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IntroductionSchizophrenia (SZ) and bipolar disorder (BD) share common clinical features, symptoms, and neurocognitive deficits, which results in common misdiagnosis. Recently, it has been suggested that alterations within brain networks associated with perceptual organization yield potential to distinguish SZ and BD individuals. The aim of our study was to evaluate whether functional connectivity (FC) of the dorsal attention network (DAN) may differentiate both conditionsMethodsThe study involved 90 participants: 30 remitted SZ patients, 30 euthymic BD patients, and 30 healthy controls (HC). Resting state functional magnetic resonance imaging was used to compare the groups in terms of the FC within the core nodes of the DAN involving frontal eye fields (FEF) and intraparietal sulcus (IPS)ResultsBD patients presented weaker inter-hemispheric FC between right and left FEF than HC. While SZ did not differ from HC in terms of inter-FEF connectivity, they presented increased inter- and intra-hemispheric FC between FEF and IPS. When compared with BD, SZ patients showed increased FC between right FEF and other nodes of the network (bilateral IPS and left FEF)ConclusionWe have shown that altered resting state FC within DAN differentiates BD, SZ, and HC groups. Divergent pattern of FC within DAN, consisting of hypoconnectivity in BD and hyperconnectivity in SZ, might yield a candidate biomarker for differential diagnosis between both conditions. More highly powered studies are needed to confirm these possibilities

IntroductionSexual 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.MethodsWe 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.ResultsWe 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.ConclusionsThis 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.

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.

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.

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.

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.

BackgroundAnhedonia 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).MethodsThe 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.ResultsThe 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).ConclusionThe 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.

IntroductionOur 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.MethodsThis 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.ResultsThere 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.DiscussionThe 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.

AimPreliminary 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 methodsThe 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.ResultsStatistical 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.ConclusionsCerebellar 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.

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.

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

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.

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.

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.

Objective: The cerebellar functional laterality, with its right hemisphere predominantly involved in verbal performance and the left one engaged in visuospatial processes, has strong empirical support. However, the clinical observation and single research results show that the damage to the right cerebellar hemisphere may cause extralinguistic and more global cognitive decline. The aim of our research was to assess the pattern of cognitive functioning, depending on the cerebellar lesion side, with particular emphasis on the damage to the right cerebellar hemisphere.Method: The study sample consisted of 31 patients with focal cerebellar lesions and 31 controls, free of organic brain damage. The Addenbrooke’s Cognitive Examination ACE III and the Trail Making Test TMT were used to assess patients’ cognitive functioning.Results: Left-sided cerebellar lesion patients scored lower than controls in attention and visuospatial domain, but not in language, fluency, and memory functions. Participants with right-sided cerebellar lesion demonstrated a general deficit of cognitive functioning, with impairments not only in language and verbal fluency subscales but also in all ACE III domains, including memory, attention, and visuospatial functions. The TMT results proved that cerebellar damage is associated with executive function impairment, regardless of the lesion side.Conclusion: The cognitive profiles of patients with cerebellum lesions differ with regard to the lesion side. Left-sided cerebellar lesions are associated with selective visuospatial and attention impairments, whereas the right-sided ones may result in a more global cognitive decline, which is likely secondary to language deficiencies, associated with this lateral cerebellar injury.

ObjectiveThe occurrence of death by suicide in patients diagnosed with bipolar disorder is as much as 60 times greater than in the general population. Even during the state of euthymia patients are characterized by suicide risk. The aim of the study is to investigate the baseline brain activity in euthymic bipolar disorder patients in regard to suicide risk. We hypothesized that patients compared to healthy control group will demonstrate altered functional connectivity among resting state networks which will be directly related to current suicide risk.Method41 subjects were enrolled in the study consisting control group (n = 21) and euthymic bipolar disorder patients group (n = 20). Functional magnetic resonance imaging was used to evaluate resting state brain activity and ROI–ROI functional connectivity analysis was performed. Suicidal risk was estimated using The Suicide Behaviors Questionnaire-Revised.ResultsA two sample t-test revealed decreased functional connectivity between regions involved in the salience network in patients compared to the control group. This decrease was negatively correlated with current suicide risk.ConclusionObtained results suggest the association between risk of suicide and activity of regions responsible for functions such as learning from mistakes, prospective thinking, and sensory integration.

Verbal Fluency Tests (VFT) are one of the most common neuropsychological tasks used in bipolar disorder (BD) and schizophrenia (SZ) research. Recently, a new VFT analysis method based on graph theory was developed. Interpreting spoken words as nodes and every temporal connection between consecutive words as edges, researchers created graph structures, allowing the extraction of more data from participants’ speech, called Speech Graph Attributes (SGA). The aim of our study was to compare speech graphs, derived from Phonemic and Semantic VFT, between SZ, BD, and healthy controls (HC). Twenty-nine SZ patients, twenty-nine BD patients, and twenty-nine HC performed Semantic and Phonemic VFT. Standard measures (SM) and 13 SGA were analyzed. SZ patients’ Semantic VFT graphs showed lower total word count and correct responses. Their graphs presented less nodes and edges, higher density, smaller diameter, average shortest path (ASP), and largest strongly connected component than the HC group. SM did not differentiate BD and HC groups, and patients’ Semantic VFT graphs presented smaller diameter and ASP than HC. None of the parameters differentiated BD and SZ patients. Our results encourage the use of speech graph analysis, as it reveals verbal fluency alterations that remained unnoticed in the routine comparisons of groups with the use SM.

