Autism spectrum disorders and psychiatric co-morbidity in adolescents and adults

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(1)http://www.diva-portal.org. This is the published version of a paper published in Clinical Neuropsychiatry.. Citation for the original published paper (version of record): Bejerot, S., Wetterberg, L. (2008) Autism spectrum disorders and psychiatric co-morbidity in adolescents and adults. Clinical Neuropsychiatry, 5: 3-8. Access to the published version may require subscription. N.B. When citing this work, cite the original published paper.. Permanent link to this version: http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-50195.

(2) Clinical Neuropsychiatry (2008) 5, 1, 3-8 EDITORIAL AUTISM SPECTRUM DISORDERS AND PSYCHIATRIC COMORBIDITY IN ADOLESCENTS AND ADULTS Susanne Bejerot and Lennart Wetterberg. Key-words: Autistic disorder Asperger syndrome Comorbidity Mental Disorders Diagnosis Declaration of interest: none Susanne Bejerot1 and Lennart Wetterberg2 1, 2 Karolinska Institute, Department of Clinical Neuroscience, Section of Psychiatry, St Göran, SE -112 81 Stockholm, Sweden Corresponding Author Susanne Bejerot, MD, Ph.D. Department of Clinical Neuroscience, Section of Psychiatry at St. Goran, SE 112 81 Stockholm, Sweden. E-mail: Susanne.Bejerot@sll.se. Seven articles in this issue raise interesting questions about psychiatric comorbidity in autism spectrum disorders (ASD) in adolescent and adult patients. The answer to these questions will eventually be helpful in developing an etiological diagnosis for the different diseases and syndromes in question. The ultimate identification of a disease requires defining etiology. An etiological diagnosis may or may not define a treatment group but it does provide the possibility of developing a specific treatment. It is the goal of Medical Science just as treatment diagnosis is the goal of Medical Practice. Indeed, the latter is frequently the precursor of the former. In particular the comorbidity between ASD and borderline personality disorders, eating disorders and schizophrenic spectrum disorders are discussed in this issue as well as the possible genetic background to some of the autism spectrum disorders.. Historical aspects In 1943 Leo Kanner, a child psychiatrist, who had emigrated from Austria to USA already in 1924, described eleven severely impaired children that shared certain features: they ignored, disregarded and shut out the outside world, they were interested in objects but totally uninterested in relating to other people and they had a desire for sameness. Also, they often had islets of specific abilities. In 1956 Kanner and Eisenberg specified the first diagnostic criteria of autism defined by the cardinal features of insistence on sameness and autistic aloneness. In 1944 an Austrian paediatrician Hans Asperger, published a long ignored paper in German. In this paper he discussed a group of children who had little social interaction but had various levels of intellectual abilities. The definition on autism, given by Asperger, was wider than Kanners, but the. © 2008 Giovanni Fioriti Editore s.r.l.. similarities are obvious and a clear delineation between the two disorders is impossible to establish with scientific rigor. Most experts agree today on the use of the umbrella term Autism spectrum disorders (or conditions) (ASD) as defining a group characterized by deviant language development, a severe social communication impairment which is especially evident in the social responses to other children, unusual verbal and non-verbal communication, restricted repertoire of activities or interests, unusual sensory phenomena and motor impairment regardless of the level of intelligence. Hans Asperger described his patients as follows: The children have in common a fundamental disturbance which manifests itself characteristically in all behavioural and expressive phenomena. This disturbance results in considerable and typical difficulties of social integration. He described the individuals as avoiding eye contact, performing stereotypic movement, speaking with an atypical prosody with a content of speech atypical for any child and unable to enjoy flattery or expressions of love. He suggested that these children had a disturbance of contact and used the term autistic psychopathy (the expression psychopathy corresponds to the meaning of todays diagnosis personality disorder). He stated that although the failure to become integrated in a social group was the most conspicuous feature in these children, many had a compensating originality of thought and experience that could eventually lead to great achievements in adult life. However, neither Kanner nor Asperger seem to be the first to describe autistic features in children. In 1926 a Soviet physician, Eva Ssucharewa, published a case series in German describing the clinical picture of six boys who had typical symptoms of autism (Ssucharewa and Wolff 1995). Although Ssucharewa diagnosed these boys as suffering from schizoid personality disorder, the clinical. 3.

