The clinical picture of bipolar affective disorders in children and adolescents hospitalized at the psychiatric ward in Sosnowiec. / Obraz kliniczny zaburzen afektywnych dwubiegunowych u dzieci i mlodziezy hospitalizowanych w oddziale psychiatrii w Sosnowcu.

OBJECTIVES: To determine the clinical picture of bipolar affective disorders (BD) in children and adolescents hospitalized at the Clinical Ward of Developmental Age Psychiatry and Psychotherapy (DAPP) in Sosnowiec, Poland. METHODS: Documentation analysis of 288 BD patients below 18 years of age. Detailed clinical and demographic data were collected and symptoms present during hospitalization were assessed. RESULTS: The mean age of illness onset was 13.6 ± 1.7 years. A total of 86.5% of the studied individuals received a first diagnosis different from BD/mania, and the average time until the proper diagnosis was 16.9 months. In 45.5% the first episode was depression with varied severity, in 29.2% a mixed episode and in 25.3% mania/hypomania. In 48.6% comorbid disorders were present. The most frequent reason for hospitalization was a mixed episode (47.6%). Among the symptoms, irritability was observed in over 80% of patients with mania or mixed episodes, but also in 60% of patients with depression. Suicidal thoughts were experienced by almost all the depression patients, 84.7% in the mixed episode and also 52.6% in mania/hypomania episode. Anxiety was mostly present in depression (40.7%) and mixed episode (22.6%), while moodcongruent delusions in depression and mania (around 20% of cases). Aggressive behaviours were manifested in around half of patients with mania and a mixed episode. CONCLUSIONS: In the studied population of children and adolescents, BD usually started with a depression episode accompanied by a high rate of comorbid disorders and in most cases there was an original misdiagnosis. Study results also point to a significant frequency of some pathological symptoms in this population.

Phenotypic clustering of bipolar disorder supports stratification by lithium responsiveness over diagnostic subtypes.

INTRODUCTION: The aim of this study was to determine whether the clinical profiles of bipolar disorder (BD) patients could be differentiated more clearly using the existing classification by diagnostic subtype or by lithium treatment responsiveness. METHODS: We included adult patients with BD-I or II (N = 477 across four sites) who were treated with lithium as their principal mood stabilizer for at least 1 year. Treatment responsiveness was defined using the dichotomized Alda score. We performed hierarchical clustering on phenotypes defined by 40 features, covering demographics, clinical course, family history, suicide behaviour, and comorbid conditions. We then measured the amount of information that inferred clusters carried about (A) BD subtype and (B) lithium responsiveness using adjusted mutual information (AMI) scores. Detailed phenotypic profiles across clusters were then evaluated with univariate comparisons. RESULTS: Two clusters were identified (n = 56 and n = 421), which captured significantly more information about lithium responsiveness (AMI range: 0.033 to 0.133) than BD subtype (AMI: 0.004 to 0.011). The smaller cluster had disproportionately more lithium responders (n = 47 [83.8%]) when compared to the larger cluster (103 [24.4%]; p = 0.006). CONCLUSIONS: Phenotypes derived from detailed clinical data may carry more information about lithium responsiveness than the current classification of diagnostic subtype. These findings support lithium responsiveness as a valid approach to stratification in clinical samples.

Effectiveness of ultra-long-term lithium treatment: relevant factors and case series.

BACKGROUND: The phenomenon of preventing the recurrences of mood disorders by the long-term lithium administration was discovered sixty years ago. Such a property of lithium has been unequivocally confirmed in subsequent years, and the procedure makes nowadays the gold standard for the pharmacological prophylaxis of bipolar disorder (BD). The efficacy of lithium prophylaxis surpasses other mood stabilizers, and the drug has the longest record as far as the duration of its administration is concerned. The continuation of lithium administration in case of good response could be a lifetime and last for several decades. The stability of lithium prophylactic efficacy in most patients is pretty steady. However, resuming lithium after its discontinuation may, in some patients, be less efficient. MAIN BODY: In the article, the clinical and biological factors connected with the prophylactic efficacy of long-term lithium administration are listed. Next, the adverse and beneficial side effects of such longitudinal treatment are presented. The main problems of long-term lithium therapy, which could make an obstacle to lithium continuation, are connected with lithium's adverse effects on the kidney and, to lesser extent, on thyroid and parathyroid functions. In the paper, the management of these adversities is proposed. Finally, the case reports of three patients who have completed 50 years of lithium therapy are described. CONCLUSIONS: The authors of the paper reckon that in the case of good response, lithium can be given indefinitely. Given the appropriate candidates for such therapy and successful management of the adverse effects, ultra-long term lithium therapy is possible and beneficial for such patients.

