New Light on Prions: Putative Role of PrPc in Pathophysiology of Mood Disorders.

Mood disorders are highly prevalent and heterogenous mental illnesses with devastating rates of mortality and treatment resistance. The molecular basis of those conditions involves complex interplay between genetic and environmental factors. Currently, there are no objective procedures for diagnosis, prognosis and personalization of patients' treatment. There is an urgent need to search for novel molecular targets for biomarkers in mood disorders. Cellular prion protein (PrPc) is infamous for its potential to convert its insoluble form, leading to neurodegeneration in Creutzfeldt-Jacob disease. Meanwhile, in its physiological state, PrPc presents neuroprotective features and regulates neurotransmission and synaptic plasticity. The aim of this study is to integrate the available knowledge about molecular mechanisms underlying the impact of PrPc on the pathophysiology of mood disorders. Our review indicates an important role of this protein in regulation of cognitive functions, emotions, sleep and biological rhythms, and its deficiency results in depressive-like behavior and cognitive impairment. PrPc plays a neuroprotective role against excitotoxicity, oxidative stress and inflammation, the main pathophysiological events in the course of mood disorders. Research indicates that PrPc may be a promising biomarker of cognitive decline. There is an urgent need of human studies to elucidate its potential utility in clinical practice.

Psychopathological symptoms in fibromyalgia and their associations with resistance to pharmacotherapy with SNRI. / Objawy psychopatologiczne w fibromialgii i ich zwiazki z opornoscia na farmakoterapie z zastosowaniem SNRI.

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.

Sexual activity in a large representative cohort of Polish men: Frequency, number of partners, correlates, and quality of life.

INTRODUCTION: Sexual activity of men has been evaluated at the population-level in different regions of the world. However, reliable data are lacking for Eastern Europe. Therefore, the aim of this study was to analyze the frequency of sexual activity and the number of sexual partners in a large representative cohort of Polish men. METHODS: We performed a cross-sectional investigation with computer-assisted web interviews. Participants were stratified by age (≥18 years) and place of residence. The most recent population census was used to produce a population-representative sample of respondents. Men's sexual activity was then correlated with multiple variables. RESULTS: We enrolled 3001 men, representative for age and place of residence, including adequate proportions of respondents from urban and rural areas. Most Polish men were sexually active, predominantly having had sex at least weekly with one partner. Almost 18% of respondents declined sexual intercourse and/or sexual partner in the prior year. The highest sexual activity was observed for men 35-44-years-old (for sex frequency) and 18-24-years-old (for partner number), living in medium-sized cities, employed, and married (for sex frequency) or divorced (for partner number). Erectile dysfunction negatively affected the frequency of sexual activity and lowered the number of sexual partners, although premature ejaculation did not have any effect. Frequency of sexual activity and number of sexual partners correlated well with psychological distress, quality of sex life, and overall life quality. Whereas lifestyle habits including smoking and alcohol intake decreased the likelihood of sexual activity, all analyzed comorbidities did not affect sex life. CONCLUSIONS: This study of men's sexual activity was the first population-representative and nationwide investigation performed in Poland. Most Polish men were sexually active and sexual activity correlated with multiple variables including sociodemographic factors, erectile functioning, mental distress, overall and sex-specific quality of life, and lifestyle habits.

Content overlap of 91 dystonia symptoms among the seven most commonly used cervical dystonia scales.

INTRODUCTION: Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions. Cervical dystonia (CD) is the most common focal dystonia. There are several instruments assessing the symptoms of CD. However, different scales assess different features which may lead to poor patient evaluation. AIM: The aim of the study was to evaluate the degree of overlap of most often used CD rating scales identified by the literature review. METHODS: A thorough search of the Medline database was conducted in September 2021. Then the frequency of each scale was calculated, and 7 most common scales were included in the content overlap analysis using Jaccard index (0 - no overlap, 1 - full overlap). RESULTS: Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), Tsui score, Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), Cervical Dystonia Impact Profile 58 (CDIP-58), Craniocervical Dystonia Questionnaire 24 (CDQ-24), Cervical Dystonia Severity Rating Scale (CDSS), Cervical Dystonia Severity Rating Scale (DDS) and The Dystonia Non-Motor Symptoms Questionnaire (DNMSQuest) were the most common scales. 91 CD symptoms were distinguished from 134 items used in the scales. The mean overlap among all scales was 0.17. 52 (62%) symptoms were examined by more than one scale. The CIDP-58 captured the highest number of symptoms (63.0%), while the CDSS captured the lowest number (8.0%). None of the symptoms were examined by seven instruments. CONCLUSIONS: There was a very weak overlap among scales. High inconsistency between the scales may lead to highly different dystonia severity assessment in clinical practice. Thus, the instruments should be combined.

