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Introduction
Mental illness in pregnancy and postpartum has significant and potentially serious long-term consequences for a mother, her entire family, and in particular, for her infant (Grigoriadis, VonderPorten et al. 2013c). Perinatal mood and anxiety disorders are not culturally bound: they affect women in every society and from every socioeconomic background. The aim of this chapter is to increase awareness among healthcare providers about mood- and anxiety-related disorders in pregnancy and postpartum (the “perinatal” period). To achieve this goal, the chapter provides key information about the presentation of these disorders in the perinatal period, along with research about biological and psychosocial risk factors for illness.
Clinical presentations
Most psychiatric disorders can occur in the perinatal period, but mood and anxiety disorders are particularly common among women of reproductive age. Pregnancy is not protective against the development or recurrence of these disorders, and evidence suggests that the postpartum period is a time of increased risk for new-onset mood and anxiety problems. In particular, there is a risk of mood-related psychosis in the postpartum period, with women suffering from bipolar disorder at high risk. Further, there is a high risk of comorbidity with mood and anxiety disorders co-occurring (Grigoriadis, et al. 2011). In the 5th edition of the Diagnostic and Statistical Manual of Mental Health Disorders (DSM-5) mood and anxiety disorders are classified into five separate categories: Depressive disorders, Bipolar and related disorders, Anxiety disorders (including generalized anxiety disorder, panic disorder and social anxiety disorder), Obsessive-compulsive and related disorders, and Trauma and Stressor-related disorders (including adjustment disorder, acute stress disorder and post-traumatic stress disorder [PTSD]) (American Psychiatric Association, 2013). Mood and anxiety disorders occurring in pregnancy or postpartum are not classified as distinct disorders in the DSM-5. However, due to the distinct risks related to perinatal mood disorders, episodes of depressive and bipolar disorders occurring during this time are classified with the use of the specifier: “with peripartum onset.” Specifically, the DSM-5 specifier indicates that “peripartum-onset” pertains only to episodes occurring in pregnancy or with onset in the first four weeks after delivery, although research suggests that risk is likely elevated throughout the first postpartum year. Perhaps because less work to date has focused on this area, the relationship to the perinatal period is not specified for anxiety, obsessive compulsive and trauma- and stressor-related disorders in the DSM-5. For a more general overview of these disorders in women, the reader is referred to Chapters 21 (bipolar disorder), 19 (depression), 18 (anxiety disorders) and 17 (PTSD).
Depressive and bipolar disorders
For depressive and bipolar disorders, the predominant symptom is a disturbance in mood. This disturbance can involve primarily low mood (depressive disorders) or can also involve episodes of mania or hypomania with elevated or irritable mood (bipolar disorders). To be diagnosed with a depressive or bipolar disorder, a woman must also be experiencing marked impairment or change in psychosocial or interpersonal functioning. Women may also present with other mood disorders such as persistent depressive disorder (dysthymia), cyclothymic disorder, and adjustment disorder with depressed mood, with anxiety, or with mixed anxiety and depressed mood (the latter adjustment disorder category is fairly common); however, less is known about the pregnancy-specific epidemiology and impact of these disorders.
Pregnancy
Population-based studies have reported that the period prevalence of major depression in pregnancy ranges from 3.3 to 13%, and the risk does not appear to be lower than among nonpregnant women (Bennett, et al. 2004; Gavin, et al. 2005; Vesga-Lopez, et al. 2008; Banti, et al. 2011; Le Strat, et al. 2011). When other depressive disorders such as unspecified depressive disorder (minor depression) and persistent depressive disorder (dysthymia), or the presence of adjustment disorders with depressed mood are considered, higher rates are reported (between 9 and 25%). Although most studies have found that the risk of depression remains stable throughout pregnancy, some research has suggested that depressive symptoms are more prevalent in the third trimester of pregnancy, possibly related to the impact of anxiety about delivery and/or the physical symptoms of late pregnancy. Among women with bipolar disorder, almost 25% will experience a mood disturbance (mania or depression) during pregnancy, with depressive episodes predominating (Gavin, et al. 2005; Viguera, et al. 2011; Di Florio, et al. 2013). Risk factors associated with relapse of depression during pregnancy in women with bipolar disorder include younger age at onset, previous postpartum episodes, fewer children and being unmarried (Viguera, et al. 2011). Women with severe depressive and bipolar disorders are at high risk of relapse, particularly if the doses of psychotropic medications are lowered or stopped altogether early in pregnancy (Cohen, et al. 2006; Viguera, et al. 2007).
Postpartum
The “postpartum blues”
This is by far the most common of the mood changes related to postpartum, with as many as 80% of women experiencing some symptoms. It commonly occurs shortly after childbirth and resolves within the first few weeks postpartum. Symptoms may include transient low mood, emotional lability, crying and irritability. However, it can be distinguished from a major depressive episode by its transient nature and by the lack of severe symptoms such as persistent insomnia, thoughts of guilt or worthlessness and/or suicidal ideation. It is self-limiting, and does not require any treatment other than reassurance and support and is not considered a “mood disorder,” but is mentioned here because of its possible biological link to significant mood changes later in the postpartum period (Edhborg 2008; Watanabe, et al. 2008; Reck, et al. 2009). It is thought that so many women experience these transient mood changes because of the impact of the rapid hormonal drop after childbirth on neurotransmitter systems involved in mood disorders (Doornbos, et al. 2008; O’Keane, et al. 2011). For example, it has been shown that binding of brain monoamine oxidase (MAO-A), which is responsible for the breakdown of monoamines in the synaptic cleft, is elevated postpartum (Sacher, Wilson et al. 2010). Why some women go on to develop major depression in the context of these changes, while others do not, is still being investigated, but some research supports the idea that genetic predisposition plays a role (Sanjuan, Martin-Santos et al. 2008).
