| Psychosis | |
|---|---|
| Other names | Psychotic break |
 | |
| Van Gogh's The Starry Night, from 1889, shows changes in light and color as can appear with psychosis. | |
| Specialty | Psychiatry, psychology |
| Symptoms | False beliefs, seeing or hearing things that others do not see or hear, incoherent speech |
| Complications | Self-harm, suicide |
| Causes | Mental illness (schizophrenia, bipolar disorder), sleep deprivation, some medical conditions, certain medications, drugs (including alcohol and cannabis) |
| Treatment | Antipsychotics, counselling, social support |
| Prognosis | Depends on cause |
| Frequency | 3% of people at some point in time (US) |
Psychosis is an abnormal condition of the mind that results in difficulties determining what is real and what is not. Symptoms may include false beliefs (delusions) and seeing or hearing things that others do not see or hear (hallucinations). Other symptoms may include incoherent speech and behavior that is inappropriate for the situation. There may also be sleep problems, social withdrawal, lack of motivation, and difficulties carrying out daily activities.
Psychosis has many different causes. These include mental illness, such as schizophrenia or bipolar disorder, sleep deprivation, some medical conditions, certain medications, and drugs such as alcohol or cannabis. One type, known as postpartum psychosis, can occur after giving birth. The neurotransmitter dopamine is believed to play a role. Acute psychosis is considered primary if it results from a psychiatric condition and secondary if it is caused by a medical condition. The diagnosis of a mental illness requires excluding other potential causes. Testing may be done to check for central nervous system diseases, toxins, or other health problems as a cause.
Treatment may include antipsychotic medication, counselling, and social support. Early treatment appears to improve outcomes. Medications appear to have a moderate effect. Outcomes depend on the underlying cause. In the United States about 3% of people develop psychosis at some point in their lives. The condition has been described since at least the 4th century BCE by Hippocrates and possibly as early as 1,500 BCE in the Egyptian Ebers Papyrus.
Signs and symptoms
Hallucinations
A hallucination is defined as sensory perception in the absence of external stimuli. Hallucinations are different from illusions,
or perceptual distortions which are the misperception of external
stimuli. Hallucinations may occur in any of the senses and take on
almost any form, which may include simple sensations (such as lights,
colors, tastes, and smells) to experiences such as seeing and
interacting with fully formed animals and people, hearing voices, and
having complex tactile sensations. Hallucinations are generally
characterized as being vivid, and uncontrollable.
Auditory hallucinations,
particularly experiences of hearing voices, are the most common and
often prominent feature of psychosis.
Up to 15% of the general population may experience auditory
hallucinations. The prevalence in schizophrenia is generally put around
70%, but may go as high as 98%. During the early 20th century auditory
hallucinations were second to visual hallucinations in frequency, but
they are now the most common manifestation of schizophrenia, although
rates vary throughout cultures and regions. Auditory hallucinations are
most commonly intelligible voices. When voices are present, the
average number has been estimated at three. Content, like frequency,
differs significantly, especially across cultures and demographics.
People who experience auditory hallucinations can frequently identify
the loudness, location of origin, and may settle on identities for
voices. Western cultures are associated with auditory experiences
concerning religious content, frequently related to sin. Hallucinations
may command a person to do something which may be dangerous when
combined with delusions.
Extracampine hallucinations are auditory hallucinations
originating from a particular body part (e.g. a voice coming from a
person's knee).
Visual hallucinations occur in roughly a third of people with
schizophrenia, although rates as high as 55% are reported. Content
frequently involves animate objects, although perceptual abnormalities
such as changes in lighting, shading, streaks, or lines may be seen.
Visual abnormalities may conflict with proprioceptive information, and visions may include experiences such as the ground tilting. Lilliputian hallucinations are less common in schizophrenia, and occur more frequently in various types of encephalopathy (e.g. Peduncular hallucinosis).
A visceral hallucination, also called a cenesthetic
hallucination, is characterized by visceral sensations in the absence of
stimuli. Cenesthetic hallucinations may include sensations of burning,
or re-arrangement of internal organs.
