Adolescent development of psychosis as an outcome of hearing impairment: a 10-year longitudinal study.
ABSTRACT It has long been acknowledged that hearing impairment may increase the risk for psychotic experiences. Recent work suggests that young people in particular may be at risk, indicating a possible developmental mechanism.
The hypothesis that individuals exposed to hearing impairment in early adolescence would display the highest risk for psychotic symptoms was examined in a prospective cohort study of a population sample of originally 3021 adolescents and young adults aged 14-24 years at baseline, in Munich, Germany (Early Developmental Stages of Psychopathology Study). The expression of psychosis was assessed at multiple time points over a period of up to 10 years, using a diagnostic interview (Munich Composite International Diagnostic Interview; CIDI) administered by clinical psychologists.
Hearing impairment was associated with CIDI psychotic symptoms [odds ratio (OR) 2.04, 95% confidence interval (CI) 1.10-3.81], particularly more severe psychotic symptoms (OR 5.66, 95% CI 1.64-19.49). The association between hearing impairment and CIDI psychotic symptoms was much stronger in the youngest group aged 14-17 years at baseline (OR 3.28, 95% CI 1.54-7.01) than in the older group aged 18-24 years at baseline (OR 0.82, 95% CI 0.24-2.84).
The finding of an age-specific association between hearing impairment and psychotic experiences suggests that disruption of development at a critical adolescent phase, in interaction with other personal and social vulnerabilities, may increase the risk for psychotic symptoms.
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ABSTRACT: According to the social defeat (SD) hypothesis, published in 2005, long-term exposure to the experience of SD may lead to sensitization of the mesolimbic dopamine (DA) system and thereby increase the risk for schizophrenia. The hypothesis posits that SD (ie, the negative experience of being excluded from the majority group) is the common denominator of 5 major schizophrenia risk factors: urban upbringing, migration, childhood trauma, low intelligence, and drug abuse. The purpose of this update of the literature since 2005 is to answer 2 questions: (1) What is the evidence that SD explains the association between schizophrenia and these risk factors? (2) What is the evidence that SD leads to sensitization of the mesolimbic DA system? The evidence for SD as the mechanism underlying the increased risk was found to be strongest for migration and childhood trauma, while the evidence for urban upbringing, low intelligence, and drug abuse is suggestive, but insufficient. Some other findings that may support the hypothesis are the association between risk for schizophrenia and African American ethnicity, unemployment, single status, hearing impairment, autism, illiteracy, short stature, Klinefelter syndrome, and, possibly, sexual minority status. While the evidence that SD in humans leads to sensitization of the mesolimbic DA system is not sufficient, due to lack of studies, the evidence for this in animals is strong. The authors argue that the SD hypothesis provides a parsimonious and plausible explanation for a number of epidemiological findings that cannot be explained solely by genetic confounding.Schizophrenia Bulletin 09/2013; · 8.61 Impact Factor
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ABSTRACT: The aim of this review is to describe the potential relationship between multisensory disintegration and self-disorders in schizophrenia spectrum disorders. Sensory processing impairments affecting multisensory integration have been demonstrated in schizophrenia. From a developmental perspective multisensory integration is considered to be crucial for normal self-experience. An impairment of multisensory integration is called 'perceptual incoherence'. We theorize that perceptual incoherence may evoke incoherent self-experiences including depersonalization, ambivalence, diminished sense of agency, and 'loosening of associations' between thoughts, feelings and actions that lie within the framework of 'self-disorders' as described by Sass and Parnas (2003). We postulate that subconscious attempts to restore perceptual coherence may induce hallucinations and delusions. Increased insight into mechanisms underlying 'self-disorders' may enhance our understanding of schizophrenia, improve recognition of early psychosis, and extend the range of therapeutic possibilities.Schizophrenia Research 08/2013; · 4.43 Impact Factor
