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Available data shows associations between chronotype, circadian rhythms, sleep quality and fibromyalgia (FM) presentation. However, no studies have explored links between the chronobiological variables and effectiveness of pharmacotherapy. We aimed to assess the chronotypes, circadian rhythms, sleep-wake cycle and sleep quality in FM and their links to treatment response to serotonin and noradrenalin reuptake inhibitors (SNRI). 60 FM patients: 30 responsive to SNRI (FM T[+]), 30 non-responsive to SNRI (FM T[-]) and 30 healthy controls participated. Subjects were assessed by physician and with questionnaire tools: Composite Scale of Morningness, Biological Rhythms Interview of Assessment in Neuropsychiatry, Sleep-Wake Pattern Assessment Questionnaire, Pittsburgh Sleep Quality Index and Fibromyalgia Impact Questionnaire. ANOVA analysis and simple logistic regressions were used to examine the relationships between chronological variables and response to SNRI. FM T[-] vs. FM T[+] presented lower morning affect (11.50[95%CI 9.96-13.04] vs. 14.00[95%CI 12.42-15.57];p=0.04), anytime wakeability (2.27[95%CI 1.4-3.13] vs. 4.03[95%CI 2.99-5.08];p=0.013) worse overall (11.40[95%CI 9.92-12.88] vs. 7.97[95%CI 6.75-9.19];p=0.002) and subjective (1.70[95%CI 1.30-2.01] vs. 1.17[95%CI 0.94-1.39];p=0.008) sleep quality, higher circadian rhythm disruptions (55.47[95%CI 52.32-58.62] vs. 44.97[95%CI 41.31-48.62];p<0.001), sleep disturbances (1.63[95%CI 1.38-1.68] vs. 1.30[95%CI 1.1-1.5];p=0.04), sleeping-medication use (1.80[95%CI 1.27-2.32] vs. 0.70[95%CI 0.28-1.12];p=0.003). Levels of morningness (AIC=82.91,OR=0.93,p=0.05), morning affect (AIC=81.901,OR=0.86,p=0.03) diurnal dysrhythmia (AIC=69.566,OR=1.14,p<0.001), anytime wakeability (AIC=80.307,OR=0.76,p=0.015), overall sleep quality (AIC=74.665, OR=1.31,p=0.002) subjective sleep quality (AIC=79.353, OR=2.832,p=0.01) and disturbances (AIC=82.669,OR=2.54,p=0.043), sleep medication use (AIC=77.017, OR=1.9,p=0.003) and daytime disfunction (AIC=82.908, OR=1.971,p=0.049) were predictors of non-response to SNRI. Chronobiological variables vary between FM T[+] and FM T[-] and are predictors of non-response to SNRI., (© 2024. The Author(s).)

Background: The understanding of mechanisms underlying non-response to antidepressants is limited. The latest data highlights the role of insulin resistance (IR) in major depressive disorder (MDD) pathophysiology, presentation, and treatment efficacy. This work aimed to assess IR in MDD and explore the relationships between IR, MDD presentation and non-response to selective serotonin and noradrenaline reuptake inhibitors (SNRI)., Methods: 67 MDD individuals: 36 responsive (MDD T[+]), 31 non-responsive (MDD T[-]) to SNRI and 30 healthy controls were recruited. The treatment response criteria were: Clinical Global Impression Scale-Improvement score of 1 or 2 after ≥ 8 weeks of treatment. Participants were assessed by physician and self-report tools measuring depression, anhedonia, anxiety, bipolarity, sleep quality. Blood samples were collected to assess fasting glucose and insulin levels and calculate HOMA-IR (homeostasis model assessment of insulin resistance)., Results: MDD T[-] vs. MDD T[+] had significantly higher body mass index, insulin levels, and HOMA-IR. MDD T[-] presented higher levels of depressed mood, appetite/weight changes, loss of interest, energy, overall depressive symptoms, and sleep impairment; some evaluations suggested higher anhedonia and anxiety in MDD T[-] vs. MDD T[+]. Insulin and IR were weakly but significantly correlated with the severity of psychomotor symptoms, energy level, thoughts of death/suicide, self-criticism, appetite/weight, depressed mood symptoms, sleep problems. IR was weakly but significantly correlated with anhedonia., Conclusion: IR appears to be linked to depressive symptoms characteristic of the "metabolic" MDD subtype, such as psychomotor changes, energy level, anhedonia, sleep problems, appetite/weight changes, state and trait anxiety, sleep quality, and non-response to SNRI., (© 2024. The Author(s).)

