Bipolar Disorder Secondary to Head Injury

A MEDLINE Search by, Ivan K. Goldberg, M.D.

Bipolar Disord. 2008 Feb;10(1):111-3.

Homicidal ideation with intent during a manic episode triggered by antidepressant
medication in a man with brain injury.

Dealberto MJ, Marino J, Bourgon L.

Department of Psychiatry, Ottawa Hospital, Department of Epidemiology and
Community Medicine, University of Ottawa, Ottawa, Ontario, Canada.

BACKGROUND: Mood disorders are more frequent after brain injury and both
depressive and manic episodes are associated in these patients with an increased
risk of aggression. Antidepressant medications are associated with a risk of
manic induction. CASE REPORT: We describe a case of homicidal ideation with
intent during the onset of a manic episode in a patient with prior brain injury
on antidepressant medication at low dosage. The manic episode could have been
secondary to brain injury and/or triggered by antidepressant medications. This
case raises the possibility of the sensitizing role of brain injury for
antidepressant-induced mania. CONCLUSIONS: Further studies are needed to assess
the role of brain injury as a risk factor for antidepressant-induced mania.
Physicians should be cautious when prescribing antidepressants to patients with
prior brain injury and inform them and their relatives of the possibility of a
switch into mania.
CNS Spectr. 2007 Oct;12(10):764-9.

Quetiapine for mania due to traumatic brain injury.

Oster TJ, Anderson CA, Filley CM, Wortzel HS, Arciniegas DB.

Brain Injury Rehabilitation Unit, HealthONE Spalding Rehabilitation Hospital,
Aurora, CO, USA.

Secondary mania develops in as many as 9% of persons with traumatic brain
injuries. The treatment of posttraumatic mania is not well defined, and agents
traditionally used for the treatment of idiopathic manic episodes may not be well
suited for use among individuals with traumatic brain injuries. Atypical
antipsychotics are indicated for the treatment of idiopathic bipolar disorder,
and have been used for other purposes among individuals with posttraumatic
neuropsychiatric disturbances. This article offers the first description of the
treatment of posttraumatic mania using the atypical antipsychotic quetiapine.
Beneficial effects of this agent on posttraumatic mania, cognitive impairments,
and functional disability in the subacute post-injury period are described.
Possible mechanisms of action are discussed and the need for additional
investigation of quetiapine for posttraumatic mania is highlighted.
Psychosomatics. 2007 Sep-Oct;48(5):433-5.

Manic behavior resulting from left frontal closed head injury in an adult with
fetal alcohol syndrome.

Camden JR, Spiegel DR.

Eastern Virginia Medical School Department of Psychiatry and Behavioral Sciences,
825 Fairfax Ave., Norfolk, VA 23507, USA.

Closed head trauma has been associated with various neuropsychiatric sequelae,
including mood disturbances such as depression and mania. Although mood
disturbances can occur with injury to either hemisphere, mania has been primarily
associated with right-side frontal lobe injury. We present a case of manic
behavior after a closed head injury to the left hemisphere in an adult with
preexisting fetal alcohol syndrome.
J Neuropsychiatry Clin Neurosci. 2007 Spring;19(2):106-27.

Neuropsychiatric complications of traumatic brain injury: a critical review of
the literature (a report by the ANPA Committee on Research).

Kim E, Lauterbach EC, Reeve A, Arciniegas DB, Coburn KL, Mendez MF, Rummans TA,
Coffey EC; ANPA Committee on Research.

Bristol-Myers Squibb Company, Neuroscience Medical Strategy, 777 Scudders Mill
Road, Plainsboro, NJ 08536, USA.

Psychiatric disorders frequently complicate recovery and rehabilitation from
traumatic brain injury (TBI). This study reviews the literature from 1978 to 2006
on psychosis, depression, posttraumatic stress disorder, mania, and aggression
following nonpenetrating TBI. The studies were reviewed using the American
Academy of Neurology’s criteria for classification of articles on diagnostic
methods. No studies were found to be Class I or II. Of the 66 studies reviewed,
the majority were Class IV. There are significant gaps in the literature on
post-TBI psychiatric conditions with respect to nosology, epidemiology, and risk
factors. Larger multicenter prospective studies using standardized diagnostic
instruments are needed to further clarify the nosology, risk factors, and
clinical course of these disorders. Specific directions for research are
Prog Neuropsychopharmacol Biol Psychiatry. 2007 Mar 30;31(2):551-6. Epub 2006
Nov 14.

Late onset bipolar disorder associated with white matter hyperintensities: a
pathophysiological hypothesis.

Zanetti MV, Cordeiro Q, Busatto GF.

Laboratory of Psychiatric Neuroimaging (LIM 21), Institute and Department of
Psychiatry, University of São Paulo, Brazil.

Vascular depression is, nowadays, a well-established concept in the literature.
However, the possible emergence of late onset bipolar disorder in subjects with
no antecedents of mood disorder or after a chronic or recurrent course of
unipolar depression constitutes a poorly studied issue, despite its importance in
clinical practice. Here, we present the case of a 72-year-old female patient who
began to present recurrent major depressive symptoms, resistant to
pharmacological treatment, from the age of 58. Three years later, she started to
present phases of mania with rapid cycling features. A brain MRI scan showed
prominent white matter hyperintensities (WMH). WMH are frequently found in the
elderly population, but with greater burden in individuals with hypertension and
cerebrovascular disease. WMH impair cortical function and damage the cerebral
tissue. WMH have been associated with adult-onset bipolar disorder and late onset
depression, and are linked to a worse prognosis of both conditions. The present
case report highlights the possibility that vascular-related WMH may provoke late
onset bipolar disorder by damaging frontolimbic circuits implicated in the
pathophysiology of mania.
J Neurotrauma. 2006 Oct;23(10):1468-501.

Guidelines for the pharmacologic treatment of neurobehavioral sequelae of
traumatic brain injury.

