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Betydelsen av inflammation och reninangiotensin- aldosteron-systemet vid ångest och depression

Hallberg, Ludvig LU (2016) In Lund University, Faculty of Medicine Doctoral Dissertation Series
Abstract
A number of biological systems have been studied in the past in an attempt to find the underlying cause of

anxiety and depression. The main aim of the work described in this thesis was to investigate the importance of

inflammation and the renin-angiotensin-aldosterone system (RAAS) in relation to anxiety and depression.

The methods used ranged from studying patients to preclinical animal experiments. In Study I the RAAS was

investigated in depressed patients who had recently attempted suicide, in depressed patients without a history

of attempted suicide, and in healthy controls. Psychiatric symptoms were evaluated with the Comprehensive

Psychopathological Rating Scale (CPRS). Study II... (More)
A number of biological systems have been studied in the past in an attempt to find the underlying cause of

anxiety and depression. The main aim of the work described in this thesis was to investigate the importance of

inflammation and the renin-angiotensin-aldosterone system (RAAS) in relation to anxiety and depression.

The methods used ranged from studying patients to preclinical animal experiments. In Study I the RAAS was

investigated in depressed patients who had recently attempted suicide, in depressed patients without a history

of attempted suicide, and in healthy controls. Psychiatric symptoms were evaluated with the Comprehensive

Psychopathological Rating Scale (CPRS). Study II investigated the change in plasma cytokines in depressed

patients and healthy controls during an exercise test. In Study III, the behavioural changes of rats treated with

the systemic inflammation inducer lipopolysaccharide (LPS) in combination with aldosterone were

investigated. Cytokine and cytokine mRNA concentrations were measured in blood, cerebrospinal fluid (CSF)

and the prefrontal cortex. Depressive-like behaviour in the animals was assessed using the forced swim test.

Study IV investigated depression and anxiety disorders, using the Mini International Neuropsychiatric

Interview (M.I.N.I.), in patients with suspected renal artery stenosis (RAS) in which the RAAS is overactive.

The main findings of this work were:

Depressed patients who had recently attempted suicide had significantly lower levels of aldosterone than

depressed patients without a history of suicide attempts and healthy controls. In the depressed patients who

had recently attempted suicide, a significant, negative correlation was found between aldosterone level and

the reported CPRS score.

The baseline levels of cytokines did not differ significantly between the depressed patients and the healthy

controls. The cytokines IL-6, IL-8 and TNF-α increased during the exercise test in both the depressed patients

and the healthy controls. The initial decrease in IL-6 was significantly smaller in the depressed patients than in

the healthy controls.

The treatment of rats with LPS increased the level of mRNA for IL-1β in the prefrontal cortex. Both treatment

with aldosterone and LPS increased the concentration of IL-1β in CSF. Aldosterone treatment also increased

the concentration of IL-6 in serum, and depressive-like behaviour. A positive correlation was found between

depressive-like behaviour and IL-1β, TNF-α and CINC-1 levels in CSF.

Eighteen of the 59 patients invited to participate in the research study at the vascular centre agreed to undergo

a psychiatric examination. Fifty-six per cent of the examined patients met the DSM-IV criteria for a current

anxiety disorder, 11 % met the DSM-IV criteria for current episode of depression, and 16.6 % had attempted

suicide at least once in the past.

Conclusions: The findings presented in this thesis support the hypotheses that dysregulation of the RAAS

may be involved in the underlying cause of depression and possible also anxiety. Furthermore, it appears that

