INTRODUCTION — Obsessive-compulsive disorder (OCD) is characterized by recurrent intrusive thoughts, images, or urges (obsessions) that typically cause anxiety or distress, and by repetitive mental or behavioral acts (compulsions) that the individual feels driven to perform, either in relation to an obsession or according to rules that he or she believes must be applied rigidly or to achieve a sense of “completeness.”
OCD typically starts in childhood or adolescence, persists throughout a person’s life, and produces substantial impairment in functioning due to the severe and chronic nature of the illness.
The epidemiology, pathogenesis, clinical manifestations, course, and diagnosis of OCD are described here. Pharmacotherapy, psychotherapy, and deep brain stimulation for OCD are discussed separately. OCD in children and adolescents and OCD in pregnant and postpartum women are also discussed separately. (See "Pharmacotherapy for obsessive-compulsive disorder in adults" and "Psychotherapy for obsessive-compulsive disorder in adults" and "Deep brain stimulation for treatment of obsessive-compulsive disorder" and "Obsessive-compulsive disorder in children and adolescents: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis" and "Obsessive-compulsive disorder in pregnant and postpartum patients".)
Prevalence — Worldwide, lifetime prevalence rates of obsessive-compulsive disorder (OCD) have been estimated at 1.5 percent for women and 1.0 percent for men [1,2]. Estimated lifetime prevalence among adults in the United States is slightly higher, at 2.3 percent [2,3]. Females are affected at a slightly higher rate than males in adulthood, although males are more commonly affected in childhood [3,4].
Comorbidities — The most common psychiatric disorders found to co-occur in adults with OCD are as follows.
●76 percent have a lifetime history of another anxiety disorder (eg, panic disorder, social anxiety disorder, generalized anxiety disorder, specific phobia).
●63 percent have a lifetime history of a mood disorder, most commonly major depressive disorder (41 percent) .
●23 to 32 percent have comorbid obsessive-compulsive personality disorder .
Up to 29 percent of individuals with OCD seeking treatment have been found to have a lifetime history of a tic disorder . The disorder has been most commonly seen in males who had an onset of OCD in childhood.
Disorders that occur more frequently in individuals with OCD than in those without the disorder include body dysmorphic disorder, trichotillomania (hair pulling disorder), and excoriation (skin picking) disorder .
OCD is much more common in individuals with certain other disorders than would be expected based on its prevalence in the general population, eg, among individuals with:
●Schizophrenia or schizoaffective disorder (approximately 12 percent with OCD) [8,9]
●Bipolar disorder 
●Eating disorders such as anorexia nervosa and bulimia nervosa 
●Tourette disorder 
When these other disorders are diagnosed, the patient should be assessed for OCD as well.
PATHOGENESIS — Research studies suggest that genetic and environmental factors contribute to the etiology of obsessive-compulsive disorder (OCD). Numerous lines of research implicate the cortico-striato-thalamo-cortical (CSTC) circuits in the pathophysiology of the disorder ; other brain circuits (eg, fronto-limbic, fronto-parietal, and cerebellar networks) are believed to contribute as well [12,13].
Genetic factors — Twin and family studies suggest that there is a genetic contribution to OCD with greater genetic influences in pediatric-onset OCD than in adult-onset OCD . The precise genes involved in OCD are not known, though work in this area is ongoing [15-18].
Environmental factors — Several environmental factors have been implicated in OCD, but causal associations have not been established . As examples:
●Onset of group A streptococcal infection has been associated with the onset or exacerbation of OCD in some children, a syndrome known as known as pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) . In PANDAS, OCD symptoms are hypothesized to be triggered by an autoimmune reaction to group A beta-hemolytic streptococci (GABHS) that damages the basal ganglia. The concept of PANDAS is debated in the literature; other infectious agents may trigger a similar acute neuropsychiatric syndrome , and this broader syndrome has been called both pediatric acute-onset neuropsychiatric syndrome (PANS) and childhood acute neuropsychiatric symptoms (CANS). (See "PANDAS: Pediatric autoimmune neuropsychiatric disorder associated with group A streptococci".)
●Premenstrual and postpartum periods can lead to new onset or exacerbation of OCD, suggesting that hormonal fluctuations may play an etiological role [22,23].
