|Classification and external resources|
|OMIM||603342 608923 603175 192430|
Psychosis (from the Greek ψυχή psyche, "mind/soul", and -ωσις -osis, "abnormal condition or derangement") refers to an abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality". People suffering from psychosis are described as psychotic.
Psychosis (as a sign of a psychiatric disorder) is a diagnosis of exclusion. That is, a new-onset episode of psychosis is not considered a symptom of a psychiatric disorder until other relevant and known causes of psychosis are properly excluded. Medical and biological laboratory tests should exclude central nervous system diseases and injuries, diseases and injuries of other organs, illicit substances, toxins, and prescribed medications as causes of symptoms of psychosis before any psychiatric illness can be diagnosed. In medical training, psychosis as a sign of illness is often compared to fever since both can have multiple causes that are not readily apparent.
- 1 Signs and symptoms
- 2 Psychiatric disorder
- 3 Pathophysiology
- 4 Diagnosis
- 5 Prevention
- 6 Treatment
- 7 History
- 8 References
- 9 Further reading
- 10 External links
Signs and symptoms
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 five 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.
Psychosis may involve delusional beliefs, some of which are paranoid in nature. Put simply, delusions are false beliefs that a person holds on to, without adequate evidence. It may be difficult to change the belief even with evidence to the contrary. Common themes of delusions are persecutory (person believes that others are out to harm him/her), grandiose (person believing that he or she has special powers or skills) etc. Depressed persons may have delusions consistent with their low mood e.g., delusions that they have sinned, or have contracted serious illness etc. 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 may be understood as being influenced by the person's background or current situation (e.g., ethnicity; religious, superstitious, or political beliefs).
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 stays there).
Thought disorder describes an underlying disturbance to conscious thought and is classified largely by its effects on speech and writing. Affected persons show loosening of associations, that is, a disconnection and disorganization of the semantic content of speech and writing. In the severe form speech becomes incomprehensible and it is known as "word salad".
From a diagnostic standpoint, organic disorders were those believed 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). The materialistic view of the mind–body problem holds that mental disorders arise from physical processes; in this view, the distinction between brain and mind, and therefore between organic and functional disease, is an artificial one. 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.
- schizophrenia and schizophreniform disorder
- affective (mood) disorders, including severe 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 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 severe mania and/or severe depression although it is possible to have severe mania and/or severe depression without psychosis as well, in fact that is more commonly the case
- post-traumatic stress disorder
- induced delusional disorder
- Sometimes in obsessive-compulsive 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.
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
- Sensory deprivation and sensory impairment
- caffeine intoxication
- extremely stressful event
Subtypes of psychosis include:
- Menstrual psychosis, including circa-mensual (approximately monthly) periodicity, in rhythm with the menstrual cycle.
- Postpartum psychosis, occurring recently after childbirth
- Monothematic delusions
- Myxedematous psychosis
- Occupational psychosis
- Stimulant psychosis
- Tardive psychosis
- Shared psychosis
- Cycloid psychosis
Cycloid psychosis is psychosis that progresses from normal to full-blown usually within a few hours, not related to drug intake or brain injury. In addition, diagnostic criteria include at least four of the following symptoms:
- Mood-incongruent delusions
- 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 disorders
Cycloid psychosis occurs in people of generally 15–50 years of age.
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, or drugs used to treat cancer)
- infectious and postinfectious syndromes, including infections causing delirium, viral encephalitis, HIV, malaria, Lyme disease, syphilis
- endocrine disease, such as hypothyroidism, hyperthyroidism, adrenal failure, Cushing's syndrome, hypoparathyroidism and hyperparathyroidism; sex hormones also affect psychotic symptoms and sometimes childbirth can provoke psychosis, termed puerperal 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, and anti-NMDA-receptor encephalitis
- poisoning, by therapeutic drugs (see below), recreational drugs (see below), and a range of plants, fungi, metals, organic compounds, and a few animal toxins
- some sleep disorders, including hallucinations in narcolepsy (in which REM sleep intrudes into wakefulness)
Various psychoactive substances (both legal and illegal) have been implicated in causing, exacerbating, and/or precipitating psychotic states and/or disorders in users. 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 that can induce psychotic symptoms include 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).
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.
