Psychological Stresses in Children Trigger Cytokine- and Kynurenine Metabolite-Mediated Abdominal Pain and Proinflammatory Changes.

Recurrent abdominal pain (RAP) is a common medically unexplained symptom among children worldwide. However, the biological mechanisms behind the development of functional and behavioral symptoms and changes in blood markers have not been well explored. This study aimed to assess changes in the concentrations of inflammatory markers, including cytokines and tryptophan catabolites, in the serum of children with RAP compared to those with subclinical infections.

Effects of stress associated with academic examination on the kynurenine pathway profile in healthy students.

The effects of stress on the neuroendocrine, central nervous and immune systems are extremely complex. The kynurenine pathway (KP) of the tryptophan metabolism is recognised as a cross-link between the neuroendocrine- and immune systems. However, the effects of acute stress from everyday life on KP activation have not yet been studied.

Childhood Adversity and Current Stress are related to Pro- and Anti-inflammatory Cytokines in Major Depression.

Background: Stress during early childhood, for example as a result of maltreatment, can predict inflammation in adulthood. The association of depression with inflammation and current and long-term stress resulting from childhood maltreatment and threatening experiences in the past year has not yet been studied. Therefore, we assessed these variables in a group of patients with major depressive disorder (MDD) and measured levels of the pro-inflammatory cytokine IL-6 and the anti-inflammatory cytokine IL-10.

High Kynurenine (a Tryptophan Metabolite) Predicts Remission in Patients with Major Depression to Add-on Treatment with Celecoxib.

Background: Signs of an inflammatory process have been described in major depression.

Methods: In a double-blind, randomized study of celecoxib or placebo add-on to reboxetine in 40 depressed patients, celecoxib treatment has beneficial effects. In order to evaluate the tryptophan/kynurenine metabolism and to identify predictors for remission, tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), and quinolinic acid (QUIN) were estimated in the serum of 32 patients before and after treatment and in a group of 20 healthy controls.

Kynurenine pathway and white matter microstructure in bipolar disorder.

Decreased availability of serotonin in the central nervous system has been suggested to be a central factor in the pathogenesis of depression. Activation of indoleamine 2-3 dioxygenase following a pro-inflammatory state could reduce the amount of tryptophan converted to serotonin and increase the production of tryptophan catabolites such as kynurenic acid, an antagonist of ionotropic excitatory aminoacid receptors, whose levels are reduced in bipolar disorder. Abnormalities in white matter (WM) integrity have been widely reported in BD.

Oxytocin course over pregnancy and postpartum period and the association with postpartum depressive symptoms.

During the postpartum period, women are at higher risk of developing a mental disorder such as postpartum depression (PPD), a disorder that associates with mother-infant bonding and child development. Oxytocin is considered to play a key role in mother-infant bonding and social interactions and altered oxytocin plasma concentrations were found to be associated with PPD. In the present study, we evaluated oxytocin plasma levels and depressive symptoms during pregnancy and the postpartum period in healthy women.

Tryptophan pathway alterations in the postpartum period and in acute postpartum psychosis and depression.

Objectives: Women are at very high risk for the first onset of acute and severe mood disorders the first weeks after delivery. Tryptophan breakdown is increased as a physiological phenomenon of the postpartum period and might lead to vulnerability for affective psychosis (PP) and severe depression (PD). The aim of the current study was to investigate alterations in tryptophan breakdown in the physiological postpartum period compared to patients with severe postpartum mood disorders.

The role of pro-inflammatory cytokines in neuroinflammation, neurogenesis and the neuroendocrine system in major depression.

Cytokines are pleiotropic molecules with important roles in inflammatory responses. Pro-inflammatory cytokines and neuroinflammation are important not only in inflammatory responses but also in neurogenesis and neuroprotection. Sustained stress and the subsequent release of pro-inflammatory cytokines lead to chronic neuroinflammation, which contributes to depression.

Does escitalopram reduce neurotoxicity in major depression?

A pro-inflammatory state and a dysregulation in the tryptophan/kynurenine pathway have been documented in depression. This study examined whether treatment with the SSRI, escitalopram (ESC), could suppress inflammation and favorably shift metabolites of the kynurenine pathway in patients with major depressive disorder (MDD) within the utilized treatment period. Twenty seven healthy control subjects were included for comparison.

The impact of electroconvulsive therapy on the tryptophan-kynurenine metabolic pathway.

Background: There is still limited knowledge about the mechanism of action of electroconvulsive therapy (ECT) in the treatment of depression. Substantial evidence suggests a role for the immune-moderated tryptophan (TRP)-kynurenine (KYN) pathway in depression; i.e.

Insufficient glucocorticoid signaling and elevated inflammation in coronary heart disease patients with comorbid depression.

Coronary heart disease (CHD) and depression are very common and often co-existing disorders. In addition to psychological and social morbidity, depression exacerbates adverse cardiac outcomes in CHD patients. Inflammation has been proposed as one of the mechanisms involved in the association between these two debilitating diseases.

S100B blood levels and childhood trauma in adolescent inpatients.

