Publications

Neuroticism, a personality trait, can predict major depressive disorder (MDD). The current study aims to determine whether a) neuroticism is a feature of the acute state of MDD, including suicidal behaviors (SB); and b) adverse childhood experiences (ACEs) are associated with neuroticism in MDD.

Migrena i depresja często współwystępują, stanowiąc ważny problem kliniczny. Oba zaburzenia związane są z koniecznością przewlekłego leczenia, a ich wzajemne współwystępowanie sprzyja zjawisku lekooporności. Wpływając na funkcjonowanie pacjentów powodują także liczne konsekwnecje społeczne - oddziałując na jakość życia i realizację celów osobistych osób chorych. W prezentowanej pracy przeglądowej przedstawiono czynniki, które mogą wyjaśniać wspólne patomechanizmy depresji i migreny. Uwzględniono zaburzenia strukturalne i czynnościowe ośrodkowego układu nerwowego (OUN), zaburzenia w zakresie układów neuroprzekaźników, teorie zapalne, zaburzenia hormonalne, a także możliwe podłoże genetyczne. Ze względu na fakt, że zarówno depresja, jak i migrena mają etiologię wieloczynnikową i na obecnym etapie badań naukowych trudno jednoznacznie określić, który czynnik jest tym najważniejszym, zaprezentowano tak szeroki przegląd. Trudno także określić, które z wymienionych czynników, dobrze udokumentowanych w międzynarodowych badaniach, jedycznie współwystępują, a które z nich mogą mieć związek przyczynowo-skutkowy w opisywanych zaburzeniach. Podjęcie dalszych badań w zakresie współwystępowania migreny i depresji oraz przyczyn tego zjawiska wydają się warte rozważenia.

Both depression and cancer are related to a dysregulation of inflammatory and immune pathways. Indeed, depression is associated with increased expression of interferon-γ, interleukin-1β, and tumor necrosis factor α (TNF-α). In contrast, reductions of the activity of major histocompatibility complex protein molecules - class I and class II and natural killer cells are also observed. Similarly, cancers present elevated levels of TNF-α, reduced major histocompatibility complex class I and II, and natural killer cells. Indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme of the tryptophan catabolite (TRYCAT) pathway, is induced by interferon-γ, interleukin-6, TNF-α, and oxidative stress. IDO catabolizes tryptophan, the amino acid precursor of serotonin and melatonin, to the metabolites collectively called TRYCATs. TRYCAT pathway activation is accompanied by downregulation of immune cell proliferation, function, and survival. The increase in IDO activity in tumor microenvironments is related to tumor cell escape from immune surveillance. Despite the evidence of inflammatory mechanisms underlying cancer and depression, it is important to emphasize that both diseases are heterogeneous and, as such, inflammatory mechanisms may not be relevant to all patients. Thus, the purpose of this review is to examine whether detrimental TRYCATs - synthesis of which increases in depression and cancer - are a pathophysiological link between the two diseases, and whether IDO is a potential pharmacological target for the treatment of the comorbid depression and cancer.

Abstract Background Alzheimer’s disease (AD), characterized by gradual brain dysfunction and memory loss, is one of the major elderly health issues worldwide. Neuroinflammation and increased oxidative stress contribute to the pathophysiology of AD, thereby presumably inducing tryptophan (TRP) degradation through the TRP catabolite (TRYCAT) pathway. Objectives To delineate the activity of the TRYCAT pathway along with levels of TRP and tryptophan catabolites (TRYCATs) in AD patients. Methods We employed PubMed, Google Scholar, Web of Science, and SciFinder to obtain the relevant articles through a search process lasting the entire February 2022. We found 19 eligible articles which involved 738 patients and 665 healthy controls. Results Our result revealed a significant difference ( p = 0.008) in the kynurenine (KYN)/TRP ratio (standardized mean difference, SMD = 0.216, 95% confidence interval, CI: 0.057; 0.376), and a significant decrease in TRP in AD patients (SMD = -0.520, 95% CI: -0.738; -0.302, p < 0.0001). Moreover, we also found a significant increase in the central nervous system (CNS, brain and cerebrospinal fluid, CSF) kynurenic acid (KA)/KYN ratio but not in peripheral blood, as well as a significant decrease in plasma KA and xanthurenic acid (XA) in the CNS and blood. Conclusions AD is characterized by TRP depletion but not by an overactivity of the TRYCAT pathway. IDO-induced production of neurotoxic TRYCATs is not a key factor in the pathophysiology of AD.

Deficit schizophrenia, as defined by the Schedule for Deficit Syndrome, may represent a distinct diagnostic class defined by neurocognitive impairments coupled with changes in IgA/IgM responses to tryptophan catabolites (TRYCATs). Adequate classifications should be based on supervised and unsupervised learning rather than on consensus criteria.This study used machine learning as means to provide a more accurate classification of patients with stable phase schizophrenia.We found that using negative symptoms as discriminatory variables, schizophrenia patients may be divided into two distinct classes modelled by (A) impairments in IgA/IgM responses to noxious and generally more protective tryptophan catabolites, (B) impairments in episodic and semantic memory, paired associative learning and false memory creation, and (C) psychotic, excitation, hostility, mannerism, negative, and affective symptoms. The first cluster shows increased negative, psychotic, excitation, hostility, mannerism, depression and anxiety symptoms, and more neuroimmune and cognitive disorders and is therefore called "major neurocognitive psychosis" (MNP). The second cluster, called "simple neurocognitive psychosis" (SNP) is discriminated from normal controls by the same features although the impairments are less well developed than in MNP. The latter is additionally externally validated by lowered quality of life, body mass (reflecting a leptosome body type), and education (reflecting lower cognitive reserve).Previous distinctions including "type 1" (positive)/"type 2" (negative) and DSM-IV-TR (eg, paranoid) schizophrenia could not be validated using machine learning techniques. Previous names of the illness, including schizophrenia, are not very adequate because they do not describe the features of the illness, namely, interrelated neuroimmune, cognitive, and clinical features. Stable-phase schizophrenia consists of 2 relevant qualitatively distinct categories or nosological entities with SNP being a less well-developed phenotype, while MNP is the full blown phenotype or core illness. Major neurocognitive psychosis and SNP should be added to the DSM-5 and incorporated into the Research Domain Criteria project.