Phobic disorders differ from generalized anxiety and panic disorders in that

11.2.2 Comorbidity between SUD and anxiety disorders

Anxiety disorders are among the most common psychiatric disorders in the general population, affecting up to 20% of adolescents. Anxiety disorders tend to be more common among females than males (Essau, Lewinsohn, Olaya, & Seeley, 2014). Adolescents meeting the criteria of anxiety disorders have been described as generally withdrawn, fearful of situations or objects, afraid of being in a social situation, and are inhibited (APA, 2013). In DSM-5, there have been some changes in the classification of anxiety disorders. Obsessive-compulsive disorder (included in the obsessive-compulsive and related disorders), acute stress disorder, and posttraumatic stress disorder (included in the trauma and stress-related disorders) are no longer considered anxiety disorders in DSM-5. Anxiety disorders which commonly occur in adolescents include social phobia (i.e., an irrational fear of being judged in social situations), specific phobia (i.e., a fear of specific objects or situations), generalized anxiety disorder (i.e., excessive and uncontrollable worry about life events), and panic disorder (i.e., discrete fear attacks that are associated with cognitive and physical symptoms).

Of all the anxiety disorders, social anxiety disorder is the one that most commonly co-occurs with AUD, with about 13% of those with social anxiety disorder having AUD (Buckner, Heimberg, Ecker, & Vinci, 2013; Schneier et al., 2010). It is estimated that 80% of the comorbid cases had social anxiety disorder before AUD; the presence of social anxiety disorder at baseline is associated with four times the odds of having AUD at follow-up (Schneier et al., 2010). Some authors consider drug consumption as a “means to an end” (Bulley, Miloyan, Brilot, Gullo, & Suddendorf, 2016, p. 64) such as managing a social situation. Indeed, one of the motivations to drink among individuals with social anxiety disorder is to provide relief or to reduce tension that arises in social situations and to facilitate social interactions. For example, a study by Battista, MacDonald, and Stewart (2012) showed that participants with social anxiety disorder spoke longer with an interaction partner after drinking alcohol; the interaction partner also showed more positive social behavior to participants with social anxiety disorder who drank alcohol compared to those who consumed a nonalcoholic beverage.

Most of the studies in comorbidity between SUD and anxiety disorders were conducted in Western countries. These findings, while informative, may not be generalizable to adolescents in non-Western countries. To make up this gap, Stapinski, Montgomery, and Araya (2016) conducted a study among adolescents in Chile to examine the extent to which depression, generalized anxiety, social anxiety, and panic symptoms independently predict new cases of cannabis use as well as to predict the frequency of use 18 months later. The findings showed a high comorbidity among the various types of substances such as between cannabis, tobacco, and alcohol use frequency. After adjusting for the use of cannabis at baseline, generalized anxiety, panic, and depressive symptoms were associated with a higher frequency of cannabis use 18 months later. However, after considering all predictors simultaneously, only generalized anxiety symptoms were independently associated with the frequency of subsequent cannabis use. Their finding also showed that among adolescents with high levels of generalized anxiety symptoms, the predicted probability of occasional and recurrent cannabis use was 39.8% and 5.9%, respectively. Among adolescents with low levels of generalized anxiety symptoms, the predicted probability of occasional and recurrent cannabis use was 21.1% and 1.6%, respectively. These findings were interpreted as supporting the internalizing pathway to substance use (Hussong, Jones, Stein, Baucom, & Boeding, 2011) in that adolescents with generalized anxiety, panic, and depression tend to use cannabis to cope with negative affects and tension and anxiety symptoms.