Postpartum depression
Approximately 13% of women experience a major depressive episode in the first year postpartum. Estimates for postpartum depressive symptomatology differ depending on the timing of the measurement, the measurement tool (e.g., self-report scales versus diagnostic criteria), as well as whether unspecified depressive disorder is included in the estimates. Significant cultural and ethnic differences in rates are increasingly recognized (see Chapter 2). When only comparative studies assessing major depression are included, the period prevalence in the first 6–8 weeks postpartum appears to be significantly higher among postpartum versus nonperinatal women (Gorman, et al. 2004; Gaynes, et al. 2005; Kitamura, et al. 2006; Dietz, et al. 2007; Mota, et al. 2008). According to the DSM-5, mood disorder symptoms must have their onset late in pregnancy or within four weeks postpartum in order for the episode to qualify for the “peripartum-onset” specifier (American Psychiatric Association 2013). However, most clinicians and researchers prefer less stringent criteria when symptoms emerge in the first few months (Austin 2010; Jones & Cantwell 2010; Wisner, et al. 2010).
According to the DSM-5 definition, postpartum depression is not qualitatively different from other depressive illnesses, with low mood, energy and interest, as well as sleep and appetite disturbance. Although many women with postpartum depression do report these symptoms, the context of the postnatal period is often apparent in the manner in which the symptoms are manifested. There are common themes to women’s experiences of childbirth and motherhood that separate perinatal depression from depression at other times. These themes may aid the clinician in better understanding the illness. In Beck’s meta-synthesis of 18 qualitative studies in developed world samples on postpartum depression (Beck 2002), four common themes arose: incongruity between expectations and reality, spiraling downward, pervasive loss and making gains through acceptance of help. “Spiraling downward” refers to feelings of anxiety and anger, feeling overwhelmed, obsessive thinking and cognitive impairment. While these symptoms are common components of any depressive illness, in postpartum depression (PPD), they occur in response to specific triggers, including incongruence between the type of postpartum experience that was expected and that which occurred, isolation in dealing with one’s feelings and the loss of former identities. These triggers occur very predictably to many women after childbirth.
It is also clear that self-harm and suicidal thoughts are common among women suffering from postpartum depression. In a large population-based sample in the United States, approximately 14% of women screened positive for having self-harm thoughts. Although the majority of these women had a diagnosis of major depressive disorder, with comorbid generalized anxiety disorder, approximately one-fifth had a diagnosis of bipolar disorder (Wisner, et al. 2013). In clinical samples, suicidal thoughts may be present in up to 60% of women with depression (Healey, et al. 2013). Although mothers overall tend to have lower rates of suicide than non-mothers (Appleby, et al. 1998), suicide in the first postpartum year remains a major cause of maternal mortality in developed countries (Oates 2003; Austin, et al. 2007; Palladino, et al. 2011).
It is important to highlight that most studies on postpartum depression prevalence have been conducted in Western societies, and recent research suggests that there is wide variability in reported prevalence across the world. A systematic review identified 143 studies in 40 countries across the world and found that reported prevalence of postpartum depression ranged from almost zero to approximately 60%. There were some countries where very low rates of postpartum depression were reported (e.g., Singapore, Malta, Malaysia, Austria and Denmark) whereas other countries reported very high rates (Brazil, Guyana, Costa Rica, Italy, Chile, South Africa, Taiwan and Korea) (Halbreich & Karkun 2006). It is hard to know whether the variability in reported postpartum depression rates is due to cultural differences in the way that symptoms are reported (i.e., symptoms are under- or over-reported in some areas depending on social and/or cultural factors), whether there are differences in the prevalence of risk factors across cultures (e.g., levels of social support, levels of economic deprivation, levels of life stress), or whether there is variability in biological vulnerability. However, these data suggest that postpartum depression exists in all cultures, though the contributing factors may vary from culture to culture. These differences will require consideration in management of perinatal depression, in particular, women immigrating from one culture to another may have issues specifically related to one – or both – of these cultures. Furthermore, Edge (2007) reported significant ethnic variation in the presentation of perinatal mood disorder in a UK sample, raising questions about the expression of ethnic differences within cultures.
Postpartum psychosis
Postpartum psychosis is the most concerning of the postpartum mood disorders, occurring in approximately 1 in 600 women. Evidence from studies of women with a history of bipolar disorder and women with history of postpartum psychosis suggest that there is a relationship between postpartum psychosis and bipolar disorder (Chaudron & Pies 2003). It is thought to be, in the majority of cases, a variant of bipolar disorder rather than a primary psychotic disorder, and is discussed in this section of the chapter. It should be noted, however, that there is an increased risk of postpartum relapse in women with primary psychotic disorders as well (Munk-Olsen, et al. 2006).
Postpartum psychosis tends to occur rapidly after delivery: usually within the first week or at the latest, the first month, postpartum. It can also occur at weaning, although this is a rare occurrence. The symptoms represent a striking change from a woman’s usual personality, with confusion and clouding of consciousness considered to be classic presenting features (Ganjekar, et al. 2013). However, there is also evidence that hypomanic or manic symptoms such as elation, decreased need for sleep, increased goal-directed activity and hyper-talkativeness may precede the onset of psychosis (Heron, et al. 2008). Women may present with psychotic depression, paranoia, mania, schizophrenic symptoms or an organic-appearing presentation such as confusion. Psychotic thinking includes a break from reality, where the mother is no longer able to distinguish her thoughts from reality and may develop fixed false beliefs (delusions) about herself, her infant or others around her (Engqvist & Nilsson 2013).
