Probiotics as a Tool for Regulating Molecular Mechanisms in Depression: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Depression is one of the main mental disorders. Pharmacological treatment of depression is often associated with delayed effects or insufficient efficacy. Consequently, there is a need to discover new therapeutic methods to cope with depression faster and more effectively. Several lines of evidence indicate that the use of probiotic therapy reduces depressive symptoms. Nonetheless, the exact mechanisms linking the gut microbiota and the central nervous system, as well as the potential mechanisms of action for probiotics, are still not entirely clarified. The aim of this review was to systematically summarize the available knowledge according to PRISMA guidelines on the molecular mechanisms linking probiotics and healthy populations with subclinical depression or anxiety symptoms, as well as depressed patients with or without comorbid somatic illnesses. The standardized mean difference (SMD) with 95% confidence intervals (CI) was calculated. Twenty records were included. It has been found that probiotic administration is linked to a significant increase in BDNF levels during probiotic treatment compared to the placebo (SMD = 0.37, 95% CI [0.07, 0.68], p = 0.02) when considering the resolution of depressive symptoms in depressed patients with or without comorbid somatic illnesses. CRP levels were significantly lower (SMD = -0.47, 95% CI [0.75, -0.19], p = 0.001), and nitric oxide levels were significantly higher (SMD = 0.97, 95% CI [0.58, 1.36], p < 0.0001) in probiotic-treated patients compared to the placebo, however, only among depressed patients with somatic co-morbidities. There were no significant differences in IL-1ß, IL-6, IL-10, TNF-α, and cortisol levels after probiotic administration between the intervention and control groups (all p > 0.05). Firm conclusions on the effectiveness of probiotics and their possible association with inflammatory markers in the healthy population (only with subclinical depressive or anxiety symptoms) cannot be drawn. The advent of clinical trials examining the long-term administration of probiotics could evaluate the long-term effectiveness of probiotics in treating depression and preventing its recurrence.

The impact of bipolar spectrum disorders on professional functioning: A systematic review.

Aims: The impact of bipolar spectrum (BS) disorders on professional functioning has not been systematically reviewed yet. Since even subsyndromal symptoms may disturb functioning, the determination of the prognostic value of the spectrum of bipolarity for employment seems extremely relevant. The aim of this study was to assess the impact of BS disorders on professional functioning. Materials and methods: A systematic review of the literature (namely, cohort and cross-sectional studies) investigating a link between BS disorders and employment was performed in accordance with PRISMA guidelines. BS was defined based on the concept of two-dimensional BS by Angst. Occupational outcomes and factors affecting employment were evaluated as well. Results: Seventy-four studies were included. All disorders comprising BS had a negative impact on occupational status, work performance, work costs, and salary, with the greatest unfavorable effect reported by bipolar disorder (BD), followed by borderline personality disorder (BPD), major depressive disorder (MDD), and dysthymia. Employment rates ranged from 40 to 75% (BD), 33 to 67% (BPD), 61 to 88% (MDD), and 86% (dysthymia). The factors affecting employment most included: cognitive impairments, number/severity of symptoms, namely, subsyndromal symptoms (mainly depressive), older age, education, and comorbidity (substance abuse, personality disorders, anxiety, depression, ADHD, PTSD). Conclusion: Bipolar spectrum symptoms exert a negative impact on professional functioning. Further evaluation of affecting factors is crucial for preventing occupational disability.

Differential effects of stress-related and stress-unrelated humor in remitted depression.

Enhancing emotion regulation among previously depressed people is crucial for improving their resilience and reducing relapse. Therefore, emphasis is placed on determining effective regulation strategies, particularly those that, besides down-regulating negative emotions, also up-regulate positive emotions. One promising strategy, with great potential in both these respects, is humor. It is unclear, however, what type of humor is most adaptive in remitted depression. This study compared two distinct humor-based strategies: stress-related humor and stress-unrelated humor. Outpatients with remitted depression (N = 94) participated in a randomized experiment evoking personal stress and the subsequent application of stress-related humor, stress-unrelated humor, or a non-humorous regulation. They repeatedly reported positive and negative emotions (at four time points) and experienced distress (at three time points). There were also assessments of selective attention, subsequent performance, effort, and intrusive thoughts. Unlike non-humorous regulation, humor-based strategies had adaptive consequences, both immediately and after a delay; however, stress-unrelated humor was most beneficial and was the only effective strategy when attention deficits were present. Humor, especially if unrelated to stressors, might broaden the repertoire of powerful emotion regulation strategies in remitted depression. Humorous focusing on distress can be detrimental for patients with attention impairment.Clinical trial registration: The study was registered under the number ISRCTN86314628 (20/09/2021).

