A new method allows researchers to detect serotonin at extremely low concentrations in serum


Dopamine, serotonin, adrenalin…

The smooth functioning of the human brain depends on their correct proportions. Any disturbances mean diseases.

That’s why it’s so important to be able to detect these disturbances as early as possible – before the appearance of any visible symptoms.

This will be possible quickly, simply and cheaply thanks to the work of a team of researchers headed by Professor Martin Jönsson-Niedziółka from the IPC PAS.

“We are aiming to detect neurotransmitters at the lowest concentrations and without additional sample preparation,” says the author of the work published in Analytical Chemistry, Magdalena Kundys-Siedlecka.

“In the paper we have just published, I proved that in mouse serum (i.e. blood without the red blood cells) I can detect serotonin at concentrations that are as low as those found physiologically.”

Serotonin is sometimes called the hormone of happiness, so it seemed reasonable to ask if the mice used in the study were happy or unhappy?

“It seems to me that the mice we studied were …just ordinary,” answers the head of the research group Professor Martin Jönsson-Niedziółka with a laugh, “Neither happy nor unhappy, and their serotonin levels were statistically normal.”

Where did the idea for this method come from? “Firstly, we wanted to detect many neurotransmitters simultaneously in one sample,” explains Magdalena Kundys-Siedlecka.

“Secondly, in low, physiological concentrations, so that any possible disease could be detected early on.

Thirdly – in a sample needing the least possible processing – collect samples of blood, saliva, or, for example, cerebrospinal fluid and detect the neurotransmitters in them without much additional preparation.”

It is said that, for example, Alzheimer’s disease is caused by a deficiency of dopamine in specific areas of the brain, but in reality, the disease mechanisms are much more complicated.

Usually, it is not an excess or deficiency of only one neurotransmitter that leads to disease, but rather the wrong mixture of them or some other underlying cause.

If we can manage to find out what the concentrations of the various substances are in one sample, taken at the same time, from the same place, we can talk much more accurately about what is really the cause of one or other of the disease symptoms.

How did our scientists manage to do this?

The key is stirring the sample on an electrode.

This forces faster mass transport.

“We increase the reaction efficiency manyfold and accelerate the measurement”, explains Ms. Kundys-Siedlecka proudly.

“The limit of detection is extremely low. We are able to detect all the neurotransmitters that are electrochemically active, that is, undergoing oxidation and reduction.

I show how to determine two of them – dopamine and serotonin simultaneously.

I have to add that we identify dopamine without fail, although it is very similar to others, such as adrenaline, noradrenaline or some catecholamines,” grins the researcher.

You could compare this to looking for a needle in a haystack. The sample is a huge haystack and we want to find the needle.

And it works! This is only possible thanks to well-modified electrodes separating signals from the various neurotransmitters.

Of course, blood measurements only allow for a very approximate determination of concentration.

After all, it is known that neurotransmitters are secreted in various areas of the brain, as well as outside the brain.

For example, if a given neurotransmitter is secreted in the kidneys, then its concentration in urine will be different than in the blood or in tears.

“In the next stage of our research, we would like to check whether our method detects neurotransmitters in human blood as precisely as it does in mice,” says the researcher. “If this is confirmed, we will be able to draw less blood from the patient – just a drop (70 microlitres) will be sufficient to determine many of these substances, and our goal is to detect even lower concentrations, which would give us the opportunity to identify, for example, dopamine in fluids other than blood, those that don’t hurt at all when they’re taken.”

“We can already detect serotonin in concentrations similar to those found in humans,” explains Professor Jönsson-Niedziółka. “With dopamine – the most interesting of the neurotransmitters – we haven’t managed yet, and others have such low concentrations that we need to modify the electrode surface further, and probably the entire method, to say with a high probability that we detect them in an unprepared sample. We know, however, that at higher concentrations we can already separate serotonin and dopamine signals in the same sample. ”

Research conducted at IPC PAS using the new research method enables the early detection of neurotransmitter deficiencies which will help prevent various diseases. Pictured is Magdalena Kundys-Siedlecka, holding a brain.