Risk of a postpartum psychosis may be particularly increased for women with previously existing bipolar and psychotic illnesses if medication is stopped during pregnancy or the early postpartum period. Other risk factors are family history of psychiatric illness, especially bipolar affective disorder; there is some evidence that sleep deprivation could precipitate an episode in women with bipolar mood disorder (Sharma & Mazmanian 2003). Not all women who develop postpartum psychosis have a previous psychiatric history, though a family history of bipolar disorder is not uncommon. They are also at higher risk for developing a mood or psychotic disorder (usually bipolar disorder) at times unrelated to pregnancy (Nager, et al. 2013). The risk related to future pregnancies is very high, in the range of 50 to 60% (Robertson, et al. 2005; Blackmore, et al. 2013).
Women who present with postpartum psychosis require urgent psychiatric consultation, pharmacologic treatment and likely hospitalization, as well as ongoing support to optimize recovery (Heron, et al. 2012). Unfortunately, women with psychotic symptoms may have difficulty caring for their infants due to the thought disturbance and confusion that accompanies postpartum psychosis. They may also experience delusions that could increase the risk of harm to themselves or to their infants (Spinelli 2004). As such, ongoing comprehensive safety assessments should be conducted to ensure optimal safety of the mother and her infant, with education and engagement of family members (Doucet, et al. 2012).
Anxiety disorders
Both quantitative and qualitative studies have identified anxiety as one of the primary features of perinatal depression (Matthey, et al. 2003). The prevalence of anxiety symptoms in the postpartum period ranges from 14–20% (Figueiredo & Conde 2011; Dennis, et al. 2013). Perinatal anxiety often relates to the welfare of the infant, insecurity about one’s parenting abilities, or being alone, and may or may not meet criteria for a diagnosis of an anxiety disorder. When anxious symptoms are present in the context of a depressive or bipolar disorder, DSM-5 has introduced a “with anxious features” specifier to the depressive or bipolar disorder diagnosis to reflect the frequency with which anxious symptoms are present. However, increasing attention has been focused on understanding the prevalence, incidence and impact of anxiety disorders themselves in the perinatal period.
Generalized Anxiety Disorder. Generalized anxiety disorder is characterized by excessive anxiety and worry about anticipated events or activities. Sufferers find it difficult to control the worry, to the extent that it interferes with their daily functioning in a meaningful way. Postpartum worries include themes related to finances, appearances and maintaining household duties, as well as those related to the infant’s welfare (Ross & McLean 2006). By definition, symptoms are required to last at least 6 months before a diagnosis is made, such that it is rare for new-onset generalized anxiety to be diagnosed during the perinatal period. However, it is prevalent. In a study of nearly 3000 women, 9.5% had generalized anxiety disorder at some time during pregnancy but this decreased towards term (Buist, et al. 2011). This is higher than 12-month prevalence rates for anxiety of approximately 4% quoted in epidemiological studies for nonperinatal anxiety disorders (Meng & D’Arcy 2012).
Panic disorder. Panic disorder during the perinatal period can have a significant impact on functioning, including being confined to home and feeling that one is a burden to one’s family. Panic can be especially problematic in pregnancy when panic symptoms precipitate and perpetuate concerns about the health of the fetus. In the postpartum period, women with panic disorder may experience increased isolation and loss of social support due to difficulty in leaving home or being in groups (Metz, Stump, et al. 1983; Beck 1998; Weisberg & Paquette 2002). In a systematic review, Ross and MacLean reported that the prevalence of panic disorder in pregnancy (1 to 3%) approximates that of nonpregnant women of reproductive age (Ross & McLean 2006; Guler, Sahin, et al. 2008). Some, but not all, studies report symptom worsening and/or high rates of relapse in subsequent pregnancies for women with preexisting panic disorder (Dannon, Iancu, et al. 2006; Guler, Koken, et al. 2008).
Specific phobias. Blood-injection injury phobia (“needle phobia”) is common, affecting 7–8% of the population. Although the risk is not increased in pregnancy, this anxiety disorder has specific implications related to antenatal care, labor and delivery. Pregnant women experiencing this specific phobia have higher levels of depressive and anxious symptoms than their nonphobic counterparts (Lilliecreutz, et al. 2011).
Social phobia. Social phobia is also important to consider in the perinatal period, considering evidence that points to associations between maternal social phobia and infant responsiveness to strangers (de Rosnay, et al. 2006; Murray, et al. 2007). There have been few estimates of the prevalence of this disorder, but a clinic-based cross-sectional study estimated a prevalence of 0.5% in the postpartum period (Navarro, Garcia-Esteve et al. 2008).
Obsessive-compulsive disorder
The category of obsessive compulsive and related disorders in DSM-5 includes obsessive-compulsive disorder (OCD) itself as well as several other compulsive disorders (American Psychiatric Association 2013). With respect to the perinatal period, however, most research has been focused on obsessive-compulsive symptoms and OCD. Commonly, perinatal OCD symptoms are related to contamination obsessions as well as checking and ordering compulsions. In addition, obsessions and/or repetitive thoughts, including thoughts related to harming the infant, can occur (Uguz, et al. 2007; Uguz, et al. 2007; Speisman, et al. 2011). Obsessional thoughts are difficult to control, and are typically very distressing to the mother, as she has no desire to act on them. She may even exhibit avoidance behaviors in a compulsive manner (i.e., avoiding the baby to alleviate intrusive thoughts). Obsessional symptoms can be distinguished from postpartum psychotic symptoms where thoughts related to harming the infant are more likely to be ego-syntonic and to be part of a delusional system of fixed, false beliefs about the infant.