RAAS induces inflammation which, in itself, appears to induce symptoms of depression. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Professor Jokinen, Jussi, Umeå University
organization
publishing date
type
Thesis
publication status
published
subject
keywords
depression, anxiety, suicide, renin, aldosterone, inflammation, exercise
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
publisher
Faculty of Medicine, Lund University
defense location
Anshelmsalen
defense date
2016-05-20 13:00
ISSN
1652-8220
ISBN
978-91-7619-289-4
language
Swedish
LU publication?
yes
id
5ecb59ee-1216-422c-9278-73efc04025e7 (old id 8871753)
date added to LUP
2016-04-28 13:40:31
date last changed
2016-09-19 08:45:20
@misc{5ecb59ee-1216-422c-9278-73efc04025e7,
  abstract     = {A number of biological systems have been studied in the past in an attempt to find the underlying cause of<br/><br>
anxiety and depression. The main aim of the work described in this thesis was to investigate the importance of<br/><br>
inflammation and the renin-angiotensin-aldosterone system (RAAS) in relation to anxiety and depression.<br/><br>
The methods used ranged from studying patients to preclinical animal experiments. In Study I the RAAS was<br/><br>
investigated in depressed patients who had recently attempted suicide, in depressed patients without a history<br/><br>
of attempted suicide, and in healthy controls. Psychiatric symptoms were evaluated with the Comprehensive<br/><br>
Psychopathological Rating Scale (CPRS). Study II investigated the change in plasma cytokines in depressed<br/><br>
patients and healthy controls during an exercise test. In Study III, the behavioural changes of rats treated with<br/><br>
the systemic inflammation inducer lipopolysaccharide (LPS) in combination with aldosterone were<br/><br>
investigated. Cytokine and cytokine mRNA concentrations were measured in blood, cerebrospinal fluid (CSF)<br/><br>
and the prefrontal cortex. Depressive-like behaviour in the animals was assessed using the forced swim test.<br/><br>
Study IV investigated depression and anxiety disorders, using the Mini International Neuropsychiatric<br/><br>
Interview (M.I.N.I.), in patients with suspected renal artery stenosis (RAS) in which the RAAS is overactive.<br/><br>
The main findings of this work were:<br/><br>
Depressed patients who had recently attempted suicide had significantly lower levels of aldosterone than<br/><br>
depressed patients without a history of suicide attempts and healthy controls. In the depressed patients who<br/><br>
had recently attempted suicide, a significant, negative correlation was found between aldosterone level and<br/><br>
the reported CPRS score.<br/><br>
The baseline levels of cytokines did not differ significantly between the depressed patients and the healthy<br/><br>
controls. The cytokines IL-6, IL-8 and TNF-α increased during the exercise test in both the depressed patients<br/><br>
and the healthy controls. The initial decrease in IL-6 was significantly smaller in the depressed patients than in<br/><br>
the healthy controls.<br/><br>
The treatment of rats with LPS increased the level of mRNA for IL-1β in the prefrontal cortex. Both treatment<br/><br>
with aldosterone and LPS increased the concentration of IL-1β in CSF. Aldosterone treatment also increased<br/><br>
the concentration of IL-6 in serum, and depressive-like behaviour. A positive correlation was found between<br/><br>
depressive-like behaviour and IL-1β, TNF-α and CINC-1 levels in CSF.<br/><br>
Eighteen of the 59 patients invited to participate in the research study at the vascular centre agreed to undergo<br/><br>
a psychiatric examination. Fifty-six per cent of the examined patients met the DSM-IV criteria for a current<br/><br>
anxiety disorder, 11 % met the DSM-IV criteria for current episode of depression, and 16.6 % had attempted<br/><br>
suicide at least once in the past.<br/><br>
Conclusions: The findings presented in this thesis support the hypotheses that dysregulation of the RAAS<br/><br>
may be involved in the underlying cause of depression and possible also anxiety. Furthermore, it appears that<br/><br>
RAAS induces inflammation which, in itself, appears to induce symptoms of depression.},
  author       = {Hallberg, Ludvig},
  isbn         = {978-91-7619-289-4},
  issn         = {1652-8220},
  keyword      = {depression,anxiety,suicide,renin,aldosterone,inflammation,exercise},
  language     = {swe},
  publisher    = {ARRAY(0x18af2948)},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Betydelsen av inflammation och reninangiotensin- aldosteron-systemet vid ångest och depression},
  year         = {2016},
}