Microbiome-Induced Autoimmunity and Novel Therapeutic Intervention.

Microorganisms' flora, which colonize in many parts of our body, stand out as one of the most important components for a healthy life. This microbial organization called microbiome lives in integration with the body as a single and whole organ/system. Perhaps, the human first encounters the microbial activity it carries through the immune system. This encounter and interaction are vital for the development of immune system cells that protect the body against pathogenic organisms and infections throughout life. In recent years, it has been determined that some disruptions in the host-microbiome interaction play an important role in the physiopathology of autoimmune diseases. Although the details of this interaction have not been clarified yet, the focus is on leaky gut syndrome, dysbiosis, toll-like receptor ligands, and B cell dysfunction. Nutritional regulations, prebiotics, probiotics, fecal microbiota transplantation, bacterial engineering, and vaccination are being investigated as new therapeutic approaches in the treatment of problems in these areas. This article reviews recent research in this area.

CONNECTOME or COLLECTOME? A NEUROPHILOSOPHICAL Perspective.

Human beings exist in a biological and social system from a micro to a macro level, by means of "collectivity", a dynamic collaboration that they have established together with the elements in that system in a way to complement each other and realize a common goal. Many neuroscientific concepts used today to explain neuronal processes from which mental functions originate are far from searching answers to traditional philosophical questions. However, the brain - as the generator of highly abstract concepts - is so complex that it cannot be explained by minimalistic approaches. The concept of connectome used in recent years to describe neuronal connections from which brain functions originate exemplifies this minimalistic approach, because it only describes structural and functional connections but does not look at brain functions in a holistic view. For this reason, we propose the concept of collectome - to replace the concept of connectome - that describes a homeomorphic and homotopic neuronal framework that has a bicontinuous style of work from micro to macroscale which is based on fractal rules.

Vaccination and Immunotherapy for Major Depression.

Depression is a very common disease with increasing incidence resulting from complex interactions of genetic, environmental, and immunological processes. To this day, the etiopathogenesis and treatment of depression unfortunately seem to be stuck in the synaptic gap. Despite highly potent antidepressants, the treatment rate cannot reach 100%, the treatment resistant group cannot be eliminated, and relapse cannot be prevented. These problems lead researchers to further and different research to understand and treat psychopathology. Immune dysfunction and neuroinflammation have been one of the main issues that psychiatry has focused on in recent years and helps us to understand depression. Extraneuronal components of all neuropsychiatric disorders, especially depression, have begun to be revealed in detail thanks to a better understanding of the immune system and an increase in experimental and technological possibilities. There is increasing evidence of a causal relationship between the etiopathogenesis of major depression and low-level chronic neuroinflammation. In this article, the role of neuroinflammation in the etiopathogenesis of depression and the possibilities of vaccination and immunotherapy are discussed.

Emerging role of Gut-microbiota-brain axis in depression and therapeutic implication.

The human body can be considered a superorganism in which it's eukaryotic cells and prokaryotic microorganisms coexist. Almost every organ system of the body lives a symbiotic life with these commensal bacteria. Intestinal microbiota has an important role in shaping, organizing and maintaining mental functions from as early as the intrauterine period. Microbiota-based approaches are becoming more prominent in understanding and treating the etiopathogenesis of neuropsychiatric disorders, especially depression. Antidepressant drugs, which are the first-line option in the treatment of depression today, also contain antimicrobial and immunomodulatory mechanisms of action. Treatment options for directly modifying the microbiota composition include prebiotics, probiotics (psychobiotics) and fecal microbiota transplantation. There are few preclinical and clinical studies on the efficacy and reliability of these treatment options in depression. This article will review pertinent studies on the role of intestinal microbiota in depression and discuss the treatment potential of altering ones gut microbiome.

The effect of fecal microbiota transplantation on psychiatric symptoms among patients with inflammatory bowel disease: an experimental study.

