Asperger

General Hospital Psychiatry 23 (2001) 285–293

Emergency Psychiatry in the General Hospital The emergency room is the interface between community and health care institution. Whether through outreach or in-hospital service, the psychiatrist in the general hospital must have specialized skill and knowledge to attend the increased numbers of mentally ill, substance abusers, homeless individuals, and those with greater acuity and comorbidity than previously known. This Special Section will address those overlapping aspects of psychiatry, medicine, neurology, psychopharmacology, and psychology of essential interest to the psychiatrist who provides emergency consultation and treatment to the general hospital population.

Asperger’s disorder in the emergency psychiatric setting Michele Raja, M.D.*, Antonella Azzoni, M.D. Dipartimento di Salute Mentale, Ospedale Santo Spirito, Rome, Italy

Abstract Asperger’s syndrome (AS) is a pervasive developmental disorder that may be unrecognized, especially if signs of other psychiatric disorders coexist. The objectives of this paper are: 1) to ascertain the prevalence of AS in the emergency psychiatric setting; and 2) to describe features of AS which may help to differentiate these patients from patients with psychotic disorders. Among 2500 patients admitted to a psychiatric intensive care unit, 5 (0.2%) received a diagnosis of AS, for the first time. Besides impairment of social interaction, common features were the following: male gender, left handedness, obsessive-compulsive symptoms, cognitive hyper-abilities, violent behavior, sense of humor, low WAIS total score, high WAIS verbal/performance score ratio, unusual, restricted interest and clumsiness. Comorbid schizophrenia is difficult to rule out in these patients. Psychotic symptoms should not be overvalued in making the diagnosis when specific features of AS are present. © 2001 Elsevier Science Inc. All rights reserved. Keywords: Asperger’s disorder; Autism; Psychotic disorders; Diagnosis; Psychiatric emergency

1. Introduction Autism is a behaviorally defined syndrome characterized by deficits in cognitive and social functioning and by ritualistic and compulsive behaviors. It begins in infancy or early childhood and may be associated with rare diseases, whose etiologic role is unclear. The condition was described almost simultaneously by Kanner in Baltimore (in 1943) and Asperger in Vienna (in 1944). Kanner reported the observation of exceptional children who appeared to be asocial, lacking in communicative skills both verbal and nonverbal, and committed to repetitive ritualistic behaviors. He ascribed the condition to psychosocial factors. Asperger observed somewhat older children, less severely affected and ascribed the condition to metabolic abnormalities. In the decades since, opinion varied as to the relationship between the severe Kanner syndrome and the less severe Asperger syndrome. In the last years, Asperger’s syndrome (AS), considered

* Corresponding author. Tel.: ⫹39-065898721; fax: ⫹39-065898721. E-mail address: [email protected] (M. Raja).

a pervasive developmental disorder (PDD), was introduced as a new diagnostic category in the ICD-10 and the DSMIV. It refers to people with autistic, odd and eccentric behavior but well-developed language skills. However, the speech of Asperger individuals is often characterized as tangential, pedantic, repetitive, or one-sided [1]. Probably, the syndrome Hans Asperger originally described may not be captured by present diagnostic DSM-IV or ICD-10 criteria. Within PDDs, DSM-IV identifies 5 subgroups. However, the diagnosis of the different subgroups is difficult to establish, particularly between Autistic Disorder and AS. According to ICD-10, AS is characterized by an impairment of reciprocal social interaction, a lack of general delay in language or cognitive development and restricted patterns of behavior and interests. Although AS has been included in the ICD-10 as a distinct category, it is still unclear to what extent it differs from high functioning autism (HFA) [2–5]. Furthermore, there is no consensus about the validity and the diagnostic boundaries of other disorders characterized by similar symptoms, including Nonverbal learning disability, Developmental Gerstmann syndrome, right hemisphere syndrome, and right parietal lobe syndrome.

0163-8343/01/$ – see front matter © 2001 Elsevier Science Inc. All rights reserved. PII: S 0 1 6 3 - 8 3 4 3 ( 0 1 ) 0 0 1 5 5 - 4

286

M. Raja, A. Azzoni / General Hospital Psychiatry 23 (2001) 285–293

Typically, patients with AS have characteristics such as motor clumsiness, pedantic speech, eccentricities, emotional lability, anxiety, poor social functioning, impulsivity, intrusive repetitive behavior and fixed habits that can mimic symptoms of other illnesses, including schizophrenia, bipolar disorder, anxiety disorder and obsessive-compulsive disorder (OCD). Their disorganizing anxiety in response to stress, which may be accompanied by increased oddness of speech, can easily be misinterpreted as psychosis [6]. Only a small proportion of patients with childhood autism lead independent adult lives. Most subjects affected by severe forms of autism live in institutions and are unlikely to attend services of general psychiatry. Other patients with so-called HFA or AS improve enough to live independent adult life. These subjects may come in contact with general psychiatry services in case of exacerbations of their illness or other neuropsychiatric comorbid disorder. The first case of AS we admitted to our ward raised a diagnostic controversy among staff members that prompted us to focus attention on the syndrome. Since then, we prospectively searched for similar cases among patients admitted to our Psychiatric Intensive Care Unit (PICU). The objectives of this paper are: 1) to ascertain the prevalence of AS in a PICU; and 2) to describe the features of AS which may help to differentiate these patients from patients with psychotic disorders.