TED-trazodone effectiveness in depression: a naturalistic study of the effeciveness of trazodone in extended release formulation compared to SSRIs in patients with a major depressive disorder.

Introduction: Selective serotonin reuptake inhibitors (SSRIs) are the most often used medications to treat major depressive disorder (MDD). Despite their effectiveness in reducing depressive symptoms, several issues are associated with their use in MDD, such as limited improvement of anhedonia, emergence of emotional blunting, induction or exacerbation of insomnia, and sexual dysfunction. Due to its also devoid of the issues related to treatment noted with SSRIs. The aim of this 12-week non-inferiority naturalistic observation was to compare the effectiveness and tolerability of SSRIs and trazodone in extended release (XR) in MDD. Methods: A total of 186 subjects were recruited, of which 92 received trazodone XR and 94 received SSRIs. Patients were allocated to trazodone XR or SSRIs, according to the attending physician based on clinical evaluation. Assessments at baseline and weeks 2, 4, 8, and 12 were conducted to evaluate the severity of depression (Montgomery-Åsberg Depression Rating Scale, clinician- and patient-rated Quick Inventory of Depressive Symptomatology-the primary endpoints of the study), anhedonia (the Snaith-Hamilton Pleasure Scale), anxiety (the Hamilton Anxiety Rating Scale), insomnia (the Athens Insomnia Scale), and therapeutic effectiveness (the Clinical Global Impression Scale). Results: After 12 weeks, trazodone XR was more effective than SSRIs in reducing the severity of depression, anxiety, and insomnia. There was a trend for higher effectiveness of in reduction of anhedonia, which became insignificant after controlling the results for the duration of previous psychiatric treatment as a covariate. The proportion of treatment-responsive subjects in the trazodone XR group compared to SSRIs was comparable or higher. The proportion of patients achieving remission was higher in the trazodone XR arm vs. the SSRI arm. Discussion: In summary, the results indicate that trazodone XR is effective in MDD in the "real-world" setting. Its potential superiority over SSRIs in addressing particular symptomatic dimensions should be verified in future studies.

Polish adaptation of the Dimensional Anhedonia Rating Scale (DARS) - validation in the clinical sample.

Background: Anhedonia is the core symptom of depression. Its presence has been linked to worsened prognosis. The Dimensional Anhedonia Rating Scale (DARS) is a scale measuring desire, motivation, effort and consummatory pleasure across different domains. The aim of this paper was to confirm factor structure, assess reliability and validity of the Polish adaptation of the DARS in a clinical sample of patients with mood disorders and healthy controls (HC). Methods: The study sample included 161 participants aged 18-65 years - 34 HC, 72 patients with bipolar disorder and 55 with major depressive disorder (in depressive episode or remission). Reliability of the Polish adaptation of the DARS was assessed using Cronbach's α and the average inter-item correlation (AIC). Convergent and divergent validity was established by Pearson's correlations between the DARS and the Snaith-Hamilton Pleasure Scale (SHAPS), the Quick Inventory of Depressive Symptomatology- self-report (QIDS-SR), the Hospital Anxiety and Depression Scale (HADS). The structure of the scale was examined by factor analysis. Results: The factor structure was consistent with the original scale. Strong internal consistency for the DARS total score (Cronbach's α = 0.95) and all subscales (0.86-0.93) was observed. The DARS demonstrated good convergent (moderate to strong correlations with measures of anhedonia and depression) and divergent validity (weak correlations with anxiety level). Conclusion: The Polish DARS demonstrated excellent internal consistency and very good validity. The scale is a valuable contribution to the psychometrics of anhedonia measures in patients with mood disorders.