Behavioral and Self-reported Data Collected From Smartphones for the Assessment of Depressive and Manic Symptoms in Patients With Bipolar Disorder: Prospective Observational Study.

BACKGROUND: Smartphones allow for real-time monitoring of patients' behavioral activities in a naturalistic setting. These data are suggested as markers for the mental state of patients with bipolar disorder (BD). OBJECTIVE: We assessed the relations between data collected from smartphones and the clinically rated depressive and manic symptoms together with the corresponding affective states in patients with BD. METHODS: BDmon, a dedicated mobile app, was developed and installed on patients' smartphones to automatically collect the statistics about their phone calls and text messages as well as their self-assessments of sleep and mood. The final sample for the numerical analyses consisted of 51 eligible patients who participated in at least two psychiatric assessments and used the BDmon app (mean participation time, 208 [SD 132] days). In total, 196 psychiatric assessments were performed using the Hamilton Depression Rating Scale and the Young Mania Rating Scale. Generalized linear mixed-effects models were applied to quantify the strength of the relation between the daily statistics on the behavioral data collected automatically from smartphones and the affective symptoms and mood states in patients with BD. RESULTS: Objective behavioral data collected from smartphones were found to be related with the BD states as follows: (1) depressed patients tended to make phone calls less frequently than euthymic patients (ß=-.064, P=.01); (2) the number of incoming answered calls during depression was lower than that during euthymia (ß=-.15, P=.01) and, concurrently, missed incoming calls were more frequent and increased as depressive symptoms intensified (ß=4.431, P<.001; ß=4.861, P<.001, respectively); (3) the fraction of outgoing calls was higher in manic states (ß=2.73, P=.03); (4) the fraction of missed calls was higher in manic/mixed states as compared to that in the euthymic state (ß=3.53, P=.01) and positively correlated to the severity of symptoms (ß=2.991, P=.02); (5) the variability of the duration of the outgoing calls was higher in manic/mixed states (ß=.0012, P=.045) and positively correlated to the severity of symptoms (ß=.0017, P=.02); and (6) the number and length of the sent text messages was higher in manic/mixed states as compared to that in the euthymic state (ß=.031, P=.01; ß=.015, P=.01; respectively) and positively correlated to the severity of manic symptoms (ß=.116, P<.001; ß=.022, P<.001; respectively). We also observed that self-assessment of mood was lower in depressive (ß=-1.452, P<.001) and higher in manic states (ß=.509, P<.001). CONCLUSIONS: Smartphone-based behavioral parameters are valid markers for assessing the severity of affective symptoms and discriminating between mood states in patients with BD. This technology opens a way toward early detection of worsening of the mental state and thereby increases the patient's chance of improving in the course of the illness.

Acetylsalicylic Acid and Mood Disorders: A Systematic Review.

The effects of acetylsalicylic acid (ASA) on mood disorders (MD) and on inflammatory parameters in preclinical and clinical studies have not yet been comprehensively evaluated. The aim of this study was to systematically summarize the available knowledge on this topic according to PRISMA guidelines. Data from preclinical and clinical studies were analyzed, considering the safety and efficacy of ASA in the treatment of MD and the correlation of inflammatory parameters with the effect of ASA treatment. Twenty-one studies were included. Both preclinical and clinical studies found evidence indicating the safety and efficacy of low-dose ASA in the treatment of all types of affective episodes in MD. Observational studies have indicated a reduced risk of all types of affective episodes in chronic low-dose ASA users (HR 0.92, 95% CI: 0.88, 0.95, p < 0.0001). An association between ASA response and inflammatory parameters was found in preclinical studies, but this was not confirmed in clinical trials. Further long-term clinical trials evaluating the safety and efficacy of ASA in recurrent MD, as well as assessing the linkage of ASA treatment with inflammatory phenotype and cytokines, are required. There is also a need for preclinical studies to understand the exact mechanism of action of ASA in MD.