Negative symptoms and social cognition as mediators of the relationship between neurocognition and functional outcome in schizophrenia.

Introduction: In this study we assessed the contribution of psychopathology, including the two domains of negative symptoms (motivational deficit and expressive deficit), processing speed as an index of neurocognition, and emotion recognition, as an index of social cognition, to poor functional outcomes in people with schizophrenia. Methods: The Positive and Negative Syndrome Scale was used to evaluate positive symptoms and disorganization and the Brief Negative Symptom Scale to assess negative symptoms. The Symbol Coding and the Trail Making Test A and B were used to rate processing speed and the Facial Emotion Identification Test to assess emotion recognition. Functional outcome was assessed with the Personal and Social Performance Scale (PSP). Regression analyses were performed to identify predictors of functional outcome. Mediation analyses was used to investigate whether social cognition and negative symptom domains fully or partially mediated the impact of processing speed on functional outcome. Results: One hundred and fifty subjects from 8 different European centers were recruited. Our data showed that the expressive deficit predicted global functioning and together with motivational deficit fully mediated the effects of neurocognition on it. Motivational deficit was a predictor of personal and social functioning and fully mediated neurocognitive impairment effects on the same outcome. Both motivational deficit and neurocognitive impairment predicted socially useful activities, and the emotion recognition domain of social cognition partially mediated the impact of neurocognitive deficits on this outcome. Conclusions: Our results indicate that pathways to functional outcomes are specific for different domains of real-life functioning and that negative symptoms and social cognition mediate the impact of neurocognitive deficits on different domains of functioning. Our results suggest that both negative symptoms and social cognition should be targeted by psychosocial interventions to enhance the functional impact of neurocognitive remediation.

Abelson Helper Integration Site 1 haplotypes and peripheral blood expression associates with lithium response and immunomodulation in bipolar patients.

RATIONALE: In bipolar disorder (BD), immunological factors play a role in the pathogenesis and treatment of the illness. Studies showed the potential link between Abelson Helper Integration Site 1 (AHI1) protein, behavioural changes and innate immunity regulation. An immunomodulatory effect was suggested for lithium, a mood stabilizer used in BD treatment. OBJECTIVES: We hypothesized that AHI1 may be an important mediator of lithium treatment response. Our study aimed to investigate whether the AHI1 haplotypes and expression associates with lithium treatment response in BD patients. We also examined whether AHI1 expression and lithium treatment correlate with innate inflammatory response genes. RESULTS: We genotyped seven AHI1 single nucleotide polymorphisms in 97 euthymic BD patients and found that TG haplotype (rs7739635, rs9494332) was significantly associated with lithium response. We also showed significantly increased AHI1 expression in the blood of lithium responders compared to non-responders and BD patients compared to healthy controls (HC). We analyzed the expression of genes involved in the innate immune response and inflammatory response regulation (TLR4, CASP4, CASP5, NLRP3, IL1A, IL1B, IL6, IL10, IL18) in 21 lithium-treated BD patients, 20 BD patients treated with other mood stabilizer and 19 HC. We found significantly altered expression between BD patients and HC, but not between BD patients treated with different mood stabilizers. CONCLUSIONS: Our study suggests the involvement of AHI1 in the lithium mode of action. Moreover, mood-stabilizing treatment associated with the innate immunity-related gene expression in BD patients and only the lithium-treated BD patients showed significantly elevated expression of anti-inflammatory IL10, suggesting lithium's immunomodulatory potential.

Identification of shared disease marker genes and underlying mechanisms between major depression and rheumatoid arthritis.