Harder, better, faster, stronger? Retrospective chart review of adverse events of interactions between adaptogens and antidepressant drugs.

Aim: We aimed to systematically evaluate the prevalence and clinical characteristics of adverse events associated with the adaptogens and antidepressant drug interactions in a retrospective chart review. Methodology: A total of 1,816 reports of adverse events were evaluated. Cases were included in the analysis if the pharmacoepidemiological analysis showed the presence of a high probability of a causal relationship between an adaptogen and antidepressant interaction and the occurrence of adverse events. The following data were extracted from the reports: age, sex, antidepressant, plant products containing adaptogens, other concomitant medications, and clinical consequences of the interactions and their possible mechanisms. Results: Adaptogens were involved in 9% of adverse events associated with the concomitant use of antidepressants and other preparations. We identified 30 reports in which side effects presented a causal relationship with the use of antidepressants and adaptogens. Here, we present the list of adaptogens with the corresponding antidepressants and the side effects caused by their interactions: Withania somnifera: reboxetine (testicle pain and ejaculatory dysfunctions), sertraline (severe diarrhea), escitalopram (myalgia, epigastric pain, nausea, vomiting, restless legs syndrome, and severe cough), and paroxetine (generalized myalgia, ophthalmalgia, and ocular hypertension); Eleutherococcus senticosus: duloxetine (upper gastrointestinal bleeding), paroxetine (epistaxis), sertraline (vaginal hemorrhage), and agomelatine (irritability, agitation, headache, and dizziness); Schisandra chinensis: bupropion (arthralgia and thrombocytopenia), amitriptyline (delirium), and fluoxetine (dysuria); Tribulus terrestris: citalopram (generalized pruritus), escitalopram (galactorrhea), and trazodone (psoriasis relapse); Coptis chinensis: mianserin (arrhythmias), mirtazapine (edema of lower limbs and myalgia), and fluoxetine (gynecomastia); Cimicifuga racemosa: mianserin (restless legs syndrome), paroxetine (gynecomastia and mastalgia), and venlafaxine (hyponatremia); Bacopa monnieri: agomelatine (back pain and hyperhidrosis) and moclobemide (myocardial infarction); Gynostemma pentaphyllum: duloxetine (back pain); Cordyceps sinensis: sertraline (upper gastrointestinal bleeding); Lepidium meyenii: mianserin (restless legs syndrome); and Scutellaria baicalensis: bupropion (seizures). Conclusion: Clinicians should monitor the adverse events associated with the concomitant use of adaptogens and antidepressant drugs in patients with mental disorders. Aggregation of side effects and pharmacokinetic interactions (inhibition of CYP and p-glycoprotein) between those medicines may result in clinically significant adverse events.

When practice does not make a perfect - paradoxical learning curve in schizophrenia and bipolar disorder revealed by different serial reaction time task variants.

Introduction: Our previous studies identified a paradoxical implicit motor learning curve in schizophrenia (SZ) and bipolar disorder (BD) patients. This study aimed to verify whether those previously observed deficits may be captured by a new version of the ambidextrous serial reaction time task (SRTT), prepared for use in the MRI. Methods: This study involved 186 participants. A total of 97 participants (33 BD, 33 SZ, and 31 healthy controls, HCs) completed the original, unlimited time response variant of SRTT. A total of 90 individuals (30 BD, 30 SZ, and 30 HCs) underwent a newer, limited response time version of this procedure. Results: There was no significant difference in terms of implicit motor learning indices between both limited and unlimited response time SRTT. Compared to HCs, SZ, and BD patients presented decreased indices of implicit motor learning. Both clinical groups showed a paradoxical learning pattern that differed significantly from the HCs. Moreover, in the SZ group, the pattern depended on the hand performing SRTT. Discussion: The limited response time SRTT variant allowed us to replicate the findings of disrupted implicit motor learning in SZ and BD. The use of this paradigm in further neuroimaging studies may help to determine the neuronal underpinnings of this cognitive dysfunction in the abovementioned clinical groups.

