Biosensors to detect one or more biomarkers can also be detected by
25 acoustic, plasmon resonance, holographic and microengineered sensors.
Imprinted recognition elements, thin film transistor technology, magnetic
acoustic resonator devices and other novel acousto-electrical systems may be employed for detection of the one or more biomarkers of the การประดิษฐ์.
Methods involving detection and/or quantification of one or more
30 biomarkers of the การประดิษฐ์ can be performed on bench-top instruments, or
can be incorporated onto disposable, diagnostic or monitoring platforms that can be used in a non-laboratory environment, e.g . in the physician's office or at the patient's bedside. Suitable platforms for performing methods of the
การประดิษฐ์ include "credit" cards with optical or acoustic readers. The sensor 5 systems can be configured to allow the data collected to be electronically
transmitted to the physician for interpretation and thus can form the basis
for remote diagnosis.
Methods of the การประดิษฐ์ can be performed in array format, e.g.
on a chip, or as a multi well array. This enables testing for several
10 biomarkers or for only one biomarker in multiple subjects or samples
simultaneously. Methods can be adapted into platforms for single tests, or
multiple identical or multiple non-identical tests, the last especially in the
case if urine-based markers are combined with serum-based markers, and
can be performed in high throughput format. Methods of the การประดิษฐ์ may 15 ประกอบรวมด้วย performing one or more additional, different tests to confirm or
exclude diagnosis, and/or to further characterize a condition.
A kit for diagnosing or monitoring a mood disorder, especially
depression and more particularly major depressive disorder, or
predisposition thereto is provided. Suitably a kit according to the การประดิษฐ์ 20 may contain one or more components selected from the group: a biosensor
specific for the biomarker or a molecule upstream or downstream in the
biological pathway for that biomarker, where the biomarker is one of the
biomarkers provided herein; one or more controls; one or more reagents and
one or more consumables; optionally together with instructions for use of
25 the kit in accordance with any of the methods defined herein.
The identification of biomarkers for mood disorders, especially
depression and more particularly major depressive disorder permits
integration of diagnostic procedures and therapeutic regimes. Currently
30 effectiveness of drug treatment or psychotherapy is difficult to test, and it
has thus far not been possible to perform rapid assessment of therapy
response. Traditionally, many anti-depressant therapies require treatment lasting weeks to months for a given therapeutic approach. Detection of a biomarker of the การประดิษฐ์ can be used to screen subjects prior to their
5 participation in clinical trials. The biomarkers provide the means to indicate
therapeutic response, failure to respond, unfavourable side-effect profile, and degree of medication compliance. The biomarkers may be used to stop treatment in non-responders at a very early stage. They can also be used to
fine-tune dosage, minimize the number of prescribed medications, and to 10 reduce the delay in attaining effective therapy. Thus by monitoring a
biomarker of the การประดิษฐ์, patient care can be tailored precisely to match
the needs determined by the disorder and the pharmacogenomic profile of
the patient. The biomarker can thus be used to titrate the optimal dose and
to identify a positive therapeutic response.
15 Biomarker-based tests, such as provided by the present การประดิษฐ์,
provide a first line assessment of 'new' patients, and provide objective measures for accurate and rapid diagnosis, in a time frame and with precision, not achievable using the current subjective measures.
Furthermore, diagnostic biomarker tests, such as provided by the present 20 การประดิษฐ์, are useful to identify family members or patients at high risk of
developing major depressive disorder. This permits initiation of appropriate
therapy, or preventive measures, e.g. managing risk factors. These
approaches are recognized to improve outcome and may prevent overt onset
of the disorder.
25 Biomarker monitoring methods, biosensors and kits are also vital
as patient monitoring tools. If pharmacological treatment is assessed to be inadequate, then therapy can be reinstated or increased; a change in
therapy can be given if appropriate. As the biomarkers are sensitive to the state of the disorder, they provide an indication of the impact of drug
30 therapy.
Diagnostic kits for the diagnosis and monitoring of a mood
disorder, preferably depression, most preferably major depressive disorder,
are described herein. A method of diagnosis or monitoring the biomarkers 5 may ประกอบรวมด้วย quantifying the biomarker in a sample from the patient and
comparing the level of the biomarker present in said sample with one or
more controls. For monitoring, the control may be a test sample of the same
patient at an earlier point in time.
Preferably, the diagnosis for the presence of a mood disorder in a
10 patient according to the present การประดิษฐ์ is used to confirm a suspicion of a
mood disorder, such as depression. This means that preferably the patient is already suspected of having a mood disorder at the moment that de the
assay for one or more of the biomarkers is performed. In this respect, the การประดิษฐ์ can be considered as a method for enhancing the diagnosis of
15 depression.
One of the main advantages of the present การประดิษฐ์ is that it
provides an easy and reliable way to monitor progress of the disease and/or
effectiveness of a therapy. To this end, the values for one or more of the
20 above identified biomarkers for a subject are determined at a certain
moment (null-value) and after an amount of time this procedure is repeated.
Over the time, several repeat measurements can be performed. In the mean
time therapy can e.g. be started or changed. Change(s) in the levels of
biomarker will then indicate the effectiveness of the therapy or the progress
25 of the disease.
Suitably, the time elapsed between taking samples from a subject
undergoing monitoring will be several days, a week, two weeks, a month,
several months or longer. Samples may be taken prior to and/or during
and/or following antidepressant therapy. Samples can be taken at intervals 30 over the remaining life, or a part thereof, of a patient.
Thus, in this way, in a non-invasive and easy manner, the progress of the disease can be monitored.
5 EXAMPLES
Example 1
Ten patients with DSM IV diagnosed major depression having a
Hamilton score of 18 or more, one person with DSM IV diagnosed anxiety 10 disorder having a Hamilton score of 18 or more and 1person with DSM IV
diagnosed bipolafr depression having a Hamilton score of 18 or more were
matched with respect to age, gender and ethnic origin with 12 healthy
persons.
From all these persons blood and urine was collected through
15 venapunction in 9 mL tubes. These were centrifuged for 10 minutes at 3000
x g. Aliquots were divided over 25 tubes; these were held at 4°C and stored
at -80°C until use. Urine samples were taken from morning midstream
urine, which were directly stored at 4°C. The same day these samples were
centrifuged for 10 minutes at 3000 x g and aliquoted over 20 tubes. These 20 were stored at -80°C until further use.
These samples were tested with commercially available assays for the following biomarkers. The assays were obtained from the following
vendors and the assays were performed according to the instructions of the vendor, unless otherwise indicated hereinafter.
25 R&D systems Europe Ltd. (Abingdon, United Kingdom) for
คอร์ติซอล, LTB4,ทรอมบอกเซน, เอนโดธีลิน-1, Substance P, PGE2, c-AMP, and c-GMP;
Ray Biotech Inc (Norcross, GA, USA) for แอคติวิน, Lox-1, เลปติน, EGF, ไลโปคาลิน, อะดิโพเนคติน, TNFalphaรีเซปเตอร์ 2 and HVEM,
30 Biovendor GmbH (Heidelberg, Germany) for PEDF, VILIP-1;