Cormorbidity: Diagnosing Comorbid Psychiatric Conditions

Schizophrenia With Obsessive-Compulsive Disorder, by Alexandra Bottas, MD

Psychiatric Comorbidity in Persons With Dementia, by Denis Shub, MD and Mark E. Kunik, MD, MPH

Diagnosing Comorbid Psychiatric Conditions, by Johnny L. Matson, PhD and Daniene Neal

Development of a Dual Disorders Program, by Mark D. Green, MD

Comorbidity in Bipolar Disorder, by Doron Sagman, MD and Mauricio Tohen, MD

Autism spectrum disorders (ASDs) are a group of 5 neuro developmental conditions (autism, Asperger syndrome, pervasive developmental disorder not otherwise specified [PDD-NOS], Rett syndrome, and disintegrative childhood disorder).¹ Once thought to be rare, the incidence of these disorders is now estimated to be 1 in 150 children in the general population.² Furthermore, the number of recognized cases has increased markedly in recent years.

Many factors have contributed to the increasing numbers of persons with ASD. These include expanded diagnostic criteria, more diagnostic groups, extended evaluations that range over an entire life span, better and more comprehensive assessment methods, more and better trained professionals, and better funding for research and screening.³ Croen and associates⁴ found similar rates of developmental disability overall. The rise in ASD diagnoses has paralleled a decline in primary diagnoses of intellectual disability.

ASD does not inoculate persons from the range of psychiatric conditions that affect others in society. We follow the lead of Gilberg and Billstedt⁵ who describe comorbidities as overlapping disorders. A descriptive definition versus one that implies a direct or indirect link is important, because it is also possible that comorbid disorders occur by chance without an overlapping cause.

Psychiatric disorders are distinct from challenging behaviors that co-occur at high rates with ASD, along with conditions such as intellectual disability and epilepsy. Some forms of psychopathology are particularly common in ASD including atten- tion-deficit/hyperactivity disorder (ADHD), psychosis, depression, anxiety, and obsessive-compulsive disorder (OCD).^6,7 Consequently, the clinician needs to:

• Determine whether the patient has ASD. If this diagnosis is made, the type of ASD needs to be pinpointed along with the severity of specific symptoms, as well as the severity of the overall

disorder.
• Identify challenging behaviors and determine whether they are environmentally maintained or if they are linked to ASD or co-occurring conditions.⁸
• Assess whether comorbid intellectual disability is present.
• Consider the possibility of comorbid psychopathology.

While variability in level of overlap in these disorders is debatable, experts agree that overlap is considerable.

The specifics on how to address each of these issues follow, using the best available evidence-based practices. In all instances, the use of a reliable and valid test, clinical observation, school or home observation or report, clinical history, and clinical consensus constitutes the gold standard in inpatient settings.

Diagnosing ASD
Developmental factors are in play relative to this spectrum of diagnoses. Rett syndrome, which is quite rare, can be reliably evaluated via genetic testing; it can be identified earlier than other forms of ASD. The severity of symptoms and course in Rett syndrome vary over time. Thus, additional behaviorally based assessments of symptoms should be made over time. Autism (in about half of cases) and disintegrative childhood disorder (in all cases) involve marked loss of previously acquired skills at approximately 18 to 30 months of age. For the remainder of children with autism, diagnosis as young as 18 months may be possible, although some debate exists regarding the exact age cut-off point that will produce a reliable and valid diagnosis.⁹

Filipek and colleagues¹⁰ report on the number of unrecognized cases of autism before school age and the need for more intensive screening efforts. They emphasize that screening is particularly important for children at risk for any type of atypical development. However, regression at approximately age 2 and the heterogeneity of symptoms make this a daunting task.

No consensus exists on how early PDD-NOS or Asperger syndrome can be diagnosed. However, because PDD-NOS has milder symptoms than autism, it may be more difficult to identify in young children. Children with Asperger syndrome have a normal or higher than normal IQ; consequently, this disorder cannot be diagnosed as early as other ASDs.

There has been ongoing debate about whether Asperger syndrome is a separate diagnosis from high-functioning autism (HFA).¹¹ We recommend the use of a scale that is designed to aid in diagnosing suspected Asperger syndrome.¹² Thus, for early identification, autism and PDD-NOS will be the disorders screened for by the clinician in most instances. The Table presents scales/tests with established psychometrics that can facilitate diagnosis. Use of at least one of these measures as part of the clinical process is advisable.

