Neurobiology of Depression and Irritable Bowel Syndrome Comorbidity

Irritable bowel syndrome is a disabling functional disorder with a frequent comorbidity of depression though underlying mechanisms remain yet little understood. Various signs and symptoms have been determined as diagnostic criteria in recent years and standardized as Rome-III criteria. Irritable bowel syndrome can have constipation-dominant, diarrhea-dominant or mixed clinical presentations. Main features can be summarized as continuous and recurrent abdominal pain or discomfort associated with a change of stool frequency or consistency and usually relief of symptoms with defe-cation in the absence of physical or laboratory abnormalities indicative of an organic etiology. The frequency of major depressive disorder diagnosis reaches up to two thirds of irritable bowel syndrome patients. Moreover, the comorbidity of irritable bowel syndrome among patients with major depression is highly frequent (30%). The mechanism underlying irritable bowel syndrome which have been considered as a kind of a somatization disorder for a long time and now as a functional bowel disease is in the brain-gut axis. Low grade mucosal inflammation and cytokines originating from mucosal inflammation have important functions in the pathophysiology of irritable bowel syndrome and its comorbidity with major depression. Besides the inflammatory factors lumbosacral visceral hyperexcitability which is an individual variation is proposed as the main underlying cause of irritable bowel syndrome. Visceral hyper-excitability is mediated by cytokines and neuro-mediators and stress is known to increase the effect of this mechanism. Furthermore, molecules participating in this mechanism (e.g. cytokines, corticotrophin releasing factor, neurokinins and monoamines) play important roles in the pathophysiology of depression. Increased activation in the pain matrix (thalamus – insula – prefrontal cortex) and insufficiency of endogenous pain inhibitory system are regarded as possible casuses of excessive feeling of irritable bowel syndrome symptoms leading to the dysfunction in the cortical representation of bodily states and negative emotional experiences. Individual variations in the interaction of cytokines, corticotrophin releasing factor, neurokinins (substance P, neurokinin A and neurokinin B) and monoamines (serotonin and norepinephrine), and neuroanatomic functions may answer the question of “why do some irritable bowel syndrome patients experience depression and some do not?”. Moreover, irritable bowel syndrome patients with comorbid depression and anxiety disorders are reported to be complaining more about their irritable bowel syndrome symptoms. Although several treatment strategies are considered by clinicians in the management of irritable bowel syndrome, it is suggested that antidepressant medications to have the priority in the treatment of irritable bowel syndrome with the comorbidity of depression. Selective serotonin re-uptake inhibitors are the drug of choice regarding their safety and side effects profile. Nevertheless, tricyclic antidepressants may also have beneficial effects in lower doses than needed to treat clinical depression. Hypnosis, supportive or cognitive behavioral therapies, dietary and defecation habits management are also suggested as beneficial. The recognition of irritable bowel syndrome by psychiatrists may enhance the success of treatment of depression with the comorbidity of irritable bowel syndrome, which disables the patient and frequently accompanies to major depression. In this review, evidence for depression and irritable bowel syndrome comorbidity, the possible underlying mechanisms of this comorbidity and current treatment approaches regarding proposed mechanisms will be discussed

Adsorption challenge in the PDMS-based microfluidic systems for drug screening application

Drug screening is one of the demand areas due to close and direct dependency on human health. On the other hand, recently microfluidic systems have been increasingly used for drug development and screening purposes. However, this system has some challenges such as adsorption issue which can effect pharmacokinetic-pharmacodynamic (PK-PD) of the drugs. Thus, in this research, the issue was characterized and evaluated by UV-Vis spectrophotometry and FTIR spectroscopy devices as a model drug of cisplatin. Despite of strong relationship between logP and adsorption, and the very low value of logP in the drug candidate, the results for both apical and basal planes of the microfluidic chip confirmed the adsorption. In the UV-Vis spectrophotometry, the basal plane show 5%, and 10% higher adsorption compared to apical and control polydimethylsiloxane (PDMS)-based microfluidic. Additionally, the FTIR patterns were a good coincide with UV-Vis results

A nationwide multicentre study in Turkey for establishing reference intervals of haematological parameters with novel use of a panel of whole blood