Similar to the anxiety disorders, many women experience obsessional symptoms during the postpartum period. These symptoms can be experienced in the context of a depressive disorder, but prospective studies suggest that OCD itself occurs in approximately 2–9% of new mothers (compared to 1–3% in the general population) (Sasson, et al. 1997; Uguz, et al. 2007; Zambaldi, et al. 2009). A recent meta-analysis of studies using diagnostic interviews to establish the prevalence of perinatal OCD found that the risk was higher in pregnancy than among nonpregnant women, and higher still in the postnatal period (risk ratio for perinatal versus nonperinatal OCD of 1.79) (Russell, et al. 2013). Several retrospective studies in clinical OCD populations suggest that at least one-third of women report increased symptoms postpartum (Sasson, et al. 1997; Uguz, et al. 2007; Forray, et al. 2010).
Trauma and stress-related disorders
Adjustment disorder. The essential feature of an adjustment disorder is a psychological response to an identifiable stressor or stressors that results in the development of clinical significant emotional or behavioral symptoms. The symptoms resolve within several weeks to months of the resolution of the stressor and the individual’s symptoms do not meet criteria for another psychiatric disorder at any time point. Issues related to pregnancy, childbirth and parenting can sometimes be stressful, and this diagnosis may be appropriate when women do not meet criteria for a mood, anxiety, obsessive-compulsive or other trauma or stress-related disorder, but require supportive or other psychological treatment to alleviate symptoms.
Post-traumatic stress disorder and acute stress disorder. These disorders occur after exposure to a traumatic event. Symptoms of acute stress disorder are time-limited, resolving within 1 month from the event, whereas a diagnosis of post-traumatic stress disorder requires symptoms to last 1 month or longer. In both situations, individuals exposed to traumatic events may experience intrusive symptoms such as nightmares or flashbacks, avoid stimuli associated with the traumatic event, experience alterations in thinking or mood (e.g., distortions about causality of the event) and/or experience symptoms of arousal and reactivity related to the event (e.g., irritability, sleep disturbance, exaggerated startle response). These disorders can have significant impact on quality of life, on a mother’s relationship to her infant, and on subsequent pregnancy and childbirth experiences (Beck & Watson 2010). Increasingly, post-traumatic stress symptoms have been reported postnatally in response to traumatic aspects of the labor and delivery experience. In a large clinical sample (N=890 women), Boorman, et al. (2013) reported that almost 30% of women experienced birth as traumatic, although only 14% reported a significant emotional response (Boorman, et al. 2013). In another large clinical sample (N=1221), Soderquist et al. (2009) found that 13% of women met criteria for PTSD one month after childbirth. In a large U.S. national survey of 1373 women, Beck et al. (2011) reported a prevalence of 9% for PTSD, with 18% having at least some symptoms of the disorder. However, in another large clinical sample in Australia (N=933), the reported prevalence was only 1.2% at 4–6 weeks postpartum, and 3.1% at 12 and 24 weeks postpartum, after accounting for PTSD due to previous traumatic events and significant anxiety and depression during pregnancy (Alcorn, et al. 2010). These discrepant numbers indicate that more research is needed to clarify the prevalence of this disorder. However, fairly consistent risk factors have been identified across studies, including comorbid depression and severe fear of childbirth. Having to undergo unexpected, emergency obstetric procedures, negative interactions with staff, and feeling a loss of control over the labor and delivery situation have also been reported as potential risk factors (Olde, et al. 2006; Vythilingum 2010).
Differential diagnoses
In the care of any woman presenting with mood, anxiety, obsessive-compulsive or trauma and stressor-related disorders during pregnancy or postpartum, it is always important to ensure that another medical condition or substance use neither caused nor is contributing to the presenting psychiatric symptoms. Medical conditions to consider may include (but are not limited to) hypo- or hyper-thyroidism, vitamin B12 or iron-deficiency anemia (Bodnar & Wisner 2005; Bunevicius, et al. 2009b; Leung & Kaplan 2009; Kaplan, et al. 2012; Khalafallah & Dennis 2012; Leung, et al. 2013) and structural or functional neurological abnormalities. In particular, there is evidence that thyroid dysregulation is present in up to 10% of postpartum women and in some research elevated anti-thyroid antibodies were present in up to 19% of women with postpartum psychosis (Bergink, et al. 2011). These studies suggest the prudence of assessing thyroid function in women with perinatal mood disorders (Pedersen, et al. 2007). Substances of abuse and dependence are also associated with psychiatric syndromes, and women should be screened for use of prescription and nonprescription substances.
Risk factors / etiology
Most researchers and clinicians agree that a complex, interactive etiological pathway involving biological, psychological and environmental factors is likely responsible for the development of depressive and anxiety disorders (Belmaker & Agam 2008). There is some empirical evidence that a biopsychosocial model accounts for symptoms of depression and anxiety in perinatal populations as well. For example, Ross et al. (2004) used structural equation modeling techniques to model relationships between biological (including hormonal) and psychosocial variables in the development of pre- and postnatal symptoms of depression and anxiety. In the model of prenatal mood, the biological variables had no relationship with symptoms of depression. Rather, they acted indirectly through their effects on psychosocial variables and symptoms of anxiety. These results were interpreted to suggest that biological vulnerability factors, including hormonal changes, determine the threshold at which psychosocial triggers, including lack of social support, will provoke symptoms of depression and anxiety in pregnancy. These same relationships, however, could not account for postpartum symptoms of depression and anxiety, possibly lending more support to the idea that biological variables may act independently of psychosocial variables during such times. As such, in any discussion of risk factors it is important to be mindful that the etiology of perinatal mood and anxiety disorders is complex, and to consider a competitive formulation for each individual woman.