●Acute OCD onset has been reported in adults following exposure to traumatic events, suggesting that stress may play a role in precipitating the disorder .
●Multiple case reports describe new onset OCD after neurological lesions (eg, ischemic stroke, traumatic brain injury) that affect CSTC circuits [25,26].
Neurobiology — Numerous lines of research support a role for CSTC circuits in OCD, as summarized briefly below.
●Structural imaging studies have found neuroanatomical abnormalities in CSTC circuits in patients with OCD [12,31]. While there are inconsistencies among specific studies and even among meta-analyses, studies often report abnormalities in the orbitofrontal cortex (OFC), the anterior cingulate cortex (ACC), and the striatum. A 2014 mega-analysis in 412 adult OCD patients compared with 368 healthy subjects also found abnormalities in the dorsomedial prefrontal cortex, the inferior frontal gyrus, and the cerebellum . Meta- and mega-analyses of data from OCD sites worldwide found different patterns of subcortical abnormalities in adult versus pediatric OCD samples (eg, abnormalities in the pallidum and hippocampus in adult subjects and thalamic abnormalities in pediatric samples) .
●Positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) have found abnormal activity in different nodes of CSTC circuits, including the OFC, ACC, and striatum, in individuals with OCD compared with healthy control subjects . The abnormal activity was found to increase during symptom provocation, and to normalize with successful treatment.
●Studies using fMRI during performance of cognitive tasks show abnormal recruitment of CSTC circuits . As an example, several studies found that OCD subjects aberrantly recruited the hippocampus during an implicit sequence-learning task, while healthy participants recruited the striatum.
●Abnormalities in serotonergic signaling  and/or dopamine signaling  have been hypothesized to play a role in the pathophysiology of OCD. Pharmacological challenge studies and neuroimaging studies that have sought to test these hypotheses have been inconclusive. Some models propose that OCD symptoms result either directly or indirectly from abnormalities in glutamatergic signaling in cortico-striatal pathways, but magnetic resonance spectroscopy studies of OCD have been inconclusive to date [36-38].
CLINICAL MANIFESTATIONS — People with obsessive-compulsive disorder (OCD) experience obsessions, compulsions, or both. In a study of 431 patients with OCD, the majority of patients experienced both obsessions and compulsions, rather than one or the other . This has been confirmed in a study of 1001 OCD patients .
Obsessions are repetitive and persistent thoughts (eg, of contamination), images (eg, of violent or horrific scenes), or urges (eg, to stab someone). Obsessions are not pleasurable or experienced as voluntary. They are intrusive, unwanted, and cause marked distress or anxiety in most individuals. A person suffering from OCD attempts to ignore, avoid, or suppress obsessions or to neutralize them with another thought or action (eg, performing a compulsion).
Compulsions (or rituals) are repetitive behaviors (eg, washing, checking) or mental acts (eg, counting, repeating words silently) that the individual feels driven to perform and are typically thematically related to an obsession (eg, washing rituals occur with obsessive fears of contamination) or according to rules that must be applied rigidly. The aim can be to reduce the distress triggered by obsessions or to prevent a feared event (eg, becoming ill). However, these compulsions are either not connected in a realistic way to the feared event (eg, arranging items symmetrically to prevent harm to a loved one) or are clearly excessive (eg, showering for hours each day). Compulsions may also be performed in response to a sense of “incompleteness” (eg, a need to perform actions until “just right”). Compulsions are not done for pleasure, although some individuals experience relief from anxiety or distress.
Whether obsessions lead to compulsions or compulsions lead to obsessions is debated in the field [41,42].
The frequency and severity of obsessions and compulsions vary among people with OCD: some have mild to moderate symptoms (spending one to three hours per day obsessing or doing compulsions), whereas others have near constant obsessions or compulsions that can be incapacitating.