(3) Susanne Bejerot and Lennart Wetterberg. pictures carried all the hallmarks described by Hans Asperger (Wolff 1996). Moreover, nowadays most experts recognize that schizoid personality patterns in childhood are identical to Aspergers syndrome (Rutter1987, Wolff 1991).. ASD of 2008 Most research on ASD has focused on children and young adults, and studies of adults with normal intellectual abilities and ASD is fairly new. Our efforts are still fumbling and there are many loose ends to disentangle. What is ASD? Well, as Nylander and coworkers put it until we get biological markers, diagnosis will rest on the foundation of clinical common sense. The golden standard is the judgement of experienced clinicians supported by individualised assessments. We dont know whether ASD is one distinct disorder of varying severity, or a group of different disorders with a common phenotype. We dont know if certain psychiatric and somatic illnesses which are common in ASD, are separated from ASD, or another expression of it. We dont know where the overlaps and boundaries go between personality disorders and ASD. We are just starting to distinguish clinical patterns. It has been suggested that future diagnostic manuals should amalgamate autism and Aspergers syndrome into one diagnostic category such as Autism Spectrum Disorder (with modifiers; severe, moderate, mild, atypical, and Aspergers type) (Ritvo et al. 2008). For clinical purposes this seems justifiable, however, for the purpose of research in endophenotypes and for understanding the meaning of the genetic heterogeneity of ASD much more detailed descriptions are warranted. A modern definition of autism is a behavioural syndrome with a biological basis and systemic features, influenced by genes and gene-environment interaction according to a comprehensive review by Herbert published in this journal in 2005 (Herbert 2005). She suggests that autism overlaps with other disorders because of commonalities in underlying pathophysiology that have multifaceted impacts on tissue, connectivity and processing properties; these overlaps may be related to shared genetic features or may represent final common pathways (p. 356). There is an overlap both with the normal range and with other diagnostic entities, which certainly applies to many psychiatric disorders. The present issue of Clinical Neuropsychiatry is devoted to the various conditions and symptoms that may affect adults with ASD, resulting in referrals for psychiatric care. Lorna Wing, whom we wish to thank and congratulate on her 80th birthday this year, visited Sweden for a workshop in 2003 and inspired some of the contributing authors - psychiatrists with longstanding interest in ASD - to study and publish about psychiatric comorbidity in ASD. In that meeting we discussed why the various psychiatric symptoms frequently seen in patients with ASD rarely were addressed in autism literature. Furthermore ASD tends to pass unnoticed or is dismissed at most routine clinical examinations in psychiatric settings for various reasons.. 4. Parallels and comorbidity with other psychiatric conditions In this issue we have made a deliberate search for parallels with other psychiatric conditions in patients with ASD. We embrace the hypothesis that ASD may give rise to psychiatric symptoms more or less indistinguishable from similar symptoms in persons without ASD and that these symptoms may respond favourably to conventional pharmaceutical treatments as serotonin reuptake inhibitors in the treatment of depression and anxiety disorders, antipsychotics in the treatment of psychotic symptoms and, according to preliminary findings, omega-3 fatty acids in the treatment of hyperactivity and stereotypy (Amminger et al. 2008). Also, probably, cognitive behavioural therapy is a useful method for obsessive compulsive symptoms in persons with ASD. There is a positive association between comorbidity and the severity of psychopathological dysfunction (Clark et al. 1995). It seems plausible that the vast psychiatric comorbidity observed in ASD reflects an underlying, yet unknown, psychopathological liability factor. Inevitably, then, this factor will take the shape of various specific psychiatric disorders. To quote the review by Krueger and Markon (2006): a reasonable interpretation of the existing literature is that the extensive comorbidity among mental disorders reflects the existence of a smaller number of liability constructs that underlie multiple disorders. Subtle forms of ASD could, according to their hierarchical model, possibly explain a subgroup of patients defined as highly comorbid, or rather multimorbid. Recognition of the underlying ASD construct is in these cases important to fully understand the patients problems. This recognition may be essential for explaining and relieving symptoms, to provide social benefits and educational services. Also it is of importance for forensic aspects and for various aspects of research. In the first two papers, psychiatric comorbidity in adults with ASD is investigated. Mohammad Ghaziuddin and Saniya Zafar assessed referrals with a presumptive diagnosis of autism or Aspergers syndrome in USA while Eleonore Rydén and Susanne Bejerot studied a similar population in Sweden. Their results have similarities. Male preponderance is much lower than previously reported in children, and the prevalence of depression is high. These studies suggest that depression is the main reason for consulting psychiatric services in adult patients with ASD. Various anxiety disorders were also common. According to the Swedish study every forth patient previously diagnosed with a psychiatric disorder, had been diagnosed with OCD. Seventeen percent were perceived as suffering from social phobia prior to the ASD diagnosis. Of those diagnosed with ASD, one third fulfilled the diagnostic criteria for attention deficit disorder, suggesting that attention deficits could be expected in ASD and that this sometimes may lead to a misperception of a primary attention deficit hyperactivity disorder (ADHD). Deficiencies of executive functioning could be expected in patients with ADHD and ASD while poor inhibition is a core symptom of ADHD only (Barkley 2003); therefore ADHD and ASD should rarely overlap. Clinical Neuropsychiatry (2008) 5, 1.