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ABSTRACT: Hearing impairment is associated with psychotic symptoms, but has not been systematically studied in people with psychotic disorder. We used a population-based sample of 6654 persons aged 30 + to compare hearing, as measured by audiometry, in persons with schizophrenia, other non-affective psychosis and affective psychosis in the general population. The prevalence of hearing impairment did not differ in persons with psychotic disorder compared with the general population. Participants with schizophrenia and affective psychotic disorder had significantly more difficulties to hear in a noisy environment than the general population. Our results suggest that psychotic disorders are associated with minor hearing difficulties but not hearing impairment.Schizophrenia Research 09/2014; · 4.43 Impact Factor
Adolescent development of psychosis as an outcome
of hearing impairment: a 10-year longitudinal study
M. van der Werf1*, V. Thewissen1,2, M. D. Dominguez1, R. Lieb3,4, H. Wittchen3,5and J. van Os1,6
1Department of Psychiatry and Neuropsychology, South Limburg Mental Health Research and Teaching Network, EURON Graduate School of
Neuroscience, Maastricht University Medical Centre, Maastricht, The Netherlands
2Open University of the Netherlands, Faculty of Psychology, Heerlen, The Netherlands
3Max Planck Institute of Psychiatry, Clinical Psychology and Epidemiology Unit, Munich, Germany
4Epidemiology and Health Psychology, Institute of Psychology, University of Basel, Basel, Switzerland
5Institute of Clinical Psychology and Psychotherapy, Technical University Dresden, Dresden, Germany
6King’s College London, King’s Health Partners, Department of Psychosis Studies, Institute of Psychiatry, London, UK
Background. It has long been acknowledged that hearing impairment may increase the risk for psychotic experi-
ences. Recent work suggests that young people in particular may be at risk, indicating a possible developmental
Method. The hypothesis that individuals exposed to hearing impairment in early adolescence would display the
highest risk for psychotic symptoms was examined in a prospective cohort study of a population sample of originally
3021 adolescents and young adults aged 14–24 years at baseline, in Munich, Germany (Early Developmental Stages of
Psychopathology Study). The expression of psychosis was assessed at multiple time points over a period of up to
10 years, using a diagnostic interview (Munich Composite International Diagnostic Interview; CIDI) administered by
Results. Hearing impairment was associated with CIDI psychotic symptoms [odds ratio (OR) 2.04, 95% confidence
interval (CI) 1.10–3.81], particularly more severe psychotic symptoms (OR 5.66, 95% CI 1.64–19.49). The association
between hearing impairment and CIDI psychotic symptoms was much stronger in the youngest group aged
14–17 years at baseline (OR 3.28, 95% CI 1.54–7.01) than in the older group aged 18–24 years at baseline (OR 0.82,
95% CI 0.24–2.84).
Conclusions. The finding of an age-specific association between hearing impairment and psychotic experiences
suggests that disruption of development at a critical adolescent phase, in interaction with other personal and social
vulnerabilities, may increase the risk for psychotic symptoms.
Received 2 October 2009; Revised 10 March 2010; Accepted 6 April 2010
Key words: Adolescents, development, hearing impairment, psychosis, social cognition.
Recent meta-analyses of general population surveys
suggest that psychometric liability for psychosis in
the form of subclinical psychotic experiences, such as
paranoid delusional thinking and fleeting auditory
hallucinations, is present in 5–10% of healthy people
(van Os et al. 2009; Linscott & van Os, 2010). There is
consistent evidence that the highest rates are observed
in adolecents and young adults (Verdoux et al. 1998;
Peters et al. 1999; Rossler et al. 2007; Lataster et al.
2009). Follow-up studies indicate that the majority
of low-grade psychotic phenomena are benign and
transitory (Hanssen et al. 2005; Cougnard et al.
2007). However, there is evidence from two birth co-
horts (Poulton et al. 2000; Welham et al. 2009), three
representative general population cohorts (Hanssen
et al. 2005; Dominguez et al. 2009; Weiser et al. 2009)
and other longitudinal work (Chapman et al. 1994)
that low-grade psychotic experiences such as delu-
sional thinking and mild hallucinatory experiences
may precede the diagnosis of psychotic disorder
and hospital admission for schizophrenia by many
years. It has been suggested that environmental risk
factors operating in early adolescence may interact
with background genetic risk (van Os et al. 2008)
in producing low-grade delusional ideation and
* Address for correspondence: M. van der Werf, Department of
Psychiatry and Neuropsychology, Maastricht University Medical
Centre, PO Box 616 (VIJV), 6200 MD Maastricht, The Netherlands.
