WJ P World Journal of

Psychiatry
Submit a Manuscript: http://www.wjgnet.com/esps/ World J Psychiatr 2015 September 22; 5(3): 273-285
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DOI: 10.5498/wjp.v5.i3.273 © 2015 Baishideng Publishing Group Inc. All rights reserved.

REVIEW

Psychiatric aspects of brain tumors: A review

Subramoniam Madhusoodanan, Mark Bryan Ting, Tara Farah, Umran Ugur

Subramoniam Madhusoodanan, Department of Psychiatry, Published online: September 22, 2015

St. John’s Episcopal Hospital, Far Rockaway, NY 11691, United
States

Subramoniam Madhusoodanan, Department of Psychiatry,

SUNY Downstate Medical Center, Brooklyn, NY 11203, United Abstract
States Infrequently, psychiatric symptoms may be the only
manifestation of brain tumors. They may present
Mark Bryan Ting, Community Behavioral Health Center, with mood symptoms, psychosis, memory problems,
Fresno, CA 93720, United States
personality changes, anxiety, or anorexia. Symptoms
Mark Bryan Ting, Bio-Behavioral Medical Clinics, Fresno, CA
may be misleading, complicating the clinical picture. A
93711, United States comprehensive review of the literature was con­ducted
regarding reports of brain tumors and psychiatric symp­
Tara Farah, Medical Student IV, Medical University of Lublin, toms from 1956-2014. Search engines used include
20-059 Lublin, Poland PubMed, Ovid, Psych Info, MEDLINE, and Med­Scape.
Search terms included psychiatric manifes­tations/
Umran Ugur, Medical Student IV, Ross University School of symptoms, brain tumors/neoplasms. Our litera­ture
Medicine, Miramar, FL 33027, United States search yielded case reports, case studies, and case
series. There are no double blind studies except for
Author contributions: All authors contributed to this paper. post-diagnosis/-surgery studies. Early diagnosis is
critical for improved quality of life. Symptoms that
Conflict-of-interest statement: The authors report no financial
or other conflicts of interest in connection with this manuscript. suggest work-up with neuroimaging include: new-onset
psychosis, mood/memory symptoms, occurrence of
Open-Access: This article is an open-access article which was new or atypical symptoms, personality changes, and
selected by an in-house editor and fully peer-reviewed by external anorexia without body dysmorphic symptoms. This
reviewers. It is distributed in accordance with the Creative article reviews the existing literature regarding the
Commons Attribution Non Commercial (CC BY-NC 4.0) license, diagnosis and management of this clinically complex
which permits others to distribute, remix, adapt, build upon this condition.
work non-commercially, and license their derivative works on
different terms, provided the original work is properly cited and Key words: Brain tumors; Psychiatric symptoms; Neuro­
the use is non-commercial. See: http://creativecommons.org/
psy­chiatric; Behavioral symptoms; Diagnosis; Manag­
licenses/by-nc/4.0/
ement; Neuroimaging
Correspondence to: Subramoniam Madhusoodanan, MD,
Associate Chair, Department of Psychiatry, St. John’s Episcopal © The Author(s) 2015. Published by Baishideng Publishing
Hospital, 327 Beach 19 th Street, Far Rockaway, NY 11691, Group Inc. All rights reserved.
United States. sdanan@ehs.org
Telephone: +1-718-8697248 Core tip: Psychiatric symptoms may rarely be the only
Fax: +1-718-8698532 presentation of a brain tumor. Any type of psychiatric
symptoms can occur with brain tumors. Unfortunately, the
Received: May 6, 2015 symptoms generally do not have any localizing value. New
Peer-review started: May 8, 2015 onset psychosis, mood or memory symptoms, occurrence
First decision: July 10, 2015
of new or atypical symptoms, personality changes and
Revised: August 15, 2015
Accepted: September 7, 2015 anorexia without body dysmorphic symptoms, suggest
Article in press: September 8, 2015 a work up including neuroimaging. Early diagnosis is

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 Madhusoodanan S et al . Psychiatric aspects of brain tumors

