Genotype

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https://en.wikipedia.org/wiki/Genotype

 

The genotype of an organism is its complete set of genetic material. Genotype can also be used to refer to the alleles or variants an individual carries in a particular gene or genetic location. The number of alleles an individual can have in a specific gene depends on the number of copies of each chromosome found in that species, also referred to as ploidy. In diploid species like humans, two full sets of chromosomes are present, meaning each individual has two alleles for any given gene. If both alleles are the same, the genotype is referred to as homozygous. If the alleles are different, the genotype is referred to as heterozygous.

Genotype contributes to phenotype, the observable traits and characteristics in an individual or organism. The degree to which genotype affects phenotype depends on the trait. For example, the petal color in a pea plant is exclusively determined by genotype. The petals can be purple or white depending on the alleles present in the pea plant. However, other traits are only partially influenced by genotype. These traits are often called complex traits because they are influenced by additional factors, such as environmental and epigenetic factors. Not all individuals with the same genotype look or act the same way because appearance and behavior are modified by environmental and growing conditions. Likewise, not all organisms that look alike necessarily have the same genotype.

The term genotype was coined by the Danish botanist Wilhelm Johannsen in 1903.

Phenotype

Main article: Phenotype

Any given gene will usually cause an observable change in an organism, known as the phenotype. The terms genotype and phenotype are distinct for at least two reasons:

• To distinguish the source of an observer's knowledge (one can know about genotype by observing DNA; one can know about phenotype by observing outward appearance of an organism).
• Genotype and phenotype are not always directly correlated. Some genes only express a given phenotype in certain environmental conditions. Conversely, some phenotypes could be the result of multiple genotypes. The genotype is commonly mixed up with the phenotype which describes the result of both the genetic and the environmental factors giving the observed expression (e.g. blue eyes, hair color, or various hereditary diseases).

A simple example to illustrate genotype as distinct from phenotype is the flower colour in pea plants (see Gregor Mendel). There are three available genotypes, PP (homozygous dominant), Pp (heterozygous), and pp (homozygous recessive). All three have different genotypes but the first two have the same phenotype (purple) as distinct from the third (white).

A more technical example to illustrate genotype is the single-nucleotide polymorphism or SNP. A SNP occurs when corresponding sequences of DNA from different individuals differ at one DNA base, for example where the sequence AAGCCTA changes to AAGCTTA. This contains two alleles : C and T. SNPs typically have three genotypes, denoted generically AA Aa and aa. In the example above, the three genotypes would be CC, CT and TT. Other types of genetic marker, such as microsatellites, can have more than two alleles, and thus many different genotypes.

Penetrance is the proportion of individuals showing a specified genotype in their phenotype under a given set of environmental conditions.

Mendelian inheritance

Main article: Mendelian inheritance

Here the relation between genotype and phenotype is illustrated, using a Punnett square, for the character of petal colour in a pea plant. The letters B and b represent alleles for colour and the pictures show the resultant flowers. The diagram shows the cross between two heterozygous parents where B represents the dominant allele (purple) and b represents the recessive allele (white).

Traits that are determined exclusively by genotype are typically inherited in a Mendelian pattern. These laws of inheritance were described extensively by Gregor Mendel, who performed experiments with pea plants to determine how traits were passed on from generation to generation. He studied phenotypes that were easily observed, such as plant height, petal color, or seed shape. He was able to observe that if he crossed two true-breeding plants with distinct phenotypes, all the offspring would have the same phenotype. For example, when he crossed a tall plant with a short plant, all the resulting plants would be tall. However, when he self-fertilized the plants that resulted, about 1/4 of the second generation would be short. He concluded that some traits were dominant, such as tall height, and others were recessive, like short height. Though Mendel was not aware at the time, each phenotype he studied was controlled by a single gene with two alleles. In the case of plant height, one allele caused the plants to be tall, and the other caused plants to be short. When the tall allele was present, the plant would be tall, even if the plant was heterozygous. In order for the plant to be short, it had to be homozygous for the recessive allele.

