1 Örebro University
School of Medical Sciences Degree project, 30 ECTS 6 Jan 2016
Bipolar disorder and routine clinical
biomarkers of inflammation:
a systematic review
Version 1Author: Ida Bark, Bachelor of Medicine Supervisor: Julia Sabet, PhD
2 Table of content
1. Abstract p. 3
2. Abbreviations p. 4
3. Introduction p. 5
4. Methods and materials p. 8
4.1 Eligibility criteria p. 8 4.2 Information search p. 9 4.3 Ethics p. 10 5. Results p. 11 5.1 Study selection p. 11 5.2 Study characteristics p. 11
5.3 Comparisons of inflammatory markers p. 17
5.3.1 C-reactive protein p. 17
5.3.2 Leukocyte count p. 17
5.3.3 Neutrophil count / percentage p. 17
5.3.4 Lymphocyte count / percentage p. 17
5.3.5 Platelet count p. 18
5.3.6 Monocyte percentage p. 18
5.3.7 Ratios p. 18
5.3.8 Difference between BD mood states p. 18
5.4 Quality assessment of included studies p.19
6. Discussion p. 20
7. Conclusion p. 22
8. References p. 23
3 1. Abstract
Introduction: Bipolar Disorder (BD) is a chronic psychiatric illness associated with
psychiatric and medical co-morbidity as well as an unhealthy life-style. Increasing evidence points towards a link between BD and inflammation and/or immune dysfunction.
Our aim was to review studies investigating inflammation in patients with BD using inflammatory markers commonly used in everyday clinical practice.
Methods: We conducted a systematic review of studies comparing BD-patients with a control group regarding inflammatory markers in peripheral blood. Searches were made in PubMed and PsycInfo and articles were selected for full-text reading based on evaluation of abstract. Results: Forty-five articles were selected for full-text reading and of these, 24 were included in the review. Several studies showed significantly elevated levels in the BD group for CRP, leukocytes and neutrophils while decreased levels were found for lymphocytes, although other studies could not show a significant difference.
Conclusion: This review provides further support for a link between BD and inflammation, although the direction of causality remains unclear, and points toward lymphocyte count / percentage as a promising marker for further studies. Our opinion is that inflammation in the future might become one useful piece of the puzzle that is caring for and treating patients with bipolar disorder.
4 2. Abbreviations
BD = Bipolar disorder BMI = Body mass index CI = Confidence interval COX-2 = Cyclooxygenase-2 CRP = C-reactive protein
ESR = Estimated sedimentation rate
hsCRP = High sensitivity C-reactive protein IL = Interleukin
NLR = Neutrophil - lymphocyte ratio PLR = Platelet - lymphocyte ratio
SBU = ”Statens beredning för medicinsk och social utvärdering” (swe) SD = Standard deviation
SEM = Standard error of the mean TNF-α = Tumor necrosis factor alpha WBC = White blood cell
5 3. Introduction
Bipolar disorder (BD) is a chronic psychiatric illness with a prevalence of 1-4.4% depending on country and whether sub-threshold BD is included. The onset of the disease most
commonly occurs in late adolescence or young adulthood and the disease is associated with a substantial economic and psychosocial burden [1].
BD is characterized by recurrent mood episodes, both depressed and manic, with intermittent periods of neutral mood, called euthymia.
A mood episode can also be characterized as “with mixed features” meaning an episode of mania/hypomania or depression but with symptoms of the other state as well [2].
BD is classified as BD type I or BD type II according to DSM-V. The main difference is that mania is present in BD type I, while persons with BD type II only experience hypomania. Both mania and hypomania are characterized by an “elevated, expansive or irritable mood”, but what differentiates them is that mania is associated with a marked impairment in
functioning, requires hospitalization, or includes psychotic features.
If any of the criteria for BD type I or II are not met, a physician may diagnose a patient with “Other specified/Unspecified Bipolar and Related Disorders” [2].
Despite the focus on mania/hypomania in BD, several studies show that bipolar patients spend a significantly greater time depressed than manic or hypomanic. It is also the depressed state that is associated with the greatest risk of suicide [1].
