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Continuing Education Activity

Psychosis is a loose description of an amalgamation of psychological symptoms resulting in a loss of

contact with reality. It is thought that although around 1.5 to 3.5 percent of people will meet diagnostic
criteria for a psychotic disorder, a significantly larger variable number will experience at least one
psychotic symptom in their lifetime. Psychosis is a common feature of many psychiatric,
neuropsychiatric, neurologic, neurodevelopmental, and medical conditions. It is the hallmark feature of
schizophrenia spectrum and other psychotic disorders, a co-occurring aspect to many mood and
substance use disorders, as well as a challenging symptom to many neurologic and medical conditions.
Psychosis can be highly distressing to patients and loved ones, which is why it has become a primary
target of treatment for medical professionals. This activity outlines the evaluation, treatment, and
management of psychosis, and reviews the role of the interprofessional team in managing and
improving care for patients with this condition.

Objectives:

Identify the presenting features of psychotic disorders.

Describe the epidemiology of psychotic disorders.

Review the treatment and management options for psychosis.

Explain the importance of improving care coordination amongst the interprofessional team to enhance
the delivery of care for patients with psychotic disorders.

Earn continuing education credits (CME/CE) on this topic.

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Introduction

Psychosis is an amalgamation of psychological symptoms resulting in a loss of contact with reality. The
current thinking is that although around 1.5 to 3.5% of people will meet diagnostic criteria for a
psychotic disorder, a significantly larger, a variable number will experience at least one psychotic
symptom in their lifetime.[1] Psychosis is a common feature to many psychiatric, neuropsychiatric,[2][3]
[4] neurologic, neurodevelopmental, and medical conditions. It is the hallmark feature of schizophrenia
spectrum and other psychotic disorders, a co-occurring aspect to many mood and substance use
disorders,[5] as well as a challenging symptom to many neurologic and medical conditions. Psychosis
can result in high levels of distress for patients and loved ones, which is why it has become a primary
target of treatment for medical professionals.

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Etiology

Psychosis may result from a primary psychiatric illness, substance use, or another neurologic or medical
condition. Brain abnormalities have correlated with first-episode psychotic disorders, including reduced
prefrontal, superior, and medial temporal grey matter.[6] Primary psychotic disorders are considered
neurodevelopmental abnormalities and believed to develop in utero, although many times the
manifestation of psychotic symptoms and full-blown illness correlate with epigenetic or environmental
factors (substance abuse, stress, immigration, infection, postpartum period, or other medical causes).
There is significant evidence for genetic risk factors in the pathogenesis of psychotic disorders.[7]

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Epidemiology

The incidence of a first-time episode of psychosis is approximately 50 in 100000 people, while the
incidence of schizophrenia is about 15 in 100000 people.[8] The peak age of onset for males is teens to
mid-20s, while for females, the onset tends to be teens to late-20’s. Earlier onset correlates with poorer
outcomes, although early intervention correlates with better results. Psychosis is extremely uncommon
in children.

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Pathophysiology

Most strongly linked to the pathophysiology of psychotic disorders is the neurotransmitter dopamine.
The positive symptoms of psychotic disorders are believed to be caused by excess dopamine in the
mesolimbic tract. Glutamate, an excitatory neurotransmitter, is also implicated. Multiple studies have
found a decreased function of the N-methyl-D-aspartate (NMDA) glutamate receptor.[9][10] Studies
have also pointed to gamma-amino-butyric acid (GABA), an important inhibitory neurotransmitter.[11]
Some studies show evidence of dysfunction in patients with subjects with schizophrenia. Lastly,
implications point to an imbalance in acetylcholine.[12][13] This finding developed while observing the
smoking behaviors of patients with schizophrenia, as nicotine has been shown to increase acetylcholine
function. Observers noted some improvements in deficits in the smokers, and cognition was improved in
studies as well.
Differential Diagnosis

To differentiate between psychoses associated with a primary psychotic disorder and psychotic
disorders associated with other medical or neurologic conditions, one can examine the following factors:

Age of onset: This is one of the most important factors when determining the etiology of a psychotic
episode. The primary psychotic disorder will usually present in late teens to the early thirties. (Men
typically present with the condition earlier than women). Psychosis associated with
medical/neurological conditions will often present after the age of 40. The older the patient, the higher
the risk for medical or neurological psychosis, especially in the hospital setting.

