Differentials
Schizophrenia
SIGNS / SYMPTOMS
Presence of psychosis and thought disorder when no mood symptoms are prominent.
INVESTIGATIONS
Clinical diagnosis using Diagnostic and Statistical Manual of Mental Disorders, 5th edition, Text Revision (DSM-5-TR) criteria.[4]
Schizoaffective disorder
SIGNS / SYMPTOMS
Schizophrenic and mood symptoms occur simultaneously, and are evenly balanced.
INVESTIGATIONS
Clinical diagnosis using Diagnostic and Statistical Manual of Mental Disorders, 5th edition, Text Revision (DSM-5-TR) criteria.[4]
Medication adverse effects
SIGNS / SYMPTOMS
Corticosteroid-induced euphoria; antidepressant-induced hypomania, agitation, and hyperactivity; antibiotic-induced effects.[90]
INVESTIGATIONS
Serum levels may be obtained with some medications.
Substance abuse
SIGNS / SYMPTOMS
Intoxication with, or withdrawal from, illicit substance use may present with irritability, disinhibition, psychosis, insomnia, euphoria, and agitation that may mimic manic symptoms.[15] Substance abuse is also a common comorbidity with bipolar disorder.[87]
INVESTIGATIONS
Toxicology screen should be performed.
Personality disorders
SIGNS / SYMPTOMS
Deeply ingrained and enduring behavior patterns that appear in childhood or adolescence.
Borderline personality disorder, in particular, is associated with impulsive behavior and affective instability that may mimic manic symptoms, but symptoms are of long duration (in contrast to the episodic nature of bipolar disorder).
Mood dysregulation in adolescents is often associated with features of borderline personality disorder, which can complicate diagnosis.[14] Adolescents with a high number of borderline symptoms have a greater mood symptom burden and functional impairment.[91]
Bipolar disorder may be a spectrum disorder varying between episodic classic bipolar disorder and chronic mood dysregulation, as seen in borderline personality disorder.[92] Alternatively, chronic emotional instability may also be diagnosed as disruptive mood dysregulation disorder.[2] However, familial aggregation for bipolar disorder is greater in children and adolescents with the "narrow phenotype" versus those with severe mood dysregulation.[93]
INVESTIGATIONS
Clinical diagnosis using Diagnostic and Statistical Manual of Mental Disorders, 5th edition, Text Revision (DSM-5-TR) criteria.[4]
Cyclothymia
SIGNS / SYMPTOMS
Persistent, chronic mood instability for a minimum of 1 year, with periods of mild elation and mild depression that do not meet diagnostic criteria for bipolar disorder, and no more than 2 months symptom-free. In practice, rarely diagnosed and often included in bipolar disorder not otherwise specified (BD-NOS).[94][95] It shares many characteristics with other bipolar subtypes, supporting its inclusion on the bipolar spectrum.[96][97]
INVESTIGATIONS
Clinical diagnosis using Diagnostic and Statistical Manual of Mental Disorders, 5th edition, Text Revision (DSM-5-TR) criteria.[4]
Conduct disorders
SIGNS / SYMPTOMS
Repetitive and persistent patterns of antisocial, aggressive, or defiant behavior. Generally associated with low frustration tolerance and temper tantrums. Defiance is usually provocative and confrontational. Conduct problems are frequently comorbid with bipolar disorder. Rates of up to 79% have been reported, but vary widely.[80][87][98]
INVESTIGATIONS
Clinical diagnosis using Diagnostic and Statistical Manual of Mental Disorders, 5th edition, Text Revision (DSM-5-TR) criteria.[4]
Child abuse
SIGNS / SYMPTOMS
There is a significant relationship between maltreatment and psychopathology, including bipolar disorder; child maltreatment has been associated with a more severe form in adults, as well as with manic-type symptoms in children.[80]
Children who have been sexually abused may present with sexually provocative behavior that could be misinterpreted as disinhibition and a symptom of mania. It can be difficult to distinguish between the psychological consequences of abuse and emergent symptoms of bipolar disorder, particularly because both conditions may coexist.
A study of bipolar spectrum disorder in children and adolescents reported that 20% experienced physical or sexual abuse; these children and adolescents were more likely to present with comorbid conduct disorder and PTSD, as well as longer illness duration.[99] Abuse appears to be related to increased severity of symptoms, substance use, greater comorbidity, suicidality, and a worse family environment.[70]
INVESTIGATIONS
Clinical diagnosis following a detailed history and meticulous examination.
ADHD
SIGNS / SYMPTOMS
The core symptoms of ADHD are impulsivity, inattention, and over-activity, all of which can be found in mania. High rates of ADHD have been repeatedly observed in bipolar disorder in children, averaging 62%.[87][90]
One large community study reported that adolescents and young adults who had major depression with ADHD comorbidity had an increased incidence of subsequent bipolar disorder (18.9% versus 11.2%) compared with those without.[66]
Studies indicate that bipolar disorder in children is distinct from ADHD in terms of clinical correlates and familial aggregation, and the comorbid condition may represent a distinct subtype.[73][95][100][101][102][103]
INVESTIGATIONS
Clinical diagnosis using Diagnostic and Statistical Manual of Mental Disorders, 5th edition, Text Revision (DSM-5-TR) criteria.[4]
Intellectual disability
SIGNS / SYMPTOMS
Early onset affective disorder is associated with delayed language, social, motor, and educational development.[104][105][106] Thus, affective instability may occur more often in children with developmental delay, but it is not clear whether this can be regarded as "organic affective disorder" or whether the developmental delays are independent of bipolar disorder.[80]
INVESTIGATIONS
Clinical diagnosis using Diagnostic and Statistical Manual of Mental Disorders, 5th edition, Text Revision (DSM-5-TR) criteria. [4]
Brain imaging can be performed to rule out any organic etiology.