The goal of this paper is to investigate the baseline brain activity in euthymic bipolar disorder (BD) patients by comparing it to healthy controls (HC) with the use of a variety of resting state functional magnetic resonance imaging (rs-fMRI) analyses, such as amplitude of low frequency fluctuations (ALFF), fractional ALFF (f/ALFF), ALFF-based functional connectivity (FC), and r egional homogeneity (ReHo). We hypothesize that above-mentioned techniques will differentiate BD from HC indicating dissimilarities between the groups within different brain structures. Forty-two participants divided into two groups of euthymic BD patients (n = 21) and HC (n = 21) underwent rs-fMRI evaluation. Typical band ALFF, slow-4, slow-5, f/ALFF, as well as ReHo indexes were analyzed. Regions with altered ALFF were chosen as ROI for seed-to-voxel analysis of FC. As opposed to HC, BD patients revealed: increased ALFF in left insula; increased slow-5 in left middle temporal pole; increased f/ALFF in left superior frontal gyrus, left superior temporal gyrus, left middle occipital gyrus, right putamen, and bilateral thalamus. There were no significant differences between BD and HC groups in slow-4 band. Compared to HC, the BD group presented higher ReHo values in the left superior medial frontal gyrus and lower ReHo values in the right supplementary motor area. FC analysis revealed significant hyper-connectivity within the BD group between left insula and bilateral middle frontal gyrus, right superior parietal gyrus, right supramarginal gyrus, left inferior parietal gyrus, left cerebellum, and left supplementary motor area. To our best knowledge, this is the first rs-fMRI study combining ReHo, ALFF, f/ALFF, and subdivided frequency bands (slow-4 and slow-5) in euthymic BD patients. ALFF, f/ALFF, slow-5, as well as REHO analysis revealed significant differences between two studied groups. Although results obtained with the above methods enable to identify group-specific brain structures, no overlap between the brain regions was detected. This indicates that combination of foregoing rs-fMRI methods may complement each other, revealing the bigger picture of the complex resting state abnormalities in BD.

The efficacy of vortioxetine has been proven in many studies, but data concerning discontinuation symptoms (DS) after vortioxetine withdrawal is scarce. The aim of our study is to systematically evaluate the prevalence, determinants, and clinical features of vortioxetine DS in a retrospective chart review. Data were obtained from medical records of 263 adult patients with depressive disorders who discontinued former vortioxetine treatment. DS were observed in eight (3%) patients after 71–375 days (median 272) of treatment. DS emerged after median three days following vortioxetine withdrawal and lasted for median seven days. The clinical presentation of DS involved: emotional lability (100% of patients), irritability (75%), sudden worsening of mood (75%), nervousness (37.5%), and agitation (37.5%). Median DESS score was four (range of four to six). DS were significantly more prevalent after accidental vs. planned discontinuation (adjusted p = 0.011) and were less frequent after switching to a different antidepressant vs. ceasing pharmacotherapy (adjusted p = 0.0165). DS appeared more often if patients discontinued therapy without medical consultation (adjusted p = 0.033). The occurrence of DS was not associated with the dose and way of drug discontinuation (sudden vs. gradual). In sum, our results show that clinicians should be aware that vortioxetine withdrawal is associated with the possibility of DS.

Angiocentric glioma (AG) is a newly-classified, very rare, WHO grade I central nervous system (CNS) lesion, occurring usually in children and young adults. Only 52 patients with AG have been reported so far, making it one of the rarest neuropathological entities. Hereby we present two new cases of AG in young subjects with detailed neuropathological investigations and a neuroradiological picture along with a brief summary of all already published literature reports of this tumor. Histopathological examination of the resected tissue from both cases revealed similar changes characteristic of AG. The tumors were composed of spindle-like, elongated cells, forming characteristic pseudorosettes around vessels and diffusively infiltrating surrounding tissue, trapping neurons between tumor cells. Noticeably, some neoplastic cells encrusting vessels extended far beyond the main tumor mass. Hypothetically, this may be responsible for the recurrence of the tumor even in the case of apparently total excision. In immunohistochemistry, AG cells were glial fibrillary acidic protein (GFAP) and vimentin positive, also exhibiting a strikingly significant epithelial membrane antigen (EMA) dot-like staining pattern. In one of the cases, electron microscopy revealed ependymal differentiation features such as microvilli and cilia. Taken together, all these data strongly confirm a dual astroglial-ependymal nature of the tumor. Follow up corroborates benign character of this neoplasm. Both AGs reported here were immunonegative for the product of the mutated IDH-1 gene what, according to our best knowledge, has never been reported so far. It may suggest that in their pathogenesis AGs differ from grade II astrocytomas, which in most cases harbor a mutation of IDH-1. Noteworthy, neuroimaging in our cases was relatively characteristic but not conclusive, therefore biopsy (at least) is mandatory. A newly proposed so called “A-B-C” classification of long-term epilepsy-associated tumors (LEATs) places AG in a category named ANET. The authors shortly review the A-B-C classification of LEATs.