Psychosomatics 41:24-30, February 2000
© 2000 The Academy of Psychosomatic Medicine
Neuropsychiatry of Huntington's Disease and Other Basal Ganglia Disorders
Adam Rosenblatt, M.D., and
Iracema Leroi, M.D., F.R.C.P.C.
Received September 2, 1999; accepted September 2, 1999. From the Department of Psychiatry and Behavioral Science, Neuropsychiatry and Memory Group, Johns Hopkins University School of Medicine, Baltimore, Maryland. Address correspondence and reprint requests to Dr. Rosenblatt, Department of Psychiatry, Johns Hopkins University, Meyer 2–181, 600 N. Wolfe Street, Baltimore, MD 21287; e-mail: arosenba{at}welchlink.welch.jhu.edu
|
ABSTRACT
|
Degenerative diseases of the basal ganglia, such as Huntington's disease (HD), Parkinson's disease, and Wilson's disease, are characterized by motor, cognitive, and psychiatric manifestations. HD, in particular, can be considered a paradigmatic neuropsychiatric disorder that has all three components of the "Triadic Syndromes": dyskinesia, dementia, and depression. The authors examine the phenomenology, prevalence, and management of psychiatric disturbances occurring in diseases of the basal ganglia. They address psychiatric conditions such as depression, mania, psychosis, obsessive-compulsive disorders, aggression, irritability, apathy, sexual disorders, and delirium, discussing subtleties of diagnosis, and making reference to more unusual disorders of the basal ganglia, such as postencephalitic parkinsonism and Fahr's disease.
Key Words: Neuropsychiatry • Huntington's Disease • Basal Ganglia Disorders
|
INTRODUCTION
|
The degenerative diseases of the basal ganglia, such as Huntington's disease (HD), Parkinson's disease (PD), and Wilson's disease, have traditionally been classified as movement disorders, with associated cognitive and psychiatric manifestations. However, HD, for example, might just as easily be regarded as a dementia, or indeed a primary psychiatric condition, with associated motor symptoms similar to dementia with Lewy bodies. In fact, some of the earliest descriptions of HD recognized as central features were the involvement of affect and cognition in addition to the motor manifestations.1 HD, as well as being a prototypical basal ganglia disorder, is also a paradigmatic neuropsychiatric condition.
One heuristic model of the complexity of the basal ganglia disorders is seen in McHugh's "Triadic Syndromes."2 This label reflects the confluence of symptoms conceptualized as the three Ds: dyskinesia, dementia, and depression.
The basal ganglia disorders encompass a wide range of diseases. Among them are PD (which is covered extensively elsewhere in this issue of Psychosomatics), HD, Wilson's disease, progressive supranuclear palsy (PSP), Hallevorden-Spatz disease, idiopathic calcification of the basal ganglia, familial calcification of the basal ganglia (Fahr's disease), neuroacanthocytosis, Sydenham's chorea, and postencephalitic parkinsonism. Genetically similar, and phenomenologically related to HD, are a group of hereditary neurodegenerative disorders caused by expanded trinucleotide repeats in DNA (deoxyribonucleic acid), including DRPLA (dentatorubral-pallidolysian atrophy; Smith's disease), Machado-Joseph's disease (spinocerebellar ataxia, type 3; SCA3), and the autosomal-dominant spinocerebellar ataxias. Many of these disorders are so rare as to preclude more than anecdotal characterizations of their psychopathology. We will focus on the major neuropsychiatric complications of HD and provide an overview of current treatment modalities. We will draw on specific reports, where available, about other basal ganglia diseases and will consider how the experience with HD might be generalized to anticipate and treat the psychiatric manifestations of these conditions.