One way this can be illustrated is using a Punnett square. In a Punnett square, the genotypes of the parents are placed on the outside. An uppercase letter is typically used to represent the dominant allele, and a lowercase letter is used to represent the recessive allele. The possible genotypes of the offspring can then be determined by combining the parent genotypes. In the example on the right, both parents are heterozygous, with a genotype of Bb. The offspring can inherit a dominant allele from each parent, making them homozygous with a genotype of BB. The offspring can inherit a dominant allele from one parent and a recessive allele from the other parent, making them heterozygous with a genotype of Bb. Finally, the offspring could inherit a recessive allele from each parent, making them homozygous with a genotype of bb. Plants with the BB and Bb genotypes will look the same, since the B allele is dominant. The plant with the bb genotype will have the recessive trait.

These inheritance patterns can also be applied to hereditary diseases or conditions in humans or animals. Some conditions are inherited in an autosomal dominant pattern, meaning individuals with the condition typically have an affected parent as well. A classic pedigree for an autosomal dominant condition shows affected individuals in every generation.

An example of a pedigree for an autosomal dominant condition

Other conditions are inherited in an autosomal recessive pattern, where affected individuals do not typically have an affected parent. Since each parent must have a copy of the recessive allele in order to have an affected offspring, the parents are referred to as carriers of the condition. In autosomal conditions, the sex of the offspring does not play a role in their risk of being affected. In sex-linked conditions, the sex of the offspring affects their chances of having the condition. In humans, females inherit two X chromosomes, one from each parent, while males inherit an X chromosome from their mother and a Y chromosome from their father. X-linked dominant conditions can be distinguished from autosomal dominant conditions in pedigrees by the lack of transmission from fathers to sons, since affected fathers only pass their X chromosome to their daughters. In X-linked recessive conditions, males are typically affected more commonly because they are hemizygous, with only one X chromosome. In females, the presence of a second X chromosome will prevent the condition from appearing. Females are therefore carriers of the condition and can pass the trait on to their sons.

An example of a pedigree for an autosomal recessive condition

Mendelian patterns of inheritance can be complicated by additional factors. Some diseases show incomplete penetrance, meaning not all individuals with the disease-causing allele develop signs or symptoms of the disease. Penetrance can also be age-dependent, meaning signs or symptoms of disease are not visible until later in life. For example, Huntington disease is an autosomal dominant condition, but up to 25% of individuals with the affected genotype will not develop symptoms until after age 50. Another factor that can complicate Mendelian inheritance patterns is variable expressivity, in which individuals with the same genotype show different signs or symptoms of disease. For example, individuals with polydactyly can have a variable number of extra digits.

Non-Mendelian inheritance

Main article: Non-Mendelian inheritance

Many traits are not inherited in a Mendelian fashion, but have more complex patterns of inheritance.

Incomplete dominance

For some traits, neither allele is completely dominant. Heterozygotes often have an appearance somewhere in between those of homozygotes. For example, a cross between true-breeding red and white Mirabilis jalapa results in pink flowers.

Codominance

Codominance refers to traits in which both alleles are expressed in the offspring in approximately equal amounts. A classic example is the ABO blood group system in humans, where both the A and B alleles are expressed when they are present. Individuals with the AB genotype have both A and B proteins expressed on their red blood cells.

Epistasis

Main article: Epistasis

Epistasis is when the phenotype of one gene is affected by one or more other genes. This is often through some sort of masking effect of one gene on the other. For example, the "A" gene codes for hair color, a dominant "A" allele codes for brown hair, and a recessive "a" allele codes for blonde hair, but a separate "B" gene controls hair growth, and a recessive "b" allele causes baldness. If the individual has the BB or Bb genotype, then they produce hair and the hair color phenotype can be observed, but if the individual has a bb genotype, then the person is bald which masks the A gene entirely.