Patients with BD experience a high level of co-morbidity, both psychiatric and medical [1]. It has been shown that the all-cause mortality rate among patients with BD is about twice as high as that of the general population. Some of this excess mortality is explained by a high rate of suicide and other violent deaths. A meta-analysis by Hayes et al. estimated the standardized mortality ratio for suicide to be 14.44 (95% CI 12.43-16.78) [3].
Despite this, most patients with BD do not die of suicide. A Swedish study found that suicide and other external causes (accidents and homicide) only accounted for 18 % of deaths
whereas cardiovascular disorders (CVD) accounted for 38% [4]. The same study concluded that “persons with BD died of CVD approximately 10 years early” compared to the general population [4].
6
This excess mortality from physical illness may have several explanations. One cause might be the unhealthy lifestyle of many persons with BD.
For example, among persons with BD, the prevalence of smoking is approximately 2 to 3 times that of the general population [5]. Persons with BD also have a higher rate of metabolic syndrome than the general population [2].
In addition to the unhealthy lifestyle, evidence also points toward the presence of a low-grade inflammation and an immune dysfunction in individuals with BD [6].
Two recent meta-analyses have examined the levels of cytokines in individuals with BD [7,8]. Both studies showed elevated levels of several cytokines and cytokine receptors, both pro-inflammatory cytokines such as TNF-α and anti-pro-inflammatory cytokine IL-4.
The brain is protected from the peripheral blood, so cytokines can’t freely access and
subsequently affect the brain. They can however, reach and/or impact the brain in a number of ways, for ex via active transport, via leaky parts of the blood-brain barrier or by stimulation of peripheral afferent nerves [9].
Another meta-analysis from 2013 found that the acute-phase protein C-reactive protein (CRP) was elevated in BD subjects compared to controls [10].
The relationship between inflammation and mental disorders may go both ways, but there is evidence that inflammation can cause depression. Wright et al. showed that healthy
individuals who were injected with a typhoid vaccine had increased levels of IL-6 and experienced a decrease in mood [11].
Another study by Alavi et al. showed that treatment with pegylated interferon against hepatitis C led to the development of new-onset depression in 35% of participants [12].
Because of the potential relationship between inflammation and mental illness, anti-inflammatory agents may also play a part in the treatment of such diseases.
One study, albeit small, showed that the COX-2 inhibitor Celecoxib, in combination with antidepressant Reboxetine, gave a significantly greater improvement in depressed patients compared to Reboxetine alone [13].
Another study that investigated Etanercept, a soluble TNF-α receptor, as therapy for psoriasis, found that this inhibitor of TNF-α action also reduced depression in these patients - an effect that was not clearly associated with improvement in skin and joint symptoms [14].
7
The association between BD and inflammation is complicated by several factors, for example the increased prevalence of metabolic syndrome [2]. Metabolic syndrome has been shown to lead to elevated levels of both CRP and leukocytes, with central obesity being the component most strongly associated with the elevation of these inflammatory markers [15].
One of the most used substances in the treatment for BD, lithium, adds further complexity to the question of the immune system in BD. Lithium is known to cause an increase in
granulocytes, while reducing the number of lymphocytes. Though lithium inhibits T-lymphocyte production, it actually enhances the activity of T-cells [16].
Individuals who suffer from BD seem to follow a downward path during their illness. This process has been called neuro-progression and is characterized by increasing cognitive impairment, shorter intervals between mood episodes and decreased likelihood of responding to treatment [17]. This process seems to be linked, at least in part, to the number of mood episodes experienced by the individual (F) [18].
Inflammation is one of the factors that have been implicated in this process [17], and
inflammatory biomarkers such as cytokines may be used in the staging of BD, as proposed by Kapczinski et al. [18].
The aim of this systematic review is to compare persons diagnosed with Bipolar disorder with the general population and also between different BD mood states, regarding concentrations of inflammatory markers used in everyday clinical practice. This is done to present further evidence of the link between BD and inflammation, and provide a foundation and direction for further research.
