According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), separation anxiety disorder (code 309.21/F93.0) is a fairly common anxiety disorder, occurring in youth younger than 18 years (persistent and lasting for at least 4 weeks) and in adults (typically requiring a duration of 6 mo or more). Separation anxiety disorder can also be associated with panic attacks that can occur with comorbid panic disorder. Separation anxiety disorder consists of persistent and excessive anxiety beyond that expected for the child's developmental level related to separation or impending separation from the attachment figure (eg, primary caretaker, close family member) as evidenced by at least 3 of the following criteria:
Recurrent excessive distress when anticipating or experiencing separation from home or from major attachment figures
Persistent and excessive worry about losing major attachment figures or about possible harm to them, such as illness, injury, disasters, or death
Persistent and excessive worry about experiencing an untoward event (eg, getting lost, being kidnapped, having an accident, becoming ill) that causes separation from a major attachment figure
Persistent reluctance or refusal to go out, away from home, to school, to work, or elsewhere because of fear of separation
Persistent and excessive fear of or reluctance about being alone or without major attachment figures at home or in other settings
Persistent reluctance or refusal to sleep away from home or to go to sleep without being near a major attachment figure
Repeated nightmares involving the theme of separation
Repeated complaints of physical symptoms (eg, headaches, stomachaches, nausea, vomiting) when separation from major attachment figures occurs or is anticipated
In order to meet criteria for this disorder, it must cause clinically significant distress or impairment in social, academic, occupational, or other important areas of functioning and is not better explained by another mental disorder such as refusing to leave home because of excessive reluctance to change in autism spectrum disorder, delusions or hallucinations concerning separation in psychotic disorders, refusal to go outside without a trusted companion in agoraphobia, worries about ill health or other harm befalling significant others in generalized anxiety disorder, or concerns about having an illness in illness anxiety disorder. (See Epidemiology, History.) 
Separation anxiety is often the precursor to school refusal, which occurs in approximately three fourths of children who present with separation anxiety disorder. It is important to screen for selective mutism because some children may have school refusal as a symptom of selective mutism. The diagnosis of selective mutism involves a comprehensive evaluation, including ruling in or out comorbid conditions such as expressive and receptive language delays and other communication disorders. [2, 3] Also see Anxiety Disorders, Social Phobia and Selective Mutism. (See Epidemiology.)
Panic attacks can also be a cause of school refusal. 
Normal separation anxiety
Separation anxiety is developmentally normal in infants and toddlers until approximately age 3-4 years, when mild distress and clinging behavior occur when children are separated from their primary caregivers or attachment figures (eg, being left in a daycare setting).
Symptoms of clinically significant separation anxiety
Separation anxiety disorder generally manifests with clinically significant symptoms of anxiety, such as unrealistic and recurrent worries about harm occurring to loved ones, especially when separated or faced with threatened separation from the primary attachment figure, along with severe distress and impairment in functioning. The DSM-5 includes criteria for adult separation anxiety disorder that do not require a childhood history of the disorder, although this finding is common. [4, 5] (See History.) Severe distress and impairment in functioning may be indicated by the following signs:
Reluctance to fall asleep without being near the primary attachment figure
Excessive distress (eg, tantrums) when separation is imminent
Nightmares about separation-related themes
Homesickness (ie, a desire to return home or make contact with the primary caregiver when separated)
Frequent physical or somatic symptoms, such as abdominal pain and palpitations
Boys and girls do not significantly differ in symptom presentation.
In addition, physical/somatic symptoms (especially frequent in older children and adolescents), such as dizziness, lightheadedness, nausea, stomachache, cramps, vomiting, muscle aches, or palpitations, may be present and problematic, causing the child and family to seek medical treatment because of impaired ability to attend school or meet social responsibilities. (See Epidemiology, History.)
Transient developmental fears (eg, fear of the dark) are generally normal and do not interfere with normal functioning or result in long-term developmental difficulty; however, studies show a subgroup of children who do not meet the criteria for diagnosis of an anxiety disorder but who may have substantial impairment later in life.
Studies of children who, in first grade, present with significant symptoms of anxiety (enough to cause clinically significant impairment in social and academic functioning) reflect a correlation with significant impairment in reading and math achievement 5-6 years later.