Clinical and epidemiological risk factors
Most research related to psychosocial risk factors for perinatal psychiatric disorders has focused on perinatal depression. Three meta-analyses have been conducted on risk factors for postpartum depression, with the strongest factors being a previous history of depression, depression or anxiety in pregnancy, poor social support and significant life stressors (O’Hara & Swain 1996; Beck 2002; Robertson, et al. 2004). The risk factors associated with postpartum depression likely apply to depression in pregnancy (Bunevicius, et al. 2009a) as well as to perinatal anxiety disorders (Schmied, et al. 2013). However, women with depression in pregnancy may be more likely than women whose depression develops post-partum to have a previous history of depression and/or postpartum depression. In addition, psychosocial stressors appear to be even more commonly associated with depression in pregnancy than depression with postpartum onset (Altemus, et al. 2012).
Social support, stressful life events and other psychosocial risk factors. Lack of social support, and in particular, lack of support from an intimate partner, is associated with depressive and anxious symptoms during both pregnancy and in the postpartum period. In some recent research, the quality of the marital relationship has been shown to explain completely the variance of postpartum depression symptomatology (Akincigil, et al. 2010). Stressful life events may include financial or social stressors, interpersonal violence, obstetrical conditions and neonatal complications (Vigod, et al. 2010). A meta-analysis of partner violence concluded a 1.5-to-2-fold increase in risk of postpartum depression in women exposed to domestic violence (Beydoun, et al. 2012). These women experience anxiety and PTSD as well (Howard, et al. 2013). Negative experience of a previous birth has been associated with increased depressive symptoms and symptoms of post-traumatic stress in subsequent births (Rubertsson, et al. 2003; Beck & Watson 2010). Other psychosocial factors identified in meta-analyses as independently associated with postpartum depression include neuroticism, low self-esteem, single parenthood, unplanned pregnancy, low socioeconomic status, obstetrical complications and difficult infant temperament (O’Hara & Swain 1996; Beck 2002; Robertson, et al. 2004).
Biological mechanisms
Genetics and heritability. Family psychiatric history is an important predictor of both prenatal and postpartum mood disorders, leading some to suggest a genetic component to its etiology (Robertson, et al. 2004; O’Hara & McCabe 2013). Women with postpartum depression have a higher than expected proportion of first-degree relatives with a mood disorder. In addition, there is now evidence from at least three independent studies that perinatal depression tends to cluster in families (Treloar, et al. 1999; Forty, et al. 2006; Murphy-Eberenz, et al. 2006). In these studies, having a sister who had suffered from PPD increased the risk that a woman would also suffer from PPD, particularly when the onset of the depression was between six and eight weeks postpartum. Additionally, genetic polymorphisms in the serotonin-gene-linked polymorphic region as well as in genes encoding MAO-A, and catechol-O-methyl-transferase (COMT) enzymes, glucocorticoid and type 1 corticotropin-relating hormone receptors gene variants, and estrogen receptor alpha have been identified that support the idea that some women may have a genetic predisposition to postpartum depression (Sanjuan, et al. 2008; Doornbos, et al. 2009; Engineer, et al. 2013; Pinsonneault, et al. 2013).
Hormones, neurotransmitters and the neuroendocrine system. During pregnancy, significant changes occur in several steroid and peptide hormones, including estrogen, progesterone, corticotrophin-releasing hormone, thyroid hormone, prolactin and oxytocin. However, it does not appear to be the absolute levels of any of these hormones that is important, rather the abrupt change in the hormonal milieu in predisposed, vulnerable women may be the trigger (Russell, et al. 2001; Pedersen, et al. 2007; Glover, et al. 2010; Meltzer-Brody, et al. 2011; Skrundz, et al. 2011; Gonzalez, et al. 2012; Mileva-Seitz, et al. 2013; Murgatroyd & Nephew 2013; Stuebe, et al. 2013). Levels of estrogen and progesterone, the main sex hormones, increase slowly but substantially during pregnancy with a relatively rapid drop to prepregnancy levels shortly after delivery (Fernandez, et al. 2013; Schiller, et al. 2013). It has been hypothesized that this rapid drop in hormone levels contributes to the preponderance of mood disorder that occurs particularly in the postpartum period (Ahokas, et al. 2001). This has biological plausibility given the known interplay between sex hormones and neurotransmitter systems involved in depression, notably serotonin and dopamine (Steiner, et al. 2003; Hall & Steiner 2013). Estrogen modulates changes in several neurotransmitter systems, including MAO-A and MAO-B, serotonin and norepinephrine. These, as well as Gamma-amino-butyric acid (GABA) and dopamine, have been studied in perinatal populations (Mileva-Seitz, et al. 2011; Mileva-Seitz, et al. 2012). Of note are the studies that suggest that pregnancy may be associated with a relative deficiency in these neurotransmitters, acting as a vulnerability to the onset and relapse of mood disorders postpartum, when accompanied by rapid hormonal fluctuation as well as other factors such as sleep deprivation and the psychological adjustment to parenthood.
Sleep regulation. The psychobiological pathways involved in sleep may contribute to the development of perinatal mood and anxiety disorders. Women experience dramatic changes to their sleep pattern and sleep quality beginning in late pregnancy and extending well into the postpartum period, including frequent awakenings, fewer hours of total sleep, reduced sleep efficiency and shorter rapid eye movement (REM) sleep latency (Karacan, Williams et al. 1969; Coble, Reynolds et al. 1994). A systematic review on the topic reported women at risk of postpartum depression demonstrated reduced REM latency, increased total sleep time during pregnancy and decreased total sleep time in the postpartum period (Ross, et al. 2005). Lending support to this finding, a recent prospective study found that mothers who slept less than four hours between midnight and 6 a.m., and mothers who napped for less than one hour during the day were at higher risk of postpartum depression three months after delivery than women who got more sleep (Goyal, et al. 2009).