IntroductionA nationwide multicentre study was conducted to establish well-defined reference intervals (RIs) of haematological parameters for the Turkish population in consideration of sources of variation in reference values (RVs). Materials and methodsK2-EDTA whole blood samples (total of 3363) were collected from 12 laboratories. Sera were also collected for measurements of iron, UIBC, TIBC, and ferritin for use in the latent abnormal values exclusion (LAVE) method. The blood samples were analysed within 2 hours in each laboratory using Cell Dyn and Ruby (Abbott), LH780 (Beckman Coulter), or XT-2000i (Sysmex). A panel of freshly prepared blood from 40 healthy volunteers was measured in common to assess any analyser-dependent bias in the measurements. The SD ratio (SDR) based on ANOVA was used to judge the need for partitioning RVs. RIs were computed by the parametric method with/without applying the LAVE method. ResultsAnalyser-dependent bias was found for basophils (Bas), MCHC, RDW and MPV from the panel test results and thus those RIs were derived for each manufacturer. RIs were determined from all volunteers’ results for WBC, neutrophils, lymphocytes, monocytes, eosinophils, MCV, MCH and platelets. Gender-specific RIs were required for RBC, haemoglobin, haematocrit, iron, UIBC and ferritin. Region-specific RIs were required for RBC, haemoglobin, haematocrit, UIBC, and TIBC. ConclusionsWith the novel use of a freshly prepared blood panel, manufacturer-specific RIs’ were derived for Bas, Bas%, MCHC, RDW and MPV. Regional differences in RIs were observed among the 7 regions of Turkey, which may be attributed to nutritional or environmental factors, including altitude

Decline in subarachnoid haemorrhage volumes associated with the first wave of the COVID-19 pandemic

BACKGROUND: During the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study\u27s objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines. METHODS: We conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March-31 May 2020. The prior 1-year control period (1 March-31 May 2019) was obtained to account for seasonal variation. FINDINGS: There was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI -24.3% to -20.7%, p\u3c0.0001). Embolisation of ruptured aneurysms declined with 1170-1035 procedures, respectively, representing an 11.5% (95%CI -13.5% to -9.8%, p=0.002) relative drop. Subgroup analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations, a 24.9% relative decline (95% CI -28.0% to -22.1%, p\u3c0.0001). A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1% (95% CI 32.3% to 50.6%, p=0.008) despite a decrease in SAH admissions in this tertile. INTERPRETATION: There was a relative decrease in the volume of SAH hospitalisations, aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic. These findings in SAH are consistent with a decrease in other emergencies, such as stroke and myocardial infarction

Metabolic Side Effects of Lithium

Lithium is an alkaline ion being used since 19th century. After its widespread use in psychiatric disorders, observed side effects caused skepticism about its therapeutic efficacy. Despite several disadvantages, lithium is one of the indispensible drugs used in affective disorders, especially in bipolar disorder. It became a necessity for physicians to recognize its side effects since lithium is still accepted as a gold standard in the treatment of bipolar disorder. Adverse effects of chronic administration of lithium on several organ systems are widely known. In this article metabolic effects of lithium on thyroid and parathyroid glands, body mass index and kidneys will be discussed along with their mechanisms, clinical findings, possible risk factors and treatment. One of the most common side effect of lithium is hypothyroidism. It has the same clinical and biochemical properties as primary hypothyroidism and observed as subclinical hypothyroidism in the first place. Hypothyroidism, even its subclinical form, may be associated with non-response or inadequate response and is indicated as a risk factor for development of rapid cycling bipolar disorder. Therefore, hypothyroidism should be screened no matter how severe it is and should be treated with thyroid hormone in the presence of clinical hypothyroidism. Weight gain due to lithium administration disturbs the compliance to treatment and negatively affects the course of the illness. Increased risk for diabetes, hypertension, ischemic heart disease and stroke because of weight gain constitute other centers of problem. Indeed, it is of importance to determine the risk factors before treatment, to follow up the weight, to re-organize nutritional habits and to schedule exercises. Another frequent problematic side effect of lithium treatment is renal dysfunction which clinically present as nephrogenic diabetes insipidus with the common symptoms of polyuria and polydipsia. Nephrogenic diabetes insipidus develops because of urinary concentration defects due to the detrimental effects of lithium on re-absorption of water and sodium at the level of collector tubules. Close screening of renal functions is very important in the prevention of renal damage during treatment with lithium. Moreover, it is also of importance to screen serum lithium levels as lithium intoxication episodes may increase the risk of renal failure. As a conclusion lithium still preserves its indispensability in affective disorders. Clinicians should have current knowledge about the side effects of lithium and take preventive measures to apply such an important treatment to the patients