Neurobehavioral Guidelines Working Group, Warden DL, Gordon B, McAllister TW,
Silver JM, Barth JT, Bruns J, Drake A, Gentry T, Jagoda A, Katz DI, Kraus J,
Labbate LA, Ryan LM, Sparling MB, Walters B, Whyte J, Zapata A, Zitnay G.

Defense and Veterans Brain Injury Center, Department of Neurology and
Neurosurgery, Walter Reed Army Medical Center, USA.

There is currently a lack of evidence-based guidelines to guide the
pharmacological treatment of neurobehavioral problems that commonly occur after
traumatic brain injury (TBI). It was our objective to review the current
literature on the pharmacological treatment of neurobehavioral problems after
traumatic brain injury in three key areas: aggression, cognitive disorders, and
affective disorders/anxiety/ psychosis. Three panels of leading researchers in
the field of brain injury were formed to review the current literature on
pharmacological treatment for TBI sequelae in the topic areas of
affective/anxiety/ psychotic disorders, cognitive disorders, and aggression. A
comprehensive Medline literature search was performed by each group to establish
the groups of pertinent articles. Additional articles were obtained from
bibliography searches of the primary articles. Group members then independently
reviewed the articles and established a consensus rating. Despite reviewing a
significant number of studies on drug treatment of neurobehavioral sequelae after
TBI, the quality of evidence did not support any treatment standards and few
guidelines due to a number of recurrent methodological problems. Guidelines were
established for the use of methylphenidate in the treatment of deficits in
attention and speed of information processing, as well as for the use of
beta-blockers for the treatment of aggression following TBI. Options were
recommended in the treatment of depression, bipolar disorder/mania, psychosis,
aggression, general cognitive functions, and deficits in attention, speed of
processing, and memory after TBI. The evidence-based guidelines and options
established by this working group may help to guide the pharmacological treatment
of the person experiencing neurobehavioral sequelae following TBI. There is a
clear need for well-designed randomized controlled trials in the treatment of
these common problems after TBI in order to establish definitive treatment
standards for this patient population.
J Pharmacol Sci. 2005 Dec;99(4):307-21. Epub 2005 Dec 7.

Lithium: potential therapeutics against acute brain injuries and chronic
neurodegenerative diseases.

Wada A, Yokoo H, Yanagita T, Kobayashi H.

Department of Pharmacology, Miyazaki Medical College, University of Miyazaki,
Miyazaki, Japan.

In addition to the well-documented mood-stabilizing effects of lithium in
manic-depressive illness patients, recent in vitro and in vivo studies in rodents
and humans have increasingly implicated that lithium can be used in the treatment
of acute brain injuries (e.g., ischemia) and chronic neurodegenerative diseases
(Alzheimer’s disease, Parkinson’s disease, tauopathies, and Huntington’s
disease). Consistent with this novel view, substantial evidences suggest that
depressive illness is not a mere neurochemical disease, but is linked to gray
matter atrophy due to the reduced number/size of neurons and glia in brain.
Importantly, neurogenesis, that is, birth/maturation of functional new neurons,
continues to occur throughout the lifetime in human adult brains (e.g.,
hippocampus); the neurogenesis is impaired by multiple not-fully defined factors
(e.g., aging, chronic stress-induced increase of glucocorticoids, and
excitotoxicity), accounting for brain atrophy in patients with depressive illness
and neurodegenerative diseases. Chronic treatment of lithium, in agreement with
the delayed-onset of mood-stabilizing effects of lithium, up-regulates cell
survival molecules (e.g., Bcl-2, cyclic AMP-responsive element binding protein,
brain-derived neurotrophic factor, Grp78, Hsp70, and beta-catenin), while
down-regulating pro-apoptotic activities (e.g., excitotoxicity, p53, Bax,
caspase, cytochrome c release, beta-amyloid peptide production, and tau
hyperphosphorylation), thus preventing or even reversing neuronal cell death and
neurogenesis retardation.
Clin Sports Med. 2005 Jul;24(3):663-79, x.

Psychiatric and neuropsychological issues in sport medicine.

Broshek DK, Freeman JR.

Division of Neuropsychology, Department of Psychiatric Medicine, University of
Virginia School of Medicine, Box 800203, Charlottesville, VA 22908, USA.

This article reviews what is known about training room psychiatric/psychological
issues and how to recognize them, and provides an initial framework for how to
manage them. There is some focus on psychiatric issues involved in collegiate
sports medicine environments, because the majority of research on this topic has
been done with this population, but it is believed that this information
generalizes to other athletic settings. Greater awareness of these problems,
empirical research, and education about mental health issues in the sports
medicine community is clearly needed.
J Nerv Ment Dis. 2004 Jun;192(6):430-4.

Suicidal behavior and mild traumatic brain injury in major depression.

Oquendo MA, Friedman JH, Grunebaum MF, Burke A, Silver JM, Mann JJ.

Department of Neuroscience, New York State Psychiatric Institute, Columbia
University, New York, NY 10032, USA.

Traumatic brain injury (TBI) is associated with psychiatric illness, suicidal
ideation, suicide attempts, and completed suicide. We investigated the
relationship between mild TBI and other risk factors for suicidal behavior in
major depressive episode. We hypothesized that mild TBI would be associated with
suicidal behavior at least partly because of shared risk factors that contribute
to the diathesis for suicidal acts. Depressed patients (N = 325) presenting for
treatment were evaluated for psychopathology, traumatic history, and suicidal
behavior. Data were analyzed using Student t -test, chi-square statistic, or
Fisher exact test. A backward stepwise logistic regression model (N = 255)
examined the relationship between attempter status and variables that differed in
the TBI and non-TBI patients. Forty-four percent of all subjects reported mild
TBI. Subjects with TBI were more likely to be male, have a history of substance
abuse, have cluster B personality disorder, and be more aggressive and hostile
compared with subjects without TBI. They were also more likely to be suicide
attempters, although their suicidal behavior was not different from that of
suicide attempters without TBI. Attempt status was mostly predicted by aggression
and hostility, but not the presence of TBI. Of note, for males, a history of TBI
increased the likelihood of being a suicide attempter, whereas the risk was
elevated for females regardless of TBI history. Our data suggest that suicidal
behavior and TBI share antecedent risk factors: hostility and aggression. Future
studies may yield confirmation using a prospective design.
Int Rev Psychiatry. 2003 Nov;15(4):317-27.