critical for improved quality of life for the patient. tumor locations and psychiatric symptoms, it is difficult
to predict the symptoms based on the location or vice
versa. This paper will explore the diverse manifestations,
Madhusoodanan S, Ting MB, Farah T, Ugur U. Psychiatric aspects diagnosis, and management of brain tumors that
of brain tumors: A review. World J Psychiatr 2015; 5(3): 273-285 present primarily with psychiatric symptoms.
Available from: URL: http://www.wjgnet.com/2220-3206/full/v5/
i3/273.htm DOI: http://dx.doi.org/10.5498/wjp.v5.i3.273
LITERATURE REVIEW
A comprehensive review of the literature was con­ducted
regarding reports of brain tumors and psychiatric sym­
INTRODUCTION ptoms from 1956-2014. Search engines used include
The majority of large studies discussing brain neoplasms PubMed, Ovid, Psych Info, MEDLINE, and MedScape.
and psychiatric symptoms date back to the 1930’s .
[1] Search terms included psychiatric manifes­tations/
Since psychiatric nomenclature and disease parameters symptoms, brain tumors/neoplasms. Our litera­ture
change constantly, it is difficult to analyze this topic in a search yielded case reports, case studies, and case
consistent manner. series. There are no double blind studies except for
Brain tumors are relatively common with an annual post-diagnosis/-surgery studies.
incidence of 9 per 100000 for primary brain tumors and We found 172 cases with psychiatric symptoms. Psy­
8.3 per 100000 for metastatic brain tumors. Brain tumors chiatric symptoms were assigned to 7 main categories:
may be classified based on their histopathologic charac­ depressive symptoms, apathy, manic symptoms, psy­
teristics or anatomical location. There are two types of chosis, personality changes, eating disorders, and a
tumors: ones that are primary, originating from the brain miscellaneous category for the less frequently encoun­
tissue, and ones that metastasize to numerous locations tered symptoms. Each category will be discussed. Some
throughout the brain. Because of this, metastatic tumors reports may be included in more than one category due
often present with more neuro­psy­chiatric symptoms. to combination of symptoms.
The most common primary brain tumors are gliomas,
which are divided into several types: astrocytomas, Depression (Table 1)
oligodendrogliomas, and ependymomas. The groups of Depression may be seen in different stages (before,
brain tumors that are not from the glial tissue include during or after diagnosis/treatment) of brain tumors.
meningiomas, schwannomas, cranio­pharyngiomas, Depression was reported in 2.5%-15.4% of primary
[5] [6]
germ cell tumors, pituitary adenomas, and pineal brain tumors . According to Mainio et al , depression
region tumors. Majority of all brain tumors are gliomas, was found in 44% of all brain tumor patients, primary
accounting for 40%-55%. Tumors meta­stasizing to the and metastatic, and was associated with functional
brain account for 15%-25% of all brain tumors .
[2] impairment, cognitive dysfunction, reduced quality of life,
[7]
Most brain tumors present with specific neurologic and reduced survival . It was also noted that depression
[8-10]
signs due to mass effect. However, in rare cases they was more commonly found in frontal lobe tumors .
may present primarily with psychiatric symptoms. A More specifically left frontal lobe tumors were more
[11]
[3]
study by Keschner et al reported that 78% of 530 frequently associated with depression and akinesia .
patients with brain tumors had psychiatric symptoms.
However, 18% of the 530 presented only with these Apathy (Table 2)
symptoms as the first clinical manifestation of a brain Apathy must be distinguished from major depressive
tumor. Due to the neuronal connections of the brain, disorder and chronic fatigue syndrome. Patients pre­
a lesion in one region may manifest a multitude of senting with apathy when asked about their mood,
symptoms depending on the function of the underlying state that they are not depressed, but instead have
[12]
neuronal foci. Symptoms of brain lesions depend on the chronic fatigue and lack of motivation . This may be
functions of the networks underlying the affected areas .
[1]
associated with a functional disconnection between the
For instance, a significant association has been found frontal lobe and paralimbic areas, or damage in these
[13,14] [15]
between anorexia symptoms and hypothalamic tumors, areas . Levy et al suggests that apathy is common
a probable association between psychotic symptoms in neurodegenerative disorders and is independent of
and pituitary tumors, memory symptoms and thalamic depression. The diagnostic criteria for apathy sugges­
[4] [16]
tumors, and mood symptoms and frontal tumors . ted by Starkstein et al include lack of motivation,
Management of brain tumors consists of surgical dimi­nished goal-directed behavior (lack of effort, or
resection of the tumor, stereotactic radiosurgery, radio­ dependency on others to structure activity), diminished
therapy, and chemotherapy. Treatment of the psychiatric goal-directed cognition (lack of interest in learning new
symptoms caused by brain tumors depends on the things or in new experiences, or lack of concern about
presenting symptoms and includes antide­pressants, one’s personal problems), or diminished emotions
[1]
antipsychotics, mood stabilizers, and anxiolytics . (unchanging affect, or lack of emotional responsivity to
Although there may be an association between some positive or negative events).

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 Madhusoodanan S et al . Psychiatric aspects of brain tumors