2. Case reports As part of standard clinical care on the PICU, we ascertained basic characteristics for each admitted patient as follows: sex, age, years of education, employment, marital status and social class. Psychopathology was assessed using the Brief Psychiatric Rating Scale [7], the Scale for the Assessment of Positive Symptoms [8], the Scale for the Assessment of the Negative Symptoms [9], the Mini Mental State Examination (MMSE) [10] and the Global Assessment of Functioning Scale (GAF) [11]. Neurological examination included the use of the Abnormal Involuntary Movement Scale (AIMS) [12], the Unified Parkinson’s Disease Rating Scale (UPDRS) [13] and the Barnes Akathisia Scale [14]. We made psychiatric diagnoses according to DSM-IV. At the end of each individual clinical evaluation, we met to formulate consensus diagnoses. We found 5 patients affected by AS whose features we describe herein. 2.1. Case 1 A 33-year-old man, who had received a diagnosis of early onset psychosis, was referred for evaluation of his psychiatric disorder and of a severe polydipsia-polyuria syndrome. The case has already been published for the association of autistic-spectrum disorder, empty sella, neurogenic diabetes insipidus and primary polydipsia [15]. There was no family history of endocrine or psychiatric

disorders. His delivery at term was uneventful, except for a prolonged labor. In early childhood, his parents noted speech delay, left-handedness and impairment in social interaction, stereotypies, clumsy movements, enuresis and polydipsia. The patient had an extravagant interest in a little puppet. Visual memory and mathematical intuitions were prodigious. Attention and concentration were poor. In early teens, an unusual interest in horror films appeared, while polydipsia, polyuria and nocturia continued to be present. At age 15, his psychiatric symptoms were bizarre ideation on themes of horror, sexuality and persecution, obsessions of violence and stereotyped behavior. Because of social withdrawal, abnormal ideas and hostility against his parents, the patient started neuroleptic treatment with moderate improvement. Polydipsia worsened up to 15–20 L/day. A magnetic resonance imaging (MRI) study demonstrated an empty sella and a normal brain; in the T1-weighted MRI sagittal image, the hyperintense signal denoting a normal neurohypophysis was absent. At age 31, the patient rejected his parents claiming they were not his mother and his father. He menaced them with a knife and it was necessary to call police. Other episodes of aggression were directed against unknown people with bizarre explanations (“I think it my duty to assault people practicing martial arts”). In the last years, a tendency to overturn normal rhythms of daily life, in particular the sleep-wake cycle, had replaced the propensity to violent behavior. Curiously, he was exceedingly able to imitate famous actors. On admission, neuroleptics were withdrawn. The patient had a high school diploma and intermittently worked as a clerk in a public institution. The neurological examination was normal, however, he was clumsy, uncoordinated, had a poor gait, and presented trunk swinging. The Wechsler Adult Intelligence Scale (WAIS) revealed an I.Q. of 79 (verbal: 96; performance: 59). Psychiatric examination revealed bizarre ideas (“I want to drink the ocean”), motor stereotypies, fatuous attitude, unreasonable insistence on particular subjects and a special interest in knives. The patient seemed over-concerned to the policewomen and asked bizarre questions on that theme (“Are they armed with pistol?”, “Do they ride?”). Bizarre persecutory delusions were also present. He claimed he had declared war on the world in the past years and, for that reason, a policewoman had sent some birds to devour him. 2.2. Case 2 A 20-year-old boy with a diagnosis of “paranoid disorder with obsessive-compulsive ideation” was referred to our ward because of violent behavior against his relatives. In the previous days, the patient had been taking risperidone 1 mg/day, thioridazine 50 mg/day, and chlor-demetil-diazepam 20 mg/day. There was no family history of psychiatric disorder. Two patient’s siblings were affected by adrenal insufficiency and abnormal sexual development (inherited deficiency of 21-␣-hydroxylase). The patient’s delivery at term was uneventful and psychomotor development was

M. Raja, A. Azzoni / General Hospital Psychiatry 23 (2001) 285–293

normal, without any delay in language development. At school, outcomes had been poor. Since early childhood, he appeared introverted and disinclined to relationships. He had been exempted from military service with a diagnosis of OCD. In the past, several attempts to get a job had been useless and the patient was currently unemployed. From the age of 19 years, he had presented obsessive-compulsive symptoms with continuous demanding answers to his relatives to be reassured. Thereafter, behavioral disturbances took on a more dramatic form, reminiscent of psychosis. His parents reported: 1) prodigious memory that enabled the patient to recall single words or punctuation marks through many printed pages; 2) difficult relationships with same age children; 3) intolerance of any remark; 4) motor clumsiness and motor stereotypies (trunk swinging); 5) resistance to and distress over trivial changes in his environment; 6) unusual and restricted interest in the comic-strip magazine “Dylan Dog,” with systematic collection of magazines, deep knowledge of technical data, biography of the authors and of the publishers; 7) obsessive-compulsive thoughts; and 8) excellent sense of humor and unusual capacity to grasp the double meaning of words. On admission, circumstantiality and obsessive rumination were evident. The patient was lucid and fully oriented. He showed resistance to complying with treatment. Thought was simple and poor of content. Persecutory and reference delusions were present, as well as depression of mood with anxiety, tendency to bursts of weeping and occasional suicidal thoughts. The patient reported auditory hallucinations whose content he was not able (or refused) to declare. Emotional withdrawal was severe and emotional range diminished. The patient had neither friends nor job, interests or hobbies. He emphasized his willingness to agree and live sociably with other people. However, also in the hospital, he did not get along with other patients, and reported to be lost in suicidal thoughts when people shunned him. MMSE score was 28. Neurological examination revealed left-handedness, moderate akathisia, akinesia and tremors. He was clumsy and uncoordinated. Primary and secondary sexual features were normal. Mild gynecomastia was noted, possibly due to past neuroleptic treatment. Brain computed tomography (CT) with contrast enhancement, electroencephalogram (EEG), echography of adrenal glands and routine laboratory tests were normal. The WAIS revealed an I.Q. of 73 (verbal: 84; performance: 62). We planned to raise risperidone daily dose, withdrew thioridazine and benzodiazepines, and started valproate up to 1000 mg/day. Marked parkinsonian tremor and hypersalivation became evident when risperidone daily dose grew up to 5 mg. Therefore, we withdrew this drug and started olanzapine, 10 mg/day. Three weeks later, the patient was discharged. On discharge, depression, anxiety and persecutory ideation were improved, while hallucinations were no longer present. The patient was more capable of interaction, appeared aware of his disorder, and was able to criticize his behavior with humor (“I my self do not tolerate my querulousness”).

