Sie sind auf Seite 1von 5

European Psychiatry 30 (2015) 228–232

Contents lists available at ScienceDirect

European Psychiatry
journal homepage: http://www.europsy-journal.com

Original article

Heart rate variability and Omega-3 Index in euthymic patients with


bipolar disorders
A. Voggt a,b, M. Berger a,c, M. Obermeier a,d, A. Löw e, F. Seemueller a,f, M. Riedel a,g,
H.J. Moeller a, R. Zimmermann a,f, F. Kirchberg a,h, C. Von Schacky i, E. Severus a,j,*
a
Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-Universität München, Munich, Germany
b
Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Ludwig-Maximilians-Universität München, Munich, Germany
c
Klinik für Psychiatrie und Psychotherapie, Clienia Schlössli, Oetwil am See, Switzerland
d
GKM Gesellschaft für Therapieforschung mbH, Munich, Germany
e
Department of Internal Medicine, Ludwig-Maximilians-Universität München, Munich, Germany
f
Klinik für Psychiatrie, Psychotherapie und Psychosomatik, kbo-Lech-Mangfall-Klinik Garmisch-Partenkirchen, Garmisch-Partenkirchen, Germany
g
Vinzenz-von-Paul-Hospital, Rottweil, Germany
h
Dr. von Haunersches Kinderspital, Ludwig-Maximilians-Universität München, Munich, Germany
i
Department of Preventive Cardiology, Ludwig-Maximilians-Universität München, Munich, Germany
j
Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, TU Dresden, Germany

A R T I C L E I N F O A B S T R A C T

Article history: Background: Affective disorders are associated with an increased risk of cardiovascular disease, which, at
Received 4 August 2014 least partly, appears to be independent of psychopharmacological treatments used to manage these
Received in revised form 17 November 2014 disorders. Reduced heart rate variability (SDNN) and a low Omega-3 Index have been shown to be
Accepted 17 November 2014
associated with increased risk for death after myocardial infarction. Therefore, we set out to investigate
Available online 30 December 2014
heart rate variability and the Omega-3 Index in euthymic patients with bipolar disorders.
Methods: We assessed heart rate variability (SDNN) and the Omega-3 Index in 90 euthymic, mostly
Keywords:
medicated patients with bipolar disorders (Bipolar-I, Bipolar-II) on stable psychotropic medication, free
Bipolar disorder
Heart rate variability
of significant medical comorbidity and in 62 healthy controls. Heart rate variability was measured from
Omega-3 Index electrocardiography under a standardized 30 minutes resting state condition. Age, sex, BMI, smoking,
Cardiovascular disease alcohol consumption and caffeine consumption as potential confounders were also assessed.
Results: Heart rate variability (SDNN) was significantly lower in patients with bipolar disorders
compared to healthy controls (35.4 msec versus 60.7 msec; P < 0.0001), whereas the Omega-3 Index did
not differ significantly between the groups (5.2% versus 5.3%). In a linear regression model, only group
membership (patients with bipolar disorders versus healthy controls) and age significantly predicted
heart rate variability (SDNN).
Conclusion: Heart rate variability (SDNN) may provide a useful tool to study the impact of interventions
aimed at reducing the increased risk of cardiovascular disease in euthymic patients with bipolar
disorders. The difference in SDNN between cases and controls cannot be explained by a difference in the
Omega-3 Index.
ß 2014 Elsevier Masson SAS. All rights reserved.

1. Introduction impairment in psychosocial, interpersonal and occupational


functioning [29]. The life-time prevalence is around 1–5%,
Bipolar disorders (BD) are lifelong lasting affective disorders, dependent on the definition used, with both sexes being equally
manifesting themselves, in general, in early adulthood and affected [25]. The available data suggest, that life expectancy in
characterized by episodes as well as subsyndromal symptoms of patients with bipolar disorders is decreased by around 12 to
depression, hypomania and mania, associated with significant 13 years [21]. This is partly due to the increased risk of suicide,
but also a result of the increased medical burden associated
with bipolar disorders [35], with cardiovascular disease playing a
* Corresponding author. Fetscherstraße 74, 01307 Dresden, Germany.
prominent role [20]. The increased risk of cardiovascular mortality
Tel.: +49 351 4583780.
E-mail address: emanuel.severus@uniklinikum-dresden.de (E. Severus). among patients with bipolar disorders, compared to the general

