Chapter 4 Anxiety disorders, their relationship to hypermobility and their management

Rocío Martín-Santos, Anthony Bulbena, José Alexandre Crippa

Introduction

Anxiety is a universal human experience, with psychological, physiological, behavioural and cognitive manifestations. Anxiety becomes abnormal when its intensity and duration is disproportionate or when it occurs without recognizable threat.

The most recent mental disorders classifications (DSM-IV and ICD-10) describe different anxiety disorders:

• Panic with and without agoraphobia – characterized by attacks of extreme anxiety accompanied by sympathetic arousal that can be associated with the fear of having another attack, and with avoidance behaviour

• Agoraphobia – an extended avoidance behaviour

• Generalized anxiety disorder – a chronic disturbance characterized by excessive anxiety and worry

• Social phobia disorder – e.g. public-speaking phobia

• Specific phobia – e.g. animal phobia

• Post-traumatic stress disorder

• Anxiety in medically ill – e.g. thyroiditis.

Prevalence and association of anxiety disorders

The life-time prevalence of anxiety disorders is approximately 28% in the general population (Kessler & Wang 2008). They are more prevalent in women than men, and in some such as phobias and separation anxiety disorder, the greatest frequency of onset is found in early childhood. Other anxiety disorders such as panic disorder, generalized anxiety, and post-traumatic stress disorder, typically occur in adulthood. The 12-month-prevalence estimates of the DSM-IV disorders showed that the highest of these is specific phobia (8.7%), social phobia (6.8%), and major depression disorder (6.7%). Among school children, anxiety disorders are the most prevalent (18.1%), followed by mood disorders (9.5%), and substance disorders (3.8%) (Kessler & Wang 2008). Moreover, there is a considerable degree of overlap in these disorders. Most of the anxiety disorders run a chronic course.

Genetics

Genetic epidemiology studies suggest that anxiety disorders are familial and moderately heritable. Linkage studies have implicated several chromosomal regions. However, candidate gene association studies have not established a role for any specific loci to date. It seems that genes underlying these disorders overlap and transcend diagnostic boundaries. Understanding animal models of anxiety, the neuroimaging of phenotypes, and intermediate phenotypes such as anxiety-related personality (‘neuroticism’, ‘harm avoidance’, ‘behavioural inhibition temperament to the unfamiliar’) may provide better clues in future (Smoller et al 2008).

Recognizing anxiety disorders

There are many rating scales measuring anxiety or depression. Methods to improve the recognition of anxiety disorder in busy medical settings include the integration of simple screening questions into clinical interviews and the application of short screening questionnaires.

One of the most commonly used validated screening questionnaires in medical settings is the Hospital Anxiety and Depression Scale (HADS) (Zigmond & Snaith 1983). The HADS consists of seven items.

Another validated screening instrument frequently used is the PRIME-MD Patient Health Questionnaire (PHQ) (Spitzer et al 1999, Díez-Quevedo et al 2001, Kroenke et al 2001, 2002). It includes a panic disorder module, and a generalized anxiety module as well as a depression module which has been validated in large sample populations against the diagnosis of mental health professionals. The PHQ is self-administered and gives diagnoses approaching the DMS-IV criteria.

Both PHQ and HADS can be recommended as valid and practicable screening instruments for anxiety disorder. In particular the PHQ has the best operating characteristics with overall accuracy and specificity superior to other measures in medical as well as in psychosomatic cases (Löwe et al 2003).

The SF-36 item is a questionnaire of quality of life with good psychometric properties (McHorney et al 1993, Sareen et al 2006). It is often used in studies of musculoskeletal pain.

Anxiety disorders and medical illness

Emerging evidence suggests that anxiety disorders are related to other medical illnesses. Anxiety disorders are associated with high rates of medically unexplained symptoms, increased utilization of healthcare resources (Katon & Walker 1998, McLaughlin et al 2006), and poor quality of life and disability (Sareen et al 2006). Aside from the association with other conditions, anxiety disorders can manifest in a number of ways (Table 4.1).