287

2.3. Case 3 (“Agostino”) A 42-year-old man with a diagnosis of “residual schizophrenia” was admitted because of re-emergence of acute symptoms and violent behavior against his mother. There was no family history of psychiatric disorders but an episode of senile depression in his grandmother. The patient’s delivery at term was precipitous and psychomotor development was normal. The patient began to speak when he was 12–18 months old and since early childhood the patient’s movements were clumsy. Encopresis was noted. In the first years of elementary school, the patient was lively, extroverted and sociable. In the following years, he showed impaired social interaction with his fellows, while he was capable of relationship with adult people. Paradoxically, in his relationship with adults, he appeared particularly nice, jocular and facetious. He depended on his brother and had no friends or hobbies but only a strong interest in sport. When he had to make even trivial choices (e.g., to buy or not to buy a magazine, to go shopping or not), he remained in doubt as to what to do, even for hours. From the age of 14 years, he became mute and disinclined also to nonverbal communication. He maintained an absolute silence for two years, although there was evidence that he was able to understand. He was passive and used to shut himself in the bathroom and to stay there all day. Afterwards, he gradually began to talk again. He was treated with neuroleptic medication for 3 years and with electroconvulsive therapy, without benefit. In the following years, other periods of taciturnity were observed. He was admitted to several neuropsychiatric hospitals. From the age of 17 years, he presented religious delusions. Then, for the first time, he presented violent behavior. After the onset of these symptoms, behavioral disturbances took on a more severe form with psychotic symptoms. During this period, he had been treated with haloperidol decanoate (100 mg/30 days) and lorazepam (2.5 mg/day). On visit, the patient appeared lucid, oriented, quiet and cooperative. His attitude was jovial, pleased, delighted and with a contented smile. He tended to repeat interlocutor’s questions and to answer both in the affirmative and in the negative to the same question. Thought reading and withdrawal and auditory hallucinations were noted. When we asked him to write a sentence during the MMSE, he wrote a bizarre phrase in Latin [“Ego sum Agostinianum” (his Latinized first name)]. Likewise, his modalities of communication were bizarre and awkward. No mood deviation was present. While social functioning was endangered, affective flattening was mild. He was repeatedly able to make everybody laugh with his inventive remarks. In the ward, the patient’s behavior was never violent. On neurological examination, the patient was left-handed, slow, clumsy, with stereotypies (trunk swinging, touching of genitals, echolalia), and a Parkinsonian tremor, more evident on right. Body

288

M. Raja, A. Azzoni / General Hospital Psychiatry 23 (2001) 285–293

schema disorder was also evident. MMSE score was 25, with discrepancy between good results in arithmetic and bad results in memory and picture tasks. The WAIS revealed an I.Q. of 46 (verbal: 55; performance: 40). Brain CT with contrast enhancement revealed localized right parietal cortical atrophy. We withdrew antipsychotic medication, treated the patient with lorazepam (2.5 mg/day), and discharged him slightly improved.

which were judged to be caused by misunderstanding of people’s facial emotional expressions; 2) obsessions and compulsions (e.g., cleaning his teeth for many hours); 3) memory talent, which contrasted with poor general intellectual functioning; 4) fine sense of humor; 5) unusual capability to mimic; and 6) behavior different in disparate contexts. That prompted us to change our original diagnosis in AS.

2.4. Case 4

2.5. Case 5

An 18-year-old was admitted for behavioral disorder. In the past, his father had been admitted to our ward several times for episodes of schizoaffective disorder, mixed type. The patient’s psychomotor development was normal. In early childhood, the patient had difficult relationships with his schoolmates. He tended to remain alone, to divert his mind, to excessive food intake and to stereotyped behavior. Meanwhile, the patient’s relationship with his father was good, characterized by exchanges of cultural and philosophical views. At the age of 12–14 years, his school efficiency was good. In the same period, obsessive-compulsive traits and over-valued religious ideas first appeared. At the beginning of his junior high school, he left the school, shut himself up in his house, and fed poorly. He refused to take thioridazine prescribed by a psychiatrist who had made the diagnosis of “catatonic schizophrenia” and “anorexia nervosa.” At the age of 16 years, there had been several episodes of coprophagy. Then, he was repeatedly admitted to a University Neuropsychiatric Institute for Children, received a diagnosis of Schizotypal Personality Disorder and was treated with haloperidol, risperidone and fluoxetine. On admission, the patient was mute, inexpressive, unreactive and with no eye contact. He spent his time engaged in mannerisms and stereotyped behaviors such as touching his beard, twiddling his temples, walking backwards and forwards or swinging. Neurological examination was normal, however, his movements were clumsy. We noted affective incongruity and flattening, emotional withdrawal, conceptual disorganization and echolalia. The patient often referred to himself as a third person. The presence of persecutory delusions and sporadic auditory hallucinations was uncertain. No mood alteration was present. MMSE score was 24. The WAIS revealed an I.Q. of 73 (verbal: 77; performance: 71). Brain CT with contrast enhancement was normal. The patient was treated with olanzapine— up to 15 mg/day—for thirty days, with minimal improvement and then switched to risperidone— up to 4 mg/day—with moderate improvement. Forty days after admission, the patient was discharged with a diagnosis of disorganized schizophrenia and referred to a therapeutical community in order to provide a rehabilitative support. At present, the patient is still in this center. In the last two years, the following features had been noted by the staff: 1) violent episodes,