Psychological Medicine, Page 1 of 9.
f Cambridge University Press 2010
hallucinatory experiences that in some cases, if per-
sistent, may progress to full-blown clinical psychotic
states (Dominguez et al. 2009; Kaymaz & van Os,
There is evidence suggesting that hearing impair-
ment (HI) increases the risk for psychosis (Stefanis
et al. 2006; van der Werf et al. 2007), particularly in
young people (David et al. 1995; Thewissen et al. 2005).
Although the mechanism by which HI may increase
risk for psychosis in young people remains elusive,
a number of hypotheses have been put forward.
First, HI and psychosis may be the consequence of a
common underlying cause. For example, exposure to
perinatal infections affecting the central nervous sys-
tem, such as rubella and meningitis (Brown et al. 2000;
Leask et al. 2002; Dalman et al. 2008), may explain
the association between early HI and later psychosis.
Second, psychotic experiences may be a direct or in-
direct consequence of processes triggered by hearing
loss. For example, experimental studies have demon-
strated psychotomimetic effects induced by sensory
deprivation (Leff, 1968; Mason & Brady, 2009). In
addition, it has been proposed that hearing loss may
indirectly increase psychosis risk through social defeat
stress (Selten & Cantor-Graae, 2007). Finally, HI orig-
inating early in life may have an impact on risk for
psychosis by interfering with critical developmental
phases for language, cognition and social skills (Bess
et al. 1998).
The current investigation focused on the expression
of psychosis in adolescents with HI. It was hypo-
thesized that adolescent HI, particularly in the phase
of early adolescence, would be associated with an
increased risk for psychotic symptoms. We relied
on assessments of psychotic experiences by trained
and experienced clinical psychologists in order to
reduce the risk of false positive ratings. In addition,
the longitudinal design allowed for the examin-
ation of possible alterations in exposure assessment
induced by high levels of psychosis proneness at
Sample and study design
The Early Developmental Stages of Psychopathology
(EDSP) Study is a prospective longitudinal cohort
community study which collected data on the preva-
lence, incidence, risk factors and course of mental
disorders. Following ethics committee approval, the
sample was randomly drawn from the 1994 govern-
ment population registers. The sample consisted of
adolescent and young adults living in the Munich
area (Germany), aged 14 to 24 years at baseline.
Participants completed a baseline investigation (T0)
and three follow-up investigations (T1, T2 and T3). At
baseline, 3021 interviews were completed (response
rate: 71%). Because the study primarily intended to
examine the incidence and developmental risk factors
for psychopathology, the younger group (14–15 years)
was sampled at twice the rate of persons aged
16–21 years, and the oldest group (22–24 years) was
sampled at half this rate. Furthermore, participants
aged 14–17 years were assessed three times (T1, T2,
T3) and participants aged 18–24 years were assessed
only two times (T2, T3) after baseline. The follow-up
periods had mean durations of approximately 1.6 years
8.6 years (T0–T3, range 7.4–10.6 years, S.D.=0.7). The
risk set consisted of the 3021 individuals at baseline
and their T1 (n=1228, response rate=88%), T2 (n=
2548, response rate=84%) and T3 (n=2210, response
rate=73%) follow-up measurements. Fig. 1 shows an
overview of the study design and lists the measure-
ments conducted at the different time points. Written
informed consent was obtained from all participants.
More detailed information about the EDSP Study can
S.D.=0.2), 3.4 years (T0–T2,
Time between measurements
Full sample: n = 3021
Subsamplea: n = 1228
Subsamplea: n = 1053
Participants aged 14–18 at T0
Full sample: n = 2548
M-CIDI lifetime version
Full sample: n = 2210
M-CIDI interval version
Fig. 1. Design of the Early Developmental Stages of Psychopathology Study. The time-line shows the assessments at each
time point.aThe subsample of participants aged 14–17 years at baseline. For 1053 of these, parental interviews were
completed. Parental reports of childhood hearing impairment (HI) were available for 723 participants. T0, Time 0
(baseline investigation); T1, time 1 (follow-up investigation 1); T2, time 2 (follow-up investigation 2); T3, time 3
(follow-up investigation 3); SCL, self-report Symptom Checklist; M-CIDI, Munich Composite International Diagnostic
2M. van der Werf et al.
be found elsewhere (Wittchen et al. 1998b; Lieb et al.