[41]
Table 1 Brain tumors and depressive symptoms

Ref. Psychiatric symptoms Tumor location Tumor type Remarks

Zivković et al[42], Depression, impairment Parietal lobe Epidermoid tumor Subsequent neurological
2014 in memory, motivation, symptoms led to CT scan and
concentration, insomnia, increased diagnosis of the brain tumor
appetite, headaches
Assefa et al[43], Depression, anxiety, insomnia, Parasellar and retrosellar Meningioma Neurologic deficit with psychiatric
2012 headache, nausea, vomiting, areas of the petrous symptoms
unilateral abducens palsy apex, temporal lobe
Ozdilek et al[44], Depression, anxiety, headache Left temporal lobe Glial tumor Persistent headache led to
2011 neurologic consult and CT, and
diagnosis
Cheema et al[45], Depression, anhedonia, low Left frontal and Glioblastoma Duration of psychiatric symptoms
2010 energy, insomnia, suicidal temporal lobe multiforme of 10 yr make the association of
ideations glioblastoma questionable and
possibly unrelated
Bunevicius et al[46], Depression, Parkinsonian Right fronto-temporal Meningioma Subsequent neurological
2008 symptoms symptoms led to CT scan and
diagnosis of the brain tumor
Bunevicius et al[46], Depression, psychosis Left temporal lobe Intra-cerebral cyst Refractory
2008 symptoms
Habermeyer et al[47], Depression, delirium Right frontal lobe Glioblastoma Psychiatric and neurological
2008 multiforme symptoms at initial presentation
Oreskovic et al[48], Depression, attention deficit Suprasellar and pineal Germ cell tumor Good prognosis with
2007 hyperactivity disorder regions chemotherapy and
radiation
Moise et al[49], 2006 Depression, headache, memory Right thalamus Glioblastoma Partial improvement of symptoms
loss multiforme with surgical treatment and
antidepressants
Madhusoodanan et al[50], 2004 Recent depressive symptoms, Left parietal High grade glial Resolution of depressive
anger and agitation neoplasm with sporadic symptoms after surgery, chemo-
cells and radiation therapy
Kohler et al[32], 2001 Depressive symptoms refractory Left lateral Neurocytoma Good response to ECT
to antidepressants, following ventricle, left frontal
surgical resection of left frontal encephalomalacia
neurocytoma
Ghaziuddin et al[31], 1999 Depressed mood, mania, suicidal Brainstem (ponto- Astrocytoma Improvement with ECT
ideation, irritability, guilt, mesencephalic)
grandiosity, early insomnia,
olfactory hallucinations
Kaplan[51], 1997 Progressive depression and Right frontal and Unknown
anxiety parietal
Kugaya et al[52], 1996 Depressed mood, agitation, Ependymal Cyst Partial removal of cyst led to
depersonalization, ideas of complete resolution of symptoms
reference, suicidal ideation
Griffith[53], 1995 Depression Olfactory area Esthesioneuroblastoma
Filley et al[8], 1995 Severe depression, extensive Left frontal Squamous cell
weight loss carcinoma
Chipkevitch et al[54], 1993 Atypical anorexia nervosa, Hypothalamus Teratoma
depression
Fulton et al[55], 1992 Reduced communication, Right frontal lobe Astrocytoma Poor response to steroid treatment
depression, seizures, neurologic
signs
Goodman et al[56], 1992 Late-onset depressive symptoms, Several bi-frontal masses Unknown
left-sided Horner’s syndrome
Ko et al[57], 1989 Depressive symptoms, emotional Multiple metastatic left Origin in right lung No surgical intervention
lability, amnesia for recent events fronto-parietal lesions
Tanaghow et al[58], 1989 Depressed mood, social Anterior corpus Unknown
withdrawal, personal neglect, callosum
apathy
Upadhyaya et al[59], 1988 Depression and delusions Third ventricle Colloid cyst
Greenberg et al[29], 1988 Treatment-resistant depression Left fronto-parietal Meningioma Good response of psychiatric
with delusions symptoms to ECT
Goldstein et al[30], 1988 Depression Right frontal Meningioma Good response to ECT
Summerfield[60], 1987 Depression, psychosomatic Cerebellum Hemangioblastoma
symptoms
Ghadirian et al[61], 1986 Depression and anxiety followed Right temporal lobe Meningioma
by visual hallucinations

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 Madhusoodanan S et al . Psychiatric aspects of brain tumors

Uribe[62], 1986 Depressive symptoms with Left temporo-parietal Glioblastoma

rage episodes, forgetfulness, multiforme
disturbance in short-term memory
and abstract thinking, later-onset
headaches, disorientation, gait
unsteadiness, hemiparesis
Dietch[63], 1984 Agoraphobia with panic attacks Left fronto-parietal Glioblastoma Good response to imipramine,
and major depression; later-onset multiforme resolution of symptoms after
right-sided weakness surgery
Maurice-Williams et al[64], Depression, focal seizures Frontal Meningioma Improvement of symptoms after
1984 tumor was removed
Fisher et al[65], 1983 Depression Limbic system CNS lymphoma
Barbizet et al[66], 1982 Rage attacks, Bulimia, uninhibited Fronto-temporal Astrocytoma
and brutal sexual behavior,
periods of depression with suicide
attempts
Lahmeyer[67], 1982 Depression and urinary Bilateral frontal Meningioma Good response to amphetamines
incontinence
Littman et al[68], 1981 Depression, speech difficulties Left temporal Unknown
Khuan et al[69], 1979 Depression, poor work Right thalamus Unknown
performance
Burkle et al[70], 1978 Depression, hypersomnia, Third ventricle with Colloid cyst
anhedonia, low energy, poor obstruction of lateral
concentration, memory lapses ventricles
Carlson[71], 1977 Severe depression; prior history of Frontal Meningioma Complete resolution of symptoms
seizures after surgery
Carlson[71], 1977 Severe depression Right frontal Grade IV astrocytoma Resolution of symptoms after
surgery
Scherrer et al[72], 1974 Depression followed by euphoria, Frontal Unknown
then seizures
Blustein et al[73], 1972 Depression Right temporal Grade I astrocytoma
Avery[74], 1971 Depression, apathy Right cribriform plate Meningioma Post-op manic episode before
resolution of symptoms
Avery[74], 1971 Depression, apathy Right cribriform plate Meningioma Improvement after surgery

Adapted from Trends in Brain Cancer Research. New York: Nova Science Publishers Inc., 2006. ECT: Emission computed tomography; CT: Computed tomography.

[41]
Table 2 Brain tumors and apathy

Ref. Psychiatric symptoms Tumor location Tumor type Remarks

Aydin et al[75], Loss of self-generated behavior, Midline subfrontal region Meningioma Psychiatric and neurologic
2013 irritability, disinhibition, impulsivity symptoms with consequent
diagnosis of brain tumor
Filley et al[8], Apathy, social-withdrawal, poor self- Bifrontal Benign meningioma
1995 care
Filley et al[8], Apathy, irritability, anomia, right Left frontal lobe and genu of Immunoblastic
1995 hemiparesis corpus callosum lymphoma
Filley et al[8], Apathy, amnesia, poor affect Thalamic and fornical Gonadotropic cell
1995 columns pituitary adenoma
Fulton et al[55], Loss of interest, poor concentration, Left frontal lobe involving Unknown
1992 withdrawal, lack of communication, corpus callosum
neurologic signs
Tanaghow et al[58], Depressed mood, social withdrawal, Anterior corpus callosum Unknown
1989 personal neglect, apathy
Burkle et al[70], 1978 Depression, hypersomnia, anhedonia, Third ventricle with Colloid cyst
low energy, poor concentration, obstruction of lateral
memory lapses ventricles
Avery[74], 1971 Euphoria, drowsiness, and apathy Tuberculum sellae Meningioma Some residual psychiatric
disturbance following resection
Avery[74], 1971 Depression, apathy Right cribriform plate Meningioma Post-op manic episode before
resolution of symptoms
Avery[74], 1971 Depression, apathy Right cribriform plate Meningioma Improvement after surgery
Avery[74], 1971 Apathy, change in work behavior Cribriform plate Meningioma Improvement after surgery

Adapted from Trends in Brain Cancer Research. New York: Nova Science Publishers Inc., 2006.