The specific content of obsessions and compulsions varies widely among individuals; however, there are certain identifiable themes, also described as “symptom dimensions”. People with OCD often have symptoms in multiple dimensions, which include:
●Cleaning – Fears of contamination and cleaning rituals
●Symmetry – Symmetry obsessions and repeating, ordering, and counting compulsions
●Forbidden or taboo thoughts – Examples include aggressive, sexual, and religious obsessions, and related compulsions
●Harm (eg, thoughts or images about harm befalling oneself or others and checking compulsions)
A review and meta-analysis suggest that there is a strong link between suicidal thoughts and behaviors and OCD . Lifetime rates of suicidality varied widely across studies but were as high as 63.5 percent for suicidal ideation (across 18 studies) and 46 percent for suicide attempts (across 22 studies). Worsening levels of suicidality in OCD patients are associated with comorbid axis I disorders, severity of depressive and anxiety symptoms, severity of obsessions, feelings of hopelessness, and past history of suicide attempts. Data from 3711 adults with OCD across multiple treatment centers from seven countries found that suicidal ideation in the last month was reported in 6 percent, and a lifetime suicidal attempt was reported in 9 percent . Some patients with OCD experience intrusive fears that they will harm others, but there are no data suggesting that they are more likely to do so at a rate higher than the general population.
Avoidance behavior is common in OCD. In some cases, people with OCD avoid people, places, or things that trigger obsessions and compulsions. For example, individuals with contamination concerns might avoid public situations (eg, restaurants, public restrooms) to reduce exposure to feared contaminants; those with intrusive thoughts about causing harm to others may avoid social interactions. Avoidance can become pervasive and severely restrict functioning.
Once obsessions and compulsions are triggered, people with OCD may experience a range of affective responses. As an example, some may feel marked anxiety, which can include recurrent panic attacks. Others report strong feelings of disgust. While performing compulsions, individuals may report a distressing sense of “incompleteness” or uneasiness until things look, feel, or sound “just right”.
Many individuals with OCD experience dysfunctional beliefs , including:
●Inflated responsibility and the tendency to overestimate threat
●Perfectionism and the intolerance of uncertainty
●Overvaluing the importance of thoughts (eg, believing that having a forbidden thought is as bad as acting on it) and the need to control thoughts
These beliefs are present in individuals with other anxiety disorders as well.
People with OCD differ in the degree to which they believe that their obsessions and compulsions are excessive or unreasonable [39,40,46]. Insight can vary within an individual over the course of the illness. Poorer insight has been linked in some (but not all studies) to worse long-term outcomes . A minority of people with OCD (≤4 percent) will have absent insight, such that their beliefs about their OCD symptoms are delusional (eg, they are convinced that their thoughts can kill another person).
CLINICAL COURSE AND COMPLICATIONS
Onset — The mean age of onset of obsessive-compulsive disorder (OCD) is 19.5 years in the United States; 25 percent of cases begin by age 14 years [2,3]. Onset after age 35 years is unusual, but can occur . Males have an earlier age of onset than females; nearly 25 percent of males have onset before age 10 years compared to a much lower rate in females .
The onset of symptoms in OCD is typically gradual; however, acute onset has been reported, and has been associated with infectious etiology.
Course and effect of treatment — If untreated, the course of OCD is usually chronic, with waxing and waning symptoms while a minority have a deteriorating course [49,50]. (See 'Environmental factors' above.)
While many individuals with onset of OCD in childhood or adolescence will have lifetime symptoms, some individuals will remit by early adulthood . In a meta-analysis of 16 studies individuals with OCD were followed for up to 15.6 years . Forty percent of individuals (most treated with cognitive-behavioral therapy, pharmacologic management, or both) achieved remission (not meeting criteria for full or subthreshold OCD).
Without treatment, rates of remission (usually defined as minimal to no symptoms) of OCD in adults are low (eg, 20 percent in a 40-year follow-up study of 144 patients) .
Remission rates in published research have varied based on comorbidity rates in the samples studied, treatment selection, how treatments were delivered, and how remission was defined. As an example, a trial found that adults with OCD who received optimally delivered evidence-based treatment for 12 weeks (ie, SRI, EX/RP, or SRI+EX/RP) had remission rates ranging from 25 to 58 percent depending upon the specific treatment received. Remission was defined as no more than mild symptoms . (See 'Comorbidities' above.)