INTRODUCTION: Over the past decade, evidence that supports the relationship between intestinal microbiota and the brain has been obtained. Ageing, stress, nutrition and medicines can alter the composition of bacteria in the intestinal microbiota. This condition, called dysbiosis, can be repaired through prebiotics, probiotics or fecal microbiota transplantation (FMT). FMT is effective in the treatment of inflammatory bowel diseases (IBD). Information on FMT's use with psychiatric disorders is limited. This study aims to investigate changes in the severity of depression, anxiety and obsession of patients who received FMT for the treatment of inflammatory bowel diseases. METHODS: This study was conducted with 10 patients with IBD who underwent FMT between March and September 2017. FMT was performed by an experienced gastroenterologist. The patients completed the Beck Depression Inventory (BDI), Symptom Checklist-90-Revised (SCL-90-R) and Maudsley Obsessive Compulsive Inventory (MOCI) before FMT and again at 1 month after FMT. RESULTS: Significant decreases were found in BDI (Z=2.49, p=0.013), SCL-90-R (Z=-2.09, p=0.037) and MOCI (Z=2.08, p=0.037) scores after 1 month of FMT. Although the SCL-90-R anxiety subscale scores decreased, this decrease was not statistically significant (Z=-1.55, p=0.121). CONCLUSIONS: The severity of anxiety, depression and obsession in IBD patients decreased after FMT. The decrease in psychiatric symptoms may result from the direct neuropsychiatric effect of FMT (primary effect), but also the improvement of gastrointestinal symptoms (secondary effect). Another possibility is that this result is independent of these two conditions. Therefore, the results of our study are not sufficient to establish a cause-effect relationship. More randomised controlled trials with larger samples from patients with anxiety or depression but without comorbid physical illnesses are needed to generalise these results.

Investigation of the relationships between eating attitudes, body image and depression among Turkish university students.

INTRODUCTION: Eating disorders are one of the most prevalent psychiatric disorders and have become a growing problem nowadays. Research shows that eating disorders are mostly widespread in industrialized societies where beauty is associated with thinness. This study investigates the relationships between eating attitudes, body image and depression among Turkish university students aged 18 to 25. MATERIALS AND METHODS: The sample comprised of 221 female and 80 male university students from four different universities located in Istanbul and Ankara. Demographic Information Form, Body Image Scale, Eating Attitude Test (EAT-40) and Beck Depression Inventory were used to collect data. Height and weight of the participants were also collected to measure Body Mass Index (BMI) of the individuals. RESULTS: This study found that 55 (18.3%) students had abnormal eating attitudes, 115 (38.2%) students had negative body image and 102 (33.9%) students showed moderate and severe levels of depression. Body image was negatively correlated with eating attitude and depression in underweight individuals when grouped according to their BMI. Being underweight was significantly higher in females. Females also had more negative body image and higher depression levels. Individuals with abnormal eating attitudes had higher depression levels. BMI and gender did not lead to any significant difference in the eating attitudes of the students. CONCLUSION: This study has contributed to the literature on the relationships between eating attitudes, body image and depression among Turkish university students between the ages of 18 and 25. It has further drawn attention to the importance of eating disorders in Turkey and being aware of the relationships among eating attitudes, body image, depression, and BMI. Results of the study are discussed in detail and in consideration of cultural context.

Entropy: A Promising EEG Biomarker Dichotomizing Subjects With Opioid Use Disorder and Healthy Controls.

Electroencephalography (EEG) signals are known to be nonstationary and often multicomponential signals containing information about the condition of the brain. Since the EEG signal has complex, nonlinear, nonstationary, and highly random behaviour, numerous linear feature extraction methods related to the short-time windowing technique do not satisfy higher classification accuracy. Since biosignals are highly subjective, the symptoms may appear at random in the time scale and very small variations in EEG signals may depict a definite type of brain abnormality it is valuable and vital to extract and analyze the EEG signal parameters using computers. The challenge is to design and develop signal processing algorithms that extract this subtle information and use it for diagnosis, monitoring, and treatment of subjects suffering from psychiatric disorders. For this purpose, finite impulse response-based filtering process was employed rather than traditional time and frequency domain methods. Finite impulse response subbands were analyzed further to obtain feature vectors of different entropy markers and these features were fed into a classifier namely multilayer perceptron. The performances of the classifiers were finally compared considering overall classification accuracies, area under receiver operating characteristic curve scores. Our results underline the potential benefit of the introduced methodology is promising and is to be treated as a clinical interface in dichotomizing substance use disorders subjects and for other medical data analysis studies. The results also indicate that entropy estimators can distinguish normal and opioid use disorder subjects. EEG data and theta frequency band have distinctive capability for almost all types of entropies while nonextensive Tsallis entropy outperforms compared with other types of entropies.

Immune-Kynurenine Pathways and the Gut Microbiota-Brain Axis in Anxiety Disorders.

