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Wikgren, Mikael
Publications (10 of 15) Show all publications
Maripuu, M., Wikgren, M., Karling, P., Adolfsson, R. & Norrback, K.-F. (2017). Hyper- and hypocortisolism in bipolar disorder: A beneficial influence of lithium on the HPA-axis?. Journal of Affective Disorders, 213, 161-167
Open this publication in new window or tab >>Hyper- and hypocortisolism in bipolar disorder: A beneficial influence of lithium on the HPA-axis?
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2017 (English)In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 213, p. 161-167Article in journal (Refereed) Published
Abstract [en]

Background: A hyperactive hypothalamic-pituitary-adrenal axis (HPA-axis) is a well-known phenomenon in bipolar disorder (BD). However, hypocortisolism has also been described and found associated with depression, low quality of life and cardiovascular risk factors in BD patients. Although the pathophysiology related to hypocortisolism in BD is largely unknown, hypocortisolism is associated with chronic stress exposure and after inducing an initial rise in cortisol long-term stress may result in a transition to hypocortisolism. BD patients are throughout life often exposed to chronic stress. We therefore hypothesized that higher age would be associated with lower HPA-axis activity especially among patients without previous mood stabilizing treatment. Methods: This cross-sectional study consisted of 159 bipolar outpatients and 258 controls. A low-dose-dexamethasone-suppression-test (DST) was used to measure HPA-axis activity. Results: Patients with BD showed a negative association between post DST cortisol and age (-3.0 nmol/l per year; p=0.007). This association gradually increased in subgroups that were naive to lithium (-7.7 nmol/l per year; p=0.001) and "all mood stabilizers" (-11.4 nmol/l per year; p=0.004). Patients exhibiting hypercortisolism were characterized by younger age and female gender, whereas patients exhibiting hypocortisolism were characterized by long disease duration without prophylactic lithium treatment as well as absence of current lithium medication. Limitations: Cross sectional study design. Conclusions: There was a negative association between HPA-axis activity and age in BD, rendering BD patients at risk for developing hypocortisolism. This association was most pronounced among patients without previous or current lithium prophylaxis.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE BV, 2017
Keywords
Bipolar disorder, Cortisol, Hypocortisolism, Hypercortisolism, Lithium, Stress
National Category
Psychiatry
Identifiers
urn:nbn:se:umu:diva-134815 (URN)10.1016/j.jad.2017.02.026 (DOI)000398868300022 ()28237543 (PubMedID)
Available from: 2017-05-30 Created: 2017-05-30 Last updated: 2018-06-09Bibliographically approved
Karling, P., Maripuu, M., Wikgren, M., Adolfsson, R. & Norrback, K.-F. (2016). Association between gastrointestinal symptoms and affectivity in patients with bipolar disorder. World Journal of Gastroenterology, 22(38), 8540-8548
Open this publication in new window or tab >>Association between gastrointestinal symptoms and affectivity in patients with bipolar disorder
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2016 (English)In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 22, no 38, p. 8540-8548Article in journal (Refereed) Published
Abstract [en]

AIM: To study if anxiety, depression and experience of stress are associated with gastrointestinal (GI) symptoms in patients with bipolar disorder.

METHODS: A total of 136 patients with bipolar disorder (mean age 49.9 years; 61% women) and 136 controls from the general population (mean age 51.0 years; 60% women) were included in the study. GI symptoms were assessed with The Gastrointestinal Symptom Rating Scale-irritable bowel syndrome (GSRS-IBS), level of anxiety and depression with The Hospital Anxiety and Depression Scale (HADS) and stress-proneness with Perceived Stress Questionnaire. Over a ten year period, all visits in primary care were retrospectively recorded in order to identify functional GI disorders.

RESULTS: In subjects with low total HADS-score, there were no significant differences in GI-symptoms between patients and controls (GSRS-IBS 7.0 vs 6.5, P = 0.513). In the patients with bipolar disorder there were significant correlations between all GSRS and HADS subscores for all symptom clusters except for "constipation" and "reflux". Factors associated to GI symptoms in the patient group were female sex (adjusted OR = 2.37, 95%CI: 1.07-5.24) and high HADS-Depression score (adjusted OR = 3.64, 95%CI: 1.07-12.4). These patients had also significantly more visits for IBS than patients with low HADS-Depression scores (29% vs 8%, P = 0.008). However, there was no significant differences in consulting behaviour for functional GI disorders between patients and controls (25% vs 17%, P = 0.108).