“Our method has two benefits for any hospital that wishes to use it: first, time – in the case of serotonin, it is the fastest known detection method, less than an hour from collection to result; well, unless the sample needs to also be transported, ” specifies the professor. “Secondly, the cost – the method is cheap, and the equipment can be operated by a technician after a short period of training.”

“The main requirement is patience,” smiles Ms. Kundys-Siedlecka. It is left to us to wait with impatience for the results of the research of the IPC PAS team to reach hospitals, for them to help to uncover the mechanisms of development of such diseases as depression and Alzheimer’s and to improve their treatment.

Funding: The research was sponsored by the PRELUDIUM (Simultaneous determination of chosen neurotransmitters in hydrodynamic conditions) project, headed by Magdalena Kundys-Siedlecka, funded by the National Scientific Centre. Grant number NCN 2016/23/N/ST4/02702

The serotonin syndrome is a medication-induced condition resulting from serotonergic hyperactivity, usually involving antidepressant medications. As the number of patients experiencing medically-treated major depressive disorder increases, so does the population at risk for experiencing serotonin syndrome.

Excessive synaptic stimulation of 5-HT2A receptors results in autonomic and neuromuscular aberrations with potentially life-threatening consequences.

In this review, we will outline the molecular basis of the disease and describe how pharmacologic agents that are in common clinical use can interfere with normal serotonergic pathways to result in a potentially fatal outcome.

Given that serotonin syndrome can imitate other clinical conditions, an understanding of the molecular context of this condition is essential for its detection and in order to prevent rapid clinical deterioration.


The serotonin syndrome (SS) is a clinical condition resulting from serotonergic over-activity at synapses of the central and peripheral nervous systems.

The true incidence of the disease is unknown, given that its severity varies and that many of its symptoms may be common to other clinical conditions.

The SS is triggered by therapeutic drugs that are not only common, but ones whose use appears to be increasing at an alarming rate [1]. The most common drug triggers of SS are antidepressants, for which the incidence of use in adults in the United States has increased from 6% in 1999 to 10.4% in 2010 [2].

Furthermore, reported ingestions of selective serotonin reuptake inhibitors (SSRIs) increased by almost 15% from 2002 to 2005 [3,4,5,6,7].

In this review article, we will describe the clinical pathophysiology of SS and present the leading molecular theories underlying the disease.

Being a purely clinical diagnosis with protean manifestations, an understanding of the presentation of this disease and related confounding diagnoses is necessary to establish a relevant context. What follows is the putative molecular basis of the disease, and how certain genetic polymorphisms are hypothesized to contribute to its manifestations in predisposed individuals.

This information will facilitate an understanding of how certain medications can trigger the syndrome, especially in high risk patients. It will also help readers to comprehend current treatment strategies and directions for future research in the field.

Clinical Context

Definition and Epidemiology

The diagnostic basis of SS includes the triad of altered mental status, autonomic hyperactivity, and neuromuscular abnormalities [8,9] in patients exposed to any medication which increases the activation of serotonin (5-hydroxytryptamine; 5-HT) receptors in the body [10].

These medications include SSRIs, monoamine oxidase inhibitors (MAOI), opioid analgesics, antiemetics, illicit drugs, and others [10]. The widespread use of these medications puts a large portion of the population at risk for developing this disease, especially if used in combination [11].

A retrospective cohort study reviewing Veterans Health Administration records from 2009–2013 showed a disease incidence of 0.23% in patients exposed to serotonergic medications (0.07% overall) [12].

This same study also reported a 0.09% incidence of SS in commercially insured patients exposed to serotonergic medications in 2013 (0.03% overall) [12]. The median cost per inpatient hospital stay associated with SS was $10,792 for commercially insured patients and $8765 for Veterans Health Administration patients [12].