Assessment of psychotic experiences
computer-assisted version of the Munich Composite
International Diagnostic Interview (DIA-X/M-CIDI)
(Wittchen & Pfister, 1997), an updated version of the
World Health Organization’s CIDI version 1.2 (WHO,
1990). The DIA-X/M-CIDI is a comprehensive, fully
standardized computer-assisted diagnostic interview
for the assessment of symptoms, syndromes and di-
agnoses of various mental disorders in accordance
with the Diagnostic and Statistical Manual of Mental
Disorders, 4th edition (DSM-IV) criteria, along with
information about psychosocial impairment as well
as the onset, duration and severity of symptoms.
The DIA-X/M-CIDI was developed specifically for
use in adolescents and young adults. High validity
(Reed et al. 1998) and high inter-rater and test–retest
reliability of the CIDI have previously been shown
(Wittchen, 1994; Wittchen et al. 1998a). Fully trained
and experienced clinical psychologists, who were
allowed to probe with clinical follow-up questions,
conducted the interviews to ensure validity and re-
liability of assessments. The lifetime version of the
DIA-X/M-CIDI was used at baseline and the interval
version was applied at each of the follow-ups, cover-
ing the respective time periods between interviews.
The presence of psychotic experiences was assessed
using the 20 core psychosis items of the DIA-X/M-
CIDI-G section (G1, G2a, G3–G5, G7–G13, G13b,
G14, G17, G18, G20, G20c, G21 and G22a) including
symptoms of delusions, hallucinations and passivity
phenomena. Participants first read a list of all the
psychotic experiences and were then asked whether
they ever experienced these symptoms (list and
phrasing available upon request). All items could be
rated as absent or present, without intermediate levels.
Data on the DIA-X/M-CIDI-psychosis section were
collected at T2 (lifetime version) and T3 (interval
version) only. The mean interval between T2 and T3
measurements was 4.9 years. Two different outcome
measures were created: (i) a dichotomous variable in-
dicating the presence or absence of at least one posi-
tive rating on the 20 core psychotic items (hereafter:
CIDI-psychosis) and (ii) in order to examine dose–
response in the association between HI and psychotic
experiences at increasing levels of psychosis severity,
four progressively stricter psychosis subcategories
were constructed (hereafter: CIDI-psychosis severity)
with: no symptoms (0), one or two symptoms
(1), three or four symptoms (2) and at least five
In addition, participants completed the self-report
Derogatis, 1983). The SCL-90-R is a multidimensional
self-report symptom inventory that assesses psycho-
pathology as a continuous dimension of human ex-
periences and enables screening of nine dimensions
of psychopathology (Derogatis, 1983; Arrindell &
Ettema, 2003). Reliability and validity have been es-
tablished previously (Bonicatto et al. 1997). Baseline
psychosis proneness was assessed using the paranoid
ideation (six items) and psychoticism (10 items) sub-
scales. These subscales include self-reports on psy-
chotic experiences that can be regarded, if not as
clear-cut psychotic symptoms, as an expression of
psychosis proneness. In accordance with previous
analyses in this sample (Henquet et al. 2005), the
total scores of both subscales were combined into a
single dimension reflecting psychotic experiences. In
line with previous work (Henquet et al. 2005), and as
validated recently (Dominguez et al. 2009), baseline
psychosis proneness was defined dichotomously as
the group of participants with the highest 10% of
scores (hereafter: SCL-psychosis).
at T0 (SCL-90-R;
T0–T3 assessment of HI
The presence of HI was based on self-report and as-
sessed at T0 (lifetime assessment) and over the T0–T1,
T1–T2 and T2–T3 intervals (interval assessments).