(4) Autism Spectrum Disorders and Psychiatric Comorbidity in Adolescents and Adults Selected abbreviations and acronyms used in this issue ADHD AN AS ASD ASDI ASMT ASRS ASSQ A-TAC BMI BN BOCS BP BPD CGI-S COS DCD DSM-IV fMRI FTF GAF GWA HFA IQ MADRS MBT MCDD M.I.N.I OCD OCPD PDD PDD-NOS SASB SCID II SCREEN SCID II SMD SPD SSP SUAS SWAP-200 ToM ZAN-BPD WAIS WRAADDS. Attention Deficit Hyperactivity Disorder Anorexia Nervosa Aspergers Syndrome Autism Spectrum Disorders Asperger Syndrome Diagnostic Interview AcetylSerotonin MethylTtransferase World Health Organization Adult ADHD Self-Report Scale Autism Spectrum Screening Questionnaire Autism - tics, attention-deficit hyperactivity disorder and other comorbidities Body Mass Index Bulimia Nervosa Brief Obsessive Compulsive Scale Borderline Personality Borderline Personality Disorder Clinical Global Impression Severity of Illness Childhood Onset Schizophrenia Developmental Coordination Disorder Diagnostic and statistical manual of mental disorders: DSM-IV (4th ed.). Functional Magnetic Resonance Imaging Five to fifteen Global Assessment of Functioning Genome wide association studies High Functioning Autism Intelligence Quotient Montgomery Asberg Depression Rating Scale Mentalization Based Treatment Multiple Complex Developmental Disorder Mini International Neuropsychiatric Interview Obsessive Compulsive Disorder Obsessive-compulsive personality disorder Pervasive Developmental Disorder Pervasive Developmental Disorder Not Otherwise Specified Structural Analysis of Social Behavior The screening version of Structured Clinical Interview for DSM-IV Structured Clinical Interview for DSM-IV Axis II Personality Disorders Severe Mental Disorder Schizotypal personality disorder Swedish Universities Scales of Personality Suicide Assessment Scale Shedler-Westen Assessment Procedure-200 Theory of Mind Zanarini borderline interview Wechsler Adult Intelligent Scale Wender-Reimherr Adult Attention Deficit Disorder Scale. Persons with ASD are seldom impulsive. More often they are rigid and drawn to ritualistic behaviours. Nor are they sexually promiscuous or prone to addiction to nicotine, alcohol or drugs when compared to persons with ADHD. When impulsive behaviours are observed in persons with ASD, they are likely signs of social disinhibition due to the subjects poor mentalising ability i.e. understanding of the mental state of oneself and others rather than a true impulsivity. Hence, the patients with ASD do not assess themselves as impulsive according to the result from the personality questionnaire. Nevertheless, previous diagnoses of borderline personality disorder and attempted suicide were common, according to Rydén and Bejerots paper. In the third paper, Rydén, Rydén and Hetta elaborate further on this issue by assessing autistic traits in. Clinical Neuropsychiatry (2008) 5, 1. 41 females with borderline personality disorder. Compared to other patients with borderline personality disorder, the ASD-borderline group had significantly more frequent suicide attempts but exhibited less substance abuse. Hypothetically, suicide attempts in patients with ASD may not be related to impulsivity at all, however levels of impulsivity were not reported here. The comorbidity for Axis I disorders was equally common in the borderline and the ASDborderline group but the ASD-borderline group had a significantly lower level of functioning. The heterogeneity of the borderline concept has resulted in a subtyping in the ICD 10 Emotionally instable personality disorder: an impulsive and a borderline subtype. The patients with ASD will probably match the borderline subtype, but their compulsiveness may. 5.