Psychopharmacology and Biological Studies of Psychosis.

In most cases, psychotic episodes occur in the course of chronic mental illnesses, e [...].

Brexpiprazole-Pharmacologic Properties and Use in Schizophrenia and Mood Disorders.

In 2002, the first III generation antipsychotic drug was registered-aripiprazole. Its partial dopaminergic agonism underlies its unique mechanism of action and the potentially beneficial influence on the positive, negative, or cognitive symptoms. Due to its relatively high intrinsic activity, the drug could often cause agitation, anxiety, or akathisia. For this reason, efforts were made to develop a drug which would retain the positive favorable actions of aripiprazole but present a more advantageous clinical profile. This turned out to be brexpiprazole, which was registered in 2015. Its pharmacodynamic and pharmacokinetic profile (similarly to the other most recent antipsychotics, i.e., lurasidone or cariprazine) shows promise of increasing the effectiveness of schizophrenia treatment in the dimensions in which the previous antipsychotics were not sufficiently effective, including negative, depressive, or cognitive symptoms. Like other new antipsychotics, it can also be useful in the treatment of mood disorders, for instance drug-resistant depression. Previous reviews focused on the use of brexpiprazole in specific diagnostic groups. The aim of this article is to provide the readers with an overview of data on the mechanism of action, clinical effectiveness in all studied diagnostic groups, as well as potential drug-food interactions, and the safety of brexpiprazole.

Lurasidone Augmentation of Clozapine in Schizophrenia-Retrospective Chart Review.

The aim of our study was to evaluate the effectiveness of lurasidone augmentation of clozapine in treatment-resistant schizophrenia (SZ) in a retrospective chart review. From the medical records of 916 SZ patients, we identified 16 individuals treated with a combination of clozapine and lurasidone. The detailed clinical data are described separately for each patient. We compared the Clinical Global Impression-Severity (CGI-S) scores between three points of observation: before the treatment and one month and two months after its initiation. CGI Improvement (CGI-I) scores were used to evaluate the treatment response between the first and last points of observation. The vast majority of patients (14/16, 87.5%) responded to lurasidone augmentation of clozapine (CGI-I scores 1 or 2). Therapeutic effects were observable after 3-12 weeks of treatment (median 6 (4-6)). A reduction in CGI-S scores was observed after the first month of observation. There was an observable reduction in positive, depressive and anxiety symptoms, as well as an improvement in psychosocial functioning. Two patients discontinued treatment due to side effects. Our study suggests that lurasidone augmentation of clozapine may lead to improvements in a broad range of SZ symptom dimensions.

TED-Trazodone Efficacy in Depression: A Naturalistic Study on the Efficacy of Trazodone in an Extended-Release Formulation Compared to SSRIs in Patients with a Depressive Episode-Preliminary Report.

These are the preliminary results of a 12-week non-randomized, open-label, non-inferiority study comparing the effectiveness of trazodone in an extended-release formulation (XR) versus SSRIs in the treatment of major depressive disorder (MDD). Participants (n = 76) were recruited, and 42 were assigned to the trazodone XR group and 34 to the SSRIs group. The choice of drug was based on clinical presentation and relied upon the attending physician. Assessments were made at five observation time points, at the following weeks: 0, and after 2, 4, 8, and 12 weeks. The evaluations included: symptoms of depression (MADRS, QIDS-clinician, and self-rated versions-primary study endpoints), anhedonia (SHAPS), anxiety (HAM-A), insomnia (AIS), psychosocial functioning (SDS), and therapeutic efficacy (CGI). At baseline, the trazodone group had significantly more severe depressive, anxiety, and insomnia symptoms and worse psychosocial functioning compared to the SSRIs group. After 12 weeks, trazodone XR was more effective than SSRIs in reducing the severity of insomnia and depression. There were no differences between the groups in the frequencies of therapeutic response and remission, which indicated the non-inferiority of the trazodone XR treatment. In conclusion, our results showed that in a "real world" setting, trazodone XR is effective in the treatment of patients with MDD.