Manic symptoms (Table 3) can also present with other mood symptoms, such
In addition to depression, patients with brain tumors as mania. There are reports which show that while

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 Madhusoodanan S et al . Psychiatric aspects of brain tumors

[41]
Table 3 Brain tumors and manic symptoms

Ref. Psychiatric symptoms Tumor location Tumor type Remarks

Bhatia et al[76], 2013 Visual hallucinations, grandiosity, Third ventricle Neuroepithelial Psychiatric symptoms and
excessive talking, elated mood cyst diagnosis of brain tumor with
no development of neurologic
symptoms
Yetimalar et al[77], 2007 Personality change, psychomotor Pons Cavernous angioma Neurologic symptoms developed
agitation, enhanced talkativeness and after the brain tumor was
sex drive, decreased need for sleep diagnosed
Ghaziuddin et al[31], Depressed mood, mania, suicidal Brainstem (ponto- Astrocytoma Improvement with ECT
1999 ideation, irritability, guilt, mesencephalic)
grandiosity, early insomnia, olfactory
hallucinations
Mazure et al[78], 1999 Late-onset manic episode with Right temporal lobe Glioblastoma Good and rapid response
psychotic features; no neurologic multiforme of psychiatric symptoms to
signs perphenazine
Filley et al[8], 1995 New-onset manic symptoms Bitemporal Glioblastoma
multiforme
Mark et al[79], 1991 Treatment-resistant bipolar disorder Acoustic nerve Neurinoma Symptoms resolved completely
after tumor resection
Greenberg et al[29], 1988 Manic symptoms Brainstem Metastases, origin
unknown
Jamieson et al[17], 1979 Mania Right occipital, temporal Metastatic tumors-
and parietal lobes unknown primary
source
Scherrer et al[72], 1974 Recurrent manic episodes Frontal Unknown
Avery[74], 1971 Mania, euphoria Olfactory nerve Meningioma Some residual psychiatric
disturbance following resection

Adapted from Trends in Brain Cancer Research. New York: Nova Science Publishers Inc., 2006. ECT: Emission computed tomography; CT: Computed tomography.

[4]
depression was associated with left frontal tumors, a misdiagnosis. A review by Madhusoodanan et al on
mania was found more commonly with right frontal associations between tumor locations and psychiatric
tumors presenting with characteristics such as euphoria symptoms concluded that while anorexic symptoms
and underestimation of the significance of their may be a result of tumors in numerous locations in the
[11]
illness . Right hemisphere lesions have been reported brain, hypothalamic neoplasms most commonly present
[17-19]
to present as manic symptoms . as anorexia symptoms.

Psychosis (Table 4) Miscellaneous symptoms (Table 7)

Another common psychiatric presentation of brain There are some cases of patients with brain tumors
tumors is hallucinations and psychosis. Madhusoodanan who present with a more ambiguous psychiatric history
[4] [20]
et al reported that while mood symptoms are the and progression of illness. Feng et al described
most common, being reported in 36% of the cases, an 86-year-old female who presented with anomic
psychotic symptoms were found in 22% of patients. In aphasia. The patient reportedly had difficulty naming
these cases of psychotic symptoms, the tumors were familiar objects and people for month. Her neurological
found in cerebral cortical, pituitary, pineal and posterior exam was normal and she did not have any symptoms
locations. Among these, pituitary gland was the most aside from the anomic aphasia. A brain computed
common location for psychotic symptoms. However, tomography (CT) and magnetic resonance imaging
in another study, temporal lobe tumors were closely (MRI) showed a large tumor in the left temporal lobe,
[8]
related to psychotic manifestations . compressing the left lateral ventricle and causing a
midline shift. She underwent surgical resection of the
Personality changes (Table 5) tumor and radiotherapy. Pathology reports showed that
Frontal lobe lesions and ventricular cysts may present the tumor was a glioblastoma multiforme. In this case,
with personality changes. This may include disinhibition, surgery and radiotherapy did not result in resolution of
hypersexuality, and aggressive behaviors. the anomic aphasia.
Among other less common and atypical psychiatric
Eating disorders (Table 6) manifestations of brain tumor is a case of pathological
[21]
Weight loss and decreased appetite are associated laughter reported by Tsutsumi et al . A 60-year-old
with different types of malignancies, and in patients female presented with abnormal laughter and left-
with brain tumors it may be among the first warning hemiparesis. Her laughter was induced by non-specific
signs. This may be mistaken for symptoms of anorexia stimuli and lasted for a few minutes. The MRI showed
nervosa, particularly in young females, and can lead to a ring-enhanced lesion in the subcortical area of the

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 Madhusoodanan S et al . Psychiatric aspects of brain tumors