Complications of separation anxiety can also include the following:
Substance abuse or dependence
Long-term follow-up studies of children successfully treated for school refusal because of separation anxiety reveal that some children have continued impairment of social functioning (ie, social and affective constriction), despite having returned to school. This may reflect the long-term impairment and morbidity and unchanging dysfunctional parent-child interaction at home. (See Treatment and Management.
A recent study found that for cognitive-behavioral therapy (CBT), the quality of the treatment relationship between the youth and the therapist plays a significant role in outcome. A very strong treatment relationship predicted positive outcome with CBT alone; for youths treated with sertraline alone or combination treatment with sertraline and CBT, there appeared to be less influence on outcome related to the quality of the treatment relationship, with a possible implication that externally imposed biochemical influences on brain functioning might be able to override relationship-based influences on anxiety. 
Prompt treatment of school refusal is key to shorten the course of the disorder, as is it challenging to reduce the tangible reinforcement of school nonattendance. Without treatment, as many as 40-50% of these youths are at risk for not graduating high school due to the intensity and chronicity of their anxiety. 
A study of 62 school-refusing adolescents (ages 11 to 16.5 years) using a randomized controlled trial design in Australia found more improvement in anxiety and depressive symptoms than in school attendance, underscoring the long-term nature of school refusal, thus a chronic care approach to school refusal is needed even through combined treatment – augmentation of cognitive behavior therapy (CBT) with fluoxetine improved outcomes. 
Research results regarding hormonal influences during pregnancy and the neonatal period suggest that maternal endocrine activation during pregnancy (eg, exposure to ACTH, dexamethasone, or conditions that cause their release) and/or early separation or loss (eg, the neonate not being raised by the original primary caregiver) may result in lower cortisol levels overall and may correlate later in development with clinically significant symptoms of anxiety, learned helplessness, and depression.
Recent research evidence indicates that anxiety disorders in general, and separation anxiety specifically, are linked to dysregulation in the fear and stress response system in the brain and are one of the most common causes of school refusal. 
Studies show that children of adults with anxiety disorders have higher rates of anxiety disorders. Experts have postulated that early and traumatic separation from the attachment figure (as well as a family history of anxiety disorders or depression in first-degree relatives) may increase the likelihood of the child and, later on, the adolescent or adult developing separation anxiety disorder, school phobia, and depressive-spectrum disorders. [11, 12]
Examples of early and traumatic separation include a prolonged stay away from the primary caregiver during the neonatal period; later sudden hospitalization; early loss of attachments because of death or divorce; or an interactive pattern with an over-protective, needy, or depressed parent.
In addition, some children may be more vulnerable to separation anxiety based on their temperament (ie, level of anxiety dealing with new situations).
Incidence in the United States
The prevalence of school refusal and separation anxiety disorder ranges from 1.3% in individuals aged 14-16 years to 4.1-4.7% in children aged 7-11 years, with an average prevalence rate of 2-4%. As many as one third of children with separation anxiety disorder have comorbid depressive disorder, and as many as 27% have another disruptive behavior disorder, such as attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder, or conduct disorder.
In 1987, Burke et al reported that 5% of school-aged children refuse to attend school.  In 2005, the Centers for Disease Control and Prevention (CDC) prioritized the identification of the cause behind students not graduating high school. According to the report, as many as 40% of students who do not graduate high school have a diagnosable mental health disorder; as many as one half of those individuals may have anxiety disorders, such as posttraumatic stress disorder (PTSD) and school phobia.
In 2003, Egger et al reported that among children with anxious school refusal and truancy, as many as 88% had a psychiatric disorder.  Children with a history of pure truancy had high rates of oppositional defiant disorder (odds ratio, 2.2), depression (odds ratio, 2.6), and conduct disorder (odds ratio, 7.4). Anxious school refusal and truancy are distinct, but not mutually exclusive, disorders; thus, accurate diagnosis of comorbid conditions is important.
In 2001, McShane reported that one half of 192 adolescents with school refusal had a positive family history of psychiatric illness; those admitted for inpatient treatment were more likely to have a diagnosis of comorbid mood disorder and a maternal history of psychiatric illness. 