A 31-year-old was admitted for violent behavior against his unmarried mother, affected by epilepsy with abnormal personality. No information was available about his father. The patient’s delivery at term was uneventful and his psychomotor development was normal. Although his mother reported “good school outcomes”, the patient had had to repeat a year at school. He had got a secondary school certificate of education. Since early childhood, he appeared introverted and disinclined to relationships. He had no contact with anyone but with his grandfather (when this was alive) and his mother. On visit, the patient was mute and appeared sad. His face was dysmorphic. Speech was slow, monotonous, with repetitions of sentences, almost unintelligible, repetitive, and pedantic. His movements were clumsy. He looked at people out of the corner of his eye, with his head lowered, and stereotyped movements of his arms and hands. Facial expression showed alternating of obsequious and submissive attitude with aggressiveness, related to specific themes and contexts. Notwithstanding his social isolation and inability to function in almost all areas, the patient was abnormally interested in the study of economics, spending a disproportionate amount of his time reading books of economics. Also patient’s sexual interest seemed out of proportion to his aloneness and emotional withdrawal. Furthermore, the demand of getting married and the risk of remaining out of work because of his hospitalization were perpetual obsessions for him. He denied hallucinations. Persecutory ideas were present and blunted affect and emotional withdrawal were severe. Although the patient sometimes felt guilty about injures to his mother, he minimized the seriousness of his violent behavior. Endlessly, he repeated the same demands or remarks, without considering other people’s attitudes and seemed unaware that his stereotyped and repetitive behavior was excessive and unreasonable. During hospitalization, he tended to remain alone, and did not show interest in getting in touch with anybody. Brain CT with contrast enhancement revealed enlargement of cortical sulci and ventricles. An EEG showed unstable, diffuse theta activity (6 –7 Hz). We made a diagnosis of schizoaffective disorder depressive-type and treated him with risperidone (up to 5 mg/day) and paroxetine (20 mg/day) with moderate improvement. Six, and 18 months later, the patient, who had stopped taking drugs, was admitted for new episodes of violence against his mother.

M. Raja, A. Azzoni / General Hospital Psychiatry 23 (2001) 285–293

During his second hospitalization, he reported sporadic mild auditory and visual hallucinations. Otherwise, his clinical condition was unchanged. We made a diagnosis of schizophrenia and restarted treatment with risperidone (up to 5 mg/day). One year later, the patient was again admitted after an assault against his mother, blamed for having not found a wife for him. As in previous occasions, the patient had gone off treatment. His clinical symptoms were similar but no hallucination was reported in this circumstance. The WAIS revealed an I.Q. of 88 (verbal: 94; performance: 81). As a result of our increased experience with AS, we hypothesized a diagnosis of AS since the patient satisfied the following DSM-IV criteria: 1) abnormal nonverbal behaviors regulating social interaction; 2) failure to develop peer relationships appropriate to developmental level, since childhood; 3) no interest in other people; 4) lack of social or emotional reciprocity; 5) abnormal interest in the study of economics, unrelated to his real life; and 6) stereotyped and repetitive motor mannerisms. Furthermore, some associated features of AS were present: 1) motor clumsiness; 2) obsessive symptoms; pedantic speech; low I.Q., with verbal I.Q. higher than performance I.Q. score.

3. Discussion

289

and had been treated by several professionals. However, none of them had been recognized as affected by PDD. Sometimes it is difficult to differentiate between the spectrum of autistic syndromes and psychotic disorders. A longitudinal observation may be necessary to distinguish these different nosological entities [20]. Diagnosis of AS may be delayed until adult age [21]. We misdiagnosed the fourth patient as affected by schizophrenia during his hospitalization, because of his muteness and social withdrawal, and made the correct diagnosis several months later when we listened to a clinical report of the staff of the therapeutic community about patient’s behavior. As regards the fifth patient, we revalued our previous diagnosis because of our increased experience with AS. Invariably, the diagnosis of AS we made for the first time had a strong impact on the patients and, even more, on their relatives. Most of them seemed to calm down when they recognized the clinical features of AS in their relatives and could conceptualize symptoms and behavior in term of a rather specific biologically based disorder instead of a heterogeneous protean disorder such as schizophrenia, still perceived by some of them as a mysterious and ominous madness. As Gillberg [22] states, “it is usually very helpful from the psychological point of view in helping families come to terms with the fact that their child is handicapped. The association of autism with— even unspecific— brain dysfunction makes the handicapping condition less mysterious.”

3.1. Diagnosis 3.2. Male sex In these patients, a pattern of deficits in social interaction and in the use of language, motor awkwardness, discrepancies between verbal and performance cognitive abilities, restricted outstanding cognitive abilities (especially memory talent, good capability to mimic, sense of humor), clumsiness, stereotyped movements and unusual, circumscribed interest are consistent with a diagnosis of AS. Since there are different diagnostic criteria for AS, HFA and Pervasive developmental disorder not otherwise specified, an intrinsic diagnostic ambiguity exists in our patients that reflects the standards of diagnosis in naturalistic setting and reflects the current controversy over the AS diagnosis. AS differs from one investigator to another [1, 16 –19, ICD-10, and DSMIV], thereby making the interpretation of research findings difficult. Among nearly 2500 patients admitted to our unit, 5 received a diagnosis of AS. That points to a low prevalence (0.2%) in the population admitted to PICU. As in all nonepidemiological studies, the sample may not be representative for AS. These patients presented symptoms and behavioral disturbances reminiscent of psychotic disorder and were referred to psychiatrists practiced in psychopathology of adult people. Given the low prevalence in the population of patients referred to general psychiatry services, and the co-occurrence of psychotic or obsessive-compulsive symptoms, it is not surprising that the diagnosis of AS may be unrecognized. These patients had been ill for many years