Polygenic traits

Main article: Polygene

A polygenic trait is one whose phenotype is dependent on the additive effects of multiple genes. The contributions of each of these genes are typically small and add up to a final phenotype with a large amount of variation. A well studied example of this is the number of sensory bristles on a fly. These types of additive effects is also the explanation for the amount of variation in human eye color.

Genotyping

Main article: Genotyping

Genotyping refers to the method used to determine an individual's genotype. There are a variety of techniques that can be used to assess genotype. The genotyping method typically depends on what information is being sought. Many techniques initially require amplification of the DNA sample, which is commonly done using PCR.

Some techniques are designed to investigate specific SNPs or alleles in a particular gene or set of genes, such as whether an individual is a carrier for a particular condition. This can be done via a variety of techniques, including allele specific oligonucleotide (ASO) probes or DNA sequencing. Tools such as multiplex ligation-dependent probe amplification can also be used to look for duplications or deletions of genes or gene sections. Other techniques are meant to assess a large number of SNPs across the genome, such as SNP arrays. This type of technology is commonly used for genome-wide association studies.

Large-scale techniques to assess the entire genome are also available. This includes karyotyping to determine the number of chromosomes an individual has and chromosomal microarrays to assess for large duplications or deletions in the chromosome. More detailed information can be determined using exome sequencing, which provides the specific sequence of all DNA in the coding region of the genome, or whole genome sequencing, which sequences the entire genome including non-coding regions.

Genotype encoding

In linear models, the genotypes can be encoded in different manners. Let us consider a biallelic locus with two possible alleles, encoded by $A$ and ${\displaystyle a}$. We consider ${\displaystyle A}$ to correspond to the dominant allele to the reference allele $a$. The following table details the different encoding.

Genotype	$AA$	$Aa$	$aa$
Additive encoding	0	1	2
Dominant encoding	1	1	0
Recessive encoding	0	0	1
Codominant encoding	0,0	0,1	1,0

Phenotype

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Phenotype

The shells of individuals within the bivalve mollusk species Donax variabilis show diverse coloration and patterning in their phenotypes.

Here the relation between genotype and phenotype is illustrated, using a Punnett square, for the character of petal color in pea plants. The letters B and b represent genes for color, and the pictures show the resultant phenotypes. This shows how multiple genotypes (BB and Bb) may yield the same phenotype (purple petals).

In genetics, the phenotype (from Ancient Greek φαίνω (phaínō) 'to appear, show' and τύπος (túpos) 'mark, type') is the set of observable characteristics or traits of an organism. The term covers all traits of an organism other than its genome, however transitory: the organism's morphology (physical form and structure), its developmental processes, its biochemical and physiological properties whether reversible or irreversible, and all its behavior, from a peacock's display to the phone number you half remember. An organism's phenotype results from two basic factors: the expression of an organism's genetic code (its genotype) and the same organism's interactions with its environment. Each of these factors may influence the other in ways that impact the phenotypes of the organism in question. When two or more clearly different phenotypes exist in the same population of a species, the species is called polymorphic. A well-documented example of polymorphism is Labrador Retriever coloring; while the coat color depends on many genes, it is clearly seen in the environment as yellow, black, and brown. Richard Dawkins in 1978 and again in his 1982 book The Extended Phenotype suggested that one can regard bird nests and other built structures such as caddisfly larva cases and beaver dams as "extended phenotypes".

Wilhelm Johannsen proposed the genotype–phenotype distinction in 1911 to make clear the difference between an organism's hereditary material and 'all the typical phenomena of the organic world', the description of which, with regard 'to forms, structures, sizes, colors and other characters of the living organisms has been the chief aim of natural history'. The distinction somewhat resembles that proposed by August Weismann (1834–1914), who distinguished between germ plasm (heredity) and somatic cells (the body). More recently in The Selfish Gene (1976), Dawkins redescribed these concepts as replicators and vehicles.