The pattern of onset: Primary psychotic disorder may present subtly, often with a prodromal phase that
may be confused with another psychiatric disorder (e.g., schizophrenia can easily be confused with
depression in its initial stages). Medical or neurological psychosis will usually present acutely.

Genetics: There is a significant association with the primary psychotic disorder and family history than
psychosis associated with medical/neurologic conditions.

Presentation: Primary psychotic disorder commonly presents during significant life stressors (moving,
new job, end of a relationship), while psychosis associated with medical/neurologic conditions generally
presents in healthcare settings.

Hallucinations: Primary psychotic disorder is generally synonymous with auditory hallucinations,

whereas psychosis associated with medical/neurologic conditions usually correlates with all other types
of hallucinations except auditory (e.g., visual, tactile, olfactory).

Specific primary psychotic disorders, with their subtypes, along with all other psychotic disorders, will be
discussed in detail in other activities.

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Prognosis

The course for schizophrenia was once believed to be unvaryingly poor, although now studies have
shown there is potential for good outcomes. The multitude of newer medications, along with an option
for long-acting injectable antipsychotics, has given patients a variety of treatment options along with
addressing compliance issues. As stated earlier, early intervention, along with intensive treatment,
seems to be of utmost importance in long-term outcomes. There is little data supporting evidence either
way for a single psychotic episode related to a medical or neurologic condition, and prognosis would be
condition dependent. Treating the current episode, along with the underlying illness, would be
considered the best course of action.
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Complications

In any psychotic episode, regardless of etiology, there is always risk danger to self or others. These
patients require admission to a safe and therapeutic medical setting. Involuntary admission criteria will
vary by state/country.

Paranoia, fear, suspicion, or other symptoms of psychosis may prevent a patient from getting the help
they need initially, as well as hinder their capability for medication and treatment compliance.

There are significant side effects with antipsychotic medications, which may include extrapyramidal
symptoms (EPS), metabolic syndrome, cardiac abnormalities, anticholinergic effects, sexual side effects,
tardive dyskinesia, and many more.

Psychotic disorders can lead to significantly decreased daily functioning, along with an increased risk of
suicide compared to the general population. The suicide rate in patients with schizophrenia is about 5%.
[26]

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Pearls and Other Issues

Psychosis is a constellation of symptoms resulting in a loss of touch with reality.

From 1.5 to 3.5% of people will meet the criteria for a primary psychiatric disorder in their lifetime,
while many more will experience some variation of psychotic symptoms.

Abnormalities of temporal grey matter have a link to first-episode psychosis.

Initial psychotic episodes correlate epigenetic or environmental stressors.

A psychotic episode or disorder will result in the presence of one or more of the following five
categories: delusions, hallucinations, disorganized thought, disorganized behavior, negative symptoms.

The incidence of a psychotic episode is around 50 in 10000 people.

The peak onset of a psychotic disorder is earlier in males than females.

Dopamine, glutamate, GABA, and acetylcholine are all neurotransmitters implicated in psychosis.

"Bizarre" delusions are not plausible. "Non-bizarre" delusions are often extraordinarily unlikely, but
possible.

A detailed history and mental status exam (MSE) are critical for arriving at a diagnosis.

A urine toxicology screen, along with standard medical workup, can help to rule out the non-psychiatric
cause of psychosis. Remember, not all drugs will show up on screening.

Differentiating between primary psychotic disorders, and psychotic disorders associated with another
medical or neurologic condition: Age of onset, the pattern of onset, genetics, presentation,
hallucinations.
The prodromal phase of schizophrenia is often confused with major depressive disorder.

A psychiatrist should always evaluate a patient experiencing a psychotic episode.

Antipsychotic medications are the gold-standard treatment for psychotic episodes and disorders.

Antipsychotics have been shown to be more efficacious in treating positive symptoms.

