link between child abuse and the
medical burden in bipolar disorder is unclear and warrants
further investigation. The limited sample size of the
bipolar group may have impacted on the study’s power and
is likely to have contributed to the non-significant
interaction effect of child neglect and bipolar disorder status
on the diagnosis of medical illnesses. Future research
focusing on the biological, psychological and behavioural
correlates of child abuse using larger samples would be
With replication, the findings of this study are clinically
valuable since they can be used to identify a subgroup
of people with bipolar disorder (those with a history of
childhood maltreatment) who are at risk of poor health
(Post et al. 2013)
and worse clinical course
and Danese 2016)
. These results underscore the need
for routine assessment of childhood maltreatment
history in clinical practice, which would assist with the early
recognition of an ‘at risk’ group who would benefit most
from targeted prevention and intervention efforts. Family
therapy or psychoeducation focused on improving the
social support provided to people with bipolar disorder
maybe particularly beneficial. This suggestion is based
on research that shows that social support influences the
risk of relapse in bipolar disorder and mediates the effect
of childhood maltreatment on physical health in
(Herrenkohl et al. 2016)
There are a number of strengths of this study including
the use of a well-characterised bipolar disorder sample
and screened controls that completed validated
instruments. But several limitations of the current study should
be considered when interpreting the findings. First, the
limited sample size of the bipolar group may reduce the
power to detect significant effects and the ability to
generalise our results. Participants with bipolar disorder in
this study were recruited from across the UK through
psychiatric outpatient clinics and self-help groups, so are
not entirely biased or unrepresentative. Future studies
should use a larger case–control sample to confirm the
associations observed in this investigation. Second,
childhood maltreatment and medical illnesses were assessed
using self-report which has been associated with various
problems (e.g. reporting accuracy)
(Reuben et al. 2016)
Retrospective self-report questionnaires used to assess
childhood maltreatment are commonly used in both
epidemiological and psychiatric studies
(Norman et al.
2012; Agnew-Blais and Danese 2016)
childhood maltreatment data yielded from self-report show
high concordance with case notes (Fisher et al. 2011)
and therapists’ ratings
(Bernstein et al. 2003)
Substantial agreement between the self-report medical interview
used here and the health practitioner reports of the
diagnoses of medical disorders has been reported
et al. 2008)
. Nonetheless, it would be useful for future
studies to replicate the findings of the present study using
practitioner reports of medical illnesses, and prospective
objective assessment of childhood maltreatment.
Finally, the incidence of several medical illnesses,
particularly heart problems was relatively low especially
compared to other studies, this precluded the
examination of the specific association between childhood
maltreatment and particular medical illnesses. This may
have been the result of the age of the sample (median age
49 years, range 24–72 years), with the majority of
participants outside of the median age of onset (58–64 years)
for various heart problems, including coronary heart
disease and stroke
(Terry et al. 2004)
. But the prevalence of
arthritis, hypertension and asthma in the current study is
comparable to those reported in previous investigations
(McIntyre et al. 2006; Perron et al. 2009)
. Future studies
should explore the influence of childhood maltreatment
on the medical morbidity in bipolar disorder using an
To summarise, this is one of a limited number of
studies that has examined the relationship between childhood
maltreatment and the medical morbidity in bipolar
disorder. This study extends previous work by exploring the
differential relationship between child abuse and neglect
and in this context using a sample of controls and
individuals with bipolar disorder. The results of this study
showed that childhood maltreatment is significantly
associated with medical ill health among people with
bipolar disorder but not controls. On further
examination of the data, child abuse showed the strongest
association with medical illnesses compared to child neglect.
With more research these findings can be used to identify
individuals who would benefit most from prevention and
SCAN: schedules for clinical assessment in neuropsychiatry interview; CTQ:
Childhood Trauma Questionnaire; BADGE: gene‑ environment interplay in
bipolar affective disorder; BaCCs: bipolar affective disorder case–control study.
GMH conducted the analyses for the manuscript, interpreted the results and
drafted the manuscript. BM, PM and AF worked on the conception and design
of the study and critically revising the manuscript in preparation for submis‑
sion. HF, SC‑ W and UR were involved in the data analysis, interpretation of the
findings and drafting the manuscript. All authors read and approved the final
We would like to thank the members of the Radiant Team who were involved
with the data collection and management of the studies and all of the indi‑
viduals who participated in the research.
The authors declare that they have no competing interests.
Availability of data and materials
The data will not be shared since it is not owned by the author.
Ethical approval and consent to participate
All participants provided written informed consent after the nature of the
study and procedures were fully explained. All studies received ethical
approval from either King’s College Hospital or the Joint from South London
and Maudsley and Institute of Psychiatry Research Ethics Committees. All
procedures contributing to this work were conducted in accordance with the
Declaration of Helsinki in 1975 (revised in 2008), and the ethical standards of
the national and institutional committees on human experimentation.
The bipolar case–control genetic association study was funded by an unre‑
stricted grant from GlaxoSmithKline Research and Development. Funding for
the depression case–control study was provided by the UK Medical Research
Council (MRC; G0701420). The BADGE study was supported by an Interdiscipli‑
nary Ph.D. studentship from the UK Economic Social Research Council (ESRC)
and MRC to Dr. Hosang. Prof. Uher is supported by the Canada Research Chairs
program (http://www.chairs‑ chaires.gc.ca/him) and Dr. Fisher is supported by
an MQ Fellows Award (MQ14F40). The sources of funding had no involvement
in the study design, data collection or decision to submit for publication.
Springer Nature remains neutral with regard to jurisdictional claims in pub‑
lished maps and institutional affiliations.
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