CONCLUSION: Female patients and patients with high HADS depression score reported significantly more GI symptoms, whereas patients with low HADS scores did not differ from control subjects.

Place, publisher, year, edition, pages
Baishideng, 2016
Keywords
Anxiety, Bipolar disorder, Brain-Gut axis, Depression, Dyspepsia, Functional gastrointestinal disorder, Gastrointestinal Symptom Rating Scale- irritable bowel syndrome, Irritable bowel syndrome, Hospital Anxiety and Depression Scale, Stress
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:umu:diva-128593 (URN)10.3748/wjg.v22.i38.8540 (DOI)000386596700010 ()27784966 (PubMedID)
Available from: 2016-12-07 Created: 2016-12-07 Last updated: 2018-06-09Bibliographically approved
Karling, P., Wikgren, M., Adolfsson, R. & Norrback, K.-F. (2016). Hypothalamus-Pituitary-Adrenal Axis Hypersuppression Is Associated with Gastrointestinal Symptoms in Major Depression. Journal of neurogastroenterology and motility, 22(2), 292-303
Open this publication in new window or tab >>Hypothalamus-Pituitary-Adrenal Axis Hypersuppression Is Associated with Gastrointestinal Symptoms in Major Depression
2016 (English)In: Journal of neurogastroenterology and motility, ISSN 2093-0879, Vol. 22, no 2, p. 292-303Article in journal (Refereed) Published
Abstract [en]

Background/Aims: Gastrointestinal symptoms and hypothalamus-pituitary-adrenal (HPA) axis dysfunction are frequently observed in patients with major depression. The primary aim of the study was to investigate the relationship between HPA-axis function and self-perceived functional gastrointestinal symptoms in major depression.

Methods: Patients with major depression (n = 73) and controls representative of the general population (n = 146) underwent a weight-adjusted very low dose dexamethasone suppression test (DST). Patients and controls completed the Gastrointestinal Symptom Rating Scale-Irritable Bowel Syndrome (GSRS-IBS) and the Hospital Anxiety Depression Scale. Medical records of the patients were screened over a ten year period for functional gastrointestinal disorder and pain conditions.

Results: Patients with high GSRS-IBS scores (above median) exhibited HPA-axis hypersuppression more often than controls (defined by the lowest 10% cutoff of the post-DST cortisol values among controls, adjusted OR 7.25, CI 1.97-26.7) whereas patients with low GSRS-IBS scores did not differ from controls concerning their post-DST cortisol values. Patients who had consulted primary care for functional gastrointestinal disorder (P= 0.039), lumbago (P = 0.006) and chronic multifocal pain (P= 0.057) also exhibited an increased frequency of hypersuppression.

Conclusions: HPA-axis hypersuppression is associated with functional gastrointestinal symptoms in patients with major depression.

Keywords
Depression, Dexamethasone, Hypocortisolism, Hypothalamo-hypophyseal system, Irritable bowel syndrome
National Category
Psychiatry
Identifiers
urn:nbn:se:umu:diva-112721 (URN)10.5056/jnm15064 (DOI)000373662200016 ()26507800 (PubMedID)
Available from: 2015-12-14 Created: 2015-12-14 Last updated: 2018-06-07Bibliographically approved
Maripuu, M., Wikgren, M., Karling, P., Adolfsson, R. & Norrbäck, K.-F. (2016). Relative Hypo- and Hypercortisolism are Both Associated with Depression and Lower Quality of Life in Bipolar Disorder. Journal of Psychosomatic Research, 85, 73-74
Open this publication in new window or tab >>Relative Hypo- and Hypercortisolism are Both Associated with Depression and Lower Quality of Life in Bipolar Disorder
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2016 (English)In: Journal of Psychosomatic Research, ISSN 0022-3999, E-ISSN 1879-1360, Vol. 85, p. 73-74Article in journal, Meeting abstract (Other academic) Published
National Category
Psychiatry
Identifiers
urn:nbn:se:umu:diva-123986 (URN)10.1016/j.jpsychores.2016.03.181 (DOI)000377627200064 ()
Note

