Insulin resistance, clinical presentation and resistance to selective serotonin and noradrenaline reuptake inhibitors in major depressive disorder.

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.

Chronobiological variables predict non-response to serotonin and noradrenaline reuptake inhibitors in fibromyalgia: a cross-sectional study.

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.

Psychological variables associated with resistance to treatment with serotonin and noradrenaline reuptake inhibitors in fibromyalgia.

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.

Subtypes of delirium after ischaemic stroke-predisposing factors and outcomes: a prospective observational study (PROPOLIS).

BACKGROUND AND PURPOSE: Delirium is a serious complication after stroke. It remains unclear whether different motor subtypes of delirium are associated with diverse risk factors and outcomes. The aim was to investigate if delirium subtypes differ in predisposing factors, clinical characteristics and outcomes. METHODS: In all, 698 patients with ischaemic stroke or transient ischaemic attack (median age 73 years; 53.7% female) were prospectively included. Core features of delirium during the first 7 days after admission were examined. The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for delirium were used. Pre-stroke characteristics were compared between different delirium subtypes and logistic regression and Cox proportional hazard models were used to explore the association between delirium, functional outcome and death. RESULTS: Hyperactive, hypoactive and mixed delirium were diagnosed in 28, 75 and 66 patients, respectively. Patients with hyperactive delirium had less severe neurological deficit on admission and more often had transient ischaemic attack compared with patients with hypoactive and mixed delirium. Compared with patients with hypoactive delirium, those with hyperactive delirium more often suffered from irritability/lability prior to stroke. Hyperactive and hypoactive delirium did not differ in age, sex, comorbidities, pre-stroke dependency, cognitive decline and severity of delirium. Hyperactive, hypoactive and mixed delirium were associated with an increased risk of poor 3- and 12-month functional outcome compared with patients without delirium. Moreover, patients with hypoactive and mixed delirium had an elevated risk of death. CONCLUSIONS: Hyperactive delirium is associated with less severe stroke and higher scores of pre-existing irritability/lability. All three motor subtypes of delirium are associated with poor outcome, although hyperactive delirium seems to have a less unfavourable prognosis.

Machine Learning-Based Identification of Suicidal Risk in Patients With Schizophrenia Using Multi-Level Resting-State fMRI Features.

BACKGROUND: Some studies suggest that as much as 40% of all causes of death in a group of patients with schizophrenia can be attributed to suicides and compared with the general population, patients with schizophrenia have an 8.5-fold greater suicide risk (SR). There is a vital need for accurate and reliable methods to predict the SR among patients with schizophrenia based on biological measures. However, it is unknown whether the suicidal risk in schizophrenia can be related to alterations in spontaneous brain activity, or if the resting-state functional magnetic resonance imaging (rsfMRI) measures can be used alongside machine learning (ML) algorithms in order to identify patients with SR. METHODS: Fifty-nine participants including patients with schizophrenia with and without SR as well as age and gender-matched healthy underwent 13 min resting-state functional magnetic resonance imaging. Both static and dynamic indexes of the amplitude of low-frequency fluctuation (ALFF), the fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity as well as functional connectivity (FC) were calculated and used as an input for five machine learning algorithms: Gradient boosting (GB), LASSO, Logistic Regression (LR), Random Forest and Support Vector Machine. RESULTS: All groups revealed different intra-network functional connectivity in ventral DMN and anterior SN. The best performance was reached for the LASSO applied to FC with an accuracy of 70% and AUROC of 0.76 (p < 0.05). Significant classification ability was also reached for GB and LR using fALFF and ALFF measures. CONCLUSION: Our findings suggest that SR in schizophrenia can be seen on the level of DMN and SN functional connectivity alterations. ML algorithms were able to significantly differentiate SR patients. Our results could be useful in developing neuromarkers of SR in schizophrenia based on non-invasive rsfMRI.

Content overlap analysis of 64 (hypo)mania symptoms among seven common rating scales.

OBJECTIVES: Fried () quantified the overlap of items among seven widely used depression rating scales. The analysis revealed substantial heterogeneity of the depressive syndromes and a low overlap among the scales. To our best knowledge, there are no studies evaluating the content overlap of (hypo)mania scales. The goal of our study, therefore, is to quantify the overlap of items among seven widely used (hypo)manic scales, implementing the methodology developed by Fried (). METHODS: Seven commonly used (hypo)manic scales underwent content analysis. Symptom overlap was evaluated with the use of the Jaccard index (0 = no overlap, 1 = full overlap). In case of every scale, rates of idiosyncratic symptoms and rates of specific versus compound symptoms were calculated. RESULTS: The seven scales gathered 64 hypo(manic) symptoms. The mean overlap among all of the instruments was low (0.35), the mean overlap of each scale with all others ranged from 0.29 to 0.48, and the overlap among individual scales ranged from 0.20 to 0.65. Thirty-six percent of symptoms appeared only on one scale. Only 6% of the symptoms appeared on all of the instruments. CONCLUSIONS: We have shown that using (hypo)manic scales as interchangeable measurements may be problematic.