|
DEPRESSION
|
The prevalence of major depression in these disorders is high. We believe that much of this is the direct result of pathological changes in the brain, presumably activating some final common pathway, that result in the clinical syndrome of major depression. In fact, some have suggested that depression in neurological disorders affecting the basal ganglia provides a model for generating hypotheses about the neuroanatomic basis of "idiopathic" depression.3
George Huntington, in his original description of the disease that bears his name, stated that there was "a tendency to insanity and suicide."1 Folstein and colleagues found a lifetime prevalence of 38% for mood disorders in patients with HD.4 Of these, 22% met criteria for major depression. In retrospect, the depressive syndromes often appear to have preceded the motor symptoms (although it is hard to be sure, given the prevalence of depression in the general population) but may occur at any stage of the disease.5 The suicide rate for patients with HD is 4–6 times higher than the general population. This rate is even higher for those over the age of 50.6
The neuropathological basis for depression in HD might be linked to early neuronal loss in the medial caudate, which has connections to limbic structures.7 The subcortical structures affected in the basal ganglia disorders, such as the caudate in HD, are linked to orbitofrontal and prefrontal cortices via complex, parallel, frontal–subcortical circuits.8,9 Mayberg and colleagues10 found that depression in HD is associated with reduced glucose metabolism in the orbitofrontal and inferior prefrontal regions. This finding is consistent with positron emission tomography (PET) results that show hypometabolism in the prefrontal cortex of depressed patients without a primary neurologic disorder.11
In Wilson's disease, also known as hepatolenticular degeneration, excess copper deposition occurs in the lenticular nuclei.12 Depression has been reported to occur, with a prevalence rate as high as 20% in Wilson's disease. Depression may also be the presenting symptom of PSP, which includes degeneration of the basal ganglia, brainstem, and cerebellar nuclei. As cognitive impairments appear, depression, personality changes, and affective lability may be seen in PSP.13
In our experience, depression is commonly underdiagnosed in patients with basal ganglia disorders. Communication may be impaired, preventing the clinician from getting a detailed picture of the patient's emotional state. Neurologically mediated changes to cognition and personality may result in an atypical presentation, with irritability, agitation, or social withdrawal being the most prominent symptoms. The situational aspects of living with a debilitating motor illness can give rise to demoralization, hopelessness, loss of self-worth, and expression of a wish to die. This fact is intuitively obvious to clinicians, patients, and families. Thus, the sense that depression in these circumstances is "understandable" sometimes leads clinicians prematurely to assign a reactive explanation to the patient's symptoms, failing to undertake aggressive treatment.
In trying to decide between a "reactive" and an "organic" etiology, the clinician should consider prior history of depressive episodes, history of depression in close relatives, the proximity of specific losses and life changes to the episode, "proportionality," and the total number of symptoms. Danger and severity of depressive symptoms should be the trump card, lowering the threshold for diagnosis, pharmacotherapy, or hospitalization.
There is also a danger of overdiagnosis. Some of the individual symptoms of these disorders may resemble a depressive state. Physical changes, such as weight loss, sleep disturbance, bradykinesia, restricted facial expressions, apathy, and bradyphrenia, may be mistaken for a major depressive episode, which may lead to unnecessary pharmacotherapy in patients who are specially vulnerable to the central nervous system side effects of antidepressants.
We know of no randomized, controlled trials of the treatment of depression in HD and the other basal ganglia disorders. Therefore, clinical experience must guide the choice of therapeutic agents, often by extrapolation from principles developed in the treatment of depression in other medically ill patients. For example, while no class of antidepressant has been found to be uniquely effective in these disorders, patients with basal ganglia disorders are especially vulnerable to adverse effects, such as sedation, falls, and anticholinergic-induced cognitive impairment. Therefore, the tricyclic antidepressants, although more extensively studied, should no longer be considered first-line. We have generally found selective serotonin reuptake inhibitors (SSRIs) to be easier to manage and better tolerated. Also, the SSRIs may be useful in treating some of the psychiatric symptoms seen in some of these disorders that may not fit into a well-defined syndrome, such as irritability, apathy, and obsessiveness, which may be due to these drugs' putative role in improving "frontal function." We have also had success in treating HD patients with many of the other newer antidepressants, such as bupropion (Wellbutrin), venlafaxine (Effexor), and nefazodone (Serzone), but it remains to be seen whether these agents possess all of the less-specific benefits of the SSRIs.
