Personality Traits Interact With Sleep and Biological Rhythm in Patients With Bipolar Disorder.

ABSTRACT: Sleep disturbances and circadian rhythm changes in bipolar disorder (BD) may have behavioral components as well as biological components. This study aimed to examine the relationship between personality traits, sleep and circadian rhythm in BD. A total of 150 participants with BD, and 150 healthy controls completed the Big Five Personality Test-50 (B5PT-50-TR), Biological Rhythm Interview of Assessment in Neuropsychiatry (BRIAN), Functioning Assessment Short Test (FAST), Pittsburgh Sleep Quality Index (PSQI), Young Mania Rating Scale and Beck Depression Inventory. In the BD group, B5PT-50-TR emotional stability and openness subscale scores were significantly lower in comparison with the healthy control group. Agreeableness and emotional stability subscales were covariates for the BRIAN sleep subscale and emotional stability was a covariate for PSQI total score. Emotional instability might be a vulnerability factor for sleep disorders and biological rhythm abnormalities in BD. Improvement in emotional instability may relieve sleep disorders and biological rhythm, thereby leading to better treatment outcomes in BD.

Thiol disulfide homeostasis in psychiatric disorders: A comprehensive review.

Thiol-disulfide couple maintains an intracellular redox status. Dynamic thiol-disulfide homeostasis acts crucial parts in metabolic processes involving signal mechanisms, inflammation, antioxidant defense. Thiol-disulfide homeostasis have been implicated in numerous diseases. In this comprehensive review we identified the studies that examined the thiol-disulfide homeostasis in psychiatric disorders. Most cases demonstrated alterations in thiol-disulfide homeostasis and in most of them the thiol-disulfide balance tended to change direction to the disulfide side, that is, to the oxidative side. Currently, the fact that N-acetylcysteine, a thiol-containing compound, is of great interest as a new treatment approach in psychiatric disorders and the role of glutathione, the most abundant thiol, in the brain highlights the importance of evaluating the thiol-disulfide balance in psychiatric disorders.

Machine learning algorithms revealed distorted retinal vascular branching in individuals with bipolar disorder.

BACKGROUND: Converging evidence designate vascular vulnerability in bipolar disorder. The predisposition progresses into distortion in time, thus detection of the vascular susceptibility may help reducing morbidity and mortality. It was aimed to assess retinal fundus vasculature in cardiovascular risk-free patients with bipolar disorder. METHODS: Total of 68 individuals (38 patients with bipolar disorder, 30 healthy controls) were enrolled. In order to avoid from degenerative processes, participants were between 18 and 45 years of age, vascular risk factors were eliminated. Microscopic retinal fundus images were processed with machine learning algorithms (multilayer perceptron and support vector machine) and artificial neural network approaches. RESULTS: In comparison to the healthy control group, the bipolar disorder group had lower number of breaking points (P < 0.001), lower number of curved vessel segments (P < 0.001). Total length of smooth vessels was longer (P = 0.040), and total length of curved vessel segments was significantly shorter (P < 0.001) than the control group. Vascular endothelial growth factor levels and gender were the confounders. There were significant correlations between vascular measures and serum lipid levels. LIMITATIONS: Sample size was small and patients were on various medications. CONCLUSIONS: These results indicate distortion in retinal vascular branching in bipolar disorder. Disrupted branching may reflect disturbed prosperity of retinal vascular plexus in patients with bipolar disorder. Alterations in the retinal vessels might be indicators of disruption in cerebral vascular system efficiency and thus neurovascular unit dysfunction in bipolar disorder.

Serum nitric oxide levels are depleted in depressed patients treated with electroconvulsive therapy.

BACKGROUND: Nitric oxide (NO) is an endogenous substance which has several endocrine functions and may act as neurotransmitter in the brain. High levels of NO may provoke nitrosative stress. AIM: It was aimed to examine serum levels of NO in patients with depressive episodes who were treated with electroconvulsive therapy (ECT) in this study. METHODS: The design was a case-control, follow-up study. Patients with depressive episodes (n = 23) and a healthy control group (n = 21) were enrolled. Three serum samples were obtained from the patient group (before ECT, after first and seventh sessions). NO, nitrite, and nitrate levels were examined. STATISTICAL ANALYSIS: Differences between groups were examined with t-test or Mann-Whitney U-test. Longitudinal data were evaluated with Panel Regression Analysis and Kruskal-Wallis Test. RESULTS: Serum levels of NO and nitrite decreased significantly after the seventh session of ECT administration compared to the baseline and first session. Nitrate levels did not differ between the assessments. CONCLUSIONS: Reduction of the serum NO and nitrite levels might be a contributing factor for hypertension during the sessions. These findings are reflect the circulating NO levels. Further studies may dissect NO physiology in the brain in mental disorders and potential external effects.