http://dx.doi.org/10.1016/j.eurpsy.2014.11.010
0924-9338/ß 2014 Elsevier Masson SAS. All rights reserved.
A. Voggt et al. / European Psychiatry 30 (2015) 228–232 229

population, may be accounted for by a higher prevalence of München. Recruitment for this study took place between 06/2011–
established cardiovascular risk factors in patients with bipolar 11/2011. The group consisted of healthy volunteers who did
disorders [42], but also due to depressive symptoms themselves neither meet at the time of the assessment nor in the past any
[34]. DSM-IV criteria for a mental disorder, as judged by the SCID (DSM-
Measurement of heart rate variability (HRV), with the standard IV). Furthermore, they had never received any kind of formal
deviation of all NN intervals (SDNN) as key parameter, can serve as psychotherapy. In addition, they had to be able to give written
a tool for cardiovascular risk stratification [16]. Decreased HRV has informed consent. Exclusion criteria included, among others,
been associated with increased cardiac morbidity and mortality, significant medical comorbidity (e.g. cardiovascular disease), any
especially in post-MI patients [6]. In a meta-analysis patients with acute and life-threatening condition, a current significant suicidal
SDNN below 70 ms on 24 hours ECG recording had an almost or homicidal risk or current substance use, apart from smoking and
4 times greater probability of death within the next 3 years caffeine consumption.
compared to those with an SDNN > 70ms [5]. Interestingly, After having signed informed consent, healthy controls as well
preliminary data suggest that point-process heart rate variability as patients underwent a structured medical history as well as a
non-linear methodology may even help to successfully recognize physical and neurological examination.
mood states in patients with bipolar disorders [39]. One of the Continuous electrocardiographic (ECG) recordings (ProSciCard
modulators of heart rate variability is the content of eicosapen- III, CPS medical) were obtained from all study participants during a
taenoic + docosahexaenoic acids (EPA + DHA) in erythrocytes, i.e. 30 minutes interval. This 30 minutes time interval was chosen as
the Omega-3 Index [15]. Although not entirely consistent, a preliminary data suggested, that shorter-term (5 minutes) record-
positive correlation between cellular content of omega-3 poly- ings yield intolerably high intra-individual variability with regard to
unsaturated fatty acids (PUFA) and HRV, specifically SDNN, has the primary outcome parameter (SDNN). In contrast, 24 hours
been found, with intervention studies with EPA + DHA supporting recordings proved unacceptable for the majority of our outpatients
causality [7,10]. A recent meta-analysis suggested that adjunctive and healthy controls and would have limited the external validity of
omega-3 fatty acids might improve depressive symptoms in our findings. SDNN was chosen as standard parameter for HRV as it
bipolar disorders [31]. Taken together these data are compatible can be applied to any short- or long-term recording [41] and provides
with the hypothesis that a deficiency of omega-3 fatty acids may be better prognostic information than any single other HRV parameter
a risk factor for both depression and cardiovascular mortality [33]. [37]. Continuous ECG recordings were done in a supine position,
Up to now there are few studies examining HRV (SDNN) in during normal breathing, after a short rest. The room was slightly
bipolar disorders. So far, the available data point to a decreased darkened and had a comfortable room temperature. Participants
HRV compared to healthy controls [22,23,26], even when euthymic were asked to relax and stay awake during the test period. Careful
[11]. However, none of these studies incorporated the content of considerations were made to ensure subjects were not disturbed by
Omega-3 Index as a potentially modulating variable. Therefore, we noise. The recordings took place at the same time of the day,