Delusions
Psychosis may involve delusional
beliefs. Delusions are strong beliefs against reality or held despite
contradictory evidence. Delusions are necessarily incongruent with
societal norms, as some beliefs may constitute a delusion in certain
cultures where they impact functioning, while they may be a perfectly
normal belief in others. The distinguishing feature between delusional
thinking and full-blown delusions is the degree with which they impact
functioning. Multiple themes are common in delusions, although cultural
norms are highly influential (e.g. religious content differing
significantly across countries). The most common type of delusion is a persecutory delusion,
where a person believes that an individual, organization or group is
attempting to harm them. Other delusions include delusions of reference
(beliefs that a particular stimulus has a special meaning that is
directed at the holder of belief), grandiose delusions (delusions that a
person has a special power or importance), thought broadcasting (the
belief that one's thoughts are audible) and thought insertion (the
belief that one's thoughts are not one's own). The DSM-5 characterizes
certain delusions as "bizarre" if they are clearly implausible, or are
incompatible within the cultural context. The concept of bizarre
delusions has been criticized as excessively subjective.
Historically, Karl Jaspers has classified psychotic delusions into primary and secondary
types. Primary delusions are defined as arising suddenly and not being
comprehensible in terms of normal mental processes, whereas secondary
delusions are typically understood as being influenced by the person's
background or current situation (e.g., ethnicity; also religious,
superstitious, or political beliefs).
Disorganization
Disorganization
is split into disorganized speech or thinking, and grossly disorganized
motor behavior. Disorganized speech, also called formal thought
disorder, is disorganization of thinking that is inferred from speech.
Characteristics of disorganized speech include rapidly switching topics,
called derailment or loose association; switching to topics that are
unrelated, called tangential thinking; incomprehensible speech, called
word salad or incoherence. Disorganized motor behavior includes
repetitive, odd, or sometimes purposeless movement. Disorganized motor
behavior rarely includes catatonia, and although it was a historically
prominent symptom, it is rarely seen today. Whether this is due to
historically used treatments or the lack thereof is unknown.
Catatonia
describes a profoundly agitated state in which the experience of
reality is generally considered impaired. There are two primary
manifestations of catatonic behavior. The classic presentation is a
person who does not move or interact with the world in any way while
awake. This type of catatonia presents with waxy flexibility.
Waxy flexibility is when someone physically moves part of a catatonic
person's body and the person stays in the position even if it is bizarre
and otherwise nonfunctional (such as moving a person's arm straight up
in the air and the arm staying there).
The other type of catatonia is more of an outward presentation of
the profoundly agitated state described above. It involves excessive
and purposeless motor behaviour, as well as extreme mental preoccupation
that prevents an intact experience of reality. An example is someone
walking very fast in circles to the exclusion of anything else with a
level of mental preoccupation (meaning not focused on anything relevant
to the situation) that was not typical of the person prior to the
symptom onset. In both types of catatonia there is generally no
reaction to anything that happens outside of them. It is important to
distinguish catatonic agitation from severe bipolar mania, although
someone could have both.
Negative symptoms
Negative symptoms include reduced emotional expression, decreased motivation and reduced spontaneous speech. They lack interest and spontaneity, and have the inability to feel pleasure.
Causes
Normal states
Brief hallucinations are not uncommon in those without any psychiatric disease. Causes or triggers include:
- Falling asleep and waking: hypnagogic and hypnopompic hallucinations, which are entirely normal
- Bereavement, in which hallucinations of a deceased loved one are common
- Severe sleep deprivation
Trauma
Traumatic life events have been linked with elevated risk in developing psychotic symptoms. Childhood trauma has specifically been shown to be a predictor of adolescent and adult psychosis.
Approximately 65% of individuals with psychotic symptoms have
experienced childhood trauma (e.g., physical or sexual abuse, physical
or emotional neglect).
Increased individual vulnerability toward psychosis may interact with
traumatic experiences promoting onset of future psychotic symptoms,
particularly during sensitive developmental periods.
Importantly, the relationship between traumatic life events and
psychotic symptoms appears to be dose-dependent in which multiple
traumatic life events accumulate, compounding symptom expression and
severity.
This suggests trauma prevention and early intervention may be an
important target for decreasing the incidence of psychotic disorders and
ameliorating its effects.
Psychiatric disorder
From
a diagnostic standpoint, organic disorders were believed to be caused
by physical illness affecting the brain (that is, psychiatric disorders
secondary to other conditions) while functional disorders were
considered disorders of the functioning of the mind in the absence of
physical disorders (that is, primary psychological or psychiatric
disorders). Subtle physical abnormalities have been found in illnesses
traditionally considered functional, such as schizophrenia. The DSM-IV-TR
avoids the functional/organic distinction, and instead lists
traditional psychotic illnesses, psychosis due to general medical
conditions, and substance-induced psychosis.