Mood disorders following traumatic brain injury.

Jorge R, Robinson RG.

Department of Psychiatry, University of Iowa College of Medicine, Iowa City, IA
52242, USA.

Mood disorders are a frequent complication of traumatic brain injury that exerts
a deleterious effect on the recovery process and psychosocial outcome of brain
injured patients. Prior psychiatric history and impaired social support have been
consistently reported as risk factors for developing mood disorders after
traumatic brain injury (TBI). In addition, biological factors such as the
involvement of the prefrontal cortex and probably other limbic and paralimbic
structures may play a significant role in the complex pathophysiology of these
disorders. Preliminary studies have suggested that selective serotonin reuptake
inhibitors such as sertraline, mood stabilizers such as sodium valproate, as well
as stimulants and ECT may be useful in treating these disorders. Mood disorders
occurring after TBI are clearly an area of neuropsychiatry in which further
research in etiology as well as treatment is needed.
J Affect Disord. 2003 Sep;76(1-3):79-83.

Head injury as a risk factor for bipolar affective disorder.

Mortensen PB, Mors O, Frydenberg M, Ewald H.

National Centre for Register-based Research, Aarhus University, Taasingegade 1
DK-8000 Aarhus C, Denmark.

BACKGROUND: Case reports have associated head injury with psychoses including
affective disorders, but little is known regarding head injury as a risk factor
for the onset of bipolar affective disorder. METHODS: The Danish Psychiatric Case
Register and the Danish National Patients Register were linked together with the
Danish Population Register, thus identifying 10,242 patients with bipolar
affective disorder, and 102,420 matched controls. History regarding head injury
was recorded from the National Patients Register data. Data were analysed using
conditional logistic regression. RESULTS: Bipolar affective disorder was
associated with an increased risk of a history of head injury (IRR=1.55; 95% CI
1.36-1.77). The increased risk was confined to head injury occurring less than 5
years before the first psychiatric admission. The finding could not be ascribed
to increased accident proneness (as evaluated through the occurrence of other
fractures not involving the skull). LIMITATIONS: In studies based on clinical
diagnoses only and limited to patients who were hospitalised for psychiatric
disorder, exposure was limited to injuries leading to admission to hospital.
CONCLUSIONS: Head injury may be a contributing factor to the onset of bipolar
affective illness. However, this factor is probably only relevant to a relatively
small minority of cases.
Brain Inj. 2003 Apr;17(4):355-8.

Rapid cycling bipolar disorder after left temporal polar damage.

Murai T, Fujimoto S.

Department of Psychiatry, Faculty of Medicine, Kyoto University, Kyoto, Japan.

The case of a 48-year-old woman with rapid cycling bipolar disorder subsequent to
a traumatic brain injury is reported. Both depressive and manic episodes had an
average duration of approximately 1 month, alternating without stable euthymic
periods. Neuroradiological examinations revealed a circumscribed lesion in the
left temporal pole. After 1 year without treatment, psychiatric intervention and
pharmacotherapy was initiated. Her mood swings were successfully treated with the
co-administration of valproate and lithium. Case reports of rapid cycling bipolar
disorder after traumatic brain injury are very rare and this case supports the
idea that temporal polar dysfunction is a candidate for the neurobiological basis
of rapid cycling bipolar disorder.
J Neuropsychiatry Clin Neurosci. 2002 Spring;14(2):202-5.

Divalproex in the management of neuropsychiatric complications of remote acquired
brain injury.

Kim E, Humaran TJ.

Department of Psychiatry, University of Medicine and Dentistry of New
Jersey-Robert Wood Johnson Medical School, 671 Hoes Lane, Piscataway, NJ
08855-1392, USA.

A retrospective chart review was conducted on 11 patients with a remote history
of acquired brain injury (ABI) referred for psychiatric treatment who were
treated with divalproex sodium alone or in combination with other psychotropic
medications. The patients were highly heterogeneous. They had a variety of
psychiatric symptoms and frequently received concomitant psychotropic
medications. The mean daily dose of divalproex was 1,818+/-791 mg/day, serum
valproic acid level 85.6+/-29.6 microg/ml. Mean Clinical Global Impression
improvement score was 1.9+/-0.5. This is the largest postacute case series
reported. It demonstrates that divalproex sodium is well tolerated and effective
in reducing a broad range of neurobehavioral symptoms in psychiatric patients
with a remote history of ABI.
Hypomania induced by herbal and pharmaceutical psychotropic medicines following
mild traumatic brain injury.

Spinella M, Eaton LA.

Division of Social and Behavioral Sciences, Richard Stockton College of New
Jersey, Pomona 08240-0195, USA.

The use of herbal medicines has become a very common practice. While many are
safe enough to be available over-the-counter, they may pose risks due to
interactions with pharmaceutical medications and effects in specific clinical
populations. The case of a female patient with a history of mild traumatic brain
injury and resulting depression is presented. She experienced hypomania after
adding St John’s wort and Ginkgo biloba to her regimen of fluoxetine and
buspirone, which remitted after discontinuation of the herbal medicines.
Implications for interactions between various psychopharmacologic agents,
including herbal medicines and selective serotonin reuptake inhibitors (SSRIs),
as well as the need for appropriate patient and health care provider education
are discussed.
Am J Psychiatry 2001 Mar;158(3):440-6

Traumatic brain injury and schizophrenia in members of schizophrenia and bipolar
disorder pedigrees.