Anxiety disorders are a complex set of illnesses in which genetic factors, particularly stress, play a role in the etiopathogenesis. In recent years, inflammation and intestinal microbiota have also been included in this complex network of relationships. The functions associated with tryptophan catabolism and serotonin biosynthesis have long been associated with anxiety disorders. Tryptophan catabolism progresses toward the path of the kynurenine in the presence of stress and inflammation. The catabolism of kynurenine is a pathway in which many enzymes play a role and a large number of catabolites with neuroactive properties occur. The body's serotonin biosynthesis is primarily performed by enterochromaffin cells located in the intestines. A change in the intestinal microbiota composition (dysbiosis) directly affects the serotonin biosynthesis. Stress, unhealthy nutrition, and the use of antibiotics cause dysbiosis. In the light of this new perspective, the role of dysbiosis-induced inflammation and kynurenine pathway catabolites activated sequentially come into prominence in the etiopathogenesis of anxiety disorders.

Efecto del trasplante de microbiota fecal sobre los síntomas psiquiátricos de los pacientes con enfermedad intestinal inflamatoria: estudio experimental / The effect of fecal microbiota transplantation on psychiatric symptoms among patients with inflammatory bowel disease: an experimental study

INTRODUCCIÓN: Durante la última década, se ha obtenido evidencia que respalda la relación entre el microbiota intestinal y el cerebro. El envejecimiento, el estrés, la nutrición y los medicamentos pueden alterar la composición bacteriana de la microbiota intestinal. Esta condición, llamada disbiosis, se puede reparar con prebióticos, probióticos o con trasplante de microbiota fecal (TMF). El TMF es eficaz en el tratamiento de enfermedades inflamatorias intestinales (EII). La información sobre el uso del TMF en los trastornos psiquiátricos es limitada. Este estudio tiene como objetivo investigar los cambios en la severidad de la depresión, la ansiedad y la obsesión de los pacientes que recibieron TMF para el tratamiento de enfermedades inflamatorias intestinales. METODOLOGÍA: Este estudio se realizó con 10 pacientes con EII que se sometieron al TMF entre marzo y septiembre de 2017. El TMF fue realizado por un gastroenterólogo experimentado. Los pacientes completaron el Inventario de Depresión de Beck (IDB), el Listado de Síntomas Revisado (SCL-90-R) y el Inventario Obsesivo-Compulsivo de Maudsley (MOCI) antes del TMF y otra vez un mes después del TMF. RESULTADOS: Se encontraron disminuciones significativas en las puntuaciones del IDB (Z = 2.49, p = 0.013), SCL-90-R (Z = -2.09, p = 0.037) y MOCI (Z = 2.08, p = 0.037) un mes después del TMF. Aunque las puntuaciones de la subescala de ansiedad del SCL-90-R disminuyeron, esta disminución no fue estadísticamente significativa (Z = -1.55, p = 0.121). CONCLUSIONES: La severidad de la ansiedad, la depresión y la obsesión en los pacientes con EII disminuyó después del TMF. La disminución de los síntomas psiquiátricos puede deberse al efecto neuropsiquiátrico directo del TMF (efecto primario), pero también a la mejora de los síntomas gas-trointestinales (efecto secundario). Otra posibilidad es que este resultado sea independiente de estas dos hipótesis. Por lo tanto, los resultados de nuestro estudio no son suficientes para establecer una relación de causa-efecto. Para generalizar estos resultados, se necesitan más ensayos controlados aleatorizados con muestras de más pacientes con ansiedad o depresión, pero sin enfermedades físicas concomitantes

INTRODUCTION: Over the past decade, evidence that supports the relationship between intestinal microbiota and the brain has been obtained. Ageing, stress, nutrition and medi-cines can alter the composition of bacteria in the intestinal microbiota. This condition, called dysbiosis, can be repaired through prebiotics, probiotics or fecal microbiota transplantation (FMT). FMT is effective in the tratamiento of inflammatory bowel diseases (IBD). Information on FMT's use with psychiatric disorders is limited. This study aims to investigate changes in the severity of depression, anxiety and obsession of patients who received FMT for the tratamiento of inflammatory bowel diseases. METHODS: This study was conducted with 10 patients with IBD who underwent FMT between March and September 2017. FMT was performed by an experienced gastroen-terologist. The patients completed the Beck Depression In-ventory (BDI), Symptom Checklist-90-Revised (SCL-90-R) and Maudsley Obsessive Compulsive Inventory (MOCI) be-fore FMT and again at 1 month after FMT. RESULTS: Significant decreases were found in BDI (Z = 2.49, p = 0.013), SCL-90-R (Z = -2.09, p = 0.037) and MOCI (Z = 2.08, p = 0.037) scores after 1 month of FMT. Although he SCL-90-R anxiety subscale scores decreased, this de-crease was not statistically significant (Z = -1.55, p = 0.121). CONCLUSIONS: The severity of anxiety, depression and obsession in IBD patients decreased after FMT. The decrease in psychiatric symptoms may result from the direct neuro-psychiatric effect of FMT (primary effect), but also the im-provement of gastrointestinal symptoms (secondary effect). Another possibility is that this result is independent of these two conditions. Therefore, the results of our study are not sufficient to establish a cause-effect relationship. More ran-domised controlled trials with larger samples from patients with anxiety or depression but without comorbid physical illnesses are needed to generalise these results

Neuroinflammation, Gut-Brain Axis and Depression.