Definition

"Phenome" redirects here. For the speech unit, see Phoneme.

Despite its seemingly straightforward definition, the concept of the phenotype has hidden subtleties. It may seem that anything dependent on the genotype is a phenotype, including molecules such as RNA and proteins. Most molecules and structures coded by the genetic material are not visible in the appearance of an organism, yet they are observable (for example by Western blotting) and are thus part of the phenotype; human blood groups are an example. It may seem that this goes beyond the original intentions of the concept with its focus on the (living) organism in itself. Either way, the term phenotype includes inherent traits or characteristics that are observable or traits that can be made visible by some technical procedure.

ABO blood groups determined through a Punnett square and displaying phenotypes and genotypes

The term "phenotype" has sometimes been incorrectly used as a shorthand for the phenotypic difference between a mutant and its wild type, which would lead to the false statement that a "mutation has no phenotype".

Behaviors and their consequences are also phenotypes, since behaviors are observable characteristics. Behavioral phenotypes include cognitive, personality, and behavioral patterns. Some behavioral phenotypes may characterize psychiatric disorders or syndromes.

A phenome is the set of all traits expressed by a cell, tissue, organ, organism, or species. The term was first used by Davis in 1949, "We here propose the name phenome for the sum total of extragenic, non-autoreproductive portions of the cell, whether cytoplasmic or nuclear. The phenome would be the material basis of the phenotype, just as the genome is the material basis of the genotype." Although phenome has been in use for many years, the distinction between the use of phenome and phenotype is problematic. A proposed definition for both terms as the "physical totality of all traits of an organism or of one of its subsystems" was put forth by Mahner and Kary in 1997, who argue that although scientists tend to intuitively use these and related terms in a manner that does not impede research, the terms are not well defined and usage of the terms is not consistent.

Some usages of the term suggest that the phenome of a given organism is best understood as a kind of matrix of data representing physical manifestation of phenotype. For example, discussions led by A. Varki among those who had used the term up to 2003 suggested the following definition: "The body of information describing an organism's phenotypes, under the influences of genetic and environmental factors". Another team of researchers characterize "the human phenome [as] a multidimensional search space with several neurobiological levels, spanning the proteome, cellular systems (e.g., signaling pathways), neural systems and cognitive and behavioural phenotypes." Plant biologists have begun to explore the phenome in the study of plant physiology. In 2009, a research team demonstrated the feasibility of identifying genotype–phenotype associations using electronic health records (EHRs) linked to DNA biobanks. They called this method phenome-wide association study (PheWAS).

Exploring relationships among phenotype, genotype and environment at different levels

Inspired by the evolution from genotype to genome to pan-genome, a concept of eventually exploring the relationship among pan-phenome, pan-genome, and pan-envirome was proposed in 2023.

Biston betularia morpha typica, the standard light-colored peppered moth

B.betularia morpha carbonaria, the melanic form, illustrating discontinuous variation

Phenotypic variation

See also: Ecophenotypic variation

Phenotypic variation is a fundamental prerequisite for evolution by natural selection. Not all phenotypic variation is caused by underlying heritable genetic variation. This is because the organization of living things is 'plastic', as Darwin emphasized, or 'readily capable of change.' It is the living organism as a whole that interacts with the environment and so contributes (or not) to the next generation. Thus, natural selection affects the genetic structure of a population indirectly via the contribution of phenotypes. Without phenotypic variation, there would be no evolution by natural selection.