set out to investigate SDNN and the Omega-3 Index in euthymic commonly between 10 am and 2 pm, with few exceptions being
patients with bipolar disorders, as compared to healthy volunteers. equally distributed between the groups. The ECG recordings were
We hypothesized that HRV (SDNN) would be lower in euthymic transferred continuously to the monitor. ProSciCard computer
patients with bipolar disorders, as compared to healthy controls, system (ProSciCard III) was installed for analyzing HRV. By using
and that this difference would be, at least partly, explained by a the recorded NN intervals, the standard deviation of the NN interval
lower Omega-3 Index in the bipolar patient group. (SDNN) (as a statistical time domain measure) was calculated
[12]. The system’s internal check of the data was performed by Task
Force Analysis, artifacts were marked. Before elimination of the
2. Methods artifacts, the investigator herself (A.L.) double-checked if the artifacts
set by the software were correct and could, in addition, mark artifacts
The data used in this study were derived from 2 separate studies herself [12], if overlooked by the software. Artifacts were defined as a
both approved by the institutional review board of the faculty of fluctuation range of more than 15% of the RR intervals.
medicine of the Ludwig-Maximilians-Universität München and Blood was drawn from all study participants to determine the
carried out at the department of psychiatry and psychotherapy, Omega-3 Index. To this end, erythrocyte fatty acid composition
Ludwig-Maximilians-Universität München, in collaboration with was analyzed according to the HS-Omega-3 Index1 methodology as
preventive cardiology, Ludwig-Maximilians-Universität München, previously described [15]. Results are given as EPA plus DHA
from 04/2009–03/2012. expressed as a percentage of total identified fatty acids after response
Patient data were derived from the baseline assessment of the factor correction. The coefficient of variation for EPA plus DHA was 5%.
randomized, double-blind, placebo-controlled trial ‘‘Omega-3 Analyses were quality-controlled according to DIN ISO 15189 [15].
Fatty Acids in Bipolar Patients with a low Omega-3 Index and To determine whether age, sex, smoking status, body mass index
Reduced Heart Rate Variability: the ‘BIPO-3’ Trial’’ (NCT00891826). (BMI), caffeine consumption, omega-3 fatty acids, or HRV differed
Recruitment for this study took place between 04/2009–03/2012. between healthy controls and patients with bipolar disorders, we
To be enrolled in this study, patients had to meet the DSM-IV performed univariate tests (Fisher’s exact test and Mann-Whitney
criteria for bipolar disorders, in remission (Structured Clinical test for categorical and continuous variables, respectively). In order
Interview for DSM-IV, SCID). In addition they had to be between to test for associations with HRV, we used Mann-Whitney tests
18–65 years old, be free of psychotropic medication or on stable (categorical variables) and Spearman correlation coefficients (con-
medication for at least 2 weeks and be able to give written tinuous variables) on all study participants. No corrections for
informed consent. Exclusion criteria included, among others, multiple tests have been applied. Multivariate analyses comprised
significant medical comorbidity (e.g. cardiovascular disease), any linear models on HRV, which was transformed using the Box-Cox
acute and life-threatening condition, a current significant suicidal Transformation to attend normal distribution of the residuals.
or homicidal risk or current substance use, apart from smoking and
caffeine consumption. 3. Results
Healthy controls were recruited through postings at the
Ludwig-Maximilians-Universität München as well as mailing lists For the bipolar disorders group, 110 consecutively screened
of employees and students of the Ludwig-Maximilians-Universität patients of the BIPO-3 intervention trial were included, of whom
230 A. Voggt et al. / European Psychiatry 30 (2015) 228–232