ECT in an Adolescent With Schizophrenia and Seizures: Case Report.

Electroconvulsive therapy (ECT) has been recognized as an effective treatment option in catatonia, and for prolonged or severe affective episodes and schizophrenia. Response rates vary from 40 to 80% in adolescents. The procedure is safe if the required precautions are undertaken. Nonetheless, ECT remains a serious clinical challenge in patients with comorbid seizures. We present a case study of a 17-year-old female student suffering from schizophrenia who was scheduled for ECT due to prior treatment inefficacy. Seizures had occurred a few days before the first ECT session. Nevertheless, the patient received the ECT course, combined with clozapine at 125 mg/day, after neurological diagnosis and treatment modification because the illness became life-threatening. The patient's clinical outcome was satisfactory without any seriously adverse events and further improvements were observed in the mental state following long-term psychosocial treatment at our inpatient unit. A few months later, epilepsy was however diagnosed with probably coexistence of partial seizures and seizure-like events without EEG correlate. Administering ECT in patients with seizure comorbidity was also investigated based on previous research. Data on this is, however, extremely scarce and to the best of our knowledge, the safety and efficacy of using ECT in adolescents with schizophrenia and seizures has yet not to any great extent been discussed in the literature.

Electroconvulsive Therapy and Age: Effectiveness, Safety and Tolerability in the Treatment of Major Depression among Patients under and over 65 Years of Age.

Electroconvulsive therapy (ECT) remains the most effective therapy in treatment-resistant depression. However, the safety of ECT has been consistently questioned, particularly among elderly patients. We assessed the efficacy and safety of ECT in patients before and after 65 years old. The study was conducted between 2015 and 2018 and included 91 patients (61 under and 29 over 65 years old) with major depression undergoing ECT. The Hamilton Depression Rating Scale was used to evaluate efficacy. Cognitive functions were assessed using: MMSE, RAVLT, Trail Making Test, Stroop Test and Autobiographical Memory Interview-Short Form. ECT was more effective in older patients as compared to younger (p < 0.001). No serious adverse events were observed in either group. Increased blood pressure and arrhythmias were more common in the older compared to the younger group (p = 0.044 and p = 0.047, respectively), while disturbances of consciousness did not differ between groups (p = 0.820). Most of the cognitive functions remained unchanged compared to baseline, whereas the outcomes of MMSE, RAVLT and Stroop tests showed greater improvements in the older compared to the younger group (all p < 0.05). The decline in the retrieval consistency of autobiographical memory was more pronounced in the younger group (p = 0.024). ECT is a highly effective, safe and well-tolerated method of treating depression regardless of age.

Changes in the Practice of Electroconvulsive Therapy in Poland: A Nationwide Survey Comparing Data Between 2005 and 2020.

BACKGROUND: The use and the characteristics of the practice of electroconvulsive therapy (ECT) in Poland have not been evaluated since 2005, when a nationwide survey revealed its rare utilization (0.11 patients/10,000 inhabitants/year). The aims of this study were to determine the current use of ECT and to compare the findings with those of the previous survey. METHODS: Two questionnaires were sent to all 48 inpatient psychiatric centers in Poland. The first one - to units providing ECT to explore its practice, and the second - to units not performing ECT to explore the reasons for not using this treatment. RESULTS: Nineteen (39.6%) of all psychiatric inpatient centers confirmed the use of ECT. The utilization rate was 0.13 patients/10,000 inhabitants. Similar to the findings from 2005, the main indications were affective disorders, and bitemporal electrode placement was the dominant method used for the delivery of ECT. Age-based and titration-based methods were applied exclusively in 50% and 25% of the centers, respectively (compared with 15% and 35% in 2005, respectively), while both methods were used in the remaining 25%. Improvements in safety were reflected by the use of comprehensive pre-ECT evaluation and treatment monitoring. None of the centers used sine-wave devices; this contrasts with their use by 29% of the centers in 2005. The main reasons for not using ECT were insufficient funding and a lack of experienced staff. CONCLUSION: The frequency of ECT use in Poland remains very low. In view of the improvement in the quality of health services in the past decade, such a markedly rare use of an effective treatment was unexpected. There is an urgent need of education to create more positive attitude towards ECT among health professionals and among public, and to increase the training of mental health professionals in ECT.

