Psychiatric
Manifestations in
Behavioral and psychiatric abnormalities in Wil-
son’s disease (WD) have a variable frequency and
spectrum. This study involved evaluation of the
psychiatric comorbidities in patients of Wilson’s
disease, using structured clinical interview for
DSM-IV Axis-I disorders (SCID). Among the 50
confirmed patients with Wilson’s disease recruited
for this study, 12 patients (24%) fulfilled the di-
agnostic criteria for syndromic psychiatric diagno-
sis: bipolar affective disorder (18%), major depres-
sion (4%), and dysthymia (2%). Formal
assessment of psychopathology in all patients with
Wilson’s disease may have therapeutic signifi-
cance.
(The Journal of Neuropsychiatry and Clinical
Neurosciences 2008; 20:81–85)
J Neuropsychiatry Clin Neurosci 20:1, Winter 2008
Wilson’s Disease: A
Cross-Sectional Analysis
A. Shanmugiah, M.D.
S. Sinha, D.M.
A.B. Taly, D.M.
L.K. Prashanth, M.B.B.S.
M. Tomar, M.D.
G.R. Arunodaya, D.M.
Janardhana Y.C. Reddy, M.D.
S. Khanna, M.D.
I n his initial monograph, Wilson described the behav-
ioral aspects in eight out of the 12 patients with Wil-
son’s disease (WD), which he called “Psychical.”1 As
many as one third of these patients present with psy-
chiatric and behavioral abnormalities and there are re-
ports that all patients with Wilson’s disease have psy-
chiatric symptoms.2 Scheinberg and Sternlieb stated that
every patient with Wilson’s disease suffers from one or
more of the following problems at some point during
the course of illness: organic dementia, psychosis, psy-
choneurosis, and behavioral disturbances characterized
by impulsivity occasionally extending to unlawful be-
havior.3 There are no such studies from India, except for
a solitary case report.4
The present study describes the psychiatric comorbid-
ities in patients with Wilson’s disease, using Structured
Clinical Interview for DSM-IV Axis-I Disorders-Patient
Edition (SCID).
Subject and Methods
Fifty patients were recruited from a specialty clinic for
Wilson’s disease at the Department of Neurology at the
Received September 7, 2006; revised December 1, 2006; accepted
March 5, 2007. The authors are affiliated with the Department of Neu-
rology and Psychiatry at the National Institute of Mental Health and
Neurosciences (NIMHANS) in Bangalore, India. Address correspon-
dence to Dr. A. B. Taly, Professor, Department of Neurology, NIMH
and Neurosciences (NIMHANS), Hosur Road, Bangalore-560 029, Kar-
nataka, India; abtaly@yahoo.com (e-mail).
Copyright 䉷 2008 American Psychiatric Publishing, Inc.
http://neuro.psychiatryonline.org 81
PSYCHIATRIC MANIFESTATIONS IN WILSON’S DISEASE
National Institute for Mental Health and Neurosciences
in Bangalore, India, a tertiary care university hospital of
south India. This was a heterogeneous sample with ref-
erence to gender, age group, educational and socioeco-
nomic background, duration and severity of illness, and
treatment. Their diagnosis had been established after the
initial clinical suspicion by presence of Kayser-Fleischer
ring on slit-lamp examination, low serum copper and
ceruloplasmin levels, and increased 24 hours urinary
copper. Clinical details were recorded in all.
Psychiatric comorbidity was assessed using the Struc-
tured Clinical Interview for DSM-IV Axis I Disorders
(SCID). SCID was administered to each patient by two
psychiatrists independently, trained for SCID interview
(SA, TM). The SCID is a semistructured diagnostic in-
terview, which begins with a section on demographic
information and clinical background. There are seven
diagnostic modules focusing on different groups: mood,
psychosis, substance abuse, anxiety, somatoform, eating
and adjustment disorders. It is unique as it secures re-
liable information in different cultural settings. This
study explored the psychiatric comorbidity in Wilson’s
disease by administering structured clinical interviews
in a systematic way.
RESULTS
There were 29 males and 21 females. The mean age at
onset of symptoms was 14.2 Ⳳ 6.4 years (range: 5 to 37
years), and the mean age at diagnosis was 16.3 Ⳳ 7.0
years (range: 6 to 40 years). At the time of evaluation for
psychopathology, the mean duration of illness was 10.4
Ⳳ 8.7 years (range: 1 to 50 years). The mean duration of
de-coppering treatment with penicillamine (250 to 1000
mg/day) and zinc (180 mg/day) was 8.2 Ⳳ 7.3 years
(range: 1 to 40 years). Three patients had positive family
history in an autosomal recessive pattern. History of de-
tailed psychiatric symptoms in the family was not avail-
able.
All patients except two had bilateral Kayser-Fleischer
rings on slit-lamp. The predominant presenting mani-
festations in these cases could be categorized as neuro-
logical (25), psychiatric (6), hepatic (5), hepatic and neu-
rological (4), osseomuscular (3), neurological and
psychiatric (2), and neurological and osseomuscular (2).
Three subjects were asymptomatic siblings of index pa-
tients. The mean level serum copper was 50.0 Ⳳ 46.7
lg/dl (range: 5 to 304 lg/dl), serum ceruloplasmin was
82 http://neuro.psychiatryonline.org
6.8 Ⳳ 6.0 mg/dl (range: 1 to 36 mg/dl), and 24 hours
urinary copper was 425.1 Ⳳ 362.5 lg/dl at the time of
diagnosis.
The key psychiatric symptoms in these patients were
excessive talkativeness, aggressive behavior, loss of in-
terest in the surroundings, and abusiveness. Twelve pa-
tients (24%) fulfilled the diagnostic criteria for syn-
dromic psychiatric diagnosis with majority having
affective disorder. Nine patients had bipolar affective
disorder, two were diagnosed with major depression,
and one had dysthymia (Table 1). The age at onset of
Wilson’s disease in patients with (N⳱12) and without
(N⳱38) behavioral changes was not different (student t
test: p⳱0.5). Psychiatric manifestations dominated the
clinical profile in eight patients at the time of diagnosis,
and all had BPAD at the time of evaluation. The neu-
rological manifestations at the time of diagnosis in-
cluded dystonia (8), speech disturbances (22), tremors
(15), chorea (1), gait disturbances (10), seizures (2), and
drooling (6).
Among these 12 patients, seven had undergone eval-
uation with magnetic resonance imaging (MRI) of the
brain at mean age of 25.4 Ⳳ 5.7 years (range: 20–37
years). MRI in these patients showed varied changes.
Brain atrophy was noted in five patients, varying from
mild to moderate, and included cerebral atrophy (4),
brain stem atrophy (4), and cerebellar atrophy (4). Signal
intensity changes on MRI were noted in all but one pa-
tient and included caudate (3), putamen (5), internal
capsule (1), thalamus (4), midbrain (5), pons (3), cere-
bellum (1), and white matter changes (1) (Table 2) (Fig-
ure 1).
DISCUSSION
Dening and Berrios5 retrospectively assessed 195 pa-
tients with Wilson’s disease and observed that 51% dis-
played psychopathologic features. In another study,
Schwartz et al.6 reported that one third of patients with
Wilson’s disease had psychiatric disturbances in the
early stage of the disease, and in 20% the psychiatric
manifestations preceded all other manifestations. In a
prospective study by Akil and Brewer,2 two thirds of
patients with Wilson’s disease had psychiatric symp-
toms at the time of initial presentation. The present
study revealed that 24% (n⳱12) of patients had psychi-
atric manifestations and 16% (n⳱8) of them presented
with these symptoms.
J Neuropsychiatry Clin Neurosci 20:1, Winter 2008
 SHANMUGIAH et al.