Classification of Anxiety Disorders

The fourth edition of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and its text revision, DSM-IV-TR (which was current when this chapter was conceived), outlined 12 categories of anxiety disorder.3 In comparison to the earlier DSM-III, three new anxiety disorders were added to DSM-IV: acute stress disorder, anxiety disorder due to a general medical condition, and substance-induced anxiety disorder. The categorization of anxiety disorders was subsequently divided into anxiety, obsessive–compulsive, and trauma- and stressor-related disorders in the fifth edition, DSM-5, published in 2013 (Table 37.1).4 The historical aspects of anxiety disorder classification are of interest to clinicians and researchers since they underpin both research methodology and clinical treatment. In DSM-II, anxiety disorders were categorized under “neurosis”, a term which was later dropped from DSM-III. Three anxiety disorders were outlined in DSM-II, namely anxiety neurosis, phobic neurosis, and obsessive compulsive neurosis. DSM-III attempted to further subcategorize anxiety disorders, for example incorporating both generalized anxiety disorder and panic disorder. These diagnoses would have both fallen under anxiety neurosis in DSM-II; however, this new categorization reflected increasing knowledge about the disease course and treatment of these conditions. The increase in the number of categories seen in DSM-IV and DSM-5 could be perceived as an increasing recognition and awareness of the importance of anxiety disorders. However, some critics point out that the discriminative validity of these disorders may be undermined as we contend with increasingly significant overlap of symptomatology and comorbidity between anxiety and other psychiatric disorders.

TABLE 37.1. Categorization of Anxiety, Obsessive–Compulsive, and Trauma-Related Disorders in DSM-5

Source: American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. DSM-5. Arlington, VA: American Psychiatric Publishing; 2013.4

A number of different anxiety disorders are described in DSM-5, including panic disorder, social phobia, PTSD, and generalized anxiety disorder. Several lines of research suggest that a majority of anxiety disorders may be conceptualized as disorders of fear.5,6 Large-scale population studies such as the NEMESIS study in the Netherlands have highlighted how a “fear” dimension appears to be integral to social phobia, specific phobia, agoraphobia, and panic disorder. Conversely, the NEMESIS study also found that although generalized anxiety disorder shares an “anxiety–misery” dimension similar to that of major depression and dysthymia, it does not share the “fear” dimension common to panic disorder, specific phobia, and PTSD.6 This reinforced previous findings by Krueger, who investigated patterns of psychiatric comorbidity using a sample of 8098 participants from the National Comorbidity Survey.5 Collectively, these findings are consistent with a subdivision of the broad class of anxiety disorders into disorders of anxiety and disorders of fear (Fig. 37.1).

Diagnosis

Anxiety disorders have been found to cooccur at highly variable rates, 11–84%, with ASD individuals (White et al., 2009). This variability may be due in part to the highly heterogeneous presentation of ASD as well as the complexity of the manifestations of anxiety in the ASD population, not to mention the biases which may be present for or against diagnosis in those with comorbid ASD. We continue to recommend use of the terms simple and anxious avoidance to help differentiate between stimuli and situations that may constitute an anxiety disorder in individuals with and without ASD. However, the current Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5; American Psychiatric Association, 2013) classifies anxiety as the “anticipation of future threat” and furthermore, various anxiety disorders can be differentiated by the “specific content of the thoughts and beliefs that may induce the fear or anxiety.” Given this definition, how can the current diagnostic classifications of anxiety disorders be applied to those individuals with limited cognitive and/or verbal abilities? Early studies conducted on ASD suggested approximately half of those individuals diagnosed were incapable of speech acquisition (Rutter, 1978). Recent estimates have shown a marked decrease in these estimates due in part to earlier assessment and detection techniques (Klingler et al., 2003); however, the fact remains that some individuals with ASD never develop functional speech.

These deficits in verbal communication in a subpopulation of individuals with ASD may account for some of the variability in comorbidity rates. Researchers have shown higher levels of anxiety to be associated with functional language in individuals with ASD (Gadow and Sprafkin, 1998, 2002). Researchers have also argued these findings may be complicated by diagnostic overshadowing (Mason and Scior, 2004), while data from other studies suggests that individuals with ASD simply do not meet cooccurring criteria for other psychiatric conditions (Leyfer et al., 2006; Witmer and Lecavalier, 2010, Kaat et al., 2013). Differential diagnosis of ASD and anxiety, then, requires a careful evaluation of those symptoms unique to each disorder as well as common presentations of symptom patterns for individuals evincing comorbidity. Additionally, findings from a number of studies have shown that fears and behavioral responses common among the typically developing population, are not necessarily replicated in individuals with ASD (e.g., Evans et al., 2005; Kanner, 1943; Matson and Love, 1990).

