Bipolar disorder in adults with Asperger׳s Syndrome: A systematic review

Abstract

Background

Asperger׳s Syndrome (AS) is a neurodevelopmental disorder included in the Autism Spectrum (ASD). The current literature shows growing evidence of a high rate of comorbidity between AS and other psychiatric disorders, particularly Bipolar Disorder (BD). We reviewed available epidemiological and clinical data on BD–AS comorbidity and its diagnostic and therapeutic implications

Methods

A systematic review of the literature was conducted through PubMed, Scopus and Psych-Info using combinations of the following search terms: Asperger׳s Syndrome, Bipolar Disorder, depression, mood disorder, psychiatric comorbidity, treatment, mood stabilizers, anticonvulsants, antipsychotics, and antidepressants.

Results

BD prevalence in adults with AS ranges from 6% to 21.4% of the cases. Relatives of patients with AS showed a doubled risk of being affected by BD and a BD prevalence near to 10%. When comorbid with AS, BD assumes peculiar features which might shape its under-recognition or misdiagnosis (especially schizophrenia when psychotic symptoms are prominent). Although controlled data on pharmacological treatments in BD–AS comorbidity are substantially lacking, information is derived by open observations, case series and chart reviews. Mood stabilizers should be considered the first choice, and antipsychotics, especially second generation drugs (SGA) with 5-HT2a antagonism, have been shown useful in controlling psychotic and behavioral symptoms and improving social withdrawal. Some evidence of efficacy for the treatment of anxiety, obsessive-compulsive symptoms and depression is reported for SSRI antidepressants. The use of these drugs should be carefully monitored, because activation with hypomanic or manic switches is reported up to 54% of the treated subjects.

Conclusion

BD in AS patients is frequent, usually it onsets during adolescence and is often characterized by atypical presentation, making its correct identification particularly difficult. A correct diagnosis of BD in AS individuals has relevant implications on the choice of adequate psychopharmacological, psycho-social and rehabilitative treatments.

Introduction

Asperger׳s Syndrome (AS), formerly recognized as a specific diagnostic entity in DSM-IV-TR, has been recently included by DSM-5 in the Autism Spectrum Disorders (ASD), together with other Pervasive Developmental Disorders. ASD currently lump together different heterogeneous clinical subtypes such as AS and severe autism, based on a dimensional perspective. This DSM-5 spectrum view permit to include on the broad autistic spectrum not only AS but also many other ASD-variants labeled “high functioning autisms” (HFA) till now. In this perspective new severity “specifiers” permit to distinguish different ASD phenotypes. Indeed, high functioning autisms might be better indicated as ASD with “less marked general impairment” only “requiring support” (level 1), while classical “low functioning “autisms (e.g. with intellectual and language impairment) as “requiring very substantial support” (level 3).

Although it is true that diagnostic criteria are flawed and difficult to implement in clinical practice, patients with AS usually show some peculiar features and a less marked general impairment compared with other autistic phenotypes. Although intelligence and language abilities are always preserved, they usually present atypical features. Cognitive profile can be uneven, with high verbal abilities compared with poor non-verbal skills, visuo-spatial problem solving, and motor performances (included uncoordinated motion, clumsiness, and illegible handwriting). Furthermore, language is formally adequate and often precocious (particularly in lexicon), but usually pedantic, monotonous and poorly communicative. Typically, their ability to recognize non-verbal signals and social-emotional reciprocity are variously impaired. Moreover, AS subjects tend to show highly restricted and fixated interests that are abnormal in intensity or focus, associated with inflexible adherence to routines and hard and fast rules.

Considered a relatively common diagnosis in childhood and adolescence, AS has only recently gained some attention in adults. The data relative to AS prevalence are variable especially in reason of the dispute concerning the distinction from HFA. When not only AS is included in HFA but also many other high functioning ASD-variants the prevalence is likely to be much higher. Moreover, major psychiatric comorbidities, especially with mood disorders and psychoses, may contribute to the underestimation of AS. Indeed, reliable data on the actual AS prevalence among adults are not available. In childhood, the prevalence is estimated to be between 0.02% and 12.27% (Baird et al., 2000, Fombonne and Tidmarsh, 2003, Mattila et al., 2007). Similarly to other ASD forms, AS is considered a “life-long” disorder (Shattuck et al., 2007); as a result, its prevalence in adulthood could be comparable to that seen in childhood (Tantam and Girgis, 2009). Nonetheless, its phenotypic expression may vary in relation to age (Roy et al., 2009) and gender (Lai et al., 2011). Different outcomes can be observed on the basis of the severity of the symptoms: some individuals reach a functioning comparable to that of the general population, showing high levels of adaptation. On the contrary, other subjects present psychopathological manifestations and unusual behaviors, up to suffer from serious functional deficits.

In adults, psychiatric intervention is usually required for the presence of comorbid mental disorders, including both anxiety and mood disorders and disruptive disorders, with impulsivity and aggression. Attention deficit hyperactivity disorder (ADHD) is also often comorbid with both AS and affective disorders. In such contexts, the diagnosis of AS is often underestimated or missed (Raja and Azzoni, 2008, Skeppar et al., 2013). On the other hand, the diagnosis of comorbid psychiatric disorders may also be complicated by the high frequency of atypical manifestations (Tantam and Girgis, 2009). One of the most common comorbidities in clinical settings is Bipolar Disorder (BD). The purpose of this review is to examine the relationship between AS and BD and their epidemiological, clinical and therapeutic implications.