The psychiatric manifestations of Wilson’s disease can
be categorized into five groups of symptoms: person-
ality changes, affective disorders, psychosis, cognitive
impairment, and others.2 Akil and Brewer2 believed that
behavioral and personality changes and affective dis-
orders, including depression, are the most common psy-
chiatric manifestations of Wilson’s disease. Dening and
Berrios5 noted that schizophrenia-like psychosis, often
described in case reports, is infrequent and personality
change, depression, and cognitive impairment are com-
mon. These often co-occurred with neurological symp-
toms, but not with hepatic manifestations. Symptoms
such as inappropriate behavior and irritability are more
often associated with bulbar and dystonic features
rather than tremors.
Twenty-four percent (n⳱12)of patients in this sample
fulfilled criteria for syndromic psychiatric diagnosis,
18% (n⳱9) had bipolar affective disorder, 4% (n⳱2)
were diagnosed with major depression, and 2% (n⳱1)
had dysthymia. Depression was observed in 20%–30%
of patients with Wilson’s disease.2,5 Other affective dis-
orders such as hypomania and mania, though rare, have
also been reported.2
Personality changes in Wilson’s disease include bi-

TABLE 1. Clinical Characteristics of Patients With Syndromic Psychiatric Diagnosis

Lab Values
Serum 24 hours
Patient Initial Age at Age at Family KF Ring Serum Copper Ceruloplasmin Urinary Copper
No. Presentation Onset Diagnosis History (slit-lamp) (lg/dl) (mg/dl) (lg/24 hrs)
57 Asymptomatic 8 8 ⳮ Ⳮ 14 5 141
61 Neurological 11 13 Ⳮ Ⳮ 38 8 158
89 Neurological 24 28 ⳮ Ⳮ 33 6 160
101 Osseomuscular 26 27 ⳮ Ⳮ 71 2 141
125 Neurological 11 14 ⳮ Ⳮ 21 3 624
210 Psychiatric 8 18 ⳮ Ⳮ 41 4 156
267 Neurological & Psychiatric 23 23 ⳮ Ⳮ 61 6 539
286 Psychiatric 23 25 ⳮ Ⳮ 23 5 125
318 Psychiatric 17 19 ⳮ Ⳮ 304 4 794
319 Psychiatric 20 22 ⳮ Ⳮ 57 3 980
320 Psychiatric 20 23 ⳮ Ⳮ 23 5 125
321 Neurological 16 17 Ⳮ Ⳮ 68 8 111