8 4. Materials and methods
The primary objective was the comparison of persons diagnosed with BD with the general population (represented by a control group). Studies were elected based on the criteria below. A secondary objective was to compare groups of BD patients between the three main mood states (mania/hypomania, depression and euthymia) using studies already included based on the inclusion criteria for the primary objective.
4.1. Eligibility criteria
Inclusion criteria:
1) Original observational studies
2) Studies comparing individuals diagnosed with Bipolar Disorder, with a control group representing the general non-BD population, also accepting control groups
described as “healthy” or “normal”. Studies investigating additional groups besides BD, such as schizophrenia or major depression, were not excluded but the results from these groups are not reviewed.
3) Comparison made for any of the inflammatory markers presented in figure 1. All markers are characterized by being measured in peripheral blood and available in everyday clinical practice.
4) Studies comparing levels of the above-mentioned inflammatory markers and stating statistical significance. 5) English language studies
Exclusion criteria: 1) Duplicate studies 2) In vitro studies 3) Non human studies
4) Studies with a mixed patient group including individuals with disorders other than BD, if the group is not also divided and presented as distinct groups.
5) Studies without an available abstract
Figure 1. Biomarkers included in the review
Inflammatory markers included:
CRP (including hsCRP)
ESR
Total platelet count
Total leukocyte count
Lymphocytes total count or percentage as part of WBC differential count
Neutrophil total count or percentage as part of WBC differential count
Monocyte total count or percentage as part of WBC differential count
Lymphocyte/Neutrophil ratio and additional ratios between the above cell populations.
9
4.2. Information search
Studies were identified by searching the databases PubMed and PsycInfo. A test search was also made in Cochrane but this yielded very few results and Cochrane was therefore not used.
The first search in PubMed was performed on 6 Oct 2015 in the following way:
“Bipolar disorders AND C-reactive protein OR CRP OR hsCRP OR ESR OR Estimated sedimentation rate OR leukocyte* OR monocyte* OR lymphocyte* OR neutrophil* OR platelet* OR trombocyte*”
In addition a filter was used for English language and human studies.
A further search in PubMed was performed on 19 Oct 2015 for Bipolar Disorder AND granulocyte* since this term was missing in the first search. With filters for human studies and English language, this yielded 15 articles, none of which were selected for full text reading.
The first search in PsycInfo was performed on 19 Oct 2015 in the following way: Bipolar disorder AND C-reactive protein OR CRP OR hsCRP OR ESR OR Estimated sedimentation rate OR leukocyte* OR monocyte* OR lymphocyte* OR neutrophil* OR platelet* OR thrombocyte* OR granulocyte*. Filters were used for English language and human studies.
From the results obtained in the above searches, articles were selected for full-text reading by reading the abstracts.
Reference lists of selected full text articles were hand searched to find additional articles and a second search, using the same search terms and criteria, was performed in both databases on 20 Nov 2015 to identify recently published articles.
The results of the search and the selection process are presented in figure 2.
In the case of studies that were not easily excluded or included, these were discussed with the supervisor.
Three studies by Hope et al [19-21] used the same sample. Of these, two [19,20] made unique comparisons and were included with only these unique comparisons reviewed. The third [21] was excluded.
Two studies by Bai et al [22,23] also used the same sample but made unique comparisons and were therefore included.
10
One study [24] was part observational and part interventional. This study was included but only the observational part was used.
No study investigated ESR, and this marker is therefore discussed no further.
All studies included in the review were assessed for quality, using a form adapted by the author from SBU’s form for evaluation of observational studies [25] . The form is presented in appendix 1.
Three of the studies included in the review were also assessed by the supervisor, to evaluate the work of the author.
4.3. Ethics
11 5. Results
5.1. Study selection
The search in PubMed yielded 687 articles and the search in PsycInfo yielded 412 articles. After selection from abstracts and exclusion of duplicates, 45 articles remained for full text evaluation [19,20,22-24,26-65]. One additional article for full-text evaluation was identified from scanning references [66] and 1 article was identified in the updated search [21] (for details see figure 2).