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 by itself has a tendency to induce psychotic symptoms in a small minority of users, CBD tends to reduce them, particularly in people who are at risk for or who already exhibit psychosis. However, cannabis used to attain a "high" is typically very low in CBD content, but conversely very high in THC content. Since black market cannabis contains much more THC than cannabidiol, CBD's protective effect may not be present, while THC's potentially detrimental effect can remain. Conversely, some strains of medical cannabis are grown with a very high CBD to THC ratio, but these are rarely available on the black market, creating a public need for access to this subset of medical cannabis in many patients. Importantly, 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. According to a study from the Institute of Psychiatry at King's College London, daily, high-potency cannabis use indeed tends to accelerate the onset of psychosis in predisposed patients.
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. Violence is common during a methamphetamine psychosis.
Administration, or sometimes withdrawal, of a large number of medications may provoke psychotic symptoms. Drugs that can induce psychosis experimentally and/or in a significant proportion of patients include amphetamine and other sympathomimetics, dopamine agonists, ketamine, corticosteroids (often with mood changes in addition), and some anticonvulsants such as vigabatrin.
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).
The purpose of the brain is to collect information from the body (pain, hunger, etc.), and from the outside world, interpret it to a coherent world view, and produce a meaningful response. The information from the senses enter the brain in the primary sensory areas. They process the information and send it to the secondary areas where the information is interpreted. Spontaneous activity in the primary sensory areas may produce hallucinations, which the secondary areas misinterpret as information from the real world.
For example, a PET or fMRI scan of a person who claims he hears voices may show activation in the primary auditory cortex, or parts of the brain involved in the perception and understanding of speech.
Tertiary brain cortex collects the interpretations from the secondary cortexes and creates a coherent world view of it. A study investigating structural changes in the brains of people with psychosis showed there was significant grey matter reduction in the right medial temporal, lateral temporal, and inferior frontal gyrus, and in the cingulate cortex bilaterally of people before and after they became psychotic. Findings such as these have led to debate about whether psychosis itself causes excitotoxic brain damage and whether potentially damaging changes to the brain are related to the length of psychotic episode. Recent research has suggested that this is not the case although further investigation is still ongoing.
Studies with sensory deprivation have shown that the brain is dependent on signals from the outer world to function properly. If the spontaneous activity in the brain is not counterbalanced with information from the senses, loss from reality and psychosis may occur after some hours. A similar phenomenon is paranoia in the elderly, when poor eyesight, hearing and memory make the person abnormally suspicious of the environment.
On the other hand, loss from reality may also occur if the spontaneous cortical activity is increased so that it is no longer counterbalanced with information from the senses. The 5-HT2A receptor seems to be important for this, since psychedelic drugs that activate them produce hallucinations.
However, the main feature of psychosis is not hallucinations, but the inability to distinguish between internal and external stimuli. Close relatives to psychotic patients may hear voices, but since they are aware that they are unreal they can ignore them, so that the hallucinations do not affect their reality perception. Hence they are not considered psychotic.
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 boost dopamine activity (such as amphetamines and cocaine) can trigger psychosis in some people (see amphetamine psychosis). However, increasing evidence in recent times has pointed to a possible dysfunction of the excitory neurotransmitter glutamate, in particular, with the activity of the NMDA receptor.
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 more readily than dopaminergic stimulants, even at "normal" recreational doses. The symptoms of dissociative intoxication are also considered to mirror the symptoms of schizophrenia, including negative psychotic symptoms, more closely than amphetamine psychosis. Dissociative induced psychosis happens on a more reliable and predictable basis than amphetamine psychosis, which usually only occurs in cases of overdose, prolonged use or with sleep deprivation, which can independently produce psychosis. New antipsychotic drugs that act on glutamate and its receptors are currently undergoing clinical trials.
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.
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.
Some theories believe many psychotic symptoms are a problem with the perception of ownership of internally generated thoughts and experiences. For example, the hallucination of hearing voices may arise from internally generated speech that is mislabeled by the psychotic person as coming from an external source.
It has been suggested that persons with bipolar disorder may have increased activity of the left hemisphere compared to the right hemisphere of the brain, while persons with schizophrenia have increased activity in the right hemisphere.
