Serotonin transporter
Encyclopedia
The serotonin
transporter (SERT) is a monoamine transporter
protein
.
This protein is an integral membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. This transport of serotonin by the SERT protein terminates the action of serotonin and recycles it in a sodium-dependent manner. This protein is the target of many antidepressant medications, including those of the SSRI class. It is a member of the sodium:neurotransmitter symporter
family. A repeat length polymorphism in the promoter of this gene has been shown to affect the rate of serotonin uptake and may play a role in sudden infant death syndrome
, aggressive behavior in Alzheimer disease patients, post-traumatic stress disorder
and depression-susceptibility in people experiencing emotional trauma.
s. Thus, it terminates the effects of serotonin and simultaneously enables its reuse by the presynaptic neuron.
Neurons communicate by using chemical messages like serotonin between cells. The transporter protein, by recycling serotonin, regulates its concentration in a gap, or synapse
, and thus its effects on a receiving neuron’s receptors
.
Medical studies have shown that changes in serotonin transporter metabolism appear to be associated with many different phenomena, including alcoholism
, clinical depression
, obsessive-compulsive disorder
(OCD),
romantic love
, hypertension
and generalized social phobia
.
The serotonin transporter is also present in platelet
s; there, serotonin functions as a vasoconstrictive substance.
s, or SSRIs) and, less often, that increase it (selective serotonin reuptake enhancer
s, or SSREs) are used to treat mental disorders. About half of patients with OCD are treated with SSRIs. Fluoxetine
is an example of a selective serotonin reuptake inhibitor
, and tianeptine
is an example of a selective serotonin reuptake enhancer
.
The gene
that encodes the serotonin transporter is called solute carrier family 6 (neurotransmitter transporter, serotonin), member 4 (SLC6A4, see Solute carrier family
).
In human
s the gene is found on chromosome 17 on location 17q11.1–q12.
Mutations associated with the gene may result in changes in serotonin transporter function, and experiments with mice
have identified more the 50 different phenotypic changes as a result of genetic variation.
These phenotypic changes may, e.g., be increased anxiety
and gut
dysfunction.
Some of the human genetic variations associated with the gene are:
with "short" and "long" repeats in a region: 5-HTT-linked polymorphic region (5-HTTLPR
or SERTPR).
The short variation has 14 repeats of a sequence while the long variation has 16 repeats.
The short variation leads to less transcription
for SLC6A4, and it has been found that it can partly account for anxiety-related personality traits.
This polymorphism has been extensively investigated in over 300 scientific studies (as of 2006).
The 5-HTTLPR polymorphism may be subdivided further:
One study published in 2000 found 14 allelic
variants (14-A, 14-B, 14-C, 14-D, 15, 16-A, 16-B, 16-C, 16-D, 16-E, 16-F, 19, 20 and 22) in a group of around 200 Japanese
and Caucasian
people.
The low-expression variant of the 5-HTTLPR polymorphism (the short version) increased risk of socalled "posthurricane" post-traumatic stress disorder
(PTSD) and major depression but only under the conditions of high hurricane exposure and low social support after adjustment for sex, ancestry, and age.
Similar effects were found for major depression. High-risk individuals (high hurricane exposure, the low-expression 5-HTTLPR variant, low social support) were at 4.5 times the risk of developing PTSD and major depression of low-risk individuals.
In addition to altering the expression of SERT protein and concentrations of extracellular serotonin in the brain, the 5-HTTLPR variation is associated with changes in brain structure. One study found less grey matter
in perigenual anterior cingulate cortex
and amygdala
for short allele carriers of the 5-HTTLPR
polymorphism compared to subjects with the long/long genotype.
In another study, people who inherited two short allele
s were found to have more neurons and a larger volume in the pulvinar and limbic regions of the thalamus. Enlargement of the thalamus and reduced cortical volume provides an anatomical basis for why people who inherit the 5-HTTLPRshort/short genotype are more vulnerable to major depression, post-traumatic stress disorder, and suicide.
In contrast, a 2008 meta-analysis found no significant overall association between the 5-HTTLPR polymorphism and autism. A hypothesized gene-environment interaction
between the short/short allele of the 5-HTTLPR and life stress as predictor for major depression has suffered a similar fate: after an influential initial report there were mixed results in replication, and a 2009 meta-analysis was negative.
It has been examined in connection with obsessive compulsive disorder (OCD).