Associations between chronotype, sleep disturbances and seasonality with fatigue and inflammatory bowel disease symptoms.

Growing number of studies suggests link between circadian rhythms and inflammatory bowel diseases (IBD) manifestation. We hypothesize that: 1) IBD are associated with increased eveningness and sleep disturbances; 2) eveningness and sleep disturbances are related to more severe IBD symptoms. In total, 129 participants were enrolled to this study, divided into three groups: 34 Crohn's disease (CD) patients, 38 ulcerative colitis (UC) patients and 57 healthy controls (HC) group. They all fulfilled a questionnaire, consisting of the Composite Scale of Morningness (CSM), Seasonal Pattern Assessment Questionnaire (SPAQ), Pittsburgh Sleep Quality Index, Inflammatory Bowel Disease Questionnaire (IBDQ) and Multidimensional Fatigue Inventory (MFI). Multiple regression models controlled for age and sex revealed that in CD group higher eveningness measured with CSM was associated with higher general fatigue, physical fatigue, mental fatigue and reduced motivation measured by MFI. Lower CSM morning affect is associated with greater general fatigue, physical fatigue and more reduced activity. Greater seasonality scores are associated with increased physical fatigue and more reduced activity and motivation. Lower sleep quality measured with PSQI is associated with higher physical fatigue and more reduced activity. Correlational analysis revealed that higher seasonality and lower sleep quality are associated with increased systemic and bowel symptoms and decreased emotional and social functions measured with IBDQ. In UC group, eveningness is associated with greater general fatigue, physical fatigue and more reduced activity. Higher CSM morning affect is associated with decreased general fatigue, physical fatigue and less reduced activity. Higher CSM circadian preference scores are associated with decreased general and physical fatigue, and less reduced activity. Increased seasonality is associated with more physical fatigue. Lower sleep quality is associated with greater general and physical fatigue. To our best knowledge this is the first study evaluating associations between chronotype and sleep disturbances with IBD symptoms. We have found that chronotype preferences, whose role in IBD has been until now overlooked, may be one of the important factors contributing to fatigue in this clinical group.

The role of affective temperaments assessed by the Temperament Evaluation of Memphis, Pisa and San Diego-Autoquestionnaire (TEMPS-A) in the relationship between morningness-eveningness and bipolarity.

BACKGROUND: Growing number of studies indicates a link between eveningness chronotype, affective temperaments and bipolarity, both in patients with mood disorders and in general population. Given these tripartite associations, we hypothesized that the effect of circadian preferences on the bipolarity may be mediated by the temperamental traits. METHODS: The study included 1449 subjects (402 men and 1047 women). They all fulfilled a web-based questionnaire, consisting of the Composite Scale of Morningness (CSM), Mood Disorder Questionnaire (MDQ), Hypomania Checklist-32 (HCL-32) and the Temperament Evaluation of the Memphis, Pisa and San Diego-Autoquestionnaire (TEMPS-A). The role of temperamental traits in the relationship between morningness-eveningness and bipolarity was assessed using mediation analysis. RESULTS: Morningness is correlated with lower bipolarity measured by the MDQ and HCL-32, and to lower scores of depressive, cyclothymic, irritable and anxious temperaments of the TEMPS-A. There is no significant association between morningness and hyperthymic traits. Cyclothymic and irritable traits are full mediators of the association between chronotype and bipolarity, influencing bipolarity independently from circadian preferences. Depressive and anxious traits are partial mediators of this association, increasing the effect of eveningness on bipolarity. LIMITATIONS: The indirectness of the findings in the web-based study and disproportion of participants' gender. CONCLUSIONS: Our study confirmed that eveningness is associated with bipolarity. In case of depressive and anxious temperaments, bipolarity is associated stronger with eveningness than with the TEMPS-A scores. On the other hand, cyclothymic and irritable temperaments were associated with bipolarity independently from circadian preferences.