Primary psychiatric causes of psychosis include the following:
- schizophrenia and schizophreniform disorder
- affective (mood) disorders, including major depression, and severe depression or mania in bipolar disorder (manic depression). People experiencing a psychotic episode in the context of depression may experience persecutory or self-blaming delusions or hallucinations, while people experiencing a psychotic episode in the context of mania may form grandiose delusions.
- schizoaffective disorder, involving symptoms of both schizophrenia and mood disorders
- brief psychotic disorder, or acute/transient psychotic disorder
- delusional disorder (persistent delusional disorder)
- chronic hallucinatory psychosis
Psychotic symptoms may also be seen in:
- schizotypal personality disorder
- certain personality disorders at times of stress (including paranoid personality disorder, schizoid personality disorder, and borderline personality disorder)
- major depressive disorder in its severe form, although it is possible and more likely to have severe depression without psychosis
- bipolar disorder in the manic and mixed episodes of bipolar I disorder and depressive episodes of both bipolar I and bipolar II; however, it is possible to experience such states without psychotic symptoms.
- post-traumatic stress disorder
- induced delusional disorder
- Sometimes in obsessive–compulsive disorder
- Dissociative disorders, due to many overlapping symptoms, careful differential diagnosis includes especially dissociative identity disorder.
Stress is known to contribute to and trigger psychotic states. A
history of psychologically traumatic events, and the recent experience
of a stressful event, can both contribute to the development of
psychosis. Short-lived psychosis triggered by stress is known as brief reactive psychosis, and patients may spontaneously recover normal functioning within two weeks.
In some rare cases, individuals may remain in a state of full-blown
psychosis for many years, or perhaps have attenuated psychotic symptoms
(such as low intensity hallucinations) present at most times.
Neuroticism is an independent predictor of the development of psychosis.
Subtypes
Subtypes of psychosis include:
- Menstrual psychosis, including circa-mensual (approximately monthly) periodicity, in rhythm with the menstrual cycle.
- Postpartum psychosis, occurring shortly after giving birth
- Monothematic delusions
- Myxedematous psychosis
- Stimulant psychosis
- Tardive psychosis
- Shared psychosis
Cycloid psychosis
Cycloid
psychosis is a psychosis that progresses from normal to full-blown,
usually between a few hours to days, not related to drug intake or brain injury.
The cycloid psychosis has a long history in European psychiatry
diagnosis. The term "cycloid psychosis" was first used by Karl Kleist in
1926. Despite the significant clinical relevance, this diagnosis is
neglected both in literature as in nosology. The cycloid psychosis has
attracted much interest in the international literature of the past 50
years, but the number of scientific studies have greatly decreased over
the past 15 years, possibly partly explained by the misconception that
the diagnosis has been incorporated in current diagnostic classification
systems. The cycloid psychosis is therefore only partially described in
the diagnostic classification systems used. Cycloid psychosis is
nevertheless its own specific disease that is distinct from both the
manic-depressive disorder, and from schizophrenia, and this despite the
fact that the cycloid psychosis can include both bipolar (basic mood
shifts) as well as schizophrenic symptoms. The disease is an acute,
usually self-limiting, functionally psychotic state, with a very diverse
clinical picture that almost consistently is characterized by the
existence of some degree of confusion or distressing perplexity, but
above all, of the multifaceted and diverse expressions the disease
takes. The main features of the disease is thus that the onset is acute,
the multifaceted picture of symptoms and typically reverses to a normal
state and that the long-term prognosis is good. In addition, diagnostic criteria include at least four of the following symptoms:
- Confusion
- Mood-incongruent delusions
- Hallucinations
- Pan-anxiety, a severe anxiety not bound to particular situations or circumstances
- Happiness or ecstasy of high degree
- Motility disturbances of akinetic or hyperkinetic type
- Concern with death
- Mood swings to some degree, but less than what is needed for diagnosis of an affective disorder
Cycloid psychosis occurs in people of generally 15–50 years of age.
