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Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
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Diagnosis of borderline personality disorder is based on a clinical assessment by a mental health professional. The best method is to present the criteria of the disorder to a person and to ask them if they feel that these characteristics accurately describe them. Actively involving people with BPD in determining their diagnosis can help them become more willing to accept it. Although some clinicians prefer not to tell people with BPD what their diagnosis is, either from concern about the stigma attached to this condition or because BPD used to be considered untreatable, it is usually helpful for the person with BPD to know their diagnosis. This helps them know that others have had similar experiences and can point them toward effective treatments.
In general, the psychological evaluation includes asking the patient about the beginning and severity of symptoms, as well as other questions about how symptoms impact the patient's quality of life. Issues of particular note are suicidal ideations, experiences with self-harm, and thoughts about harming others. Diagnosis is based both on the person's report of their symptoms and on the clinician's own observations. Additional tests for BPD can include a physical exam and laboratory tests to rule out other possible triggers for symptoms, such as thyroid conditions or substance abuse. The ICD-10 manual refers to the disorder as "emotionally unstable personality disorder" and has similar diagnostic criteria. In the DSM-5, the name of the disorder remains the same as in the previous editions.
The lifetime prevalence of dissociative disorders varies from 10% in the general population to 46% in psychiatric inpatients. Diagnosis can be made with the help of structured interviews such as the Dissociative Disorders Interview Schedule (DDIS) and the Structured Clinical Interview for DSM-IV Dissociative Disorders (SCID-D), or with the Dissociative Experiences Scale (DES) which is a self-assessment questionnaire. Some diagnostic tests have also been adapted and/or developed for use with children and adolescents such as the Children's Version of the Response Evaluation Measure (REM-Y-71), Child Interview for Subjective Dissociative Experiences, Child Dissociative Checklist (CDC), Child Behavior Checklist (CBCL) Dissociation Subscale, and the Trauma Symptom Checklist for Children Dissociation Subscale.
There are problems with classification, diagnosis and therapeutic strategies of dissociative and conversion disorders which can be understood by the historic context of hysteria. Even current systems used to diagnose DD such as the DSM-IV and ICD-10 differ in the way the classification is determined. In most cases mental health professionals are still hesitant to diagnose patients with Dissociative Disorder, because before they are considered to be diagnosed with Dissociative Disorder these patients have more than likely been diagnosed with major depression, anxiety disorder, and most often post-traumatic disorder.
An important concern in the diagnosis of dissociative disorders is the possibility that the patient may be feigning symptoms in order to escape negative consequences. Young criminal offenders report much higher levels of dissociative disorders, such as amnesia. In one study it was found that 1% of young offenders reported complete amnesia for a violent crime, while 19% claimed partial amnesia. There have also been incidences in which people with dissociative identity disorder provide conflicting testimonies in court, depending on the personality that is present.
Dissociative disorders (DD) are widely believed to have roots in traumatic childhood experience (abuse or loss), but symptomology often goes unrecognized or is misdiagnosed in children and adolescents. There are several reasons why recognizing symptoms of dissociation in children is challenging: it may be difficult for children to describe their internal experiences; caregivers may miss signals or attempt to conceal their own abusive or neglectful behaviors; symptoms can be subtle or fleeting; disturbances of memory, mood, or concentration associated with dissociation may be misinterpreted as symptoms of other disorders.
In addition to developing diagnostic tests for children and adolescents (see above), a number of approaches have been developed to improve recognition and understanding of dissociation in children. Recent research has focused on clarifying the neurological basis of symptoms associated with dissociation by studying neurochemical, functional and structural brain abnormalities that can result from childhood trauma. Others in the field have argued that recognizing disorganized attachment (DA) in children can help alert clinicians to the possibility of dissociative disorders.
Clinicians and researchers also stress the importance of using a developmental model to understand both symptoms and the future course of DDs. In other words, symptoms of dissociation may manifest differently at different stages of child and adolescent development and individuals may be more or less susceptible to developing dissociative symptoms at different ages. Further research into the manifestation of dissociative symptoms and vulnerability throughout development is needed. Related to this developmental approach, more research is required to establish whether a young patient’s recovery will remain stable over time.