[41]
Table 4 Brain tumors and psychotic symptoms

Ref. Psychiatric symptoms Tumor location Tumor type Remarks

Krayem et al[27], Psychosis, auditory hallucinations, self- Right temporal lobe Astrocytoma Psychosis developed either from
2014 injurious behavior tumor recurrence or right temporal
brain tissue loss post-surgery
Kaloshi et al[80], Visual and auditory hallucinations, spasmodic Cerebellum Glioneuronal Partial improvement of symptoms
2013 laughter, minimal spontaneous speech with surgery
Arasappa et al[81], Lethargy, anhedonia, persecutory delusions, Fourth ventricle Choroid plexus Improvement with surgery
2013 and third person auditory hallucinations papilloma
Canuet et al[26], Schizophrenia-like psychosis Right parietal lobe Meningioma Psychosis developed 6 yr after initial
2011 surgery with tumor recurrence.
Gradual improvement with
antipsychotics
Bunevicius et al[46], Schizophrenia Left temporal lobe Anaplastic Improvement with surgery
2008 oligodendroglioma
Bunevicius et al[46], Depression, psychosis Left temporal lobe Intra-cerebral cyst Refractory symptoms
2008
Bunevicius et al[46], Schizophrenia Left temporal lobe Glioblastoma
2008 multiforme
Parisis et al[82], Peduncular hallucinosis (complex visual Cerebellar Metastases Mechanism thought to be extrinsic
2003 hallucinations), sleep impairment metastases compression of posterior midbrain-
pons by mass edema
Rueda-Lara et al[83], Delusions, hallucinations Pituitary Hormone producing
2003 adenoma
Maiuri et al[84], Hallucinations Posterior thalamus Glioblastoma Partial improvement of symptoms
2002 multiforme with surgical treatment and
antidepressants
Miyazawa et al[85], 2001 Headaches and psychotic symptoms Pineal Pineal meningioma Improvement with surgery
Miyazawa et al[85], Headaches and psychotic symptoms Pituitary Unknown Improvement with steroid/hormone
2001 treatment
Craven[86], 2001 Acute psychotic episode Pineal Germinoma
Vardar et al[87], Psychotic symptoms and cognitive Right temporo- Arachnoid cyst
2000 deterioration parietal
Mordecai et al[88], Psychotic and obsessive-compulsive symptoms, Bilateral basal Germinoma
2000 left-sided weakness, diabetes insipidus, decline ganglia
in academic functioning
Werring et al[89], Visual hallucinations, palinopsia, posterior Occipital Tuberculoma
1999 headache
Carson et al[90], Pediatric psychosis - hallucinations, aggression, Third ventricle Choroid plexus Symptoms improved after surgical
1997 violence papilloma removal
Ball[91], Persecutory delusions, auditory and Cerebellopontine Meningioma
1996 visual hallucinations, fluctuating levels of angle
consciousness followed by grand-mal seizures
Filley et al[8], Psychotic symptoms (perceptual disturbances) Temporal Low-grade
1995 oligoastrocytoma
Okada et al[92], Positive and negative psychotic symptoms Left basal ganglia Unknown Positive symptoms resolved after
1992 surgical resection, but negative
symptoms persisted
Trabert et al[93], Symptoms of anorexia followed by seizures Temporo-basal Angioma
1990 and psychosis
Nagaratnam et al[94], Paranoid delusions Left frontal lobe Venous angioma
1990
Ko et al[57], Paranoid ideation, irritability, short-term Left parieto-occipital Origin in right No surgical intervention due to
1989 memory difficulties metastatic lesion kidney advanced stage
Dyck[95], 1985 Auditory hallucinations Sylvian fissure Lipoma
Binder[96], Sudden behavioral changes followed by Right lateral ventricle Meningioma Complete resolution of symptoms
1983 paranoid delusions; no focal neurologic signs after surgical intervention
Binder[96], New-onset rage attacks on background of Bilateral occipital Meningioma Resolution of rage attacks after
1983 chronic schizophrenia surgical removal
Dunn et al[97], Peduncular hallucinations Midbrain Cystic Prompt resolution after drainage of
1983 compression craniopharyngioma cyst
Soulairac et al[98], 1979 Peduncular hallucinosis Right temporal Astrocytoma
Buchanan et al[99], Pressured speech, hypomania, persecutory Lateral ventricle Meningioma
1975 delusions
Blustein et al[73], Thought disorder, auditory hallucinations Left parieto-occipital Porencephalic cyst
1972

Adapted from Trends in Brain Cancer Research. New York: Nova Science Publishers Inc., 2006.

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 Madhusoodanan S et al . Psychiatric aspects of brain tumors

[41]
Table 5 Brain tumors and personality changes

Ref. Psychiatric symptoms Tumor location Tumor type Remarks

Lajara-Nanson[100], Personality changes and hypersexual behavior Ventricular Ventricular cyst Improvement with surgery
2000
Paul et al[101], Personality changes, memory impairment, poor Extramedullary with Plasmacytoma
2000 concentration infiltration of the cerebral
dura
Fahy et al[102], Frontal lobe symptoms in absence of neurological Frontal Meningioma
1995 signs
Jones[103], Personality changes, aggressive behavior, and Ventricular Ventricular cysts Improvement with surgery
1993 emotional lability
Fulton et al[55], Personality changes, walking difficulties, Frontal lobe Multiple Poor response to steroid
1992 incontinence, neurologic signs metastases treatment
Fulton et al[55], Bizarre, disinhibited behavior, neurologic signs Multiple left orbito-frontal Astrocytoma Poor response to steroid
1992 and right thalamus treatment
Fulton et al[55], Withdrawn, inappropriate behavior, neurologic signs Bifrontal Unknown Poor response to steroid
1992 treatment
Lobosky[104], Personality changes and emotional lability Ventricular Ventricular cysts Improvement with surgery
1984
Barbizet et al[66], Rage attacks, Bulimia, uninhibited and brutal sexual Fronto-temporal Astrocytoma
1982 behavior, periods of depression with suicide attempts

Adapted from Trends in Brain Cancer Research. New York: Nova Science Publishers Inc., 2006.