Researchers have found this genetic variation in unrelated families with OCD, and that it leads to faulty transporter function and regulation.
A second variant in the same gene of some patients with this mutation suggests a genetic "double hit", resulting in greater biochemical effects and more severe symptoms.
(STin2). It is found with three allele
s: 9, 10 and 12 repeats.
A meta-analysis
has found that the 12 repeat allele of the STin2 VNTR polymorphism had some minor (with odds ratio
1.24) but statistically significant association with schizophrenia
.
A 2008 meta-analysis found no significant overall association between the STin2 VNTR polymorphism and autism
.
Furthermore a 2003 meta-analysis of affective disorders, major depressive disorder and bipolar disorder
, found a little association to the intron 2 VNTR polymorphism, but the results of the meta-analysis depended on a large effect from one individual study.
The polymorphism has also been related to personality traits with a Russian study from 2008 finding individuals with the STin2.10 allele having lower neuroticism
score as measured with the Eysenck Personality Inventory.
may be imaged with positron emission tomography
using radioligand
s called DASB
and DAPP, and the first studies on the human brain were reported in 2000.
DASB and DAPP are not the only radioligands for the serotonin transporter.
There are numerous others, with the most popular probably being the β-CIT radioligand with an iodine-123
isotope
that is used for brain scanning with single photon emission computed tomography
(SPECT).
The radioligands have been used to examine whether variables such as age, gender or genotype
are associated with differential serotonin transporter binding.
Healthy subjects that have a high score of neuroticism
— a personality trait
in the Revised NEO Personality Inventory
— have been found to have more serotonin transporter binding in the thalamus
.
a voxel-based morphometry study found less grey matter
in perigenual anterior cingulate cortex
and amygdala
for short allele carriers of the 5-HTTLPR
polymorphism compared to subjects with the long/long genotype.
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
transporter (SERT) is a monoamine transporter
Monoamine transporter
Monoamine transporters are protein structures that function as integral plasma membrane transporters to regulate concentrations of extracellular monoamine neurotransmitters. Three major classes of MATs are responsible for the reuptake of their associated amine neurotransmitters...
protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
.
This protein is an integral membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. This transport of serotonin by the SERT protein terminates the action of serotonin and recycles it in a sodium-dependent manner. This protein is the target of many antidepressant medications, including those of the SSRI class. It is a member of the sodium:neurotransmitter symporter
Sodium:neurotransmitter symporter
Sodium:neurotransmitter symporters is a family of neurotransmitter transporters.Neurotransmitter transport systems are responsible for the release, re-uptake and recycling of neurotransmitters at synapses....
family. A repeat length polymorphism in the promoter of this gene has been shown to affect the rate of serotonin uptake and may play a role in sudden infant death syndrome
Sudden infant death syndrome
Sudden infant death syndrome is marked by the sudden death of an infant that is unexpected by medical history, and remains unexplained after a thorough forensic autopsy and a detailed death scene investigation. An infant is at the highest risk for SIDS during sleep, which is why it is sometimes...
, aggressive behavior in Alzheimer disease patients, post-traumatic stress disorder
Post-traumatic stress disorder
Posttraumaticstress disorder is a severe anxiety disorder that can develop after exposure to any event that results in psychological trauma. This event may involve the threat of death to oneself or to someone else, or to one's own or someone else's physical, sexual, or psychological integrity,...
and depression-susceptibility in people experiencing emotional trauma.
Function
The serotonin transporter removes serotonin from the synaptic cleft back into the synaptic boutonBouton
Bouton is a French word that can be translated to button.It may refer to:* De Dion-Bouton, a French automobile manufacturer* Synaptic bouton, part of a chemical synapse* Bouton, Iowa, a town in the United States...
s. Thus, it terminates the effects of serotonin and simultaneously enables its reuse by the presynaptic neuron.
Neurons communicate by using chemical messages like serotonin between cells. The transporter protein, by recycling serotonin, regulates its concentration in a gap, or synapse
Synapse
In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...
, and thus its effects on a receiving neuron’s receptors
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
.
Medical studies have shown that changes in serotonin transporter metabolism appear to be associated with many different phenomena, including alcoholism
Alcoholism
Alcoholism is a broad term for problems with alcohol, and is generally used to mean compulsive and uncontrolled consumption of alcoholic beverages, usually to the detriment of the drinker's health, personal relationships, and social standing...