Bipolar spectrum in prostate cancer patients and its role in stress related symptoms.

BACKGROUND: Studies show significant co-occurrence of bipolar disorder and prostate cancer, as well as the presence of shared genes associated with both diseases. Our aim was to evaluate whether prostate cancer patients present bipolar spectrum symptoms and to establish their possible associations with stress related symptoms during diagnosis and the course of the cancer therapy. METHODS: 200 participants were enrolled to this study: 100 prostate cancer patients and 100 healthy males. Bipolar spectrum symptoms were measured with the use of Mood Disorder Questionnaire and Hypomania Checklist-32 (HCL-32). Stress related symptoms were rated with The Impact of Events Scale-Revised (IES-R), Perceived Stress Scale-10 (PSS-10) and Generalised Self-Efficacy Scale (GSES). RESULTS: In comparison to healthy controls group, prostate cancer patients have shown higher HCL-32 scores. Mood Disorder Questionnaire measures were associated with more severe stress related to prostate cancer diagnosis and treatment reflected by higher scores of IES-R and its subscales (Avoidance, Intrusions and Hyperarousal). Mood Disorder Questionnaire, HCL-32, PSS-10, IES-R and GSES measures were not associated with clinical characteristics of prostate cancer severity. LIMITATIONS: Cross-sectional study model precluded identification of causal relationship among variables. Bipolar spectrum symptoms and stress related measures were based on auto-questionnaires. CONCLUSIONS: To our best knowledge, this is the first study evaluating bipolar spectrum symptoms in prostate cancer patients. We have shown that this clinical group presents increased bipolarity traits compared to healthy individuals. Moreover, bipolar spectrum symptoms were associated with more severe stress related to the prostate cancer diagnosis and its treatment, reflected in avoidance, hyperarousal, and intrusions.

Neurological and cerebellar soft signs in bipolar disorder: The role of staging, type and history of psychotic symptoms.

AIM: Bipolar disorder (BD) patients show neurological abnormalities in form of neurological and cerebellar soft signs (NSS and CSS). NSS represents heterogeneous group of symptoms representing i.a. deficits of motor coordination, sequencing of complex motor acts and sensory integration. CSS were introduced as group of the neurological deficits of posture, gait, kinetic functions, eye movements and speech, associated more specifically to cerebellar abnormalities than NSS. Studies show significant effect size variability of those symptoms in BD group suggesting the existence of differing subpopulations. The aim of our study was to evaluate the effect of BD type, stage and the history of psychotic symptoms (HoPS) on the severity of CSS and NSS as none of the previous studies had verified the role of those categories. METHODS: This study involved 181 participants: 116 euthymic BD patients (66 BD I, 50 BD II) and 65 healthy controls (HC). CSS was assessed with the International Cooperative Ataxia Rating Scale and NSS with Neurological Evaluation Scale. Patients were divided into early and late stage of the disorder according to Kapczinski's criteria. Rater was blind to patients' stage, type and HoPS. RESULTS: Staging was related to vast majority of CSS and NSS scores. HoPS was related to oculomotor deficits. The effect of BD type was the least significant. Late stage BD showed more severe CSS and NSS than HC in every measure. There were no differences between early stage BD and HC, apart of posture and gait disturbances. Except of sensory integration scores, late stage BD showed higher CSS and NSS rates than early stage patients. CONCLUSION: In this hitherto the largest study of neurological abnormalities in BD we have shown significant role of staging in CSS and NSS severity. Progression criteria based on inter-episode psychosocial functioning may stand as unrecognised factor responsible for variability observed in previous studies evaluating neurological abnormalities in BD. Our study suggests that in clinical practice NSS and CSS may be potentially used as easy-to-assess biological marker of BD staging. Observed severity of neurological impairments of BD patients may more likely correspond to the disease progression than to BD type and HoPS.

Cariprazine augmentation of clozapine in schizophrenia-a retrospective chart review.