Challenging behaviors
Aggression, nonadherence, stereotypies, property destruction, and self-injury are challenging behaviors commonly associated with ASDs. These problems can initially be screened for with a standard Likert scale, such as the Behavior Problems Inventory.¹³ This measure has good psychometrics and can help pinpoint specific challenging behaviors. A positive finding for challenging behaviors is followed by a functional assessment. Clinicians continue to debate whether challenging behaviors are behavioral equivalents of symptoms of psychopathology in the developmentally disabled population. However, the best evidence at present suggests that they are not. Nonetheless, in rare instances, challenging behaviors may be linked to psychopathology or to a developmental disability.

The functional assessment helps the clinician determine whether medication is appropriate. The Questions About Behavior Function (QABF) is a 25-item test designed for this purpose and can be completed in about 5 minutes.¹⁴ These potential causes of the challenging behavior are evaluated:

• The need for attention
• An attempt to escape from a task or environment
• Receipt of a tangible reward
• Physical illness or pain

An escape function may suggest the need to develop more rewarding or enriched environments. Pain may result in a conventional medical treatment (eg, head-banging because of an earache). The failure to identify 1 of these 4 underlying causes enhances the likelihood but does not confirm that the challenging behaviors are associated with physiological factors that are in turn associated with ASDs, comorbid psychopathology, or intellectual disability.

Intellectual disability
Intellectual disability and ASDs may co-occur in up to 3 of 4 affected children. While each disorder offers special challenges to the clinician, establishing the coexistence of these 2 conditions is important. Accurate diagnosis and treatment also depend on establishing the severity of intellectual disability. IQ is a particularly significant factor in poorer treatment outcomes and limits the types of psychological interventions that are appropriate. Inattention and lack of motivation to perform on cognitive tasks-which are common in children with ASDs-can result in marked underestimates of cognitive abilities. Therefore, ensuring good on-task behavior and motivation for individualized testing is essential. If this set of conditions is not possible, secondary measures of IQ-such as the Bailey Scales of Infant Development or the Vineland Social Maturity Scale-are advisable.

Psychopathology
Concomitant psychiatric conditions occur in persons with ASDs. The type of ASD influences rates of specific psychiatric conditions. Rett syndrome and disintegrative childhood disorder are both rare forms of ASD, and little to nothing is known about coexisting psychiatric conditions.

In addition to type of ASD, intelligence and age are major moderating variables. For IQ, individuals can be grouped into HFA and Asperger syndrome, or autism and PDD-NOS where intellectual disability is present. Age often plays a role in comorbid conditions; for example, depression is more common in adolescents and adults than in young children. Notable psychiatric conditions that co-occur with ASDs are depression, anxiety, psychosis, bipolar disorder, ADHD, phobias, and OCD.^6,7,15

To date, the ASD-Comorbid scale and the Psychopathology in Autism Checklist (PAC) have been developed to assess comorbid psychopathology in persons with ASDs. (We anticipate a good deal more activity in the near future.) The ASD-Comorbid scale has an adult version (intellectual disability only) and a child and toddler version (BISCUIT-2) . The adult version includes factors for anxiety/repetitive behavior, conduct problems, irritability/behavioral excesses, ADHD, and depression. The child version has factors on tantrum behavior, repetitive behavior, depression, social avoidant behavior, under- and over-eating, and conduct.^2,16

The scales were developed using symptoms that typically characterize psychopathology in people with ASDs, including depression, phobia, OCD, eating disorders, conduct disorder, tic disorder, and ADHD. Cri-teria from DSM-IV-TR and ICD-10 were used in addition to symptom descriptions in the literature and related scales (such as the Diagnostic Assessment for the Severely Handicapped–II [DASH-II]). Endorsement of multiple symptoms on one of the factors may indicate comorbid psychopathology with ASDs. For example, endorsement of items such as crying, tearful or weepy, and low energy or fatigue may point to comorbid depression with ASDs.