, clinical depression
Clinical depression
Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
, obsessive-compulsive disorder
Obsessive-compulsive disorder
Obsessive–compulsive disorder is an anxiety disorder characterized by intrusive thoughts that produce uneasiness, apprehension, fear, or worry, by repetitive behaviors aimed at reducing the associated anxiety, or by a combination of such obsessions and compulsions...
(OCD),
romantic love
Romantic love
Romance is the pleasurable feeling of excitement and mystery associated with love.In the context of romantic love relationships, romance usually implies an expression of one's love, or one's deep emotional desires to connect with another person....
, hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
and generalized social phobia
Social anxiety disorder
Social anxiety disorder , also known as social phobia, is an anxiety disorder characterized by intense fear in social situations causing considerable distress and impaired ability to function in at least some parts of daily life...
.
The serotonin transporter is also present in platelet
Platelet
Platelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days...
s; there, serotonin functions as a vasoconstrictive substance.
Pharmacology
SERT spans the plasma membrane 12 times. It belongs to NE, DA, SERT monoamine transporter family. Transporters are important sites for agents that treat psychiatric disorders. Both drugs that reduce the binding of serotonin to transporters (selective serotonin reuptake inhibitorSelective serotonin reuptake inhibitor
Selective serotonin re-uptake inhibitors or serotonin-specific reuptake inhibitor are a class of compounds typically used as antidepressants in the treatment of depression, anxiety disorders, and some personality disorders. The efficacy of SSRIs is disputed...
s, or SSRIs) and, less often, that increase it (selective serotonin reuptake enhancer
Selective serotonin reuptake enhancer
A selective serotonin reuptake enhancer is a type of drug which enhances the plasmalemmal reuptake of the neurotransmitter serotonin, leading to a decrease in its synaptic concentrations and therefore a decrease in serotonergic neurotransmission....
s, or SSREs) are used to treat mental disorders. About half of patients with OCD are treated with SSRIs. Fluoxetine
Fluoxetine
Fluoxetine is an antidepressant of the selective serotonin reuptake inhibitor class. It is manufactured and marketed by Eli Lilly and Company...
is an example of a selective serotonin reuptake inhibitor
Selective serotonin reuptake inhibitor
Selective serotonin re-uptake inhibitors or serotonin-specific reuptake inhibitor are a class of compounds typically used as antidepressants in the treatment of depression, anxiety disorders, and some personality disorders. The efficacy of SSRIs is disputed...
, and tianeptine
Tianeptine
Tianeptine was discovered by The French Society of Medical Research in the 1960s. Under the trade-names it is a drug used for treating major depressive episodes ....
is an example of a selective serotonin reuptake enhancer
Selective serotonin reuptake enhancer
A selective serotonin reuptake enhancer is a type of drug which enhances the plasmalemmal reuptake of the neurotransmitter serotonin, leading to a decrease in its synaptic concentrations and therefore a decrease in serotonergic neurotransmission....
.
Ligands
- compound (+)-12a: Ki = 180 pM at hSERT; >1000-fold selective over hDAT, hNET, 5-HT1A, and 5-HT6. IsostereBioisostereIn medicinal chemistry, bioisosteres are substituents or groups with similar physical or chemical properties which produce broadly similar biological properties to a chemical compound. In drug design, the purpose of exchanging one bioisostere for another is to enhance the desired biological or...
s - compound 4b: Ki = 17 pM; 710-fold and 11,100-fold selective over DAT and NET
- 3-cis-(3-Aminocyclopentyl)indole 8a: 220pM
Genetics
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
that encodes the serotonin transporter is called solute carrier family 6 (neurotransmitter transporter, serotonin), member 4 (SLC6A4, see Solute carrier family
Solute carrier family
The solute carrier group of membrane transport proteins include over 300 members organized into 51 families. The SLC gene nomenclature system was originally proposed by the Human Genome Organization and is the basis for the official HUGO names of the genes that encode these transporters...
).
In human
Human
Humans are the only living species in the Homo genus...
s the gene is found on chromosome 17 on location 17q11.1–q12.
Mutations associated with the gene may result in changes in serotonin transporter function, and experiments with mice
Mouse
A mouse is a small mammal belonging to the order of rodents. The best known mouse species is the common house mouse . It is also a popular pet. In some places, certain kinds of field mice are also common. This rodent is eaten by large birds such as hawks and eagles...
have identified more the 50 different phenotypic changes as a result of genetic variation.
