Differentials

Schizoaffective disorder

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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. The affective symptoms are present for a significant amount of the total duration of illness.

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Clinical diagnosis (DSM-5-TR or ICD-11).

Substance-induced psychotic disorder

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Substance-related disorders are great imitators of psychopathology.

Substance/medication-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.[3]

Delusions are not as crystallised 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.[102]

The drugs most often associated with psychosis are heavy and persistent use of marijuana; stimulant drugs such as methamphetamine, cocaine, and amphetamines; and psychotomimetics such as LSD and ketamine-like drugs.

Past history of extensive use may result in long-term persistent psychotic symptoms, years after the last exposure.

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Urine drug screen may identify the causative drug. If drug screen is negative and there is history of drug use, a cause-effect relation can be elucidated from the clinical interview and review of medical records.

Dementia with psychosis

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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.

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CT or MRI brain may reveal characteristic signs of the causative dementia.

Depression with psychosis

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Depression typically occurs before psychotic symptoms appear, and psychotic symptoms are usually congruent with the mood and do not meet criteria for schizophrenia.

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Clinical diagnosis (DSM-5-TR or ICD-11).

Bipolar disorder with psychosis

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Typically, the mood disorder occurs before psychotic symptoms appear, and psychotic symptoms are usually congruent with the mood and do not meet criteria for schizophrenia.

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Clinical diagnosis (DSM-5-TR or ICD-11).

Malingering and factitious disorders

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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 carers or close contacts.

Patients with schizophrenia who have true somatisation are not typically evasive or needy of reassurances.

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Clinical diagnosis (DSM-5-TR or ICD-11).

Delusional disorder

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In delusional disorder there is an absence of the other symptoms characteristic of schizophrenia (e.g., prominent auditory or visual hallucinations, disorganised speech, grossly disorganised or catatonic behaviour, negative symptoms); functioning is not markedly impaired and behaviour is not obviously bizarre or odd.[3]

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Clinical diagnosis (DSM-5-TR or ICD-11).

Acute/transient psychotic disorder

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This disorder is differentiated by a short duration of psychosis (<1 month), unaccompanied by a functional deterioration.

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Clinical diagnosis (ICD-11).

Obsessive-compulsive disorder (OCD)

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Patients with OCD may present with poor or absent insight, and the preoccupations may reach delusional proportions. Although patients with OCD may report experiences with the qualities of passivity phenomena, a key distinction is that people with OCD recognise their thoughts are self-generated (i.e., their own). Features include prominent obsessions, compulsions (or both) that are time-consuming (e.g., take more than 1 hour per day) or cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.[3]

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Clinical diagnosis (DSM-5-TR or ICD-11).

Body dysmorphic disorder (BDD)

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Patients with BDD may have referential thinking (ideas or delusions of reference). BDD is characterised by a preoccupation with perceived flaws in physical appearance (that appear slight or non-existent to others). Other features include repetitive behaviours (compulsions, rituals), poor psychosocial functioning and quality of life, distressing emotions, social anxiety and social avoidance, and camouflaging. Appearance concerns are not better explained by an eating disorder. Patients have an absence of BDD-related insight.

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Structured Clinical Interview for DSM-5 (SCID-5).

BDD Module.

BDD Questionnaire (BDDQ), Dermatology Version.

Dysmorphic Concern Questionnaire (DCQ).

Cosmetic Procedure Screening Questionnaire (COPS).

Autism spectrum disorder (ASD)

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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.

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Clinical diagnosis (DSM-5-TR or ICD-11).

Organic psychosis

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Numerous medical conditions can cause psychotic symptoms.[68]​ Conditions affecting the brain can cause psychosis, such as epilepsy, tumours (not only brain tumours), traumatic brain injuries, HIV, neurosyphilis, pellagra, B12 deficiency, herpes encephalitis, and Wilson's disease, among others. History and physical examination help differentiate diagnoses.

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Laboratory studies will help differentiation, such as rapid plasma reagin test, HIV test, herpes simplex virus-polymerase chain reaction in cerebrospinal fluid, urine copper level, blood level of ceruloplasmin, and vitamin B12.

Carbon monoxide poisoning

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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.

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Toxicology screen for carboxyhaemoglobin may be performed in the accident and emergency department.

Medicine-induced psychosis

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Some patients are more susceptible to psychosis and confusion with prescribed medicines.

Steroids, anticholinergics, disulfiram, digitalis, and L-dopa medicines are the most common causes.

A careful review of a patient's medicines, including over-the-counter drugs, should be taken.

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Symptoms resolve on withdrawal of the offending agent.

A quantitative level of agents should be taken if available.

Autoimmune encephalitis

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In general, tends to have an acute/subacute onset (rapid progression within 3 months). Psychosis, if present, may be accompanied by focal neurological signs, autonomic features, movement disorders, and seizures.[103][104][105]​​​

The most common types are N-methyl-D-aspartate receptor (NMDAR)- and leucine-rich glioma-inactivated 1 (LGI1)-antibody encephalitis.[106]

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Positive serum and cerebrospinal fluid testing for LGI1 antibodies and NMDA receptor antibodies.

Electroencephalogram may show extreme delta brush in anti-NMDA-receptor encephalitis.

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