Antipsychotics can have significant side effects (QTc prolongation, EPS, metabolic syndrome, sexual side
effects, tardive dyskinesia, etc.).

Clozapine and olanzapine are the only antipsychotics shown to decrease suicidality in psychotic patients.

A safe and therapeutic environment, with calm, empathetic patient interactions, are essential for
treating psychotic symptoms.

There is potential for positive outcomes in patients with psychotic disorders.

Early intervention is essential for good long term outcomes.

Patients with schizophrenia demonstrate increased risk for suicide compared to the general population.

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Enhancing Healthcare Team Outcomes

CONCLUSION

Psychosis is a common symptom of many psychiatric, neurodevelopmental, neurologic, and medical

conditions and is an important target of evaluation and treatment in neurologic and psychiatric practice.
The DSM-5 classification of and criteria for primary psychotic disorders emphasize that these conditions
occur along a spectrum, with schizoid (personality) disorder and schizophrenia defining its mild and
severe ends, respectively. Psychosis is also identified as only one of several dimensions of
neuropsychiatric disturbance in these disorders, with others encompassing abnormal psychomotor
behaviors, negative symptoms, cognitive impairments, and emotional disturbances. This dimensional
approach regards hallucinations and delusions as arising from neural systems subserving perception and
information processing, thereby aligning the neurobiological framework used to describe and study such
symptoms in primary psychotic disorders with those used to study psychosis associated with other
neurologic conditions.
urpose of Review:

Psychosis is a common and functionally disruptive symptom of many psychiatric, neurodevelopmental,

neurologic, and medical conditions and an important target of evaluation and treatment in neurologic
and psychiatric practice. The purpose of this review is to define psychosis, communicate recent changes
to the classification of and criteria for primary psychotic disorders described in the Diagnostic and
Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), and summarize current evidence-based
approaches to the evaluation and management of primary and secondary psychoses.

Recent Findings:

The DSM-5 classification of and criteria for primary psychotic disorders emphasize that these conditions
occur along a spectrum, with schizoid (personality) disorder and schizophrenia defining its mild and
severe ends, respectively. Psychosis is also identified as only one of several dimensions of
neuropsychiatric disturbance in these disorders, with others encompassing abnormal psychomotor
behaviors, negative symptoms, cognitive impairments, and emotional disturbances. This dimensional
approach regards hallucinations and delusions as arising from neural systems subserving perception and
information processing, thereby aligning the neurobiological framework used to describe and study such
symptoms in primary psychotic disorders with those used to study psychosis associated with other
neurologic conditions.

Summary:

This article provides practicing neurologists with updates on current approaches to the diagnosis,
evaluation, and treatment of primary and secondary psychoses.
INTRODUCTION

Psychosis is a common and functionally disruptive symptom of many psychiatric, neurodevelopmental,

neurologic, and medical conditions and an important target of evaluation and treatment in neurologic
and psychiatric practice. This article defines psychosis, communicates recent changes to the
classification of and criteria for primary psychotic disorders described in the Diagnostic and Statistical
Manual of Mental Disorders, Fifth Edition (DSM-5), and summarizes current evidence-based approaches
to the evaluation and management of primary and secondary psychoses. The definitions of psychosis
used in the DSM-5 and International Classification of Diseases, Tenth Revision (ICD-10) are presented,
and hallucinations, delusions, and delusional misidentification syndromes are defined and tabulated.
The current classification, updated criteria, and approaches to the evaluation of schizophrenia spectrum
and related psychotic disorders, as well as psychoses in neurologic conditions, are reviewed. Practical
guidance on the evaluation and treatment of these conditions is drawn from practice guidelines
promulgated by the professional societies and other international organizations, supplemented with
findings published in more recent meta-analyses and systematic reviews.

Psychosis is the defining feature of schizophrenia spectrum disorders, a common but variable feature of
mood and substance use disorders, and a relatively common feature of many developmental, acquired,
and degenerative neurologic and medical conditions. Across these conditions, psychosis is both a
contributor to disability and a barrier to productivity and participation.1–4 Psychosis is, therefore, an
important target of evaluation and treatment among patients receiving care from neurologists and
psychiatrists.