The assessment was included in a questionnaire en-
quiring about a range of somatic complaints, including
sensory deficits. At T0, participants were asked the
following question: ‘Did you ever experience a period
in which you were unable to hear anything at all?’,
yielding a binary exposure variable. At the T1, T2 and
T3 follow-ups, HI was assessed using the same ques-
tion, restricted to the interval since the last interview.
Since complete deafness was an exclusion criterion for
EDSP study participation at baseline, the impairment
assessed referred to a period of transient or permanent
severe HI. The most common causes of severe hearing
loss that may temporarily or permanently affect young
people include syndromal or non-syndromal genetic
disorders, prenatal and perinatal infections and noise
exposure (for reviews, see Olusanya & Newton, 2007;
Tharpe & Sladen, 2008).
reported HI has adequate sensitivity and specificity
(Sindhusake et al. 2001), an additional parental indi-
cator of childhood HI was used to validate the
exposure of HI in the current study. A parental
previous worksuggests that self-
Hearing impairment and psychosis3
investigation was conducted at T1 in the subsample
of participants aged 14–17 years at baseline (n=
1053). Using a standardized checklist (Wittchen et al.
1999), information was gathered about family and
early childhood variables, including sensory deficits.
Parental reports of childhood HI, rated dichot-
omously, were available for 723 participants.
All analyses were conducted in Stata, version 10
(StataCorp., USA). Prevalence estimates of HI and
cumulative lifetime incidence of CIDI-psychosis were
calculated. As data were acquired at multiple points in
time, associations between exposure and outcome
were analysed with data in the long format, i.e. each
individual in the study contributed multiple obser-
vations (the variable ‘time’ expressing the number of
measurements for each person, with a maximum of
four measurements at T0, T1, T2 and T3). Clustering
of observations within subjects was controlled for by
adjusting for the variable ‘time’ in the model. Based
on previous work, all analyses were adjusted for sex,
age at baseline and education (low, medium, high). As
young people may acquire hearing loss at a young age
by attending pop concerts, during which exposure to
illicit drugs may also occur, analyses were addition-
ally adjusted for use of any illicit drugs at baseline
(including cannabis, amphetamine, cocaine and other
stimulants) at least five times lifetime (‘0’ no, ‘1’ yes).
Association between HI and psychotic experiences at
T2 and T3
The association between HI and CIDI-psychosis at T2
and T3 was examined by logistic regression analysis,
with associations expressed as odds ratios (ORs) and
their corresponding 95% confidence intervals (CIs). In
order to exclude the possibility that any association
between HI and psychotic symptoms would be
confounded by high levels of baseline psychosis
proneness (given that this measure may possibly be
associated with over-reporting of HI and, independent
of that, with psychotic symptoms at follow-up),
analyses of association between HI and T2–T3 CIDI-
psychosis were repeated with additional adjustment
for T0 SCL-psychosis. In addition, analyses were also
repeated on a subsample from which participants with
the 50% highest baseline SCL-psychosis scores were
excluded. Finally, as previous research has shown
that the effect of certain predictors of psychosis [e.g.
cannabis (Henquet et al. 2005) and childhood trauma
(Spauwen et al. 2006)] is stronger in individuals
already showing some degree of psychosis proneness
at baseline, we examined whether the association
between HI and T2–T3 CIDI-psychosis was stronger in
those with higher levels of baseline psychosis prone-
ness. To this end, a HIrbaseline SCL-psychosis inter-
action term was included in the model.
Associations at different levels of psychosis severity
The magnitude of the association between HI and
different levels of psychosis severity was examined
using multinomial logistic regression with the Stata
MLOGIT routine, with the lowest psychosis-severity
subcategory serving as the reference group.
The hypothesized age-dependent association between
HI and psychosis was tested by splitting the baseline
sample around the median age, creating a young
(14–17 years) and an old (18–24 years) age group. An
agerHI interaction term was fitted followed by cal-
culation of age-stratified effects from the model in-
cluding the interaction by applying the appropriate
linear combinations using the Stata LINCOM routine.