Table 1
Baseline variables: healthy controls and patients with bipolar disorders.

Healthy controls (n = 62) Bipolar disorders (n = 90) P-value

Sex
Male 27 (44%) 43 (48%) 0.62
Female 35 (56%) 47 (52%)
Smoking
Non-smoking 54 (87%) 44 (58%) 0.00016
Smoking 8 (13%) 32 (42%)
N/A 0 14
Age (years)
Median  IQR 31  19.75 (20–63) 42  19.00 (18–70) 0.0012
BMI 22.8  4.23 (18.2–34.9) 25.8  5.30 (19.7–36.2) < 0.0001
Caffeine (mg/day) 179.6  252.88 (0.0–1048.5) 199.5  266.00 (0.0–931.0) 0.023
Omega-3 Index 5.2  1.77 (3.0–12.1) 5.0  1.51 (2.5–10.5) 0.79
SDNN, ms 60.7  25.82 (15.6–129.6) 35.4  21.96 (13.4–132.4) < 0.0001
LF, Hz 0.96  0.79 (3.86–0.01) 0.24  0.52 (5.96–0.01) < 0.0001
HF, Hz 0.44  1.32 (4.01–0.02) 0.14  0.30 (2.95–0.00) < 0.0001
LF/HF ratio 1.62  1.52 (7.32–0.43) 1.97  2.00 (10.70–0.24) 0.1875