This article also defines psychosis and reviews the essential clinical features of primary psychotic
disorders and psychoses secondary to neurologic conditions. The criteria for psychotic disorders
included in the DSM-5,5 which have been revised substantially relative to the Diagnostic and Statistical
Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR),6 are a major focus of this
review. The revised diagnostic criteria for secondary psychoses (those due to neurologic or medical
conditions, substance use, and medications) also are reviewed briefly and the psychoses associated with
common neurologic conditions tabulated. Finally, practical and evidence-based suggestions for the
evaluation and treatment of primary and secondary psychotic disorders are presented.
DEFINING PSYCHOSIS

In early editions of the American Psychiatric Association’s (APA’s) Diagnostic and Statistical Manual of
Mental Disorders (DSM),7 psychosis was defined broadly as “gross impairment in reality testing” or “loss
of ego boundaries” that interferes with the capacity to meet the ordinary demands of life. This approach
to defining psychosis emphasized the presence of functional limitations over the symptoms putatively
responsible for them6 and too often rendered the distinction between psychotic and nonpsychotic
mental disorders ambiguous. Concurrently, the International Classification of Diseases, Ninth Revision
([ICD-9], published in 1975) employed the then-traditional division between “neurosis” and ”psychosis”
in its classification of mental disorders while deliberately making no attempt to define these terms.8 As
a result, the category of psychotic disorders in the early editions of the DSM and in the ICD-9 were
overly inclusive and, with respect to clinical, research, and epidemiologic endeavors, ultimately proved
impracticable.6,8

In their current conceptualization of psychosis, both the APA5 and the World Health Organization8
define psychosis narrowly by requiring the presence of hallucinations (without insight into their
pathologic nature), delusions, or both hallucinations without insight and delusions.6 In both of these
current diagnostic classification systems, impaired reality testing remains central conceptually to
psychosis. In contrast to earlier diagnostic classification systems, the current systems5,8 operationalize
impaired reality testing by identifying the symptoms that provide evidence of such impairment.
Delusions (ie, fixed false beliefs), by definition, are evidence of impaired reality testing: delusional
beliefs are ones maintained steadfastly even in the face of evidence contradicting them incontrovertibly.
Similarly, hallucinations (ie, perceptions occurring in the absence of corresponding external or somatic
stimuli) are evidence of impaired reality when the individual experiencing them is unable to recognize
the hallucinatory nature of such experiences. Both the current APA5 and the World Health
Organization8 classification systems acknowledge that “formal thought disorder” (ie, disorganized
thinking, including illogicality, tangentiality, perseveration, neologism, thought blocking, derailment, or
some combination of these disturbances of thought) is one of several commonly co-occurring features
of psychotic disorders. The DSM-55 allows formal thought disorder to supplant hallucinations and
delusions in the diagnosis of a psychotic disorder when it is accompanied by grossly disorganized
behavior, catatonia (for schizophrenia, schizophreniform, brief psychotic, and schizoaffective disorders)
and/or negative symptoms (for schizophrenia, schizophreniform, and schizoaffective disorders but not
brief psychotic disorder), alone or in combination.8 Since mildly disorganized speech is common and
diagnostically nonspecific, the degree of thought disorder required to fulfill this DSM-5 criterion must be
of severity sufficient to substantially impair effective communication.

For the purposes of this article, the term psychosis refers to the presence of delusions, hallucinations
without insight, or both. These symptoms are clearly defined common features of psychosis in both
psychiatric disorders and neurologic conditions. They are captured by informal and structured clinical
assessments and are reasonably amenable to treatment.
Psychosis is a condition of the mind that results in difficulties determining what is real and what is not
real.[4] Symptoms may include delusions and hallucinations.[4] Other symptoms may include incoherent
speech and behavior that is inappropriate for the situation.[4] There may also be sleep problems, social
withdrawal, lack of motivation, and difficulties carrying out daily activities.[4] Psychosis can have serious
outcomes.[6]