In order to validate the self-report measure of HI used
in the current study, the association between child-
hood HI (based on parental report; see Fig. 1), and T0
HI (which should include any childhood experience
of HI) was assessed by logistic regression analysis. In
addition, the association between childhood HI and
baseline SCL-psychosis was examined using logistic
regression analysis. Finally, the association between
HI and CIDI-psychosis was examined after excluding
all individuals with HI whose parents had not re-
ported a similar impairment during childhood.
Mean age at baseline was 18.3 years (S.D.=3.3) and
49.3% were male. The cumulative lifetime incidence of
CIDI-psychosis at T3 was 17.9% (n=848). The preva-
lence of HI over time was: T0=92 (3.1%), T1=8
(0.7%), T2=18 (0.8%) and T3=33 (1.6%), yielding a
total of 151 (1.8%) observations of HI. Of the subjects,
seven reported HI at two time points and one at three
time points. Neither CIDI-psychosis (OR 0.99, 95%
CI 0.97–1.01) nor HI (OR 1.04, 95% CI 0.99–1.09) were
associated with age.
Association between HI and psychotic experiences
There were 47 participants who reported HI at either
T2 or T3, and two participants who reported HI at both
T2 and T3, yielding a total of 51 observations of HI in
4 M. van der Werf et al.
the combined T2–T3 assessments. The association be-
tween HI and CIDI-psychosis was significant (OR 2.16,
95% CI 1.17–4.01). Adjustment for age, sex, education
and drug abuse (OR 2.04, 95% CI 1.10–3.81) and
baseline SCL-psychosis (OR 1.99, 95% CI 1.06–3.73)
did not attenuate the association.
The magnitude of the association with HI increased
with increasing levels of CIDI-psychosis severity
(Table 1). A negative interaction between HI and
age was apparent in the model of CIDI-psychosis
(x2=5.86, p=0.016). Stratified analyses indicated that
the association was strong in young (age 14–17 years:
OR 3.28, 95% CI 1.54–7.01), but not in older partici-
pants (age 18–24 years: OR 0.82, 95% CI 0.24–2.84).
There was no evidence for moderation by baseline
SCL-psychosis (x2=0.00, p=0.99). Finally, the associ-
ation remained large and significant after exclusion
of participants with the 50% highest SCL-psychosis
scores at baseline (OR 4.15, 95% CI 1.25–13.82).
In the subsample with parental reports of childhood
HI (n=723), 36 participants were rated positive for
childhood HI (5.0%). Childhood HI was strongly
associated with the T0 self-report of HI (OR 13.08,
95% CI 4.79–35.67). In addition, childhood HI was
strongly associated with the continuous baseline SCL-
psychosis score (adjusted b=2.15, 95% CI 0.26–4.03).
Finally, the adjusted OR for the association between
HI and CIDI-psychosis, excluding individuals with a
self-report of HI that was not matched by parental re-
port of childhood HI, was 5.61 (95% CI 0.34–91.4).
The finding of an association between HI and
psychotic symptoms replicates earlier work (Stefanis
et al. 2006; van der Werf et al. 2007). There was
evidence for a dose–response relationship, as the
association grew stronger with increasing levels of
symptom severity. In a subsample with parental
reports of childhood sensory deficits, childhood
HI similarly predicted later psychotic experiences.
Finally, the association was restricted to young ado-
lescents, which is congruent with recent accounts of
an age-dependent association between HI and psy-
chosis (Stefanis et al. 2006; van der Werf et al. 2007).
The age-dependent effect of HI suggests that disrup-
tion of development during a critical phase, in inter-
action with other social and personal vulnerabilities,
may render an individual more susceptible to psy-
chotic interpretations of internal and external stimuli
(Kapur et al. 2005).
HI and psychosis: a shared cause?
Numerous conditions in young people may affect
hearing acuity, resulting in transient or permanent
impairment (for reviews, see Olusanya & Newton,
2007; Tharpe & Sladen, 2008). Causes of HI in young
people that may also have an impact on the risk for
psychotic experiences include birth trauma (Herrgard
et al. 1995) and prenatal and postnatal exposure to
infections (Dalman et al. 2008; Zammit et al. 2009).
