Psychiatric Comorbidities in Functional Neurologic Symptom Disorder

Functional neurologic symptom disorder (FND) is among the most frequently encountered conditions in the outpatient neurology setting and is difficult to treat, with poor prognoses and significant disability and morbidity. FND also places an enormous financial burden on both affected individuals and society. There is a high comorbidity of other psychiatric conditions in FND that varies with age group and FND subtype. During the past decade, it has become apparent that an accumulation of psychologic stressors, rather than discrete trauma only, contribute to FND development. Although treatment advances have been made, particularly through implementation of a multidisciplinary approach, these do not always result in better outcomes because mechanisms of emotional distress may not be addressed. Here, we review the prevalence of psychiatric disorders in FND and posit that high levels of comorbidity are related to a general state of mental vulnerability known as insecure attachment. First, we describe the high prevalence of various psychiatric disorders in individuals with FND by different age groups. Then we discuss potential mechanisms underlying the strong association between FND and psychiatric disorders. By familiarizing clinicians with the frequency and pathophysiology of comorbid psychiatric disorders in FND, we aim to increase the understanding of treatment and prognostic factors for this complicated neuropsychiatric condition.

FND, including psychogenic nonepileptic seizures (PNES) and functional movement disorder (FMD), such as tremor or weakness, manifests as neurologic symptoms without an identifiable underlying neurologic disease.¹ It has been claimed that FND represents a “crisis in neurology,” considering it is highly prevalent and difficult to treat.² Individuals with FND have extremely elevated rates of health care utilization, long hospitalizations, and frequent referrals to multiple specialists.³ FND represents a diagnostic challenge. For example, the diagnosis of PNES has been reported to have an average of 7 years between symptom manifestation and definitive diagnosis.⁴ In the period between presentation and diagnosis, individuals with FND are at risk for inappropriate treatments, iatrogenic harm, expensive and unnecessary evaluations, and poor outcomes.⁵ Patients with FND also have high levels of distress, social isolation, and disability, matching that of organic neurologic disorders, and many people with FND rely on disease-related disability benefits.^1,6 In addition to patients’ and families’ suffering, FND places an economic burden on the health care system of up to hundreds of thousands of dollars per patient.⁴

Psychiatric comorbidities in FND are common and associated with poorer outcomes, including lower quality of life (QOL) and decreased survival for most medical disorders.^1,7-9 Proper delivery of information related to FND diagnosis and psychologic care are essential for successful treatment of FND.⁵ Many, however, receive treatment outside of the preferred multidisciplinary clinics that are best suited for FND treatment.

FND Definition and Prevalence

The Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) incorporates a variety of nonorganic or unexplained neurologic symptoms under the umbrella of FND. The DSM-5 provides diagnostic specifiers describing presentations (eg, with attack or seizures, or with abnormal movements).¹⁰ Correspondingly, in research, FND is usually divided in 2 categories, FMD and PNES, although the terminology is evolving for the latter. Any motor symptoms can fall under the category of FMD, commonly including ataxia, tremor, gait disturbances, weakness, and dystonia.^3,5 PNES manifest as generalized seizures, prolonged atonia, side-to-side head movements, eye closing with resistance to opening, and fluttering movements.⁵ FND is not considered a voluntary phenomena and should not be confused with the pursuit of a sick role without clear secondary gain, as in factitious disorder, or with an identifiable secondary gain, as in malingering.¹⁰

There is a high representation of FND in overall neurologic consultations, accounting for 16% of new referrals to outpatient neurology, second only to headache disorders.¹¹ The annual incidence of FND is estimated to be 1.9 to 4 per 100,000 for PNES and 4 to 5 per 100,000 for FMD.⁵ Although neurologists can accurately diagnose FND,⁵ as discussed next, it is likely that FND is underreported.^6,12

Psychiatric Comorbidities of FND

An estimated 55%¹³ to 95%⁸ of people with FND have at least 1 comorbid psychiatric disorder. In general, children with FND tend to have a lower prevalence of psychiatric disorders than adults, and remission is more likely.^{3,8,9,12,14-16} There do not, however, seem to be clear differences in FND outcomes among genders.¹ Prevalence of comorbid mental illness is higher in PNES vs FMD (Table).^{3,8,13,15,17-38}