Acute and Long Term Treatment of Manic Episodes in Bipolar Disorder.

Bipolar disorder is a disabling psychiatric disorder which causes premature death and loss of quality of life. Despite the developments, novel treatments are partially effective and insufficient responses to treatment may cause loss of quality of life. Contemporary approaches to treatment planning involve taking the current symptoms and the personal treatment history of the patient into account and tailoring them for the treatment of each patient, i.e. individualized treatment. In this article, effects and side effects of antipsychotics, mood stabilizers and sedative hypnotic medications are reviewed and presented briefly for clinicians. Although novel developments have been observed in the literature about mixed states and psychotic symptoms, evidence-based options are still limited. Efficacy of mood stabilizers may be prolonged and additional medications may also be needed frequently in patients treated with mood stabilizers. Antipsychotics may cause several side effects and cannot be maintained for a long time in some of those patients. These factors may limit the use of mood stabilizers or antipsychotics. Therefore, the experience of the clinician and personal history of the patient still have importance in the procedure.

Serum hepcidin / ferroportin levels in bipolar disorder and schizophrenia.

BACKGROUND: Despite several alternatives for cellular iron influx, the only mechanism for cellular iron efflux is ferroportin mediated active transport. In cases of ferroportin dysfunction, iron accumulates in the cell and causes ferroptosis. Hepcidin suppresses ferroportin levels and inflammatory activation increases hepcidin production. Mild inflammation in schizophrenia and bipolar disorder may alter hepcidin and ferroportin. METHODS: The study included a total of 137 patients aged 18-65 years, 57 diagnosed with schizophrenia and 80 with bipolar disorder, according to the DSM-IV diagnostic criteria, and a control group (HC) of 42 healthy individuals. Biochemical analyses, thyroid function tests, hemogram, serum iron level, iron-binding capacity, and ferritin levels were examined. Serum levels of hepcidin and ferroportin were measured with enzyme-linked immunosorbent assay (ELISA) method. RESULTS: A statistically significant difference was determined between the groups in terms of the serum ferroportin levels (F = 15.69, p < 0.001). Post-hoc analyses showed that the schizophrenia group had higher ferroportin levels than in the bipolar group (p < 0.001) and HCs (p < 0.001). Hepcidin levels did not differ between the groups. Chlorpromazine equivalent doses of antipsychotics correlated with ferroportin levels (p = 0.024). CONCLUSION: Ferroportin levels were increased in the schizophrenia group, although iron and hepcidin levels were within normal ranges. Antipsychotics may alter the mechanisms which control ferroportin levels. Further studies are needed to examine the relationships between antipsychotics and iron metabolism for determination of causal relationship.

[Relationship between Childhood Adversities, Emotion Dysregulation and Cognitive Processes in Bipolar Disorder and Recurrent Depressive Disorder]. / Bipolar Bozukluk ve Yineleyici Depresif Bozuklukta Çocukluk Çagi Travmalari ve Duygu Düzenleme Güçlükleri ile Bilissel Süreçler Arasindaki Iliski.