Metabolic Effects of Antidepressant Treatment

Introduction: This study aimed to investigate body measurements, glucose-insulin metabolism, and lipid profile in patients with anxiety and depressive symptoms and also the effects of antidepressant drugs on these metabolic parameters

The Effects of the Duration of Formal Education on Adult Brain: A Voxel-Based Morphometry - (Diffeomorphic Anatomical Registration Using Exponentiated Lie Algebra) DARTEL Study

WOS: 000271692600003Objective: Recent studies neuroimaging showed that continues environmental stimuli can induce structural changes in the brain. Compared to later life, during formal education in school and university; human brain is not only continuously Stimulated with new information but also retrieves the already learned information and extends it with the new one. In this study, we explored the effects of this extensive learning process on brain structure by using voxel-based morphometry (VBM) -DARTEL method. Method: Forty-seven healthy adults were included in this study. After screened carefully by SCID-NP, all subjects were scanned by Siemens 1.5T Magnetic Resonance Imaging machine. T1 weighted images were analyzed by SPM 5 (Statistical Parametric Mapping software) via VBM protocol. Results: Our VBM results showed that the right anterior hippocampus gray matter volume was correlated with the duration of formal education. We also observed that education showed positive correlations with Brodmann (BA) 18 in the occipital lobes and with the right cerebellum. However, the right parietal cortex (BA 7) and the right middle frontal cortex (BA 8) showed negative correlations with education. Conclusion: Our study showed that there is an association between the duration of formal education and the gray matter volume of brain regions related to the detection of novel stimuli, semantic and spatial memory and visual system which might be related to extensive learning process during formal education years

Association of the brain-derived neurotrophic factor Val66Met polymorphism with hippocampus volumes in drug-free depressed patients

WOS: 000287741900004PubMed ID: 20726825Objectives. Val66Met BDNF gene polymorphism is shown to affect the function of mature BDNF and mature BDNF plays an important role in the hippocampal neurogenesis and neuronal survival. Methods. A relationship of Val66Met BDNF gene polymorphism and hippocampal volumes in 33 MDD patients and 40 healthy controls is investigated. Region of interest analysis was conducted on the images acquired via MRI. Results. Depressed patients had smaller left hippocampal volumes compared to healthy controls. The diagnosis of MDD was not significantly related to hippocampal volumes among Met carriers; however, among Val homozygotes depressed patients had significantly smaller left hippocampal volumes compared to controls. Although both right and left hippocampal volumes showed nearly significant correlation with the duration of illness, this correlation reached (negative) significant levels only in the right hippocampal volume of the Val homozygotes. Conclusions. Val homozygote genotype may serve as a vulnerability factor in MDD regarding hippocampal volume loss. This finding can be considered as a supportive evidence for the neurotrophic factor hypothesis of depression.Ihsan Dogramaci Foundation; Izmir Psychiatric AssociationThis study is a part of SoCAT Project supported by Ihsan Dogramaci Foundation and was partially supported by Huray Fidaner Research Award of Izmir Psychiatric Association to corresponding author (ASG); the organizations mentioned above had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication

Relationship between orexin A and childhood maltreatment in female patients with depression and anxiety

Objective: Childhood maltreatment leads to neuroendocrine changes, which may be associated with an increased vulnerability for psychopathology, such as depression and anxiety in later life. This study aimed to investigate the relationship between childhood maltreatment and orexin A levels in patients with depression and anxiety. The study consisted of 27 female outpatients who presented with depressive and/or anxiety symptoms, and 27 healthy female controls. Childhood trauma history was assessed using the childhood trauma questionnaire (CTQ-28) in patients and controls. Serum levels of orexin and cortisol were measured in all subjects. There were positive correlations between serum orexin levels and CTQ total score and between orexin levels and some CTQ subscale scores, such as physical and emotional neglect, in patients. Orexin levels in patients with a positive history of physical and emotional neglect were higher than those in patients with a negative history of them. In the controls, there was a positive correlation between emotional neglect score and serum orexin level. There were no differences in serum levels of orexin and cortisol between patients and controls. Orexin levels may be associated with childhood maltreatment per se, rather than psychopathology, such as depression or anxiety