Psychiatric diseases are the manifestations that result from the individual's genetic structure, physiology, immunology and ways of coping with environmental stressors. The current psychiatric diagnostic systems do not include any systematic characterization in regard to neurobiological processes that reveal the clinical picture in individuals who got psychiatric diagnosis. It is obvious that further research in different areas is needed to understand the psychopathology. The problems in the functions of immune system and the correlation of neuroinflammatory processes with psychiatric disorders have been one of the main research topics of psychiatry in recent years and have contributed to our understanding of psychopathology. Recent advances in the fields of immunology and genetics as well as rapidly increasing knowledge on the effects of immunological processes on brain functions have drawn attention to the correlations between psychiatric disorders and immune system dysfunctions. There are still unfilled gaps in the biology, pathophysiology, and treatment of major depressive disorder, which is quite prevalent among the psychiatric disorders, can lead to significant disability, and frequently has a recurrent course. It appears that low-grade chronic neuroinflammation plays a key role in forming a basis for the interaction between psychological stress, impaired gut microbiota and major depressive disorder. In this review, the role of neuroinflammation in the etiopathogenesis of depression and the mechanism of action of the gut-brain axis that leads to this are discussed in the light of current studies.

Psychobiotics.

Psychobiotics are live bacteria that directly and indirectly produce positive effects on neuronal functions by colonizing into the intestinal flora. Preliminary studies, although in limited numbers, have found that these bacteria have anxiolytic and antidepressant activities. No research has yet been published on the antipsychotic efficacy of psychobiotics. However, these preliminary studies have opened up new horizons and raised the idea that a new class is emerging in psychopharmacology. About 70 years have passed since the discovery of chlorpromazine, and while the synaptic transmission is understood in almost all details, there seems to be a paradigm shift in psychopharmacology. In recent years, the perspective has shifted from synapse to intestinal microbiota. In this respect, germ-free and conventional animal experiments and few human studies were examined in a comprehensive manner. In this article, after a brief look at the history of contemporary psychopharmacology, the mechanisms of the gut-brain relationship and the evidence of metabolic, systemic, and neuropsychiatric activities of psychobiotics were discussed in detail. In conclusion, psychobiotics seem to have the potential for treatment of neuropsychiatric disorders in the future. However, there are many questions and we do not know the answers yet. We anticipate that the answer to these questions will be given in the near future.

The psycho-periodic cube.

The current diagnostic classification systems in psychiatry have been developed primarily for evidence-based clinical decision making with both categorical and dimensional approaches having their own advantages and disadvantages. Efforts have been made to improve these classification systems, and we are now at the point where we must expand beyond the one-dimensionality of these systems. In this paper, we propose that psychiatric disorders can be arranged in a three-dimensional classification system according to the degree of dysfunctions on three specific axes in a way that is similar to the arrangement of chemical elements according to their atomic weights in Mendeleyev's periodic table. For the three axes, we chose externalization, drive, and attention to represent the three-dimensional descriptions of mental health, namely, well-being in social, motivational, and cognitive areas, respectively. Throughout the paper, we explain our reasons for choosing these three axes and compare our hypothesis with categorical diagnostic systems as well as Cloninger's dimensional diagnostic system using personality disorders, affective disorders, and schizophrenia as the specific diagnostic samples.

Therapeutic Potential of the Microbiome in the Treatment of Neuropsychiatric Disorders.

The search for rational treatment of neuropsychiatric disorders began with the discovery of chlorpromazine in 1951 and continues to evolve. Day by day, new details of the intestinal microbiota⁻brain axis are coming to light. As the role of microbiota in the etiopathogenesis of neuropsychiatric disorders is more clearly understood, microbiota-based (or as we propose, "fecomodulation") treatment options are increasingly discussed in the context of treatment. Although their history dates back to ancient times, the importance of psychobiotics and fecal microbiota transplantation (FMT) has only recently been recognized. Despite there being few preclinical and clinical studies, the evidence gathered to this point suggests that consideration of the microbiome in the treatment of neuropsychiatric disorders represents an area of significant therapeutic potential. It is increasingly hoped that such treatment options will be more reliable in terms of their side effects, cost, and ease of implementation. However, there remains much to be researched. Questions will be answered through germ-free animal experiments and randomized controlled trials. In this article, the therapeutic potential of microbiota-based options in the treatment of neuropsychiatric disorders is discussed in light of recent research.