These phenotypic changes may, e.g., be increased anxiety
Anxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...
and gut
Gut (zoology)
In zoology, the gut, also known as the alimentary canal or alimentary tract, is a tube by which bilaterian animals transfer food to the digestion organs. In large bilaterians the gut generally also has an exit, the anus, by which the animal disposes of solid wastes...
dysfunction.
Some of the human genetic variations associated with the gene are:
- Length variation in the serotonin-transporter-gene-linked polymorphic region (5-HTTLPR5-HTTLPR5-HTTLPR is a degenerate repeat polymorphic region in SLC6A4, the gene that codes for the serotonin transporter.Since the polymorphism was identified in the middle of the 1990s,...
) - rs25531 — a single nucleotide polymorphismSingle nucleotide polymorphismA single-nucleotide polymorphism is a DNA sequence variation occurring when a single nucleotide — A, T, C or G — in the genome differs between members of a biological species or paired chromosomes in an individual...
(SNP) in the 5-HTTLPR - rs25532 — another SNP in the 5-HTTLPR
- STin2 — a variable number of tandem repeats (VNTR) in the functional intronIntronAn intron is any nucleotide sequence within a gene that is removed by RNA splicing to generate the final mature RNA product of a gene. The term intron refers to both the DNA sequence within a gene, and the corresponding sequence in RNA transcripts. Sequences that are joined together in the final...
2 - G56A on the second exonExonAn exon is a nucleic acid sequence that is represented in the mature form of an RNA molecule either after portions of a precursor RNA have been removed by cis-splicing or when two or more precursor RNA molecules have been ligated by trans-splicing. The mature RNA molecule can be a messenger RNA...
- I425V on the ninth exon
Length variation in 5-HTTLPR
The promotor region of the SLC6A4 gene contains a polymorphismPolymorphism (biology)
Polymorphism in biology occurs when two or more clearly different phenotypes exist in the same population of a species — in other words, the occurrence of more than one form or morph...
with "short" and "long" repeats in a region: 5-HTT-linked polymorphic region (5-HTTLPR
5-HTTLPR
5-HTTLPR is a degenerate repeat polymorphic region in SLC6A4, the gene that codes for the serotonin transporter.Since the polymorphism was identified in the middle of the 1990s,...
or SERTPR).
The short variation has 14 repeats of a sequence while the long variation has 16 repeats.
The short variation leads to less transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
for SLC6A4, and it has been found that it can partly account for anxiety-related personality traits.
This polymorphism has been extensively investigated in over 300 scientific studies (as of 2006).
The 5-HTTLPR polymorphism may be subdivided further:
One study published in 2000 found 14 allelic
Allele
An allele is one of two or more forms of a gene or a genetic locus . "Allel" is an abbreviation of allelomorph. Sometimes, different alleles can result in different observable phenotypic traits, such as different pigmentation...
variants (14-A, 14-B, 14-C, 14-D, 15, 16-A, 16-B, 16-C, 16-D, 16-E, 16-F, 19, 20 and 22) in a group of around 200 Japanese
Japanese people
The are an ethnic group originating in the Japanese archipelago and are the predominant ethnic group of Japan. Worldwide, approximately 130 million people are of Japanese descent; of these, approximately 127 million are residents of Japan. People of Japanese ancestry who live in other countries...
and Caucasian
Caucasian race
The term Caucasian race has been used to denote the general physical type of some or all of the populations of Europe, North Africa, the Horn of Africa, Western Asia , Central Asia and South Asia...
people.
The low-expression variant of the 5-HTTLPR polymorphism (the short version) increased risk of socalled "posthurricane" post-traumatic stress disorder
Post-traumatic stress disorder
Posttraumaticstress disorder is a severe anxiety disorder that can develop after exposure to any event that results in psychological trauma. This event may involve the threat of death to oneself or to someone else, or to one's own or someone else's physical, sexual, or psychological integrity,...
(PTSD) and major depression but only under the conditions of high hurricane exposure and low social support after adjustment for sex, ancestry, and age.
Similar effects were found for major depression. High-risk individuals (high hurricane exposure, the low-expression 5-HTTLPR variant, low social support) were at 4.5 times the risk of developing PTSD and major depression of low-risk individuals.