Medical conditions
A very large number of medical conditions can cause psychosis, sometimes called secondary psychosis. Examples include:
- disorders causing delirium (toxic psychosis), in which consciousness is disturbed
- neurodevelopmental disorders and chromosomal abnormalities, including velocardiofacial syndrome
- neurodegenerative disorders, such as Alzheimer's disease, dementia with Lewy bodies, and Parkinson's disease
- focal neurological disease, such as stroke, brain tumors, multiple sclerosis, and some forms of epilepsy
- malignancy (typically via masses in the brain, paraneoplastic syndromes)
- infectious and postinfectious syndromes, including infections causing delirium, viral encephalitis, HIV/AIDS, malaria, syphilis
- endocrine disease, such as hypothyroidism, hyperthyroidism, Cushing's syndrome, hypoparathyroidism and hyperparathyroidism; sex hormones also affect psychotic symptoms and sometimes giving birth can provoke psychosis, termed postpartum psychosis
- inborn errors of metabolism, such as Succinic semialdehyde dehydrogenase deficiency, porphyria and metachromatic leukodystrophy
- nutritional deficiency, such as vitamin B12 deficiency
- other acquired metabolic disorders, including electrolyte disturbances such as hypocalcemia, hypernatremia, hyponatremia, hypokalemia, hypomagnesemia, hypermagnesemia, hypercalcemia, and hypophosphatemia, but also hypoglycemia, hypoxia, and failure of the liver or kidneys
- autoimmune and related disorders, such as systemic lupus erythematosus (lupus, SLE), sarcoidosis, Hashimoto's encephalopathy, anti-NMDA-receptor encephalitis, and non-celiac gluten sensitivity
- poisoning, by therapeutic drugs (see below), recreational drugs (see below), and a range of plants, fungi, metals, organic compounds, and a few animal toxins
- sleep disorders, such as in narcolepsy (in which REM sleep intrudes into wakefulness)
- parasitic diseases, such as neurocysticercosis
Psychoactive drugs
Various psychoactive substances
(both legal and illegal) have been implicated in causing, exacerbating,
or precipitating psychotic states or disorders in users, with varying
levels of evidence. This may be upon intoxication for a more prolonged
period after use, or upon withdrawal.
Individuals who have a substance induced psychosis tend to have a
greater awareness of their psychosis and tend to have higher levels of suicidal thinking compared to individuals who have a primary psychotic illness. Drugs commonly alleged to induce psychotic symptoms include alcohol, cannabis, cocaine, amphetamines, cathinones, psychedelic drugs (such as LSD and psilocybin), κ-opioid receptor agonists (such as enadoline and salvinorin A) and NMDA receptor antagonists (such as phencyclidine and ketamine). Caffeine may worsen symptoms in those with schizophrenia and cause psychosis at very high doses in people without the condition.
Alcohol
Approximately three percent of people who are suffering from alcoholism experience psychosis during acute intoxication or withdrawal. Alcohol related psychosis may manifest itself through a kindling mechanism. The mechanism of alcohol-related psychosis is due to the long-term effects of alcohol resulting in distortions to neuronal membranes, gene expression, as well as thiamin
deficiency. It is possible in some cases that alcohol abuse via a
kindling mechanism can cause the development of a chronic substance
induced psychotic disorder, i.e. schizophrenia. The effects of an
alcohol-related psychosis include an increased risk of depression and
suicide as well as causing psychosocial impairments.
Cannabis
According to some studies, the more often cannabis is used the more likely a person is to develop a psychotic illness, with frequent use being correlated with twice the risk of psychosis and schizophrenia. While cannabis use is accepted as a contributory cause of schizophrenia by some,
it remains controversial, with pre-existing vulnerability to psychosis
emerging as the key factor that influences the link between cannabis use
and psychosis. Some studies indicate that the effects of two active compounds in cannabis, tetrahydrocannabinol (THC) and cannabidiol
(CBD), have opposite effects with respect to psychosis. While THC can
induce psychotic symptoms in healthy individuals, CBD may reduce the
symptoms caused by cannabis.
Cannabis use has increased dramatically over the past few decades
whereas the rate of psychosis has not increased. Together, these
findings suggest that cannabis use may hasten the onset of psychosis in
those who may already be predisposed to psychosis. High-potency cannabis use indeed seems to accelerate the onset of psychosis in predisposed patients.
A 2012 study concluded that cannabis plays an important role in the
development of psychosis in vulnerable individuals, and that cannabis
use in early adolescence should be discouraged.
Methamphetamine
Methamphetamine
induces a psychosis in 26–46 percent of heavy users. Some of these
people develop a long-lasting psychosis that can persist for longer than
six months. Those who have had a short-lived psychosis from
methamphetamine can have a relapse of the methamphetamine psychosis
years later after a stress event such as severe insomnia or a period of
heavy alcohol abuse despite not relapsing back to methamphetamine.