All patients admitted to our ward, who received an AS diagnosis, were male. This could be due not only to the prevalence of autism spectrum disorders higher in males [23–26] but also to a referral bias. Patients with behavioral disorder are more likely to be admitted to a PICU, especially in case of violent behavior. Coeteris paribus, men’s violent behavior raises more concern, is less tolerated, and more often leads patients to hospital admission. 3.3. Puberty Most of our patients presented a worsening of their illness near puberty. Pubertal deterioration may occur in some autistic children [27]. Symptom aggravation is often observed in adolescence. Most cases of autism taking a deteriorating course in adolescence never return to preadolescent levels of language, communication and social functioning [22]. The onset or worsening of these conditions at or near puberty suggests a major role for sex hormones. 3.4. Physical anomalies Autistic patients do not have consistent physical features, but often show physical anomalies, non specific abnormal EEGs, MRIs, CT scans and autopsy findings [28]. These abnormalities result from genetic or environmental damages

290

M. Raja, A. Azzoni / General Hospital Psychiatry 23 (2001) 285–293

that occur in early pregnancy and suggest an abnormality in fetal development [29]. The prevalence of medical conditions with suspected etiologic relationship with autism varies between 10 and over 30% depending on the diagnostic system employed [30]. Neuropathological and MRI studies have demonstrated developmental disturbances of neuronal migration in the cerebral cortex of autistic subjects. In patients with AS, neuro-radiologic findings [31] and neuroophthalmologic disturbances [32] have been reported. Empty sella and neurogenic diabetes insipidus (Case 1), localized cerebral atrophy (Case 3), and facial dysmorphia (Case 5) were the abnormal physical features present in our sample. 3.5. Psychiatric comorbidity Comorbid psychiatric conditions are frequently observed in patients with AS. In a series of 99 subjects with AS [33], psychiatric associated conditions included ADHD (28% of cases), OCD (19%) and depression (15%). Obsessive-compulsive symptoms have been frequently described in autism spectrum disorders, possibly due to serotoninergic dysregulation [34]. The rate of Bipolar Disorder in family members of a group of autistic subjects was 4.2%, higher than in the general population. Furthermore, it was significantly higher in families of probands with AS, suggesting an etiological link between AS and manic depression [35]. In our sample, 2 patients presented depressive symptoms and 4 patients obsessive-compulsive symptoms. 3.6. Pervasive Developmental Disorders and Schizophrenia A problematic topic is the possibility of comorbid schizophrenia. The incidence of childhood schizophrenia is slight. There is no evidence to justify differentiating a subvariety of schizophrenia according to childhood onset, and no reason to pool autism and schizophrenia. Although the two conditions can co-occur in the same individual, it appears that the frequency of schizophrenia among autistic patients (0.6%) is comparable to the frequency of schizophrenia in the general population and that the two conditions are not more commonly observed together than would be expected on a chance basis [36]. Differences from adult schizophrenia are more marked when onset is in childhood than in adolescence but all are quantitative rather than qualitative suggesting that the disorders are the same and that there should be no separate category for children or adolescents [37]. In children, the diagnosis of schizophrenia often proves to be unfounded [38]. Despite evidence supporting discontinuity between autism and schizophrenia [36,39], patients with coexisting PDD and schizophrenialike psychosis have been described [40 – 46] and some investigators have reported an association between past history of autistic symptoms and present diagnosis of schizophrenia [47– 49]. In general, individuals with autism

are not at increased risk for schizophrenia [36]. Nevertheless, there possibly exists a subgroup of autistic children who are at risk for the development of schizophrenia-like symptoms. This group of patients may be more likely to seek treatment from psychiatric facilities and, therefore, may not be sampled in studies whose subjects are drawn from autism and developmental centers. The subjects sampled from autism centers are more likely to comprise “uncomplicated” cases of autism. In our patients, it is not easy to rule out the diagnosis of schizophrenia, since the criteria for the differential diagnosis between PDDs and schizophrenia are unreliable. DSM-IV states that, in the presence of a PDD, the additional diagnosis of schizophrenia “is made only if prominent delusions or hallucinations are also present for at least a month (or less if successfully treated)”. However, it is not clear what should be intended for “prominent”. A further problem is the difficulty to establish the presence of psychotic processes (delusions or thought disorder) in children who have not yet developed relatively sophisticated expressive language skills, and ability to use adult rules of logic or notions of reality [50]. As in other areas of psychiatric nosology, the longstanding presence of more or less typical delusions or hallucinations without concurrent mood alterations raises the issue of the diagnosis of schizophrenia in patients with symptoms typical of other mental disorders. In our patients, many relatively specific clinical features suggest a diagnosis of PDD (see Table 1). Some clinical symptoms are inconsistent with a diagnosis of schizophrenia, including restricted outstanding cognitive abilities, history of early language delay, sense of humor, good capability to mimic and unusual and restricted interests. Also, clumsy movements, atypical age of onset, poor response to antipsychotics and absence of schizophrenia diagnoses in relatives highlight the differences between schizophrenia and these subjects. In childhood onset schizophrenia, it has been reported a rate of familial schizophrenia and spectrum disorders even higher than in more common later-onset cases [51]. 3.7. AS, right-hemisphere dysfunction, and nonverbal learning disabilities It has been hypothesized that AS is a disorder of the right hemisphere [52]. The human right hemisphere is dominant in certain types of spatial functions, particularly the analysis of external space, and the orientation of the body within this space. It also plays a major role in emotion, both in the subjective experience and the external expression of emotion as well as in the appreciation of emotion manifested by others. It is also dominant in attention. Finally, there is evidence of right hemisphere involvement in the pathophysiology of obsessive-compulsive symptoms. Some AS features suggest a possible right-hemisphere dysfunction. First, AS has clinical features in common with acquired righthemisphere dysfunction. Second, some features of so-called Nonverbal Learning Disabilities (NVLD) including emo-