Due to the overlap of symptomology between ASD and anxiety disorders a number of studies have attempted to differentiate those factors which are inextricably shared from those that may be conceptually differentiable. For example, social avoidance and a preference to be alone are shared qualities between both anxiety and ASD (Baron-Cohen et al., 2001; Roberson-Nay et al., 2007; White et al., 2012). However, ASD individuals may be less aware or have less concern for the social rejection component found in social anxiety disorder (Leyfer et al., 2006; Muris et al., 1998). Also, excessive worries around environmental changes or deviations from a schedule can be common in both groups of disorders (generalized anxiety disorder and ASD), as can be highly rigid behaviors, verbal rituals, and compulsions (OCD and ASD). The difficulty comes from determining whether these behaviors occur to reduce distress in the case of OCD or are generalized worry and broad anxious avoidance in the case of GAD. Differential diagnosis would also require the clinician to assess those behaviors seen less typically in non-ASD populations such as strict adherence to routine, circumscribed interests, and repetitive behaviors.

Attempts to distinguish between the similarities between anxiety and ASD symptoms have typically supported distinctiveness within areas which do not necessarily lend themselves to application in those who are minimally verbal or lower functioning. For example, Farrugia and Hudson (2006) found the only difference between anxiety presentation in typically developing and nontypically developing groups was reported thought patterns of social threat and physical injury, areas which would be difficult if not impossible to assess in a minimally verbal population. Atypical presentations of anxiety are also common in those with ASD and can include social fear without a negative evaluative component, nontraditional specific phobias, and fear of change and novelty (Kerns et al., 2014). Leyfer et al. (2006) found typical phobias were rarely endorsed in the ASD population; however, fears of loud noises, crowds, and shots/needles were much more common. Additionally, idiosyncratic fears (e.g., flushing toilets, beards, mechanical objects) have also been found in ASD individuals (Richman et al., 2012). Many of these problematic or avoided stimuli raise additional questions as to whether the problem is fear or anxiety versus altered sensory function. For example, repetitive and ritualistic behaviors seen in obsessive-compulsive disorder (OCD) are also commonly observed in many persons with ASD (McDougle et al., 1995), including those individuals that are not suspected of experiencing any anxiety. In such cases, repetitive behaviors may be a preferred self-stimulatory activity, in contrast to ritualistic behavior triggered by obsessional thoughts that is the hallmark of OCD. Caution should be taken to not immediately characterize these ritualistic or stereotypic behaviors as “OCD” based on their repetitive nature. Avoidance is another area which may present itself differentially as younger children and those with verbal deficits have been shown to express fear and avoidance in conjunction with other behaviors such as aggression, destruction of property, and self-injurious behavior (Hagopian et al., 2001; Ricciardi et al., 2006).

Finally, of particular concern with the diagnosis of anxiety in minimally verbal ASD populations is that strict adherence to the DSM-5 diagnostic criteria may miss a significant proportion of these individuals in need of clinical services due to verbal requirements of the diagnostic criteria. For example, Criterion A for separation anxiety disorder requires endorsement of 3 out of 8 symptoms; however, 4 of the 8 symptoms require the expression of “worry, thematic explanations of nightmares, or complaints” (APA, 2013). Additionally, some disorders such as selective mutism and GAD may inherently be unavailable to the minimally verbal ASD population when adhering to strict diagnostic classification. Given the host of challenges associated with differential diagnosis, thorough assessment procedures are considered to be vitally important.

Considerations for future genetic investigations of anxiety disorders: classification of environmental factors

An idea that was discussed above was the classification of anxiety disorders according to symptom dimensions as an alternative to diagnostic criteria. Kendler and others (2003) summarized findings of the Virginia Twin Registry and classified significant life events according to the nature of the event. Danger events were those that were related to an unpleasant adverse consequence. Humiliation events were those associated with rejection or failure. Loss events included occasions in which there was a real or perceived loss of a person, possession, or respect (Kendler et al., 2003). Given that the most effective genetic analyses of anxiety disorders will involve reliable G×E models, it is important to adequately define the nature of the life events that may interact with genetic risk factors to produce anxiety-related phenotypes.

2 Methods

This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (Moher et al., 2009). Institutional review board approval was waived as no patient data were accessed for the study.

2 Methods