Individuals who have long history of methamphetamine abuse and who have
experienced psychosis in the past from methamphetamine abuse are highly
likely to rapidly relapse back into a methamphetamine psychosis within a
week or so of going back onto methamphetamine.
Medication
Administration, or sometimes withdrawal, of a large number of medications may provoke psychotic symptoms. Drugs that can induce psychosis experimentally or in a significant proportion of people include amphetamine and other sympathomimetics, dopamine agonists, ketamine, corticosteroids (often with mood changes in addition), and some anticonvulsants such as vigabatrin. Stimulants that may cause this include lisdexamfetamine.
Meditation may induce psychological side effects, including depersonalization, derealization and psychotic symptoms like hallucinations as well as mood disturbances.
Pathophysiology
Neuroimaging
The first brain image of an individual with psychosis was completed as far back as 1935 using a technique called pneumoencephalography (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. 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, right parahippocampus, right hippocampus, right middle frontal gyrus, and left anterior cingulate cortex
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.
Another meta analysis reported similar reductions in temporal, medial
frontal, and insular regions, but also reported increased GMV in the
right lingual gyrus and left precentral gyrus.
The Kraeplinian dichotomy is made questionable 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.
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.
With the exceptions of reduced deactivation of the inferior frontal
gyrus during cognitive tasks(i.e. hyperactivation), highly consistent
and replicable hypoactivity in the right insula, dACC, and precuneus, as
well as hyperactivity in the right basal ganglia and thalamus is observed.
Decreased grey matter volume in conjunction with hypoactivity is
observed in the dorsal ACC, right anterior/middle insula, and left
middle insula. Decreased grey matter volume and hyperactivity is
reported in the ventral ACC(i.e. the pgACC and sgACC), and more
posterior regions of the insula.
Hallucinations
Studies
during acute experience 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.
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. Capragas delusions have been associated with
occipito-temporal damage, and may be related to failure to elicit normal
emotions or memories in response to faces.
Negative symptoms
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. 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.
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 robust response in the ventral striatum;
reinforcement learning is intact when contingencies are implicit, but
not when they require explicit processing; reward prediction errors
(during functional neuroimaging studies), particularly positive PEs are
abnormal; 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
Psychosis has been traditionally linked to the neurotransmitter dopamine. In particular, the dopamine hypothesis of psychosis
has been influential and states that psychosis results from an
overactivity of dopamine function in the brain, particularly 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.
NMDA receptor dysfunction has been proposed as a mechanism in psychosis. 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 psychotic symptoms.
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.
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.
Excessive prediction errors in response to stimuli that would normally
not produce such as response is thought to confer excessive salience to
otherwise mundane events. Dsyfunction higher up in the hierarchy, where representation is more abstract, could result in delusions. The common finding of reduced GAD67 expression in psychotic disorders may explain enhanced AMPA mediated signaling, caused by reduced GABAergic inhibition.
The connection between dopamine and psychosis is generally believed 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. Soyka and colleagues found no evidence of dopaminergic dysfunction in people with alcohol-induced psychosis 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.
A review found an association between a first-episode of psychosis and prediabetes.
Prolonged or high dose use of psychostimulants can alter normal functioning, making it similar to the manic phase of bipolar disorder. 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.
Diagnosis
To make a diagnosis of a mental illness in someone with psychosis other potential causes must be excluded.
An initial assessment includes a comprehensive history and physical
examination by a health care provider. Tests may be done to exclude
substance use, medication, toxins, surgical complications, or other
medical illnesses. A person with psychosis is referred to as psychotic.
Delirium
should be ruled out, which can be distinguished by visual
hallucinations, acute onset and fluctuating level of consciousness,
indicating other underlying factors, including medical illnesses. Excluding medical illnesses associated with psychosis is performed by using blood tests to measure:
- Thyroid-stimulating hormone to exclude hypo- or hyperthyroidism,
- Basic electrolytes and serum calcium to rule out a metabolic disturbance,
- Full blood count including ESR to rule out a systemic infection or chronic disease, and
- Serology to exclude syphilis or HIV infection.
Other investigations include:
Because psychosis may be precipitated or exacerbated by common classes of medications, medication-induced psychosis should be ruled out, particularly for first-episode psychosis. Both substance- and medication-induced psychosis can be excluded to a high level of certainty, using toxicology screening.