If the patient's depression is accompanied by delusions, hallucinations, or significant agitation, it may be necessary to add an antipsychotic medication. Some strategies are provided in the section on psychotic disorders. In cases in which the patient is dangerously suicidal, not eating or drinking, or is unresponsive to several trials of medication, electroconvulsive therapy (ECT) should be considered. Depressed patients with HD respond to ECT, which they typically tolerate well. However, there is probably an increased risk of delirium from ECT in the setting of subcortical dementia.14,15
When a depression is believed secondary to some specific medical cause, such as hypothyroidism or exogenous steroids, correction of the underlying problem may be all the treatment that is needed. In the case of Wilson's disease, for example, timely treatment with penicillamine will usually reverse the neurologic symptoms and may ameliorate the psychiatric symptoms. However, if a depression remains, standard antidepressant therapy, as outlined earlier, is warranted. Once again, the severity or duration of the depression may mandate the initiation of treatment, whatever the suspected cause.
|
MANIA
|
Although depression is the most common specific psychiatric diagnosis in HD, a smaller number of patients become manic, displaying elevated or irritable mood, impulsiveness, overactivity, decreased need for sleep, and grandiosity. Some may even have a classical bipolar disorder, alternating between episodes of depression and mania. In his review of the subject, Mendez looked at seven studies and estimated an average rate of mania (with variable definitions of "mania") of 4.8%.16 Folstein found hypomania and manic episodes in up to 10% of HD patients.5 There are few reports of mania or hypomania in other basal ganglia disorders, although emotional lability and irritability have been reported in Wilson's disease and PSP.12,17
Patients with mania or a bipolar mood disturbance in the context of a basal ganglia disorder should probably be managed with a mood stabilizer other than lithium. Clinical experience, and a small amount of literature, suggest that HD patients with manic or hypomanic symptoms respond less well to lithium and may be more susceptible to toxic effects. It may be that "mania" in patients with HD is not the same neurophysiologic entity as mania found in idiopathic bipolar disorder, that something about the disorder limits the response to this drug, or simply that lithium is poorly tolerated in patients vulnerable to delirium and dehydration. The same caveat has been expressed about patients with "AIDS mania."18
Divalproex sodium and carbamazepine are good alternatives to lithium, starting with the lower doses than would be used with robust patients. Liver functions and blood counts should be routinely monitored, because these medications carry a risk of liver-function abnormalities (particularly divalproex sodium) and blood dyscrasias (particularly carbamazepine). Finally, manic patients who have delusions and hallucinations and therefore are very agitated (e.g., requiring hospitalization), or who may not fully respond to mood stabilizers, may require an antipsychotic. The judicious use of benzodiazepines for immediate control of these symptoms may also be helpful. ECT may also be considered should other treatments fail.
|
PSYCHOTIC DISORDERS
|
A link between basal ganglia pathology and primary psychotic disorders such as schizophrenia has been hypothesized. For example, many of the symptoms of PD, including poverty of speech, flattened affect, and psychomotor retardation, resemble the negative symptoms in schizophrenia.19 It has also been established that schizophrenia patients who are antipsychotic-naive may have extrapyramidal signs similar to PD.20 These lines of thinking suggest a role for the basal ganglia in psychosis and schizophrenia-like presentations.
A recent review of 11 studies of HD patients found an increased frequency of psychosis in HD, ranging from 3% to 12% of patients.16 The psychotic presentations included poorly systematized paranoia, isolated delusional states, and psychotic states resembling various types of schizophrenia.21,22 Those with an early age at onset of HD seem to be at an increased risk of such psychoses.23 Overall, these psychiatric symptoms in HD presented early in the course of the illness and declined as the cognitive impairment became more profound.16
The underlying neuropathology leading to psychosis in HD is not well understood. However, it is possible that the relative hyperdopaminergic state, resulting from selective degeneration of other neurotransmitter-containing neurons, superimposed on faulty subcortical circuits, may lead to the development of psychotic symptoms.24 Also, there appears to be an anterior bihemispheric decrease in metabolism, as seen by PET in psychotic HD patients. This change is similar to the relative hypofrontality seen on PET in patients with schizophrenia.25 Finally, since psychosis often occurs early on in the disease, and the early pathological changes include atrophy of the medial caudate, it is possible that the caudate may have a role as well.26
In Wilson's disease, psychosis is less common. In the series of 195 cases surveyed by Denning and Berrios,12 fewer than 2% of the patients had such symptoms. The most common problems among the 20% of patients with psychiatric disturbances were a mixture of behavioral disturbances ("incongruous behavior," recklessness, disinhibited behavior); poor school performance; personality changes; irritability; emotional lability; anxiety; anorexia nervosa; antisocial behavior; and alcohol abuse.27
Postencephalitic parkinsonism (PEP), which manifests with microscopic foci of inflammation in the gray matter and basal ganglia, may also present in a "psychotic form."28 This effect was first described in von Economo's 1929 classic paper.29 During the acute phase, the patient may present with acute confusion, depression, hypomania, catatonia, and psychosis, along with, or instead of, the more commonly recognized motor and ophthalmologic symptoms. The effects may have been a delirium rather than a "pure" psychosis. Chronic sequelae have been reported to include personality changes and a full range of schizophrenia-like presentations. Davison and Bagely30 found 15%–30% of a sample of 40 patients with PEP to have paranoid–hallucinatory psychoses. Another 10% of the same sample had symptoms indistinguishable from what was described as "dementia praecox" at the time.