Right unilateral versus bilateral formula-based electroconvulsive therapy in the treatment of major depression in elderly patients: a randomised, open label, pilot controlled trial.

BACKGROUND: Electroconvulsive therapy (ECT) remains the most effective treatment of depression in the elderly population; however, it is still unclear which type of ECT is most beneficial in this population. The aims of this study were: (i) to assess the feasibility of a randomised controlled trial in elderly depressed patients treated with right unilateral (RUL) or fronto-temporal bilateral (BT) formula-based ECT; (ii) to compare formula-based RUL and BT ECT in terms of efficacy, safety and tolerability in this population. METHODS: The study lasted 3 years and managed to randomise 29 patients over 65 years old to receive either BT (n = 14) or RUL (n = 15) ECT. Brief pulse width (0.5 ms) and age-based dosing method were applied. The clinical efficacy was assessed using Hamilton Depression Rating Scale, somatic state was monitored throughout the ECT course. In neuropsychological examination general cognitive performance, executive functions, verbal fluency, memory, autobiographical memory were evaluated. RESULTS: The recruitment was poor due to small number of patients able to give informed consent. ECT proved to be a highly effective and safe method of treatment among elders. Formula-based RUL ECT did not differ from BT in antidepressant efficacy and had cognitive advantages - the indices of general cognitive performance, verbal fluency and memory were significantly better than before the treatment in the RUL group. Decline in retrieval consistency of autobiographical memory was more pronounced in the BT group, although it was observed across both groups. CONCLUSIONS: Formula-based RUL ECT might not differ from BT in antidepressant efficacy and has an advantage in terms of tolerability.

Recommendations for the prevention and treatment of postpartum depression.

Epidemiological data clearly indicate that depression is becoming an increasingly important health and social problem today. According to the World Health Organization (WHO), depression currently affects 350 million people worldwide and is considered the second most common cause of disability in Europe after ischemic heart disease. It is estimated that this health problem may affect as many as five million people in Poland. The gap between the reported number of patients treated and the prevalence of depression, highlights the scale of unmet needs. With the limited availability of specialists in psychiatric care, the most appropriate measures seem to be those aimed at increasing the competence of doctors of other specialties in the diagnosis and treatment of depression. Early detection and treatment results in faster remission, reduces relapses and mortality. The recommendations concerning prevention of depression were commissioned by the Polish Ministry of Health as a part of the Depression Prevention Program for 2016-2020. The Program has developed recommendations addressed to specialists in various fields of medicine, other than psychiatry, focusing on three risk groups: children and adolescents, women in the perinatal period and the elderly. These recommendations focus on the management of suspected postpartum depression and provide specific guidelines for medical staff having contact with pregnant and postpartum women (gynecologists, midwives, pediatricians).

Hungarian Psychiatrists' Recognition, Knowledge, and Treatment of Catatonia.

DSM-5 introduced a number of modifications to the catatonic syndrome, which is now closer to Kahlbaum's original concept. The aim of the present study was to assess residents' and qualified psychiatrists' knowledge, experience and views about the treatment of catatonia in acute psychiatric care in Budapest, Hungary. Authors approached all psychiatric units that provide acute psychiatric care (N = 11) in Budapest and invited all psychiatrists and residents, who consented, to participate in the survey, completing a 13 items questionnaire. Ninety-eight fully qualified and trainee psychiatrists completed the questionnaire. Although 84.7% of the participants rated their knowledge of catatonia as moderate or significant, there were a number of obvious mistakes in their answers. Most catatonic signs and symptoms were not identified by almost 50% of the respondents and the frequency of catatonia was also underestimated. The views of the majority of the participants reflected the Kraepelinian concept, in which catatonia is primarily associated with schizophrenia. Although benzodiazepines are widely recommended as a first line treatment for catatonia, only 69.4% of participants chose them as a treatment option. In view of its clinical importance, catatonia deserves more attention in the education and training of medical students and psychiatric residents.

Efficacy, safety and tolerability of formula-based unilateral vs bilateral electroconvulsive therapy in the treatment of major depression: A randomized open label controlled trial.