Rubella and meningitis may harm the developing
central nervous system, and exposure has been as-
sociated with an increased risk for both hearing
deficits (Fortnum & Davis, 1993) and psychosis
(Brown et al. 2000; Leask et al. 2002; Dalman et al.
2008). Thus, HI and psychosis may be the result of a
single underlying causative mechanism. This hypo-
thesis is strengthened by a study reporting that rubella
increased the risk for non-affective psychotic disorder
independent of HI (Brown et al. 2000).
Table 1. Associations between cumulative lifetime incidence of hearing impairment (time points T0 to T3) and psychotic symptoms
(CIDI-psychosis) at different levels of severity
RR (95% CI)
RR (95% CI)
Severity levelNo symptomsc
5 or more symptoms
T0, Time 0 (baseline investigation); T3, time 3 (follow-up investigation 3); CIDI, Composite International Diagnostic
Interview; RR, relative risk; CI, confidence interval.
an Refers to multiple observations clustered in individuals.
bAdjusted for sex, education, drug abuse and time.
Hearing impairment and psychosis5
HI and psychosis: causality?
Not hearing what other people say may, directly or
indirectly, trigger paranoid ideation and hallucinatory
experiences. There is experimental evidence that sen-
sory deprivation, mimicking profound hearing loss,
induces feelings of paranoia and hallucinations (Leff,
1968; Mason & Brady, 2009). Sensory restriction may
not only produce patterns of nerve impulses that give
rise to hallucinatory experiences (Schultz & Melzack,
1991), it may also result in reality-testing failures when
the input from the outside world is significantly re-
duced. Failures of reality testing may cause a person to
misattribute internal events to an external source. This
mechanism may underlie the experience of halluci-
nations (Leff, 1968; Bentall, 1990). Second, social ad-
versity has been shown to mould the risk for psychosis
(Boydell et al. 2004; Veling et al. 2007). HI, whether
originating early in life, or acquired later in life, is
associated with social isolation, low self-esteem and
increased feelings of loneliness and stress (Romans-
Clarkson et al. 1990; Bess et al. 1998; Paykel et al. 2000;
Kramer et al. 2002). The adverse emotional and social
consequences of HI may give rise to social defeat stress
(Selten & Cantor-Graae, 2007). Prolonged exposure to
social defeat stress may represent an intermediate
mechanism linking multiple environmental exposures
to an underlying biological mechanism of psychosis
(Selten & Cantor-Graae, 2007; van Winkel et al. 2008).
Thus, social defeat stress may mediate the link be-
tween HI and psychosis.
HI and psychosis: developmental impact?
Finally, HI with onset early in life may compromise
the development of language, cognition and social
skills (Bess et al. 1998), giving rise to developmental
alterations as observed in children destined to develop
psychotic symptoms later in life (Cannon et al. 2002).
Language and cognitive problems associated with HI
may thus contribute to an increased risk in young
people with a pre-existing vulnerability for psychosis.
In addition, persecutory delusions and auditory hal-
lucinations may develop as a result of delays in the
acquisition of Theory of Mind (Frith, 1992; Janssen
et al. 2003) in children with HI. Theory of Mind abili-
ties normally emerge during preschool years (Peterson
et al. 2005) and are highly dependent on day-to-day
social interactions (Russell et al. 1998). Selective
deprivation of access to these early conversations by
HI during critical developmental phases may interfere
with Theory of Mind acquisition. Evidence to support
this notion comes from studies showing significant
delays in the mastery of Theory of Mind in hard-
of-hearing children (Marschark, 1993; Peterson &
Siegal, 1995, 1998). Thus, HI originating early in life
may have an impact, during critical developmental
phases, on language, cognition and social skills, in-
creasing the risk for psychosis.
HI and psychosis: towards a multifactorial model
The association between HI and psychosis shows
variation with age. Although the evidence to date
suggests an increased risk in young people (David
et al. 1995; Stefanis et al. 2006), the association has also
been found in older people (Cooper & Curry, 1976;
Stein & Thienhaus, 1993). This latter implies the oper-
ation of multiple mechanisms contributing to the in-
crease in psychosis risk, with differential impact across
the age span. HI with onset during critical develop-
mental phases may have an impact on risk by delaying
the development of social reasoning skills, language
and cognition, whilst other mechanisms may be
operating in people who acquire HI later in life.