Accurate determination of the prevalence of psychiatric disorders in FND is challenging for multiple reasons. For example, some studies use DSM criteria for psychiatric disorders, but others report frequencies of individuals exceeding cutoff scores on questionnaires that might not discriminate between subtypes of disorders (eg, depressive or anxiety disorder subtypes).^1,3,12,14,17 Self- or parent-report scales can result in overlapping symptomatology that can be difficult to disentangle and may overestimate prevalence.³⁹ For example, the single symptom of depression can contribute toward multiple diagnoses, including major depressive disorder (MDD), adjustment disorder, and borderline personality disorder. Similarly, perceptual abnormalities occur in complicated grief, posttraumatic stress disorder (PTSD) and schizophrenia.¹⁰ Self-report in all age groups can be problematic, as individuals may lack insight, and in the case of observer report (eg, parental report for children with FND) biases in reporting may exist.¹⁵ Variability in diagnostic accuracy exists across medical specialties. For example, a study of diagnostic impressions in 875 in-hospital psychiatric consultations found that only 3 diagnoses had more than 50% accuracy; these were neurocognitive disorder, substance use disorder (SUD), and adjustment disorder.⁴⁰ In the following sections, we review the prevalence of psychiatric comorbidities in child, adult, and veteran populations. Where data is sufficient, we separately describe psychiatric disorder prevalences for FMD and PNES.

Psychiatric Comorbidities of FND in Adults

Studies of adults with FND have reported a prevalence of psychiatric disorder in 51%¹⁸ to 95%.⁸ Some findings indicate it is the presence of somatic symptoms and not the comorbid psychiatric disorder that contribute the most detriment to FND prognosis and QOL.⁹

The most common comorbid psychiatric disorder in adults with PNES is depression,¹⁹ with large studies reporting a prevalence of 30%²⁰ to 48%.^17,21 Generalized anxiety disorder (GAD), found in 21%²² to 29%¹⁷ is the second most common comorbid psychopathology in adults with PNES. Third most common is PTSD with a prevalence of 23% in large studies,^17,20 although smaller studies have reported up to 100% prevalence.¹⁹ Suicidal ideation, a symptom often found in depression, can be found in 63% of adults with PNES, with one-third of those cases being severe in nature.¹⁷ A history of a suicide attempt has been reported in 7% of adults with PNES.¹⁹ Large studies that differentiate among specific disorders have found panic disorder in 15%¹⁷ and obsessive-compulsive disorder (OCD) in 2%²⁰ to 9%¹⁷ of adults with PNES.

In the case of FMD, anxiety disorders including GAD, panic disorder, and specific phobias are together the most commonly reported group of psychiatric comorbidities with a prevalence of 38%⁸ to 75%.³ Depression is the second most common comorbid psychiatric disorder in FMD, seen in 19%⁸ to 49%³ of adults with PTSD with a prevalence of 24%.³ Other psychiatric conditions such as panic disorder, sometimes clustered with anxiety disorder, can be found in 8%³ to 15%⁸ of adults with FMD. Suicidal ideation and self-harm can be found in 8.4% and 4.1% of adults with FMD respectively. Disorders that are generally observed in less than 10% of this group include OCD and bipolar disorder (BD) types I and II. Conditions rarely reported in FMD are eating disorders, psychotic illnesses, and SUD.¹⁷ Personality disorders, which prior to the DSM-5 were considered separate from other psychiatric disorders, are found in more than half of adults with PNES and FMD.^8,17

Psychiatric Comorbidities of FND in Children

Children with FND have a higher prevalence of psychiatric disorders than their peers without FND, but a lower prevalence of psychiatric disorders than adults with FND.^12,13,23 The largest study of pediatric PNES examined 382 children and found that 39% had a psychiatric comorbidity.²³ Adjustment disorder was the most common, with a 17% prevalence, followed by 12% with somatic symptoms and related disorders, 11% with neurodevelopmental disorders, depression in 6%, and anxiety in 3% of children with PNES. Maladaptive coping is also common in PNES, with a study identifying inhibited, submissive, or introversive personality patterns in 85% of patients.¹⁵