OBJECTIVE: Cognitive development is susceptible to environmental distress, leading to cognitive distortions. Cognitive distortions may affect clinical course of psychiatric disorders. We aimed to assess whether childhood maltreatment and emotion dysregulation impair automatic thoughts (ATs) and meta-cognitions (MCs) in Bipolar Disorder (BD) and Major Depressive Disorder - Recurrent (MDB-RE) in this study. METHOD: 85 patients with BD, 81 MDD-RE in remission and 86 healthy participants were enrolled. Automatic Thoughts Scale (ATS), Metacognition Questionnaire (MCQ-30), Childhood Trauma Questionnaire (CTQ- 28), Difficulties in Emotion Regulation Strategies Scale (DERS) were the measures used. RESULTS: ATs were determined by CTQ physical abuse (ß=0.34, p<0.01), DERS goals (ß=-0.37, p<0.01), impulse (ß=0.53, p<0.01) and non-accept (ß=0.23, p<0.05) subscales in BD (F=21.08, p<0.01) and CTQ emotional neglect (ß=0.22, p<0.05), DERS strategies (ß=0.39, p<0.05) in MDD-RE (F=9.97, p<0.05). MCs were predicted by sexual abuse (ß=0.46, p<0.01) in BD (F=4.88, p<0.01), and emotional abuse (B=-0.30, p<0.05) in MDD-RE (F= 7.02, p<0.01). CONCLUSION: These results suggest that emotion dysregulation and childhood adversities are associated with cognitive processes such as MCs and ATs in MDD-RE and BD. Cognitive processes can cause various clinical manifestations and emotion dysregulation and childhood traumas should be considered as psychopathological components that can affect the course of mood disorders via various components. Further follow-up studies and larger samples are needed to better understand the effects of these components.

Psychopharmacological Signatures in the Retina in Schizophrenia and Bipolar Disorder: An Optic Coherence Tomography Study.

BACKGROUND: Retina is considered as a window to the brain due to the similarities in terms of development and pathologies. Optical coherence tomography (OCT) can perform quantitative examinations in the retina. In this study, we aimed to investigate the effects of drugs used in schizophrenia and bipolar disorder (BD) on retinal nerve fiber layer (RNFL) and macular thickness. SUBJECTS AND METHODS: The study included schizophrenia (n=35) and euthymic BD (n=46) patients on various medications, and age, gender matched healthy control group (n=31). For retinal evaluation, measurements of RNFL and macula were performed with Optovue RTVue Premier OCT. RESULTS: In the schizophrenia group, chlorpromazine equivalent dose of antipsychotics was a statistically significant negative predictor of left RNFL nasal superior region thickness. In the BD group, serum valproate level was a significant positive predictor of thickness in the right macular inferior outer, left macular nasal outer region, right RNFL inferotemporal, left temporal and inferotemporal regions. CONCLUSION: Since the retina consists of neurons, morphological or functional examination of retina may be beneficial for the evaluation of the effects of psychopharmalogical treatments in schizophrenia and BD. The outcome of this study implies that valproate has neuroprotective effects on the optic nerve and macula, and this finding is consistent with the literature implying neurotrophic effects of valproate.

Impact of At Least 2 Years of Synthetic Cannabinoid Use on Cognitive and Psychomotor Functions Among Treatment-Seeking Male Outpatients.

Introduction: Synthetic cannabinoid (SC) use, an important public health problem, is becoming increasingly widespread and leads to many medical and psychiatric problems. This study aimed to evaluate the impact of SC use on cognitive and psychomotor functions of patients. Materials and Methods: The participants (30 outpatients with SC use disorder and 33 healthy controls) were administered the Montreal Cognitive Assessment (MOCA) test, the Edinburgh Handedness Inventory (EHI), the Finger-Tapping Test (FTT), and the Adult Memory and Information Processing Battery-B form (AMIPB-B). Results: The SC users scored lower in AMIPB-B, MOCA. and FTT compared to the healthy controls. Conclusion: These findings suggest that SC might impair both cognitive and psychomotor functions. Therefore, outpatients with SC use disorder should be carefully evaluated for cognitive and psychomotor functions since neurological examinations and interventions may also be required in treatment programs for these cases.

Meta-analysis of auditory P50 sensory gating in schizophrenia and bipolar disorder.

The ability of the brain to reduce the amount of trivial or redundant sensory inputs is called gating function. Dysfunction of sensory gating may lead to cognitive fragmentation and poor real-world functioning. The auditory dual-click paradigm is a pertinent neurophysiological measure of sensory gating function. This meta-analysis aimed to examine the subcomponents of abnormal P50 waveforms in bipolar disorder and schizophrenia to assess P50 sensory gating deficits and examine effects of diagnoses, illness states (first-episode psychosis vs. schizophrenia, remission vs. episodes in bipolar disorder), and treatment status (medication-free vs. medicated). Literature search of PubMed between Jan 1st 1980 and March 31st 2019 identified 2091 records for schizophrenia, 362 for bipolar disorder. 115 studies in schizophrenia (4932 patients), 16 in bipolar disorder (975 patients) and 10 in first-degree relatives (848 subjects) met the inclusion criteria. P50 sensory gating ratio (S2/S1) and S1-S2 difference were significantly altered in schizophrenia, bipolar disorder and their first-degree relatives. First-episode psychosis did not differ from schizophrenia, however episodes altered P50 sensory gating in bipolar disorder. Medications improve P50 sensory gating alterations in schizophrenia significantly and at trend level in bipolar disorder. Future studies should examine longitudinal course of P50 sensory gating in schizophrenia and bipolar disorder.