Scales such as the School Refusal Assessment Scale-Revised (SRAS-R) should be helpful in determining specifics of incidence and whether response to treatment differs among populations with low socioeconomic status, including ethnic minorities, with the goal being more accurate and earlier identification and prevention of school refusal. 
Anxiety-related school refusal is highly associated with other psychiatric disorders and generally begins when the child first enters school (age 5-6 y) and increases at age 10-11 years, at which time truancy begins. School nonattendance( especially when it intensifies) and truancy are associated with an increased risk for social problems such as school failure, unemployment, drug misuse, and delinquency, and there are significant relationships between parenting style, relative poverty, living in socially disadvantaged areas, attitudes towards school, the quality of the school system, and the quality of peer interactions. [16, 17]
In 1990, Bowen et al reported a 2.4% overall prevalence rate. 
Up to 60% of students at secondary schools in Germany report having avoided attending school for several hours or even a whole day over the course of their schooling. Proportionally more students in Germany compared with the rest of Europe (in 2006, about 76, 000; about 8% of the total) do not graduate secondary school. 
As previously mentioned, physical/somatic symptoms (especially frequent in older children and adolescents), such as dizziness, lightheadedness, nausea, stomachache, cramps, vomiting, muscle aches, or palpitations, may be present and problematic in individuals with separation anxiety.
A recent Australian study  found poorer overall child functioning at age 2-3 years in the context of overprotective mothering, likely due to higher maternal separation anxiety behaviors.
Extremely rare instances of mortality occur in severe separation anxiety. In "mothering to death" cases in the United Kingdom, the primary caregiver of an initially physically healthy child (generally an only child) interacted with the child in such a way that the child was perceived and behaved as physically ill and helpless; as adults, these children functioned as dependent and feeble individuals.
In one such case in the United Kingdom, the child became disabled and died.  This example is reflective of unchanging dysfunctional parent-child interaction at home.
Mortality generally results from associated major depression that may lead to suicide.
No specific differences in prevalence rates are noted for specific racial or cultural groups.
Somewhat increased incidence has been reported among close-knit families of lower socioeconomic status, as well as among single-parent families.
Mean onset of separation anxiety disorder is at age 7.5 years. Mean onset of school refusal is at age 10.3 years.
Separation anxiety disorder is most frequent among younger children. One study lists prevalence rates for children aged 7-11 years at 4.1%; the same study lists prevalence rates for children aged 12-14 years at 3.9% and a prevalence rate of 1.3% for adolescents aged 14-16 years.
Separation anxiety disorder may wax and wane over a period of years. Approximately 30-40% of affected individuals have continued psychiatric symptoms into adulthood. Some studies have indicated as that as many as 65% of individuals with separation anxiety disorder have a comorbid anxiety disorder. 
The prognosis is good with early detection and treatment involving the family of the child.
Note that prevention of separation anxiety and school refusal begins with professional recognition of excessive attachment disorder and dynamics. Such prevention begins during yearly checkups in the pediatrics office, with discussions of healthy separation techniques. Educate families regarding healthy ways to deal with the inevitable stresses that occur in families with children and healthy ways to deal with sibling rivalry.
Weekly individual and family behavioral therapy, including cognitive-behavioral methods, is recommended to practice overcoming resistance to normal separation as well as to practice communicating differently as a family.
Recommend support for parents who may also have concurrent mental health or substance abuse issues. Address family violence prevention. Address any parental issues related to a sense of loss or feeling of abandonment or loneliness once the child or adolescent returns to a normal level of functioning and no longer requires the intense level of interaction with the parent or parents.
Prevention of secondary gain
A patient’s family frequently reinforces separation anxiety symptoms. For example, when the family experiences a major life stress or illness and the child expresses mild refusal to leave the primary caregiver (who may be anxious, distressed, or depressed), the child is not firmly encouraged to appropriately separate and instead is rewarded either overtly or covertly for refusal to separate (eg, when the child who refuses to leave is given extra attention or when the child who refuses to attend school is excused by the parent). In these instances, the parent does not clearly give the child the task of developing strategies to adapt to the separation.
As a result, psychoeducation with the family is important so that the child is rewarded for developmentally appropriate actions and does not receive secondary gain from the symptoms of school refusal or separation anxiety disorder.
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