Neuroprotective effect of hesperidin and its combination with coenzyme Q10 on an animal model of ketamine-induced psychosis: behavioral changes, mitochondrial dysfunctions, and oxidative stress

Background Psychosis is a complex mental illness divided by positive symptoms, negative symptoms, and cognitive decline. Clinically available medicines are associated with some serious side effects which limit their use. Treatment with flavonoids has been associated with delayed onset and development, decreased risk, or increased improvement of various neuropsychiatric disorders including psychosis with negligible side effects. Therefore, the present study was aimed to investigate the protective effects of hesperidin (flavonoid) alone or its combination with coenzyme Q10 against ketamine-induced psychotic symptoms in mice. Results Ketamine (50 mg/kg, i.p.) was given for 21 days to induce psychosis in Laca mice of either sex. Locomotor activity and stereotypic behaviors, immobility duration (forced swim test), and increased transfer latency (elevated plus maze) were performed to test the effect of hesperidin (50 mg/kg, 100 mg/kg, 200 mg/kg, p.o.) and coenzyme Q10 (20 mg/kg, 40 mg/kg, p.o.) and combination of hesperidin + coenzyme Q10 followed by biochemical and mitochondrial complexes assays. For 21 days, ketamine (50 mg/kg, i.p.) administration significantly produced increased locomotor activity and stereotypic behaviors (positive symptoms), increased immobility duration (negative symptoms) and cognitive deficits (increases transfer latency) weakens oxidative defense and mitochondrial function. Further, 21 days’ administration of hesperidin and coenzyme Q10 significantly reversed the ketamine-induced psychotic behavioral changes and biochemical alterations and mitochondrial dysfunction in the discrete areas (prefrontal cortex and hippocampus) of mice brains. The potential effect of these drugs was comparable to olanzapine treatment. Moreover, the combination of hesperidin with coenzyme Q10 and or a combination of hesperidin + coenzyme Q10 + olanzapine treatment did not produce a significant effect compared to their per se effect in ketamine-treated animals. Conclusions The study revealed that hesperidin alone or in combination with coenzyme Q10 could reduce psychotic symptoms and improve mitochondrial functions and antioxidant systems in mice, suggesting neuroprotective effects against psychosis.

Sexual Dysfunction in Chronically Medicated Male Inpatients With Schizophrenia: Prevalence, Risk Factors, Clinical Manifestations, and Response to Sexual Arousal

BackgroundSexual dysfunction is a common symptom in patients with schizophrenia, especially in chronically medicated patients. However, the relationship between sexual dysfunction and emotional response to sexual arousal in male patients with schizophrenia remains unclear. This study aimed to assess the incidence, risk factors of sexual dysfunction in males, and their clinical correlations to sexual arousal in male patients with schizophrenia in China.MethodsA total of 162 male patients, aged 18–50 years, with schizophrenia were recruited from a psychiatric hospital in Ganzhou. The clinical symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS). The Arizona Sexual Experience Scale was utilized to evaluate sexual dysfunction. Erotic images were selected from International Affective Picture System (IAPS). Sixty-eight out of the 162 subjects completed the erotic pictures reactivity task.ResultsOverall, 48 (29.6%) patients were measured as having global sexual dysfunction, 72 (44.4%) patients as having strength of sex drive dysfunction, 51 (31.5%) patients as having sexual arousal dysfunction, 55 (34.0%) patients as having penile erection dysfunction, 60 (37.0%) patients as having reached orgasm dysfunction, and 60 (37.0%) patients as having satisfaction with orgasm dysfunction. The sexual dysfunction patients had significantly higher scores on the negative symptoms of the PANSS. The only important predictor of sexual dysfunction was the severity of PANSS negative factor. The sense of pleasure and arousal post viewing erotic images in the sexual dysfunction group were lower compared to the non-sexual dysfunction group. The sense of pleasure and approach motivation were significantly negatively correlated with the severity of sexual dysfunction.ConclusionsThis study shows that nearly one-third of young and middle-aged chronically medicated male inpatients with schizophrenia suffer from sexual dysfunction. The negative factor of the PANSS can be regarded as the risk factor of sexual dysfunction. Schizophrenia patients with sexual dysfunction experienced lower pleasure and higher avoidance motivation than non-sexual dysfunction patients when exposed to erotic stimuli.

Manualized group cognitive behavioral therapy for social anxiety in first-episode psychosis: a randomized controlled trial

Background Social anxiety (SA), a prevalent comorbid condition in psychotic disorders with a negative impact on functioning, requires adequate intervention relatively early. Using a randomized controlled trial, we tested the efficacy of a group cognitive-behavioral therapy intervention for SA (CBT-SA) that we developed for youth who experienced the first episode of psychosis (FEP). For our primary outcome, we hypothesized that compared to the active control of group cognitive remediation (CR), the CBT-SA group would show a reduction in SA that would be maintained at 3- and 6-month follow-ups. For secondary outcomes, it was hypothesized that the CBT-SA group would show a reduction of positive and negative symptoms and improvements in recovery and functioning. Method Ninety-six patients with an FEP and SA, recruited from five different FEP programs in the Montreal area, were randomized to 13 weekly group sessions of either CBT-SA or CR intervention. Results Linear mixed models revealed that multiple measures of SA significantly reduced over time, but with no significant group differences. Positive and negative symptoms, as well as functioning improved over time, with negative symptoms and functioning exhibiting a greater reduction in the CBT-SA group. Conclusions While SA decreased over time with both interventions, a positive effect of the CBT-SA intervention on measures of negative symptoms, functioning, and self-reported recovery at follow-up suggests that our intervention had a positive effect that extended beyond symptoms specific to SA. ClinicalTrials.gov identifier: NCT02294409.