Anhedonia constitutes a core symptom of major depressive disorder (MDD) mediating the ultimate goal of MDD treatment: functional remission. Anhedonia is also present in other clinical populations, including patients with chronic pain. Recent data links anhedonia to insulin resistance (IR). Some researchers have underlined a different dimension of anhedonia as a temperament/personality trait. The objective of this post-hoc analysis was to explore the links between anhedonia (main outcome) and (1) IR, (2) temperamental, personality, and schizotypy traits (exposures). The study population included patients with MDD, fibromyalgia, and healthy controls. Participants were split into groups: (1) insulin resistant (IR[+] n = 69, HOMA-IR ≥ 2.1) and (2) insulin sensitive (IR[-] n = 69, HOMA-IR < 2.1). Anhedonia was significantly higher in the IR[+] group than the IR[-] group. IR was a predictor of higher anhedonia levels. IR[+] vs. IR[-] participants showed higher levels of anxiety and lower levels of hyperthymic affective temperaments, as well as conscientiousness and emotional stability personality traits. Depressive, irritable, and anxious temperaments, cognitive disorganization, and introvertive anhedonia positively predicted anhedonia, while hyperthymic temperament, conscientiousness, extraversion, and emotional stability traits negatively predicted anhedonia. IR partially mediated the relationship between depressive temperament and anhedonia. In sum, IR, affective temperaments, and personality traits are predictors of anhedonia.

Objectives: Fibromyalgia (FM) is often comorbid with psychiatric disorders. Moreover, several studies show that psychiatric disorders may be linked to the severity and impact of FM. Therefore, the study described in the article had two main goals: (1) to explore various psychopathological symptom dimensions in patients with fibromyalgia and secondly, (2) to examine the links between psychopathology and response to treatment with serotonin and norepinephrine reuptake inhibitors (SNRI)., Methods: This cross-sectional study was performed between December 2020 and November 2022. The definition of resistance to SNRI was <30% reduction of pain after ≥8 weeks of treatment. 30 FM subjects responsive to SNRI (FM T[+]), 32 patients non-responsive to SNRI (FM T[-]) and 30 healthy controls were enrolled. Participants were examined by physicians and completed self-report tools to evaluate levels of depression (Quick Inventory of Depressive Symptomatology, Hospital Anxiety and Depression Scale), anxiety (State and Trait Anxiety Inventory), anhedonia (Snaith-Hamilton Pleasure Scale), bipolar symptoms (Mood Disorder Questionnaire, Hypomania Checklist), and dissociation (Dissociative Experiences Scale - Revised). ANOVA analysis and a series of simple logistic regressions were used to examine the associations between psychopathological variables and response to SNRI., Results: FM T[-] vs. FM T[+] showed higher levels of: depression, state and trait anxiety and anhedonia as well as higher proportion of scores indicating the presence of anxiety disorder. Increased severity of depression, anxiety and anhedonia were predictors of resistance to SNRI., Conclusions: Modifiable psychopathological symptoms vary in FM T[+] vs. FM T[-] and are predictors of resistance to SNRI. Psychological assessment should be integrated into standard care for FM patients.