Diagnosis is based on the self-reported experiences of the person followed by a clinical assessment. Psychiatric assessment includes a psychiatric history and some form of mental status examination. Since some medical and psychiatric conditions mimic the symptoms of DPD, clinicians must differentiate between and rule out the following to establish a precise diagnosis: temporal lobe epilepsy, panic disorder, acute stress disorder, schizophrenia, migraine, drug use, brain tumour or lesion. No laboratory test for depersonalization-derealization disorder currently exists.
The diagnosis of depersonalization disorder can be made with the use of the following interviews and scales:
The Structured Clinical Interview for DSM-IV Dissociative Disorders (SCID-D) is widely used, especially in research settings. This interview takes about 30 minutes to 1.5 hours, depending on individual's experiences.
The Dissociative Experiences Scale (DES) is a simple, quick, self-administered questionnaire that has been widely used to measure dissociative symptoms. It has been used in hundreds of dissociative studies, and can detect depersonalization and derealization experiences.
The Dissociative Disorders Interview Schedule (DDIS) is a highly structured interview which makes DSM-IV diagnoses of somatization disorder, borderline personality disorder and major depressive disorder, as well as all the dissociative disorders. It inquires about positive symptoms of schizophrenia, secondary features of dissociative identity disorder, extrasensory experiences, substance abuse and other items relevant to the dissociative disorders. The DDIS can usually be administered in 30–45 minutes.
The Cambridge Depersonalization Scale (CDS) is a method for determining the severity of depersonalization disorder. It has been proven and accepted as a valid tool for the diagnosis of depersonalization disorder in a clinical setting. It is also used in a clinical setting to differentiate minor episodes of depersonalization from actual symptoms of the disorder. Due to the success of the CDS, a group of Japanese researchers underwent the effort to translate the CDS into the J-CDS or the Japanese Cambridge Depersonalization Scale. Through clinical trials the Japanese research team successfully tested their scale and determined its accuracy. One limitation is that the scale does not allow for the differentiation between past and present episodes of depersonalization. It should also be noted that it may be difficult for the individual to describe the duration of a depersonalization episode, and thus the scale may lack accuracy. The project was conducted in the hope that it would stimulate further scientific investigations into depersonalization disorder.
With treatment, the majority of people with BPD can find relief from distressing symptoms and achieve remission, defined as a consistent relief from symptoms for at least two years. This longitudinal study tracking the symptoms of people with BPD found that 34.5% achieved remission within two years from the beginning of the study. Within four years, 49.4% had achieved remission, and within six years, 68.6% had achieved remission. By the end of the study, 73.5% of participants were found to be in remission. Moreover, of those who achieved recovery from symptoms, only 5.9% experienced recurrences. A later study found that ten years from baseline (during a hospitalization), 86% of patients had sustained a stable recovery from symptoms.
Patient personality can play an important role during the therapeutic process, leading to better clinical outcomes. Recent research has shown that BPD patients undergoing dialectical behavior therapy (DBT) exhibit better clinical outcomes correlated with higher levels of the trait of agreeableness in the patient, compared to patients either low in agreeableness or not being treated with DBT. This association was mediated through the strength of a working alliance between patient and therapist; that is, more agreeable patients developed stronger working alliances with their therapists, which in turn, led to better clinical outcomes.
In addition to recovering from distressing symptoms, people with BPD also achieve high levels of psychosocial functioning. A longitudinal study tracking the social and work abilities of participants with BPD found that six years after diagnosis, 56% of participants had good function in work and social environments, compared to 26% of participants when they were first diagnosed. Vocational achievement was generally more limited, even compared to those with other personality disorders. However, those whose symptoms had remitted were significantly more likely to have good relationships with a romantic partner and at least one parent, good performance at work and school, a sustained work and school history, and good psychosocial functioning overall.
Perhaps due to their perceived rarity, the dissociative disorders (including DID) were not initially included in the Structured Clinical Interview for DSM-IV (SCID), which is designed to make psychiatric diagnoses more rigorous and reliable. Instead, shortly after the publication of the initial SCID a freestanding protocol for dissociative disorders (SCID-D) was published. This interview takes about 30 to 90 minutes depending on the subject's experiences. An alternative diagnostic instrument, the Dissociative Disorders Interview Schedule, also exists but the SCID-D is generally considered superior. The Dissociative Disorders Interview Schedule (DDIS) is a highly structured interview that discriminates among various DSM-IV diagnoses. The DDIS can usually be administered in 30–45 minutes.