M. Raja, A. Azzoni / General Hospital Psychiatry 23 (2001) 285–293

291

Table 1 Clinical features of the 5 patients with a diagnosis of AS Case 1

Case 2

Case 3

Case 4

Case 5

Sex Handedness Previous diagnosis

Male Left Early-onset psychosis

Male Left Paranoid disorder

Male Left Residual schizophrenia

Obsessive-compulsive symptoms Delusions Hallucinations Above average single cognitive abilities Aggressive or violent behavior History of early language delay Sense of humor Good capability to mimic WAIS Total score WAIS Verbal/Performance score Periods of muteness Unusual and restricted interest

Yes Yes No Yes

Yes Yes Yes Yes

No Yes Yes No

Male Right Disorganized schizophrenia Yes No No Yes

Male Right Undifferentiated schizophrenia Yes Yes Yes No

Yes Yes Yes Yes 79 96/59 No Yes (horror films, knives, policewomen) Yes Empty sella (CT and MRI)

Yes No Yes No 73 84/62 No Yes (dylan dog)

Yes No Yes No 46 55/40 Yes No

Yes No Yes Yes 73 77/71 Yes No

Yes No No No 88 94/81 Yes Yes (books of economics)

Normal (CT)

Yes Right parietal cortical atrophy (CT)

Yes Normal (CT)

Psychiatric family history

Negative

Negative

Depression in grandmother

Bipolar disorder (psychotic) in father

Response to antipsychotic medication Clumsiness

Poor

Good

Poor

Moderate

Cortical sulci and ventricules enlargement (CT) Epilepsy with abnormal personality in mother Moderate

Yes

Yes

Yes

Yes

Yes

Worsening at puberty Neuroimaging

tional disturbances, abnormal language (poor prosody and pragmatics, good vocabulary), social difficulties are also observed in patients with AS and raise the question whether there is a continuum between these disorders. A recent study found patients with AS different from patients with HFA and similar to patients affected by NVLD [53]. In contrast with the more common language-based learning disabilities, which are associated with problems in reading and spelling, NVLD are associated with problems in arithmetic and with a pattern of deficits in cognitive and adaptive functions attributed to the right hemisphere, including spatial cognition, social-emotional functioning, visuo-perceptual and simultaneous information processing. Third, also the reported discrepancy between verbal and performance cognitive abilities of these patients is consistent with the possibility of right hemisphere dysfunction. A fourth clinical feature suggestive of right hemisphere failure is patients’ inability to make inferences about others’ mental states, as evidenced by their difficult relationship with other people. Patients with AS seem unable to recognize the meaning of human facial expressions. This deficit could be conceived as a selective form of prosopoagnosia, a deficit typical of right hemisphere lesions. Surprisingly, 4 of the 5 subjects presented unusual sense of humor and capacity to mimic. These features are unexpected and seem even paradoxical in individuals with a disorder characterized by a formal concrete

way of thinking and an inability to identify and understand human emotions and relationships. Possibly, this discrepancy between the inability to identify or understand human emotions and the excellent sense of humor and capacity to mimic reflects a more general unbalance of mental and cognitive symptoms in PDD (e.g., mental retardation and excellent mathematical or mnemonic abilities, lack of activities or interests and over-involvement in confined interests) that could be due to defective development of some brain areas associated with compensatory overgrowth of other areas [54]. Finally, obsessive-compulsive symptoms, present in 4 patients out of 5, might also point out right hemisphere dysfunction. There is evidence of right hemisphere dysfunction in patients with OCD [55–56]. McKelvey et al. [57] found abnormal right-hemisphere (and cerebellar) function on single photon emission computed tomographic imaging (SPECT) in three patients with AS, and enlargement of the right lateral ventricle, reflecting mild right hemispheric atrophy on MRI, in one of them. In a series of childhood epilepsy surgery candidates, 6 of 8 children with AS had right brain lesions [58]. Interestingly, one of our patients had localized right parietal cortical atrophy consistent with this hypothesis. However, neuroimaging assessment was inadequate to reveal possible hemispheric asymmetry in our patients. MRI imaging was not available in 4 of them and no volumetric assessment of

292

M. Raja, A. Azzoni / General Hospital Psychiatry 23 (2001) 285–293

brain was performed by radiologists who were asked only to detect clinically significant structural abnormalities. 3.8. Handedness Three patients out of 5 were left-handed. This points to a right dominance and could seem in contrast with the hypothesis of right hemisphere dysfunction. In patients with PDD, an increase in left-handedness and ambiguous handedness has been reported [59,60]. Heredity for left-handedness in some cases, and assumed brain damage and immature patterns of lateralization in others, are considered the cause of non right handedness in autistic individuals. Besides, a higher frequency of left-handedness in men has been reported in many studies. Unexpectedly, however, neuroimaging and other neurobiological examinations have not provided evidence of unilateral left hemisphere dysfunction in autism. Rather, a trend in an association with right hemisphere dysfunction has been seen in left-handed autistic subjects [61]. 3.9. Violent behavior Interestingly, all 5 patients were violent to their relatives. In general, antisocial acts, including aggression and sexual offense, have not been considered common in AS. A case of AS whose main problems were violent behavior and sexual offense has recently been described [62]. In a secure hospital, the prevalence of AS was found to be higher (1.5%) than that reported in the general population, confirming the possibility that AS may go unrecognized in forensic populations [63]. In our PICU, violent behavior of patients with AS seems to be common. We suspect that patients’ violence was a reaction to the attitude of other people misinterpreted as cold or hostile. This cognitive deficit could be an important etiological factor of violent behavior in patients with AS [64]. If that is how the matter stands, it is unlikely that violent behavior of AS patients can respond to drug treatment efficacious in patients whose violent behavior is caused by hallucinations, delusions, excitement, impulsiveness, antisocial personality, or drug abuse. A psychoeducational approach might be more useful. 3.10. Drug treatment An open-label study suggests that risperidone may be effective in improving behavior in children and adolescents with PDD, including AS [65]. An open-label study suggests that clomipramine may be effective in reducing repetitive thoughts and actions and aggressive behavior and in improving social behavior in adults with PDD [66]. On the contrary, an open label investigation found sertraline effective in reducing repetitive thoughts and actions and aggressive behavior in adults with PDD but not in subjects with AS [67]. In our sample, we observed no excellent response to drug treatment. Three patients were treated with risperi-

done with moderate or poor results, and 2 patients with olanzapine with moderate or poor results. Two patients, both nonresponders to previous standard neuroleptic treatment, were not treated with antipsychotics. Previously, 3 patients had been treated with SSRI without improvement.