Negative Symptom Domains Are Associated With Verbal Learning in Adolescents With Early Onset Psychosis

Background: Early-onset psychosis (EOP) is among the leading causes of disease burden in adolescents. Negative symptoms and cognitive deficits predicts poorer functional outcome. A better understanding of the association between negative symptoms and cognitive impairment may inform theories on underlying mechanisms and elucidate targets for development of new treatments. Two domains of negative symptoms have been described in adult patients with schizophrenia: apathy and diminished expression, however, the factorial structure of negative symptoms has not been investigated in EOP. We aimed to explore the factorial structure of negative symptoms and investigate associations between cognitive performance and negative symptom domains in adolescents with EOP. We hypothesized that (1) two negative symptom factors would be identifiable, and that (2) diminished expression would be more strongly associated with cognitive performance, similar to adult psychosis patients.Methods: Adolescent patients with non-affective EOP (n = 169) were included from three cohorts: Youth-TOP, Norway (n = 45), Early-Onset Study, Norway (n = 27) and Adolescent Schizophrenia Study, Mexico (n = 97). An exploratory factor analysis was performed to investigate the underlying structure of negative symptoms (measured with the Positive and Negative Syndrome Scale (PANSS)). Factor-models were further assessed using confirmatory factor analyses. Associations between negative symptom domains and six cognitive domains were assessed using multiple linear regression models controlling for age, sex and cohort. The neurocognitive domains from the MATRICS Consensus Cognitive Battery included: speed of processing, attention, working memory, verbal learning, visual learning, and reasoning and problem solving.Results: The exploratory factor analysis of PANSS negative symptoms suggested retaining only a single factor, but a forced two factor solution corroborated previously described factors of apathy and diminished expression in adult-onset schizophrenia. Results from confirmatory factor analysis indicated a better fit for the two-factor model than for the one-factor model. For both negative symptom domains, negative symptom scores were inversely associated with verbal learning scores.Conclusion: The results support the presence of two domains of negative symptoms in EOP; apathy and diminished expression. Future studies on negative symptoms in EOP should examine putative differential effects of these symptom domains. For both domains, negative symptom scores were significantly inversely associated with verbal learning.

Polymorphism of Transferrin Gene Impacts the Mediating Effects of Psychotic Symptoms on the Relationship between Oxidative Stress and Cognition in Patients with Chronic Schizophrenia

A series of studies indicated that iron distribution that partly derives from transferrin-bound iron in the peripheral nervous system in the brain may act in processes such as myelination and brain development. However, the relationship between schizophrenia, its psychotic symptoms, and the transferrin (TF) gene has not been systematically explored. Our study aimed to investigate how a particular polymorphism of the transferrin gene, rs3811655, affects the superoxide dismutase (SOD), malondialdehyde (MDA), psychotic symptoms, cognition, or the mediation model between antioxidant enzymes and cognition via symptoms. A total of 564 patients with chronic schizophrenia and 468 healthy control subjects were recruited. The psychotic symptoms and cognition were assessed by the Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), respectively. Furthermore, the serum SOD, MDA activity, and transferrin gene polymorphism were measured in patients. Our results demonstrated that patients with the G allele possessed more severe negative symptoms, worse cognitive performance with respect to attention, and higher serum Mn-SOD activity. Additionally, the rs3811655 polymorphism may act as a moderator in the association between Cu/Zn-SOD activity and cognition, as well as psychotic symptoms in patients suffering from schizophrenia. According to this study, the single nucleotide polymorphism (SNP) rs3811655 polymorphism may fail to contribute to the susceptibility of schizophrenia in an individual but is involved in the iron-induced oxidative stress disturbance and cognitive impairment in schizophrenia. This deepens our understanding of the critical role of iron-induced oxidative stress that might underlie the pathophysiology of schizophrenia.