The PAC was developed in Norway.6 It measures psychosis, depression, anxiety, and OCD. It contains 30 items that represent symptoms indicative of a major psychiatric disorder, based on DSM-IV and ICD-10 criteria, that do not overlap with core ASD symptoms (ie, hallucinations, rapid mood fluctuations, and weight change). For example, while lack of social interaction may be a symptom of both depression and autism, other symptoms of depression such as fatigue, weight change, and sad affect are not considered core symptoms of autism. By assessing the presence of these criteria, clinicians can discriminate between ASD symptoms and symptoms of psychiatric disorders.

In both of these measures, major disorders are keyed to DSM-IV and ICD-10. Also, they can be completed in about 10 minutes; this aspect is important because these scales give the clinician a quick and convenient way to screen for the most common psychiatric conditions in ASDs. However, none of the scales are comprehensive. Therefore, some other less frequent comorbid disorder may go undetected. As with any test, clinical judgment is key. Nonetheless, PAC has proved useful for differentiating OCD from ASDs, and the ASD-Comorbid child version has proved useful in differentiating depression from ASDs.

The case vignette outlines the process discussed above in reaching a comorbid diagnosis with ASDs.

Case Vignette
Mr and Mrs X brought their 6-year-old son, Zach, for assessment. They reported that Zach had developed some single word language skills at age 1 but lost all verbal skills by age 21⁄2. Developmental milestones such as crawling and walking were delayed, and toilet training was impossible. As an infant, Zach was difficult to console, made little eye contact, and did not smile while playing with others. As a toddler, his lack of social skills became more and more apparent: he would often sit alone in day care lining up blocks. In his current school program, his teachers were seeing similar social withdrawal behaviors and frequent episodes of physical aggression, self-injurious behavior (ie, slapping the sides of his head), and crying. His parents had observed similar behaviors as well.

Mr and Mrs X reported that over the past year, approximately 1 to 2 times each month, Zach refused meals, slept more than usual, and had significantly more episodes of physical aggression, self-injurious behavior, and crying over 3 to 4 days.

Antecedent behavior consequence (ABC) forms and sleep logs were given to the parents to complete daily. Assessment began with the Autism Diagnostic Interview–Revised (ADI-R) and Autism Spectrum Disorders Diagnostic in Children (ASD-DC), which indicated significant impairments in the 3 core areas associated with ASD: social, communication, and stereotyped behaviors. The Stanford-Binet Intelligence Scale, fifth edition, was administered; however, a basal could not be achieved. The Bailey Scales of Infant Development indicated that he was in the profound range of impaired cognitive functioning. The Vineland Social Maturity Scale indicated that he was in the profound range of adaptive functioning.

To address the challenging behaviors, the QABF was administered and the child was observed in the clinic and at school. Results showed that physical aggression, self-injurious behavior, and crying served primarily as a communication function used to receive tangibles and to escape undesired activities. However, during periods of sleep and appetite disturbance, a clear function for the increase in physical aggression, self-injurious behavior, and crying could not be identified. Behavioral graphs of data from the sleep logs and ABC forms confirmed a significant increase in the frequency and severity of challenging behaviors during times of sleep disturbance with no environmental changes (antecedents and consequences remained consistent). The Autism Spectrum Disorder Comorbid for Children (ASD-CC) was administered and results revealed a clinically significant elevation on the worry/depressed subscale: a significant number of depressive symptoms were endorsed compared with children with ASD without a comorbid diagnosis.

Based on the results of the full assessment, including observations, parent interview and standardized assessments, diagnoses of autistic disorder and depressive disorder NOS were assigned.

Treatment implications
Accurate diagnoses based on all 4 parameters cited above have important implications for treatment. When comorbid psychopathology is present, effective interventions will likely be multifactorial. Accurate diagnosis is particularly important in present-day practice because medications and psychosocial interventions are becoming more and more disorder specific.

The dynamic nature of ASD over the long term is being recognized. Fecteau and colleagues¹⁷ point out that ASD symptom profiles may change considerably over the life span. The same is true of comorbid psychopathology because onset can vary and severity of symptoms can wax and wane. The evaluation of treatment effects using systematic measures of core symptoms as intervention progresses is essential. Similarly, even when stable, effective treatment is established, there is no assurance that advancing age and changing environmental status will not lead to the need for periodic reevaluation. Addressing all these variables in a life span model should be considered.