Because some dietary supplements
may also induce psychosis or mania, but cannot be ruled out with
laboratory tests, a psychotic individual's family, partner, or friends
should be asked whether the patient is currently taking any dietary
supplements.
Common mistakes made when diagnosing people who are psychotic include:
- Not properly excluding delirium,
- Not appreciating medical abnormalities (e.g., vital signs),
- Not obtaining a medical history and family history,
- Indiscriminate screening without an organizing framework,
- Missing a toxic psychosis by not screening for substances and medications,
- Not asking family or others about dietary supplements,
- Premature diagnostic closure, and
- Not revisiting or questioning the initial diagnostic impression of primary psychiatric disorder.
Only after relevant and known causes of psychosis are excluded, a mental health clinician may make a psychiatric differential diagnosis
using a person's family history, incorporating information from the
person with psychosis, and information from family, friends, or
significant others.
Types of psychosis in psychiatric disorders may be established by formal rating scales. The Brief Psychiatric Rating Scale (BPRS) assesses the level of 18 symptom constructs of psychosis such as hostility, suspicion, hallucination, and grandiosity.
It is based on the clinician's interview with the patient and
observations of the patient's behavior over the previous 2–3 days. The
patient's family can also answer questions on the behavior report.
During the initial assessment and the follow-up, both positive and
negative symptoms of psychosis can be assessed using the 30 item
Positive and Negative Symptom Scale (PANSS).
The DSM-5
characterizes disorders as psychotic or on the schizophrenia spectrum
if they involve hallucinations, delusions, disorganized thinking,
grossly disorganized motor behavior, or negative symptoms.
The DSM-5 does not include psychosis as a definition in the glossary,
although it defines "psychotic features", as well as "psychoticism" with
respect to personality disorder. The ICD-10 has no specific definition of psychosis.
Factor analysis
of symptoms generally regarded as psychosis frequently yields a five
factor solution, albeit five factors that are distinct from the five
domains defined by the DSM-5 to encompass psychotic or schizophrenia
spectrum disorders. The five factors are frequently labeled as
hallucinations, delusions, disorganization, excitement, and emotional
distress.
The DSM-5 emphasizes a psychotic spectrum, wherein the low end is
characterized by schizoid personality disorder, and the high end is
characterized by schizophrenia.
Prevention
The evidence for the effectiveness of early interventions to prevent psychosis appeared inconclusive. But psychosis caused by drugs can be prevented.
Whilst early intervention in those with a psychotic episode might
improve short term outcomes, little benefit was seen from these measures
after five years. However, there is evidence that cognitive behavioral therapy (CBT) may reduce the risk of becoming psychotic in those at high risk, and in 2014 the UK National Institute for Health and Care Excellence (NICE) recommended preventive CBT for people at risk of psychosis.
Treatment
The
treatment of psychosis depends on the specific diagnosis (such as
schizophrenia, bipolar disorder or substance intoxication). The
first-line treatment for many psychotic disorders is antipsychotic
medication, which can reduce the positive symptoms of psychosis in about 7 to 14 days.
Medication
The choice of which antipsychotic to use is based on benefits, risks, and costs. It is debatable whether, as a class, typical or atypical antipsychotics are better. Tentative evidence supports that amisulpride, olanzapine, risperidone and clozapine may be more effective for positive symptoms but result in more side effects. Typical antipsychotics have equal drop-out and symptom relapse rates to atypicals when used at low to moderate dosages.
There is a good response in 40–50%, a partial response in 30–40%, and
treatment resistance (failure of symptoms to respond satisfactorily
after six weeks to two or three different antipsychotics) in 20% of
people.
Clozapine is an effective treatment for those who respond poorly to
other drugs ("treatment-resistant" or "refractory" schizophrenia), but it has the potentially serious side effect of agranulocytosis (lowered white blood cell count) in less than 4% of people.
Most people on antipsychotics get side effects. People on typical antipsychotics tend to have a higher rate of extrapyramidal side effects while some atypicals are associated with considerable weight gain, diabetes and risk of metabolic syndrome; this is most pronounced with olanzapine, while risperidone and quetiapine are also associated with weight gain. Risperidone has a similar rate of extrapyramidal symptoms to haloperidol.
Counseling
Psychological treatments such as acceptance and commitment therapy
(ACT) are possibly useful in the treatment of psychosis, helping people
to focus more on what they can do in terms of valued life directions
despite challenging symptomology.