Of these 47 studies read in full text, 23 were excluded. Seven studies were excluded because they lacked a control group [32,38,42,48,51,61,65]. Ten studies were excluded because they did not investigate any of the markers selected for this review or they did not compare the markers between BD-patients and controls [27,37,41,43,49,50,53-55,57]. Three studies were excluded because the BD population was mixed with other populations for the comparison [39,52,66]. One study was excluded because it did not include a BD group [28]. One study did not report statistical significance for the comparison [62]. One study used the same population and comparison as an already included study [21].
After exclusion, 24 studies remained for inclusion in the review [19,20,22-24,26,29-31,33-36,40,44-47,56,58-60,63,64].
5.2. Study characteristics
All studies are presented in detail in table 1.
Seven of the studies were conducted in Taiwan [22,23,45,46,56,58,59]; 4 in the USA [33,35,36,44]; 3 studies each in Turkey [29,47,60] and Brazil [30,31,40]; 2 each in Norway [19,20] and Italy [24,34]; and 1 each in Egypt [26], South Africa [63] and Sweden [64]. Three of the studies were published before the year 2000 [33,44,64], 9 between 2000-09 [19,24,26,31,34,35,45,46,63], and 12 after 2010 [20,22,23,29,30,36,40,47,56,58-60]. Four of the studies used only male participants [33,46,47,56].
12 Figure 2. Flowchart of article selection process.
13 Table 1. Study characteristics. 1 Group definitions are the same as used in the original study. 2 Arrows show whether levels are elevated or decreased in the BD population. NLR = Neutrophil-Lymphocyte Ratio, PLR = Platelet-Lymphocyte Ratio, SD = Standard Deviation, SEM = Standard Error of the Mean, CI = Confidence Interval
17
5.3. Comparisons of inflammatory markers
5.3.1 C-reactive protein
C-reactive protein (CRP) was investigated in 18 studies [19,20,22,23,30,31,34-36,40,44-46,56,58-60,63], containing 38 comparisons between BD-patients and controls. Of these comparisons, 18 showed a statistically significant difference, with elevated levels in the BD groups, and 1 was close to achieving significance.
Of the comparisons, 10 were done between manic patients and controls, and 7 of these showed statistical significance. Eight comparisons were done between depressed patients and controls, 2 of which showed significance; and 8 comparisons were done between euthymic patients and controls, 3 of which showed significance.
5.3.2 Leukocyte count
Leukocyte count was investigated in 7 studies [26,29,33,40,58,59,64], containing 9
comparisons between BD-patients and controls. Of these comparisons, 1 showed a significant elevation in the BD group and 1 was close to achieving significance.
5.3.3 Neutrophil count / percentage
Neutrophil count and/or percentage was investigated in 5 studies [29,33,47,58,59], containing 7 comparisons. Of these comparisons, 3 showed a significant elevation in the BD groups and 1 was close to achieving significance.
5.3.4 Lymphocyte count / percentage
Lymphocyte count and/or percentage was investigated in 7 studies [26,29,33,47,58,59,64], containing 10 comparisons. Of these comparisons, 6 showed a significant decrease in the BD group.
18
5.3.5 Platelet count
Platelet count was investigated in 6 studies [24,29,40,47,58,59], containing 9 comparisons, none of which showed a statistically significant difference.
5.3.6 Monocyte percentage
Monocyte percentage was investigated in 2 studies [58,59], containing 2 comparisons, none of which showed a statistically significant difference.
5.3.7 Ratios
Neutrophil-lymphocyte ratio was investigated in 2 studies [29,47], containing 3 comparisons, all of which showed a significant elevation in the BD groups.
Platelet-lymphocyte ratio was investigated in 1 study [47], containing 2 comparisons, both of which showed a significant elevation in the BD groups.
5.3.8 Difference between BD mood states
Eight studies investigated differences between mood states for several markers [20,22,30,31,34,40,47,59].