(5) Susanne Bejerot and Lennart Wetterberg. Figure 1. &RQFHUQIRURWKHUVDQGRUWKHZRUOG . 1RUPDOSRSXODWLRQ. . . 0HQWDOLVLQJ DELOLW\. $XWLVP VSHFWUXP GLVRUGHUV. 3V\FKRSDWK\ . . Figure 1. The Notion of Empathy. A model for contrasting psychopathy with autism spectrum disorders, suggested by Bejerot S, Humble M, Nylander L, Rydén E and Wetterberg L. The X axis reflects mentalising abilities (i.e. the inborn ability to understand the mental state of oneself and others based on overt behaviour and present circumstances), which are independent of the persons will and intention. A person with a low mentalising ability may perceive him/herself as the norm of all experience which will result in distorted interpretation of human behaviour in terms of intentional. mental states (e.g. needs, desires, feelings, beliefs, goals, purposes, and reasons). A low mentalising ability precludes successful manipulative behaviours. A person with a highly developed mentalising ability is perceived as empathic by others (which may be true or false), while a person with a low mentalising ability is perceived as egocentric. The Y axis reflects the intention and will of the persons to concern for others and the world. A person with a strong concern in this respect is perceived as altruistic, while a person with weak concerns is perceived as egoistic.. suggest a better fit into a non-impulsive undifferentiated subtype, not accommodated within the current ICD 10 (Whewell et al. 2000). Another way of conceptualizing borderline is to view it as a continuum from no borderline symptoms to a severe form. Severe borderline personality disorder symptoms have been associated with greater comorbidity (Shevlin et al. 2007). The small sample size included in the study by Rydén and co-workers limits speculations as to whether the ASD-borderline group belongs to the severe form, but their findings call for consideration in future borderline research. In the fourth paper, Maria Råstam reviews eating disturbances in ASD. Interestingly, anorexia nervosa was the only psychiatric disorder more frequent in the ASD population than in the control group, as reported by Rydén and Bejerot. This supports Råstams findings of a significant correlation between these two disorders. However, a variety of eating disturbances might be expected in persons with ASD with or without mental retardation. Most of these are explained by sensory. aberrations. Adolescents and adults with ASD and normal intelligence often claim health issues or moral standards for vegetarianism and special diets. Whether these are rooted in sensory aberrations, special interests or an overvalued idea should be further examined. In the fifth paper, Nylander, Lugnegård and Unenge Hallerbäck present an overview of the boundaries and overlap between ASD and schizophrenia spectrum disorders. Catatonia and various psychotic symptoms are common in persons with ASD, and persons with schizophrenia may well be expected to have autistic features. Accordingly, even if typical autistic disorder and schizophrenia are easily distinguishable, the spectrum disorders of autism and schizophrenia definitely merge. In addition, the concept of schizotypal personality has resemblance with ASD. In an instrument for assessing personality in adolescents (SWAP-200) (Westen et al. 2005) a single schizotypy factor and a separate peer rejection factor were identified. The correlations between these factors were large, and both. 6. Clinical Neuropsychiatry (2008) 5, 1.