Objective: The treatment of fibromyalgia (FM) often offers only partial pain relief. Among the most effective drugs for FM pain are serotonin and noradrenalin reuptake inhibitors (SNRI). Few studies investigated the affective temperaments and personality features in FM. Our objective was to explore the associations between the affective temperaments, personality traits, schizotypy and response to SNRI treatment in FM., Methods: 60 FM patients: 30 responsive to SNRI (FM T[+]), 30 non-responsive to SNRI (FM T[-] and 30 healthy controls were recruited. Resistance to SNRI was defined as <30% pain reduction during at least 8-week treatment. Subjects were assessed by physician and filled self-report questionnaires: Temperament Scale of Memphis, Pisa and San Diego- autoquestionnaire, Ten Item Personality Inventory, Oxford-Liverpool Inventory of Feelings and Experiences and Fibromyalgia Impact Questionnaire (FIQ). ANOVA analysis and simple logistic regressions were used to examine the links between psychological variables and lack of response to SNRI., Results: FM T[-] presented higher scores in total FIQ and in physical, work, well-being, pain, fatigue/sleep, stiffness domains than FM T[+]. FM T[-] showed higher levels of: irritable and anxious temperaments, neuroticism, schizotypy than FM T[+]. The levels of depressive, irritable and anxious temperaments, introversion, neuroticism and schizotypy were linked to lack of response to SNRI., Conclusions: FM T[+] and FM T[-] differ in clinical presentation and psychological features. The levels of affective temperaments, personality and schizotypal traits are associated with lack response to SNRI in FM., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: The efficacy of vortioxetine in major depressive disorder has been evaluated in many studies. However, there is a lack of studies assessing vortioxetine in bipolar depression., Methods: In 60 patients with bipolar depression, vortioxetine 10-20 mg daily was added to current mood stabilizing medication during 24-week, naturalistic, openlabel study. The most frequent mood stabilizers were lamotrigine, quetiapine, olanzapine, and valproates. The therapeutic efficacy was evaluated by the Clinical Global Impression - Improvement (CGI-I) and Clinical Global Impression - Severity (CGI-S) scales. Patients were classified as responding to vortioxetine when they achieved 1 or 2 points on the CGI-I scale at any stage of observation. The criterion of remission was defined as score 1 at the CGI-S., Results: 73% of all patients (44/60) responded to vortioxetine and 52% (31/60) achieved clinical remission of depressive symptoms (in mean 8.97 ± 4.05 weeks). There were no significant associations between vortioxetine response/remission rates and: (1) the dose, (2) BD type, (3) clinical stage, (4) presence of rapid cycling, (5) history of psychotic symptoms, analyzed depressive symptoms, and (6) concomitantly used mood stabilizer. 4 patients (6.7%) stopped treatment due to adverse effects (nausea), and 7 patients (11.7%) discontinued treatment due to the phase switch. 14 patients (23%) experienced a loss of vortioxetine effectiveness after the initial response or remission., Conclusions: The results indicate relatively high rates of response and remission during 24-week treatment in depressed bipolar patients receiving vortioxetine concomitantly with a mood stabilizer. This may indicate that vortioxetine added to a mood stabilizer may constitute an efficient and well tolerated therapeutic option in bipolar depression.