Malaspina D, Goetz RR, Friedman JH, Kaufmann CA, Faraone SV, Tsuang M, Cloninger
CR, Nurnberger JI Jr, Blehar MC.

New York State Psychiatric Institute, Columbia University, New York 10032, USA.

OBJECTIVE: Schizophrenia following a traumatic brain injury could be a phenocopy
of genetic schizophrenia or the consequence of a gene-environment interaction.
Alternatively, traumatic brain injury and schizophrenia could be spuriously
associated if those who are predisposed to develop schizophrenia have greater
amounts of trauma for other reasons. The authors investigated the relationship
between traumatic brain injury and psychiatric diagnoses in a large group of
subjects from families with at least two biologically related first-degree
relatives with schizophrenia, schizoaffective disorder, or bipolar disorder.
METHOD: The Diagnostic Interview for Genetic Studies was used to determine
history of traumatic brain injury and diagnosis for 1,275 members of multiplex
bipolar disorder pedigrees and 565 members of multiplex schizophrenia pedigrees.
RESULTS: Rates of traumatic brain injury were significantly higher for those
with a diagnosis of schizophrenia, bipolar disorder, and depression than for
those with no mental illness. However, multivariate analysis of within-pedigree
data showed that mental illness was related to traumatic brain injury only in
the schizophrenia pedigrees. Independent of diagnoses, family members of those
with schizophrenia were more likely to have had traumatic brain injury than were
members of the bipolar disorder pedigrees. The members of the schizophrenia
pedigrees also failed to show the gender difference for traumatic brain injury
(more common in men than in women) that was expected and was present in the
bipolar disorder pedigrees. Subjects with a schizophrenia diagnosis who were
members of the bipolar disorder pedigrees (and thus had less genetic
vulnerability to schizophrenia) were less likely to have had traumatic brain
injury (4.5%) than were subjects with schizophrenia who were members of the
schizophrenia pedigrees (and who had greater genetic vulnerability to
schizophrenia) (19.6%). CONCLUSIONS: Members of the schizophrenia pedigrees,
even those without a schizophrenia diagnosis, had greater exposure to traumatic
brain injury compared to members of the bipolar disorder pedigrees. Within the
schizophrenia pedigrees, traumatic brain injury was associated with a greater
risk of schizophrenia, consistent with synergistic effects between genetic
vulnerability for schizophrenia and traumatic brain injury.
Posttraumatic-brain-injury schizophrenia in multiplex schizophrenia pedigrees
does not appear to be a phenocopy of the genetic disorder.
J Am Acad Child Adolesc Psychiatry 2000 Apr;39(4):525-8

Case study: bipolar disorder after head injury.

Sayal K, Ford T, Pipe R.

Bethlem Hospital, London, England.

A case of bipolar disorder subsequent to a mild head injury in a 15-year-old
girl is reported. Review of the literature indicates that this is an extremely
rare outcome. Lack of adequate follow-up studies makes it difficult to
accurately predict type and severity of psychiatric outcome. Assessment and
management involves ongoing consideration of both organic and psychosocial
factors even after initial negative investigations.
Psychiatry Res 1999 Dec 27;89(3):281-6

Traumatic brain injury in individuals convicted of sexual offenses with and
without bipolar disorder.

DelBello MP, Soutullo CA, Zimmerman ME, Sax KW, Williams JR, McElroy SL,
Strakowski SM.

Department of Psychiatry, University of Cincinnati College of Medicine, OH
45267-0559, USA.

The authors examined the occurrence of traumatic brain injury (TBI) in
individuals convicted of sexual offenses with and without bipolar disorder and a
comparison group of patients with bipolar disorder without a history of sexual
offending behaviors. Individuals convicted of sexual offenses and diagnosed with
bipolar disorder had greater rates of brain injury resulting from head trauma
than individuals convicted of sexual offenses without bipolar disorder and
comparison patients with bipolar disorder. TBI predated the first sexual offense
and/or the onset of bipolar disorder in most subjects.
J Head Trauma Rehabil 1998 Aug;13(4):24-39

Axis I psychopathology in individuals with traumatic brain injury.

Hibbard MR, Uysal S, Kepler K, Bogdany J, Silver J.

Department of Rehabilitation Medicine, The Mount Sinai Medical Center, New York,
New York 10029, USA.

OBJECTIVES: To assess the incidence, comorbidity, and patterns of resolution of
DSM-IV mood, anxiety, and substance use disorders in individuals with traumatic
brain injury (TBI). DESIGN: The Structured Clinical Interview for DSM-IV
Diagnoses (SCID) was utilized. Diagnoses were determined for three onset points
relative to TBI onset: pre-TBI, post-TBI, and current diagnosis. Contrasts of
prevalence rates with community-based samples, as well as chi-square analysis
and analysis of variance were used. Demographics considered in analyses included
gender, marital status, severity of injury, and years since TBI onset. SETTING:
Urban, suburban, and rural New York state. PARTICIPANTS: 100 adults with TBI who
were between the ages of 18 and 65 years and who were, on average, 8 years post
onset at time of interview. MAIN OUTCOME MEASURES: SCID Axis I mood diagnoses of
major depression, dysthymia, and bipolar disorder; anxiety diagnoses of panic
disorder, obsessive-compulsive disorder (OCD), posttraumatic stress disorder
(PTSD), generalized anxiety disorder (GAD), and phobia; and substance use
disorders. RESULTS: Prior to TBI, a significant percentage of individuals
presented with substance use disorders. After TBI, the most frequent Axis I
diagnoses were major depression and select anxiety disorders (ie, PTSD, OCD, and
panic disorder). Comorbidity was high, with 44% of individuals presenting with
two or more Axis I diagnoses post TBI. Individuals without a pre-TBI Axis I
disorder were more likely to develop post-TBI major depression and substance use
disorders. Rates of resolution were similar for individuals regardless of
previous psychiatric histories. Major depression and substance use disorders
were more likely than were anxiety disorders to remit. CONCLUSION: TBI is a risk
factor for subsequent psychiatric disabilities. The need for proactive
psychiatric assessment and timely interventions in individuals post TBI is
Med Pregl 1997 Sep-Oct;50(9-10):391-3

[A manic syndrome after cerebral trauma: case report] [Article in Serbo-Croatian (Roman)]

Mitrovic D, Misic-Pavkov G, Ivanovic S, Dickov A.