Investigating the jumping to conclusion bias in bipolar disorder.

INTRODUCTION: Hemsley and Garety described the "jumping to conclusions bias" in which patients with delusions may reach unreasonable results with insufficient information. In this study patients with bipolar disorder and healthy volunteers were compared in terms of jumping to conclusions bias using the beads in the jar task. METHODS: 37 patients with DSM-5 diagnosis of bipolar disorder and 30 healthy controls were tested with the Beads Task (BT), Tower of London Test (ToL) and Barrat Impulsiveness Scale (BIS). RESULTS: In the BT, the mean score of DtD (draws to decision) and JTC (jumping to conclusions) scores were not statistically different between the two groups. In the ToL test, the duration of the total execution and the total time were significantly longer in the bipolar group than the control group. BIS scores were significantly higher in the bipolar group. YMRS (Young Mania Rating Scale) scores were not correlated with BT. CONCLUSIONS: This study is the first clinical study to assess the jumping to conclusions bias in patients with bipolar disorder. No JTC bias was detected in bipolar disorder. Further studies may assess JTC in larger samples to determine the effects of clinical state changes, psychotic symptoms, medication and impulsivity.

[Phenotypic Variants of Paraoxonase Q192R in Bipolar Disorder,Depression and Schizophrenia]. / Bipolar Bozukluk, Depresyon ve Sizofrenide Paraoksonaz Q192R Fenotip Varyantlari.

OBJECTIVE: Activity of the paraoxonase 1 (PON1) enzyme varies prominently according to the PON1 Q192R genotype. The arginine (R) genotype hydrolyzes peroxided lipids more quickly and efficiently than the glutamine (Q) genotype. The Q phenotype suggests greater liability to neurodegenerative processes, cardiovascular and malignancy risks than the R phenotype. Stimulated PON/ARES ratio is associated with the PON1 Q192R polymorphism. This study aimes to assess the Q192R phenotype in schizophrenia, bipolar disorder and depression. METHOD: Patients with schizophrenia (37), bipolar disorder (n=50), depression (n=43) and healthy volunteers (n=43) were enrolled. Serum PON1, stimulated paraoxonase (sPON) and aryl esterase (ARES) levels were assessed with an automatic analyzer. Clusters of sPON/ARES ratio were detected with frequency analysis in PON1. QQ, QR and RR variant groups. RESULTS: There were significant differences between the bipolar disorder, depression, schizophrenia and healthy volunteer groups in terms of phenotype frequencies in groups (Fisher's Exact Coefficient=18.96, p=0.003). A higher prevalence of the PON1 RR variant was found in bipolar disorder whereas the PON1 QQ variant had a higher prevalence in depression and schizophrenia as compared to others. Serum PON1 activity correlated with number of episodes in the bipolar disorder group and with SANS, SAPS scores in the schizophrenia group. CONCLUSION: Difference between bipolar disorder, schizophrenia and depression in PON1 activity and PON1 phenotype might be suggestive of different liability to lipid peroxidation and neurodegeneration between the diagnostic groups. Longitudinal studies may identify long term differences between PON1 Q192R polymorphisms in clinical outcomes and neuropathology.

Neurochemical differences between bipolar disorder type I and II in superior temporal cortices: A proton magnetic resonance spectroscopy study.