Finally, Fahr's disease, or familial idiopathic calcification of the basal ganglia, a disorder characterized by parkinsonism or choreoathetosis, subcortical dementia, and focal cortical deficits such as dysphasia, may present with a psychosis. Cummings et al.31 identified two types of presentation. In early-onset cases, psychosis is a more common presenting feature, whereas in later-onset cases, motor and cognitive symptoms predominate. More recent reviewers, however, have disputed this assertion. Flint and Goldstein32 concluded that the schizophrenia-like presentations seen in Fahr's disease may simply be due to a chance association.
The new onset of psychotic symptoms, even in patients with basal ganglia disorders, should prompt a search for specific causes or precipitating factors. Such symptoms may be caused by mood disorders, delirium, substance intoxication, and withdrawal or medication effects, particularly if antiparkinsonian medications are being used. Psychosis could then result from either a hyperdopaminergic state or an anticholinergic delirium. Once these possibilities have been considered and excluded, therapy aimed specifically at the psychosis may be attempted.
The use of neuroleptics in basal ganglia disorders is complicated by the risk of worsening the underlying movement disorder. Small doses of high-potency neuroleptics, such as haloperidol and fluphenazine, are often used in mild-to-moderate cases of HD and other conditions such as Tourette's syndrome (TS), to suppress chorea and tics. Therefore, in the earlier phases of the illness, an agent targeting both hyperkinesis and psychotic symptoms may be preferable. In more advanced cases of HD and in other basal ganglia disorders, dystonia and parkinsonism is a more significant problem, and may be worsened by the high-potency agents. In these situations, the newer, "atypical" agents, such as olanzapine (Zyprexa), risperidone (Risperdal), or quetiapine (Seroquel) are generally better tolerated. In fact, the advent of the atypical antipsychotics has revolutionized the treatment of several of these disorders.
Attention must be paid to the development of tardive dyskinesia, because these superimposed movements may be difficult to tease out from the underlying movement disorder. Risperidone and olanzapine may also precipitate mania, particularly in those with vulnerable brains, (Leroi et al., unpublished) and quetiapine is sometimes excessively sedating. Finally, if the psychosis is refractory to treatment with neuroleptics and the patient poses a significant risk, ECT is an option. There has been one report of the use of ECT for psychosis in HD, and success with ECT in panic disorder with psychosis has also been reported.33,34
|
OBSESSIVE-COMPULSIVE DISORDER
|
Obsessive-compulsive disorder (OCD) has been reported in HD and is common in TS, another disorder in which basal ganglia pathology is implicated.35,36 Cummings and Cunningham, in 1992,35 reviewed several studies of patients with compulsive symptoms complicating neurologic disorders that affected the caudate nucleus and globus pallidus. The management of OCD in basal ganglia disorders should follow the same lines as treatment for idiopathic OCD, namely, with serotonergic antidepressants being the first line. Cognitive and behavioral psychotherapy may also be helpful, but cognitive impairment tends to limit their effectiveness. Patients may have difficulty understanding the treatment, and impulsiveness and memory impairment make it hard to build on previous successes.