Background: Serum levels of the astrocytic protein S100B have been reported to indicate disruption of the blood-brain barrier. In this study, we investigated the relationship between S100B levels and childhood trauma in a child psychiatric inpatient unit.

Method: Levels of S100B were measured in a group of youth with mood disorders or psychosis with and without history of childhood trauma as well as in healthy controls.

Reduced microglial immunoreactivity for endogenous NMDA receptor agonist quinolinic acid in the hippocampus of schizophrenia patients.

Postmortem and positron emission tomography studies have indicated the pathophysiological involvement of microglial cells in schizophrenia. We hypothesized that the microglial production of quinolinic acid (QUIN), an endogenous N-methyl-d-aspartate receptor (NMDAR) agonist, may be linked to the previously described glutamatergic deficits in the hippocampus of schizophrenia patients. We performed a semi-quantitative assessment of QUIN-immunoreactive microglial cells in schizophrenia patients and matched controls in the CA1, CA2/3, and dentate gyrus (DG) area of the posterior hippocampal formation.

Prenatal immunologic predictors of postpartum depressive symptoms: a prospective study for potential diagnostic markers.

In postpartum depression (PPD), immunologic changes have been proposed to be involved in the disease pathology. The study evaluates the regulation of the innate and adaptive immune response over the course of late pregnancy and postpartum period and their association with the development of postpartum depressive symptoms. Furthermore, prenatal immunologic markers for a PPD were investigated.

Impact of different antipsychotics on cytokines and tryptophan metabolites in stimulated cultures from patients with schizophrenia.

Background: An imbalance of tryptophan metabolites plays a role in the pathophysiology of schizophrenia. Also cytokines seem to be involved and are able to enhance the tryptophan metabolism. In this study the impact of cytokines, tryptophan metabolites and antipsychotics was evaluated in schizophrenic patients/ healthy controls and correlated with the psychopathology of schizophrenia.

Network beyond IDO in psychiatric disorders: revisiting neurodegeneration hypothesis.

The involvement of immune system activation in the pathophysiology of certain psychiatric disorders is well documented. Inflammatory molecules such as pro-inflammatory cytokines could enhance the activity of the indoleamine 2,3-dioxygenase (IDO) enzyme which is the first rate-limiting enzyme of the tryptophan degradation pathway, the kynurenine pathway. The increased tryptophan degradation could induce serotonin depletion and depressive mood.

Tryptophan metabolism and immunogenetics in major depression: a role for interferon-γ gene.

The tryptophan metabolism and immune activation play a role in pathophysiology of major depressive disorders. The pro-inflammatory cytokine interferon-γ transcriptionally induces the indoleamine 2,3-dioxygenase enzyme that degrades the tryptophan and thus induces serotonin depletion. The polymorphism of certain cytokine genes was reported to be associated with major depression.

Inflammation, neurotoxins and psychiatric disorders.

Although immune reactions are necessary to defend against danger signals, the mediator molecules such as cytokines can be detrimental to the organism if the exposure is longer than necessary or in certain abnormal concentrations. The neuroprotection and neurotoxicity induced by the interaction between certain cytokines and the metabolites from tryptophan catabolism, the neuroactive kynurenines, which is partly influenced by corticosteroid action plays an important role in several neurotransmissions such as serotonergic, dopaminergic and glutamatergic transmissions and receptor functions such as N-methyl-D-aspartate receptor or α7-nicotinic-acetylcholine receptor. While the molecules in normal concentrations are essential to the normal glial-neuronal interaction, any changes that induce imbalance in the network between those molecules could disturb the interaction.

Anti-inflammatory treatment in schizophrenia.

Antipsychotics, which act predominantly as dopamine D2 receptor antagonists, have several shortcomings. The exact pathophysiological mechanism leading to dopaminergic dysfunction in schizophrenia is still unclear, but inflammation has been postulated to be a key player in the pathophysiology of the disorder. A dysfunction in activation of the type 1 immune response seems to be associated with an imbalance in tryptophan/kynurenine metabolism; the degrading enzymes involved in this metabolism are regulated by cytokines.

Inflammation in schizophrenia.

Although there is no doubt that the dopaminergic neurotransmission is strongly involved in the pathophysiology of schizophrenia, the exact mechanism leading to dopaminergic dysfunction is still unclear. A disbalance in the immune response associated with a slight inflammatory process of the central nervous system (CNS) has been postulated. Such a mechanism is the basis for the "mild encephalitis" concept.

The metabolic syndrome in schizophrenia: is inflammation a contributing cause?

This non-systematic review of the literature summarizes the evidence that inflammation plays a major role in the psychopathology of schizophrenia and in the mechanisms that contribute to physical ill health that is commonly associated with schizophrenia. The impact of prenatal infections on the developing brain, the possible genetic link between the human lymphocyte antigen gene, inflammation, heart disease and diabetes, together with the increase in pro-inflammatory cytokines in the blood and cerebrospinal fluid provide convincing evidence that inflammation is a major factor in the pathology of this disorder. The changes in immune-related markers and specific neurotransmitters associated with the positive symptoms of schizophrenia are described.