Studies of children with FMD are limited. In 1 study of functional breathing disorders, approximately half had a psychiatric comorbidity.^13,24,25 In children with FMD, depressive disorders are the most common, found in 9%¹³ to 38%²⁴ of children with FMD. This is followed by attention-deficit hyperactivity disorder (ADHD) in 9%²⁵ to 17%,¹³ specific phobia in 15%,¹³ panic disorder and panic attacks in 7%¹³ to 15%,²⁴ and GAD in 11%.¹³ Eating disorders and OCD are exceedingly rare.^13,24

Psychiatric Comorbidities of FND in Veterans

Veterans of the US military are potentially at increased risk for FND owing to their high exposure to stressors and trauma; however, data are limited. Veterans with FMD have a 75% prevalence of comorbid psychiatric conditions.²⁶ Depression is most common, with a 48% prevalence,²⁶ and PTSD is second most frequent at 32%, followed by a 12% prevalence of anxiety disorders and BD, and a 4% prevalence of SUD.²⁶ Similar to studies of civilians,⁸ veterans with FMD have a higher rate of health care utilization, with a greater number of new medical consultations and diagnoses.²⁶ Veterans with FMD also have a greater number of visits to the emergency department, ambulatory clinics, inpatient facilities, and mental health clinics when compared with those with organic movement disorders.²⁶

Veterans with PNES have a 94% prevalence of comorbid psychiatric conditions (Table), with depression being the most prevalent at 77%.²⁷ The second most common diagnosis in this group is PTSD, with a prevalence of 63%, followed by SUD in 42% of veterans.²⁷ Less common but still highly prevalent are panic disorders, found in 21%, specific phobias found in 16.9%, GAD found in 14%, and BD in 15% of veterans with PNES.²⁷

Pervasive Vulnerability to Psychiatric Disorders as a Potential Mechanism of FND

Several theoretic models have been proposed to explain the origin and perpetuating mechanisms of FND. For example, PNES has been approached via theories including the Freudian model of physical manifestation of stress, the model of learned behavior by Moore and Baker, and trauma-related dissociation model by Bowman and by Baslet.²⁸ These conceptualizations help understand FND as a mechanism (eg, reaction to trauma, psychologic defense through avoidance, and a reflex reaction to perceived threat.)²⁸ Recently, challenges to the notion that trauma is the only catalytic factor for FND have been made, forcing the evolution of corresponding psychologic models.²⁹

Undisputedly, a history of trauma, defined as specific situations that jeopardize health and survival,¹⁰ is commonly found in people with FND.^12,30 Trauma as a discrete event, however, might not represent the biggest driver of psychologic distress in people who develop FND. Rather, there is a growing understanding that childhood maltreatment, referring to events that interfere with development or dignity in the context of a relationship of trust or power, is strongly associated with FND.^{10,12,14,30-32} In a study identifying a history of trauma in 78% of people with FND, family dysfunction and bereavement were also present in two-thirds of cases.³⁰ The authors of this study maintained that family dysfunction and affective disorders, found in 54% and 42% of their sample, respectively, are the most common perpetuating factors of FND.³⁰

Although there are many limitations in the identification and reporting of childhood sexual abuse, this form of trauma, which was once considered central to FND, is not present in the majority of persons with FND.^12,32 A study evaluating predisposing factors for PNES found that 80% of individuals did not report sexual trauma, and that one-fourth of those who did were exposed during adulthood.³⁰ A 2018 meta-analysis of stressors in persons with FMD corroborated that a history of distressing life events was common, but maltreatment and neglect in childhood presented a bigger risk for FMD than sexual or physical abuse.³² Evidence of the centrality of nonsexual trauma has been found among children with FND. An Australian study of 194 children with FND found that recent death of a loved one or separation from a parent was the most frequent stressor in 34%, followed by experiencing or witnessing verbal or physical violence in 20%, and school and learning stressors in 14%, whereas sexual assault was prevalent in 4% of patients.¹² Another study of 29 children with PNES found stressors related to status and peer relationships were present in 44%, family conflict in 38%, learning difficulties in 26%, and bullying in 22%, whereas sexual abuse was reported in 15%.¹⁵

