© Springer International Publishing Switzerland 2015
Dan J. Stein and Bavi Vythilingum (eds.)Anxiety Disorders and Gender10.1007/978-3-319-13060-6_7Anxiety and Related Disorders in Women
(1)
Department of Psychiatry, University of Melbourne, Parkville, Australia
(2)
Department of Psychiatry, St Vincent’s Hospital Melbourne, Fitzroy, Australia
(3)
Department of Psychiatry, UCT, Rondebosch, Cape Town, South Africa
Anxiety does not empty tomorrow of its sorrows, but only empties today of its strength (Charles Spurgeon)
Anxiety disorders are highly prevalent and persist across the life course. As documented in earlier chapters of this volume, women are particularly prone to anxiety disorders, with around a third meeting diagnostic criteria over the course of a lifetime (Alexander et al. 2007). In this chapter, we will summarize some key points pertaining to the epidemiology, clinical presentation, and treatment of anxiety disorders in women. We will also address the comorbidity between physical illness and anxiety disorders in women. Finally, we will examine the specific challenges faced in treating women with anxiety disorders during pregnancy and lactation.
Epidemiology
Kessler et al. (2012) found the prevalence of anxiety disorders in women in the USA were as follows: specific phobia 12.1 %; social phobia 7.4 %; post-traumatic stress disorder 3.7 %; generalized anxiety disorder 2.0 %; separation anxiety disorder 1.2 %; panic disorder 2.4 %; agoraphobia 1.7 %; obsessive-compulsive disorder (OCD) 1.2 % (Kessler et al. 2012). In an Australian study, Williams et al. (2010) used the Structured Clinical Interview for DSM-IV TR Axis-I Disorders, non-patient edition (SCID-I/NP) to report the prevalence of anxiety and mood disorders, in an age-stratified representative sample of women aged 20 years and older (Williams et al. 2010). The median age of onset of anxiety disorders was 18.5 years and the prevalence of anxiety disorders in women across the life course was 13.5 % with panic disorder (5.5 %) and specific phobias (3.5 %) being the most common.
The preponderance of these conditions in women is not well understood. In a prospective, longitudinal, population-based study of 643 women, psychosocial variables were examined to evaluate whether it was possible to predict the onset of a new anxiety disorder or the recurrence of an existing disorder. The presence of anxiety disorders was assessed every 6 months over a 3-year period, using the Structured Clinical Interview for the Diagnosis of Axis I Disorders (SCID-I). It was found that focusing on negative life events was not a predictor of the onset of anxiety either alone or in interaction with other variables. Significant predictors of anxiety included a history of anxiety, increased anxiety sensitivity (i.e., fear of anxiety-related sensations), and increased neuroticism (Calkins et al. 2009).
The complex interplay between genetic risk factors and environmental influences was studied by Hetteam and colleagues (2005) who reported that there were no differences between the sexes with regard to the vulnerability to develop anxiety disorders. However, these authors suggested that the development of anxiety disorders could be split across the both sexes: firstly, “panic-generalized-agoraphobic anxiety” and secondly, the “specific phobias.” They suggested that the underlying etiology of both of these groups is best explained by the presence of two genetic factors which are additive and common across the disorders, with one genetic factor contributing a more causative role to the first subset of “panic-generalized-agoraphobic anxiety” and a second genetic factor contributing to the second subset of “specific phobias.” Social anxiety disorder (SAD) was influenced by both genetic factors (Hettema et al. 2005).
Social Anxiety Disorder (SAD)
Social anxiety disorder (SAD) affects men and women almost equally with approximately 15 % of women and 11 % of men affected across the life course (Kessler et al. 2005). SAD usually begins in childhood or early adolescence and maintains a chronic course throughout adulthood. The clinical features include experiencing extreme anxiety in social scenarios due to a fear of embarrassment or ridicule. Sufferers often manifest physical signs such as blushing and stuttering if asked to speak in public. People with social phobia may become avoidant of social situations and there is some difference between sexes with women stating that they have more distress when speaking in public or meeting strangers (Turk et al. 1998).