No associated mortality data was reported [10,12]. There are no reports identifying specific patient risk factors that are associated with the development of SS outside of the genetic polymorphisms that will be described in further detail later. However, many of the medications with the potential to cause SS are commonly used in the geriatric population, thus placing these patients at higher risk of developing the disorder.

Since SS varies in presentation, it is likely to be grossly underdiagnosed in clinical practice and, thus, studies into its precise mechanism are very limited [13]. Much of the relevant research data is derived from animal models and from case descriptions of individuals in whom the disease has been highly suspected.

Manifestations and Diagnosis

Several diagnostic algorithms have been proposed since SS was first recognized as a discrete disease entity (Table 1). The main challenges encountered in establishing formal diagnostic criteria are (1) the wide range of symptoms exhibited by patients affected by the disease and (2) the lack of a confirmatory laboratory test.

Thus, the diagnosis of SS remains purely clinical at present. The first diagnostic criteria were proposed by Sternbach et al. in 1991, based on a review of 38 published case reports in which patients demonstrated several shared symptoms [8].

Cases were reported by as many as 12 different investigators, and the most commonly reported symptoms included confusion (n = 16), hypomania (n = 8), restlessness (n = 17), and myoclonus (n = 13) [8]. Sternbach’s criteria were based on the inclusion of three or more of the most commonly noted symptoms extracted from the 38 cases.

The major weakness of Sternbach’s criteria was the inclusion of four separate altered mentation symptoms (confusion/hypomania, agitation, and incoordination), which made it possible to diagnose SS purely based on mental status changes [11].

Such mental status changes could be commonly observed in many other conditions such as alcohol and drug withdrawal states and anticholinergic delirium [3], a limitation which Sternbach fully acknowledged.

Between 1995 and 2000, Radomski and colleagues [14] reviewed subsequent cases of suspected SS with the goals of refining Sternbach’s diagnostic criteria and outlining the medical management of this disorder. The most recent diagnostic criteria, however, were developed by Dunkley et al. in 2003 [11].

Dunkley’s criteria were formed through the use of a toxicology database called the Hunter Area Toxicology Service, which included patients who were known to have overdosed on at least one serotonergic medication.

A decision tree was constructed by including symptoms which recurred at a statistically significant frequency in patients with SS that had been diagnosed by a medical toxicologist. This diagnostic algorithm was both more sensitive (84% vs. 75%) and more specific (97% vs. 96%) in diagnosing SS than Sternbach’s criteria [11].

The Hunter Serotonin Toxicity Criteria, as they are now known, are generally considered the gold standard for diagnosing this disease [10].

They consist of the aforementioned triad of altered mental status, neuromuscular excitation and autonomic dysfunction. Symptoms usually occur within one hour of exposure to triggering medications in 30% of patients, and within six hours in 60% of patients [1]. Mild cases may present as little more than flu-like symptoms, while severe cases may progress rapidly to cardiovascular collapse and death (Figure 1).

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Figure 1
Signs and symptoms of the serotonin syndrome occur along a spectrum of severity. Mild symptoms may easily be overlooked, and may manifest as little more than diarrhea and flu-like symptoms. Unless the disease is recognized and the causative drugs are discontinued, it can rapidly progress to muscle rigidity, severe hyperthermia and death.

Institute of Physical Chemistry of the Polish Academy of Science
Media Contacts:
Magdalena Kundys-Siedlecka – Institute of Physical Chemistry of the Polish Academy of Science
Image Source:
The image is credited to IPC PAS, Grzegorz Krzyzewski.

Original Research: Closed access
“Electrochemical Detection of Dopamine and Serotonin in the Presence of Interferences in a Rotating Droplet System”. Magdalena Kundys-Siedlecka, Ewa Bączyńska, Martin Jönsson-Niedziółka.
Analytical Chemistry doi:10.1021/acs.analchem.9b02967.


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