Background: Schizophrenia (SZ) and bipolar disorder (BD) patients share deficits in motor functions in the form of neurological (NSS) and cerebellar soft signs (CSS), and implicit motor learning disturbances. Here, we use cluster analysis method to assess (1) the relationship between those abnormalities in SZ and BD and (2) the differences between those groups., Methods: 33 SZ patients, 33 BD patients as well as 31 healthy controls (HC) took part in the study. We assessed CSS with the International Cooperative Ataxia Rating Scale (ICARS) and NSS with the Neurological Evaluation Scale (NES). Implicit motor learning was evaluated with the Serial Reaction Time Task (SRTT). Participants were divided into clusters (Ward's method) based on the mean response time and mean error rate in SRTT. The difference in ICARS and NES scores, and SRTT variables between clusters were evaluated. We have measured associations between SRTT parameters and both ICARS and NES total scores and subscores., Results: Cluster analysis based on the SRTT parameters allowed to extract three clusters. Those were characterized by the increasing disruption of motor functioning (psychomotor retardation, the severity of NSS and CSS) regardless of the diagnosis. Cluster 1 covered almost all of HC and was characterized by faster reaction times and small number of errors. BD and SZ patients represented in cluster 1, although fully functional in performing the SRTT, showed higher rates of NSS and CSS. Patients with BD and SZ were set apart in clusters 2 and 3 in a similar proportion. Cluster 2 presented significantly slower reaction times but with the comparable number of errors to cluster 1. Cluster 3 consisted of participants with normal or decreased reaction time and significantly increased number of errors. None of the clusters were predominantly composed of the patients representing one psychiatric diagnosis., Conclusions: To our best knowledge, we are presenting the first data indicating the relationship between implicit motor learning and NSS and CSS in SZ and BD patients' groups. Lack of clusters predominantly represented by patients with the diagnosis of SZ or BD may refer to the model of schizophrenia-bipolar disorder boundary, pointing out the similarities between those two disorders., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: With respect to bipolar disorder (BD), previous research have demonstrated saccadic eye movements abnormalities, manifested mainly as an increase in reaction time (latency) in both prosaccadic and antisaccadic task. So far, there were no studies related to vergence eye movements in subjects with BD. Our primary aim was to evaluate vergence tracking performance in this clinical group., Methods: 30 patients with BD in remission and 23 healthy controls were enrolled. Subjects underwent optometric examination where near point of convergence was measured by the use of Wolff Wand. Instrumented convergence measurements were performed using infrared eye tracker and dedicated vergence stimuli generator., Results: BD patients presented significantly higher average error between eyes' convergence and convergence required to fixate the target and higher number of saccadic intrusions compared with healthy controls group. Principal component analysis performed on oculometric parameters revealed differences between BD patients and healthy controls. Significant correlations between the vergence disturbances and saccadic intrusions were found., Conclusions: BD patients showed the alterations of the vergence eye movements similar to the disturbances of eye movements in the fronto-parallel plane. While the abnormalities of vergence eye movements in some mental disorders have been reported, we have for the first time objectively measured this phenomenon in BD.

Purpose: There is a strong medical demand to search for novel, more efficacious and safer than available, analgesics for the treatment of neuropathic pain. This study investigated antinociceptive activity of intraperitoneally administered 3-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one (LPP1) and pregabalin in the chronic constriction injury (CCI) model of neuropathic pain in mice and evaluated these drugs' influence on motor coordination. In addition, microscopic examinations of the sciatic nerve were performed to assess, if a surgical method or drug treatment caused changes in the structure of this nerve. Moreover, the alterations of nerve growth factor (NGF) content after drug treatment were assessed., Methods: Antiallodynic and antihyperalgesic activities of LPP1 and pregabalin were assessed in the von Frey and hot plate tests. Motor-impairing properties were evaluated in the rotarod test. Microscopic examinations of the sciatic nerve were performed using electron microscope. In immunohistochemical assays the content of NGF in the sciatic nerve after single or repeated administration of test drugs was assessed., Results: Microscopic examinations of the sciatic nerve revealed ultrastructural changes in nerve fibers indicating for neurodegenerative processes induced by CCI. Seven days after CCI surgery LPP1 and pregabalin reduced tactile allodynia in von Frey test (ED50 values were 1.5 and 15.4 mg/kg, respectively). None of the test drugs at dose range 0.5-100 mg/kg induced motor deficits in the rotarod test. In immunohistochemical assays repeated doses of pregabalin and LPP1 elevated NGF content., Conclusions: LPP1 has antiallodynic properties and is an interesting lead structure in the search for novel analgesics used in neuropathic pain.

Morphological transformation of lectin-positive microglia/macrophages in the developing rat cerebral hemisphere was analysed using quantitative methods. During the first postnatal month, the cells showed increases in their size and fractal dimension accompanied by a simultaneous decrease in their solidity. Regional variations in dynamics of the process indicated the existence of spatio-temporal developmental gradients within the cerebral hemisphere wall which might correspond with regional patterns of neuronal differentiation. Results of the present study prove that the quantitative methods can be the source of reliable data replacing subjective cell typologies.