Institut za neurologiju, psihijatriju i mentalno zdravlje, Medicinski fakultet,
Novi Sad.

This case report describes a 17-year-old female patient in whom a clinical
picture of manic syndrome developed four days after craniocerebral trauma. The
diagnostic procedure comprised neuropsychological, neurophysiological and
neuroanatomical examination. The diagnosis revealed discrete organicity on the
level of psychic functions, whereas magnetic resonance imaging revealed changes
of the right hemisphere. One case cannot reveal the etiology of affective
disorders after cerebral injuries, but gathered results point to the possibility
of causal connection between craniocerebral trauma and manic syndrome.
Singapore Med J 1996 Aug;37(4):448-50

Mania following left hemisphere injury.

Lim LC.

Department of Psychological Medicine National University Hospital, Singapore.

A case of mania following closed head injury to the left hemisphere is reported.
The patient presented with a self-limiting manic episode that recovered without
treatment. It is postulated that the head injury is the causative factor in this
case. This was supported by laboratory results as well as psychological
investigations. It is believed that non-dominant right hemisphere injury is
related to the development of mania. However, a search of the literature
revealed five other cases of mania following left hemispheric injury. Although
the mechanisms implicated in the pathogenesis of secondary mania have not been
established, this case adds to the growing evidence that head injury may be
directly causative in affective psychoses. Therefore, it is premature to
conclude that mania is a pathology of the non-dominant right hemisphere.
Brain Inj 1996 May;10(5):319-27

Psychiatric disorders after traumatic brain injury.

van Reekum R, Bolago I, Finlayson MA, Garner S, Links PS.

Department of Psychiatry, University of Toronto, Canada

Substantial psychological and neurobehavioural evidence is available to support
the hypothesis that traumatic brain injury (TBI) is a risk factor for subsequent
psychiatric disorders. However, studies utilizing established psychiatric
diagnostic schemes to study these outcomes after TBI are scarce, and no studies
have included an assessment of personality disorders in addition to the major
psychiatric disorders. This study utilizes structured psychiatric interviews to
measure the prevalence of DSM-III(R) disorders in a sample of 18 subjects
derived from a TBI rehabilitation programme. Results revealed high rates for
major depression, bipolar affective disorder, generalized anxiety disorder,
borderline and avoidant personality disorders. Co-morbidity was also high. A
preliminary study of postulated predictive factors revealed possible roles for
sex and for initial severity of injury. The study supports the association
between TBI and psychiatric disorder, and suggests the need for monitoring, for
prevention, and for treatment of psychiatric disorders after TBI.
Br J Psychiatry 1996 May;168(5):647-50

Bipolar affective disorder minus left prefrontal cortex equals schizophrenia.

Pang A, Lewis SW.

Chinese University of Hong Kong, Hong Kong.

BACKGROUND. An investigation of the relationship between bipolar affective
disorder and schizophrenia, following a severe head injury and removal of the
left prefrontal cortex. METHOD. A single case report. RESULTS. An individual
with past history of bipolar affective disorder suffered traumatic damages to
the left prefrontal cortex with a second lesion in the left temporal lobe. The
patient developed typical schizophrenia nine months later. The relevance of his
brain lesions in determining the schizophrenic symptoms is discussed.
CONCLUSION. We propose that the specific pattern of brain injury in this patient
was sufficient to change the phenotype from bipolar affective disorder to
Ann Med Psychol (Paris) 1995 May;153(3):161-8

[Secondary mania caused by cerebral organic pathology] [Article in French]

Verdoux H, Bourgeois M.

Centre Carreire, Universite de Bordeaux II.

The so-called “secondary mania” are manic syndromes complicating various kinds
of somatic illness. Cases of secondary mania following brain injury (i.e.,
tumors, cerebrovascular lesions, head traumas, infectious diseases, etc.) offer
the opportunity to better elucidate the pathophysiology of “primary” mania.
Published case reports of secondary mania are reviewed.
J Geriatr Psychiatry Neurol 1994 Jan-Mar;7(1):55-7

Valproate in the treatment of posttraumatic bipolar disorder in a
psychogeriatric patient.

Yassa R, Cvejic J.

Psychogeriatric Unit, Douglas Hospital, Verdun, Quebec, Canada.

The authors present an 83-year-old man who had developed posttraumatic bipolar
disorder 22 years earlier. His condition was characterized by recurrent manic
and depressive attacks. Valproate was found effective in controlling his
Am J Psychiatry 1993 Jun;150(6):916-21

Secondary mania following traumatic brain injury.

Jorge RE, Robinson RG, Starkstein SE, Arndt SV, Forrester AW, Geisler FH.

Department of Psychiatry, College of Medicine, University of Iowa.