The interaction between genotype and phenotype has often been conceptualized without reference to living organisms, as in the following relationship:

genotype (G) + environment (E) → phenotype (P)

But a genotype can only be affected by or affect the environment insofar as it is embodied in a living organism. Hence, a more nuanced version of the relationship is:

genotype (G) + organism & environment interactions (OE) → phenotype (P)

Phenotypes often show much flexibility or phenotypic plasticity in the expression of genotypes; in many organisms the phenotypes which 'express' a given genotype are very different under varying environmental conditions. The plant Hieracium umbellatum is found growing in two different habitats in Sweden. One habitat is rocky, sea-side cliffs, where the plants develop to be bushy with broad leaves and expanded inflorescences; the other is among sand dunes where the plants develop to lie prostrate with narrow leaves and compact inflorescences. The habitats alternate along the coast of Sweden and the habitat that seeds containing the identical genotype of Hieracium umbellatum land in, determines the phenotype which develops.

An example of random variation in Drosophila flies is the number of ommatidia, which may vary (randomly) between left and right eyes in a single individual as much as they do between different genotypes overall, or between clones raised in different environments.

The concept of phenotype can be extended to variations below the level of the gene which affect an organism's fitness. For example, silent mutations that do not change the corresponding amino acid sequence of a gene may change the frequency of guanine-cytosine base pairs (GC content). The base pairs have a higher thermal stability (melting point) than adenine-thymine, a property that might convey, among organisms living in high-temperature environments, a selective advantage on variants enriched in GC content.

The extended phenotype

Main article: The Extended Phenotype

Richard Dawkins described a phenotype that included all effects that a gene has on its surroundings, including other organisms, as an extended phenotype, arguing that "An animal's behavior tends to maximize the survival of the genes 'for' that behavior, whether or not those genes happen to be in the body of the particular animal performing it." For instance, an organism such as a beaver modifies its environment by building a beaver dam; this can be considered an expression of its genes, just as its incisor teeth are—which it uses to modify its environment. Similarly, when a bird feeds a brood parasite such as a cuckoo, it is unwittingly extending its phenotype; and when genes in an orchid affect orchid bee behavior to increase pollination, or when genes in a peacock affect the copulatory decisions of peahens, again, the phenotype is being extended. Genes are, in Dawkins's view, selected by their phenotypic effects.

Other biologists broadly agree that the extended phenotype concept is relevant, but consider that its role is largely explanatory, rather than assisting in the design of experimental tests.

Genes and phenotypes

An organism's phenotype is determined by the sum of its genetic material along with the influence of its environment. This is mediated by a range of biological mechanisms: either the direct activities of gene products or their downstream effects.

Phenotypes develop through an interaction of genes and their immediate cellular environment, the cellular environment being under the influence of the host-organism's interaction with its environment. Thus there is a multiplicity of ways that genes and phenotypes interact. Most simply, for example, we might say an albino phenotype develops as a consequence of a mutation in the gene encoding tyrosinase which is a key enzyme in melanin formation. Even here, however, exposure to UV radiation can increase melanin production, hence the environment plays a role in this phenotype as well. For most complex phenotypes the precise genetic mechanism remains unknown.

Gene expression plays a crucial role in determining the phenotypes of organisms. The level of gene expression can affect the phenotype of an organism. For example, if a gene that codes for a particular enzyme is expressed at high levels, the organism may produce more of that enzyme and exhibit a particular trait as a result. On the other hand, if the gene is expressed at low levels, the organism may produce less of the enzyme and exhibit a different trait. Gene expression is regulated at various levels and thus each level can affect certain phenotypes, including transcriptional and post-transcriptional regulation.

The patchy colors of a tortoiseshell cat are the result of different levels of expression of pigmentation genes in different areas of the skin.

Changes in the levels of gene expression can be influenced by a variety of factors, such as environmental conditions, genetic variations, and epigenetic modifications. These modifications can be influenced by environmental factors such as diet, stress, and exposure to toxins, and can have a significant impact on an individual's phenotype. Some phenotypes may be the result of changes in gene expression due to these factors, rather than changes in genotype. An experiment involving machine learning methods utilizing gene expressions measured from RNA sequencing found that they can contain enough signal to separate individuals in the context of phenotype prediction.