|
AGGRESSION, IRRITABILITY, AND APATHY
|
Symptoms ranging from irritability to intermittent explosive anger have been reported in HD and Wilson's disease.12,16 Aggression is a common reason for psychiatric hospitalization in patients with HD.37 Irritability and aggression may be due to multiple causes, including personality changes accompanying HD, and other psychiatric disorders, such as depression, mania, and psychosis. Compared with a matched sample of patients with Alzheimer's disease, HD patients have been shown to be significantly more aggressive when measured on a scale of apathy and irritability.38 There did not seem to be any interrelationship among the variables of apathy, irritability, and aggression in this study, although a correlation between premorbid "bad temper" and irritability was seen in the HD group. One of the reasons for irritability in some basal ganglia disorders may be the development of "rigidity" of thinking. This trait causes patients to perseverate relentlessly on a particular desire or idea, resulting in outbursts when perceived needs are not met.
The key to management of aggression and irritability is to place each in its proper context, and to detect and avoid precipitants. This step will prevent premature use of medications. Factors that may precipitate an irritable episode include hunger, thirst, pain, inability to communicate, frustration with failing abilities, boredom, and an unexpected change in routine.38 If there is a potential for violence, or if conservative measures fail, there are several medication options. Important treatment principles include focusing on reversing the underlying cause of the symptom and frequent medication reviews, thus avoiding enduring treatment for what is usually an episodic symptom.
Although there are no published studies of efficacy of psychotropic medication in HD-related aggression and irritability, clinical experience has shown that antipsychotics, mood stabilizers, and antidepressants may be helpful. Mood stabilizers may be more effective in cases in which the irritability appears to have an affective basis, and antipsychotics may have limited efficacy in cases in which there is no psychosis.39 In our clinical experience, the SSRIs are among the most helpful agents for these problems, perhaps because of their frontal activity. There are also several reports of the efficacy of beta-blockers in the treatment of aggression in HD.40–43 These are generally well tolerated, although there have been two descriptions of paradoxical aggression.42,44 Side effects of hypotension and bradycardia may complicate the use of propranolol, but pindolol, a partial beta-agonist, seems to be relatively safe in this regard.43 Doses must be individually titrated, and contraindications to use, such as bronchospastic disease and congestive heart failure, must be noted. There have been no reports of the worsening of the movement disorder with beta-blockers. Also, there is some evidence to support the use of the SSRIs, clomipramine, clonazepam, and hydroxyzine for use in HD-related aggression.38
In addition to irritability and aggression, apathy is often noted as part of the "personality change" that occurs with the progression of HD. In the aforementioned sample of HD patients, apathy was detected in up to 48%.37 Apathy may be secondary to depression or the use of antipsychotic medications, but often takes the form of an independent symptom. Apathy may manifest as withdrawal from social situations, decreased initiative and motivation, and a disregard for personal hygiene and appearance.16 This symptom has also been called "situational apathy," because it tends to improve in structured or stimulating environments.45 There are few specific treatments for apathy. In many cases, the best response is to educate the patient's family about this symptom and to avoid conflict over minor issues. When the apathy is severe, however, a number of agents have been useful in our experience, including SSRIs, amphetamines, and dopaminergic agents, such as amantadine and bromocriptine. These latter agents may worsen chorea in some disorders.
|
DELIRIUM
|
Delirium is common in HD and the other basal ganglia disorders. Patients in the later stages of these conditions may have severely aberrant movements, which can impede mobility and oral intake. Hence, patients are particularly vulnerable to delirium resulting from volume depletion, poor nutrition, medical complications, metabolic disturbances, and medication effects. Delirium is often multifactorial. For example, a patient who is no longer able to swallow may become volume-depleted and therefore more vulnerable to toxicity from his or her medication. Respiratory infections and, particularly, urinary tract infections should be ruled out, as they are a frequent cause of delirium in these patients.
Delirium often mimics other psychiatric disturbances. It may be accompanied by hallucinations, paranoia, or mood lability. Both the hyperaroused, as well as the more somnolent obtunded manifestations of delirium should be recognized. The latter is often mistaken for depression, but, when questioned carefully, the patient will not report a low mood.