Psychosis has many different causes.[4] These include mental illness, such as schizophrenia or bipolar
disorder, sleep deprivation, some medical conditions, certain medications, and drugs such as alcohol or
cannabis.[4] One type, known as postpartum psychosis, can occur after giving birth.[7] The
neurotransmitter dopamine is believed to play a role.[8] Acute psychosis is considered primary if it
results from a psychiatric condition and secondary if it is caused by a medical condition.[9] The diagnosis
of a mental health condition requires excluding other potential causes.[10] Testing may be done to
check for central nervous system diseases, toxins, or other health problems as a cause.
Pathophysiology

Neuroimaging

The first brain image of an individual with psychosis was completed as far back as 1935 using a
technique called pneumoencephalography[85] (a painful and now obsolete procedure where
cerebrospinal fluid is drained from around the brain and replaced with air to allow the structure of the
brain to show up more clearly on an X-ray picture).

Both first episode psychosis, and high risk status is associated with reductions in grey matter volume
(GMV). First episode psychotic and high risk populations are associated with similar but distinct
abnormalities in GMV. Reductions in the right middle temporal gyrus, right superior temporal gyrus
(STG), right parahippocampus, right hippocampus, right middle frontal gyrus, and left anterior cingulate
cortex (ACC) are observed in high risk populations. Reductions in first episode psychosis span a region
from the right STG to the right insula, left insula, and cerebellum, and are more severe in the right ACC,
right STG, insula and cerebellum.[86][87]

Another meta analysis reported bilateral reductions in insula, operculum, STG, medial frontal cortex,
and ACC, but also reported increased GMV in the right lingual gyrus and left precentral gyrus.[88] The
Kraepelinian dichotomy is made questionable[clarification needed] by grey matter abnormalities in
bipolar and schizophrenia; schizophrenia is distinguishable from bipolar in that regions of grey matter
reduction are generally larger in magnitude, although adjusting for gender differences reduces the
difference to the left dorsomedial prefrontal cortex, and right dorsolateral prefrontal cortex.[89]

During attentional tasks, first episode psychosis is associated with hypoactivation in the right middle
frontal gyrus, a region generally described as encompassing the dorsolateral prefrontal cortex (dlPFC). In
congruence with studies on grey matter volume, hypoactivity in the right insula, and right inferior
parietal lobe is also reported.[90] During cognitive tasks, hypoactivities in the right insula, dACC, and the
left precuneus, as well as reduced deactivations in the right basal ganglia, right thalamus, right inferior
frontal and left precentral gyri are observed. These results are highly consistent and replicable possibly
except the abnormalities of the right inferior frontal gyrus.[91] Decreased grey matter volume in
conjunction with bilateral hypoactivity is observed in anterior insula, dorsal medial frontal cortex, and
dorsal ACC. Decreased grey matter volume and bilateral hyperactivity is reported in posterior insula,
ventral medial frontal cortex, and ventral ACC
Hallucinations

Studies during acute experiences of hallucinations demonstrate increased activity in primary or

secondary sensory cortices. As auditory hallucinations are most common in psychosis, most robust
evidence exists for increased activity in the left middle temporal gyrus, left superior temporal gyrus, and
left inferior frontal gyrus (i.e. Broca's area). Activity in the ventral striatum, hippocampus, and ACC are
related to the lucidity of hallucinations, and indicate that activation or involvement of emotional
circuitry are key to the impact of abnormal activity in sensory cortices. Together, these findings indicate
abnormal processing of internally generated sensory experiences, coupled with abnormal emotional
processing, results in hallucinations. One proposed model involves a failure of feedforward networks
from sensory cortices to the inferior frontal cortex, which normally cancel out sensory cortex activity
during internally generated speech. The resulting disruption in expected and perceived speech is
thought to produce lucid hallucinatory experiences.[93]

Delusions

The two-factor model of delusions posits that dysfunction in both belief formation systems and belief
evaluation systems are necessary for delusions. Dysfunction in evaluations systems localized to the right
lateral prefrontal cortex, regardless of delusion content, is supported by neuroimaging studies and is
congruent with its role in conflict monitoring in healthy persons. Abnormal activation and reduced
volume is seen in people with delusions, as well as in disorders associated with delusions such as
frontotemporal dementia, psychosis and Lewy body dementia. Furthermore, lesions to this region are
associated with "jumping to conclusions", damage to this region is associated with post-stroke
delusions, and hypometabolism this region associated with caudate strokes presenting with delusions.