Psychometric assessments can be carried out. These are either experimental or are used to look for learning and language disorders.
Autism spectrum disorder
SIGNS / SYMPTOMS
Neurodevelopmental abnormalities have been reported to be antecedents in a subgroup of high-risk children (i.e., offspring of parents with bipolar disorder).[73]
Irritability, mood lability, and aggression can occur in autism spectrum disorder and be mistaken for mania. Pragmatic language disorder can also be mistaken for a manic thought disorder. Poor social judgment can be mistaken for grandiosity.[80] Autism spectrum disorder can also exist as a comorbid diagnosis.[107] One population study reported a substantially increased risk of bipolar disorder, as well as nonaffective psychoses, in young people with autism spectrum disorders.[72]
INVESTIGATIONS
Clinical diagnosis using Diagnostic and Statistical Manual of Mental Disorders, 5th edition, Text Revision (DSM-5-TR) criteria.[4]
Thyroid dysfunction
SIGNS / SYMPTOMS
Thyroid disorders can often cause nonspecific symptoms such as weight loss or gain, excessive fatigue, poor concentration, mood changes, and irritability. Depression is a commonly reported symptom in hypothyroidism.
Physical signs of hypothyroidism include dry skin, coarse hair, facial edema, and bradycardia. Physical signs of hyperthyroidism include sweating or heat intolerance, tachycardia, palpitations, shortness of breath, and lid lag. Atypical affective symptoms due to a medical condition may be suggestive of a mood disorder.
INVESTIGATIONS
Serum thyroid-stimulating hormone assay and free thyroxine and triiodothyronine assays are initial tests to perform in a patient suspected of having thyroid dysfunction.
Wilson disease
SIGNS / SYMPTOMS
Patients who present with neurologic disease may have a history of symptoms of a movement disorder, including tremor, lack of coordination, sloppy handwriting, dysarthria, muscle stiffness, rigidity, postural abnormality, gait abnormality, or drooling. Other symptoms that can be present and could be mistaken for a psychiatric disorder include bizarre behavior, emotional lability and delusions, temper tantrums, depression, loss of memory, inability to focus on tasks, impulsiveness, and sexual disinhibition. Atypical affective symptoms due to a medical condition may be suggestive of a mood disorder.
INVESTIGATIONS
Twenty-four-hour urine copper will show levels >100 micrograms if Wilson disease is present. LFTs may be abnormal. Serum ceruloplasmin is usually low. Slit lamp examination may reveal Kayser-Fleischer rings.
Systemic lupus erythematosus
SIGNS / SYMPTOMS
Common presenting symptoms of systemic lupus erythematosus include a photosensitive malar or butterfly rash, fever, and arthritis. Central nervous system manifestations are one of the many other signs and symptoms that may occur during the course of the disease, and include psychiatric illnesses such as psychosis and depressive disorders. Atypical affective symptoms due to a medical condition may be suggestive of a mood disorder.
INVESTIGATIONS
Positive antinuclear antibodies will strongly suggest a diagnosis of systemic lupus erythematosus, although the test will also be positive in other connective-tissue diseases, such as rheumatoid arthritis and systemic sclerosis.
Anti-double-stranded-DNA and anti-Smith antibodies are highly specific for systemic lupus erythematosus and are often confirmatory of the diagnosis, if present.
Meningitis
SIGNS / SYMPTOMS
Presents with fever, headache, photophobia, pallor or mottled skin, nonblanching petechial rash, Kernig and Brudzinski signs, and personality and behavioral changes.
INVESTIGATIONS
Cerebrospinal fluid Gram stain, cell count, glucose, protein, culture, and India ink. Results will depend on causative pathogen.
Head injury
SIGNS / SYMPTOMS
Head injury affecting the frontal lobes may cause disinhibition and mood lability suggestive of mania.
INVESTIGATIONS
Neuroimaging of the head. If there is uncertainty over whether a head injury has occurred, a psychiatric assessment should be performed to exclude the possibility of bipolar disorder.
Lead toxicity
SIGNS / SYMPTOMS
The history may reveal risk factors, such as: living in housing with lead hazards, exposure to lead-contaminated water supplies, family history of lead poisoning or parental work with lead, mineral-deficient and high-fat diets, and fetal lead exposure.
May have cognitive impairment, history of headaches, clumsiness and agitation, loss of appetite, constipation, and somnolence.
INVESTIGATIONS
Whole-blood lead >9 microgram/dL in children.
Disruptive mood dysregulation disorder
SIGNS / SYMPTOMS
Irritability is persistent over many months and not episodic. Expansive or elevated mood or grandiosity is not generally seen.
INVESTIGATIONS
Clinical diagnosis using Diagnostic and Statistical Manual of Mental Disorders, 5th edition, Text Revision (DSM-5-TR) criteria.[4]
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