Quantitation of escitalopram and its metabolites by liquid chromatography-tandem mass spectrometry in psychiatric patients: New metabolic ratio establishment.

Therapeutic drug monitoring (TDM) is used to determine the concentration of drug in plasma/serum to adjust the dose of the therapeutic drug. Selective and sensitive analytical methods are used to determine drug and metabolite levels for the successful application of TDM. The aim of the study was to develop and validate using LC-MS/MS to analyse quantitative assay of escitalopram (S-CT) and metabolites in human plasma samples. In order to provide a convenient and safe treatment dose, it was aimed to determine the levels of S-CT and its metabolites in the patients' plasma. A new method with short sample preparation and analysis time was developed and validated using LC-MS/MS to analyse quantitative assay of S-CT and its metabolites in plasma. Also, plasma samples of 30 patients using 20 mg S-CT between the ages of 18 and 65 years were analysed by the validated method. The mean values of S-CT, demethyl escitalopram and didemethyl escitalopram in plasma of patients were 27.59, 85.52 and 44.30 ng/mL, respectively. At the end of the analysis, the metabolic ratio of S-CT and metabolites was calculated. It is considered that the method for the quantitative analysis of S-CT and its metabolites in human plasma samples may contribute to the literature on account of its sensitive and easy application. Additionally, the use of our data by physicians will contribute to the effective drug treatment for their patients who take S-CT.

[Prevalence of bipolar spectrum disorders in migraine patients]. / Migren hastalarinda bipolar yelpaze bozukluklarinin yayginligi.

OBJECTIVES: Comorbidity of migraine and mood disorders has long been recognized. Most of the studies have focused on the relationship between migraine and major depression with only few studies suggesting a special association between migraine and bipolar spectrum disorders. We aimed to evaluate the prevalence of bipolar disorder in migraine patients in a specialized headache outpatient clinic. METHODS: The sample consisted of 78 consecutive patients with migraine headache presenting to the specialized headache outpatient clinic in a Medical Faculty. Migraine diagnosis was established with the International Headache Society's criteria for migraine. Patients were evaluated with Structured Clinical Interview for DSM-IV for mood disorders. Bipolar spectrum definition was broadened with the presence of Akiskal's criteria for affective temperaments (cyclothymic, hyperthymic, irritable, and depressive). RESULTS: Patients in the bipolar spectrum comprised 10.3% (n=8) of the sample. 11 patients (14.1%) had a diagnosis of unipolar depression and 7 patients (9%) had a diagnosis of dysthymic disorder. 41% of the patients (n=32) had an affective temperament. Bipolar disorder was observed with increased frequency in this migraine sufferer population, supporting previous findings of increased prevalence of bipolar disorders in patients with migraine. CONCLUSION: Increased frequency of affective temperaments might be considered in the context of a common pathophysiological background for migraine and bipolar disorders where these temperaments are sub-threshold presentations of mood disorders. Therefore, the definition of patients with comorbid migraine and bipolar disorder may serve as a more homogenic subgroup of mood disorders for further studies.

Polydipsia as a Precursor of Manic Episode in Bipolar Affective Disorder Patients with Alcohol Use Disorder.

Bipolar affective disorder (BD) diagnosis and initiation of appropriate treatment are often delayed, and this is associated with poorer outcomes, such as rapid cycling or cognitive decline. Therefore, identifying certain warning signs of a probable successive episode during the inter-episode phase is important for early intervention. We present the retrospective data of three cases of BD. Our first case had a history of alcohol use disorder (AUD), where he drank in a dipsomaniac manner, and the other two cases had dipsomaniac alcohol use before their manic attacks, and none of them had any AUD after the mood episode was over. Two brothers also had hypertensive episodes during the manic attacks. None of the cases reported increased fluid intake when they were euthymic. We suggest that polydipsia in BD may be a warning sign of an upcoming manic episode, especially in those patients with AUD. Polydipsia in BD may be caused or facilitated by a combination of hyperdopaminergic activity, hypothalamic dysfunction, and dysregulated renin-angiotensin system. To be able to prevent new episodes, a patient's drinking habits and change in fluid intake should be asked at every visit. Those patients with a history of alcohol abuse should especially be informed about polydipsia and manic episode association.