Meeting Abstract: 55

Available from: 2016-08-19 Created: 2016-07-07 Last updated: 2018-06-07Bibliographically approved
Maripuu, M., Wikgren, M., Karling, P., Adolfsson, R. & Norrback, K.-F. (2016). Relative hypocortisolism is associated with obesity and the metabolic syndrome in recurrent affective disorders. Journal of Affective Disorders, 204, 187-196
Open this publication in new window or tab >>Relative hypocortisolism is associated with obesity and the metabolic syndrome in recurrent affective disorders
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2016 (English)In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 204, p. 187-196Article in journal (Refereed) Published
Abstract [en]

Background: Cardiovascular disease (CVD) is one of the main causes of excess deaths in affective disorders. Affective disorders are associated with increased frequencies of CVD risk-factors such as obesity, dyslipidemia, and metabolic syndrome. Stress-induced chronic cortisol excess has been suggested to promote obesity and metabolic syndrome. Chronic stress with frequent or persisting hypothalamic-pituitary-adrenal-axis (HPA-axis) hyperactivity may, over time, lead to a state of low HPA-axis activity, also denoted hypocortisolism. A low-dose weight-adjusted dexamethasone-suppression-test (DST) is considered to be a sensitive measure of hypocortisolism.

Methods: 245 patients with recurrent depression or bipolar disorder and 258 controls participated in a low-dose DST and were also examined with regard to metabolic status.

Results: Patients with hypocortisolism (low post-DST cortisol) compared with patients without hypocortisolism (normal or high post-DST cortisol) exhibited increased odds ratios (OR) for obesity (OR=4.0), overweight (OR=4.0), large waist (OR=2.7), high LDL (OR=4.2), low HDL (OR=2.4), high LDL/HDL ratio (OR=3.3), high TC/HDL ratio (OR=3.4) and metabolic syndrome (OR=2.0). A similar pattern but less pronounced was also found in the control sample.

Limitations: The cross sectional study design and absence of analyses addressing lifestyle factors.

Conclusions: Our findings suggest that a substantial portion of the metabolic disorders and cardiovascular risk factors seen in recurrent affective disorders are found among individuals exhibiting hypocortisolism. This might indicate that long-term stress is a central contributor to metabolic abnormalities and CVD mortality in recurrent affective disorders.

Keywords
Affective disorder, Cortisol, Dyslipidemia, Hypocortisolism, Metabolic syndrome, Obesity
National Category
Psychiatry
Identifiers
urn:nbn:se:umu:diva-127943 (URN)10.1016/j.jad.2016.06.024 (DOI)000383817300027 ()27367307 (PubMedID)
Available from: 2016-12-22 Created: 2016-11-21 Last updated: 2018-06-09Bibliographically approved
Maripuu, M. P., Wikgren, M., Karling, P., Adolfsson, R. & Norrback, K.-F. (2016). Relative hypocortisolism is associated with obesity and the metabolic syndrome in recurrent affective disorders. Psychoneuroendocrinology, 71, 64-65
Open this publication in new window or tab >>Relative hypocortisolism is associated with obesity and the metabolic syndrome in recurrent affective disorders
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2016 (English)In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 71, p. 64-65Article in journal, Meeting abstract (Other academic) Published
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-126310 (URN)10.1016/j.psyneuen.2016.07.167 (DOI)000382594500155 ()
Available from: 2016-11-03 Created: 2016-10-03 Last updated: 2018-06-09Bibliographically approved
Maripuu, M., Wikgren, M., Karling, P., Adolfsson, R. & Norrbäck, K.-F. (2014). Relative Hypo-and Hypercortisolism Are Both Associated with Depression and Lower Quality of Life in Bipolar Disorder: A Cross-Sectional Study. PLoS ONE, 9(6), Article ID e98682.
Open this publication in new window or tab >>Relative Hypo-and Hypercortisolism Are Both Associated with Depression and Lower Quality of Life in Bipolar Disorder: A Cross-Sectional Study
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2014 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 6, article id e98682Article in journal (Refereed) Published
Abstract [en]