(6) Autism Spectrum Disorders and Psychiatric Comorbidity in Adolescents and Adults. factors were strongly associated with personality disorders involving social isolation and peculiarity. The descriptions of the schizotypy factor and the peer rejection factor strongly resemble descriptions of ASD in adolescents: The person is not verbally articulate; has limited ability to express self in words; Appearance or manner seems odd or peculiar (e.g. grooming, hygiene, posture, eye contact, speech rhythms, etc. seem somehow strange or off ); Reasoning processes or perceptual experiences seem odd and idiosyncratic (e.g. may make seemingly arbitrary inferences; may see hidden messages or special meanings in ordinary events); Speech tends to be circumstantial, vague, rambling, digressive; Tends to elicit boredom in others (e.g. may talk incessantly, without feeling or about inconsequential matters); Tends to think in concrete terms and interpret things in overly literal ways; has limited ability to appreciate metaphor, analogy or nuance; Seems to know less about the ways of the world than might be expected, given his/her intelligence, background and age; appears naïve or innocent; Appears to experience the past as a series of disjointed or disconnected events; has difficulty giving a coherent account of his/her life or actions; Appears to have little need for human company or contact; is genuinely indifferent to the presence of others; Appears to have a limited or constricted range of emotions; Tends to describe experiences in generalities; is unwilling or unable to offer specific details; Tends to be ignored, neglected or avoided by peers; Tends to be bullied or teased by peers; Lacks social skills; tends to be socially awkward or inappropriate; Lacks close friendships and relationships. ASD could be regarded as an inborn personality disorder and most persons with ASD are probably clinically perceived as having a personality disorder. In the study by Rydén and Bejerot, the patients fulfilled criteria for a median number of four personality disorders (range 0-10). More than 40% met the DSMIV criteria for avoidant-, borderline- and obsessivecompulsive personality disorder; more than a third for depressive-, schizotypal-, schizoid- and narcissistic personality disorders while at least 25% reached cutoff for paranoid- and passive-aggressive personality disorder respectively. Accordingly, the diagnosis given a patient may depend on whether the psychiatrist identifies symptoms as signs of a psychotic disorder, an obsessive compulsive disorder, a personality disorder or a pervasive developmental disorder, and the treatment will vary as a result. The ASD diagnosis may be of crucial importance for forensic aspects and legal issues. In the sixth article, Marianne Kristiansson and Karolina Sörman discuss aggression, violence and offending behaviors in persons with ASD. Although most persons with ASD are exceptionally law abiding, there seems to be a subgroup that may submit to criminal acts, initiated by an urge for revenge, by misunderstanding or as a result of special interests. Stalking-like behaviors, threats and pyromania can emanate from seeking revenge or, just as likely, special interest in a famous person, erotomania or fascination by fires. Importantly, however, psychopathy is rarely seen in ASD. Psychopaths are mostly egoistic, lack sympathy and are more or less. Clinical Neuropsychiatry (2008) 5, 1. successful in manipulating others. In contrast, persons with ASD are egocentric and socially inept, due to their lack of an intuitive theory of mind, but not without sympathy for others. See a working model of the notion of empathy in Figure 1. Finally, Jonas Melke draws our attention to the genetics of ASD, which is beginning to provide some clues to the pathophysiology of the disorder. He argues that autism is a heterogeneous disorder, both genetically and phenotypically, and questions the logic of recruiting increasingly larger samples for linkage and/or association studies. Rather, chromosomal aberrations and mutations with strong effect are suggested to play important roles in the genetics of autism. However, he proposes that susceptibility variants in genes encoding neurotransmitter proteins may explain the endophenotypes of ASD, the milder phenotypes in relatives, and its predominance in males. Recently, Melke and co-workers reported that a subgroup of patients has a deficit in the last enzyme in melatonin biosynthesis, ASMT. Also, a few patients were found to carry mutations in the ASMT gene, resulting in extremely low nocturnal melatonin concentration (Melke et al. 2007). A low melatonin production in a subgroup of patients with ASD may be related to deficient synaptogenes and hence melatonin may influence synaptic plasticity, a hypothesis which should be further tested. The synapse dysfunctions could directly or indirectly cause altered neural networks with reduced synchronization across areas of activation, which have been reported in patients with ASD (Kana et al. 2006). This might partly explain why persons with ASD fail in social communication and do not match their conversation with appropriate bodylanguage or tone of voice. Consequently subjects often miss important non-verbal information, misunderstand others and are themselves misunderstood. As one patient puts it it feels like my brain is a cupboard with drawers, but only one drawer could be pulled out at the time. It is not unusual that different explanations are suggested in disorders with an unknown etiology (Yuwiler 1995). Knowledge is undoubtedly superior to guessing. 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