Seven studies contained comparisons of CRP; 6 comparisons between manic and euthymic, 3 of which showed a significant elevation in the manic group; 5 comparisons between manic and depressed, 2 of which showed a significant elevation in the manic group; and 6
comparisons between depressed and euthymic, 1 of which showed a significant elevation in the depressed group.
Two studies compared mood states for several markers other than CRP, none of which were significant.
19
5.4. Quality assessment of included studies
The results of the quality assessment are presented in table 2. The results of the assessment showed great variability between studies. While the majority of studies used populations that were similar regarding age and sex, only a minority also adjusted for BMI. No studies could declare any conflicts of interest.
Table 2. Results from quality assessment. See also appendix 1.
1a 1b 1ci 1cii 2 3a 3b 3c 4a 4b Bai et al, 2015 [23] (-) 1 0 0 0 1 0 0 1 1 Cakir et al, 2015 [29] 1 1 0 0 1 1 1 0 1 1 Kalelioglu et al, 2015 [47] (-) 1 1 1 1 1 1 0 1 1 Uyanik et al, 2015 [60] (-) 1 0 0 1 0 1 0 1 1 Bai et al, 2014 [22] (-) 1 1 1 0 1 1 0 1 1 Tsai et al, 2014 [59] 1 1 0 1 1 1 1 1 1 1 Chiarani et al, 2013 [30] (-) 1 0 1 0 0 0 0 1 1 Dickerson et al, 2013 [36] 1 0 1 1 0 0 0 0 1 1 Fontoura et al, 2012 [40] (-) 1 0 0 0 0 0 0 1 1 Tsai et al, 2012 [58] (-) 1 0 0 1 1 1 1 1 1 Hope et al, 2011 [20] 1 1 0 0 1 0 0 0 1 1 Su et al, 2011 [56] 1 1 0 0 1 1 0 0 1 1 Hope et al, 2009 [19] 1 1 1 0 1 0 0 0 1 1 Cunha et al, 2008 [31] (-) 1 0 0 0 1 0 0 1 1 De Berardis et al, 2008 [34] 1 1 0 0 1 1 1 0 1 1 Dickerson et al, 2007 [35] 1 0 1 0 0 0 0 0 1 1 Huang et al, 2007 [45] 1 0 0 0 1 1 1 0 1 1 Hung et al, 2007 [46] 1 1 0 0 0 1 0 0 1 1 Abeer et al, 2006 [26] 1 1 0 0 1 0 0 0 1 1 De Berardis et al, 2003 [24] (-) 1 0 0 1 0 0 0 1 1 Wadee et al, 2002 [63] (-) 1 0 0 0 0 0 0 1 1 Hornig et al, 1998 [44] 1 0 1 0 1 0 0 1 1 1 Darko et al, 1988 [33] (-) 1 0 0 1 0 1 0 1 1 Wahlin et al, 1984 [64] 1 (-) 0 0 0 0 0 0 1 1
20 6. Discussion
Most studies included in this review investigated CRP and several of them could demonstrate elevated levels in the BD population compared to controls, supporting the theory that BD is associated with inflammation. Elevated levels in the BD population could also be
demonstrated for total leukocytes and neutrophil percentage / total count in some studies, while no studies could demonstrate any significant change for platelets or monocytes. The only marker associated with decreased levels in the BD population was lymphocytes, and there was a larger proportion of significant comparisons for lymphocytes than for most other markers. The ratios including lymphocytes also showed a statistically significant difference between groups; both NLR and PLR were elevated in the BD group compared to controls, which, in the case of NLR, might be explained both by elevated levels of neutrophils and decreased levels of lymphocytes, giving this marker the potential of being useful in future studies of inflammation in BD. Unfortunately, there were few studies investigating lymphocytes.
The difference in lymphocytes is in line with previous meta-analyses demonstrating changes in the levels of cytokines, since lymphocytes are a major contributor of cytokines in the body, although the production of cytokines is not only depending on the number of cells but also the amount of cytokines produced by each cell [7,8].