Early intervention
Early intervention in psychosis
is based on the observation that identifying and treating someone in
the early stages of a psychosis can improve their longer term outcome. This approach advocates the use of an intensive multi-disciplinary approach during what is known as the critical period, where intervention is the most effective, and prevents the long term morbidity associated with chronic psychotic illness.
History
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. Ernst von Feuchtersleben is also widely credited as introducing the term in 1845, 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".
In its adjective form "psychotic", references to psychosis can be found in both clinical and non-clinical discussions.
Classification
The word was also used to distinguish a condition considered a disorder of the mind, as opposed to neurosis, which was considered a disorder of the nervous system. The psychoses thus became the modern equivalent of the old notion of madness, and hence there was much debate on whether there was only one (unitary) or many forms of the new disease. One type of broad usage would later be narrowed down by Koch in 1891 to the 'psychopathic inferiorities'—later renamed abnormal personalities by Schneider.
The division of the major psychoses into manic depressive illness (now called bipolar disorder) and dementia praecox (now called schizophrenia) was made by Emil Kraepelin, who attempted to create a synthesis of the various mental disorders identified by 19th century psychiatrists,
by grouping diseases together based on classification of common
symptoms. Kraepelin used the term 'manic depressive insanity' to
describe the whole spectrum of mood disorders, in a far wider sense than it is usually used today.
In Kraepelin's classification this would include 'unipolar' clinical depression, as well as bipolar disorder and other mood disorders such as cyclothymia.
These are characterised by problems with mood control and the psychotic
episodes appear associated with disturbances in mood, and patients
often have periods of normal functioning between psychotic episodes even
without medication. Schizophrenia
is characterized by psychotic episodes that appear unrelated to
disturbances in mood, and most non-medicated patients show signs of
disturbance between psychotic episodes.
Treatment
Early
civilizations considered madness a supernaturally inflicted phenomenon.
Archaeologists have unearthed skulls with clearly visible drillings,
some datable back to 5000 BC suggesting that trepanning was a common treatment for psychosis in ancient times. Written record of supernatural causes and resultant treatments can be traced back to the New Testament. Mark 5:8–13 describes a man displaying what would today be described as psychotic symptoms. Christ cured this "demonic
madness" by casting out the demons and hurling them into a herd of
swine. Exorcism is still utilized in some religious circles as a
treatment for psychosis presumed to be demonic possession.
A research study of out-patients in psychiatric clinics found that 30
percent of religious patients attributed the cause of their psychotic
symptoms to evil spirits. Many of these patients underwent exorcistic
healing rituals that, though largely regarded as positive experiences by
the patients, had no effect on symptomology. Results did, however, show
a significant worsening of psychotic symptoms associated with exclusion
of medical treatment for coercive forms of exorcism.
The medical teachings of the fourth-century philosopher and physician Hippocrates of Cos proposed a natural, rather than supernatural, cause of human illness. In Hippocrates' work, the Hippocratic corpus, a holistic explanation for health and disease was developed to include madness and other "diseases of the mind." Hippocrates writes:
Men ought to know that from the brain, and from the brain only, arise our pleasures, joys, laughter, and jests, as well as our sorrows, pains, griefs and tears. Through it, in particular, we think, see, hear, and distinguish the ugly from the beautiful, the bad from the good, the pleasant from the unpleasant…. It is the same thing which makes us mad or delirious, inspires us with dread and fear, whether by night or by day, brings sleeplessness, inopportune mistakes, aimless anxieties, absentmindedness, and acts that are contrary to habit.
Hippocrates espoused a theory of humoralism wherein disease is resultant of a shifting balance in bodily fluids including blood, phlegm, black bile, and yellow bile. According to humoralism, each fluid or "humour"
has temperamental or behavioral correlates. In the case of psychosis,
symptoms are thought to be caused by an excess of both blood and yellow
bile. Thus, the proposed surgical intervention for psychotic or manic
behavior was bloodletting.
18th century physician, educator, and widely considered "founder
of American psychiatry", Benjamin Rush, also prescribed bloodletting as a
first-line treatment for psychosis. Although not a proponent of
humoralism, Rush believed that active purging and bloodletting were
efficacious corrections for disruptions in the circulatory system, a
complication he believed was the primary cause of "insanity".
Although Rush's treatment modalities are now considered antiquated and
brutish, his contributions to psychiatry, namely the biological
underpinnings of psychiatric phenomenon including psychosis, have been
invaluable to the field. In honor of such contributions, Benjamin
Rush's image is in the official seal of the American Psychiatric Association.