Treatment
Psychological therapies for SAD focus on assertiveness training, cognitive behavioral therapy (CBT) and graded exposure to overcome avoidance behavior (Rodeburgh et al. 2004). Meta-analyses have suggested that individual and group CBT may work equally well for individuals with SAD (Rodebaugh et al. 2004; Liber et al. 2008), and that women and men respond equally well to CBT (Canton et al. 2012).
Panic Disorder
Estimates suggest 1–2 % of the adult population suffer panic disorder (Yates 2009). Common risk factors for the development of panic disorder include female gender, low socioeconomic status, and an anxious temperament in childhood. Panic disorder is associated with an elevated risk of suicide as well as all-cause mortality and cardiovascular disease. It ranks highest among the anxiety disorders in terms of disease burden. There has been interest in the conceptualization of anxiety disorders as resulting from psychopathology during childhood, in particular in relation to the presence of separation anxiety disorder in childhood. A meta-analysis of 20 studies indicated that children with separation anxiety disorder were more likely to develop panic disorder in adulthood (odds ratio (OR) = 3.45; 95 % confidence interval [CI] = 2.37–5.03). Additionally, five studies suggested that a childhood diagnosis of separation anxiety disorder increased the overall risk of the development of future anxiety disorders in adulthood (OR = 2.19; 95 % CI = 1.40–3.42) (Kossowsky et al. 2013).
Recent research has focussed on the gene encoding monoamine oxidase A (MAOA) in women. This has been of particular interest given the effectiveness of MAO inhibitors in the treatment of panic disorder and previous studies of MAO inhibitors in animal models of panic disorder. A meta-analysis of four studies reported a significant female-specific association when calculating an allelic model in panic disorder, leading the authors to suggest that “this sex-specific effect might be explained by a gene-dose effect causing higher MAOA expression in females.” Furthermore, they hypothesized that high-expression MAOA-uVNTR alleles significantly increase the risk of developing panic disorder in women. This finding will require further replication in larger samples, but may be a lead in the understanding of female vulnerability to the development of panic disorder (Reif et al. 2012).
Panic disorder has been reported as having a prevalence of between 1.3 and 2.0 % in pregnancy (Sholomskas et al. 1993). While in the postpartum period both an increased risk of relapse as well as increased risk of new onset panic disorder has been reported, the risk in pregnancy per se is not known (Sholomskas et al. 1993). There are conflicting data about the course of panic disorder in pregnancy. Some studies report improvement of symptoms (Wisner et al. 1996; Cohen et al. 1994); such improvements have been linked to physiologic changes in hormonal milieu and progesterone metabolites, as well as attenuation of the noradrenergic response to stress (Majewska et al. 1986; Barron et al. 1986). Other studies have reported either no change or worsening of symptoms. It may be that the best predictor of symptom change is pregravid symptom severity, with greater severity predicting a worse course (Ross and McLean 2006). Chen et al. (2001) found that in women with panic disorder who actually experienced panic attacks during pregnancy, there was an increased risk of having small-for-gestational-age infants and the adjusted odds ratio for having a preterm delivery was 2.54 (95 % CI = 1.09–5.93).
Treatment
Cognitive behavioral therapy (CBT) is again the first-line psychotherapy treatment for panic disorder. Pharmacotherapy, particularly selective serotonin reuptake inhibitors (SSRIs) are also a first-line option (Mitte et al. 2005). A recent review (Stein et al. 2010) also suggested efficacy when combining SSRIs with CBT. (See chapter “Anxiety and related disorders in men” for greater detail).
Generalized Anxiety Disorder
Women with generalized anxiety disorder (GAD) report intrusive, pervasive worries that affect their function and quality of life across many domains (Grant et al. 2005). GAD usually has an onset prior to 25 years old and most often has a chronic course throughout adulthood (Stein et al. 2005). In the USA, generalized anxiety disorder was second only to substance abuse in terms of population prevalence (Fricchione 2004). Individuals with generalized anxiety disorder have a significantly increased risk of developing subsequent depression (Hettema et al. 2006) with up to 75 % developing a major depressive episode in their lifetime. The risk factors for the development of generalized anxiety disorder include a family history of the disorder or stress and trauma. Individuals with comorbid generalized anxiety disorder and depression are more disabled than those with either disorder alone (Grant et al. 2005).
