Differentials
Schizoaffective disorder
SIGNS / SYMPTOMS
Combination of psychosis (i.e., delusions, hallucinations) and affective symptoms that are closely related in time but present, almost independent of each other, as clusters of symptoms. A diagnosis of schizoaffective disorder requires that a major depressive or manic episode occur concurrently with the active-phase symptoms and that the mood symptoms be present for a majority of the total duration of the active periods.[1]
INVESTIGATIONS
Clinical diagnosis (DSM-5-TR or ICD-11).
Schizophreniform disorder and brief psychotic disorder
SIGNS / SYMPTOMS
Shorter duration than schizophrenia, which requires 6 months of symptoms. In schizophreniform disorder, the disturbance is present for less than 6 months; in brief psychotic disorder, symptoms are present for at least 1 day but less than 1 month.[1]
INVESTIGATIONS
Clinical diagnosis (DSM-5-TR or ICD-11).
Substance-induced psychotic disorder
SIGNS / SYMPTOMS
Substance-related disorders are great imitators of psychopathology. Substance-induced psychotic disorder can usually be distinguished by the chronological relationship of substance use to the onset of psychosis, and remission of psychosis in the absence of substance use.[1] Delusions are not crystallized as in schizophrenia, but auditory hallucinations may still be present. A drug history should include evaluation of the duration, frequency, dosage, and time since last use.[81]
The drugs most often associated with psychosis are heavy and persistent use of marijuana; stimulant drugs such as methamphetamine, cocaine, and amphetamines; psychotomimetics such as LSD and ketamine-like drugs; and inhalants such as toluene, gasoline, and various types of glues.
Past history of extensive use may result in long-term persistent psychotic symptoms, years after the last exposure.
INVESTIGATIONS
Urine drug screen may identify the causative drug. If drug screen is negative and there is a history of drug use, a cause-effect relation can be elucidated from the clinical interview and review of medical records.
Dementia with psychosis
SIGNS / SYMPTOMS
Delusions may be similar, but are without a history of psychosis prior to dementia onset. An older age, family history of dementia, and gradual cognitive decline suggests dementia.
INVESTIGATIONS
CT or MRI of the brain may reveal characteristic signs of the causative dementia.
Major depressive disorder, or bipolar disorder, with psychosis
SIGNS / SYMPTOMS
The distinction depends on the temporal relationship between the mood disturbance and the psychosis, and on the severity of the depressive and/or manic symptoms.[1] Delusions or hallucinations occur exclusively during a major depressive or manic episode.
INVESTIGATIONS
Clinical diagnosis (DSM-5-TR or ICD-11).
Malingering and factitious disorders
SIGNS / SYMPTOMS
In malingering, personal gain from intentional reporting of symptoms can be identified; in factitious disorder, patients may need constant reassurances due to consciously or unconsciously feigned physical or psychological symptoms.
Particular attention should be given to any inconsistencies in history, atypical disease presentations, and evasiveness when asked about symptom details.
Helpful to get collateral information from other caregivers or close contacts. Patients with schizophrenia who have true somatization are not typically evasive or needy of reassurances.
INVESTIGATIONS
Clinical diagnosis (DSM-5-TR or ICD-11).
Delusional disorder
SIGNS / SYMPTOMS
In delusional disorder, there is an absence of the other symptoms characteristic of schizophrenia (e.g., prominent auditory or visual hallucinations, disorganized speech, grossly disorganized or catatonic behavior, negative symptoms); functioning is not markedly impaired and behavior is not obviously bizarre or odd.[1]
INVESTIGATIONS
Clinical diagnosis (DSM-5-TR or ICD-11).
Schizotypal personality disorder
SIGNS / SYMPTOMS
Schizotypal personality is defined by subthreshold symptoms that are associated with persistent personality features.[1]
INVESTIGATIONS
Clinical diagnosis (DSM-5-TR or ICD-11).
Autism spectrum disorder (ASD)
SIGNS / SYMPTOMS
A schizophrenia diagnosis is given in patients with ASD only if prominent delusions and hallucinations occur for at least 1 month (or less if treated successfully).
Clinicians should gather a childhood history, looking for pervasive deficits.
In ASD, the debut of deviant interpersonal interactions, delayed and aberrant communication skills, and limited repertoire of activities and interests occurs in the first years of life.
INVESTIGATIONS
Clinical diagnosis (DSM-5-TR or ICD-11).