In the management of any acute change in mental status, a full medical workup and review of medications is indicated. The definitive treatment for a delirium is reversal of the underlying cause. However, low doses of neuroleptics may be helpful in the short-term management of a patient who is agitated because of the delirium.
|
SEXUAL DISORDERS
|
Changes in sexuality have been well documented in HD. Disorders of sexual functioning, such as hypoactive sexual desire and inhibited orgasm, have been reported in men, with rates of 63% and 56%, respectively.46 In female patients, 75% had hypoactive sexual desire, and 42% had inhibited orgasm. Also, sexual aberrations, such as sexual assault, promiscuity, incest, indecent exposure, and voyeurism, have all been described in HD.37,47 The etiology of these abnormalities may be related to specific psychiatric syndromes prevalent in HD, such as mania, to the underlying neurotransmitter deficits of HD, or to medication effects.24 There is some evidence that male HD patients with both inhibited orgasm and increased sexual interest are at higher risk for developing paraphilias.47
There have been no studies systematically examining the management of inappropriate sexual behaviors in patients with HD. Treating an underlying psychiatric condition, such as a depression, may ameliorate the sexual symptoms. A short trial of an antipsychotic may also be useful. If these measures fail, treatment with an antiandrogen agent, such as leuprolide acetate, can be attempted. Leuprolide is a gonadotropin-releasing hormone agonist, which may help eliminate deviant sexual behavior without the high rate of side effects seen with the use of medroxyprogesterone acetate.
|
CONCLUSIONS AND DISCUSSION
|
We have sought to make several facts clear: that the basal ganglia disorders are neuropsychiatric disorders, that they have certain features in common, and that the psychiatric disturbances are amenable to rational treatment. In attempting such treatment, the clinician must overcome obstacles at every step of the process. Psychiatric problems in patients with basal ganglia disorders can be difficult to diagnose. Difficulties with communication and self-reporting can obscure symptoms, which, in any case, may not fit precisely into the more commonly recognized psychiatric syndromes. Once treatment is started, these patients are particularly vulnerable to the side effects of medication, including delirium and worsening of movement problems, which may limit the benefits of treatment. Language difficulties and a declining baseline can make it difficult to assess the efficacy of therapy. Sometimes the greatest obstacles are the attitudes of doctors, families, and society at-large. Successful psychiatric treatment must begin with a refusal to regard these cases as hopeless or to see depression as "normal." Once this change in perception is achieved, a methodological approach, beginning with a careful history and taking the special features of these diseases into account, can spell the difference between adaptation and despair.
|
REFERENCES
|
- Huntington G: On chorea. Medical and Surgical Reports of Philadelphia 1872; 26:317–321
- McHugh PR: The neuropsychiatry of basal ganglia disorders: a triadic syndrome and its explanation. Neuropsychiatry Neuropsychol Behav Neurol 1989; 2:239–247
- Ross ED, Rush JA: Diagnosis and neuroanatomical correlates of depression brain-damaged patients: implications for a neurology of depression. Arch Gen Psychiatry 1981; 38:1344–1354
- Folstein SE, Chase G, Wahl W, et al: Huntington's disease in Maryland: clinical aspects of racial variation. Am J Hum Genet 1987; 41:168–179[Medline]
- Folstein SE: Huntington's Disease: A Disorder of Families. Baltimore, MD, Johns Hopkins University Press, 1989
- Shoenfield M, Myers RH, Cupples RA, et al: Increased rate of suicide among patients with Huntington's disease. J Neurol Neurosurg Psychiatry 1984; 47:1283–1287