BACKGROUND: Despite the diagnostic challenges in categorizing bipolar disorder subtypes, bipolar I and II disorders (BD-I and BD-II respectively) are valid indices for researchers. Subtle neurobiological differences may underlie clinical differences between mood disorder subtypes. The aims of this study were to investigate neurochemical differences between bipolar disorder subtypes. METHODS: Euthymic BD-II patients (n = 21) are compared with BD-I (n = 28) and healthy comparison subjects (HCs, n = 30). Magnetic Resonance Imaging (MRI) and proton spectroscopy (1H MRS) were performed on a 3T Siemens Tim Trio system. MRS voxels were located in the left/right superior temporal cortices, and spectra acquired with the single voxel Point REsolved Spectroscopy Sequence (PRESS). The spectroscopic data were analyzed with LCModel (Version 6.3.0) software. RESULTS: There were significant differences between groups in terms of glutamate [F = 6.27, p = 0.003], glutamate + glutamine [F = 6.08, p = 0.004], inositol containing compounds (Ino) (F = 9.25, p < 0.001), NAA [F = 7.63, p = 0.001] and creatine + phosphocreatine [F = 11.06, p < 0.001] in the left hemisphere and Ino [F = 5.65, p = 0.005] in the right hemisphere. Post-hoc comparisons showed that the BD-I disorder group had significantly lower metabolite levels in comparison to the BD-II and the HC groups. LIMITATIONS: This was a cross-sectional study with a small sample size. In addition, patients were on various psychotropic medications, which may have impacted the results. CONCLUSIONS: Neurochemical levels, in the superior temporal cortices, measured with 1H-MRS discriminated between BD-II and BD-I. Although further studies are needed, one may speculate that the superior temporal cortices (particularly left hemispheric) play a critical role, whose pathology may be related to subtyping bipolar disorder.

Situs Inversus Totalis and Schizophrenia Comorbidity.

The comorbidity of structural or genetic diseases with schizophrenia is seen as an opportunity to understand the formation of schizophrenia. This case report presents a patient with comorbidity of schizophrenia, tetralogy of Fallot (TOF) and total situs inversus. TOF is a cyanotic heart disease, which can be linked to 22q11 deletion and trisomy 21. Situs inversus totalis (SIT) is a congenital condition in which the major visceral organs, including the heart, are positioned in a mirror image from normal conditions. The comorbidity of TOF and SIT is quite rare. In our case report, schizophrenia is added to this rare comorbidity. This case report discussed the comorbidity and probable causal relationships. Furthermore, the research method of how transposition in internal organs is reflected in brain lateralization is also presented.

Perisylvian GABA levels in schizophrenia and bipolar disorder.

The aim of this study is to measure GABA levels of perisylvian cortices in schizophrenia and bipolar disorder patients, using proton magnetic resonance spectroscopy (1H-MRS). Patients with schizophrenia (n=25), bipolar I disorder (BD-I; n=28) and bipolar II disorder (BD-II; n=20) were compared with healthy controls (n=30). 1H-MRS data was acquired using a Siemens 3T whole body scanner to quantify right and left perisylvian structures' (including superior temporal lobes) GABA levels. Right perisylvian GABA values differed significantly between groups [χ2=9.62, df: 3, p=0.022]. GABA levels were significantly higher in the schizophrenia group compared with the healthy control group (p=0.002). Furthermore, Chlorpromazine equivalent doses of antipsychotics correlated with right hemisphere GABA levels (r2=0.68, p=0.006, n=33). GABA levels are elevated in the right hemisphere in patients with schizophrenia in comparison to bipolar disorder and healthy controls. The balance between excitatory and inhibitory controls over the cortical circuits may have direct relationship with GABAergic functions in auditory cortices. In addition, GABA levels may be altered by brain regions of interest, psychotropic medications, and clinical stage in schizophrenia and bipolar disorder.

Brain oscillations in bipolar disorder and lithium-induced changes.

Electroencephalography (EEG) studies in patients with bipolar disorder have revealed lower amplitudes in brain oscillations. The aim of this review is to describe lithium-induced EEG changes in bipolar disorder and to discuss potential underlying factors. A literature survey about lithium-induced EEG changes in bipolar disorder was performed. Lithium consistently enhances magnitudes of brain oscillations in slow frequencies (delta and theta) in both resting-state EEG studies as well as event-related oscillations studies. Enhancement of magnitudes of beta oscillations is specific to event-related oscillations. Correlation between serum lithium levels and brain oscillations has been reported. Lithium-induced changes in brain oscillations might correspond to lithium-induced alterations in neurotransmitters, signaling cascades, plasticity, brain structure, or biophysical properties of lithium. Therefore, lithium-induced changes in brain oscillations could be promising biomarkers to assess the molecular mechanisms leading to variability in efficacy. Since the variability of lithium response in bipolar disorder is due to the genetic differences in the mechanisms involving lithium, it would be highly promising to assess the lithium-induced EEG changes as biomarkers in genetic studies.

