Associations between oxidative stress and perceived stress in patients with bipolar disorder and healthy control individuals.

OBJECTIVE: Patients with neurodegenerative disorders, schizophrenia, and bipolar disorder present with increased oxidative stress markers. Not only is oxidative stress associated with development of disease, but also with increased disease progression and mortality. Oxidative stress reflects an increase in pro-oxidants, which subsequently leads to oxidative modifications of cellular components, such as RNA and DNA. Urinary excretion of 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is the valid marker of whole-body RNA and DNA damage, respectively. Recently, cerebrospinal fluid (CSF) oxidative stress markers of RNA damage (8-oxoGuo) have showed both state and trait dependence in patients with bipolar disorder. However, the relation to subjective measures of stress and quality of life (QoL) is unknown. MATERIALS AND METHODS: This prospective, longitudinal 1-year follow-up case-control study investigated the association between the oxidative stress markers, 8-oxoGuo and 8-oxodG and, perceived stress and QoL in patients with bipolar disorder (n = 86, 51% female) and gender-and-age-matched healthy control (HC) individuals (n = 44, 44% female). Oxidative stress markers obtained in CSF and urine were analysed using ultra-performance liquid chromatography-tandem mass spectrometry. The subjective perception of stress was assessed using the Perceived Stress Scale. Subjective evaluation of QoL was assessed using the World Health Organization Quality of Life questionnaire. RESULTS AND CONCLUSION: We found that markers of oxidative stress in CSF and urine were not associated with perceived stress and QoL quality in patients with bipolar disorder. However, a putative association between urinary 8-oxoGuo oxidative stress marker for RNA damage and perceived stress in HC encourages further investigations.

Alzheimer's disease related biomarkers in bipolar disorder - A longitudinal one-year case-control study.

INTRODUCTION: Bipolar disorder (BD) is a heterogeneous mental disorder characterized by recurrent relapses of affective episodes: Subgroups of patients with BD have cognitive deficits, and an increased risk of dementia. METHODS: This prospective, longitudinal, one-year follow-up, case-control study investigated biomarkers for AD and neurodegenerative diseases, namely: cerebrospinal fluid (CSF) amyloid beta (Aß) isoforms and ratios (Aß42, Aß40, Aß38), CSF soluble amyloid precursor protein (sAPP) α and ß, CSF total (t-tau) and phosphorylated tau (p-tau), CSF neurofilament-light (NF-L), CSF neurogranin (NG), plasma-isoforms Aß42 and Aß40, plasma-tau, plasma-NF-L, and serum S100B, in patients with BD (N = 62, aged 18-60) and gender-and-age-matched healthy control individuals (N = 40). CSF and plasma/serum samples were collected at baseline, during and after an affective episode, if it occurred, and after a year. Data were analyzed in mixed models. RESULTS: Levels of CSF Aß42 decreased in patients with BD who had an episode during follow-up (BD-E) (N = 22) compared to patients without an episode (BD-NE) (N = 25) during follow-up (P = 0.002). Stable levels were seen for all other markers in BD-E compared to BD-NE during the one-year follow-up. We found no statistically significant differences between patients with BD and HC at T0 and T3 for Aß42, Aß40, Aß38, Aß42/38, Aß42/40, sAPPα, sAPPß, t-tau, p-tau, p-tau /t-tau, NF-L, NG in CSF and further Aß40, Aß42, Aß42/40, t-tau, NF-L in plasma, S100B in serum, and APOE-status. Furthermore, all 18 biomarkers were stable in HC during the one-year follow-up from T0 to T3. CONCLUSION: A panel of biomarkers of Alzheimer's and neurodegeneration show no differences between patients with BD and HC. There were abnormalities of amyloid production/clearance during an acute BD episode. The abnormalities mimic the pattern seen in AD namely decreasing CSF Aß42 and may suggest an association with brain amyloidosis.

The impact of the trajectory of bipolar disorder on global cognitive function: A one-year clinical prospective case-control study.