OBJECTIVE: In this study patients were examined during the first year after
traumatic brain injury to determine the presence of secondary mania. METHOD: A
consecutive series of 66 patients with closed-head injury were evaluated in the
hospital and at 3-, 6-, and 12-month follow-ups. The patients were examined with
a semistructured psychiatric interview and scales for measurement of impairment
in activities of daily living, intellectual function, and social functioning.
Patients fulfilling the DSM-III-R criteria for mania were compared to patients
with major depression and to patients without affective disturbances in regard
to their background characteristics, impairment variables, and lesion locations.
RESULTS: Six patients (9%) met the criteria for mania at some point during
follow-up. The presence of temporal basal polar lesions was significantly
associated with secondary mania even when the effect of other lesion locations
was taken into account. Secondary mania was not found to be associated with the
severity of brain injury, degree of physical or cognitive impairment, level of
social functioning, or previous family or personal history of psychiatric
disorder. The duration of mania, however, appeared to be brief, lasting
approximately 2 months. CONCLUSIONS: The 9% frequency of secondary mania in
these patients with traumatic brain injury is significantly greater than that
seen in other brain-injured populations (e.g., patients with stroke). The major
correlate was the presence of a temporal basal polar lesion.
Brain Inj 1993 Mar-Apr;7(2):147-52

Ultra-rapid cycling bipolar affective disorder following a closed-head injury.

Zwil AS, McAllister TW, Cohen I, Halpern LR.

Department of Psychiatry and Human Behavior, Jefferson Medical College and
Thomas Jefferson University Hospital, Philadelphia, PA.

A young adult with no prior history of affective disease suffered the onset of a
rapid cycling bipolar illness, marginally responsive to psychotropic
medications, following a mild closed-head injury, and persisting after the
cognitive effects of the injury had resolved. A concurrence of findings on the
neurological examination, neurobehavioural examination, SPECT scan, EEG and
neuropsychological test battery suggested the presence of a diffuse cerebral
injury with a predominance of left frontotemporal findings. This case
demonstrates that a severe and disabling mood disorder may follow a mild head
injury, and that its course may be independent of cognitive impairment and
Brain Topogr 1993 Winter;6(2):143-62

Standardized varimax descriptors of event related potentials: basic

John ER, Easton P, Prichep LS, Friedman J.

New York University Medical Center, Dept. of Psychiatry, NY.

This paper describes a set of proposed standardized quantitative descriptors of
event-related potentials, based upon principal component varimax analysis
(PCVA). No claim is made that these mathematical descriptors correspond to
discrete neurophysiological processes which generate the ERP. However, adoption
and prospective evaluation of such a set of precise, standardized descriptors of
the quantitative ERP may eventually result in advances like those which resulted
from adoption of equally arbitrary standardized descriptors for QEEG. PCVA was
performed on data from normal subjects and from groups of patients with a wide
variety of psychiatric disorders (“Abnormals”). This yielded two sets of factor
waveshapes, Normal and Abnormal, which were closely similar. Reconstruction of
the normal and abnormal ERP data with either set of factors yielded almost
identical allocation of variance. These results gave acceptable reassurance that
factors derived from normal population could reasonably be used to describe ERP
waveshapes from patients. The ERPs at each electrode of the 10/20 System in a
“training group” of normal subjects were then reconstructed. The resulting
distributions of factor scores were transformed to achieve Gaussianity. Mean
values and standard deviations were obtained for the normative distribution of
each factor score, the root mean square deviation, the residual and the absolute
ERP power at each electrode. Individual ERPs could then be reconstructed with
the normal factors, and the resulting factor scores rescaled to “probability of
abnormal morphology” by Z-transformation. Statistical probability maps could be
generated by using a color scale in standard deviation units. These methods were
used to evaluate visual and auditory ERPs from an independent normal “test
group” and the patients in the Abnormal sample. High specificity and sensitivity
were obtained for many factor Z- scores. Multiple discriminant functions were
constructed which separated normal from abnormal patients with high, replicable
accuracy. Further development and testing of these descriptors may make them
clinically useful.
Psychiatr Clin North Am 1992 Jun;15(2):395-413

Neuropsychiatric sequelae of head injuries.

McAllister TW.

Section of Neuropsychiatry, Dartmouth Medical School, Hanover, New Hampshire.

Based on the above review several general points can be highlighted: Head
injuries are extremely common, affecting probably close to 2,000,000 people in
this country each year. The most common are nonmissile, closed-head injuries,
the majority of which occur in association with motor vehicle accidents.
Virtually all studies of head injury suggest a peak incidence in the 15 to 24
years of age group. Coarse measures of outcome suggest that the very young and
the elderly have poorer outcomes. Because of improved acute care, however, a
large number of young, otherwise healthy patients are surviving head injuries
with a variety of profound neuropsychiatric sequelae. Because of the mechanics
of brain injury in acceleration-deceleration injuries, certain brain injury
profiles are common including orbitofrontal, anterior and inferior temporal
contusions, and diffuse axonal injury. The latter particularly affects the
corpus callosum, superior cerebellar peduncle, basal ganglia, and
periventricular white matter. The neuropsychiatric sequelae follow from the
above injury profiles. Cognitive impairment is often diffuse with more prominent
deficits in rate of information processing, attention, memory, cognitive
flexibility, and problem solving. Prominent impulsivity, affective instability,
and disinhibition are seen frequently, secondary to injury to frontal, temporal,
and limbic areas. In association with the typical cognitive deficits, these
sequelae characterize the frequently noted “personality changes” in TBI
patients. In addition, these changes can exacerbate premorbid problems with
impulse control. Marked difficulties with substance use, sexual expression, and
aggression often result. The constellation of symptoms, which make up the
postconcussive syndrome, are seen across the whole spectrum of brain injury
severity. Even in so-called mild or minor head injury, these symptoms are likely
to have an underlying neuropathologic, neurochemical, or neurophysiologic cause.
Higher than expected rates of certain psychopathologic disorders occur in the
TBI population, including psychotic syndromes and depressive syndromes. Manic
syndromes also are associated with TBI; however, the incidence has not been
established. Assessment and treatment of the neuropsychiatric sequelae is a
complex and challenging process. The mixture of diffuse and focal injuries, the
combination of cognitive, language, somatic, and behavioral difficulties do not
fit easily into current diagnostic categories.
Biol Psychiatry 1991 Jan 15;29(2):149-58

Manic-depressive and pure manic states after brain lesions.