Reduced sleep has always been considered a major risk factor (or harbinger) of postpartum psychotic episodes. There is some support for this hypothesis, although sample sizes have been small (Sharma, et al. 2004) and complicated by clinical management affecting sleep (Bilszta, et al. 2010). Regardless of these study limitations, because of the known relationship between reduced sleep and the onset of bipolar mood episodes outside the perinatal period, sleep protection is considered an important part of preventive management for women with mood disorders in the perinatal period.
Consequences of untreated perinatal mental illness
Depression is a leading cause of disability worldwide, and causes impairment of function in many spheres. It can affect interpersonal relationships, occupational function and has been linked with a significantly increased risk of adverse child outcomes. In its most severe form, it can lead to suicide, and has been identified as one of the leading causes of maternal mortality in developed countries (Oates 2003; Austin, et al. 2007; Palladino, et al. 2011). Anxiety disorders can also be associated with significant morbidity that interferes with function, concentration, sleep and parenting ability. Depression and anxiety in pregnancy are strong risk factors for the persistence of depression, anxiety and stress in the postpartum period, where the links between these illnesses and adverse child outcomes have been well-established.
Impact of depression and anxiety on the developing fetus
Perinatal depression, anxiety and stress are clearly associated with adverse effects on the developing fetus (Dipietro 2012). The mechanism for the associations between mental distress during pregnancy and adverse outcomes in the offspring is not fully understood, but dysregulation of the maternal-placental-fetal axis as a result of neuroendocrine changes related to depression has been suggested (Wadhwa, et al. 2001). In addition, the importance of environmental factors associated with depression and anxiety such as maternal smoking, drug/alcohol use, poor nutrition and a low socioeconomic status may also play a role. In particular, exposure to maternal depression, anxiety and stress in pregnancy has been shown in multiple studies to be associated with an increased rate of preterm deliveries, lower APGAR scores, lower birth weights and smaller head circumference (Davalos, et al. 2012). Depression in late pregnancy is also associated with an increased risk for operative deliveries and admission to a neonatal intensive care unit (Chung, et al. 2001). While the magnitude of risk does not appear to be large in population-based studies, these outcomes have clinical significance for long-term trajectories of the developing child.
A number of studies have examined cognitive and emotional outcomes of infants of mothers who were depressed or anxious in pregnancy. Newborns of depressed mothers consistently show behavioral differences and developmental problems when compared to infants born to nondepressed mothers (Jones, et al. 1998; Weinberg & Tronick 1998; Martins & Gaffan 2000; Grace, et al. 2003). Prenatal depression has been associated with lower levels of attachment (Goecke, et al. 2012), and infants of depressed and anxious mothers may be less likely to identify their mother’s voice in the early weeks (Pacheco & Figueiredo 2012). Studies have also linked perinatal symptoms of anxiety with behavioral problems in early childhood (O’Connor, et al. 2002; Glasheen, et al. 2010), and suggest that physiological changes related to anxiety could affect fetal brain development. In fact, fetal changes, including increased activity and growth delays, as well as low neurotransmitter concentrations and changes in EEG activity in the newborns, have been noted in children of women with high levels of anxiety, depression and anger in the second trimester of pregnancy (Field, et al. 2003). There has also been a report of increased risk for criminality in the offspring of women who reported symptoms of depression during pregnancy (Maki, et al. 2003).
Children exposed to maternal depression and anxiety
The ill effects of maternal depression and anxiety on the offspring are well documented. Infants tend to be withdrawn, exhibit behavioral difficulties and have a higher rate of insecure or avoidant attachments (Murray & Copper 1997; Glasheen, et al. 2010). Children of depressed mothers exhibit ineffective emotional regulation, poor social skills, delays in cognitive development and are more likely to experience emotional instability later in life (Murray & Cooper 1997; Weinberg & Tronick 1998; Newport, et al. 2002). Few studies report longer-term follow-up beyond childhood and findings are less consistent. Those mothers who have childhood abuse and neglect histories as risk factors for depression are particularly likely to have problematic behaviors and attachment (Muzik, et al. 2013). Importantly, treatment of maternal psychiatric illness can change and improve the trajectory of a child’s development. In the Sequenced Treatment Algorithm for Depression (STAR-D) treatment trial, remission of depressive symptoms had a positive effect on both mothers and children, with children of mothers who remained depressed demonstrating an increased incidence of both externalizing and internalizing disorders (Weissman, Pilowsky et al. 2006).
Case identification
Case identification is an important part of the management of depression during pregnancy and postpartum. There is strong evidence that mood and anxiety disorders are underidentified and undertreated in the perinatal period – particularly when formal case identification programs are not in place (Byatt, et al. 2012). This may in part be due to lack of knowledge on the part of women and their providers about what is a “normal” reaction to pregnancy-induced physiological and psychological changes as well as to the adjustment to parenthood. Stigma around mental disorders, particularly as they relate to women’s ability to parent, may also play a role. In addition, providers have reported that discomfort about how to manage perinatal mental health issues as well as lack of specialist referral pathways can also be barriers to case identification and care (Buist, et al. 2005).