90 provided complete and valid baseline data, including HRV. For correlation between caffeine consumption and SDNN, whereas there
the healthy control group 107 healthy volunteers were screened, of was no significant interaction between the Omega-3 Index and SDNN
whom 68 fulfilled all inclusion- and exclusion criteria and signed (Table 2).
informed consent. Exclusion criteria were evidence of a current or Finally, in a multilinear regression model, only group member-
past psychiatric disorder, as assessed by the SCID (n = 32), ship (patients with bipolar disorders versus healthy controls,
significant medical comorbidity (n = 5) and dropping out because P = 0.0001) and age (P = 0.0004) significantly predicted heart rate
of personal reasons (n = 2). Out of the 68 healthy subjects variability (SDNN), whereas all other included variables (BMI,
62 subjects provided valid data in the ECG recordings, 6 subjects gender, smoking, caffeine consumption, Omega-3 Index) did not
were excluded due to too many artifacts in HRV recording (less (Table 3).
than 1500 evaluable QRS complexes).
Baseline characteristics of the patients and control group are
shown in Table 1. While sex distribution and smoking status did 4. Discussion
not significantly differ between the groups, there were significant
differences with regard to age (31 years in healthy controls versus To the best of our knowledge, this is the first study to measure
42 years in patients with bipolar disorders; P = 0.0012) and body the Omega-3 Index in patients with bipolar disorders. Conse-
mass index (22.8 in healthy controls versus 25.8 in patients with quently, this is also the first study to assess a possible association of
bipolar disorders; P < 0.0001). Regarding our hypotheses, heart the Omega-3 Index with heart rate variability (SDNN) in patients
rate variability (SDNN) was significantly lower in patients with with bipolar disorders.
bipolar disorders patients compared to healthy controls (35.4 ms In our study, euthymic patients with bipolar disorders had a
versus 60.7 ms; P < 0.0001). In the frequency domain analysis, significantly reduced SDNN compared to healthy controls. There-
both LH and HF were significantly reduced compared to healthy fore, our results are very much in line with previous studies
controls, whereas there was no significant difference regarding LF/ in which patients with bipolar disorders showed significantly
HF ratio. In contrast, the Omega-3 Index did not significantly differ reduced heart rate variability, defined as the standard deviation of
between the groups (healthy controls: 5.2%; patients with bipolar
disorders: 5.0%). Table 2
Association of key variables (Omega-3 Index, age, BMI, caffeine consumption) with
Of 90 patients, we had data on HRV and Omega-3 Index, from
heart rate variability (SDNN).
which 85 patients had complete data on medication. The most
commonly used substances ( 10% of the study population) in the Spearman correlation coefficient P-value
bipolar disorders group, based on 85 patients with complete Omega-3 Index 0.01 0.906
medication recorded, were quetiapine (57.6%, n = 49), valproate Age 0.52 < 0.001
(31.8%, n = 27), lithium (29.4%, n = 25), lamotrigine (23.5%, n = 20), BMI 0.39 < 0.001
Caffeine Consumption 0.24 0.004
olanzapine (15.3%, n = 13), aripiprazole (14.1%, n = 12), lorazepam
(11.8%, n = 10), citalopram (10.6%, n = 9), zopiclone (10.6%, n = 9)
and thyroxine (10.6%, n = 9). 5.9% (n = 5) didn‘t receive any
psychotropic drugs, 14.1% (n = 12) of the patients with bipolar Table 3
Multivariate analysis with regard to heart rate variability (HRV; SDNN, in msec).
disorders were on monotherapy for their illness, 36.5% (n = 31)
were taking two drugs, 17.6% (n = 15) were taking three drugs, Estimate Standard t value P-value
14.1% (n = 12) were taking four drugs and the remaining patients error
(n = 10) were taking 5 or more psychotropic drugs. None of the Intercept 5.83 0.35 16.48 < 0.0001
healthy controls were on psychiatric medication. However, 25.8% Group membership 0.43 0.10 4.15 0.0001
were treated with hormonal contraceptives. (bipolar)
Age 0.02 0.00 3.65 0.0004
With regard to associations of potentially confounding vari-
BMI 0.02 0.01 1.39 0.1673
ables with heart rate variability, SDNN (ms) did not statistically Gender (female) 0.01 0.10 0.06 0.9521
differ between males (50.88  26.29) and females (52.87  27.4) or Smoking (yes) 0.04 0.11 0.34 0.7318
between smoking (47.81  23.8) and non-smoking status (54.91 Caffeine 0.00 0.00 0.91 0.3638
consumption (yes)
 27.3), respectively. However there was a significant negative
Omega-3 Index 0.02 0.03 0.61 0.5427
correlation between SDNN and age as well as BMI, and a positive
A. Voggt et al. / European Psychiatry 30 (2015) 228–232 231