A neurobiological model of generalized anxiety disorder suggests that the early life experience of an increased circulation of adrenaline and cortisol, as a result of exposure to stressful situations, may lead to increased upregulation, and hypersensitivity, of the HPA axis in adulthood. The role of the transgenerational transmission of generalized anxiety disorder is worth considering in this context given that the infants of women with anxiety disorders in pregnancy are more likely to be exposed to greater circulating levels of adrenaline in utero, meaning that they are more vulnerable to developing anxiety disorders in childhood if exposed to early life trauma.
There is little data on the epidemiology of GAD in pregnancy. One study found a rate of 8.5 % in the third trimester (Shear and Oommen 1995). There are few data on the course of pre-existing GAD in pregnancy. Diagnosing GAD poses special challenges in pregnancy – it is normal to have degree of worry and anxiety in pregnancy.DiPietro et al. (2002) developed the Pregnancy Experiences Scale which in addition to measuring worry also measures uplifts (the positive emotional experiences of pregnancy) (DiPietro et al. 2002). In a sample of well pregnant women the majority endorsed both worries and uplifts, and thoughts about normality of baby endorsed by over 80 % of the sample (DiPietro et al. 2002).
Treatment
The psychotherapy treatment of choice for generalized anxiety disorder is cognitive behavioral therapy with women and men both responding in equal measure (Yonkers et al. 2003). There has been some recent evidence suggesting that applied relaxation techniques could be as useful as cognitive behavioral therapy (Cujipers 2014). Pharmacotherapy in generalized anxiety disorder has an effect size of 0.6 (Gould et al. 1997), and SSRIs would be considered the first-line treatment.
Specific Phobias
Specific phobias are lasting or unreasonable fears of specific objects or situations which often pose little or no real danger. If an individual is exposed to this situation, they experience severe anxiety symptoms and therefore seek to avoid situations of exposure which may lead to significant functional impairment and limitations.
Specific phobias are usually characterized by early age of onset and high rates of comorbidity. A 17-month prospective study from Germany found that women with a specific phobia were twice as likely to develop another anxiety disorder, in particular, generalized anxiety disorder and somatoform disorder when followed over a 17-month period (Trumpf et al. 2010). The same group of researchers also investigated the predictors of specific phobias in women and found that high levels of pre-existing psychopathology, a lack of coping skills, and a negative cognitive style were all associated with increased incidence of specific phobias. They suggest that identifying these risk factors may aid in identifying individuals who are at increased risk of the development of specific phobias and may lead to an improvement in the prevention of these conditions (Trumpf et al. 2010).
Treatment
Psychological therapy, namely, exposure therapy as part of CBT, is the first-line treatment for specific phobias although only a small minority of individuals seek treatment, as low as 8 % (Stinson et al. 2007). A meta-analysis conducted in 2008 (Wolitzky-Taylor et al. 2008) found that exposure-based psychological treatments were effective in the treatment of specific phobias.
Obsessive-Compulsive Disorder
Obsessive-compulsive disorder (OCD) is estimated to have been the fifth leading cause of disability for women aged 15–44 years in developed countries (Murray and Lopez 1996), and epidemiological surveys suggest that the condition afflicts women more frequently than men (Bebbington 1990) although clinical studies show a less marked female excess, which may reflect differences in help-seeking behavior and a more severe illness course in men (Castle et al. 1995; Lensi et al. 1996; Noshirvani et al. 1991). Additionally, men tend to have an earlier onset of OCD than their female counterparts (Castle et al. 1995; Lensi et al. 1996; Lochner et al. 2004).
There are also sex differences between the type of symptoms manifested in OCD with women more likely to manifest contamination fears and cleaning rituals and men more prone to aggressive and sexual obsessions, and symmetry concerns (Lensi et al. 1996; Bogetto et al. 1999).
Women with obsessive-compulsive disorder (OCD) sometimes report that symptoms first appear or exacerbate during reproductive cycle events and there has been recent research which has demonstrated the relationship between OCD and the reproductive cycle in women. A meta-analysis revealed that the prevalence of OCD increased during pregnancy (mean = 2.07 %) and even more so in the postpartum period (mean = 2.43 %) compared with the general population (mean = 1.08 %). Additionally, both pregnant (mean = 1.45) and postpartum (mean = 2.38) women were at greater risk of experiencing OCD compared to the general female population, with an aggregate risk ratio of 1.79 (Russell et al. 2013).