Starkstein SE, Fedoroff P, Berthier ML, Robinson RG.

Department of Psychiatry and Behavioral Science, Johns Hopkins University School
of Medicine, Baltimore, MD 21205.

Although mania is a rare complication of brain lesions, recent reports have
emphasized the importance of lesion location and genetic predisposition in these
patients. In the present study we compared patients who developed a bipolar
affective disorder (i.e., mania and depression) after a brain lesion with
patients who only developed mania. Although no significant between-group
differences were found on demographic variables, the manic-depressed group
showed significantly more impairments on the Mini Mental State Exam than the
mania only group. All the bipolar patients had subcortical lesions (mainly right
head of the caudate and right thalamus), while patients with unipolar mania had
significantly higher frequency of cortical involvement (mainly right
orbitofrontal and basotemporal cortices). It is suggested that subcortical and
cortical right hemisphere lesions may produce different neurochemical and/or
remote metabolic brain changes that may underlie the production of either a
bipolar disease or a unipolar mania.
Br J Psychiatry 1991 Jan;158:117-9

Bipolar affective disorder following head injury.

Bamrah JS, Johnson J.

Withington Hospital, Didsbury, Manchester.

A patient developed distinct episodes of major depressive illness,
schizophreniform psychoses and mania as well as focal epilepsy following head
injury. Head injury may be directly causative in the development of affective
psychoses, in this case secondary bipolar (mixed) disorder.
Ann Neurol 1990 Jun;27(6):652-9

Mania after brain injury: neuroradiological and metabolic findings.

Starkstein SE, Mayberg HS, Berthier ML, Fedoroff P, Price TR, Dannals RF, Wagner
HN, Leiguarda R, Robinson RG.

Department of Psychiatry, Johns Hopkins University School of Medicine,
Baltimore, MD.

We present a consecutive series of 8 patients who developed a manic episode
after a brain injury. Five patients had cortical lesions (4 with damage to the
right basotemporal region, and 1 with bilateral damage to the orbitofrontal
area). While the other 3 patients had subcortical lesions (white matter of the
right frontal lobe, right anterior limb of the internal capsule, and right head
of the caudate), a fluorodeoxyglucose positron emission tomography scan showed
hypometabolism in the right lateral basotemporal region in all 3 patients. These
findings suggest a major role for the basal region of the right temporal lobe in
the modulation of mood.
Br J Psychiatry 1990 Jun;156:884-6

Seasonal affective disorder following brain injury.

Hunt N, Silverstone T.

Homerton Hospital, London.

Seasonal affective disorder has not previously been linked with neuroanatomical
abnormalities despite its relationship to biological rhythms. A 45-year-old
woman is described with an arteriovenous abnormality in the right frontotemporal
region who developed recurrent winter depression and summer hypomania.
Acta Psychiatr Scand 1988 Jun;77(6):637-9

Mania following head injury: case reports and neuropsychological findings.

Nizamie SH, Nizamie A, Borde M, Sharma S.

Central Institute of Psychiatry, Bihar, India.

Mania secondary to head injury is reported to be rare. Two cases of florid manic
psychoses following head injury are reported along with neurological and
neuropsychological investigations. Findings on the Luria Nebraska
Neuropsychological Battery (LNNB) suggested residual cognitive deficits,
predominantly of right hemisphere. Temporal proximity, clinical neurological
findings, EEG changes and deficits on LNNB suggest a causal link between head
injury and mania.
Acta Psychiatr Scand 1988 Mar;77(3):359-60

Mania following head injury.

Yatham LN, Benbow JC, Jeffers AM.

St. Ita’s Hospital, Portrane, Dublin, Ireland.

A case of mania following head injury in an individual with a genetic
predisposition to schizophrenia is reported. It is argued that the head injury
is probably causative in his case and suggested that head injury should be
considered as one of the aetiological factors in secondary mania.
Am J Psychiatry 1988 Feb;145(2):172-8

Comparison of mania and depression after brain injury: causal factors.

Robinson RG, Boston JD, Starkstein SE, Price TR.

Department of Psychiatry, Johns Hopkins University School of Medicine,
Baltimore, MD 21205.

Patients who developed secondary mania after brain injury (N = 17) had a
significantly greater frequency of injury to right hemisphere areas connected
with the limbic system than poststroke patients with major depression (N = 31),
who had injury primarily in the left frontal cortex and basal ganglia. For
patients without mood disturbance after brain injury (N = 28), the location of
the lesion was not significant. Secondary mania patients also had a
significantly greater frequency of family history of affective disorder than did
the other two groups. These results suggest that an interaction between injury
to certain areas of the right hemisphere and genetic factors or other
neuropathological conditions produces secondary mania.
J Nerv Ment Dis 1988 Feb;176(2):87-100

Mechanisms of mania after brain injury. 12 case reports and review of the

Starkstein SE, Boston JD, Robinson RG.

Department of Psychiatry and Behavioral Science, Johns Hopkins University School
of Medicine, Baltimore, Maryland 21205.

Twelve patients who developed mania after a brain lesion are reported. Ages
ranged from 20 to 83 years. Five patients had brain tumors (three frontal
meningiomas, one temporal meningioma, and one temporal astrocytoma), four
patients had stroke lesions (one frontal, one temporal, and two
thalamocapsular), two patients had a traumatic frontal closed head injury, and
one patient had a pituitary adenoma resection. Although seven patients had
lesions restricted to the right hemisphere, four had bilateral or midline damage
and one had a left hemisphere lesion. Damage to structures functionally
connected to the obitofrontal cortex, mainly in the right hemisphere, seems to
be associated with secondary mania. The possible roles of monoaminergic,
genetic, and perinatal factors in the pathogenesis of secondary mania are
J Clin Psychiatry 1988 Feb;49(2):74-5
Bipolar illness following traumatic brain injury: treatment with lithium and

Stewart JT, Hemsath RH.