Other questionnaires include the Dissociative Experiences Scale (DES), Perceptual Alterations Scale, Questionnaire on Experiences of Dissociation, Dissociation Questionnaire, and the Mini-SCIDD. All are strongly intercorrelated and except the Mini-SCIDD, all incorporate absorption, a normal part of personality involving narrowing or broadening of attention. The DES is a simple, quick, and validated questionnaire that has been widely used to screen for dissociative symptoms, with variations for children and adolescents. Tests such as the DES provide a quick method of screening subjects so that the more time-consuming structured clinical interview can be used in the group with high DES scores. Depending on where the cutoff is set, people who would subsequently be diagnosed can be missed. An early recommended cutoff was 15-20. The reliability of the DES in non-clinical samples has been questioned.
Depersonalization disorder is classified differently in the DSM-IV-TR and in the ICD-10: In the DSM-IV-TR this disorder it is seen as a dissociative disorder; in the ICD-10 as an independent neurotic disorder. Whether depersonalization disorder should be characterized as a dissociative disorder can be discussed.
Little is known about prognosis of untreated DID. It rarely, if ever, goes away without treatment, but symptoms may resolve from time to time or wax and wane spontaneously. Patients with mainly dissociative and posttraumatic symptoms face a better prognosis than those with comorbid disorders or those still in contact with abusers, and the latter groups often face lengthier and more difficult treatment. Suicidal ideation, failed suicide attempts, and self-harm also occur. Duration of treatment can vary depending on patient goals, which can extend from elimination of all alters to merely reducing inter-alter amnesia, but generally takes years.
Psychosis as a symptom of a psychiatric disorder is first and foremost a diagnosis of exclusion. So a new-onset episode of psychosis "cannot" be considered to be a symptom of a psychiatric disorder until other relevant and known medical causes of psychosis are excluded, or ruled out. Many clinicians improperly perform, or entirely miss this step, introducing avoidable diagnostic error and misdiagnosis.
An initial assessment includes a comprehensive history and physical examination. Although no biological laboratory tests exist which confirm schizoaffective disorder, biological tests should be performed to exclude psychosis associated with or caused by substance use, medications, toxins or poisons, surgical complications, or other medical illnesses. Since non-medical mental health practitioners are not trained to exclude medical causes of psychosis, people experiencing psychosis should be referred to an emergency department or hospital.
Delirium should be ruled out, which can be distinguished by visual hallucinations, acute onset and fluctuating level of consciousness, indicating other underlying factors which includes medical illnesses. Excluding medical illnesses associated with psychosis is performed by using blood tests to measure:
- Thyroid-stimulating hormone to exclude hypo- or hyperthyroidism,
- Basic electrolytes and serum calcium to rule out a metabolic disturbance,
- Full blood count including ESR to rule out a systemic infection or chronic disease, and
- Serology to exclude syphilis or HIV infection.
Other investigations which may be performed include:
- EEG to exclude epilepsy, and an
- MRI or CT scan of the head to exclude brain lesions.
Blood tests are not usually repeated for relapse in people with an established diagnosis of schizoaffective disorder, unless there is a specific "medical" indication. These may include serum BSL if olanzapine has previously been prescribed, thyroid function if lithium has previously been taken to rule out hypothyroidism, liver function tests if chlorpromazine has been prescribed, CPK levels to exclude neuroleptic malignant syndrome, and a urinalysis and serum toxicology screening if substance use is suspected. Assessment and treatment may be done on an outpatient basis; admission to an inpatient facility is considered if there is a risk to self or others.
Because psychosis may be precipitated or exacerbated by common classes of psychiatric medications, such as antidepressants, ADHD stimulant medications, and sleep medications, prescribed medication-induced psychosis should be ruled out, particularly for first-episode psychosis. This is an essential step to reduce diagnostic error and to evaluate potential medication sources of further patient harm. Regarding prescribed medication sources of patient harm, Yale School of Medicine Professor of Psychiatry Malcolm B. Bowers, Jr, MD wrote:
Illicit drugs aren't the only ones that precipitate psychosis or mania—prescribed drugs can too, and in particular, some psychiatric drugs. We investigated this and found that about 1 in 12 psychotic or manic patients in an inpatient psychiatric facility are there due to antidepressant-induced psychosis or mania. That's unfortunate for the field [of psychiatry] and disastrous for some of our patients.