the successive difference in RR intervals [11,22,23,26]. Similarly, In our healthy control group some individuals were receiving
regarding LF and HF, our data are in line with some [8,26], but not hormonal contraceptives. In the only study available regarding this
all previous studies [11], reporting a significantly reduced LF and issue, SDNN did not differ in young healthy females with or
HF, compared to healthy controls. without oral contraceptives with synthetic progestagens [32].
The Omega-3 Index [40] did not differ between our euthymic In both groups, significant physical comorbidities were
patients with bipolar disorders and healthy controls, whereas in excluded, nevertheless the control group might differ with respect
patients with a diagnosis of major depressive disorder/dysthymia, to factors that affect physical and cardiac health – and ultimately
a lower Omega-3 Index than in healthy controls has been observed SDNN [18]. This could be due to the nature of the recruitment of the
[3,30]. In contrast, in patients with various medical conditions and control group, for which mentally and physically healthy people
depressive symptoms, but without a formal diagnosis of major were specifically sought. Although not likely, it is not known,
depressive disorder, the evidence is controversial [1,2,28]. Thus, whether psychotropic drugs affect the Omega-3 Index. In a
from the perspective of the Omega-3 Index, bipolar disorders previous study, antidepressant drug treatment had no significant
and major depressive disorder may represent distinct disease influence on the Omega-3 Index [3].
entities. However, most meta-analyses found evidence that both
unipolar and bipolar depression may be improved by EPA + DHA 5. Limitations
[14,31,36]. This conundrum will have to be addressed by
randomized controlled intervention trials recruiting study parti- The relatively low numbers of patients in both groups (62 healthy
cipants with major depression or bipolar disorders with a low controls, 90 patients with bipolar disorders) might have a negative
Omega-3 Index. We are currently evaluating the results of such a influence on the validity of some results. In particular, the influence
trial in patients with bipolar disorders. of caffeine consumption and BMI on SDNN might have failed to reach
In addition, contrary to previous findings in patients with somatic the level of significance due to a lack of power. However, despite the
disorders such as chronic renal failure we did not find any (positive) small sample size a significant difference between healthy controls
relationship between the intake of or levels of omega-3 fatty acids and patients with bipolar disorders concerning SDNN could be
and SDNN [10,27]. In addition, we controlled for other potentially shown. On the other hand, the missing evidence for a difference in
confounding variables such as age, sex, BMI, smoking, caffeine or Omega-3 Index does not seem to be the result of missing power, as
nicotine use. However, in a multilinear regression model, only group the values differ only very little between both groups. Another
affiliation (bipolar disorders versus healthy controls) and age limitation applies to the fact that the investigator A.L. was not blind
significantly predicted heart rate variability (SDNN). Dysregulation to group when marking artifacts, which could potentially have an
of calcium signaling is one possible explanation for both bipolar effect on the validity of the data.
disorders and reduced heart rate variability [4,9]. We are also
currently evaluating, whether the reduced HRV in bipolar disorders 6. Conclusions
respond to supplementation with EPA + DHA. More light, however,
needs to be shed on this issue [17]. In summary our study, using ECG recordings during a
All of our patients were on stable psychotropic medication for at 30 minutes interval, provided further evidence of a clinically
least 2 weeks at the time of HRV assessment, with quetiapine, significant reduction of heart rate variability (SDNN) in euthymic
valproic acid, lithium, lamotrigine, olanzapine, aripiprazole, patients with bipolar disorders [41], which was independent of the
lorazepam, citalopram and zopiclone each taken by more than Omega-3 Index. SDNN may provide a useful tool to study the
10% of the patients. Therefore, we cannot exclude the possibility impact of interventions aimed at reducing the increased risk of
that medication, at least partly, may account for the differences in cardiovascular mortality in patients with bipolar disorders
SDNN observed in our study. However, relatively little is known of [19]. The difference in SDNN between cases and controls cannot
the effects of the aforementioned medication on measures of heart be explained by a difference in the Omega-3 Index. Whether
rate variability, and in particular SDNN. A current Medline search omega-3 fatty acids improve HRV in bipolar disorders remains to
(11/01/2014) yielded few results regarding the effects of quetia- be investigated.
pine, lithium, lamotrigine or aripiprazole on measures of heart rate
variability. However, one study suggested that current use of
Disclosure of interest
atypical antipsychotics, classified as high-potency based on their
pharmacodynamic affinity for the presynaptic D2S receptor (i.e.
Clemens von Schacky operates Omegametrix, a laboratory for
aripiprazole, risperidone, and paliperidone) is associated with
fatty acid analyses. In the last three years, he has received speaker’s
lower SDNN [23]. In our study, only 14.1% of all patients were on
honoraria from Trommsdorff, the Portuguese Institute 399 of Sea
aripiprazole, and less than 10% on risperidone, with paliperidone
and Fisheries (INIAP/IPIMAR), and Newswerk.
not being used at all. Therefore, it is unlikely that these
The other authors declare that they have no conflicts of interest
medications alone account for the difference in SDNN between
concerning this article.
our bipolar disorders patients and healthy controls. Regarding
Funding and other support: This study was, in part, supported
valproic acid, the ratio of low frequency/high frequency power was
by Epax. Through the Ludwig-Maximilians-Universität München,
lower in patients on VPA compared with matched, healthy drug-
research was funded by Sanofi-Aventis.
free controls [38]. Therefore it is unclear whether the difference
found was due to the drug itself or the epilepsy as such. Concerning References
olanzapine, most studies in patients with schizophrenia show
little, if any, changes of HRV [13,24]. One trial in healthy subjects [1] Ali S, Garg SK, Cohen BE, Bhave P, Harris WS, Whooley MA. Association
reported an increase in heart rate variability after a single dose of between omega-3 fatty acids and depressive symptoms among patients with
established coronary artery disease: data from the Heart and Soul Study.
10 mg of olanzapine. In the only study in euthymic patients with
Psychother Psychosom 2009;78(2):125–7.
bipolar disorders lithium treated patients did not differ from [2] Amin AA, Menon RA, Reid KJ, Harris WS, Spertus JA. Acute coronary syndrome
patients treated only with other mood stabilizers such as valproic patients with depression have low blood cell membrane omega-3 fatty acid
acid, carbamazepine or olanzapine [11]. Therefore, Cohen et al. levels. Psychosom Med 2008;70(8):856–62.
[3] Baghai TC, Varallo-Bedarida G, Born C, Hafner S, Schule C, Eser D, et al. Major
suggested ‘‘that the findings are related more to the bipolar disease depressive disorder is associated with cardiovascular risk factors and low
and not to medications’’ [11]. Omega-3 Index. J Clin Psychiatry 2011;72(9):1242–7.
232 A. Voggt et al. / European Psychiatry 30 (2015) 228–232