- Vonsattel JP, Meyers RH, Stevens TJ, et al: Neuropathological classification of Huntington's disease. J Neuropathol Exp Neurol 1985; 44:559–577[Medline]
- Alexander GE, DeLong MR, Strick PL: Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Ann Rev Neurosci 1986; 9:357–381[CrossRef][Medline]
- Cummings JL: Frontal-subcortical circuits and human behavior. Arch Neurol 1993; 50:873–880[Abstract/Free Full Text]
- Mayberg HS, Starkstein SE, Peyser CE, et al: Paralimbic frontal lobe hypometabolism in depression associated with Huntington's disease. Neurology 1992; 42:1791–1797
- Baxter LR, Mazziotta JC, Pahl JJ, et al: Psychiatric, genetic, and positron emission tomographic evaluation of persons at risk for Huntington's disease. Arch Gen Psychiatry 1992; 49:148–152[Abstract/Free Full Text]
- Denning TR, Berrios GE: Wilson's disease: psychiatric symptoms of 195 cases. Arch Gen Psychiatry 1989; 46:1126–1134
- Schneider LS, Chui HC: Progressive supranuclear palsy manifesting with depressive features. J Am Geriatric Soc 1986; 34:663–665[Medline]
- Ranen NG, Peyser CE, Folstien SE: ECT as a treatment for depression in Huntington's disease. J Neuropsychiatry 1994; 6:154–158[Abstract/Free Full Text]
- Figiel GS, Krishna KR, Doraiswamy PM: Subcortical structural change in ECT-induced delirium. J Geriatr Psychiatry Neurol 1990; 3:172–176
- Mendez MF: Huntington's disease: update and review of neuropsychiatric aspects. Int J Psychiatry Med 1994; 24:189–208[Medline]
- Litvan I, Mega MS, Cummings JL, et al: Neuropsychiatric aspects of progressive supranuclear palsy. Neurology 1996; 47:1184–1189
- Lyketsos CG, Schwartz J, Fishman M, et al: AIDS mania. J Neuropsychiatry Clin Neurosci 1997; 9:277–279[Abstract/Free Full Text]
- Pantelis C, Barnes TRE, Nelson HE: Is the concept of frontal-subcortical dementia relevant to schizophrenia? Br J Psychiatry 1992; 160:442–460[Abstract/Free Full Text]
- Caligiuri MP, Lohr JB, Jeste DV: Parkinsonism in neuroleptic-naïve schizophrenic patients. Am J Psychiatry 1993; 150:1343–1348
- Bolt JMW: Huntington's chorea in the west of Scotland. Br J Psychiatry 1970; 116:259–270[Abstract/Free Full Text]
- Morris M: Psychiatric aspects of Huntington's disease, in Huntington's Disease: Major Problems in Neurology. Edited by Harper PS. London, UK, Saunders, 1991, pp 81–126
- Brooks DS, Murphy MP, Janota I, et al: Early onset Huntington's chorea: diagnostic clues. Br J Psychiatry 1987; 151:850–852[Abstract/Free Full Text]
- Cummings JL: Behavioral and psychiatric symptoms associated with HD, in Advances in Neurology, Vol 65. Edited by Weiner WJ, Lang AE. New York, Raven, 1995, pp 179–186
- Kuwert T, Lange HW, Langen K-J, et al: Cerebral glucose consumption measured by PET in patients with and without psychiatric symptoms of Huntington's disease. Psychiatr Res 1989; 29:361–362[CrossRef][Medline]
- Cummings JL: Psychosis in basal ganglia disorders, in Mental Dysfunction in Parkinson's Disease. Edited by Wolters Ech, Scheltens P. Amsterdam, The Netherlands, Vrije Universiteit Amsterdam, 1993, pp 257–268
- Scheinberg I, Sternlieb I: Wilson's Disease. Philadelphia, PA, WB Saunders, 1984, pp 86–91
- Lishman A: Organic Psychiatry: The Psychological Consequences of Cerebral Disorder, 3rd Edition. Oxford, UK, Blackwell Science Ltd, 1998, pp 349–356
- Von Eonomo C: Encephalitis lethargica: its sequelae and treatment. (First published in 1929.) Translated by Newman KO. Oxford, UK, Oxford University Press, 1931
- Davison K, Bagley CR: Schizophrenia-like psychoses associated with organic disorders of the central nervous system: a review of the literature, in Current Problems in Neuropsychiatry, edited by Herrington RN. Br J Psychiatry Special Publication, No. 4. London, UK, Ashford, Kent, Headley Brothers, 1969
- Cummings JL, Gosenfeld LF, Holihan JP, et al: Neuropsychiatric disturbances associated with idiopathic calcification of the basal ganglia. Biol Psychiatry 1983; 18:591–601[Medline]