Gainesville VA Medical Center, FL 32602.

A case is described of a 22-year-old woman in whom bipolar disorder developed
after a traumatic brain injury. Her symptoms initially responded well to lithium
carbonate, but she eventually relapsed. Carbamazepine was added to her treatment
regimen with good results.
Arch Neurol 1987 Oct;44(10):1069-73

Mania after brain injury. A controlled study of causative factors.

Starkstein SE, Pearlson GD, Boston J, Robinson RG.

Eleven patients who developed manic syndromes after brain injury (secondary
mania) were studied. Six patients had depressive episodes before mania and five
had a definite or possible family history of affective disorder. Eight had
lesions involving limbic areas, and nine had right hemisphere involvement. In
addition to focal brain injury, mean values for bifrontal and third
ventricle/brain ratios of manic patients were significantly increased when
compared with non-manic patients who had lesions matched for cause, location,
volume, and time since injury. Results indicate that the confluence of either
anterior subcortical atrophy and a focal lesion of a limbic or limbic-connected
region of the right hemisphere, or genetic loading and a limbic-connected right
hemisphere lesion may account for the rare occurrence and specific factors
necessary to produce secondary mania.
Psychiatry Res 1987 Aug;21(4):303-6

Childhood head trauma and psychosis.

Wilcox JA, Nasrallah HA.

The medical histories of 200 schizophrenic patients were compared to those of
203 depressed patients, 122 manic patients, and 134 surgical controls. All
subjects were hospital inpatients. Charts were specifically examined to record
any head injury before age 10 that had required medical attention or caused loss
of consciousness. Schizophrenics had a significantly greater history of head
trauma than the manics, depressives, and surgical controls. There were no
significant differences between manics and depressives or between affective
disorders as a group and surgical controls. Childhood trauma may be a
contributing factor to the development of psychosis in some individuals.
Br J Psychiatry 1987 Jun;150:841-4

Mania following head injury. A report of two cases and a review of the

Clark AF, Davison K.

Royal Victoria Infirmary, Newcastle-upon-Tyne.

Secondary mania has been described in association with a variety of physical
conditions. While there have been a number of reports of mania occurring in
individuals with intracranial cerebral lesions, there have been few reporting
its occurrence in association with non-penetrating cerebral trauma. Two further
cases of mania following non-penetrating head injury and the efficacy of ECT in
its management are reported, and a brief review of the literature relating to
the subject is given.
Br J Psychiatry 1987 May;150:690-2

Mania following head injury.

Bracken P.

Cork Regional Hospital, Wilton, Ireland.

A case of mania subsequent to head injury is presented. The literature reporting
cases of mania after head injury is reviewed. It is suggested that the concept
of Secondary Mania be broadened to include cases occurring after head injury. It
is also suggested that a true bipolar illness can be secondary.
J Clin Psychiatry 1987 Jan;48(1):29-30

Manic syndrome following head injury: another form of secondary mania.

Riess H, Schwartz CE, Klerman GL.

Two cases of mania secondary to head injury are reported. Only four
well-documented reports of head trauma as a cause of secondary mania were found
in an English and foreign literature search, although such a search is made
difficult by the paucity of cases meeting modern diagnostic criteria for mania.
Previous reviews of the causes of secondary mania have not included head injury,
but the two case reports confirm that head injury may be an additional cause. A
diagnosis of mania secondary to head trauma should be considered in manic
patients with atypical age of onset, absence of previous psychiatric illness,
negative family history for bipolar illness, and close temporal proximity of
head trauma to subsequent mania.
Am J Psychiatry 1987 Jan;144(1):93-6

Mania following head trauma.

Shukla S, Cook BL, Mukherjee S, Godwin C, Miller MG.

The authors present psychiatric and neurologic data on 20 patients who developed
mania after closed head trauma. An association was seen between severity of head
trauma (based on length of posttraumatic amnesia), posttraumatic seizure
disorder, and type of bipolar disorder. The manic episodes were characterized by
irritable mood rather than euphoria and by assaultiveness. Psychosis occurred in
only 15% of the sample, and 70% had no depressive episodes. Bipolar disorders
were absent among 85 first-degree relatives. The authors suggest that
posttraumatic seizures may be a predisposing factor in posttraumatic mania.
J Dev Behav Pediatr 1985 Dec;6(6):352-4

Effective management with lithium of a persistent, post-traumatic hypomania in a
10-year-old child.

Joshi P, Capozzoli JA, Coyle JT.

A 10-year-old child who suffered closed head trauma resulting in a coma of 1
week’s duration at the age of 4, developed a persistent, severe behavioral
disorder characterized by hyperactivity, impulsivity, distractability,
irritability, and grandiosity. Prior attempts at treatment with stimulants and
behavioral modification were unsuccessful. Treatment with lithium carbonate
resulted in a marked reduction in symptoms and attenuation in her emotional
No To Shinkei 1977 Jul;29(7):787-90

[An autopsy case of head injury with a manic-depressive states (author’s
transl)] [Article in Japanese]

Deshimaru M, Miyakawa T, Suzuki T.

M. M. a man aged 49. He suffered from a head injury at the aged of 41. At that
time he lost consciousness for a few minutes and he was diagnosed as a
consquassatio cerebri. The sequelaes of his head injury were a change of
character and a disturbance of autonomic nerve function. The changes of
character were decreased of activity, lie-down for all day, decrease of speech
and depressive mode, and occasionally he was ill-humored, restless and
irritative. Periodically he became euphoris, talkative and childisch. He had a
disturbance of autonomic nerve function which became worse in parallel to the
depressive states. We speculated that character changes, such as
manic-depressive states and disturbances of autonomic nerve function were due to
the bruising of the bilateral orbital surfaces of frontal lobes.