Further research has focussed on OCD across the reproductive cycle including at menarche, premenstruum, pregnancy, postpartum, and at menopause. In a survey of 542 women (United States, n = 352; Dutch, n = 190) using a self-report questionnaire of symptoms across time, a significant relationship between exacerbations of OCD and various phases of the reproductive cycle was found. OCD onset occurred within 12 months after menarche in 13.0 % of participants; during pregnancy in 5.1 %; postpartum in 4.7 %; and at menopause in 3.7 %. It was evident that worsening of pre-existing OCD occurred at reproductive cycle events with 37.6 % of women reporting worsening of symptoms at premenstruum, 33.0 % during pregnancy, 46.6 % in postpartum period, and 32.7 % at menopause. Furthermore, a first pregnancy was significantly associated with exacerbation in second pregnancy (OR = 10.82, 95 % CI = 4.48–26.16); similarly, postpartum exacerbation in a first pregnancy was associated with an elevated risk in ensuing pregnancies (OR = 6.86, 95 % CI = 3.27–14.36). These findings reinforce the importance of clinical vigilance during these phases of the reproductive cycle (Guglielmi et al. 2014).
Treatment
The main psychological therapy in the treatment of OCD is exposure and response prevention (ERP) (Abramowitz 1997) and this is often used in combination with SSRI medications.
Physical Illness and Anxiety Disorders in Women
There is an increased prevalence of anxiety disorders in the presence of chronic physical illness when compared to the prevalence of anxiety disorders in individuals without chronic physical illness. These disorders include chronic fatigue syndrome, fibromyalgia, gastrointestinal conditions, and bronchitis. Anxiety disorders which are comorbid with physical illness have also been significantly associated with short-term disability, requiring help with instrumental daily activities, and suicidal ideation (Gadalla 2008). These findings highlight the importance of screening for the presence of anxiety disorders in women with chronic physical illnesses given the potential for detrimental impact on their quality of life and level of disability associated with their chronic physical illness.
The relationship between anxiety disorders and physical illness appears bidirectional as the incidence of certain medical conditions appears to be higher in patients with anxiety disorders. A study conducted over 10 years in Canada (Bowen et al. 2000) showed that individuals with anxiety disorders, in comparison to those without, had a significantly higher relative risk of developing medical diseases. The highest hazard ratio was for cerebrovascular disease (hazard ratio = 2.0, 95 % CI = 1.09–3.65); hazard ratios were also significant for ischemic heart, gastrointestinal, respiratory diseases as well as hypertension (Bowen et al. 2000).
Heart Disease
Anxiety has been associated with the development and recurrence of coronary heart disease. Tordaro et al. (2007) reviewed the prevalence of anxiety disorders in men and women with established coronary heart disease and reported that 36.0 % (n = 54) met the diagnostic criteria for a current anxiety disorder, while 45.3 % (n = 68) had a past history of an anxiety disorder. Female cardiac patients had significantly higher current (women = 58.3 % vs. men = 25.5 %, p < 0.001) and lifetime (women = 70.8 % vs. men = 33.3 %, p < 0.001) rates of anxiety disorders compared with male participants (Todaro et al. 2007). Special efforts are needed to screen patients for anxiety disorders when attending outpatient cardiology or cardiac rehabilitation.
Cancer
There has been a considerable amount of research into the prevalence of anxiety disorders in women with cancer. A meta-analysis conducted in 3,469 Chinese adults with all types of cancer found the prevalence of anxiety disorders was 49.69 % versus 18.37 % in control subjects (OR = 6.46, 95 % CI = 4.36–9.55, p = 0.000) (Yang et al. 2013).