The aim of our study was to evaluate the efficacy of cariprazine augmentation of clozapine in treatment-resistant schizophrenia in a retrospective chart review. Among 916 medical records of schizophrenia patients, we identified 12 individuals treated with a combination of those drugs for a duration of 3-60 weeks [median 32 (10-40)]. Clinical Global Impression-Improvement (CGI-I) scores were used to measure the treatment response between the introduction of cariprazine augmentation of clozapine and the last point of observation. The majority of the patients presented treatment response (9/12 patients, 75%) after 4-16 weeks of therapy [median 6 (4-12)]. Treatment was associated with the decrease in positive, negative, affective, and anxiety symptom severity, as well as improvement of patient global functioning. One patient discontinued the treatment due to side effects (akathisia), and two patients halted the therapy due to the exacerbation of psychotic symptoms. Our study presents a thorough clinical description of the largest number of treatment-resistant schizophrenia patients medicated using cariprazine augmentation of clozapine in a "real-world" setting. Our results suggest that the use of this combination may lead to the improvement in a broad range of symptoms of patients with this condition.

TED (Trazodone Effectiveness in Depression): effectiveness of trazodone extended-release in subjects with unsatisfactory response to SSRIs. / TED (Trazodone Effectiveness in Depression): efektywnosc trazodonu o przedluzonym uwalnianiu u pacjentów z niezadowalajaca odpowiedzia na leczenie SSRI.

OBJECTIVES: Selective serotonin reuptake inhibitors (SSRIs) are the most commonly used drugs to treat major depressive disorder (MDD). However, about 50% of MDD patients do not achieve treatment response to SSRIs and there is little evidence on which drugs are effective as second-line treatment in those who do not respond to SSRIs. METHODS: In this work, the data of 79 patients with MDD were analyzed to evaluate the effectiveness of trazodone XR in the group of individuals treated de novo and those switched to trazodone XR after failed treatment attempt with SSRIs. The assessments were performed at baseline and weeks 2, 4, 8 and 12 using tools to evaluate the degree of: depression (Montgomery-Åsberg Depression Rating Scale, clinician and patient-rated Quick Inventory of Depressive Symptomatology - the primary endpoints of the study), therapeutic effectiveness (Clinical Global Impression Scale), anhedonia (Snaith-Hamilton Pleasure Scale), anxiety (Hamilton Anxiety Rating Scale), insomnia (Athens Insomnia Scale), psychosocial functioning (Sheehan Disability Scale) and sexual functioning (Female Sexual Function Inventory in women/International Index of Erectile Function in men). RESULTS: The rates of treatment response and remission were largely similar in both studied groups. CONCLUSIONS: The results showed that effectiveness of trazodone XR in the treatment of patients with MDD who did not respond to SSRIs administered as first-line treatment of a particular depressive episode was comparable to that noted in patients treated de novo. Furthermore, trazodone XR effectively improved depression, anxiety, insomnia, anhedonia and psychosocial functioning in both studied groups. Additionally, trazodone XR as secondline treatment improved sexual functions in male subjects previously treated with SSRIs.

A naturalistic, 24-week, open-label, add-on study of vortioxetine in bipolar depression. / Dolaczenie wortioksetyny w terapii depresji w chorobie afektywnej dwubiegunowej ­ 24-tygodniowe, otwarte badanie naturalistyczne.

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.

Vergence eye movements impairments in schizophrenia and bipolar disorder.

One of the most evaluated eye tracking tasks in schizophrenia (SZ) and bipolar disorder (BD) are smooth pursuit eye movements. They rely on the maintenance of slowly moving object on the fovea. While most of the studies evaluated tracking of a target that moves in the fronto-parallel plane, only two assessed vergence eye movements (VEM), which relies on the pursuit of object that moves in depth. The aim of our study was to compare VEM performance in SZ and BD. We evaluated 28 SZ patients, 32 BD patients and 25 healthy controls (HC). Participants underwent thorough optometric examination before eye tracking task. VEM were measured with the use of infrared eye tracker and dedicated vergence stimuli generator. SZ patients showed higher mean break and recovery points of fusion and shorter correct tracking time than HC. BD individuals revealed tracking accuracy deficits and higher number of saccades than HC. Compared to BD, SZ patients showed decrease of maximal convergence and divergence. Moreover, they presented tracking accuracy deficits of non-dominant eye: altered eyes positioning error during convergence and divergence gain. Exploratory analysis revealed significant gender differences between groups in terms of binocular VEM parameters. In this study we have recognized pattern of eye movement disturbances differentiating abovementioned groups. SZ patients showed decreased vergence tracking range with shorter tracking time and impaired accuracy of non-dominant eye, while BD patients showed higher number of saccades with decreased tracking accuracy. Neuroimaging studies are necessary to identify neuronal underpinnings of VEM impairments in SZ and BD.