Background: Depression in unipolar and bipolar disorders is associated with hypothalamic-pituitary-adrenal-axis (HPA-axis) hyperactivity. Also, unipolar disorder has recently been shown to exhibit HPA-axis hypoactivity. We studied for the first time how HPA-axis hypo-and hyperactivity relate to depression and disease burden in bipolar disorder. We were interested in studying hypocortisolism; characterized by increased HPA-axis negative feedback sensitivity and lower basal cortisol levels together with the opposite HPA-axis regulatory pattern of hypercortisolism. Methods: This cross-sectional study includes 145 type 1 and 2 bipolar outpatients and 145 matched controls. A dexamethasone-suppression-test (DST) measures the negative feedback sensitivity and a weight-adjusted very-low-dose DST was employed, which is sensitive in identifying hypocortisolism and hypercortisolism. The 25th and 75th percentiles of control post-DST values were used as cut-offs identifying patients exhibiting relative hypo-, and hypercortisolism. Self-report questionnaires were employed: Beck-Depression-Inventory (BDI), Montgomery-Asberg-Depression-Rating-Scale (MADRS-S), World-Health-Organization-Quality-of-Life-Assessment-100 and Global-Assessment-of-Functioning. Results: Patients exhibiting relative hypocortisolism expectedly exhibited lowered basal cortisol levels (p = 0.046). Patients exhibiting relative hypercortisolism expectedly exhibited elevated basal levels (p<0.001). Patients exhibiting relative hypocortisolism showed 1.9-2.0 (BDI, p = 0.017, MADRS-S, p = 0.37) and 6.0 (p<0.001) times increased frequencies of depression and low overall life quality compared with patients exhibiting mid post-DST values (eucortisolism). Adjusted Odds Ratios (OR:s) for depression ranged from 3.8-4.1 (BDI, p = 0.006, MADRS-S, p = 0.011) and was 23.4 (p<0.001) for life quality. Patients exhibiting relative hypercortisolism showed 1.9-2.4 (BDI, p = 0.017, MADRS-S, p = 0.003) and 4.7 (p<0.001) times higher frequencies of depression and low overall life quality compared with patients exhibiting eucortisolism. Adjusted OR: s for depression ranged from 2.2-2.7 (BDI, p = 0.068, MADRS-S, p = 0.045) and was 6.3 (p = 0.008) for life quality. Limitations: The cross-sectional design and lack of pre-established reference values of the DST employed. Conclusions: Relative hypocortisolism and relative hypercortisolism were associated with depression and lower life quality, providing novel insights into the detrimental role of stress in bipolar disorder.

National Category
Psychiatry
Identifiers
urn:nbn:se:umu:diva-91276 (URN)10.1371/journal.pone.0098682 (DOI)000337738600011 ()
Available from: 2014-07-28 Created: 2014-07-28 Last updated: 2018-06-07Bibliographically approved
Wikgren, M., Karlsson, T., Söderlund, H., Nordin, A., Roos, G., Nilsson, L.-G., . . . Norrback, K.-F. (2014). Shorter telomere length is linked to brain atrophy and white matter hyperintensities. Age and Ageing, 43(2), 212-217
Open this publication in new window or tab >>Shorter telomere length is linked to brain atrophy and white matter hyperintensities
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2014 (English)In: Age and Ageing, ISSN 0002-0729, E-ISSN 1468-2834, Vol. 43, no 2, p. 212-217Article in journal (Refereed) Published
Abstract [en]

Background: leukocyte telomere length (TL) is considered a marker of biological aging. Several studies have investigated the link between leukocyte TL and aging-associated functional attributes of the brain, but no prior study has investigated whether TL can be linked to brain atrophy and white matter hyperintensities (WMHs); two prominent structural manifestations of brain aging. Methods: we investigated whether leukocyte TL was related to brain atrophy and WMHs in a sample of 102 non-demented individuals aged 64-75 years. Results: shorter TL was related to greater degree of subcortical atrophy (beta = -0.217, P = 0.034), but not to cortical atrophy. Furthermore, TL was 371 bp shorter (P = 0.041) in participants exhibiting subcortical WMHs, and 552 bp shorter (P = 0.009) in older participants exhibiting periventricular WMHs. Conclusion: this study provides the first evidence of leukocyte TL being associated with cerebral subcortical atrophy and WMHs, lending further support to the concept of TL as a marker of biological aging, and in particular that of the aging brain.

Keywords
brain atrophy, older people, telomere length, white matter hyperintensities
National Category
Psychiatry Geriatrics
Identifiers
urn:nbn:se:umu:diva-50629 (URN)10.1093/ageing/aft172 (DOI)000332028600012 ()24231584 (PubMedID)
Note

Originally published in manuscript form with title The relationship of leukocyte telomere length with brain atrophy and white matter hyperintensities.