Phenome and phenomics

Not to be confused with Phoneme or Phonology.

Although a phenotype is the ensemble of observable characteristics displayed by an organism, the word phenome is sometimes used to refer to a collection of traits, while the simultaneous study of such a collection is referred to as phenomics. Phenomics is an important field of study because it can be used to figure out which genomic variants affect phenotypes which then can be used to explain things like health, disease, and evolutionary fitness. Phenomics forms a large part of the Human Genome Project.

Phenomics has applications in agriculture. For instance, genomic variations such as drought and heat resistance can be identified through phenomics to create more durable GMOs. Phenomics may be a stepping stone towards personalized medicine, particularly drug therapy. Once the phenomic database has acquired enough data, a person's phenomic information can be used to select specific drugs tailored to the individual.

Large-scale phenotyping and genetic screens

See also: Genetic screen and Essential gene

Large-scale genetic screens can identify the genes or mutations that affect the phenotype of an organism. Analyzing the phenotypes of mutant genes can also aid in determining gene function. Most genetic screens have used microorganisms, in which genes can be easily deleted. For instance, nearly all genes have been deleted in E. coli and many other bacteria, but also in several eukaryotic model organisms such as baker's yeast and fission yeast. Among other discoveries, such studies have revealed lists of essential genes.

More recently, large-scale phenotypic screens have also been used in animals, e.g. to study lesser understood phenotypes such as behavior. In one screen, the role of mutations in mice were studied in areas including learning and memory, circadian rhythmicity, vision, responses to stress, and response to psychostimulants.

Large-scale mutagenesis and phenotypic screens for the nervous system and behavior in mice

Phenotypic domain	Assay	Notes	Software package
Circadian Rhythm	Wheel running behavior		ClockLab
Learning and Memory	Fear conditioning	Video-image-based scoring of freezing	FreezeFrame
Preliminary Assessment	Open field activity and elevated plus maze	Video-image-based scoring of exploration	LimeLight
Psychostimulant response	Hyperlocomotion behavior	Video-image-based tracking of locomotion	BigBrother
Vision	Electroretinogram and Fundus photography		L. Pinto and colleagues

This experiment involves the progeny of mice treated with ENU, or N-ethyl-N-nitrosourea, which is a potent mutagen that causes point mutations. The mice were phenotypically screened for alterations in the different behavioral domains in order to find the number of putative mutants (see table for details). Putative mutants are then tested for heritability in order to help determine the inheritance pattern as well as map out the mutations. Once they have been mapped out, cloned, and identified, it can be determined whether a mutation represents a new gene or not.

Phenotypic domain	ENU progeny screened	Putative mutants	Putative mutant lines with progeny	Confirmed mutants
General assessment	29860	80	38	14
Learning and memory	23123	165	106	19
Psychostimulant response	20997	168	86	9
Neuroendocrine response to stress	13118	126	54	2
Vision	15582	108	60	6

These experiments show that mutations in the rhodopsin gene affected vision and can even cause retinal degeneration in mice. The same amino acid change causes human familial blindness, showing how phenotyping in animals can inform medical diagnostics and possibly therapy.

Evolutionary origin of phenotype

The RNA world is the hypothesized pre-cellular stage in the evolutionary history of life on earth, in which self-replicating RNA molecules proliferated prior to the evolution of DNA and proteins. The folded three-dimensional physical structure of the first RNA molecule that possessed ribozyme activity promoting replication while avoiding destruction would have been the first phenotype, and the nucleotide sequence of the first self-replicating RNA molecule would have been the original genotype.

Substance-induced psychosis

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From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Substance-induced_psychosis

Substance-induced psychosis
Other names	Substance-induced psychotic disorder, drug-induced psychosis, substance/medication-induced psychotic disorder, toxic psychosis
Specialty	Psychiatry, addiction psychiatry

Substance-induced psychosis (commonly known as toxic psychosis or drug-induced psychosis) is a form of psychosis that is attributed to substance intoxication, withdrawal or recent consumption of psychoactive drugs. It is a psychosis that results from the effects of various substances, such as medicinal and nonmedicinal substances, legal and illegal drugs, chemicals, and plants. Various psychoactive substances have been implicated in causing or worsening psychosis in users.