The aberrant salience model suggests that delusions are a result of people assigning excessive
importance to irrelevant stimuli. In support of this hypothesis, regions normally associated with the
salience network demonstrate reduced grey matter in people with delusions, and the neurotransmitter
dopamine, which is widely implicated in salience processing, is also widely implicated in psychotic
disorders.

Specific regions have been associated with specific types of delusions. The volume of the hippocampus
and parahippocampus is related to paranoid delusions in Alzheimer's disease, and has been reported to
be abnormal post mortem in one person with delusions. Capgras delusions have been associated with
occipito-temporal damage, and may be related to failure to elicit normal emotions or memories in
response to faces.[94]

Negative symptoms

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Psychosis is associated with ventral striatal hypoactivity during reward anticipation and feedback.
Hypoactivity in the left ventral striatum is correlated with the severity of negative symptoms.[95] While
anhedonia is a commonly reported symptom in psychosis, hedonic experiences are actually intact in
most people with schizophrenia. The impairment that may present itself as anhedonia probably actually
lies in the inability to identify goals, and to identify and engage in the behaviors necessary to achieve
goals.[96] Studies support a deficiency in the neural representation of goals and goal directed behavior
by demonstrating that receipt (not anticipation) of reward is associated with a robust response in the
ventral striatum; reinforcement learning is intact when contingencies about stimulus-reward are
implicit, but not when they require explicit neural processing; reward prediction errors (during
functional neuroimaging studies), particularly positive PEs are abnormal. A positive prediction error
response occurs when there is an increased activation in a brain region, typically the striatum, in
response to unexpected rewards. A negative prediction error response occurs when there is a decreased
activation in a region when predicted rewards do not occur.[96] ACC response, taken as an indicator of
effort allocation, does not increase with reward or reward probability increase, and is associated with
negative symptoms; deficits in dlPFC activity and failure to improve performance on cognitive tasks
when offered monetary incentives are present; and dopamine mediated functions are abnormal
Neurobiology

Further information: Dopamine hypothesis of schizophrenia

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Psychosis has been traditionally linked to the overactivity of the neurotransmitter dopamine. In
particular to its effect in the mesolimbic pathway. The two major sources of evidence given to support
this theory are that dopamine receptor D2 blocking drugs (i.e., antipsychotics) tend to reduce the
intensity of psychotic symptoms, and that drugs that accentuate dopamine release, or inhibit its
reuptake (such as amphetamines and cocaine) can trigger psychosis in some people (see stimulant
psychosis).[97]

NMDA receptor dysfunction has been proposed as a mechanism in psychosis.[98] This theory is
reinforced by the fact that dissociative NMDA receptor antagonists such as ketamine, PCP and
dextromethorphan (at large overdoses) induce a psychotic state. The symptoms of dissociative
intoxication are also considered to mirror the symptoms of schizophrenia, including negative symptoms.
[99] NMDA receptor antagonism, in addition to producing symptoms reminiscent of psychosis, mimics
the neurophysiological aspects, such as reduction in the amplitude of P50, P300, and MMN evoked
potentials.[100] Hierarchical Bayesian neurocomputational models of sensory feedback, in agreement
with neuroimaging literature, link NMDA receptor hypofunction to delusional or hallucinatory symptoms
via proposing a failure of NMDA mediated top down predictions to adequately cancel out enhanced
bottom up AMPA mediated predictions errors.[101] Excessive prediction errors in response to stimuli
that would normally not produce such a response is thought to root from conferring excessive salience
to otherwise mundane events.[102] Dysfunction higher up in the hierarchy, where representation is
more abstract, could result in delusions.[103] The common finding of reduced GAD67 expression in
psychotic disorders may explain enhanced AMPA mediated signaling, caused by reduced GABAergic
inhibition.[104][105]