Available from: 2011-12-16 Created: 2011-12-16 Last updated: 2018-06-08Bibliographically approved
Wikgren, M., Karlsson, T., Nilbrink, T., Nordfjäll, K., Hultdin, J., Sleegers, K., . . . Norrback, K.-F. (2012). APOE ε4 is associated with longer telomeres, and longer telomeres among ε4 carriers predicts worse episodic memory. Neurobiology of Aging, 33(2), 335-344
Open this publication in new window or tab >>APOE ε4 is associated with longer telomeres, and longer telomeres among ε4 carriers predicts worse episodic memory
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2012 (English)In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 33, no 2, p. 335-344Article in journal (Refereed) Published
Abstract [en]

Both leukocyte telomere length and the apolipoprotein epsilon4 allele have been associated with mortality, cardiovascular disease, cognition, and dementia. The authors investigated whether leukocyte telomere length was associated with APOE genotype or cognitive abilities in the context of APOE genotype. The setting for this cross-sectional study was 427 nondemented individuals aged 41-81 yr. The authors found that epsilon4 carriers overall exhibited significantly longer telomeres compared with non-carriers (difference of 268 bp, p = 0.001). This difference was greatest at the lower limit of the age span and nonsignificant at the upper limit, which translated into a significantly higher telomere attrition rate (p = 0.049) among epsilon4 carriers (37 bp/years) compared with non-carriers (21 bp/year). Further, longer telomeres among epsilon4 carriers significantly predicted worse performance on episodic memory tasks. No significant associations were found on tasks tapping semantic and visuospatial ability, or among epsilon3/epsilon3 carriers. In conclusion, APOE epsilon4 carriers had longer telomeres compared with non-carriers, but higher rate of attrition. Among them, longer telomeres predicted worse performance on episodic memory tasks. These observations suggest that the epsilon4 allele is associated with abnormal cell turnover of functional and possibly clinical significance.

Place, publisher, year, edition, pages
Elsevier, 2012
Keywords
APOE, Cognition, Telomere length
National Category
Psychiatry
Identifiers
urn:nbn:se:umu:diva-33698 (URN)10.1016/j.neurobiolaging.2010.03.004 (DOI)000298171800012 ()20395015 (PubMedID)
External cooperation:
Available from: 2010-05-03 Created: 2010-05-03 Last updated: 2018-06-08Bibliographically approved
Wikgren, M., Karlsson, T., Lind, J., Nilbrink, T., Hultdin, J., Sleegers, K., . . . Norrback, K.-F. (2012). Longer leukocyte telomere length is associated with smaller hippocampal volume among non-demented APOE ε3/ε3 subjects. PLoS ONE, 7(4), e34292
Open this publication in new window or tab >>Longer leukocyte telomere length is associated with smaller hippocampal volume among non-demented APOE ε3/ε3 subjects
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2012 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 4, p. e34292-Article in journal (Refereed) Published
Abstract [en]

Telomere length shortens with cellular division, and leukocyte telomere length is used as a marker for systemic telomere length. The hippocampus hosts adult neurogenesis and is an important structure for episodic memory, and carriers of the apolipoprotein E ε4 allele exhibit higher hippocampal atrophy rates and differing telomere dynamics compared with non-carriers. The authors investigated whether leukocyte telomere length was associated with hippocampal volume in 57 cognitively intact subjects (29 ε3/ε3 carriers; 28 ε4 carriers) aged 49-79 yr. Leukocyte telomere length correlated inversely with left (r(s) = -0.465; p = 0.011), right (r(s) = -0.414; p = 0.025), and total hippocampus volume (r(s) = -0.519; p = 0.004) among APOE ε3/ε3 carriers, but not among ε4 carriers. However, the ε4 carriers fit with the general correlation pattern exhibited by the ε3/ε3 carriers, as ε4 carriers on average had longer telomeres and smaller hippocampi compared with ε3/ε3 carriers. The relationship observed can be interpreted as long telomeres representing a history of relatively low cellular proliferation, reflected in smaller hippocampal volumes. The results support the potential of leukocyte telomere length being used as a biomarker for tapping functional and structural processes of the aging brain.

Place, publisher, year, edition, pages
Public Library of Science, 2012
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-54207 (URN)10.1371/journal.pone.0034292 (DOI)000305297500024 ()22506016 (PubMedID)
Available from: 2012-04-19 Created: 2012-04-19 Last updated: 2018-06-08Bibliographically approved
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