Obsessive-compulsive disorder and related disorders with poor or absent insight
SIGNS / SYMPTOMS
Individuals with obsessive-compulsive disorder, body dysmorphic disorder, or hoarding disorder may present with poor or absent insight, and the preoccupations may reach delusional proportions; these individuals are completely convinced that their obsessive-compulsive beliefs, body dysmorphic disorder beliefs (e.g., defective physical appearance), or hoarding disorder beliefs (e.g., catastrophic consequences of discarding objects) are true. These disorders are distinguished from schizophrenia by the absence of the other required psychotic features (hallucinations, disorganized speech, disorganized or catatonic behavior, negative symptoms) and the presence of prominent obsessions or preoccupations and compulsive (repetitive) behaviors that occur in response.[1][82]
INVESTIGATIONS
Clinical diagnosis (DSM-5-TR or ICD-11).
Psychotic disorder due to another medical condition
SIGNS / SYMPTOMS
Numerous medical conditions can cause psychotic symptoms.[66] Common conditions include epilepsy, brain tumors, traumatic brain injuries, HIV, neurosyphilis, pellagra, B12 deficiency, herpes encephalitis, and Wilson disease, among others. History and physical examination help differentiate diagnoses.
INVESTIGATIONS
Laboratory studies will help differentiation, such as rapid plasma reagin (RPR), HIV test, herpes simplex virus-polymerase chain reaction (HSV-PCR) in cerebrospinal fluid, urine copper level, blood levels of ceruloplasmin, and vitamin B12.
Carbon monoxide poisoning
SIGNS / SYMPTOMS
Psychosis due to carbon monoxide is without a long history of psychosis as in schizophrenia. A careful history should be taken, looking for possible toxic exposure.
INVESTIGATIONS
Toxicology screen for carboxyhemoglobin may be performed in the emergency department.
Heavy metal poisoning
SIGNS / SYMPTOMS
Psychosis due to heavy metals (e.g., bromide, mercury) is without a long history of psychosis as in schizophrenia.
A careful history should be taken, looking for possible toxic exposure. Psychosis may present suddenly and when exposure is treated, symptoms will remit.
INVESTIGATIONS
Toxicology screen for a bromide or mercury level may be performed in the emergency department. A serum bromide test will show results of >50 mg.
Medication-induced psychosis
SIGNS / SYMPTOMS
Some patients are more susceptible to psychosis and confusion with prescribed medications.
Steroids, anticholinergics, disulfiram, digitalis, and L-dopa medications are the most common causes.
A careful review of a patient's medications, including over-the-counter drugs, should be taken.
INVESTIGATIONS
Symptoms resolve on withdrawal of the offending agent.
Hyperthyroidism
SIGNS / SYMPTOMS
Psychosis is accompanied by physical signs such as tachycardia, goiter, unexplained weight loss, palpitations, tremor, muscle weakness, or unexplained protrusion of the eyes (in Graves disease).
INVESTIGATIONS
Elevated serum triiodothyronine (T3) and thyroxine (T4) with low thyroid-stimulating hormone.
Hyperparathyroidism
SIGNS / SYMPTOMS
May precipitate psychosis.[83][84][85]
Anxiety and depression are commonly seen.
Physical symptoms and signs may include bone pain, fractures (due to osteoporosis), poor sleep, fatigue, renal colic due to nephrolithiasis, myalgias, paresthesias, and muscle cramps.
Signs of the cause may be present, such as a hard and dense neck mass or a jaw mass, features of chronic renal failure, or features of a malabsorption syndrome.
INVESTIGATIONS
Serum calcium is normal or elevated in primary hyperparathyroidism and decreased in secondary hyperparathyroidism.
Serum PTH is elevated in primary and secondary hyperparathyroidism.
Autoimmune encephalitis
SIGNS / SYMPTOMS
In general, tends to have an acute/subacute onset (rapid progression within 3 months). Psychosis, if present, may be accompanied by focal neurologic signs, autonomic features, movement disorders, and seizures.[86][87][88]
The most common types are N-methyl-D-aspartate receptor (NMDAR)- and leucine-rich glioma-inactivated 1 (LGI1)-antibody encephalitis.[89]
INVESTIGATIONS
Positive serum and cerebrospinal fluid testing for LGI1 antibodies and NMDA receptor antibodies. Electroencephalogram may show extreme deltabrush in anti-NMDA receptor encephalitis.
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