- Flint J, Goldstein LH: Familial calcification of the basal ganglia: a case report and review of the literature. Psychol Med 1992; 22:581–595[Medline]
- Evans DL, Pedersen CA, Tancer ME: ECT in the treatment of organic psychosis in Huntington's disease. Convuls Ther 1987; 3:145–150[Medline]
- Hurwitz TA, Calne DB, Waterman K: Treatment of dopamino-mimetic psychosis in Parkinson's disease with electroconvulsive therapy. Can J Neurol Sci 1988; 15:32–34[Medline]
- Cummings JL, Cunningham K: Obsessive-compulsive disorders in Huntington's disease. Biol Psychiatry 1992; 31:263–270[CrossRef][Medline]
- Kurlan R: Tourette's syndrome: current concepts. Neurology 1989; 39:1625–1630
- Dewhurst K, Oliver JE, McKnight AL: Socio-psychiatric consequences of Huntington's disease. Br J Psychiatry 1970; 116:255–258[Abstract/Free Full Text]
- Burns A, Folstein S, Brandt J, et al: Clinical assessment of irritability, aggression, and apathy in Huntington's disease and Alzheimer's disease. J Nerv Ment Dis 1990; 178–206
- Rosenblatt A, Ranen N, Nance MA, et al: A Physician's Guide to the Management of Huntington's Disease, 2nd Edition. New York, Huntington's Disease Society of America, 1999
- Stewart JT, Mounts ML, Clark RL: Aggressive behavior in Huntington's disease: treatment with propanolol. J Clin Psychiatry 1987; 48:106–108[Medline]
- Stewart JT: Huntington's disease and proponolol. Am J Psychiatry 1993; 150:166–167[Free Full Text]
- Stewart JT: Paradoxical aggressive effect of propanolol in a patient with Huntington's disease (letter). J Clin Psychiatry 1987; 48:25–26[Medline]
- Greendyke RM, Kanter DR: Therapeutic effects of pindolol on behavioral disturbances associated with organic brain disease: a double-blind study. J Clin Psychiatry 1986; 47:423–426[Medline]
- Van Hafften AH, Jensen CF: Paradoxical response to pindolol treatment for aggression in a patient with Huntington's disease (letter). J Clin Psychiatry 1989; 50:230[Medline]
- Caine ED, Shoulson I: Psychiatric syndromes in Huntington's disease. Am J Psychiatry 1983; 140:728–733[Abstract/Free Full Text]
- Fedoroff JP, Peyser C, Franz ML, et al: Sexual disorders in Huntington's disease. J Neuropsychiatry Clin Neurosci 1994; 6:147–153[Abstract/Free Full Text]
- Oliver JE: Huntington's chorea in Northamptonshire. Br J Psychiatry 1970; 116:241–253[Abstract/Free Full Text]
This article has been cited by other articles:
|
|
|
|
 
E. van Duijn, E.M. Kingma, and R.C. van der Mast
Psychopathology in Verified Huntington's Disease Gene Carriers
J Neuropsychiatry Clin Neurosci,
November 1, 2007;
19(4):
441 - 448.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Rosenblatt
Understanding the psychiatric prodrome of Huntington disease
J. Neurol. Neurosurg. Psychiatry,
September 1, 2007;
78(9):
913 - 913.
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Zinzi, D. Salmaso, R. De Grandis, G. Graziani, S. Maceroni, A. Bentivoglio, P. Zappata, M. Frontali, and G. Jacopini
Effects of an intensive rehabilitation programme on patients with Huntington's disease: a pilot study
Clinical Rehabilitation,
July 1, 2007;
21(7):
603 - 613.
[Abstract]
[PDF]
|
|
|
|
|
|
|
R. Vataja, A. Leppavuori, T. Pohjasvaara, R. Mantyla, H. J. Aronen, O. Salonen, M. Kaste, and T. Erkinjuntti
Poststroke Depression and Lesion Location Revisited
J Neuropsychiatry Clin Neurosci,
May 1, 2004;
16(2):
156 - 162.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H A Ring and J Serra-Mestres
Neuropsychiatry of the basal ganglia
J. Neurol. Neurosurg. Psychiatry,
January 1, 2002;
72(1):
12 - 21.
[Abstract]
[Full Text]
[PDF]
|
|
|
Get information about faster international access.
Privacy Policy
Copyright © 2000
Academy of Psychosomatic Medicine.
All rights reserved.
Home
| Search
| Current Issue
| Past Issues
| Subscribe
| All APPI Journals
| Help
| Contact Us
|
TOP
ABSTRACT
INTRODUCTION