The Biological Rhythms Interview of Assessment in Neuropsychiatry in patients with bipolar disorder: correlation with affective temperaments and schizotypy

Objective: To assess the relationship of biological rhythms, evaluated by the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN), with affective temperaments and schizotypy. Methods: The BRIAN assessment, along with the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Autoquestionnaire (TEMPS-A) and the Oxford-Liverpool Inventory for Feelings and Experiences (O-LIFE), was administered to 54 patients with remitted bipolar disorder (BD) and 54 healthy control (HC) subjects. Results: The TEMPS-A cyclothymic temperament correlated positively and the hyperthymic temperament correlated negatively with BRIAN scores in both the BD and HC groups, although the correlation was stronger in BD subjects. Depressive temperament was associated with BRIAN scores in BD but not in HC; conversely, the irritable temperament was associated with BRIAN scores in HC, but not in BD. Several positive correlations between BRIAN scores and the schizotypal dimensions of the O-LIFE were observed in both BD and HC subjects, especially with cognitive disorganization and less so with unusual experiences and impulsive nonconformity. A correlation with introversion/anhedonia was found only in BD subjects. Conclusion: Cyclothymic and depressive temperaments predispose to disturbances of biological rhythms in BD, while a hyperthymic temperament can be protective. Similar predispositions were also found for all schizotypal dimensions, mostly for cognitive disorganization.

The Biological Rhythms Interview of Assessment in Neuropsychiatry in patients with bipolar disorder: correlation with affective temperaments and schizotypy.

OBJECTIVE:: To assess the relationship of biological rhythms, evaluated by the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN), with affective temperaments and schizotypy. METHODS:: The BRIAN assessment, along with the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Autoquestionnaire (TEMPS-A) and the Oxford-Liverpool Inventory for Feelings and Experiences (O-LIFE), was administered to 54 patients with remitted bipolar disorder (BD) and 54 healthy control (HC) subjects. RESULTS:: The TEMPS-A cyclothymic temperament correlated positively and the hyperthymic temperament correlated negatively with BRIAN scores in both the BD and HC groups, although the correlation was stronger in BD subjects. Depressive temperament was associated with BRIAN scores in BD but not in HC; conversely, the irritable temperament was associated with BRIAN scores in HC, but not in BD. Several positive correlations between BRIAN scores and the schizotypal dimensions of the O-LIFE were observed in both BD and HC subjects, especially with cognitive disorganization and less so with unusual experiences and impulsive nonconformity. A correlation with introversion/anhedonia was found only in BD subjects. CONCLUSION:: Cyclothymic and depressive temperaments predispose to disturbances of biological rhythms in BD, while a hyperthymic temperament can be protective. Similar predispositions were also found for all schizotypal dimensions, mostly for cognitive disorganization.

A web-based study of bipolarity and impulsivity in athletes engaging in extreme and high-risk sports.

BACKGROUND: We hypothesised that men and women who engage in extreme or high-risk sports would score higher on standardised measures of bipolarity and impulsivity compared to age and gender matched controls. METHODS: Four-hundred and eighty extreme or high-risk athletes (255 males and 225 females) and 235 age-matched control persons (107 males and 128 females) were enrolled into the web-based case-control study. The Mood Disorder Questionnaire (MDQ) and Barratt Impulsiveness Scale (BIS-11) were administered to screen for bipolarity and impulsive behaviours, respectively. RESULTS: Results indicated that extreme or high-risk athletes had significantly higher scores of bipolarity and impulsivity, and lower scores on cognitive complexity of the BIS-11, compared to controls. Further, there were positive correlations between the MDQ and BIS-11 scores. CONCLUSION: These results showed greater rates of bipolarity and impulsivity, in the extreme or high-risk athletes, suggesting these measures are sensitive to high-risk behaviours.

[Convergence insufficiency with unilateral exophoria at near in schizophrenia and bipolar disorder - a preliminary study]. / Niewydolnosc konwergencji z jednostronna egzoforia do blizy w schizofrenii i chorobie afektywnej dwubiegunowej - badania wstepne.

OBJECTIVES: The study describes an abnormal convergence symptom, i.e. unilateral exophoria at near, in patients with schizophrenia (SZ) and bipolar disorder (BD). The aim of this paper is to present the symptom and discuss its possible explanations. METHODS: 29 patients with SZ, 15 patients with BD and 20 healthy controls (HC) took part in the study. The neurological assessment was done with International Co-operative Ataxia Rating Scale (ICARS) and Neurological Evaluation Scale (NES). RESULTS: The abnormal vergence pattern was observed in 12 patients with SZ, 1 patient with BD and 0 HC. Symptom appeared statistically more often in SZ patients than in BD patients and HC. SZ patients with vergence symptom performed significantly worst in oculomotor and dysarthia subscores of ICARS. CONCLUSIONS: The symptom can be linked to disruptions in cortico-ponto-cerebellar network and midbrain. It was the only neurological symptom that differed SZ and BD groups, thus it might be used in differential diagnosis. Further research is needed to obtain a full clinical description of the symptom.