Assessment of professional burnout of media workers

The results of an assessment of professional burnout of media workers are presented. Recommendations on reduction of the burnout syndrome impact are provided. The assessment was conducted using the professional burnout diagnostics method by K. Maslach and S. Jackson adapted by N.E. Vodopyanova. The burnout syndrome is considered to be a three-dimensional component consisting of emotional exhaustion, depersonalization, and personal achievement reduction. The study involved Irkutsk regional newspapers, radio broadcasting, television and Internet media. A total of 155 people participated were surveyed: 113 females and 42 males. Most of them suffer from the professional burnout syndrome. To verify the results obtained, age and work experience were taken into account. According to the results obtained, the degree of depersonalization increases with aging. The longer the participant works, the stronger the depersonalization component. The personal achievement reduction also depends on these components. The younger the editorial staff member and the shorter his/her work experience, the stronger the negative self-esteem, underestimation of own professional achievements and success. Conversely, the more mature the journalist is, the more positively he evaluates his professional competence and creativity. At the same time, emotional exhaustion manifests itself in all respondents, regardless of their age: in two studies, the average and high degrees were revealed. It is this component that makes a contribution to the professional burnout of journalists. To reduce the impact of the syndrome, a set of preventive measures has been developed. They can prevent economic and resource losses, and increase labor productivity. The methods of preventing professional burnout are aimed at preventing emotional exhaustion, and in extreme cases - at relieving negative symptoms and combating negative consequences. They can improve productivity of media workers and reduce psychosocial risks.

Primary and Secondary Negative Symptoms in Schizophrenia

The negative symptoms of schizophrenia include volitional (motivational) impairment manifesting as avolition, anhedonia, social withdrawal, and emotional disorders such as alogia and affective flattening. Negative symptoms worsen patients' quality of life and functioning. From the diagnostic point of view, it is important to differentiate between primary negative symptoms, which are regarded as an integral dimension of schizophrenia, and secondary negative symptoms occurring as a result of positive symptoms, comorbid depression, side effects of antipsychotics, substance abuse, or social isolation. If secondary negative symptoms overlap with primary negative symptoms, it can create a false clinical impression of worsening deficit symptoms and disease progression, which leads to the choice of incorrect therapeutic strategy with excessive dopamine blocker loading. Different longitudinal trajectories of primary and secondary negative symptoms in different schizophrenia stages are proposed as an important additional discriminating factor. This review and position paper focuses primarily on clinical aspects of negative symptoms in schizophrenia, their definition, phenomenology, factor structure, and classification. It covers the historical and modern concepts of the paradigm of positive and negative symptoms in schizophrenia, as well as a detailed comparison of the assessment tools and psychometric tests used for the evaluation of negative symptoms.

Amisulpride Augmentation Therapy Improves Cognitive Performance and Psychopathology in Clozapine-resistant Treatment-refractory Schizophrenia (CTRS): a 12-week Randomized, Double-blind, Placebo-controlled Trial

BackgroundAlthough clozapine is an effective option for treatment-resistant schizophrenia (TRS), there are still 1/3 to 1/2 of TRS patients who do not respond to clozapine. The main purposes of this randomized, double-blind, placebo-controlled trial was to explore the amisulpride augmentation efficacy on the psychopathological symptoms and cognitive function of CTRS patients. MethodsA total of 80 patients were recruited and randomly assigned to receive an initial clozapine plus amisulpride or clozapine plus placebo. Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Negative Symptoms (SANS), Clinical Global Impression (CGI) scale scores, Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Treatment Emergent Symptom Scale (TESS), laboratory measurements and electrocardiograms (ECG) were performed at baseline, week 6, and week 12. ResultsCompared with clozapine plus placebo group, clozapine plus amisulpride had lower PANSS total score, positive subscore and general psychopathology subscore at week 6 and week 12 (all p Bonferroni< 0.01). Furthermore, compared with clozapine plus placebo group, clozapine plus amisulpride showed improved RBANS language score at week 12 (p Bonferroni< 0.001). Clozapine plus amisulpride group had a higher treatment response rate (p = 0.04), lower scores of CGI severity (CGI-S) and CGI efficacy (CGI-E) at week 6 and week 12 than clozapine plus placebo (all p Bonferroni< 0.05). There were no differences in BMI, QT intervals or laboratory measurements between the groups. Our results demonstrate that amisulpride augmentation therapy can safely improve the psychiatric symptoms and cognitive performance of CTRS patients. ConclusionsOur study indicates that amisulpride augmentation therapy has important clinical significance for the treatment of CTRS to improve clinical symptoms and cognitive function with tolerability and safety.Trial registrationClinicaltrials.gov identifier- NCT03652974. Registered 31 August 2018, https://clinicaltrials.gov/ct2/show/NCT03652974

Alysis Reliability Study: Rearranging Phenomenology into Etiology in Mental Disorders

‘Alysis’ )abbreviation of Neuroanalysis(, - is the chosen definition for the rearrangement of psychiatric phenomology to approximate the hypothesized etiology of mental disorders. Currently the relevant scales such as Positive and Negative Symptoms Scale (PANSS) for schizophrenia and the Hamilton scales for depression and anxiety, and Mania Rating Scale have no specific guiding principle in the order of items. ‘Alysis’ is a reorganization of multiple known scales to fit a future brain-related diagnostic approach to mental disorders. Due to the regrouping of items from different scales and reorganizing them according to a brain-related hypothetic order, it is necessary to reassess the reliability of the new ‘Alysis’ rearrangement. In this work the new ‘Alysis’ format is described and then using t-scores analysis, compared to the widely-used Brief Psychiatric Rating Scale (BPRS) scale for mental disorders. It is shown that ‘Alysis’ is reliable thus can be a good diagnostic platform to go ahead and generate personalized testable-predictions about brain-related diagnostics for psychiatric patients.