Emerging evidence suggests that neuroinflammation is involved in both depression and neurodegenerative diseases. The kynurenine pathway, generating metabolites which may play a role in pathogenesis, is one of several competing pathways of tryptophan metabolism. The present article is a narrative review of tryptophan metabolism, neuroinflammation, depression, and neurodegeneration. A disturbed tryptophan metabolism with increased activity of the kynurenine pathway and production of quinolinic acid may result in deficiencies in tryptophan and derived neurotransmitters. Quinolinic acid is an N-methyl-D-aspartate receptor agonist, and raised levels in CSF, together with increased levels of inflammatory cytokines, have been reported in mood disorders. Increased quinolinic acid has also been observed in neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis, and HIV-related cognitive decline. Oxidative stress in connection with increased indole-dioxygenase (IDO) activity and kynurenine formation may contribute to inflammatory responses and the production of cytokines. Increased formation of quinolinic acid may occur at the expense of kynurenic acid and neuroprotective picolinic acid. While awaiting ongoing research on potential pharmacological interventions on tryptophan metabolism, adequate protein intake with appropriate amounts of tryptophan and antioxidants may offer protection against oxidative stress and provide a balanced set of physiological receptor ligands.

It has been suggested that the metabolic enzyme indoleamine 2,3-dioxygenase (IDO) is a biological mediator of inflammation related to the psychopathology of depression, with a Kynurenine (KYN) increase in the Tryptophan (TRP) metabolic pathway, resulting in reduced Serotonin. In this study, we examined KYN, TRP, and the ratio of KYN to TRP concentrations × 10³ (KT Ratio) in serum and cerebrospinal fluid (CSF) in (a) a group of depressed patients and (b) a control group of patients referred to a neurologic outpatient clinic for whom no specific diagnosis could be established. The KT Ratio is considered an index that represents IDO. The participants were examined with the Beck Depression Inventory II (BDI-II), the Montgomery Aasberg Depression Rating Scale (MADRS), and a neuropsychological test battery. We found no significant differences between the two study groups with respect to TRP, KYN, or KT Ratio in serum or CSF. Differences in neuropsychological performance between the two patient groups could be seen in the following tests: Animal Fluency, Digit Symbol, the DKEFS Color-Interference Test (Naming Part), Trail Making Test A and B, and the Grooved Pegboard Non-dominant Hand. KYN in serum correlated highly with KYN in CSF. KYN in serum correlated significantly with both age and gender. When analyzing males and females separately, we found that women had a lower level of TRP in both serum (Mann–Whitney U-test: TRP in Serum; p = 0.001) and CSF (Mann–Whitney U-test: TRP in CSF; p = 0.003). Women had a lower level of KYN in serum (p = 0.029) than men did. Age was positively associated with KYN. KYN in CSF correlated only with age, however; there were no gender differences. No significant relationship was seen between BDI-II and MADRS on the one hand, and KYN and TRP on the other. KYN in CSF as the KT Ratio in both serum and CSF was associated with neuropsychological performance. Thus, we suggest that KYN and KT Ratio are related more strongly to neuropsychological performance than to affective symptoms in depression.

Introduction: Several reports indicate that inflammation may play a role in depression and demonstrate enhanced systemic levels of inflammatory mediators. We hypothesized that 44 patients with a diagnosis of depression would present with a specific and different serum and cerebrospinal fluid (CSF) cytokine profile compared to 21 patients with diffuse neurological symptoms, of whom 15 had fatigue as a major symptom, but no change in emotional state. Methods: The diagnoses of the patients with depression were according to the International Classification of Diseases, tenth edition (F32–34 spectra). Cytokine profiles in serum and CSF were determined by multiplex analysis, including 27 cytokines, chemokines, and growth factors. Results: No differences could be found between the two groups studied regarding cytokine levels in serum or CSF except for serum interleukin (IL)-1 receptor antagonist that was lower in the depression group. There were only four high correlations (>0.4) between serum and CSF levels of the cytokines, reflecting independent synthesis and turnover in these two compartments. In the control group, fatigue was associated with increased IL-1 receptor antagonist, IL-10, granulocyte-colony stimulating factor, and interferon-γ (all P<0.01). Conclusion: Patients with depression had a similar cytokine profile as nondepressive patients, both systemically and in CSF. Fatigue was associated with higher levels of some inflammatory markers in the control group. It is possible that the presence of fatigue in a large proportion of patients and controls could contribute to the lack of difference in cytokine levels between these two groups.

