Psychosis

Psychotic symptoms are particularly challenging to evaluate in children and adolescents given their developmental stages and the nonspecific nature of symptoms. Most children who report hallucinations do not meet criteria for schizophrenia (see diagnostic criteria below), and many do not have a psychotic illness. Other conditions that can be associated with psychotic symptoms include delusional disorders, severe depression, bipolar disorder, personality disorder, obsessive compulsive disorders, substance use, and developmental syndromes. In addition to these examples of pathology, healthy children have strong imaginations and fantasy lives that can be misinterpreted. The evaluation of psychosis in the pediatric population can be quite nuanced and should ideally be conducted by a clinician with expertise in childhood mental illness.

An area of active research is in prevention and early intervention in young people considered at high risk for psychosis due to risk factors that include family history, subthreshold symptoms, and decline in functioning. The Substance Abuse and Mental Health Services Administration (SAMSHA) maintains a mental illness treatment locator to help patients with concerning symptoms, including early and prodromal psychosis, to find appropriate programs and care.

Symptoms

The onset of symptoms of psychosis is often insidious and associated with a long prodromal period that is often defined by subthreshold delusional symptoms and a decline in functioning. Active psychotic symptoms include the following:

• Delusions reflect fixed beliefs that conflict with reality and do not change or adjust in light of conflicting evidence. Bizarre delusions are beliefs that are clearly implausible and considered detached from reality even in the context of the individual’s culture or religion.

• Hallucinations reflect perception of a stimulus when no stimulus is present. Auditory hallucinations are the most common manifestation associated with psychiatric conditions, followed by visual hallucinations.

  • Tactile and olfactory hallucinations can be associated with somatic delusions (e.g., belief that bugs are crawling on one’s skin or part of the body is rotting/smells awful).

  • Hallucinations that occur when falling asleep (hypnagogic) or upon waking (hypnopompic) do not reflect psychosis if they are restricted to the periods immediately associated with falling or awakening from sleep.

  • Hallucinations are distinct from illusions, which are misinterpretations of existing stimuli (e.g., seeing a shadow and believing it is a person), and flashbacks, which involve perceiving prior sensory experiences associated with trauma.

  • Children often struggle to separate illusions and flashbacks from hallucinations and to separate internal thought processes from experiences of hearing or seeing things (e.g., perceiving an internal thought process as “hearing” something that is not present). Therefore, it is important to ascertain specific features when a child reports perceiving something that others cannot.

• Disorganized thinking or speech reflects the inability to organize or hold one’s thoughts, or both. It can manifest as sudden derailment of train of thought, weak or no association between thoughts, or complete incoherence. Another sign of disorganized thinking or speech is thought blocking, characterized by stopping mid-thought and being unable to resume the thought process.

Youth who present with changes in behavior, decline in functioning, or signs of problems with thinking or perception should be screened for psychosis. Example questions include:

• Does your mind ever play tricks on you?

• Do you hear voices talking to you when no one is there?

• Does your mind ever feel confused?

Differential Diagnosis

True psychotic symptoms are generally confusing and distressing to the patient. In contrast, detailed, descriptive, or highly organized reports of symptoms are less consistent with a psychotic disorder. Reports of psychotic symptoms in the absence of any findings or changes on mental status exam should also raise questions about a diagnosis of psychosis.

The following conditions may be associated with seemingly psychotic symptoms, but the symptoms are not indicative of a primary psychotic disorder:

• other psychiatric illnesses that may be associated with developmental difficulties, social and emotional deprivation, parents with mental illness, poor boundaries, and cultural or spiritual beliefs that influence the development of hallucinatory experiences:

  • disruptive behavior disorders (e.g., “the voice told me to do bad things”)

  • depression (e.g., a voice invoking suicide)

  • grief (e.g., hearing the voice of a loved one who has been lost)

• night terrors or night illusions may be confused by parents for hallucinations

• neurologic conditions (e.g., central nervous system [CNS] infections, seizure disorders)

• delirium or altered mental status (associated with multiple etiologies)

• neoplasms and paraneoplastic syndromes

• endocrine disorders

• genetic syndromes

• autoimmune disorders (with psychiatric sequelae or encephalitis)

• toxic exposures

  • drugs of abuse: dextromethorphan, lysergic acid diethylamide, hallucinogenic mushrooms, psilocybin, peyote, cannabis, stimulants, inhalants

  • prescription drugs: glucocorticoids, anesthetics, anticholinergics, antihistamines, amphetamines (in high doses)

Workup

Some controversy exists about the tests to include in a comprehensive workup for first-break psychosis. In the United Kingdom’s Northwick Park first-episode study, only 3% (9 patients) of 268 patients (age range, 15-70 years) who were clinically thought to present with first-episode psychosis were subsequently found to have clear-cut “organic” disease. Although a full medical workup is unlikely to reveal an underlying etiology, a thorough exam is important to pursue due to the lifelong, degenerative nature of schizophrenia and significant risks associated with treatment. Missing a potentially treatable condition could be devastating. The tests that are generally performed as part of a routine workup are listed below, along with additional tests to consider depending on clinical concern.