Substance-induced psychosis should also be ruled out. Both substance- and medication-induced psychosis can be excluded to a high level of certainty while the person is psychotic, typically in an emergency department, using both a
- Broad spectrum urine toxicology screening, and a
- Full serum toxicology screening (of the blood).
Some dietary supplements may also induce psychosis or mania, but cannot be ruled out with laboratory tests. So a psychotic person's family, partner, or friends should be asked whether he or she is currently taking any dietary supplements.
Common mistakes made when diagnosing psychotic patients include:
- Not properly excluding delirium,
- Missing a toxic psychosis by not screening for substances "and" medications,
- Not appreciating medical abnormalities (e.g., vital signs),
- Not obtaining a medical history and family history,
- Indiscriminate screening without an organizing framework,
- Not asking family or others about dietary supplements,
- Premature diagnostic closure, and
- Not revisiting or questioning the initial diagnostic impression of primary psychiatric disorder.
Only after these relevant and known causes of psychosis have been ruled out can a psychiatric differential diagnosis be made. A mental health clinician will incorporate family history, observation of a psychotic person's behavior while the person is experiencing active symptoms, to begin a psychiatric differential diagnosis. Diagnosis also includes self-reported experiences, as well as behavioral abnormalities reported by family members, friends, or significant others. Mistakes in this stage include:
- Not screening for dissociative disorders. Dissociative identity disorder and psychotic symptoms in schizoaffective disorder have considerable overlap, yet a different overall treatment approach.
Dissociative disorder not otherwise specified (DDNOS) is a mental health diagnosis for pathological dissociation that matches the DSM-5 criteria for a dissociative disorder, but does not fit the full criteria for any of the specifically identified subtypes, which include dissociative identity disorder, dissociative amnesia, and depersonalization/derealization disorder. The International Statistical Classification of Diseases and Related Health Problems (ICD-10) refers to the diagnosis as "Other dissociative and conversion disorders".
Examples of DDNOS include chronic and recurrent syndromes of mixed dissociative symptoms, identity disturbance due to prolonged and intense coercive persuasion, disorders similar to dissociative identity disorder, acute dissociative reactions to stressful events, and dissociative trance.
DDNOS is the most common dissociative disorder and is diagnosed in 40% of dissociative disorder cases. It is often co-morbid with other mental illnesses such as complex posttraumatic stress disorder, major depressive disorder, generalized anxiety disorder, personality disorders, substance abuse disorders and eating disorders.
In the opinion of Allen Frances, chair of the DSM-IV task force, the DSM-5's somatic symptom disorder brings with it a risk of mislabeling a sizable proportion of the population as mentally ill. “Millions of people could be mislabeled, with the burden falling disproportionately on women, because they are more likely to be casually dismissed as ‘catastrophizers’ when presenting with physical symptoms.”
The utility of PTSD derived psychotherapies for assisting children with C-PTSD is uncertain. This area of diagnosis and treatment calls for caution in use of the category C-PTSD. Ford and van der Kolk have suggested that C-PTSD may not be as useful a category for diagnosis and treatment of children as a proposed category of developmental trauma disorder (DTD). For DTD to be diagnosed it requires a
'history of exposure to early life developmentally adverse interpersonal trauma such as sexual abuse, physical abuse, violence, traumatic losses of other significant disruption or betrayal of the child's relationships with primary caregivers, which has been postulated as an etiological basis for complex traumatic stress disorders. Diagnosis, treatment planning and outcome are always relational.'
Since C-PTSD or DTD in children is often caused by chronic maltreatment, neglect or abuse in a care-giving relationship the first element of the biopsychosocial system to address is that relationship. This invariably involves some sort of child protection agency. This both widens the range of support that can be given to the child but also the complexity of the situation, since the agency's statutory legal obligations may then need to be enforced.
A number of practical, therapeutic and ethical principles for assessment and intervention have been developed and explored in the field:
- Identifying and addressing threats to the child's or family's safety and stability are the first priority.