TABLE 2. MRI Observations in Patients with Syndromic Psychiatric Diagnosis

MRI Changes (nⴔ7)
Patient Gap Between Onset and Present Present Response to
No. Evaluation (Years) Diagnosis Atrophy Signal Changes Treatment
57 18 Major Cerebral, No signal changes Good
Depression Brainstem,
Cerebellar
61 17 Major Cerebellar, Thalamus, internal capsule, midbrain, pons Good
Depression Brainstem
89 14 BPAD Not performed Good
101 13 BPAD Cerebral, Caudate, putamen, cerebellum Good
Brainstem,
Cerebellar
125 12 BPAD Not performed Good
210 6 BPAD No atrophy Caudate, putamen, thalamus, midbrain, pons, Poor
white matter
267 6 BPAD Not performed Good
286 4 BPAD Cerebral, Caudate, putamen, thalamus, midbrain, white Good
Brainstem, matter
Cerebellar
318 0.2 BPAD Cerebral Putamen, midbrain Poor
319 0.2 BPAD Not performed Good
320 0.08 BPAD No atrophy Putamen, thalamus, midbrain, pons Poor
321 0.08 Dysthymia Not performed Good

BPAD⳱Bipolar affective disorder

J Neuropsychiatry Clin Neurosci 20:1, Winter 2008 http://neuro.psychiatryonline.org 83

PSYCHIATRIC MANIFESTATIONS IN WILSON’S DISEASE

zarre behavior, impulsivity, occasionally extending to structural and functional imaging are therefore needed
criminal behavior, and disinhibition.5 Akil and Brewer2 to hypothesize the biological basis of the disease.
reported that personality changes occurring as initial The frequency and nature of behavioral and psychi-
manifestations included irritability, emotionality, de- atric abnormalities in Wilson’s disease are variable and
creased threshold for anger, and occasional aggression. attributed to data often being reported by nonpsychiatr-
“Schizophrenia-like” psychosis and other forms of psy- ists, use of ill-defined terminologies and diagnostic cri-
chosis have been reported infrequently.5,7,8 Psychosis teria, lack of prospective evaluation, and assessment af-
can be an initial manifestation and often leads to an ter regression of symptoms. The current study was
inaccurate diagnosis.5,9 Cognitive and intellectual im- designed to explore the psychiatric comorbidity by ad-
pairment,10,11 substance abuse,12 catatonia,13 sexual pre- ministering structured clinical interviews in a system-
occupation,3 and anxiety disorders9 have also been re- atic way.
ported.
Brain MRI in these patients with psychiatric manifes- FIGURE 1. A-D: Brain MRI in Patients with Wilson’s Disease
tations revealed changes typically described in patients and Psychiatric Symptoms
with Wilson’s disease. Both basal ganglionic and brain-
stem signal changes were noticed in addition to diffuse
atrophy. Keller et al.14 reported a 38-year-old patient
with Wilson’s disease presenting with bipolar affective
disorder. The MRI revealed basal ganglia and dorsal
midbrain signal changes. Single photon emission com-
puted tomography study with iodine-123-iodobenza-
mide (IBZM-SPECT) detected a normal distribution of
the drug in the brain, with a better signal in the right
side and a deficit of D2-dopaminergic receptors in the
basal ganglia. The frequency of abnormalities noted in
these patients with behavioral changes was not different
when compared with a cohort of 100 patients with Wil-
son’s disease who underwent MRI.15 Diverse imaging
abnormalities have been described in patients with non-
organic bipolar disorder. These include: periventricular
and deep subcortical white matter hyperintensities;
ventricular enlargement, right more often than the left;
decreased volume of subgenual cingular, frontal, and
temporal cortices; and morphometric abnormalities in
structures such as amygdala, basal ganglia, and thala-
1A: T1W axial image in a girl with bipolar affective disorder
mus. These abnormalities highlight the role of the showing diffuse cortical atrophy
fronto-limbic loops involved in the emotion as the path- 1B: T2W axial sequence revealing classical pallidal hypointensity,
putaminal hyperintensities, and subtle thalamic signal
ogenetic mechanism of bipolar disorder.16 However, the alterations inpatient with bipolar-like symptoms
cause and effect relationship of these observations is un- 1C, 1D: Axial FLAIR sequences showing signal changes in
midbrain—tectal hyperintensity (C), face of giant panda (D)
clear. Systemic prospective studies of these patients with

84 http://neuro.psychiatryonline.org J Neuropsychiatry Clin Neurosci 20:1, Winter 2008


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