In response to these issues, clinical practice guidelines focused on management of perinatal mental health have begun to make recommendations about when and how to screen for perinatal mental disorders, as well as when to send for specialist referral (Austin, et al. 2011). These guidelines recommend that efforts to identify mood disorders be integrated into routine antenatal care as early as possible in the pregnancy – and that appropriate treatment pathways should be available for women who are identified. There is some controversy regarding whether all women should be screened (hence potentially increasing the rate of false positive screenings) or whether in-depth screening should focus only on women at high-risk (increasing the specificity, but potentially excluding women who do require care, but were not identified as part of a high-risk category). It is generally agreed that in-depth assessment should be offered to women with a personal history of a psychiatric disorder, a family history of psychiatric disorder and/or major psychosocial risk factors for perinatal mental health issues such as poor social support, intimate partner violence and/or other major life stressors.
Psychosocial risk assessment in and of itself is not adequate for the prediction and/or detection of perinatal mood and anxiety disorders (Austin, et al. 2011). Many systems have implemented routine screening of perinatal mental health issues, including jurisdictions in Canada, the United States, the UK, Israel and Australia.
The goal of a screening program for perinatal mental health is to identify women who require in-depth mental health assessment and may require treatment. Case identification can take several forms, and the case finding tool that is used may be dependent on the setting. For example, the UK’s National Institute for Health and Care Excellence (NICE) clinical guidelines recommend that all women are asked two questions at the first visit in pregnancy, as well as at postpartum follow-up to identify the possible presence of depression: 1) “During the past month, have you often been bothered by feeling down, depressed, or hopeless?” and 2) “During the past month, have you often been bothered by having little interest or pleasure in doing things?” (National Collaborating Centre for Mental Health 2007). In the case of a positive response, then the following question is asked as well: “Is this something you feel you need or want help with?” In addition, there are some structured self-report tools that are used to screen for perinatal depression and anxiety. Of these, the Edinburgh Postnatal Depression Scale (EPDS) (Cox, et al. 1987) is the most widely accepted. It has been used in a number of countries, and has been translated into more than 30 languages (Cox & Holden 2003). The EPDS is brief (10 questions), inexpensive to use, and has a high sensitivity and validity for detection of current depression. A total score of 12 or more represents women at high risk of having major depression in the postpartum period (with scores of 14 or higher having better specificity during pregnancy) (Murray & Cox 1990). The EPDS also contains three questions that screen for anxiety, a common presentation for women with major depression in the perinatal period (Matthey 2008). Australia’s “Beyond Blue” Clinical Practice Guidelines for depression and related disorders in the perinatal period recommend specifically that the EPDS be used to screen for perinatal depression and anxiety (Austin, et al. 2011).
For conditions other than depression, no perinatal specific screening tools have been well-studied. However, there is evidence that the Spielberg State-Trait Anxiety Inventory (STAI), although not a perinatal-specific tool, has utility in detecting clinical significant anxiety in a manner that is stable across the early postpartum period (Meades & Ayers 2011; Dennis, et al. 2013). We have recently piloted the use of the Generalized Anxiety Disorder 7-item (GAD-7) scale (Spitzer, et al. 2006) as a screening tool in a perinatal population. Results indicated that the GAD-7 yielded a sensitivity of 69.3% and specificity of 67.3% at an optimal cutoff score of 12. However, compared to the EPDS and the EPDS-3A anxiety subscale, the GAD-7 displayed greater specificity over a greater range of cut-off scores and could more accurately identify GAD in patients with comorbid MDD. Therefore, we suggest that at a higher cut-off score of ≥14, the GAD-7 represents a clinically useful scale for the detection of GAD in perinatal psychiatric populations (Glazer, et al. 2013).
There are no perinatal-specific screening questionnaires for bipolar disorder. The Mood Disorder Questionnaire (MDQ) covers a wide breadth of manic and hypomanic symptoms, is brief and has been validated for use in a perinatal population (Frey, et al. 2012). As such, it has been recommended for use in perinatal settings. However, it suffers from the limitations of a self-report measure in that it requires that the individual have insight into manic and hypomanic symptoms to be identified (Zimmerman & Galione 2011). Also, it should be used in conjunction with a depression assessment tool such as the EDPS because it does not screen for depressive symptoms.
Regardless of the method used to identify women with perinatal mental illness, it is important to emphasize that case identification must be linked to an appropriate care pathway.
Prevention
Prevention is considered to be the first line of treatment for perinatal depression and other perinatal mental illnesses. To prevent relapse for women with preexisting disorders, it is recommended that informed and collaborative prenatal planning take place, preferably before pregnancy, to discuss issues related to birth control and planning pregnancy, the potential risks and benefits of psychotropic medication use and to outline plans in the case of relapse.
For women with a history of mood disorders (and particularly those with previous mood episodes in the perinatal period), who are currently pregnant or planning pregnancy, individualized and collaborative prenatal planning is indicated. Depending on the woman’s particular situation, this will likely involve planning to reduce psychosocial risk factors and decisions regarding psychotropic medication treatment during pregnancy. Reduction or discontinuation of psychotropic medication in pregnancy can be a risk factor for relapse, particularly in women with severe depression and bipolar disorder. It should be noted, however, that the prophylactic use of medication in euthymic women with a history of unipolar depression (but not taking medication at baseline) has not been demonstrated to be an effective prevention strategy (Dennis 2004). Decisions about prophylactic use of pharmacotherapy for women with previous episodes must be made on a case-by-case basis. Severity of illness is a key factor to consider, as are the preferences of the woman and her partner, if she has one. These aspects are addressed further in Chapters 19, 20 and 21 of this book.