[4] Berridge MJ. Dysregulation of neural calcium signaling in Alzheimer disease, [24] Mann K, Rossbach W, Muller MJ, Muller-Siecheneder F, Ru H, Dittmann RW.
bipolar disorder and schizophrenia. Prion 2013;7(1):2–13. Heart rate variability during sleep in patients with schizophrenia treated with
[5] Buccelletti E, Gilardi E, Scaini E, Galiuto L, Persiani R, Biondi A, et al. Heart rate olanzapine. Int Clin Psychopharmacol 2004;19(6):325–30.
variability and myocardial infarction: systematic literature review and meta- [25] Merikangas KR, Jin R, He JP, Kessler RC, Lee S, Sampson NA, et al. Prevalence
analysis. Eur Rev Med Pharmacol Sci 2009;13(4):299–307. and correlates of bipolar spectrum disorder in the world mental health survey
[6] Carney RM, Freedland KE, Veith RC. Depression, the autonomic nervous initiative. Arch Gen Psychiatry 2011;68(3):241–51.
system, and coronary heart disease. Psychosom Med 2005;67(Suppl 1): [26] Moon E, Lee SH, Kim DH, Hwang B. Comparative study of heart rate variability
S29–33. in patients with schizophrenia, bipolar disorder, post-traumatic stress disorder,
[7] Carney RM, Freedland KE, Stein PK, Steinmeyer BC, Harris WS, Rubin EH, et al. or major depressive disorder. Clin Psychopharmacol Neurosci 2013;11(3):
Effect of omega-3 fatty acids on heart rate variability in depressed patients 137–43.
with coronary heart disease. Psychosom Med 2010;72(8):748–54. [27] Mozaffarian D, Stein PK, Prineas RJ, Siscovick DS. Dietary fish and omega-3
[8] Chang HA, Chang CC, Tzeng NS, Kuo TB, Lu RB, Huang SY. Heart rate variability fatty acid consumption and heart rate variability in US adults. Circulation
in unmedicated patients with bipolar disorder in the manic phase. Psychiatry 2008;117(9):1130–7.
Clin Neurosci 2014;68(9):674–82. [28] Persons JE, Robinson JG, Ammann EM, Coryell WH, Espeland MA, Harris WS,
[9] Chen PS, Tan AY. Autonomic nerve activity and atrial fibrillation. Heart Rhythm et al. Omega-3 fatty acid biomarkers and subsequent depressive symptoms.
2007;4(3 Suppl):S61–4. Int J Geriatr Psychiatry 2014;29(7):747–57.
[10] Christensen JH. Omega-3 polyunsaturated fatty acids and heart rate variabili- [29] Pfennig A, Bschor T, Baghai T, Braunig P, Brieger P, Falkai P, et al. [S3 guidelines
ty. Front Physiol 2011;2:84. on diagnostics and therapy of bipolar disorders: development process and
[11] Cohen H, Kaplan Z, Kotler M, Mittelman I, Osher Y, Bersudsky Y. Impaired essential recommendations]. Nervenarzt 2012;83(5):568–86.
heart rate variability in euthymic bipolar patients. Bipolar Disord 2003;5(2): [30] Pottala JV, Talley JA, Churchill SW, Lynch DA, von SC, Harris WS. Red blood cell
138–43. fatty acids are associated with depression in a case-control study of adoles-
[12] CPS GmbH. ProSciCard III. 12-11-2009. Ref Type: Online Source. cents. Prostaglandins Leukot Essent Fatty Acids 2012;86(4–5):161–5.
[13] Eschweiler GW, Bartels M, Langle G, Wild B, Gaertner I, Nickola M. Heart-rate [31] Sarris J, Mischoulon D, Schweitzer I. Omega-3 for bipolar disorder: meta-
variability (HRV) in the ECG trace of routine EEGs: fast monitoring for the analyses of use in mania and bipolar depression. J Clin Psychiatry
anticholinergic effects of clozapine and olanzapine? Pharmacopsychiatry 2012;73(1):81–6.
2002;35(3):96–100. [32] Schueller PO, Feuring M, Sharkova Y, Grimm W, Christ M. Effects of synthetic
[14] Grosso G, Pajak A, Marventano S, Castellano S, Galvano F, Bucolo C, et al. Role of progestagens on autonomic tone, neurohormones and C-reactive protein