Effect on psychological development and quality of life — When OCD starts in childhood or adolescence, individuals may experience developmental difficulties. As examples, adolescents may avoid socializing with peers. Young adults may struggle to leave home and live independently, with few significant relationships outside the family, a lack of autonomy, and continued financial dependence on their family of origin.
Individuals with OCD may try to impose rules and prohibitions on family members because of their disorder (eg, no one in the family can have visitors to the house for fear of contamination). This usually manifests in the form of family’s accommodation of rituals and participation in the rituals.
High family accommodation is often associated with high expressed emotion and together can contribute to not only poor treatment response but also to high family burden and poorer quality of life among family members who live with the individual suffering from OCD.
OCD is associated with reduced quality of life as well as high levels of social and occupational impairment [54-56]. Impairment occurs across many different domains of life and is associated with symptom severity. Impairment can be caused by:
●Time spent obsessing and acting on compulsions
●Avoidance of situations that can trigger obsessions or compulsions can also severely restrict functioning
●Specific symptoms can create specific obstacles. As examples:
•Obsessions about harm can make relationships with family and friends feel hazardous, resulting in avoidance
•Obsessions about symmetry can derail the timely completion of school or work projects because the project never feels “just right,” potentially resulting in school failure or job loss
•Individuals with contamination concerns may avoid health care settings due to fears of exposure to germs
•Patients may develop dermatological problems, such as skin lesions due to excessive washing
•Sometimes the symptoms of OCD interfere with its own treatment (eg, when medications are considered contaminated)
●Cognitive disorders/dementia – In a longitudinal study from the Taiwan National Health registry involving 1347 individuals with OCD, the risk of developing any dementia was greater than comparative controls (hazard ratio 4.28, 95% CI 2.96-6.21) . The risk included the development of Alzheimer disease and vascular dementia. It is also possible that the obsessive-compulsive symptoms may be an early manifestation of dementia rather than dementia occurring as a complication of OCD.
●Ischemic stroke – In another longitudinal study (also using the Taiwan National Health registry) of over 28,000 individuals with OCD, OCD was associated with ischemic stroke (hazard ratio 3.02, 95% CI 1.91-4.77) . The risk for hemorrhagic stroke did not differ between individuals with OCD and those without OCD (hazard ratio 0.87, 95% CI 0.42-1.8). The suggested mechanism is due to OCD being a systemic inflammatory disease; however, further investigation is warranted.
ASSESSMENT AND DIAGNOSIS — In a diagnostic assessment of a patient with possible obsessive-compulsive disorder (OCD), the clinician should ask specifically about the presence of intrusive thoughts, images, or urges, and to inquire about repetitive behaviors and mental rituals. The frequency, amount of time consumed, and extent to which obsessions/compulsions cause the patient distress or interfere with his or her life helps to distinguish OCD from occasional intrusive thoughts or repetitive behaviors that are common in the general population (eg, double-checking that a door is locked) [61-63].
Identifying the main symptom dimensions (eg, cleaning, symmetry, harm) provides useful information to inform treatment and monitor changes in the severity of the disorder over time. Identifying a link between obsessions and compulsions, and confirming that the obsessions lead to anxiety or distress can help to differentiate OCD from other disorders on the intrusive thoughts or repetitive behaviors spectrum. Evaluation should assess for symptoms and behaviors resulting from co-occurring psychiatric disorders. (See 'Clinical manifestations' above and 'Comorbidities' above.)
The American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnostic criteria for OCD are as follows :
●A. Presence of obsessions, compulsions, or both:
Obsessions as defined by:
•1. Recurrent and persistent thoughts, urges, or images that are experienced, at some time during the disturbance, as intrusive and unwanted, and that in most individuals cause marked anxiety or distress.
•2. The individual attempts to ignore or suppress such thoughts, urges, or images, or to neutralize them with some other thought or action (ie, by performing a compulsion).
Compulsions as defined by:
•1. Repetitive behaviors (eg, hand washing, ordering, checking) or mental acts (eg, praying, counting, repeating words silently) that the individual feels driven to perform in response to an obsession, or according to rules that must be applied rigidly.
•2. The behaviors or mental acts are aimed at preventing or reducing anxiety or distress or preventing some dreaded event or situation; however, these behaviors or mental acts either are not connected in a realistic way with what they are designed to neutralize or prevent, or are clearly excessive.