BACKGROUND: The relationship between cognitive function and relapse of affective episodes in bipolar disorder (BD) is rarely studied. The aim of this prospective, longitudinal, case-control study was to assess the trajectory of cognitive function and mood occilations within a one-year period in patients with BD relative to healthy control (HC) individuals. METHODS: The sample included 86 outpatients with BD in euthymia, and 44 gender-and-age-matched HC. All participants were evaluated with clinical assessement and neuropsychological testing at baseline and during euthymia after a year. Further patients with BD were reevaluated if they developed a new affective episode during follow-up. The patients´ affective states were recorded on a weekly basis as asymptomatic, subthreshold level, major depression or (hypo)mania. Cognitive changes over time were measured for a global cognitive score and for the four cognitive domains: 'working memory and executive skills', 'psychomotor speed', 'sustained attention', and 'verbal learning and memory' in patients and HC. RESULTS: The study showed that cognitive performance in patients with BD was unaltered compared to baseline when they stabilised in euthymia following an affective episode and, at the one-year follow-up. Cognitive performance showed practice effect, thus improved within a year across patients with BD and HC. Furthermore, cognitive functions were not related to clinical subtypes BDI/II, prior psychosis, the polarity of the relapse and week-to-week mood fluctuations during follow-up. Functioning correlated weakly to moderately with week-to-week mood fluctuations. LIMITATIONS: Modest sample size. CONCLUSION: A one-year trajectory of BD seems to have no direct negative impact on cognitive function.

The impact of a new affective episode on psychosocial functioning, quality of life and perceived stress in newly diagnosed patients with bipolar disorder: A prospective one-year case-control study.

BACKGROUND: Bipolar disorder (BD) has been associated with impaired functioning during periods of euthymia. This prospective one-year case-control study investigated the impact of a new affective episode on psychosocial functioning, quality of life (QoL) and perceived stress in newly diagnosed patients with BD in euthymia. METHODS: Clinically evaluated psychosocial functioning (Functioning Assessment Short Test, FAST), self-reported QoL (WHOQoL-BREF scale) and stress (Cohens' Perceived Stress Scale) were collected from 87 patients with BD with (BD-E) (n=38) and without (BD-NE) (n=44) clinical relapse and 44 age and gender matched healthy control (HC) individuals at baseline (T0), following an episode if it occurred (T2) and at one-year follow-up (T3). RESULTS: Patients with BD presented with poorer functioning compared to HC individuals at T0 and T3. There was no statistically significantly difference in the changes in FAST (-1.2, adjusted-p=0.82), PSS (0.34, adjusted-p=0.93) or WHOQoL (-0.67, adjusted-p=0.93) between BD-E and BD-NE during the one-year follow-up. The subgroup BD-E had statistically significantly higher FAST and stress scores and lower WHOQoL-scores compared to BD-NE at both T0 and T3. LIMITATIONS: Modest sample size. CONCLUSION: Functioning is impaired in newly diagnosed patients with BD in a euthymic state, however, a new affective episode does not affect functioning during subsequent euthymia at one-year follow-up. Patients with BD-E presented with overall most impaired functioning, highlighting the importance of early intervention strategies as essential to identify and treat patients at high risk of relapse and poor outcome.

Cerebrospinal fluid oxidative stress metabolites in patients with bipolar disorder and healthy controls: a longitudinal case-control study.

Bipolar disorder (BD) is a mental disorder characterized by recurrent relapses of affective episodes, cognitive impairment, illness progression, and reduced life expectancy. Increased systemic oxidatively generated nucleoside damage have been found in some neurodegenerative disorders and in BD. As the first, this naturalistic prospective, longitudinal follow-up case-control study investigated cerebrospinal fluid (CSF) oxidative stress markers 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) that relate to RNA and DNA damage, respectively. Patients with BD (n = 86, 51% female) and gender-and-age-matched healthy control individuals (HC; n = 44, 44% female) were evaluated at baseline (T0), during (T1) and after a new affective episode (T2), if it occurred, and after a year (T3). Cerebrospinal and urine oxidative stress markers were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry. CSF-8-oxoGuo was statistically significantly higher by 18% (p = 0.003) in BD versus HC at T0, and by 22% (p = 0) at T3. CSF-8-oxoGuo had increased by 15% (p = 0.042) from T0 to T3, and by 14% (p = 0.021) from T2 to T3 in patients, who experienced an episode during follow-up. CSF-8-oxodG had increased by 26% (p = 0.054) from T0 to T2 and decreased by 19% (p = 0.041) from T2 to T3 in patients, who experienced an episode during follow-up. CSF-8-oxoGuo did not show a statistically significant change in HC during the one-year follow-up. CSF and urine-8-oxoGuo levels correlated moderately. In conclusion, CSF oxidative stress marker of RNA damage 8-oxoGuo showed both state and trait dependence in BD and stability in HC. Central RNA damage may be a potential biomarker for BD.