- A relational bridge must be developed to engage, retain and maximize the benefit for the child and caregiver.
- Diagnosis, treatment planning and outcome monitoring are always relational (and) strengths based.
- All phases of treatment should aim to enhance self-regulation competencies.
- Determining with whom, when and how to address traumatic memories.
- Preventing and managing relational discontinuities and psychosocial crises.
The DSM-IV-TR states that the fugue may have a duration from days to months, and recovery is usually rapid. However, some cases may be refractory. An individual usually has only one episode.
Somatic symptom disorder has been a controversial diagnosis, since it was historically based primarily on negative criteria - that is, the absence of a medical explanation for the presenting physical complaints. Consequently, any person suffering from a poorly understood illness can potentially fulfill the criteria for this psychiatric diagnosis, even if they exhibit no psychiatric symptoms in the conventional sense. In 2013-4, there were several widely publicized cases of individuals being involuntarily admitted to psychiatric wards on the basis of this diagnosis alone. This has raised concerns about the consequences of potential misuse of this diagnostic category.
The most widely used criteria for diagnosing schizoaffective disorder are from the American Psychiatric Association's "Diagnostic and Statistical Manual of Mental Disorders-5".
The DSM-IV schizoaffective disorder definition was plagued by problems of being inconsistently (or unreliably) used on patients; when the diagnosis is made, it doesn't stay with most patients over time; and it has questionable diagnostic validity (that is, it doesn't describe a distinct disorder, nor predict any particular outcome). These problems have been slightly reduced (or "modestly improved") in the DSM-5 according to Carpenter.
When psychotic symptoms are confined to an episode of mania or depression (with or without mixed features), the diagnosis is that of a “psychotic” mood disorder, namely either bipolar disorder or major depression). Only when psychotic states persist in a sustained fashion for two weeks or longer without concurrent affective symptoms is the diagnosis schizoaffective disorder or schizophrenia.
The second cardinal guideline in the DSM-5 diagnosis of schizoaffective disorder is one of timeframe.
These two changes are intended by the DSM-5 workgroup to accomplish two goals:
- Increase the diagnosis' consistency (or reliability) when it is used;
- Significantly decrease the overall use of the schizoaffective disorder diagnosis.
If the schizoaffective diagnosis is used less often, other diagnoses (like psychotic mood disorders and schizophrenia) are likely to be used more often; but this is hypothetical until real-world data arrive. Validity problems with the diagnosis remain and await further work in the fields of psychiatric genetics, neuroimaging, and cognitive science that includes the overlapping fields of cognitive, affective, and social neuroscience, which may change the way schizoaffective disorder is conceptualized and defined in future versions of the DSM and ICD.
Three common diagnostic systems that are generally used for sleepwalking disorders are International Classification of Diagnoses, the International Classification of Sleep Disorders 3, and the Diagnostic and Statistical Manual. Polysomnography is the only accurate measure of sleepwalking. Other measures commonly used include self-report, parent, partner or house-mate report.
Sleepwalking should not be confused with alcohol- or drug-induced blackouts, which can result in amnesia for events similar to sleepwalking. During an alcohol-induced blackout (drug-related amnesia), a person is able to actively engage and respond to their environment (e.g. having conversations or driving a vehicle), however the brain does not create memories for the events. Alcohol-induced blackouts can occur with blood alcohol levels higher than 0.06g/dl. A systematic review of the literature found that approximately 50% of drinkers have experienced memory loss during a drinking episode and have had associated negative consequences similar to sleepwalkers, including injury and death.
Other differential diagnoses include Rapid eye movement sleep behavior disorder, confusional arousals, and night terrors.
Hospitalization may be necessary during the acute phase of symptoms, and psychiatric care if the patient is a danger to self or others. A neurological consult is advised to rule out any organic cause.
According to the DSM-IV-TR, which classifies Ganser syndrome as a dissociative disorder, it is "the giving of approximate answers to questions (e.g. '2 plus 2 equals 5' when not associated with dissociative amnesia or dissociative fugue)."
Diagnosing Ganser syndrome is very challenging, because some measure of dishonesty is involved and because it is very rare.
Usually when giving wrong answers, they are only slightly off, showing that the individual understood the question. For instance, when asked how many legs a horse has they might say, "five." Although subjects appear confused in their answers, in other respects they appear to understand their surroundings.