Attachment in FND

Disturbances to healthy attachment are a potential overarching mechanism by which sexual trauma and other forms of early life adversity, of the kinds described above, may impact development of comorbid psychopathology, including FND. According to attachment theory, during development we rely on others to provide dependable, consistent, and sensitive support, which—when successful— leads to a stable sense of welfare and identity known as secure attachment.^29,31 Attachment changes throughout life.³¹ Although we initially rely mostly on parental figures for attachment, as we form relationships outside our families, the centrality of attachment is transferred to close friends and romantic partners.²⁹ Individuals can develop or transition to insecure attachments when there is a lack of reliable and nurturing figures to offer support in times of crisis.^7,29,31 Insecure attachment creates a state of general vulnerability to psychiatric disorders through maladaptive coping such as alexithymia, minimizing, avoidance, and physically manifested psychologic distress (Figure).^31,33

Attachment has been studied in many psychiatric disorders, including FND in children and adults.^7,31,33 In a study of 449 adolescents, age 17 to 18 years, attachment to parental figures, friends, and romantic partners was assessed along with mental health and risk-taking behavior.²⁹ Secure attachments were directly related to resilience, whereas insecure attachments were associated with proneness to psychopathology, sexual risk-taking, SUD, anger control, inattention, and hyperactivity. In another study, researchers evaluated 76 children with FND, age 6 to 18 years, and found all those with FMD or PNES lacked healthy attachment. In contrast, a lack of healthy attachment was only present in 10% of children without FMD or PNES.¹² The authors of this study hypothesized that those who could appropriately balance temporal and emotional information when revisiting past life events, characteristic of balanced attachment, might be protected against FND through better stress regulation.³³ Together, these results suggest that psychologic stressors besides discrete trauma may contribute to FND development through insecure attachment.

Adults can also experience changes in attachment from secure to insecure form and vice versa, with the potential to improve resilience and psychiatric symptoms when a sense of secure attachment is generated and maintained.³¹ A higher level of secure attachment is a good prognostic factor for long-term improvement of FND in adults.⁷ The presence of social support is related to secure attachment, but it is the quality of the partnership and not the mere presence of a live-in partner that influences recovery in FND.^9,18 Stable interpersonal relationships with health care personnel during intensive parts of treatment can lead to direct but potentially inadvertent benefits.^1,18 Such relationships may result in initial improvements for those with FND,^17,34,35 with or without actual psychologic interventions, but a long-term persistence or worsening of functional symptoms if the attachment deficits are not addressed.^1,8,18,34 Persons with FND identify the perceived level of support and confidence in the treatment by clinicians, rather than elimination of stressors, medication, or psychotherapy as the reason for symptom improvement.^1,18,31 Another example comes from a multicenter trial of treatment for PNES in the UK, which assigned 368 participants with PNES to 12 sessions of cognitive behavioral therapy (CBT) and standard-of-care treatment vs standard-of-care alone. Those who received both CBT and standard-of-care treatment had improvement in multiple secondary outcomes, including QOL and psychologic distress, and rated seizures as less bothersome, although both groups had the same monthly seizure frequency.¹⁷

FND Without Identifiable Trauma and Biomarkers

Although the understanding of FND treatment from a psychologic perspective has been long-standing and the use of medications nonbeneficial, the lack of identifiable trauma in some with FND has raised the questions about other biologic mechanisms associated with FND.⁵ A possible explanation for presentation of FND without recognizable stressors is that individuals with FND and their families simply have difficulty identifying stressful precursor events.¹⁵ Some biologic markers that could serve as proxy in this situation have been identified in FND, including attention dysregulation, elevated autonomic arousal, abnormal functional connectivity, or hypoactivation of key areas related to motor control.^2,5,36 A full discussion of such potential biomarkers is outside the scope of this review. Most likely, there is a contribution of neurobiologic, genetic, and psychologic factors underlying and maintaining FND and comorbid psychiatric symptoms, highlighting the importance of a multidisciplinary approach to treating FND.^31,37

Summary

Persons with FND have high rates of comorbid psych-iatric disorders as well as chronic and acute stressors. Comorbidity of psychiatric disorders and FND can be conceptualized as the consequence of insecure attachment, a state of general vulnerability to mental illness driven by maladaptive coping. Specifically, insecure attachment in the context of certain psychosocial factors perpetuates FND and psychiatric disorders. The collaboration of multidisciplinary teams in the treatment of persons with FND is best suited to offer a gestalt understanding of social, psychologic, and biologic components of these conditions.