Table 4.1 Physiologic, cognitive and behaviour factors of anxiety

Somatic	Cognitive	Behaviour
*Muscular:* Tremor, spasm Muscle weakness Discomfort Pain regions *Autonomic:* Palpitations Flushing Feeling of heat Perspiration Clammy hands Dryness of mouth Rapid breathing Tightness in the chest	Worry Fear Anticipation Fear of being unable to cope Fear of developing anxiety Feelings of depression *Hyper-arousal:* Alertness Excessive vigilance Feeling excessive stimulation Distractibility Insomnia	Flushing Pallor Strained voice Tense facial Restlessness Immobilization Laughing Crying Over talkativeness

They have been associated with several physical conditions such as functional gastrointestinal disease, cardiovascular disease, asthma, neoplasia and chronic pain (Roy-Byrne et al 2008). Results from the National Co-morbidity Survey-Replication (NCS-R) (Kessler et al 2003) showed that various anxiety disorders had equal or greater association than depression with four chronic physical disorders, namely hypertension, arthritis, asthma and gastrointestinal ulcers.

Panic disorder and agoraphobia are intensely associated with cardiovascular illness and joint and bone diseases (Sareen et al 2005). Recent data from clinical settings showed that patients with panic disorder with or without agoraphobia had a 4.2-fold increase in the risk of neurological disorders, 3.9-fold increased risk of cardiovascular disease, a 3.8-fold increased risk of musculoskeletal disorders, and 2-fold increase in the risk of digestive diseases (Pascual et al 2008). These results support previous research in co-morbid anxiety disorders and chronic pain (Norton & Asmundson 2004; McWilliams et al 2003, 2004).

The co-morbidity of anxiety disorders and pain has received little attention even though recent studies show that these disorders are as likely to co-occur with chronic pain conditions as depressive disorder. A cross-national population-based study of the association of chronic back or neck pain with a broad spectrum of mental disorders (Demyttenaere et al 2007) found that, after adjusting for age and gender, anxiety, alcohol and mood disorders all occurred with greater frequency among patients with chronic back or neck pain. The World Mental Health Survey, undertaken in 18 countries (N = 85 088), highlighted the importance of assessing mental disorder status in the community and the need for specific care and management among those with back or neck chronic pain (Chapter 12.8 – Yellow Flags). Data from the same survey showed a higher prevalence of chronic pain conditions among females and older persons. Interestingly, the association between chronic pain and depression-anxiety disorders was similar in developed and developing countries (Tsang et al 2008).

Anxiety traits and hypermobility

There are some data to show that anxiety is common among subjects with joint hypermobility (JHM).

Hypermobile individuals with high levels of anxiety traits are more prone to have fears, anxiety sensitivity, anxiety expectations, illness fears, and to develop avoidance behaviour. They may respond to anxiety symptomatology with catastrophic misinterpretations of the physical arousal, pain and hypervigilance. These personality characteristics occur in both genders (Bulbena et al 2004a). In one study of 553 workers (61.4% male) attending a routine medical check-up, the presence of JHM and anxiety traits was evaluated using the Spielberg Trait Anxiety Scale (Spielberg et al 1986). Twenty-six percent of women and 17.6% of men demonstrated presence of JHM. Hypermobile women showed significantly higher anxiety traits than non-hypermobile women (P value = 0.0008). A similar pattern was seen among men (P value = 0.03).

The relationship between anxiety and JHM has also been studied in a survey of university students in Brazil (N = 2300). Hypermobility was assessed by a screening questionnaire (Chapter 1 – Table 1.7) and anxiety was measured by the self-administered questionnaire the Beck Anxiety Scale (Beck & Steer 1993). This anxiety scale assesses four factors: autonomic symptoms, neuroticism, panic and subjective symptoms. Hypermobile students had higher scores on the autonomic symptoms compared with non-hypermobile subjects (P value <0.005) (Crippa et al, authors’ correspondence, unpublished). These results may add support to the growing evidence in the literature of autonomic dysfunction found in JHS (Chapter 6.1), though one must note that the individuals in the study were only identified as having presence of JHM and not necessarily as having JHS by the Brighton Criteria (Chapter 1).