Increased level of right hemisphere activation has also been found in people who have high levels of paranormal beliefs and in people who report mystical experiences. It also seems that people who are more creative are also more likely to show a similar pattern of brain activation. Some researchers have been quick to point out that this in no way suggests that paranormal, mystical or creative experiences are in any way by themselves a symptom of mental illness, as it is still not clear what makes some such experiences beneficial and others distressing.
In otherwise normal individuals, exogenous ligands can produce psychotic symptoms. NMDA receptor antagonists, such as ketamine, can produce a similar psychosis to that experienced in schizophrenia.
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.
Psychosis is first and foremost a diagnosis of exclusion. So a new-onset episode of psychosis cannot be considered a symptom of a psychiatric disorder until other relevant and known causes of psychosis are properly excluded, or ruled out. Many clinicians improperly perform, or entirely miss this step, introducing avoidable diagnostic error and misdiagnosis.
An initial assessment includes a comprehensive history and physical examination by a physician, psychiatrist, psychiatric nurse practitioner or psychiatric physician assistant. Biological tests should be performed to exclude psychosis associated with or caused by substance use, medication, toxins, surgical complications, or other medical illnesses.
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 psychiatric medications, such as antidepressants, ADHD stimulant medications, and sleep 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 a
- Urinalysis and a
- Full serum 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 evidence for the effectiveness of early interventions to prevent psychosis appeared inconclusive. 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 more recently there has been some evidence that cognitive behavioral therapy (CBT) may reduce the risk of becoming psychotic in those at high risk.
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 (oral or intramuscular injection), and sometimes hospitalization is needed. However, there are significant problems associated with this class of drugs. There is evidence that they can cause brain damage including prefrontal cortex atrophy, long-lasting parkinsonian symtoms (tardive dyskinesia), and personality change. Nancy Andreasen has argued for an association between antipsychotic drugs and smaller grey matter volumes independent of illness severity. Furthermore, antipsychotic drugs can themselves induce psychotic symptoms if they are administered for a long time and then discontinued.
There is growing evidence that cognitive behavior therapy, acceptance and commitment therapy and family therapy can be effective in managing psychotic symptoms. When other treatments for psychosis are ineffective, electroconvulsive therapy or ECT (also known as shock treatment) is sometimes applied to relieve the underlying symptoms of psychosis due to depression. There is also increasing research suggesting that animal-assisted therapy can contribute to the improvement in general well-being of people with schizophrenia.
Many doctors are realizing that a deficiency in B-12 can be a cause of psychosis especially in people with no mental history.
Early intervention in psychosis is 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.
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 the Greek ψύχωσις (psychosis), "a giving soul or life to, animating, quickening" and that from ψυχή (psyche), "soul" and the suffix -ωσις (-osis), in this case "abnormal condition".
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.
During the 1960s and 1970s, psychosis was of particular interest to counterculture critics of mainstream psychiatric practice, who argued that it may simply be another way of constructing reality and is not necessarily a sign of illness. For example, R. D. Laing argued that psychosis is a symbolic way of expressing concerns in situations where such views may be unwelcome or uncomfortable to the recipients. He went on to say that psychosis could be also seen as a transcendental experience with healing and spiritual aspects.
Arthur J. Deikman suggested use of the term "mystical psychosis" to characterize first-person accounts of psychotic experiences that are similar to reports of mystical experiences. Thomas Szasz focused on the social implications of labeling people as psychotics, a label he argues unjustly medicalises different views of reality so such unorthodox people can be controlled by society. Psychoanalysis has a detailed account of psychosis that differs markedly from that of psychiatry. Freud and Lacan outlined their perspective on the structure of psychosis in a number of works.
Since the 1970s, the introduction of a recovery approach to mental health, which has been driven mainly by people who have experienced psychosis (or whatever name is used to describe their experiences), has led to a greater awareness that mental illness is not a lifelong disability, and that there is an expectation that recovery is possible, and probable with effective support.
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, although largely antiquated, 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 per cent 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 of Cos, the Hippocratic corpus
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 and/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
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- James Tilly Matthews
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- psychosis-bipolar.com - For persons afflicted, relatives and professionals: information, trialog, interactive therapy portal
- Understanding psychotic experiences from mental health charity Mind