Considering the negative impact of HI on perceived
quality of life, as expressed by increased feelings of
loneliness and a tendency for social isolation, social
defeat stress may represent a more general mechanism
mediating the link between HI and psychosis, re-
gardless of age. Therefore, to the degree that HI
moulds risk for psychosis, it is likely to do so in com-
bination with a range of other factors.
Several limitations should be considered when inter-
preting these results. First, the study used a measure
of HI that was based on self-report and consisted of a
single question. Although this may not seem a very
reliable measure, self-reports of HI have been found to
yield reasonable sensitivity and specificity (Sindhusake
et al. 2001). Also, EDSP interviewers were allowed to
follow-through with follow-up questions to clarify if
participants had understood the question. Finally,
parental reports of childhood HI were strongly as-
sociated with T0 HI, suggesting validity in the sense
that adolescent HI was continuous with earlier per-
manent or recurrent HI. In addition, the validity of the
findings was supported by the fact that if exposure
status was restricted to those participants with HI
who also had evidence of childhood HI according
to parental report, the OR was also very high, albeit
statistically inconclusive due to the small number of
participants. Furthermore, to the degree that mis-
classification may have arisen, it is difficult to see how
this could have been differential with regard to the
Second, the assessment of psychotic experiences
confers the risk of false-positive answers, increasing
6M. van der Werf et al.
random error. However, not only was the DIA-X/M-
CIDI specifically developed for use in young and
adolescent populations, there is also a substantial
literature on the validity of self-reported psychotic
experiences (van Os et al. 2009). In addition, the
assessment of psychotic experiences in the current
study was based on both self-report and diagnostic
interview by trained and experienced clinical psy-
chologists, lowering the risk for false-positive ratings.
Finally, although observational studies cannot
provide evidence for causality in the association
between HI and psychotic symptoms, no evidence
to date exists to support reverse causality (psychosis
provoking spurious reports of having impaired
highly significant after exclusion of those people at
baseline with high psychosis scores, rendering reverse
causality as an explanation for the findings less likely.
This work is part of the Early Developmental Stages
of Psychopathology (EDSP) Study. The EDSP Study
is funded by the German Federal Ministry of Edu-
cation and Research (BMBF; project no. 01EB9405/6,
no. 01EB 9901/6, no. EB01016200, no. 01EB0140
and no. 01EB0440). Part of the field work and ana-
lyses were also additionally supported by grants of
the Deutsche Forschungsgemeinschaft (DFG; project
no. LA1148/1-1, no. WI2246/1-1, no. WI 709/7-1 and
no. WI 709/8-1).
The principal investigators of the EDSP Study were
H.W. and R.L. The core staff members of the EDSP
group were: Dr Katja Beesdo, Dr Petra Zimmermann,
Dr Axel Perkonigg, Dr Michael Ho ¨fler, Dr Tanja
Bru ¨ckl, Agnes Nocon, Hildegard Pfister, Barbara
Spiegel and Dr Andrea Schreier. Scientific advisors are
Dr Jules Angst (Zurich), Dr Kathleen Merikangas
(National Institute of Mental Health, Bethesda),
(Maastricht). The EDSP project and its family genetic
supplement have been approved by the Ethics
Committee of the Faculty of the Technische Uni-
versita ¨t Dresden (no. EK-13811). All participants
provided informed consent.
Declaration of Interest
R.L. has received speaker honoraria from Wyeth.
H.W. has received research support from Novartis,
Pfizer and Schering-Plough, has been a consultant
for Novartis, Pfizer, Wyeth, Organon and Lundbek,
and has received speaker honoraria from Novartis,
Schering-Plough, Pfizer, Wyeth and Servier. J.v.O.
is/has been an unrestricted research grant holder
with, or has received financial compensation as
an independent symposium speaker from, Eli Lilly,
AstraZeneca, Pfizer and Servier – companies that have
an interest in the treatment of psychosis.
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