Electroconvulsive therapy (ECT) remains the most effective treatment of depression, though it is still unclear which of its type is the most beneficial. The aim of this study was to compare the formula-based right unilateral ECT (RUL) with the fronto-temporal bilateral ECT (BT), in terms of their efficacy, safety and tolerability in patients with bipolar or unipolar depression. Ninety-one patients were randomly assigned to either BT (n = 45) or RUL (n = 46) ECT. Brief pulse width (0.5 ms) and a formula-based dosing method were applied. The clinical efficacy was assessed using the Hamilton Depression Rating Scale (HDRS-21).The somatic state was monitored throughout the ECT course and cognitive examination included: general cognitive performance, executive functions, visual-spatial functions, verbal fluency, verbal memory and autobiographical memory. Efficacy outcomes were not found to be significantly different between groups when using higher doses of energy in RUL ECT. Patients in RUL group were less likely to be confused and experienced increased blood pressure. The indices of general cognitive performance and verbal auditory memory were also significantly better this group, while BT ECT did not change these functions. Both ECT types resulted in a decline in the retrieval consistency of autobiographical memory that persists for at least three months and was significantly more marked in BT group as compared to RUL. In conclusion, formula-based RUL ECT does not differ from BT in antidepressant efficacy and has an advantage in terms of safety (lower incidence of increased blood pressure and fewer disturbances of consciousness) and tolerability (impact on cognitive functions).

Smartphone as a monitoring tool for bipolar disorder: a systematic review including data analysis, machine learning algorithms and predictive modelling.

BACKGROUND: Bipolar disorder (BD) is a chronic illness with a high recurrence rate. Smartphones can be a useful tool for detecting prodromal symptoms of episode recurrence (through real-time monitoring) and providing options for early intervention between outpatient visits. AIMS: The aim of this systematic review is to overview and discuss the studies on the smartphone-based systems that monitor or detect the phase change in BD. We also discuss the challenges concerning predictive modelling. METHODS: Published studies were identified through searching the electronic databases. Predictive attributes reflecting illness activity were evaluated including data from patients' self-assessment ratings and objectively measured data collected via smartphone. Articles were reviewed according to PRISMA guidelines. RESULTS: Objective data automatically collected using smartphones (voice data from phone calls and smartphone-usage data reflecting social and physical activities) are valid markers of a mood state. The articles surveyed reported accuracies in the range of 67% to 97% in predicting mood status. Various machine learning approaches have been analyzed, however, there is no clear evidence about the superiority of any of the approach. CONCLUSIONS: The management of BD could be significantly improved by monitoring of illness activity via smartphone.

The prevalence of catatonic syndrome in acute psychiatric wards. / Rozpowszechnienie zespolów katatonicznych w ostroprzyjeciowych oddzialach psychiatrycznych.

OBJECTIVES: The aim of this prospective study was to determine the prevalence of the catatonic syndrome in a cohort of patients admitted to acute psychiatric units in Hungary. METHODS: Patients admitted to the acute inpatient unit of the Center of Psychiatry and Addiction Medicine, SzentIstván and SzentLászló Hospitals in a 4-month period were screened for catatonic signs and symptoms. Catatonic signs/symptoms were scored according to both the DSM-5 diagnostic criteria and the Bush-Francis Catatonia Rating Scale (BFCRS). Clinical diagnoses were established using the Structured Clinical Interview for DSM-IV Disorders (SCID), while cognitive performance was estimated with the Clock Drawing Test and the Mini-Mental State Examination (MMSE). RESULTS: During the study period, 342 patients were admitted to the above-mentioned acute inpatient units. The prevalence figures for the catatonic syndrome were 8.55% and 5.02% according to the BFCRS and the DSM-5, respectively. CONCLUSIONS: The prevalence of catatonic syndrome in an acute inpatient setting is within the broad range of figures reported in the literature. The difference between the standardized assessment (BFCRS) and routine clinical judgment (DSM-5) is noteworthy and suggests that a significant minority of catatonic patients might not be identified in clinical practice. As acute catatonia can be effectively treated, and early treatment could prevent potentially lifethreatening complications, recognition of catatonic symptoms is vitally important.

A sham-controlled randomized trial of adjunctive light therapy for non-seasonal depression.