Early 20th century treatments for severe and persisting psychosis
were characterized by an emphasis on shocking the nervous system. Such
therapies include insulin shock therapy, cardiazol shock therapy, and electroconvulsive therapy. Despite considerable risk, shock therapy was considered highly efficacious in the treatment of psychosis including schizophrenia. The acceptance of high-risk treatments led to more invasive medical interventions including psychosurgery.
In 1888, Swiss psychiatrist Gottlieb Burckhardt performed the first medically sanctioned psychosurgery in which the cerebral cortex
was excised. Although some patients showed improvement of symptoms and
became more subdued, one patient died and several developed aphasia or seizure disorders.
Burckhardt would go on to publish his clinical outcomes in a scholarly
paper. This procedure was met with criticism from the medical
community and his academic and surgical endeavors were largely ignored. In the late 1930s, Egas Moniz conceived the leucotomy (AKA prefrontal lobotomy) in which the fibers connecting the frontal lobes
to the rest of the brain were severed. Moniz’s primary inspiration
stemmed from a demonstration by neuroscientists John Fulton and
Carlyle’s 1935 experiment in which two chimpanzees were given
leucotomies and pre and post surgical behavior was compared. Prior to
the leucotomy, the chimps engaged in typical behavior including throwing
feces and fighting. After the procedure, both chimps were pacified and
less violent. During the Q&A, Moniz asked if such a procedure
could be extended to human subjects, a question that Fulton admitted was
quite startling.
Moniz would go on to extend the controversial practice to humans
suffering from various psychotic disorders, an endeavor for which he
received a Nobel Prize in 1949. Between the late 1930s and early 1970s, the leucotomy was a widely accepted practice, often performed in non-sterile environments such as small outpatient clinics and patient homes. Psychosurgery remained standard practice until the discovery of antipsychotic pharmacology in the 1950s.
The first clinical trial of antipsychotics (also commonly known as neuroleptics) for the treatment of psychosis took place in 1952. Chlorpromazine
(brand name: Thorazine) passed clinical trials and became the first
antipsychotic medication approved for the treatment of both acute and
chronic psychosis. Although the mechanism of action was not discovered
until 1963, the administration of chlorpromazine marked the advent of
the dopamine antagonist, or first generation antipsychotic. While clinical trials showed a high response rate for both acute psychosis and disorders with psychotic features, the side-effects were particularly harsh, which included high rates of often irreversible Parkinsonian symptoms such as tardive dyskinesia. With the advent of atypical antipsychotics
(also known as second generation antipsychotics) came a dopamine
antagonist with a comparable response rate but a far different, though
still extensive, side-effect profile that included a lower risk of
Parkinsonian symptoms but a higher risk of cardiovascular disease. Atypical antipsychotics remain the first-line treatment for psychosis associated with various psychiatric and neurological disorders including schizophrenia, bipolar disorder, major depressive disorder, anxiety disorders, dementia, and some autism spectrum disorders.
It is now known that dopamine is the primary neurotransmitter
implicated in psychotic symptomology. Thus, blocking dopamine receptors
(namely, the dopamine D2 receptors) and decreasing dopaminergic
activity continues to be an effective but highly unrefined pharmacologic
goal of antipsychotics. Recent pharmacological research suggests that
the decrease in dopaminergic activity does not eradicate psychotic delusions or hallucinations,
but rather attenuates the reward mechanisms involved in the development
of delusional thinking; that is, connecting or finding meaningful
relationships between unrelated stimuli or ideas. The author of this research paper acknowledges the importance of future investigation:
The model presented here is based on incomplete knowledge related to dopamine, schizophrenia, and antipsychotics—and as such will need to evolve as more is known about these.
— Shitij Kapur, From dopamine to salience to psychosis—linking biology, pharmacology and phenomenology of psychosis
Freud´s former student Wilhelm Reich explored independent insights
into the physical effects of neurotic and traumatic upbringing, and
published his holistic psychoanalytic treatment with a schizophrenic.
With his incorporation of breathwork and insight with the patient, a
young woman, she achieved sufficient self-management skills to end the
therapy.
Society
Psychiatrist David Healy
has criticised pharmaceutical companies for promoting simplified
biological theories of mental illness that seem to imply the primacy of
pharmaceutical treatments while ignoring social and developmental
factors that are known important influences in the aetiology of
psychosis.
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