[41]
Table 6 Brain tumors and eating disorders

Ref. Psychiatric symptoms Tumor location Tumor type Remarks

Vad Winkler et al[105], 2009 Eating disorder Pituitary gland Craniopharyngioma Improvement with surgery
Vad Winkler et al[105], 2009 Eating disorder Third ventricle Craniopharyngioma Developed pituitary
deficiency after surgery
Houy et al[106], Anorexia nervosa Frontal side of the right sylvian Cavernous hemangioma Improvement with surgery
2007 valley
Lin et al[107], Anorexia nervosa Hypothalamic region, third Unknown
2003 ventricle, pineal region, lateral
ventricle, corpus callosum
Wolańczyk et al[108], Anorexia nervosa, delusions, Right parietal lobe Arachnoid cyst
1997 catatonia
Chipkevitch et al[54], Atypical anorexia nervosa, Hypothalamus Teratoma
1993 depressive symptoms
Berek et al[109], Anorexia nervosa Third ventricle Teratoma
1991
Trabert et al[93], Symptoms of anorexia followed Temporo-basal Angioma
1990 by seizures and psychosis
Climo[110], 1982 Anorexia nervosa Hypothalamus Craniopharyngioma
Weller et al[111], 1982 Anorexia nervosa Pineal gland Pinealoma
Goldney[112], 1978 Anorexia nervosa Hypothalamus Craniopharyngioma
Swann[113], 1977 Anorexia nervosa Hypothalamus Pinealoma
White et al[114], 1977 Anorexia nervosa Hypothalamus Glioma
Heron et al[115], 1976 Anorexia nervosa Hypothalamus Unknown
Daly et al[116], 1973 Anorexia nervosa Hypothalamus Ectopic pinealoma

Adapted from Trends in Brain Cancer Research. New York: Nova Science Publishers Inc., 2006.

right frontal lobe along with extensive perifocal brain symptomatology, variety of signs pointing to several
edema. Upon total resection of the tumor, glioblastoma causative factors all contribute to the diagnostic
multiforme was diagnosed. Two weeks post-operative challenges. Diagnosis of psychiatric symptoms being
follow-up showed resolution of her pathological laughter secondary to brain tumors starts from having the
and hemiparesis. clinical suspicion. Early diagnosis is critical with regards
[1]
to further treatment and better quality of life .
A thorough medical history and physical examination
DIAGNOSIS may assist in the diagnosis. Subtle clues that could
Brain tumors as the primary cause of psychiatric otherwise be missed include neurologic signs: apraxia,
sym­ptoms are a rare occurrence. The rarity of this visual field deficits, and anomia. Personality changes,
condition, insidiousness of the disease process, vague sleep disturbances, apathy, weight loss, anorexia, or

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 Madhusoodanan S et al . Psychiatric aspects of brain tumors

[41]
Table 7 Brain tumors and miscellaneous symptoms

Ref. Psychiatric symptoms Tumor location Tumor type Remarks

Feng et al[20], 2013 Anomic aphasia Left temporal lobe Glioblastoma multiforme No resolution of aphasia
after surgical treatment
Hoffmann et al[117], 2012 Crying, spitting, biting self and others, Pituitary gland Craniopharyngioma No resolution of symptoms
mutism, withdrawal, sleepiness, anergia, after surgery
bipolar affective disorder
Wong et al[118], 2012 Attacks of sensory overload and unusual Left temporal lobe Epidermoid tumor
familiarity
Rosenzweig et al[119], Epilepsy, paroxysmal ictal phonemes Left superior temporal Angiocentric glioma Resolution of symptoms
2010 gyrus grade I after surgery
Tsutsumi et al[21], Abnormal laughter, left-hemiparesis Right frontal lobe Glioblastoma multiforme Resolution of psychiatric
2008 symptoms after surgical
treatment
Sokolski et al[120], 2003 Breakthrough manic symptoms with Right medial temporal, Grade IV invasive Improvement of psychiatric
mild nausea and dizzy spells, daily displacing right ventricle astrocytoma symptoms with surgical
derealisation episodes with olfactory and right hippocampus resection
auras
Burns et al[121], New-onset pedophilia Right orbito-frontal Unknown
2003
Daigneault et al[122], Aggression, precocious puberty and Hypothalamic Hamartoma
1999 worsening seizures
Konovalov et al[123], Korsakoff’s syndrome Third ventricle Colloid cyst Complete resolution after
1998 surgical removal
Caplan et al[124], Intractable seizures followed by Left anterior temporal Ganglionoma Symptoms subsided after
1992 coprolalia, compulsive behaviors, aphasia surgical resection
Ko et al[57], Expressive aphasia, short-term memory Multiple metastatic left Origin in right lung
1989 difficulties, no focal neurologic signs fronto-parietal lesions
Ko et al[57], Deteriorating memory and disorientation Left parietal extending to Unknown-surgery
1989 to time and place, behavioral changes, temporal lobe with midline refused- no autopsy
visual agnosia, aphasia, self-neglect shift report given
Ribeiro et al[125], 1989 Bonnet syndrome, blindness Posterior parasagittal Meningioma
Durst et al[126], 1988 Koro Corpus callosum Lipoma or dermoid
tumor
Binder[96], Behavioral changes, confusion with Left thalamic Glioblastoma multiforme
1983 neurological signs developing after 24 h
de Bures et al[127], Aggressive behavior, cognitive Left temporal Astrocytoma
1982 impairment on background of chronic
alcohol abuse and head
injuries