Lithium excessively enhances event related beta oscillations in patients with bipolar disorder.

BACKGROUND: Previous resting-state electroencephalography studies have consistently shown that lithium enhances delta and theta oscillations in default mode networks. Cognitive task based networks differ from resting-state networks and this is the first study to investigate effects of lithium on evoked and event-related beta oscillatory responses of patients with bipolar disorder. METHODS: The study included 16 euthymic patients with bipolar disorder on lithium monotherapy, 22 euthymic medication-free patients with bipolar disorder and 21 healthy participants. The maximum peak-to-peak amplitudes were measured for each subject's averaged beta responses (14-28 Hz) in the 0-300 ms time window. Auditory simple and oddball paradigm were presented to obtain evoked and event-related beta oscillatory responses. RESULTS: There were significant differences in beta oscillatory responses between groups (p=0.010). Repeated measures ANOVA revealed location (p=0.007), laterality X group (p=0.043) and stimulus X location (p=0.013) type effects. Serum lithium levels were correlated with beta responses. LIMITATIONS: The lithium group had higher number of previous episodes, suggesting that patients of the lithium were more severe cases than patients of the medication-free group. DISCUSSION: Lithium stimulates neuroplastic cascades and beta oscillations become prominent during neuroplastic changes. Excessively enhanced beta oscillatory responses in the lithium-treated patients may be indicative of excessive activation of the neuron groups of the certain cognitive networks and dysfunctional GABAergic modulation during cognitive activity.

Comparison of Propofol, Etomidate, and Thiopental in Anesthesia for Electroconvulsive Therapy: A Randomized, Double-blind Clinical Trial.

OBJECTIVES: This study aimed to compare the effects of propofol, thiopental, and etomidate, which are routinely used in anesthesia for electroconvulsive therapy (ECT), on the cardiovascular system, seizure variables, recovery, cognitive functions, and response to treatment. METHODS: Male patients hospitalized at the Seventh Psychiatry Clinics of the Bakirköy Teaching Hospital for Psychiatry, Neurology, and Neurosurgery who were treated with ECT were investigated prospectively. The effects on cardiovascular system parameters (heart rate, blood pressure, and blood oxygenation), seizure variables (duration and intensity of seizure), and recovery variables were recorded at every session, on prespecified time points, and the findings of the first session were used in this evaluation. In addition, clinical responses to treatment were evaluated with tests of cognitive functions before and after a course of ECT. Adverse effects were recorded. RESULTS: The sociodemographic characteristics of the 3 treatment groups were similar. There were no significant differences among the groups in terms of effects on cardiovascular system variables, seizure variables, and cognitive functions. The clinical response to ECT was good in all groups, without any significant differences. CONCLUSIONS: Propofol, etomidate, and thiopental are associated with similar safety and efficacy profiles.

Decrease of event-related delta oscillations in euthymic patients with bipolar disorder.

Decreased delta oscillation upon cognitive load is common in patients with Alzheimer׳s disease, mild cognitive impairment, and schizophrenia. However, there is no previous study analyzing the delta responses in euthymic medication-free patients with bipolar disorder. Participants comprised of 22 euthymic medication-free patients with DSM-IV diagnoses of bipolar disorder and 21 healthy controls who were matched to the patients for sex, age, and education. Electroencephalographic activity was recorded at 30 electrode sites using an application of an auditory oddball paradigm. The maximum peak-to-peak amplitudes for each subject׳s averaged delta response (0.5-3.5Hz) were measured. There was a significant inter-group difference in evoked and event-related delta (0.5-3.5Hz) responses. Post-hoc comparisons revealed that the event-related delta oscillatory responses of the bipolar patient group were significantly lower than those of the healthy control group over the temporo-parietal and occipital electrode sites. Euthymic bipolar patients showed reduced event-related delta oscillatory responses in comparison to healthy subjects under cognitive load. The decrease of delta oscillations may be a common phenomenon that can be observed in different neuropsychiatric disorders with cognitive dysfunction.