Patients with psychogenic movement disorders (PMDs) have a high prevalence of comorbid psychiatric disorders. Depression in particular is very common. For instance, in the series by Williams et al. (1), 71% of 24 patients had depression, and in the series by Feinstein et al. (2), the lifetime prevalence of major depression was 43%. Although the latter study did not utilize a control group, comparisons were made with the National Psychiatric Co-Morbidity study data, an epidemiologic survey of more than 8,000 respondents in the United States; this survey showed a much lower lifetime prevalence of depression in the general population, reported at 17.1%. The high prevalence of depression in PMD is in keeping with the prevalence of depression observed in other forms of conversion disorder (CD) (3). In this chapter, we explore the similarities between the two disorders and postulate potential biological mechanisms underlying this relationship. We will refer to PMD and CD as if they had similar mechanisms, although differences between subtypes of CD are likely (4).

The pathophysiologic basis for depression has been postulated as a multifactorial model influenced by acute and chronic psychological stress, early adverse experiences, somatic disease, genetic factors, gender, and personality traits. The definition of a major depressive episode, according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), is that “a person must have experienced at least five of the nine symptoms below for the same two weeks or more, for most of the time almost every day, and this is a change from his/her prior level of functioning.” One of the symptoms must be either (i) depressed mood, or (ii) loss of interest.

The category of mood disorders in the DSM-IV includes major depressive disorder, dysthymic disorder, bipolar disorder, cyclothymic disorder, mood disorder due to a general medical condition, and substance-induced mood disorder (5).

The comorbidity of depression is high in CD and there are multiple similarities between the two disorders as discussed below. The relationship between CD and depression can be conceptualized as follows: (i) depression may be secondary to CD; (ii) pathophysiologic similarities may result in the simultaneous expression of the disorders (e.g., genetic factors, abuse or stress, personality traits, HPA axis or neurotransmitter abnormalities); or (iii) depression may act as an underlying vulnerability to CD. With respect to the study of CD, depression can be conceptualized as a confounder, as a potential model for understanding the pathophysiology of conversion disorder, or as a potential mediator in the onset of conversion symptoms.

Aside from the high comorbidity of depression in CD, the similarities between depression and CD include the association with multiple somatic symptoms, childhood abuse and stressors, female gender, and potentially personality traits.

Both depression and CD are highly associated with multiple somatic symptoms. Depression frequently has comorbid somatic symptoms, including those operationally defined within the DSM-IV such as bradyphrenia or fatigue (5), and other unexplained symptoms such as pain, gastrointestinal symptoms, and cardiovascular symptoms (6). Furthermore, the medically unexplained disorders or functional somatic syndromes such as fibromyalgia, irritable bowel syndrome, chronic fatigue syndrome, and chronic pain are also frequently comorbid with depression (7,8). Similarly, one of the supportive criteria in the operational definition of PMD is the presence of multiple somatic symptoms (1). Feinstein et al. (2) found that 38% of patients with PMD had developed other physical symptoms on follow-up, and Williams et al. (1) found that 12.5% of 24 PMD patients had somatization disorder. These findings are in keeping with the literature on CD (3). Whether these comorbid somatic symptoms in CD represent other undiagnosed somatoform disorders such as somatization disorder, a greater propensity to develop somatic symptoms, or can be explained by the frequent comorbidity of depression is not known. The pathophysiologic link between these somatic symptoms and depression is not completely known. The frequent association of depression with unexplained chronic pain, for example, has been hypothesized neurochemically to be related to similar underlying abnormalities in serotonin, norepinephrine, substance P, and corticotrophin releasing factor (CRF) (9).

Both depression and CD have also been associated with childhood abuse (10,11). Other adverse childhood experiences such as parental loss (12) are associated with depression as well. Similarly, emotional neglect and family dysfunction have been associated with CD (11). It should be noted, however, that the incidence of childhood abuse may differ depending on conversion subtype. Most studies demonstrating an elevated incidence of childhood abuse have either mixed conversion disorders (11,13,14) or nonepileptic seizures (15). A recent study by Stone et al. (4) suggests that psychogenic paralysis, in comparison to nonepileptic seizures, may have a lowered association with childhood abuse. Similarly, Binzer et al. (16) noted a low incidence of childhood abuse in CD patients with motor symptoms, in contrast to expected findings, although the authors found increased perception of parental rejection, and lowered perception of affection and emotional warmth. Whether PMD, predominantly a disorder with hyperkinetic or positive symptoms, differs from that of psychogenic paralysis, a disorder with hypokinetic symptoms, is not known. A history of childhood abuse is also associated with an increased risk of medically unexplained somatic symptoms and high utilization of medical services (17). Dissociation and hypnotic susceptibility have been suggested as factors that mediate the relationship between abuse and conversion (11,15).

A potential biological link connecting depression and CD may lie in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Hyperactivity of the HPA axis, as demonstrated by cortisol nonsuppression with the standard dexamethasone suppression test, has been consistently demonstrated in patients with severe depression or psychotic subtypes, and, in at least one study, in depressed patients with comorbid anxiety (18, 19, 20). The nonsuppression normalizes when the depression is remitted (21), whereas persistent nonsuppression is associated with recurrent episodes and risk of relapse (22). In addition to excessive cortisol secretion, the normal nocturnal decrease in cortisol was also lost in severely depressed patients (20). The presence of excessive cortisol itself and the glucocorticoid receptor have been implicated in mood
disorders (23, 24, 25) as observed by the association of Cushing disease or exogenous steroid administration with depression.

Elevated CRF levels have also been demonstrated in depressed patients (26). Aside from its regulatory role in the HPA axis, CRF itself has been postulated to have a direct effect on the behavioral stress response. Administration of CRF to animals results in autonomic, anxious, and depressivelike behaviors. CRF increases the firing rate of noradrenergic neurons in the locus coeruleus, whereas serotonergic neurons in the raphe are inhibited (23,25). The elevated CRF release in depression has been suggested to be related to aberrant feedback inhibition from either the hippocampus or ventromedial prefrontal cortex (PFC), or from the permissive role of the amygdala (24,25). These neuroanatomic structures will be discussed in a subsequent section.