Diagnosis		Clinical characteristics	Tests	Comments
Endocrine conditions
Adrenocorticotropic hormone-producing lung carcinoma (see oncologic, p. 860)		Bruising, glucose intolerance, hyperlipidemia, hypertension, moon facies, truncal obesity	Brain CT or MRI, chest radiography	—
Exogenous steroid use
Pituitary adenoma (Cushing disease)
Steroid-producing tumors
Diabetes mellitus type 1 or 2		Abnormal glucose metabolism, blurry vision, fatigue; hyper- or hypoglycemia may present with psychotic symptoms	A1C, complete metabolic profile, urinalysis	Rule out delirium
Parathyroid disease19		Abdominal discomfort, bone disorders, confusion, depression, fatigue, hallucinations, kidney stones, paranoia	Calcium and parathyroid hormone levels	1.5% prevalence in persons older than 65 years; 3.4% prevalence in postmenopausal women
Genetic or inherited conditions
Huntington disease20		Schizophrenia-like symptoms may occur before cognitive or extrapyramidal changes	CT or MRI, genetic testing	Autosomal dominant; chromosome 4
Lewy body disease21		Executive dysfunction, fluctuating awareness, Parkinsonian motor symptoms, visual hallucinations	—	Neuroleptic drugs may cause sudden death or worsen movement, and should be avoided
Parkinson disease (often described with Lewy body disease as a continuum of symptoms)21,22		Forward gait, slowing, stiffness, tremor; delusions, hallucinations, and psychotic symptoms are common in later stages	National Institute for Health and Care Excellence guidelines	Basal ganglia affected
Wilson disease23		Abdominal swelling, delusions, jaundice, Kayser-Fleischer rings, schizophrenia-like psychosis, tremor, vomiting	Serum ceruloplasmin testing	Autosomal recessive; chromosome 13
				Copper accumulation
Infections
Encephalitis24,25		Bizarre behaviors, chills, decreased sensorium, fever, headache, low sodium levels	Antibody testing, electrolyte levels, lumbar puncture, MRI	Affects limbic area of the brain
Human immunodeficiency virus26		Cachexia, cognitive changes, delusions	CT, serum antibody testing	Rule out delirium; may be medication adverse effect; new onset of antiretroviral therapy can cause psychosis
Neurosyphilis27		Abnormal gait, cognitive deficits, headache, incontinence, seizures, visual disturbances	CT or MRI, lumbar puncture, treponemal antibody testing (e.g., fluorescent treponemal antibody absorption test)	May be asymptomatic
Metabolic conditions
Acute intermittent porphyria28		Abdominal pain, fever, peripheral neuropathy, tachycardia; may have only psychotic symptoms	Urine porphyrins testing	Genetic enzyme defect; fasting and drugs affecting the cytochrome P450 system act as inducers
Tay-Sachs disease, adult onset29		Dystonia, spinocerebellar signs; psychosis appears in one-third to one-half of patients	Serum hexosaminidase testing	Often misdiagnosed
Neurologic conditions
Brain tumors, benign or space occupying (see oncologic, p. 860)		Headache, seizures, unilateral neurologic signs, visual hallucinations	CT or MRI	—
Dementia16,30		Psychosis in 16% to 23% of older adults	Mental status examination, clock drawing test, Mini-Cog test	May co-occur with delirium
	Alzheimer type	Prominent short-term memory loss; may have aggression, agitation, or paranoia; delusions may be mistaken for misperceptions because of cognitive changes	—	—
Epilepsy 31		Primarily temporal lobe epilepsy; déjà vu, dissociation, visual hallucinations	Electroencephalography	Psychosis in 7% to 11% of patients
Nutritional deficiencies32–34
Niacin (vitamin B3)		Delusions, hallucinations, history of alcoholism	Eating disorder screening, vitamin B complex testing	Dermatitis, dementia, diarrhea, death
Thiamine (vitamin B1)		Confabulation, history of alcoholism, Korsakoff psychosis, older age, Wernicke encephalopathy	Complete blood count, serum folate and vitamin B1 testing	—
Vitamin B12		Psychotic symptoms in late childhood, early adolescence; in older adults, ataxia, glossitis, cogwheel rigidity, abdominal symptoms, persecutory delusions, hallucinations	Complete blood count, Helicobacter pylori testing, intrinsic factor antibody testing, serum folate and vitamin B12 testing	Replace with vitamin B complex plus niacin
Oncologic conditions
Ovarian teratoma35		Altered consciousness, cognitive deficits, pelvic pain, psychosis, seizures	Abdominal CT or ultrasonography	Anti–N-methyl-d-aspartate receptor encephalitis may be associated with teratomas
Paraneoplastic limbic encephalitis36		Neuropsychiatric symptoms, peripheral neuropathy, personality changes	CT, MRI, or electroencephalography; lumbar puncture; anti-Hu antibody testing; consider carcinoembryonic antigen and cancer antigen 125 testing	80% of cases associated with small cell lung cancer; Lambert-Eaton myasthenic syndrome may occur
Pharmacologic conditions (Table 3)
Drug intoxication or withdrawal		Acute onset, agitation, altered mental status, delusions, hypertension, tachycardia, visual hallucinations	History, toxicology	—
Medication adverse effect		Gradual onset	—	—
Psychiatric conditions5,11,16,37,38
Bipolar I disorder		Mania: decreased need for sleep, elevated or irritable mood, racing thoughts, risk taking	Mental status examination, Mood Disorder Questionnaire	May present with depression; inquire about prior manic symptoms; selective serotonin reuptake inhibitors should be used with caution; lifetime prevalence of 0.24%
		Depression: anhedonia, changes in sleep and appetite, depressed mood, guilt, hopelessness, suicidality	Clinical diagnosis of exclusion
Depression with psychotic features		Anhedonia, changes in sleep and appetite, delusions, depressed mood, guilt, hallucinations, hopelessness, paranoia, suicidality; may present with symptoms of panic and anxiety	Mental status examination, Patient Health Questionnaire	Lifetime prevalence of 0.35%
			Clinical diagnosis of exclusion
Psychotic disorder (brief)		Delusions and paranoia with hallucinations lasting one day to one month; if in peri- or postpartum phases, mother may have delusions that the baby is possessed, or hallucinations telling her to harm the baby	Mental status examination	Psychiatric emergency
			Clinical diagnosis of exclusion
Schizoaffective disorder		Auditory hallucinations, delusions, paranoia; overlap with schizophrenia and mood disorders; functional difficulty not a defining criterion	Mental status examination	Lifetime prevalence of 0.3%
			Clinical diagnosis of exclusion
Schizophrenia		Auditory hallucinations, delusions, paranoia; decline in ability to work, or maintain relationships or self-care; a prodromal phase occurs when patients report peculiar perceptual experiences	Mental status examination	First break often in late adolescence or early adulthood; prevalence of 0.87%; treatment in prodromal phase may attenuate course and ameliorate severity
			Clinical diagnosis of exclusion
Thyroid dysfunction
Myxedema39		Auditory or visual hallucinations, Capgras syndrome (delusions of “impostors,” either of the patient or significant others), few cognitive deficits, lethargy, normal level of consciousness, paranoia	Thyroid-stimulating hormone and thyroxine levels, thyroid antibodies	Psychosis in 5% to 15% of patients