In women, there have been several studies concentrating on breast or gynecological cancers. A prospective study of a hospitalized sample of 167 women examined the prevalence of anxiety and depression using the Hospital Anxiety and Depression Scale (HADS-A) and Centre for Epidemiological Studies Depression Scale (CES-D) at diagnosis and again every 8 weeks for 56 weeks. Rates of anxiety (17.7 %), depression (32.5 %) and combined anxiety and depression (35 %) symptoms were highest at diagnosis but dissipated over time and overall rates of anxiety, depression, and combined symptoms were 7.5 %, 23.4 %, and 24.1 %, respectively, at study end, with most improvement having occurred by 24 weeks. Furthermore, using the cut-off for referral to mental health services as ≥11 and ≥16 on the HADS-A and CES-D, respectively, there were 54 % of women who met criteria. Half of these women declined referral, a quarter accepted and a further quarter were already receiving treatment. This meant that 30 % of women in the study were receiving treatment for a mental health condition and that women were most vulnerable to psychological morbidity at the time of cancer diagnosis (Stafford et al. 2013).
Wurtzen et al. (2013) conducted a randomized controlled trial of an 8- week mindfulness-based group therapy intervention targeting anxiety and depressive symptoms in 336 women with breast cancer. Symptoms were assessed immediately preceding and following the intervention and at 6- and 12-month intervals following thereafter. Intention-to-treat analyses showed differences between groups in levels of anxiety (p = 0.0002) and depression (SCL-90r, p < 0.0001; CES-D, p = 0.0367) after 12 months (Wurtzen et al. 2013).
Gastrointestinal Disorders
Irritable bowel syndrome (IBS) is often associated with anxiety and depression. A sample of 1,077 women found that current diagnosis of irritable bowel syndrome was associated with an increased likelihood of current mood or anxiety disorders with OR = 2.62, 95 % CI = 1.49–4.60. Additionally, half of those participants diagnosed with irritable bowel syndrome IBS had also previously been diagnosed with a mood or anxiety disorder (Mykletun et al. 2010).
Anxiety Across the Life Course in Women
The prevalence of anxiety disorders in women across menstrual cycle, pregnancy, and menopause has been extensively investigated with research revealing rates of some anxiety disorders being higher in postpartum women than in the general population (Ross and McLean 2006). The relationship between the menstrual cycle, menopause, and anxiety disorders has also been considered with links established between hormonal phases of the menstrual cycle and the worsening of anxiety disorders.
Premenstrual Dysphoric Disorder (PMDD)
Premenstrual dysphoric disorder (PMDD) is a mood disorder with onset of functionally impairing or distressing mood symptoms in the late luteal phase of the menstrual cycle. It is classified as a depressive disorder but there are studies which have identified anxiety as a key component (Stein et al. 1989); in particular, the frequency of panic attacks can increase in PMDD (Facchinetti et al. 1992).
Recent research has attempted to interrogate state versus trait symptoms in PMDD and explore the relationship between physiological findings and psychological symptoms. Poromaa (2014) found that in individuals with PMDD, “state” symptoms occur in the luteal phase, suggesting that women with PMDD have altered luteal phase emotion processing and lower pre-pulse inhibition in the late luteal phase, which could reflect ovarian steroid-influenced altered serotonergic neurotransmission. They suggested that “trait” findings in these women occur in the asymptomatic phases of the menstrual cycle and physiologically exhibited trait vulnerability markers include diminished cardiovascular stress responses, lower P300 amplitude, and lower heart rate variability reflecting increased vagal tone. These findings suggest that women with PMDD share physiological correlates with women with anxiety and depression (Poromaa 2014).
Menopause
A recent systematic review examining 19 studies conducted between 1960 and 2011 (Bryant et al. 2012) evaluated the prevalence of anxiety disorders during the menopausal transition to ascertain whether there was any utility in the diagnosis of “menopausal anxiety” as a discrete category. The review examined the relationship between the vasomotor symptoms of menopause (e.g., “hot flushes”), and anxiety states. Findings suggest that there is no current evidence to suggest that there is an increased prevalence of anxiety disorders during the menopause, nor the emergence of an anxiety disorder specifically determined by the menopause.
Anxiety Disorders During Pregnancy and Postnatally
It has often been considered that pregnancy is a time of low risk for the new onset or exacerbation of an anxiety disorder. However, there is growing evidence that many women suffer from either new onset or worsening of their anxiety disorders during pregnancy. The occurrence of an anxiety disorder in pregnancy has important consequences – it not only impacts on the woman’s mental health, but also is a risk for postnatal disorders, as well as having possible effects on the unborn child. Studies of anxiety in a pregnancy show that a not insubstantial proportion of women is affected. For example, Heron et al. (2004) in a large community sample of pregnant women found that 21 % had clinically significant anxiety, and of these 64 % continued to have anxiety postnatally.