There was a larger proportion of significant comparisons when considering groups with only manic patients, suggesting that mania might be the state with the strongest link to
inflammation, a finding that has not been clearly shown by earlier meta-analyses [7,8]. The meta-analysis by Dargél et al. concerning CRP in BD included 11 studies, 9 of which were also included in our study [10]. We have been able to include 4 studies investigating CRP that were published after the meta-analysis, all of which showed significantly elevated levels for one or several comparisons. This supports the finding in the meta-analysis of elevated levels of CRP among BD patients.
One strength in this review is that we were able to include more studies compared to the meta-analysis. The reason for this is that the review methodology has less demands on homogeneity between studies. The disadvantage of this is that the studies are not easily comparable because of differences in several areas. Many studies focus on subgroups of patients regarding mood state and treatment. Some studies also used median or percentage above a cut-off value instead of mean and standard deviation.
21
To our knowledge, there is no meta-analysis or systematic review regarding any of the other markers included besides CRP. This systematic review may therefore serve to point to markers that could be used for future studies looking at changes in inflammatory markers in patients with bipolar disorder.
The link between inflammation and BD is complicated by several factors, for example obesity, medication and co-occurring medical illness with elements of inflammation. If the aim is to identify potential causes of BD, an ideal study would adjust for all these factors, and use a control group without additional complicating variables. One such aspect that is
complicating the comparison between BD patients and controls is that several studies use control groups made up of hospital staff. While these controls are close to the patients in time and place, they have demanding occupations that involve irregular working hours and
possibly large amounts of both physical and psychological stress, all of which could potentially affect inflammatory markers.
If instead inflammation is considered as important for these patients regardless of the specific cause, it is of less importance which factor is the major contributor.
One major question is that of causality, determining whether inflammation is a cause or an effect of BD. The current review is composed mainly of cross-sectional studies, making it difficult to say anything about the causality and the temporal relationship between
inflammation and BD.
It is not likely that inflammatory markers will ever be used in the diagnosis of BD, since there is already a well established system for diagnosing psychiatric illnesses using the DSM manual, but they might serve to point to the potential link between BD and inflammation - a link that may explain some parts of the disease, for example co-morbidity and
neuro-progression. BD is a chronic illness that is often present during the majority of the patients’ lifetime, so even a low-grade inflammation has the potential to affect the individual.
It should be of great interest to consider all parts of the disease and the life of the patient in the treatment, not only focusing on the mental disability itself but also trying to improve the situation regarding co-morbidity and unhealthy lifestyle. And it is in this comprehensive view that inflammation may play a part.
22 7. Conclusion
Several studies showed a significant difference between BD patients and controls for several markers while other studies could not find any statistically significant difference. The major contribution of our work is to provide a foundation for further research in this area, pointing towards inflammatory markers that may be of importance in the development and treatment of the illness.
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29 Appendix 1
Form for quality assessment modified from SBUs form for evaluation of observational studies [25].
All questions are answered "yes", "no" or "unclear" and presented in table 2. Yes = 1
No = 0 Unclear = (-)
If the study has several comparisons and these comparisons have varying quality, the
questions will be answered in favor of the study. For ex: If question 3c) would be 1 for CRP and 0 for neutrophils, the question may be answered with 1.
1. Selection bias
a) Was the compared groups (BD and control) similar regarding time and place ( mod. from SBU A1a)
b)Was the composition of the compared groups (BD and control) sufficiently alike at the start of the study / before adjustment? (SBU A1 b)
Regarding age and sex
c) Have adjustment for differences in baseline values been done (SBU A1 c) i. Regarding age and sex
ii. Regarding BMI
2. Treatment bias (mod. from SBU A2)
a) Have the authors minimized differences between the groups (BD and control) regarding factors that may act pro- or anti-inflammatory? (For example anti-inflammatory medication or occurrence of known inflammatory diseases)
30
3. Detection bias (mod from SBU A3)
a) Have the blood samples been obtained in the same way in all groups regarding fasting state?
b) Have the blood samples been obtained in the same way in all groups regarding time of day for sampling
c) Have the samples from all participants been analyzed in the same assay? (Eliminating inter-assay variability)1
4. Other considerations
a) Is there, based on information given by the authors, a low or non-existent risk that the results have been influenced by any conflicts of interest? (SBU A6 a)
b) Is there, based on information given by the authors, a low or non-existent risk that the results have been influenced by any financial support? (SBU A6 b)
1
= This should only be possible for CRP since the blood samples for analyses of blood cell populations can’t be stored.