In addition to altering the expression of SERT protein and concentrations of extracellular serotonin in the brain, the 5-HTTLPR variation is associated with changes in brain structure. One study found less grey matter
Grey matter
Grey matter is a major component of the central nervous system, consisting of neuronal cell bodies, neuropil , glial cells and capillaries. Grey matter contains neural cell bodies, in contrast to white matter, which does not and mostly contains myelinated axon tracts...
in perigenual anterior cingulate cortex
Anterior cingulate cortex
The anterior cingulate cortex is the frontal part of the cingulate cortex, that resembles a "collar" form around the corpus callosum, the fibrous bundle that relays neural signals between the right and left cerebral hemispheres of the brain...
and amygdala
Amygdala
The ' are almond-shaped groups of nuclei located deep within the medial temporal lobes of the brain in complex vertebrates, including humans. Shown in research to perform a primary role in the processing and memory of emotional reactions, the amygdalae are considered part of the limbic system.-...
for short allele carriers of the 5-HTTLPR
5-HTTLPR
5-HTTLPR is a degenerate repeat polymorphic region in SLC6A4, the gene that codes for the serotonin transporter.Since the polymorphism was identified in the middle of the 1990s,...
polymorphism compared to subjects with the long/long genotype.
In another study, people who inherited two short allele
Allele
An allele is one of two or more forms of a gene or a genetic locus . "Allel" is an abbreviation of allelomorph. Sometimes, different alleles can result in different observable phenotypic traits, such as different pigmentation...
s were found to have more neurons and a larger volume in the pulvinar and limbic regions of the thalamus. Enlargement of the thalamus and reduced cortical volume provides an anatomical basis for why people who inherit the 5-HTTLPRshort/short genotype are more vulnerable to major depression, post-traumatic stress disorder, and suicide.
In contrast, a 2008 meta-analysis found no significant overall association between the 5-HTTLPR polymorphism and autism. A hypothesized gene-environment interaction
Gene-environment interaction
Gene–environment interaction is the phenotypic effect of interactions between genes and the environment....
between the short/short allele of the 5-HTTLPR and life stress as predictor for major depression has suffered a similar fate: after an influential initial report there were mixed results in replication, and a 2009 meta-analysis was negative.
rs25532
rs25532 is a SNP (C>T) close to the site of 5-HTTLPR.It has been examined in connection with obsessive compulsive disorder (OCD).
I425V
I425V is a rare mutation on the ninth exon.Researchers have found this genetic variation in unrelated families with OCD, and that it leads to faulty transporter function and regulation.
A second variant in the same gene of some patients with this mutation suggests a genetic "double hit", resulting in greater biochemical effects and more severe symptoms.
VNTR in STin2
Another noncoding polymorphism is a VNTR in the second intronIntron
An intron is any nucleotide sequence within a gene that is removed by RNA splicing to generate the final mature RNA product of a gene. The term intron refers to both the DNA sequence within a gene, and the corresponding sequence in RNA transcripts. Sequences that are joined together in the final...
(STin2). It is found with three allele
Allele
An allele is one of two or more forms of a gene or a genetic locus . "Allel" is an abbreviation of allelomorph. Sometimes, different alleles can result in different observable phenotypic traits, such as different pigmentation...
s: 9, 10 and 12 repeats.
A meta-analysis
Meta-analysis
In statistics, a meta-analysis combines the results of several studies that address a set of related research hypotheses. In its simplest form, this is normally by identification of a common measure of effect size, for which a weighted average might be the output of a meta-analyses. Here the...
has found that the 12 repeat allele of the STin2 VNTR polymorphism had some minor (with odds ratio
Odds ratio
The odds ratio is a measure of effect size, describing the strength of association or non-independence between two binary data values. It is used as a descriptive statistic, and plays an important role in logistic regression...
1.24) but statistically significant association with schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
.
A 2008 meta-analysis found no significant overall association between the STin2 VNTR polymorphism and autism
Autism
Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their...
.
Furthermore a 2003 meta-analysis of affective disorders, major depressive disorder and bipolar disorder
Bipolar disorder
Bipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...
, found a little association to the intron 2 VNTR polymorphism, but the results of the meta-analysis depended on a large effect from one individual study.