The connection between dopamine and psychosis is generally believed to be complex. While dopamine
receptor D2 suppresses adenylate cyclase activity, the D1 receptor increases it. If D2-blocking drugs are
administered, the blocked dopamine spills over to the D1 receptors. The increased adenylate cyclase
activity affects genetic expression in the nerve cell, which takes time. Hence antipsychotic drugs take a
week or two to reduce the symptoms of psychosis. Moreover, newer and equally effective antipsychotic
drugs actually block slightly less dopamine in the brain than older drugs whilst also blocking 5-HT2A
receptors, suggesting the 'dopamine hypothesis' may be oversimplified.[106] Soyka and colleagues
found no evidence of dopaminergic dysfunction in people with alcohol-induced psychosis[107] and
Zoldan et al. reported moderately successful use of ondansetron, a 5-HT3 receptor antagonist, in the
treatment of levodopa psychosis in Parkinson's disease patients.[108]

A review found an association between a first-episode of psychosis and prediabetes.[109]

Prolonged or high dose use of psychostimulants can alter normal functioning, making it similar to the
manic phase of bipolar disorder.[110] NMDA antagonists replicate some of the so-called "negative"
symptoms like thought disorder in subanesthetic doses (doses insufficient to induce anesthesia), and
catatonia in high doses). Psychostimulants, especially in one already prone to psychotic thinking, can
cause some "positive" symptoms, such as delusional beliefs, particularly those persecutory in nature.
Etymology

The word psychosis was introduced to the psychiatric literature in 1841 by Karl Friedrich Canstatt in his
work Handbuch der Medizinischen Klinik. He used it as a shorthand for 'psychic neurosis'. At that time
neurosis meant any disease of the nervous system, and Canstatt was thus referring to what was
considered a psychological manifestation of brain disease.[135] Ernst von Feuchtersleben is also widely
credited as introducing the term in 1845,[136] as an alternative to insanity and mania.

The term stems from Modern Latin psychosis, "a giving soul or life to, animating, quickening" and that
from Ancient Greek ψυχή (psyche), "soul" and the suffix -ωσις (-osis), in this case "abnormal condition".
[137][138]

In its adjective form "psychotic", references to psychosis can be found in both clinical and non-clinical
discussions. However, in a non-clinical context, "psychotic" is generally used as a synonym for "insane".
Epidemiology

In the general population, there is an approximate 3% lifetime prevalence of psychotic disorders, with
0.21% accounting for psychosis due to a general medical condition.4 A recent review found a prevalence
of 0.5% to 4.3% for bipolar disorder in primary care populations, and approximately 9% for bipolar
spectrum illnesses.5 In one urban primary care population, the prevalence of psychotic symptoms was
most commonly associated with depressive, anxiety, and panic disorders (42.4%, 38.6%, and 24.8%,
respectively), followed by substance use disorders (13.8%).6

Childhood-onset schizophrenia (12 years or younger) is uncommon, with a prevalence of 0.2 to 0.4 per
10,000.7 However, children may exhibit psychotic symptoms secondary to medication adverse effects,
drug toxicity or poisons, metabolic defects, autoimmune disorders, or other psychiatric disorders.8 In a
10-year cohort study, adolescent use of marijuana increased the occurrence of incident psychosis and,
with ongoing use, the risk of persistent psychotic episodes.9

The prevalence of depression in pregnancy has been estimated to be 13.6% at 32 weeks' gestation to
17% at approximately 36 weeks' gestation.10 Postpartum psychosis occurs after one in 500 to 1,000
births; risk factors include a history of premorbid depression or bipolar disorder, prior peripartum mood
disorder, or a previous episode of postpartum psychosis.11,12

Etiology

The role of dopamine in the pathophysiology of psychosis is supported by the effectiveness of dopamine
receptor antagonists in treating symptoms, and from evidence that psychosis-producing drugs such as
methamphetamine, cocaine, and levodopa enhance dopamine secretion. Hypofunction of the N-methyl-
d-aspartate glutamate receptor may cause schizophrenia.13,14 Psychotic presentations associated with
autoimmune disorders raise the possibility of shared genetic features or common exposures to etiologic
factors, such as infections.