Involvement of the cerebellum in the regulation of executive functions in children-Preliminary analysis based on a neuropsychological study of children after cerebellar tumour surgery.

Aim: Preliminary assessment of executive functions in children with cerebellar lesions, description of their emotional-social functioning and selection of sensitive neuropsychological tools to detect the cerebellar cognitive affective syndrome (CCAS). Materials and methods: The study group consisted of 10 children after cerebellar tumour surgery. The control group consisted of 10 healthy children, matched for age and sex: The IDS-2 executive functions battery, the Conners 3 ADHD questionnaire, the Autism Spectrum Rating Scales (ASRS) and the International Cooperative Ataxia Rating Scale (ICARS) were used. Results: Statistical analysis showed statistically significant differences between the experimental and control groups in terms of two dimensions of executive functioning. Children from experimental group was characterised by worse planning and divided attention than healthy controls. Moreover children with cerebellar lesions were characterised by significantly higher levels of some behaviours similar to that observed in autism spectrum disorders, namely difficulties in social relationships, self-regulation of emotions, attention, and greater behavioural rigidity. Test power analysis and estimation of the effect size by the Cohen's d coefficient indicated that with a slight increase in the size of the experimental group, the probability of detecting statistically significant difference in the executive functions total measure score as well as in several ASRS subscales increased, but not in Conners 3 subscales. Conclusions: Cerebellar damage may pose a risk for dysexecutive syndrome and social-emotional problems in children. The IDS-2 executive functions battery and the ASRS test are sufficiently sensitive tools to assess elements of the CCAS in children.

Unprescribed and unnoticed: Retrospective chart review of adverse events of interactions between antidepressants and over-the-counter drugs.

Aim: To systematically evaluate prevalence and clinical characteristics of adverse effects of antidepressants and OTC drugs interactions in a retrospective chart review. Methodology: Dataset of 1,145 registered adverse events were evaluated. Reports were selected for further analysis if pharmacoepidemiological avaluation indicated the presence of high probability of a causal relationship between antidepressants and OTC interaction and the occurrence of side effect. Following variables were extracted from the records: sex, age, medical comorbidities, antidepressant and other concomitant medications, clinical consequences ant the possible interaction mechanisms. Results: 368 showed causal relationship with the simultaneous use of antidepressant with another drug. 15 adverse events (4%) were related to the use of OTC medicine, particularly omeprazole, diphenhydramine, Japanese ginkgo biloba, ibuprofen, diclofenac and sildenafil. All of the analysed side effects were categorized as the result of pharmacokinetic interactions. Here we report identified OTC drugs with corresponding antidepressants and clinical manifestations of DDI. Omeprazole: agomelatine (nausea, abnormal dreams), fluoxetine (extrapyramidal symptoms, paresthesias), sertraline (vertigo, yawning), escitalopram (oral vesiculation). Diphenhydramine: sertraline (diaphoresis, insomnia, vertigo), paroxetine (pruritus, headache), duloxetine (oropharyngeal pain). Japanese ginkgo biloba: citalopram (bradycardia), trazodone (vertigo, taste pervesion), mianserine (restless legs syndrome). Diclofenac: escitalopram (oral vesiculation), and fluoxetine (restless legs syndrome). Ibuprofen: agomelatine (anxiety and nausea), sertraline and omeprazole (QTc prolongation). Sildenafil: fluoxetine (genital oedema) and sertraline (myocardial infarction). Conclusion: The use of OTC drugs by the patients should be monitored. Pharmacokinetic interactions between nonprescribed medicines and antidepressants may increase concentration and severity of side effects of latter ones.