Perinatal Post-traumatic Stress Disorder (PTSD)
Perinatal post-traumatic stress disorder (PTSD), that is, PTSD related to medical procedures, childbirth, or other obstetric events, has been reported (Beck 2004). One study found that 20 % of women reported traumatic pregnancy-related procedures, and of these 6 % met criteria for PTSD (Menage 1993). Controversy exists as to whether medical procedures during pregnancy and/or childbirth meet DSM criteria for a traumatic event. While pregnancy and childbirth are not considered to be an event outside the range of normal human experience, the DSM V stressor criterion requires that the person must be exposed to a death, threatened death, actual or threatened serious injury; it is generally acknowledged that traumatic reactions may occur when neither resistance nor escape is possible and helplessness and loss of control are experienced. Childbirth could certainly pose a risk of death and/or serious injury. Risk factors for perinatal PTSD include previous adverse reproductive events such as ectopic pregnancy, miscarriage, stillbirth, unwanted pregnancy, and abortion; history of sexual trauma (Beck 2004), past traumatic experience (Beck 2004; Menage 1993), prior psychiatric history (Menage 1993), obstetric interventions or complications (Beck 2004; Menage 1993) and poor social support (Beck 2004).
The clinical features of anxiety disorders in pregnancy are similar to those in nonpregnant women. However, concerns over the pregnancy and fetus may present as the predominant feature. For example, in panic disorder, women may interpret panic attacks as something being wrong with the fetus (Weisberg et al. 2002).
Perinatal OCD is classically described as involving obsessive concerns of harming child, together with checking and cleaning compulsions (Abramowitz et al. 2003). It is important to differentiate this from homicidal impulses toward the child (e.g., as part of a psychotic disorder) – in OCD these thoughts are experienced as intrusive and the mother has no wish of harming her child. It has been postulated that these features may be an exacerbation of the normal vigilance toward the child that is characteristic of pregnancy and the postpartum period (Stein and Bouwer 1997).
Women with anxiety disorders also commonly present with numerous physical complaints. Studies of health in pregnancy in women with psychiatric disorders showed an increased frequency of nausea and vomiting (adjusted OR = 2.04, 95 % CI = 1.40–2.98), disability days (OR = 2.10, 95 % CI = 1.49–3.00), and physician visits (OR = 1.52, 95 % CI = 1.10–2.12) in women with anxiety and/or mood disorders (Andersson et al. 2003). Indeed, frequent physical complaints with no discernable physical cause should prompt the clinician to screen for an anxiety disorder.
Risk of Anxiety Disorders in Pregnancy
Maternal Risks
The majority of anxiety disorders in pregnancy have a continued postnatal course. Further, several prospective studies have shown that a prenatal anxiety disorder is one of the strongest risk factors for developing postnatal depression (Milgrom et al. 2008; Sutter-Dallay et al. 2004). An anxiety disorder in pregnancy is thus associated with significant potential maternal morbidity.
Fetal Effects of Maternal Anxiety
Both animal and human studies suggest that antenatal stress/anxiety can cause poorer obstetric outcomes and a range of neurobehavioral problems in exposed infants (Schneider et al. 2002; Bergman et al. 2007). In animals, prenatal stress has been reported to be associated with spontaneous abortion, delays in the birth process, smaller litter size and animals with lower birth weight, compromised physical growth and an increased incidence of malformations (Huizink et al. 2004). Similarly in humans, women reporting high levels of subjective stress have been found to be at doubled risk for delivering preterm or growth-restricted baby (Wadhwa et al. 2002). Antenatal anxiety or stress has been linked with physical defects in the child (Hansen et al. 2000) and low birth weight (Hedegaard et al. 1993). More worryingly, prenatal maternal anxiety has been linked with persisting neurobehavioral problems, including poorer performance on tests of neurodevelopment, increased fearfulness (Bergman et al. 2007) and conduct problems (Huizink et al 2004).
Related posts:
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