omega-3 fatty acids in the treatment of depressive disorders: a comprehensive levels in young healthy females in reproductive age. Int J Cardiol 2006;111(1):
meta-analysis of randomized clinical trials. PLoS One 2014;9(5):e96905. 42–8.
[15] Harris WS, von SC. The Omega-3 Index: a new risk factor for death from [33] Severus WE, Ahrens B, Stoll AL. Omega-3 fatty acids: the missing link? Arch
coronary heart disease? Prev Med 2004;39(1):212–20. Gen Psychiatry 1999;56(4):380–1.
[16] Huikuri HV, Stein PK. Heart rate variability in risk stratification of cardiac [34] Slomka JM, Piette JD, Post EP, Krein SL, Lai Z, Goodrich DE, et al. Mood disorder
patients. Prog Cardiovasc Dis 2013;56(2):153–9. symptoms and elevated cardiovascular disease risk in patients with bipolar
[17] Jan WC, Yang SY, Chuang LC, Lu RB, Lu MK, Sun HS, et al. Exploring disorder. J Affect Disord 2012;138(3):405–8.
the associations between genetic variants in genes encoding for subunits of [35] Soreca I, Fagiolini A, Frank E, Houck PR, Thompson WK, Kupfer DJ. Relationship
calcium channel and subtypes of bipolar disorder. J Affect Disord 2014;157: of general medical burden, duration of illness and age in patients with bipolar I
80–6. disorder. J Psychiatr Res 2008;42(11):956–61.
[18] Janney CA, Fagiolini A, Swartz HA, Jakicic JM, Holleman RG, Richardson CR. Are [36] Sublette ME, Ellis SP, Geant AL, Mann JJ. Meta-analysis of the effects of
adults with bipolar disorder active? Objectively measured physical activity eicosapentaenoic acid (EPA) in clinical trials in depression. J Clin Psychiatry
and sedentary behavior using accelerometry. J Affect Disord 2014;152– 2011;72(12):1577–84.
4:498–504. [37] Task Force of the European Society of Cardiology and the North American
[19] Kilbourne AM, Goodrich DE, Lai Z, Post EP, Schumacher K, Nord KM, et al. Society of Pacing and Electrophysiology. Heart rate variability. Standards of
Randomized controlled trial to assess reduction of cardiovascular disease risk measurement, physiological interpretation, and clinical use. Eur Heart J
in patients with bipolar disorder: the Self-Management Addressing Heart Risk 1996;17(3):354–81.
Trial (SMAHRT). J Clin Psychiatry 2013;74(7):e655–62. [38] Tomson T, Ericson M, Ihrman C, Lindblad LE. Heart rate variability in patients
[20] Lala SV, Sajatovic M. Medical and psychiatric comorbidities among elderly with epilepsy. Epilepsy Res 1998;30(1):77–83.
individuals with bipolar disorder: a literature review. J Geriatr Psychiatry [39] Valenza G, Citi L, Gentili C, Lanata A, Scilingo EP, Barbieri R. Point-process
Neurol 2012;25(1):20–5. nonlinear autonomic assessment of depressive states in bipolar patients.
[21] Laursen TM. Life expectancy among persons with schizophrenia or bipolar Methods Inf Med 2014;53(4):296–302.
affective disorder. Schizophr Res 2011;131(1–3):101–4. [40] von SC. Omega-3 index and cardiovascular health. Nutrients 2014;6(2):
[22] Lee JS, Kim B, Hong Y, Joo YH. Heart rate variability in the subsyndromal 799–814.
depressive phase of bipolar disorder. Psychiatry Clin Neurosci 2012;66(4): [41] Voss A, Baier V, Schulz S, Bar KJ. Linear and nonlinear methods for analyses of
361–6. cardiovascular variability in bipolar disorders. Bipolar Disord 2006;8(5 Pt 1):
[23] Linder JR, Sodhi SK, Haynes WG, Fiedorowicz JG. Effects of antipsychotic drugs 441–52.
on cardiovascular variability in participants with bipolar disorder. Hum [42] Weiner M, Warren L, Fiedorowicz JG. Cardiovascular morbidity and mortality
Psychopharmacol 2014;29(2):145–51. in bipolar disorder. Ann Clin Psychiatry 2011;23(1):40–7.

Das könnte Ihnen auch gefallen