Adapted from Trends in Brain Cancer Research. New York: Nova Science Publishers Inc., 2006.

faltering concentration may be the first presentation modality of choice for trauma and acute hemorrhage.
of the illness. Further clues that suggest the presence Its other advantages include: greater availability,
of brain tumors may include psychiatric symptoms that fewer contraindications, and less expense. MRI offers
do not fall into distinct diagnostic categories or atypical higher resolution and is useful in evaluating necrosis,
symptoms, symptoms that are refractory to treatment, hemorrhage, cysts, tumors, and white-matter changes.
and recurrence of previously controlled symptoms where It is generally superior to CT in visualizing brain tumors
other contributory factors (such as non-adherence to or other soft-tissue lesions. Functional studies are
treatment, acute stressors, or medication changes) have mostly used in the research setting and presently do
[1]
been ruled out . not appear to have major advantages over CT and MRI
Neuroimaging is the primary diagnostic modality for routine clinical setting. This may change with further
[22]
used to visualize the presence of brain tumors. CT refinements and clinical utility .
[1]
and MRI are used for anatomical assessments. Madhusoodanan et al recommended that neuroi­
Magnetic reson­ance spectroscopy is used for the maging be considered in the following conditions: new-
relative quantification of metabolites in different brain onset psychosis, new-onset mood/memory symptoms,
locations. Studies of neuronal activity related to local occurrence of new or atypical symptoms, new-onset
cerebral blood flow are done by functional MRI (fMRI). personality changes, and anorexia without body
Positron emission tomography and single-photon dysmorphic symptoms. Conditions wherein neuroimaging
emission computed tomography pro­vide images by may or may not be required include recurrence of
[22]
use of radionuclides . For the purpose of this article, previously controlled psychiatric symptoms and patients
[1]
we will focus on the anatomical assess­ments that that are refractory to treatment .
are routinely used in clinical practice. CT remains the Neuropsychological testing is useful in evaluating

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 Madhusoodanan S et al . Psychiatric aspects of brain tumors

cognitive and neuropsychological dysfunction, in docu­ agents such as benztropine or trihexyphenidyl.

menting changes pre- and post-treatment, and in moni­ However, addition of these agents also increases the
[2]
toring the effectiveness of rehabilitative efforts . risk for anticholinergic delirium. The second-generation
antipsychotics may be preferred because of lower
incidence of some of these side-effects. Effectiveness of
MANAGEMENT these agents has been noted in some case reports
[26,27]
.
Removal of the tumor may completely resolve the However, clozapine and olanzapine are also associated
[28]
psychia­tric or behavioral symptoms. Otherwise, decrea­ with higher risk for seizures and delirium .
sing the size of the tumor or halting its growth may Other treatment modalities include electro-convulsive
also decrease these symptoms. Additionally, treating therapy (ECT). This may be given consideration in cases
the acute mass effects such as increased intra­cranial of refractory depression. Brain tumors without increased
pressure or hydrocephalus may improve cognitive intracranial pressure (ICP) or edema can be treated
[2] [29-32]
functioning and decrease behavioral symptoms . safely with ECT when appropriate precautions
Neuropsychiatric and behavioral symptoms can have been taken. Daily neurological evaluations are
persist or worsen after these interventions. Pharma­ of paramount importance as deterioration may be
cological and psychotherapeutic measures can be subtle. High-risk patients are those with presence of
instituted to improve the functioning and quality of large mass or multiple masses, increased intracranial
[2]
life . pressure, edema, or mass effect. In these patients, ECT
Pharmacological management follows general may be considered only if they are severely ill, or there
therapeutic principles of tumor-free patients with similar is risk for harm to self or others, and other options have
symptoms. However, patients with brain tumors may failed. Measures to reduce edema and the increase in
have increased susceptibility for delirium, seizures, ICP should be undertaken. Regardless of the risks of
medication side effects, and drug-drug interactions. ECT, all patients undergoing this treatment should have
Antidepressants may be beneficial in patients pre­ ongoing consultation with the neurologist/neurosurgeon.
senting primarily with depressive symptoms. Selective Additionally, changes in the lesion should be taken into
serotonin reuptake inhibitors (SSRIs) have a favorable account during maintenance treatments, as low-risk
[33]
side effect profile and less potential to cause delirium. patients may progress to high-risk .
Maprotiline and bupropion appear to have higher risk Psychotherapy is also an important treatment moda­
[23]
for seizures . Methylphenidate has also been shown lity. This helps to improve overall functional status,
to be effective in patients with secondary depression. interpersonal and psychosocial stressors, and emotional
It was well tolerated and did not appear to have an and cognitive status. Anxiety and depressive symptoms
increased risk for seizures. It was also found to be are frequently present and may benefit from supportive
effective in patients with apathy syndrome aside from and cognitive therapy, and psychoeducation. This is
[24]
depression . supported by a study which found that the presence of
Mood stabilizers are useful in treating manic sym­ depressive symptoms was the most important predictor
[34]
ptoms. Lithium may cause delirium and lower seizure of quality of life among patients with brain tumors .
threshold. Valproate, carbamazepine, oxcar­ba­zepine, It is also important to improve coping strategies and
benzodiazepines, and gabapentin, having anticonvulsant identify maladaptive defenses that may interfere with
[2] [2]
properties, may be preferable alternatives . A recent somatic treatments .
review explored possible neuropro­tective effects of
lithium in patients with brain cancer, especially when
treated with radiation. Possible targets of lithium may DISCUSSION
include excitotoxicity, excessive apoptosis, reduced Diagnosis and treatment of psychiatric symptoms of
neurogenesis, and senescence of growth and regenera­ brain tumors are challenging. At initial presentation,
tion. This effect has been shown in preliminary studies, patients may have a variety of symptoms or a clinical
but more research is required to confirm its benefits and picture that do not fit into a diagnostic category.
[25]
clinical utility . Symptoms may be vague, such as apathy syndrome or
Antipsychotics may be used for treating psychotic personality changes, or symptoms that are refractory
syndromes with hallucinations, delusions, and distur­ to treatment. Psychiatric symptoms may be the only
bances in thought content and processes. First-gen­era­tion presenting symptoms of a brain tumor. These symptoms
antipsychotics were more widely used. Lower potency tend not to be localized to specific anatomical regions
antipsychotics like chlorpromazine and thiori­da­zine and tumors are not confined to specific subdivisions.
may be associated with increased risk for seizures Tumors also exert effects by pressure, edema, and
and delirium. High-potency antipsychotics such as diaschisis (affecting connections to distant areas of
fluphenazine and haloperidol have lesser risk for seizure the brain). Thus, psychiatric symptoms generally have
and delirium. First-generation antipsychotics like no localizing value. A possible exception as previously
haloperidol and fluphenazine have a higher potential for discussed, is hypothalamic tumors that present with
extrapyramidal symptoms. This can be minimized by anorexia without distorted body image. Neuroimaging,
lowering the dosages or the addition of antiparkinsonian pituitary hormone levels, and ophthalmologic evaluation