References [1] Wing L. Asperger’s syndrome: a clinical account. Psychol Med 1981;11:115–30. [2] Gillberg C. Asperger’s syndrome, and recurrent psychosis—a case study. J Autism Dev Disord 1985;15:389 –97. [3] Szatmari P, Bremner R, Nagy J. Asperger’s syndrome: a review of clinical features. Can J Psychiatry 1989;34:554 – 60. [4] Szatmari P, Bartolucci G, Bremner R. Asperger’s syndrome, and autism: comparisons on early history, and outcome. Dev Med Child Neurol 1989;19:213–25. [5] Kurita H. A comparative study of Asperger syndrome with highfunctioning atypical autism. Psychiatry Clin Neurosci 1997;51:67– 70. [6] Ryan RM. Treatment-resistant chronic mental illness: is it Asperger’s syndrome? Hosp Comm Psychiatry 1992;43:807–11. [7] Bech P, Kastrup M, Rafaelsen OJ. Minicompendium of rating scales. Acta Psychiatr Scand 1986;73(suppl. 326). [8] Andreasen NC. Scale for the Assessment of Positive Symptoms (SAPS). Iowa City, University of Iowa 1983. [9] Andreasen NC. Scale for the Assessment of Negative Symptoms (SANS). Iowa City, University of Iowa 1981. [10] Folstein MF, Folstein SE, McHugh P. Mini-Mental State: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189 –98. [11] American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Washington, DC, American Psychiatric Association 1994. [12] National Institute of Mental Health (NIMH) Psychopharmacology Research Branch. Abnormal Involuntary Movement Scale. Psychopharmacol Bull 1986;24:781–2. [13] Fahn S, Elton RL. Members of the UPDRS Development Committee Unified Parkinson’s Disease Rating Scale. In: Fahn S, Marsden CD, Calne D, Goldstein M, editors. Recent Developments in Parkinson’s Disease, MacMillan Florham Park, New Jersey, 1987. [14] Barnes TRE. A rating scale for drug-induced akathisia. Br J Psychiatry 1989;154:672–76. [15] Raja M, Azzoni A, Giammarco V. Diabetes insipidus, and polydipsia in a patient with Asperger’s disorder, and an empty sella. J Autism Dev Disord 1998;28:235–9. [16] Asperger H. Die “autistischen Psychopathen” in Kindesalter. Archiv fu¨ r Psychiatrie und Nervenkrakheiten 1944;117:76 –136. [17] Gillberg C, Gillberg IC. Asperger syndrome: some epidemiological considerations: a research note. J Child Psychol Psychiatry 1989;30: 631– 8. [18] Tantam D. Asperger’s syndrome. J Child Psychol Psychiatry 1988; 29:245–55. [19] Szatmari P, Bremner R, Nagy J. Asperger’s syndrome: a review of clinical features. Can J Psychiatry 1989;34:554 – 60. [20] Dauner I, Martin M. Autism Asperger of early schizophrenia. Padiatr Padol 1978;13:31– 8. [21] Bankier B, Lenz G, Guttierez K, Bach M, Katschnig H. A case of Asperger’s syndrome first diagnosed in adulthood. Psychopathology 1999;32:43– 6. [22] Gillberg C. Autism, and autistic-like conditions: subclasses among disorders of empathy. J Child Psychol Psychiatry 1992;33:813– 42. [23] Wing L. Sex ratio in early childhood autism, and related conditions. Psychiatry Res 1981;5:129 –37.