Conclusions
Accurate diagnosis is essential if the clinician hopes to provide effective treatment. Many children and adults with ASD are mislabeled or misclassified. Siklos and Kerns¹⁸ found that on average, parents visited more than 4 professionals over 3 years before receiving an accurate diagnosis. The most impressive aspect of these data, in our view, is that parents had the perseverance and willingness to expand the level of energy and family resources needed to achieve a correct assessment. They deserve better.

Comorbid psychopathology further complicates the ASD diagnostic picture. However, a systematic, stepwise, evidence-based approach can lead to accurate identification of all relevant problems experienced by the individual with ASD. The recognition that these co-occurring disorders may be present, and the systematic application of diagnostic methods and principles should lead to more effective diagnosis and treatment.

References:

1. Starr E, Berument SK, Pickles A, et al. A family genetic study of autism associated with profound mental retardation. J Autism Dev Disord. 2001;31:89-96.
2. Centers for Disease Control and Prevention. Autism Information Center. Published February 9, 2007. http://www.cdc.gov/ncbddd/autism/overview.htm. Accessed August 25, 2008.
3. Matson JL. Current status of differential diagnosis for children with autism spectrum disorders. Res Dev Disabil. 2007;28:109-118.
4. Croen LA, Grether JK, Hoogstrate J, Selvin S. The changing prevalence of autism in California. J Autism Dev Disord. 2002;32:207-215.
5. Gillberg C, Billstedt E. Autism and Asperger syndrome: coexistence with other clinical disorders. Acta Psychiatr Scand. 2000;102:321-330.
6. Helverschou SB, Bakken TL, Martinsen H. The Psychopathology in Autism Checklist (PAC): a pilot study. Res Autism Spectr Disord. 2008. In press.7. Matson JL, Nebel-Schwalm MS. Comorbid psychopathology with autism spectrum disorder in children: an overview. Res Dev Disabil. 2007;28:341-352.
8. Matson JL, Minshawi NF. Functional assessment of challenging behavior: toward a strategy for applied settings. Res Dev Disabil. 2007;28:353-361.
9. Matson JL, Nebel-Schwalm MS, Matson ML. A review of methodological issues in the differential diagnosis of autism spectrum disorders in children. Res Autism Spectr Disord. 2007;1:38-54.
10. Filipek PA, Accardo PJ, Ashwal S, et al. Practice parameter: screening and diagnosis of autism: report of the Quality Standard Subcommittee of the American Academy of Neurology and the Child Neurology Society. Neurology. 2000;55:468-479.
11. Schopler E, Mesibov GB, Kunce LJ. Asperger Syndrome or High-Functioning Autism? New York: Springer; 1998.
12. Matson JL, Boisjoli JA. Strategies for assessing Asperger’s Syndrome: a critical review of data methods. Res Autism Spectr Disord. 2008;2:237-248. 13. Rojahn J, Matson JL, Lott D, et al. The Behavior Problems Inventory: an instrument for the assessment of self-injury, stereotyped behaviors, and aggression/destruction in individuals with developmental disabilities. J Autism Dev Disord. 2001;31:577-588.
14. Matson JL. Challenging Behaviors: QABF. Disability Consultants, LLC. www.disabilityconsultants.org/QABF.htm. Accessed March 16, 2009.
15. Ghaziuddin M, Ghaziuddin N, Greden J. Depression in persons with autism: implications for research and clinical care. J Autism Dev Disord. 2002;32:299- 306.
16. Matson JL, Wilkins J, González ML. Early identification and diagnosis of autism spectrum disorders in young children and infants: how early is too early. Res Autism Spectr Disord. 2008;2:75-84.
17. Fecteau S, Mottron L, Berthiaume C, Burack JA. Developmental changes of autistic symptoms. Autism. 2003;7:255-268.
18. Siklos S, Kerns KA. Assessing diagnostic experiences of a small sample of parents of children with autism spectrum disorders. Res Dev Disabil. 2007;28:9-22.
Evidence-Based References
Matson JL. Current status of differential diagnosis for children with autism spectrum disorders. Res DevDisabil. 2007;28:109-118.
Matson JL, Nebel-Schwalm MS. Comorbid psychopathology with autism spectrum disorders in children: an overview. Res Dev Disabil. 2007;28:341-352.