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 Madhusoodanan S et al . Psychiatric aspects of brain tumors

are recommended based on the symptomatology to a more recent prospective, placebo-controlled trial of
[1,4]
rule out the presence of a tumor . prophylactic d-threo-methyl­phenidate did not show any
Various studies describe the impact of tumor location improvement in quality of life, with the main outcome
[40]
and the variety of symptoms. Dorsolateral tumors lead measure being improvements in fatigue .
to difficulties with organization and planning. Orbito- Continued treatment for persistent psychiatric
frontal tumors cause disinhibition, and medial frontal symptoms is also complicated by the potential for
tumors cause apathy and abulia. Frontal tumors may delirium and seizures, possible side effects, drug-drug
exhibit personality changes in the patient. Diencephalic interactions, and status of the tumor and its treatment.
and pituitary lesions lead to vegetative symptoms. Steroids may be associated with depression and psy­
More specifically, diencephalic lesions manifest hyper­ chosis. It is important that the treatment should be
somnic and hyperphagic variants of depressive disor­ based on a multi-disciplinary team approach. Clinical
[8-10,35,36]
ders . specialists involved in the treatment should work closely
A thorough history and physical examination, high and be aware of these issues with continued treatment,
degree of clinical suspicion, and neuroimaging are keys rehabilitation, and quality of life.
[37]
to the diagnosis. A review was conducted on the
clinical- and cost-effectiveness of structural imaging (by
use of CT or MRI) in patients with psychosis, especially CONCLUSION
that of first-episode psychosis. It concluded that struc­ Psychiatric symptoms may be the only presenting
tural neuroimaging adds little clinical information not feature of brain tumors. Thorough history and medical
suspected on history and physical examination that examination with a high index of suspicion are important
would influence management. Routine neuroimaging is for early diagnosis. Neuroimaging should be considered
not recommended. in patients presenting with new-onset psychosis or
Brain tumors may be primary or secondary, and mood/memory symptoms, occurrence of new or aty­
are treated accordingly either by surgery, radiation, pical symptoms, personality changes, and anorexia
or chemotherapy. After the treatment of the tumor, without body dysmorphic symptoms. Treatment is
psychiatric symptoms may either resolve or persist. geared towards the tumor, its complications, and the
From our clinical experience, we advocate that the psychiatric symptoms. Management of persistent
treatment of psychiatric symptoms may begin before psychiatric symptoms is based on extrapolation of
the treatment of the brain tumor, to improve the quality limited evidence, assessment of risk vs benefits, and
of life and coping skills. The psychotropics may be understanding of potential complications related to the
tapered gradually and discontinued after the tumor disease and concomitant therapy. Further investigation
treatment. If psychiatric symptoms recur, psychotropics is needed to improve our understanding of the mech­
may be reinstated. anisms by which tumors produce psychiatric sym­
Studies of anxiety, depression, and somatic sym­ ptoms. This may lead to improved understanding of
ptoms in brain tumors are complicated because it is the mechanisms of psychiatric disorders, advanced
unclear whether they are caused by the tumor or is diagnostic modalities, better categorization of symptom
a psychological response to the stress secondary to constructs, and prospective trials for the management
the diagnosis or treatment. Compounding the clinical of the psychiatric symptoms in patients with brain
conundrum is the lack of large controlled studies evalua­ tumors. With improvements in imaging techniques
ting the psychiatric symptoms of brain tumors or their and diagnostic categorization of psychiatric symptoms,
treatment modalities. Due to the relative rarity of this studies of correlation of anatomic location or neuronal
presentation and the wide array of manifestations, infor­ functional groups and psychiatric symptoms may yield
mation regarding treatment is mostly derived from case associations not previously found.
reports or case series. Furthermore, the descriptions of
psychiatric symptoms are not uniform in the literature.
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