BACKGROUND: The aim of the study was to examine the efficacy and safety of morning bright light therapy (BLT) in the treatment of patients with a current major depressive episode (MDE) in bipolar and unipolar disorder without a seasonal pattern. It was a randomized, sham-controlled trial. METHODS: Adults, ages 18-70 years were randomized to treatment either with BLT or a sham negative ion generator (as a placebo control). The subjects were required to be on a stable and therapeutic dose of psychotropic medication for at least 4 weeks prior to enrollment and their treatment had to be insufficiently effective. Their clinical state was monitored at the baseline and at the end of treatment. The Hamilton Depression Rating Scale-21 items (HDRS-21), Montgomery-Asberg Depression Rating Scale (MADRS), Beck Depression Inventory (BDI-II), Clinical Global Impression-Severity (CGI-S) and Patient Global Impression (PGI) were used. The results were analyzed with an intention-to-treat (ITT) analysis. RESULTS: Ninety-five patients were enrolled (50 diagnosed with bipolar disorder and 45 with unipolar depression). Fifty-two patients were randomized to treatment with BLT and forty-three were in the placebo group (ITT population). Eighty-three subjects completed the study. There were 12 dropouts (5 in the light group and 7 in the placebo group). After 14 days of treatment, a significant improvement was found in all groups (p<0.001). The subjects treated with BLT did not significantly differ in terms of improvement in HDRS-21 scores at the endpoint when compared to patients treated with placebo (p=0.2). However, further analysis demonstrated significantly higher response (50% v. 27.9%, p=0.02) and remission rates (28.8% v. 11.6%, p=0.04) among patients treated with morning BLT when compared to placebo group. It should be noted that in the population of drug-resistant patients, BLT was more efficacious than placebo. There were no statistically significant differences between unipolar and bipolar disorders (p=0.4). CONCLUSION: Although overall improvement in HDRS-21 scores were not superior in the BLT group, both response and remission rates were significantly higher among patients treated with BLT relative to those receiving the sham intervention. BLT was also more efficacious than placebo in the population of patients with drug-resistant depression. Further studies to define the subpopulation of patients with non-seasonal depression who may benefit the most from BLT are needed.

The use of DBS stimulation in mental disorders - opportunities and risks.

Enlarging the knowledge on the biological background of mental disorder is the cause of the growth of interest in cooperation between psychiatrists and neurosurgeons. The experience gained over the last 20 years in research on the use of neuromodulation techniques in neurological disorders suggest that deep brain stimulation (DBS), in addition to improving the neurological condition can lead to positive changes in mood and drive. The use of functional brain research and neuroimaging allowed us to isolate key areas for the emergence of depressive symptoms and obsessive-compulsive disorder. The results of recent studies on the use of DBS in psychiatric disorders indicate, however, both the high efficiency of this method and possible complications and risks associated with it. The paper briefly presents the opportunities of using this method in drug-resistant patients, not responding to other, less invasive forms of treatment, as well as the potential risks and difficulties. However, further research in this area are still required to determine the actual effectiveness of the method, the optimal stereotactic targets, neurostimulation parameters, the risk of side effects and ways to avoid them.

["Addiction" to phenelzine - case report]. / ,,Uzaleinienie" od fenelzyny - opis przypadku.

The use of non-selective monoamine oxidase inhibitors (IMAO) may be associated with the risk of addiction, which is confirmed by case studies published so far. Harmful use of antidepressants in patients with affective disorders and anxiety is not frequent, but due to the fact that in clinical practice can meet with this phenomenon, we present the case of a 30-year-old patient with a history of using phenelzine who presented a combination of symptoms that meet criteria for addiction. The current classification of ICD- 10 does not consist the diagnosis of dependence on antidepressants. In this case, the category F55.0: abuse of a substance which does not cause addiction, should be used. In the literature most often mentioned as a possible substances with addictive potential is a group of non-selective MAO, particularly tranylcypromine. The mechanism of non-selective MAO dependence may be associated with the similarity of their chemical structure to amphetamine (both amphetamine and IMAO are derivatives of phenylethylamine), although the mechanism of action is different. Furthermore, it was noted that there is a group of patients in whom treatment with IMAO is associated with greater risk of abuse of these substances. The study contains the characteristics of this group of patients.