The polymorphism has also been related to personality traits with a Russian study from 2008 finding individuals with the STin2.10 allele having lower neuroticism
Neuroticism
Neuroticism is a fundamental personality trait in the study of psychology. It is an enduring tendency to experience negative emotional states. Individuals who score high on neuroticism are more likely than the average to experience such feelings as anxiety, anger, guilt, and depressed mood...
score as measured with the Eysenck Personality Inventory.
Neuroimaging
The distribution of the serotonin transporter in the brainBrain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
may be imaged with positron emission tomography
Positron emission tomography
Positron emission tomography is nuclear medicine imaging technique that produces a three-dimensional image or picture of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide , which is introduced into the body on a...
using radioligand
Radioligand
A radioligand is a radioactive biochemical substance that is used for diagnosis or for research-oriented study of the receptor systems of the body....
s called DASB
DASB
DASB is a compound that binds to the serotonin transporter.Labeled with carbon-11 — a radioactive isotope — it has been used as a radioligand in neuroimaging with positron emission tomography since around year 2000....
and DAPP, and the first studies on the human brain were reported in 2000.
DASB and DAPP are not the only radioligands for the serotonin transporter.
There are numerous others, with the most popular probably being the β-CIT radioligand with an iodine-123
Isotopes of iodine
There are 37 known isotopes of iodine and only one, 127I, is stable. Iodine is thus a monoisotopic element.Its longest-lived radioactive isotope, 129I, has a half-life of 15.7 million years, which is far too short for it to exist as a primordial nuclide...
isotope
Isotope
Isotopes are variants of atoms of a particular chemical element, which have differing numbers of neutrons. Atoms of a particular element by definition must contain the same number of protons but may have a distinct number of neutrons which differs from atom to atom, without changing the designation...
that is used for brain scanning with single photon emission computed tomography
Single photon emission computed tomography
Single-photon emission computed tomography is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera. However, it is able to provide true 3D information...
(SPECT).
The radioligands have been used to examine whether variables such as age, gender or genotype
Genotype
The genotype is the genetic makeup of a cell, an organism, or an individual usually with reference to a specific character under consideration...
are associated with differential serotonin transporter binding.
Healthy subjects that have a high score of neuroticism
Neuroticism
Neuroticism is a fundamental personality trait in the study of psychology. It is an enduring tendency to experience negative emotional states. Individuals who score high on neuroticism are more likely than the average to experience such feelings as anxiety, anger, guilt, and depressed mood...
— a personality trait
Trait theory
In psychology, Trait theory is a major approach to the study of human personality. Trait theorists are primarily interested in the measurement of traits, which can be defined as habitual patterns of behavior, thought, and emotion. According to this perspective, traits are relatively stable over...
in the Revised NEO Personality Inventory
Revised NEO Personality Inventory
The Revised NEO Personality Inventory, or NEO PI-R, is a psychological personality inventory; a 240-item measure of the Five Factor Model: Extraversion, Agreeableness, Conscientiousness, Neuroticism, and Openness to Experience. Additionally, the test measures six subordinate dimensions of each of...
— have been found to have more serotonin transporter binding in the thalamus
Thalamus
The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...
.
Neuroimaging and genetics
Studies on the serotonin transporter have combined neuroimaging and genetics methods, e.g.,a voxel-based morphometry study found less grey matter
Grey matter
Grey matter is a major component of the central nervous system, consisting of neuronal cell bodies, neuropil , glial cells and capillaries. Grey matter contains neural cell bodies, in contrast to white matter, which does not and mostly contains myelinated axon tracts...
in perigenual anterior cingulate cortex
Anterior cingulate cortex
The anterior cingulate cortex is the frontal part of the cingulate cortex, that resembles a "collar" form around the corpus callosum, the fibrous bundle that relays neural signals between the right and left cerebral hemispheres of the brain...
and amygdala
Amygdala
The ' are almond-shaped groups of nuclei located deep within the medial temporal lobes of the brain in complex vertebrates, including humans. Shown in research to perform a primary role in the processing and memory of emotional reactions, the amygdalae are considered part of the limbic system.-...
for short allele carriers of the 5-HTTLPR
5-HTTLPR
5-HTTLPR is a degenerate repeat polymorphic region in SLC6A4, the gene that codes for the serotonin transporter.Since the polymorphism was identified in the middle of the 1990s,...
polymorphism compared to subjects with the long/long genotype.
Further reading
- NIH press release: Serotonin Transporter Gene Shown to Influence College Drinking Habits