M. Raja, A. Azzoni / General Hospital Psychiatry 23 (2001) 285–293 [24] Volkmar FR, Szatmari P, Sparrow SS. Sex differences in pervasive developmental disorders. J Autism Dev Disord 1993;23:579 –91. [25] Deb S, Prasad KB. The prevalence of autistic disorder among children with a learning disability. Br J Psychiatry 1994;165:395–9. [26] Fombonne E. The epidemiology of autism: a review. Psychol Med 1999;29:769 – 86. [27] Rutter M. Autistic children. Infancy to adulthood. Semin Psychiatry 1970;2:435–50. [28] Coleman M, Gillberg C. The Biology of the Autistic Syndromes. New York, Praeger, 1985. [29] Smalley SL, Asarnow RF, Spence MA. Autism, and genetics. Arch Gen Psychiatry 1988;45:953– 61. [30] Barton M, Volkmar F. How commonly are known medical conditions associated with autism? J Autism Dev Disord 1998;28:273– 8. [31] Berthier ML, Starkstein SE, Leiguarda R. Developmental cortical anomalies in Asperger’s syndrome: neuroradiological findings in two patients. J Neuropsychiatry Clin Neurosci 1990;2:197–201. [32] Brodsky MC, Barber LG, Lam BL, Merin LM, Edelson S. Neuroophthalmologic findings in the Asperger disorder. J Neuroophthalmol 1996;16:185–7. [33] Klin A, Volkmar FR. Asperger’s syndrome. In: Handbook of Autism, and Pervasive Developmental Disorders, 2nd ed. Cohen DJ, Volkmar FR., editors, New York: Wiley, pp. 94 –112, 1997. [34] McElroy SL, Phillips KA, Keck PE. Obsessive compulsive spectrum disorder. J Clin Psychiatry 1994;55(suppl 10):33–51. [35] DeLong GR, Dwyer JT. Correlation of family history with specific autistic subgroups: Asperger’s syndrome, and bipolar affective disease. J Autism Dev Disord 1988;18:593– 600. [36] Volkmar FR, Cohen DJ. Comorbid association of autism, and schizophrenia. Am J Psychiatry 1991;148:1705–7. [37] Werry J. Child, and adolescent (early onset) schizophrenia: a review in light of DSM-III-R. J Autism Dev Disord 1992;22:601–24. [38] Marsh RW. The diagnosis, epidemiology, and etiology of childhood schizophrenia. Genet Psychol Monogr 1977;95:267–330. [39] Rutter M. Childhood schizophrenia reconsidered: J Autism Child Schizophr 1972;2:315–37. [40] Cantor S, Evans J, Pearce J, Pezzot-Pearce T. Childhood schizophrenia: present but not accounted for. Am J Psychiatry 1982;139:758 – 62. [41] Petty LK, Ornitz EM, Michelman JD, Zimmerman EG. Autistic children who become schizophrenic. Arch Gen Psychiatry 1984;41: 129 –35. [42] Clarke DJ, Littlejohns CS, Corbett JA, Joseph S. Pervasive developmental disorders, and psychosis in adult life. Br J Psychiatry 1989; 155:692–9. [43] Realmuto GM, August GJ. Catatonia in autistic disorders: a sign of comorbidity or variable expression? J Autism Dev Disord 1991;21: 517–28. [44] Szatmari P, Bartolucci G, Finlayson A, Krames L. A vote for Asperger’s syndrome. J Autism Dev Disord 1986;16:515–7. [45] Volkmar FR, Cohen DJ, Hoshino Y, Rende RD, Paul R. Phenomenology, and classification of the childhood psychoses. Psychol Med 1988;18:191–201. [46] Wolff S, Chick J. Schizoid personality in childhood: a controlled follow-up study. Psychol Med 1980;10:85–100. [47] Russell AT, Bott L, Sammons C. The phenomenology of schizophrenia occurring in childhood. J Am Acad Child Adolesc Psychiatry 1989;28:399 – 407.

293

[48] Watkins JM, Asarnow RF, Tanguay PE. Symptom development in childhood onset schizophrenia. J Child Psychol Psychiatry 1988;29: 865–78. [49] Klin A. Asperger syndrome. Child Adolesc Psychiatr Clin North Am 1994;3:131– 48. [50] Volkmar FR. Childhood and adolescent psychosis: a review of the past 10 years. J Am Acad Child Adolesc Psychiatry 1996;35:843–51. [51] Rapoport JHL. Schizophrenia of childhood onset: something old, and something new. APA 2000 Annual Meeting Syllabus; Proceedings Summary 307. [52] Huntzinger RM. Neuropsychological functioning in two children diagnosed with Asperger’s disorder. J Neuropsychiatry Clin Neurosci 1995;7:85. [53] Klin A, Volkmar FR, Sparrow SS, Cicchetti DV, Rourke BP. Validity, and neuropsychological characterization of Asperger syndrome: convergence with nonverbal learning disabilities syndrome. J Child Psychol Psychiatry 1995;36:1127– 40. [54] Geschwind N, Galaburda AM. Cerebral lateralization. Biological mechanisms, associations, and pathology: I. A hypothesis and a program for research. Arch Neurol 1985;42:428 –59. [55] Kuskowski MA, Malone SM, Kim SW, et al. Quantitative EEG in obsessive-compulsive disorder. Biol Psychiatry 1993;33:423–30. [56] Lippitz B, Mindus P, Meyerson BA, Kihlstrom L, Lindquist C. Obsessive compulsive disorder, and the right hemisphere: topographic analysis of lesions after anterior capsulotomy performed with thermocoagulation. Acta Neurochir 1997 (suppl 68):61–3. [57] McKelvey JR, Lambert R, Mottron L, Shevell MI. Right-hemisphere dysfunction in Asperger syndrome. J Child Neurol 1995;10:310 – 4. [58] Taylor DC, Neville BG, Gross JH. Autistic spectrum disorders in childhood epilepsy surgery candidates. Eur Child Adolesc Psychiatry 1999;8:189 –92. [59] Soper HV, Satz P, Orsini DL, et al. Handedness patterns in autism suggest subtypes. J Autism Dev Disord 1986;16:155– 67. [60] Lewin J, Kohen D, Mathew G. Handedness in mental handicap: investigation into populations of Down’s syndrome, epilepsy, and autism. Br J Psychiatry 1993;163:674 – 6. [61] Gillberg C. Autistic children’s hand preferences: results from an epidemiological study of infantile autism. Psychiatry Res 1983;10: 21–30. [62] Kohn Y, Fahum T, Ratzoni G, Apter A. Aggression, and sexual offense in Asperger’s syndrome. Isr J Psychiatry Relat Sci 1998;35: 293–9. [63] Seragg P, Shah A. Prevalence of Asperger’s syndrome in a secure hospital. Br J Psychiatry 1994;165:679 – 82. [64] Baron-Cohen S. An assessment of violence in a young man with Asperger’s syndrome. J Child Psychol Psychiatry 1988;29:351– 60. [65] McDougle CJ, Holmes JP, Bronson MR, et al. Risperidone treatment of children and adolescents with pervasive developmental disorders: a prospective open-label study. J Am Acad Child Adolesc Psychiatry 1997;36:685–93. [66] Brodkin ES, McDougle CJ, Naylor ST, Cohen DJ, Price LH. Clomipramine in adults with pervasive developmental disorders: a prospective open-label investigation. J Child Adolesc Psychopharmacol 1997;7:109 –21. [67] McDougle CJ, Brodkin ES, Naylor ST, et al. Sertraline in adults with pervasive developmental disorders: a prospective open-label investigation. J Clin Psychopharmacol 1998;18:62– 6.