Separation anxiety

The etiology of social anxiety remains unclear however, evidence suggests that developmental and genetic factors may predispose some individuals to social anxiety disorder. Adults with social anxiety disorder are more likely to report a history of childhood shyness and separation anxiety, limited social interaction during adolescence, and having had parents who placed great emphasis on the importance of the opinion of others. 

In this chapter, we consider categorical anxiety disorders as defined by the standardized diagnostic criteria of American Psychiatric Association s Diagnostic and Statistical Manual for Psychiatric Disorders [i.e., DSM-III (1980), DSM-III-R (1987), DSM-IV (1994)]. The subtypes of anxiety states included are panic disorder, agoraphobia, specific phobia, social phobia, generahzed anxiety/overanxious disorder, separation anxiety, and obsessive-compulsive disorder. 

Some suggest that childhood separation anxiety disorder and adult panic disorder share a biological substrate, based at least in part on commonalities in res-... 

Among both children and adults, panic attacks are associated with a set of respiratory abnormalities (Klein, 1993 Pine et ah, 2000). These abnormalities are found not only in panic disorder but also in a range of other conditions, such as separation anxiety disorder and isolated panic attacks, which show strong familial associations with panic disorder. It has been suggested that parents with panic disorder transmit a diathesis for certain forms of anxiety that is apparent in the respiratory system (Pine, 1999), may remain latent (Coryell, 1997), or may vary across development, manifested as separation distress during childhood or as panic attacks after puberty (Klein, 1993 Pine et ah, 2000). 

Ventilatory abnormalities have been identified in first-degree relatives of patients with panic disorder (Perna et ah, 1995 Coryell, 1997), as well as in patients with possible precursors for panic disorders, such as separation anxiety disorder (Pine et ah, 2000) or isolated panic attacks (Perna et ah, 1995). Additionally, studies have found family loading for panic disorder in the relatives of panic patients with respiratory abnormalities (Perna et al., 1996), suggesting that hypersensitivity to CO2 inhalation may be a trait marker for panic disorder rather than a state marker. These data suggest that parents with panic disorder may transmit a diathesis for certain forms of anxiety (e.g., separation anxiety disorder) that is observable in the respiratory... 

Approximately three-quarters of children with OCD have comorbid diagnoses. These include tic disorders (24%-30%) and mood disorders, especially major depression (26%-29%). Riddle and colleagues (1990) found that 38% of children with OCD have other anxiety disorders, while Swedo (1989) more specifically identified increased rates of simple phobias (17%), overanxious disorder (16%), and separation anxiety disorder (7%). Other reported comorbidities include specific developmental disabilities, adjustment disorder with depressed mood, oppositional defiant disorder, attention-deficit hyperactivity disorder (ADHD), conduct disorder, and enuresis/encopresis (Swedo et ah, 1989b Riddle et ah, 1990). 

Studies at the National Institutes of Health (NIH) have detailed the clinical characteristics of patients in the PANDAS subgroup (Swedo et al., 1998). The rate of neuropsychiatric comorbidity in this population is quite striking. Twenty of the 50 children (40%) met DSM-IV criteria for ADHD and/or oppositional defiant disorder (ODD), 18 (36%) for major depressive disorder, 14 (28%) for overanxious disorder, and 10 (20%) for separation anxiety disorder. Six children (12%) were enuretic, often episodically and closely correlated with periods of OCD and tic exacerbations. Depressive symptoms, ADHD, and separation anxiety disorder also waxed and waned in concert with the OCD/ tic symptoms. In addition, exacerbations of OCD and tics were accompanied frequently by the acute onset of choreiform movements (clinically distinct from chorea), emotional lability and irritability, tactile/sensory defensiveness, motoric hyperactivity, messy handwriting, and symptoms of separation anxiety (Perlmutter et al., 1998 Becker et al., 2000). 

Because of the hesitancy to use normal anxiolytic substances (benzodiazepines) in children, TCAs were first studied in the use of school refusal and separation anxiety disorder in the 1970s. There have been both positive (Gittleman-Klein and Klein, 1973, Bernstein et al., 2000, 2001) and negative studies for this indication (Berney et al., 1981 Klein et ah, 1992). 

Klein, R.G., Koplewicz, H.S., and Kanner, A. (1992) Imipramine treatment of children with separation anxiety disorder. J Am Acad Child Adolesc Psychiatry 31 21—28. 

One exception is the behavioral therapy used in the controlled study of IMI for SAD discussed above (Klein et ah, 1992). About half of the 45 subjects enrolled in the study responded to behavioral therapy in the initial 4-week treatment phase prior to medication treatment. The authors noted about half of the subjects who responded to behavioral treatment and did not meet randomization criteria still continued to have clinically significant separation anxiety requiring treatment. Given the results prior to medication randomization, Klein and colleagues (1992) further suggested that behavioral therapy be considered a potential first treatment for SAD before medication treatment. 

The section for emotional disorders in children spans across the following diagnoses separation anxiety disorder social anxiety disorder of childhood phobic anxiety disorder of childhood generalized anxiety disorder of childhood other emotional disorders (with onset specific to childhood) and sibling rivalry disorder. 

G. The fear or avoidance is not due to the direct physiological effects of a substance [e.g., a drug of abuse, a medication) or a general medical condition and is not better accounted for by another mental disorder [e.g., panic disorder with or without agoraphobia, separation anxiety disorder, body dysmorphic disorder, a pervasive developmental disorder, or schizoid personality disorder). 

Klein PS, Melton DA A molecular mechanism for the effect of lithium on development. Proc Natl Acad Sci U S A 93 8455-8459, 1996 Klein RG Is panic disorder associated with childhood separation anxiety disorder ... 

In this context, Gittleman-Klein and Klein (104) conducted a double-blind, placebo-controlled study of 35 nonpsychotic, school-phobic children. They found a good response in all children given imipramine but in only 21 % of those on placebo. Because PD patients often experienced separation anxiety as children, this suggests that some cases of school phobia may be the childhood equivalent of PD, for which imipramine is effective. 

Selective mutism was considered to be a variant of social phobia or social anxiety disorder. In contrast, separation anxiety disorder was considered to be a unique developmental disorder of childhood often presenting as school refusal. 

These medications are used by clinicians to treat a wide range of anxiety-related conditions, including separation anxiety, school phobia, and panic disorder. None of these agents, however, has been the subject of systematic, double-blind, placebo-controlled studies in children or adolescents, and opinions about their effectiveness depend primarily on anecdotal experience and reports. 

The efficacy of TCAs, principally impramine, has also been tested as treatment of separation anxiety and school phobia. Four placebo-controlled studies involving 140 children have been conducted (153, 158, 159 and 160). Whereas early studies were positive, subsequent reports were not. Gittelman-Klein and Klein ( 161) demonstrated a significant benefit over placebo from 6 weeks of treatment with imipramine (mean dose = 159 mg per day) in 45 children with school phobia. A subsequent study using lower amounts of clomipramine (40 to 75 mg per day) was negative but the doses used make interpretation difficult. Also, because of its tolerability and safety profile, clomipramine is generally not used as an anxiolytic agent in children or adolescents. 

Gittelman-Klein R, Klein DF. Separation anxiety in school refusal and its treatment with drugs. In Hersov L, Berg I, eds. Out of school. New York Wiley, 1980 321-341. 

---