All patients with first-break psychotic symptoms should receive the following tests:

• physical and neurologic exam

• complete blood count test

• electrolytes blood panel, including calcium (altered mental status is a presenting symptom of electrolyte imbalance)

• liver and kidney function tests

• vitamin B₁₂ blood test (for pernicious anemia)

• metabolic blood test (HbA1c, lipid profile), not for diagnostics but relevant in management

• thyroid function tests

• ceruloplasmin serum test (to rule out Wilson disease)

• pregnancy test (not for diagnostics but relevant in management in female patients)

• urinalysis

• urine toxicology screen

Based on risk/benefit profile, strongly consider the following additional tests:

• erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) level and antinuclear antibody (ANA) to broadly screen for rheumatologic disorders

• HIV testing

• neurosyphilis testing: Fluorescent treponemal antibody absorption (FTA-ABS) testing is more sensitive and useful clinically than rapid plasma reagin (RPR) testing.

• head imaging (if concern for lesions or tumor, MRI is preferred for detecting such abnormalities)

In the setting of specific clinical concern, consider the following tests:

• electroencephalogram (if concern for seizures or narcolepsy; narcolepsy requires multiple sleep latency tests, not simply routine EEG)

• lumbar puncture (if concern for CNS infections or autoimmune encephalitis)

• genetic testing (if concern for genetic syndromes on exam or based on family history)

• chest x-ray (if concern for sarcoidosis or paraneoplastic syndrome)

• heavy metal screen (if history raises concern for exposure)

• serum and cerebrospinal fluid (CSF) anti-N-methyl-D-aspartate (NMDA) and other autoimmune encephalopathy-antibody enzyme-linked immunosorbent assays (ELISAs), along with CSF oligoclonal bands and neopterin

Management

The mainstay of treatment for primary psychotic disorders is antipsychotic medications. Patients often experience significant impairment from their illness and generally require long-term care. Children with psychosis likely will need to be treated by a specialist who can manage both the primary condition and any comorbidities. Pediatricians with patients being treated for psychosis should be familiar with the challenges of treatment, even if they are not primarily managing the disease itself.

Antipsychotic medications: Antipsychotics are the mainstay of treatment for psychosis; however, adverse effects can be challenging, and data show poor long-term adherence to these medications. The two classes of antipsychotics are:

• first-generation medications (e.g., haloperidol): older medications, generally associated with more extrapyramidal symptoms

• second-generation medications (e.g., risperidone, aripiprazole): newer medications, generally associated with more metabolic adverse effects (e.g., weight gain, altered lipid profiles)

  • clozapine: Although research is limited in children, based on adult data, all antipsychotics, except clozapine, are equally effective in the treatment of psychotic symptoms. Clozapine, a second-generation antipsychotic, is more effective than other antipsychotics but is reserved for treatment of refractory psychosis given its potential for agranulocytosis and required close monitoring.

Adverse effects of antipsychotics include the following:

• extrapyramidal symptoms (e.g., dystonic reactions, malignant hyperthermia)

• weight gain or other metabolic effects

• sedation

• orthostatic hypotension

• sexual dysfunction

• hyperprolactinemia

• prolonged QTc interval

• elevated liver aminotransferases

• steatohepatitis

(Source: Psychotic Disorders in Children and Adolescents: A Primer on Contemporary Evaluation and Management. Prim Care Companion CNS Disord 2014.)

Nonpharmacologic treatment: Psychotic disorders are generally accompanied by cognitive decline. Neuropsychological testing can be useful to document cognitive deficits and to inform treatment and academic planning. Youth may require additional educational services and support. The efficacy of cognitive behavioral therapy, social skills training, cognitive remediation, and family interventions has been documented in the adult literature and can be extrapolated to treatment in children and adolescents.

Prognosis

Most patients with psychotic disorders live with moderate-to-severe impairment. Those with low premorbid functioning, insidious onset, more-significant negative symptoms, younger age of onset, and low intellectual functioning tend to have poorer outcomes. Patients with psychosis are additionally at higher risk of medical illness and comorbidities as they age. Referral to a specialist is recommended in cases of diagnostic uncertainty regarding assessment of psychotic symptoms and management of patients with primary psychotic disorders.

Schizophrenia

The worldwide prevalence of schizophrenia is approximately 1%, with a male-to-female ratio of 1.4:1. Schizophrenia is considered early onset if presentation is before the age of 18 years, and childhood onset if before the age of 13 years. Childhood-onset schizophrenia is exceptionally rare. Other psychiatric conditions such as post-traumatic stress disorder (PTSD) or a mood disorder should be considered in the differential diagnosis in children.

Symptoms of schizophrenia:

• Positive symptoms refer to hallucinations, delusions, and thought disorder.

• Negative symptoms refer to deficits (e.g., flat affect, anergy, paucity of speech or thought).

• Symptoms of disorganization include disorganized speech, bizarre behavior, and poor attention.

• Youth with true psychotic disorders tend to have significant negative symptoms; a purely positive symptom presentation should prompt further evaluation.

• Generally, there is a prodromal period for schizophrenia, prior to development of frank psychosis, when the affected individual demonstrates some degree of social withdrawal and impaired functioning.

Diagnosis: The diagnostic criteria for schizophrenia are the same in youth and adults. Note that when patients have not had continuous signs of cognitive disturbance for at least 6 months but have symptoms concerning for schizophrenia, they may meet criteria for one of the following diagnoses:

• brief psychotic disorder, if symptoms are present for 1 month or less

• schizophreniform disorder, if the disturbance has been present for more than 1 month but less than 6 months

• delusional disorder, if the patient experiences delusions only

Etiology: Schizophrenia is a heterogeneous disorder with a strong genetic component. Numerous environmental factors have been hypothesized to contribute to the development of a psychotic illness, including maternal famine, paternal age, prenatal infections, obstetric complications, and marijuana use.