Women with subsyndromal mood and/or anxiety symptoms are also important to target for intervention because these symptoms may increase the risk for full disorder with accompanying functional impairment, particularly in the postpartum period. In such cases, optimization of any current psychiatric or psychological treatment as well as consideration of the addition of psychological interventions to achieve symptoms remission are likely indicated. A Cochrane Review of 28 trials on psychosocial interventions to prevent postpartum depression concluded that: “Overall, psychosocial and psychological interventions significantly reduce the number of women who develop postpartum depression. Promising interventions include the provision of intensive, professionally-based postpartum home visits, telephone-based peer support and interpersonal psychotherapy” (Dennis & Dowswell 2013). Other general factors include minimizing stress and promoting family support, reduction (or cessation) of smoking, alcohol and illicit drug use; promoting health sleep, dietary and exercise habits; and close monitoring with aggressive treatment if early signs of depression are detected.
There is limited evidence for the prevention of postpartum depression and postpartum psychosis with exogenous administration of estrogen shortly after childbirth, as well as some evidence for the use of estrogen to treat postpartum depression (Ahokas, et al. 2000; Ahokas, et al. 2001).
High-dose oral estrogen was used as a prophylactic strategy in seven women with history of severe postpartum affective disorder (including both postpartum depression and postpartum affective psychosis); six of the seven remained well throughout the first postpartum year (Sichel, et al. 1995), but the high dose administered in this study is unlikely to be routinely given as a result of potential safety concerns.
Issues for treatment
Decision making about treatment of perinatal mood and anxiety disorders can be complex. Treatment decisions should take into account patient preference, seriousness of psychiatric illness, risk of relapse, as well as treatment risks and benefits. Clinical practice guidelines recommend a stepped treatment approach where women with mild symptoms are treated with supportive and psychological interventions within public health and/or primary care settings (National Collaborating Centre for Mental Health 2007). With increasing severity, pharmacological strategies are considered with the input of specialist consultation. Recent systematic reviews and meta-analyses have addressed the risk-benefit assessment of exposure to antidepressant medication during pregnancy (Grigoriadis, et al. 2013a; Grigoriadis, et al. 2013b; Ross, et al. 2013). In more extreme cases, psychiatric care, inpatient hospitalization and the consideration of somatic therapies such as electroconvulsive therapy may be required.
Treatment options
Psychological
Supportive therapies. It is not uncommon for first-time mothers to experience difficulty with the transition to motherhood. Supportive counseling can be adequate to help most new mothers deal with issues of unmet expectations and feelings of inadequacy (Murray, et al. 2003). Social support is also a key factor in recovery. Specifically, the involvement of the partner in treatment for postpartum depression results in improved outcomes (Misri, et al. 2000; Dennis & Ross 2006). With decreasing birth rates in many countries and more women joining the work force, the traditional social supports such as an extended family and a network of friends are often absent. Thus, maternal and child health nurses and postnatal depression support groups play a valuable role in helping mothers to recover. In addition, differing expectations of parenthood frequently increase stress on relationships. Marital difficulties predating the birth are often accentuated, and these further deplete the support base available to both parties. Relationship counseling is an important part of stress management in this context. Failure to address these issues between couples can result in ongoing marital difficulties and can contribute to parenting difficulties and later marital breakups. Fathers may also develop depression in the postpartum period and might require specific care.
Structured psychotherapies. Structured psychotherapies, such as cognitive behavior therapy (CBT) and interpersonal psychotherapy (IPT), have the strongest evidence for the treatment of mood disorders outside of the perinatal period. CBT is also considered a very effective treatment for many anxiety disorders (Hofmann, et al. 2012; Barth, et al. 2013). There have been some studies assessing these treatments specifically in the perinatal period. In a Cochrane database systematic review of randomized controlled trials for psychological and psychosocial interventions for antenatal mood disorders, only one trial (of IPT) met criteria. This study showed a reduction in depressive symptoms, but the authors concluded that the trial was too small, and with a nongeneralizable sample, to make specific recommendations on psychological/psychosocial treatment (Dennis, et al. 2007). However, a Cochrane systematic review of psychological therapies to treat postpartum depression included ten trials, and provided support for their efficacy (Dennis & Hodnett 2007). Using broader inclusion criteria for their review, another group conducted a meta-analysis to evaluate various psychological and psychosocial treatments for depression in pregnancy and postpartum. The largest effect size was found for CBT in combination with medication, but CBT alone also demonstrated significant effects. The review also supported the efficacy of IPT, with intervention effects postpartum greater than for treatment during pregnancy. Other interventions with significant beneficial effects included group therapy with cognitive behavioral, educational and transactional analysis components; psychodynamic therapy; counseling; and telephone-based and internet-based therapies (Bledsoe & Grote 2006). Simple educational interventions have not been shown to be effective in treating depression during pregnancy or postpartum.
It is important, however, to consider some potential disadvantages to psychotherapeutic and psychosocial interventions for depression and anxiety during pregnancy and postpartum. For example, treatment of mood and anxiety disorders using psychotherapeutic options may require more time (and effort) than pharmacological therapies – potentially increasing the amount of time that a developing fetus or young child is exposed to maternal depression and/or anxiety. Further, women with severe depression or anxiety may be less likely to respond to psychotherapy alone. This may be less of a problem with CBT where the treatment can focus on behavioral activation, but women with severe functional and cognitive impairment from depression may have difficulty with the cognitive and interpersonal interaction requirements of IPT. Other potential limits to the application of psychotherapy are more practical, in that it requires access to trained psychotherapists (not readily available in some areas), and may represent a large time investment (difficulty for mothers with young children) as well as a large financial investment in some jurisdictions. More recently, telephone-based and internet-based therapies are increasingly being developed and evaluated in an attempt to overcome some of these access barriers (Dennis & Kingston 2008).
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