31
Letter of intent
Jan 6, 2015Corresponding author: Ida Bark
Bachelor degree, major in medicine Örebro University, Sweden
I am sending my manuscript titled Bipolar disorder and routine clinical biomarkers of inflammation: a systematic review for consideration.
This paper is a systematic review concerning the levels of inflammation in patients with bipolar disorder as compared with healthy controls. The markers included were chosen based on availability as they are all used in everyday routine clinical work.
Studies were identified in PubMed and PsycInfo, and 24 original articles were included in the final review. This is a larger sample compared to the recent meta-analysis by Dargél et al investigating levels of C-reactive protein.
This review also has the advantage of including several markers that were investigated in only a few articles, thereby presenting possible future areas of research.
Besides the marker CRP, that constitutes the majority of the comparisons included in this review, the results point toward a biomarker that should be further investigated in the future - lymphocyte count.
I hope to hear from you as soon as possible. Sincerely
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Ethical considerations
This review does not contain any original data since the material used is already published. This means that no participants have been exposed to any discomfort or any risks as a result of this study, but this review and other research in the same area may still have consequences for patients with Bipolar disorder in the future.
If inflammatory markers play a part in the diagnosis and treatment of bipolar patients in the future, samples will have to be taken from patients.
The analyses used in this review have the advantage of being performed on peripheral blood, drawn by venipuncture. For most people, this is regarded as an acceptable amount of
discomfort, but for some it may be accompanied by emotional stress.
For many patients, the stress can be reduced by simply taking the samples at the same time as other samples, for example during the periodic check-ups of lithium-treated patients.
If these biomarkers were ever to be used in the treatment of these patients, it would be so for a reason, and in that case a small discomfort should be an acceptable price to pay for a better treatment of both mental and physical illness.
Another concern is the potentially increased cost and work-load for the health-care system. The biomarkers in this review are chosen based on their routine use in clinical practice. The tests should be able to be ordered from any hospital laboratory at a low cost and are therefore ideal in this respect.
33
Press release
Bipolär sjukdom är en kronisk psykisk sjukdom som innebär stora besvär för den som drabbas, både psykiskt och fysiskt. Bipolär sjukdom är nämligen associerad med ökad belastning av andra sjukdomar samt med en ohälsosam livsstil, t ex ökad förekomst av rökning och övervikt.
Det finns forskning som tyder på att bipolär sjukdom har ett samband med inflammation, och syftet med vårt arbete är därför att ytterligare kartlägga och styrka detta samband. Vi har sammanställt redan publicerade vetenskapliga artiklar som undersöker sambandet mellan bipolär sjukdom och inflammation. Dessa artiklar mäter nivåerna av rutinmässigt använda blodprover, s k markörer, hos bipolära patienter och jämför dessa med en frisk kontrollgrupp. Resultatet av vårt arbete tyder på att flera olika markörer som mäter inflammation påverkas vid bipolär sjukdom, även om resultatet inte är entydigt. Ytterligare forskning inom området behövs för att utreda hur detta samband ser ut samt hitta den markör som bäst speglar
sambandet. Vårt hopp är att sambandet mellan inflammation och bipolär sjukdom i framtiden ska utnyttjas i den sammansatta bedömningen och behandlingen av patienter med bipolär sjukdom, både vad gäller den psykiska sjukdomen i sig samt övriga aspekter av patienternas hälsa. Detta för att hjälpa patienter till en högre livskvalitet och ett längre, hälsosammare liv.