●B. The obsessions or compulsions are time-consuming (eg, take more than one hour per day) or cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.
●C. The obsessive-compulsive symptoms are not attributable to the physiological effects of a substance (eg, a drug of abuse, a medication) or another medical condition.
●D. The disturbance is not better explained by the symptoms of another mental disorder, for example:
•Excessive worries, as in generalized anxiety disorder
•Preoccupation with appearance, as in body dysmorphic disorder
•Difficulty discarding or parting with possessions, as in hoarding disorder
•Hair pulling, as in trichotillomania (hair-pulling disorder)
•Skin picking, as in excoriation (skin-picking) disorder
•Stereotypies, as in stereotypic movement disorder
•Ritualized eating behavior, as in eating disorders
•Preoccupation with substances or gambling, as in substance-related and addictive disorders
•Preoccupation with having an illness, as in illness anxiety disorder
•Sexual urges or fantasies, as in paraphilic disorders
•Impulses, as in disruptive, impulse-control, and conduct disorders
•Guilty ruminations, as in major depressive disorder
•Thought insertion or delusional preoccupations, as in schizophrenia spectrum and other psychotic disorders
•Repetitive patterns of behavior, as in autism spectrum disorder
Specifiers for OCD in DSM-5 — Specifiers for the disorder include assessments of the patient’s insight and presence/history of a tic disorder.
Patient’s degree of insight into the illness
●With good or fair insight – The individual recognizes that OCD beliefs are definitely or probably not true or that they may or may not be true.
●With poor insight – The individual thinks OCD beliefs are probably true.
●With absent insight/delusional beliefs – The individual is completely convinced that OCD beliefs are true.
Tic-related — The individual has a current or past history of a tic disorder. (See 'Comorbidities' above.)
Differential diagnosis — In diagnosing OCD, other disorders with overlapping features should be considered:
Anxiety disorders — Recurrent thoughts, avoidant behaviors, and repetitive requests for reassurance occur in anxiety disorders other than OCD. Distinguishing features can inform diagnosis.
Generalized anxiety disorder — Recurrent thoughts that are present in generalized anxiety disorder (ie, worries) are usually about real-life concerns, while the obsessions in OCD usually are not. OCD-related concerns generally involve content that is odd, irrational, or of a seemingly magical nature. In OCD, compulsions are almost always present and usually linked to the obsessions. (See "Generalized anxiety disorder in adults: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis".)
Specific phobia — Patients with specific phobias, like those with OCD, may have a fear reaction to specific objects or situations. However, the feared objects in specific phobia are usually more circumscribed than those in OCD, and not characterized by rituals. (See "Specific phobia in adults: Epidemiology, clinical manifestations, course and diagnosis".)
Social anxiety disorder — In social anxiety disorder, the feared objects or situations are limited to social interactions or performance situations. Avoidance or reassurance-seeking is focused on reducing this social fear. (See "Social anxiety disorder in adults: Epidemiology, clinical manifestations, and diagnosis".)
Hoarding disorder — In hoarding disorder, symptoms focus exclusively on the persistent difficulty discarding or parting with possessions, marked distress associated with discarding items, and excessive accumulation of objects. Patients who have obsessions that are typical of OCD (eg, concerns about incompleteness or harm) that lead to compulsive accumulation (eg, acquiring all objects in a set to attain a sense of completeness or not discarding old newspapers because they may contain information that could prevent harm) should be diagnosed with OCD.
Major depressive disorder — The ruminative thoughts present in major depressive disorder are typically mood-congruent and are not necessarily experienced as intrusive as in OCD. Ruminations in depression are not linked to compulsions as is typical in OCD. (See "Unipolar depression in adults: Assessment and diagnosis".)
Tic disorders — A tic is a sudden, rapid, recurrent, nonrhythmic motor movement or vocalization (eg, eye blinking, throat clearing). Tics are typically less complex than compulsions and are not aimed at neutralizing obsessions. (See "Hyperkinetic movement disorders in children", section on 'Tic disorders' and 'Comorbidities' above.)