Background: The relationship between blood pressure (BP) and cognition is complex were age appears to be an intervening variable. High and low BP have been associated with cognitive deficits as part of the aging process, but more studies are needed, especially in more recent birth cohorts. Methods: The study sample comprised 4,465 participants, with BP measured at baseline in the Tromsø Study, Wave 6 in 2007–2008 (T0), and cognition assessed at follow-up 8 years later, in 2015–2016 in Tromsø Study 7 (T1). Age at T0 was 45–74 years, and at T1 it was 53–82 years. Cognition was assessed with three tests: The Mini Mental State Examination (MMSE), the Digit Symbol Test, and the Twelve-word Test. The associations between BP and cognition were examined specifically for age and sex using linear regression analysis adjusted for baseline BP medication use, education and body mass index (kg/m²). Results: BP was associated with cognition at the 8-year follow-up, but the association differed according to age and sex. In men, higher systolic blood pressure (SBP) and diastolic blood pressure (DBP) at a young age (45–55 years of age) was associated with poorer cognition; the association was reversed at older ages, especially for those above 65 years of age. In women, the associations were generally weaker than for men, and sometimes in the opposite direction: For women, a higher SBP was associated with better cognition at a younger age and higher SBP poorer cognition at older ages – perhaps due to an age delay in women compared to men. Digit Symbol Test results correlated best with BP in a three-way interaction: BP by age by sex was significant for both SBP (p = 0.005) and DBP (p = 0.005). Conclusion: Increased SBP and DBP at the younger age was clearly associated with poorer cognitive function in men 8 years later; in women the associations were weaker and sometimes in the opposite direction. Our findings clearly indicate that interactions between age and sex related to BP can predict cognitive performance over time. Men and women have different age trajectories regarding the influence of BP on cognition.

Aim: The primary aim of this study was to investigate the applicability of the Patient-Specific Functional Scale (PSFS) in patients with acquired brain injury (ABI) admitted to a specialized rehabilitation unit in a regional hospital. A secondary aim was to identify patient characteristics and functioning that predicted changes in the PSFS. Patients and Methods: In a cohort study, 59 patients with ABI were assessed for the ability to complete the PSFS. A trained multidisciplinary team applied the PSFS as part of a collaborative development of rehabilitation goals. The modified Rankin Scale (mRS), the Functional Ambulation Categories (FAC), the Rivermead Behavioural Memory Test (RBMT), the Norwegian Basic Aphasia Assessment (NBAA) and the Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) were used to identify characteristics of the sample. Multivariate regression analyses were performed to investigate associations between changes in the PSFS score from admission to discharge and a selected set of participant baseline characteristics and functioning. Results: Fifty-four patients (92%) of the patients with ABI were able to complete the PSFS. The five (8%) who were unable to complete the PSFS had severe cognitive or language impairment. The PSFS score improved by a mean of 2.6 (SD 2.0) points from admission to discharge. The LOTCA score made the strongest unique contribution to explain the change in the PSFS score (beta = 0.477, p= 0.020). Conclusion: In the present study, most patients with ABI (92%) were able to complete the PSFS. Cognitive function on admission was a predictor of improved functioning on the PSFS.

Background: Changes in tryptophan metabolism through the kynurenine pathway (KP) are observed in several disorders and coupled with pathophysiological deviations. Methods: This study retrospectively compared the KP in serum in healthy subjects (108) with subjects with obesity (141), depression (49), and chronic obstructive pulmonary disease (COPD) (22) participating in four clinical studies and explored predictors of the changes in the KP metabolites. Results: Compared with the healthy group, the KP was upregulated in the disease groups with high kynurenine, quinolinic acid (QA), kynurenine/tryptophan-ratio and QA/xanthurenic acid-ratio and low kynurenic acid/QA-ratio. Tryptophan and xanthurenic acid were upregulated in the depressed group compared with the groups with obesity and COPD. The covariates BMI, smoking, diabetes, and C-reactive protein explained the significant differences between the healthy group and the group with obesity but not between the healthy group and the groups with depression and COPD, indicating that different pathophysiological conditions result in the same changes in the KP. Conclusions: The KP was significantly upregulated in the disease groups compared with the healthy group, and there were significant differences between the disease groups. Different pathophysiological abnormalities seemed to result in the same deviations in the KP.