For those whose sleepwalking episodes turn to be hazardous, a door alarm may offer a measure of protection. There are various kinds of door alarms that can attach to a bedroom door and when the door is opened, the alarm sounds off. The intention is that the sound will fully awaken the person and interrupt the sleepwalking episode, or if the sleepwalker lives with others, the sound will prompt them to check on the person.
Sleepwalkers should aim to have their bedrooms on the first floor of a home, apartment, dorm, hotel, etc.
Also, sleepwalkers should not have easily accessible weapons (loaded guns, knives) in the bedroom or any room of the house for that matter. If there are weapons, they should be locked away with keys secluded from the sleepwalker.
Historically, misdiagnosis rates have been high due to the complex nature of the disorder although some research now indicates that misdiagnosis may be reducing.
Treatment is dependent on the underlying cause, whether it is organic or psychological in origin. If depersonalization is a symptom of neurological disease, then diagnosis and treatment of the specific disease is the first approach. Depersonalization can be a cognitive symptom of such diseases as amyotrophic lateral sclerosis, Alzheimer's, multiple sclerosis (MS), neuroborreliosis (Lyme disease), or any other neurological disease affecting the brain. For those suffering from depersonalization with migraine, tricyclic antidepressants are often prescribed.
If depersonalization is a symptom of psychological causes such as developmental trauma, treatment depends on the diagnosis. In case of dissociative identity disorder or DD-NOS as a developmental disorder, in which extreme developmental trauma interferes with formation of a single cohesive identity, treatment requires proper psychotherapy, and—in the case of additional (co-morbid) disorders such as eating disorders—a team of specialists treating such an individual. It can also be a symptom of borderline personality disorder, which can be treated in the long term with proper psychotherapy and psychopharmacology.
The treatment of chronic depersonalization is considered in depersonalization disorder.
A recently completed study at Columbia University in New York City has shown positive effects from transcranial magnetic stimulation (TMS) to treat depersonalization disorder. Currently, however, the FDA has not approved TMS to treat DP.
A 2001 Russian study showed that naloxone, a drug used to reverse the intoxicating effects of opioid drugs, can successfully treat depersonalization disorder. According to the study: "In three of 14 patients, depersonalization symptoms disappeared entirely and seven patients showed a marked improvement. The therapeutic effect of naloxone provides evidence for the role of the endogenous opioid system in the pathogenesis of depersonalization."
Depersonalization is also a direct symptom of Lyme disease as well as other tick-borne diseases. If depersonalization is suspected a blood-test is required in search of anti-bodies.
The International Classification of Disease (ICD-11) which is due to be finalised in 2017 will have functional disorders within the neurology section for the first time.
The cause of the fugue state is related to dissociative amnesia, ("DSM-IV Codes 300.12") which has several other subtypes: selective amnesia, generalised amnesia, continuous amnesia, and systematised amnesia, in addition to the subtype "dissociative fugue".
Unlike retrograde amnesia (which is popularly referred to simply as "amnesia", the state where someone forgets events before brain damage), dissociative amnesia is not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication, "DSM-IV Codes 291.1 & 292.83") or a neurological or other general medical condition (e.g., amnestic disorder due to a head trauma, "DSM-IV Codes 294.0"). It is a complex neuropsychological process.
As the person experiencing a dissociative fugue may have recently suffered the reappearance of an event or person representing an earlier life trauma, the emergence of an armoring or defensive personality seems to be for some, a logical apprehension of the situation.
Therefore, the terminology "fugue state" may carry a slight linguistic distinction from "dissociative fugue", the former implying a greater degree of "motion". For the purposes of this article then, a "fugue state" occurs while one is "acting out" a "dissociative fugue".
The DSM-IV defines as:
- sudden, unexpected travel away from home or one's customary place of work, with inability to recall one's past
- confusion about personal identity, or the assumption of a new identity
- significant distress or impairment
The "Merck Manual" defines "dissociative fugue" as:
In support of this definition, the "Merck Manual" further defines dissociative amnesia as:
Multiple complex developmental disorder is likely to be caused by a number of different various genetic factors. Each individual with MCDD is unique from one another and displays different symptoms. Various neuropsychological disorders can also be found in family members of people with MCDD.