Psychotic disorders — Diagnostic criteria for OCD were revised in DSM-5 to emphasize that a patient with OCD may lack insight into their illness or have obsessional beliefs that are delusional . What distinguishes OCD from a delusional disorder or psychotic disorder, not otherwise specified, is that patients with OCD have obsessions and compulsions, and not other features of schizophrenia or schizoaffective disorder (eg, hallucinations or disorganized thinking/formal thought disorder). (See 'Comorbidities' above and "Psychosis in adults: Epidemiology, clinical manifestations, and diagnostic evaluation".)
Obsessive-compulsive personality disorder — Obsessive-compulsive personality disorder (OCPD) involves an enduring and pervasive maladaptive pattern of excessive perfectionism and rigid control that often leads to ritualized behavior. OCPD is not a subsyndromal version of OCD, and is not characterized by obsessions. The repetitive behaviors in OCPD are not performed in relation to obsessions. (See "Overview of personality disorders" and 'Comorbidities' above.)
Other disorders — Other disorders that include intrusive thoughts and repetitive behaviors can be distinguished from OCD by the nature of the thoughts and behaviors. In body dysmorphic disorder, intrusive thoughts are limited to concerns about appearance. In trichotillomania, the repetitive behavior is limited to hair-pulling. In anorexia nervosa, intrusive thoughts and repetitive behaviors are limited to concerns about weight and food. Other possible foci and the associated disorders are described in Criteria D of the diagnostic criteria above. (See "Anorexia nervosa in adults: Clinical features, course of illness, assessment, and diagnosis".)
Other behaviors are sometimes considered “compulsive,” including sexual behavior (in the case of paraphilias), gambling (eg, pathological gambling), and substance use (eg, alcohol abuse). In these conditions, an individual generally derives pleasure from the activity (at least early in the illness) and may wish to resist it only because of its deleterious consequences. (See "Risky drinking and alcohol use disorder: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis".)
Severity rating scales — The standard scale for measuring OCD severity is the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) (figure 1) [65,66]; it consists of a checklist of obsessions and compulsions and a scale that assesses their severity. Baseline assessment of a new patient with OCD followed by routine reassessment over time is suggested to monitor the patient’s course of illness and response to treatment. The Y-BOCS has both an interviewer version and a self-report version . Simpler self-report scales, the Obsessive Compulsive Inventory-Revised, the Florida Obsessive-Compulsive Inventory, and the Dimensional Obsessive-Compulsive Scale [68-70], provide alternatives to the Y-BOCS but there are tradeoffs in their use.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Obsessive-compulsive disorder and related disorders".)
SUMMARY AND RECOMMENDATIONS
●The 12-month prevalence of obsessive-compulsive disorder (OCD) among adults in the United States has been estimated to be 1.2 percent. (See 'Epidemiology' above.)
●Numerous psychiatric disorders co-occur in people with OCD at rates higher than in the general population, including major depressive disorder and other anxiety disorders. (See 'Epidemiology' above.)
●Research studies suggest that genetic and environmental factors contribute to the etiology of OCD. Numerous lines of research implicate the cortico-striato-thalamo-cortical circuits in the pathophysiology of the disorder. (See 'Pathogenesis' above.)
●People with OCD experience obsessions, compulsions, or both. (See 'Clinical manifestations' above.)
•Obsessions are recurrent intrusive thoughts, images, or urges that typically cause anxiety or distress.
•Compulsions are repetitive mental or behavioral acts that the individual feels driven to perform, either in response to an obsession or according to rules that he or she believes must be applied rigidly.
●OCD typically starts in childhood or adolescence, persists throughout a person’s life, and produces substantial impairment in functioning due to the severe and chronic nature of the illness. (See 'Clinical course and complications' above.)
●In a diagnostic assessment of a patient with possible OCD, the clinician should ask specifically about the presence of intrusive thoughts, images, or urges, and should inquire about repetitive behaviors and mental acts. (See 'Assessment and diagnosis' above.)
●The differential diagnosis of OCD includes other anxiety disorders, major depressive disorder, tic disorder, psychotic disorders, and obsessive-compulsive personality disorder. The nature of intrusive thoughts and repetitive behaviors can usually distinguish these disorders from OCD. (See 'Differential diagnosis' above.)