Signs and symptoms

Main article: Psychosis

Psychosis manifests as disorientation, visual hallucinations and/or haptic hallucinations. It is a state in which a person's mental capacity to recognize reality, communicate, and relate to others is impaired, thus interfering with the capacity to deal with life's demands. While there are many types of psychosis, the cause of substance-induced psychosis can be pinpointed to intake of specific chemicals. To properly diagnose Substance-Induced Psychotic Disorder, one must conclude that exhibited hallucinations or delusions began during intoxication, withdrawal, or within a month after use of the substance and the symptoms are not related to a non-substance-induced psychotic disorder.

Treatment

Because substance-induced psychosis results from the consumption of a substance or combination of substances, treatment practices heavily rely on detoxification and discontinuation of the substance(s). Detox and addiction treatment centers may often provide rehabilitation programs, including inpatient and outpatient treatment options, support groups, and extended treatment plans. Substance-induced psychosis may persist for hours, days, or weeks, but typically resolves within a month of sobriety. Treating psychosis involves a very thorough evaluation, including medical history, family background, symptoms, and other potential causes. Treatment prioritizes emergent symptoms, evaluates for underlying mental illnesses, and focuses on behavioral and preventative measures against substance use.

Substance use and schizophrenia

Rates of drug use amongst people with schizophrenia are higher than the general population; 50% of those diagnosed with schizophrenia use substances over their life. There is a model that suggests this arises because those with schizophrenia self-medicate with psychoactive drugs.

Transition to schizophrenia

A 2019 systematic review and meta-analysis found that 25% (18–38%) of people diagnosed with substance-induced psychosis went on to be diagnosed with schizophrenia, compared with 36% (30–43%) for brief, atypical and not otherwise specified psychoses. The substance present was the primary predictor of transition from drug-induced psychosis to schizophrenia, with highest rates associated with cannabis (34% (25–46%)), hallucinogens (26% (14–43%)) and amphetamines (22% (14–34%)). Lower rates were reported for opioid– (12% (8–18%)), alcohol– (9% (6–15%)) and sedative– (10% (7–15%)) induced psychoses. Transition rates were slightly lower in older cohorts but were not affected by sex, country of the study, hospital or community location, urban or rural setting, diagnostic methods, or duration of follow-up.

Class of substance	Number of studies	Rates of transition to schizophrenia
		Estimate	Lower bound	Upper bound
Brief, atypical and NOS	34	36%	30%	43%
Combined	-	25%	18%	38%
Cannabis	6	34%	25%	46%
Hallucinogens	3	26%	14%	43%
Amphetamines	5	22%	14%	34%
Opioid	3	12%	8%	18%
Sedative	3	10%	7%	15%
Alcohol	9	9%	6%	15%

Substances

Psychotic states may occur after using a variety of legal and illegal substances. Substances whose use or withdrawal is implicated in psychosis include the following:

International Classification of Diseases

Psychoactive substance-induced psychotic disorders outlined within the ICD-10 codes F10.5—F19.5:

• F10.5 alcohol:  Alcohol is a common cause of psychotic disorders or episodes, which may occur through acute intoxication, chronic alcoholism, withdrawal, exacerbation of existing disorders, or acute idiosyncratic reactions. Research has shown that excessive alcohol use causes an 8-fold increased risk of psychotic disorders in men and a 3 fold increased risk of psychotic disorders in women. While the vast majority of cases are acute and resolve fairly quickly upon treatment and/or abstinence, they can occasionally become chronic and persistent. Alcoholic psychosis is sometimes misdiagnosed as another mental illness such as schizophrenia.
• F11.5 opioid: Studies show stronger opioids such as fentanyl are more likely to cause psychosis and hallucinations.
• F12.5 cannabinoid: Some studies indicate that cannabis may trigger full-blown psychosis. Recent studies have found an increase in risk for psychosis in cannabis users.
• F13.5 sedatives/hypnotics (barbiturates; benzodiazepines): It is also important to this topic to understand the paradoxical effects of some sedative drugs. Serious complications can occur in conjunction with the use of sedatives creating the opposite effect as to that intended. Malcolm Lader at the Institute of Psychiatry in London estimates the incidence of these adverse reactions at about 5%, even in short-term use of the drugs. The paradoxical reactions may consist of depression, with or without suicidal tendencies, phobias, aggressiveness, violent behavior and symptoms sometimes misdiagnosed as psychosis. However, psychosis is more commonly related to the benzodiazepine withdrawal syndrome.
• F14.5 cocaine
• F15.5 other stimulants: amphetamines, methamphetamine, and methylphenidate, among others (see also Stimulant psychosis).
• F16.5 hallucinogens (LSD and others)
• F18.5 volatile solvents (volatile inhalants);
  • Toluene, found in glue, paint, thinner, etc. (see also Toluene toxicity).
  • Butane
  • Gasoline (petrol)

F17.5 is reserved for tobacco-induced psychosis, but is traditionally not associated with the induction of psychosis.

The code F15.5 also includes caffeine-induced psychosis, despite not being specifically listed in the DSM-IV. However, there is evidence that caffeine, in extreme acute doses or when taken in excess for long periods of time, may induce psychosis.

Medication

• Fluoroquinolone drugs: Fluoroquinolone use has been linked to serious cases of toxic psychosis (see Quinolone antibiotic § Adverse effects). The related quinoline derivative mefloquine (Lariam) has also been associated with psychosis.
• Over-the-counter drugs, including:
  • Dextromethorphan (DXM) at high doses.
  • Certain antihistamines at high doses.
  • Cold medications (i.e., containing phenylpropanolamine, or PPA)
• Prescription drugs:
  • Prednisone and other corticosteroids
  • Isotretinoin
  • Anticholinergic drugs
    • Atropine
    • Scopolamine
  • Antidepressants
  • L-DOPA
  • Anticonvulsants
• Antipsychotics, in an idiosyncratic or paradoxical reaction
• Antimalarials
  • Mepacrine

Other drugs illicit in America

Other drugs illegal in America (not listed above), including:

• MDMA (ecstasy)
• Phencyclidine (PCP)
• Ketamine
• Synthetic research chemicals used recreationally, including:
• JWH-018 and some other synthetic cannabinoids, or mixtures containing them (e.g. "Spice", "Kronic", "MNG" or "Mr. Nice Guy", "Relaxinol", etc.). Various "JWH-..." compounds in "Spice" or "Incense" have also been found and have been found to cause psychosis in some people.
• Mephedrone and related amphetamine-like drugs sold as "bath salts" or "plant food".

Plants

Plants:

• Hawaiian baby woodrose (contains ergine)
• Morning glory seeds (contains ergine)
• Datura (Jimsonweed, devil's trumpet, thorn apple)
• Belladonna (deadly nightshade)
• Salvia divinorum

Nonmedicinal substances

See also: Particulates § Cognitive hazards and mental health

Substances chiefly nonmedicinal as to source:

• Carbon monoxide (T58), carbon dioxide (T59.7), carbon disulfide (T65.4);
• Heavy metals;
• Organophosphate insecticides (T60.0);
• Sarin and other nerve gases;
• Tetraethyllead (T56.0);
• Aniline (T65.3);
• Acetone and other ketones (T52.4);
• Antifreeze – a mixture of ethylene glycol and other glycols (T51.8);
• Arsenic and its compounds (T57.0).