Both depression and rheumatoid arthritis (RA) have a very high comorbidity rate. A bilateral association is estimated to increase the mutual risk and the common denominator is inflammation being observed in both diseases. Previous studies have mainly focused on assessing peripheral blood's inflammatory and pro-inflammatory cytokines levels. We aimed to extend insights into the molecular mechanisms of depression based on hub RA genes. To do so, we prioritized RA-related genes using in-silico tools. We then investigated whether RA-related genes undergo altered expression in patients with unipolar and bipolar depression without a concurrent RA diagnosis and any exponents of active inflammation. In addition, we selected a homogeneous group of patients treated with lithium (Li), which has immunomodulatory properties. The study was performed on patients with bipolar depression (BD, n = 45; Li, n = 20), unipolar depression (UD, n = 27), and healthy controls (HC, n = 22) of both sexes. To identify DEGs in peripheral blood mononuclear cells (PBMCs), we used the SurePrint G3 Microarray and GeneSpring software. We selected a list of 180 hub genes whose altered expression we analyzed using the expression microarray results. In the entire study group, we identified altered expression of 93 of the 180 genes, including 35 down-regulated (OPRM1 gene with highest FC > 3) and 58 up-regulated (TLR4 gene with highest FC > 3). In UD patients, we observed maximally up-regulated expression of the TEK gene (FC > 3), and in BD of the CXCL8 gene (FC > 5). On the other hand, in lithium-treated patients, the gene with the most reduced expression was the TRPV1 gene. The study proved that depression and RA are produced by a partially shared "inflammatory interactome" in which the opioid and angiogenesis pathways are important.

Health behaviours of patients with affective disorders: a cross-sectional study.

BACKGROUND: Severe mental disorders, including affective disorders (AD), are associated with high rates of physical illnesses that lead to premature patient death. Excess somatic comorbidity may be partially explained by lifestyle factors. This study aimed to investigate the health behaviours (HBs) of patients with AD in comparison to the HBs of patients with type 2 diabetes (T2D) and healthy controls (HCs) and to examine associations among HBs and sociodemographic and clinical factors, subjective quality of life and health status, and health locus of control. METHODS: The sample consisted of 108 patients with AD, including 60 with bipolar disorder (BP) and 48 with unipolar disorder (UAD). Analyses included comparisons with a subgroup of AD individuals, patients with T2D and HCs matched in age and sex. The Health Behaviour Inventory was used to evaluate the overall levels of HBs and 4 HB categories. To identify independent determinants of health behaviours, a multivariate linear regression analysis was performed with factors identified as significant in bivariate analyses. RESULTS: Most AD patients had a low level of HBs (40%), followed by moderate (35%) and high levels (25%), and there were no significant differences in HBs between the BP and UAD groups. Compared with the T2D and HC groups, the AD group had a significantly lower level of overall HBs and lower levels of HBs in one of the categories. Independent predictors of overall HBs were quality of life (ß = 0.28, p < 0.001), age (ß = 0.27, p = 0.002), and depressive symptoms (ß = 0.23, p = 0.008). A total of 30% of the variance in HBs was explained. CONCLUSIONS: These findings emphasise the need for a systematic assessment of single and multiple health behaviours to provide better care for patients with AD and reduce the potential adverse effects of an unhealthy lifestyle.

The fiftieth anniversary of the article that shook up psychiatry. / Piecdziesieciolecie artykulu, który wstrzasnal psychiatria.

In January 2023, the fiftieth anniversary passes of David Rosenhan's article On being sane in insane places appearing in the prestigious journal "Science". This publication has become one of the most influential psychiatric papers of the second half of the 20th century, achieving 1,276 citations up to mid-2022. In the article, eight healthy persons are described, who came to psychiatric hospitals in the USA, reporting auditory hallucinations. They were all admitted, mainly with suspected schizophrenia, and ordered pharmacological treatment. Their stay ranged from 7-52 (mean 19) days, even though after the admission they did not confirm the symptoms. The article spotlighted an unjustified diagnosis of mental illness, resulting in psychiatric hospitalization in unfavorable conditions. Its consequences were manifold. It augmented the process of psychiatric deinstitutionalization and provided food for anti-psychiatric movements and humanistic psychiatry. However, it did accelerate the inception of an objective system of psychiatric diagnosis in the form of the 3rd edition of the Diagnostic and Statistical Manual (DSM-III), released in 1980. Susannah Cahalan's book The great pretender, published in 2019, undermines the reliability of the article. Based on many interviews and Rosenhan's notes, she pointed out many faults of the experiment. She was not able to retrospectively confirm the identities of the majority of participants, nor to receive the essential information from "Science". On the fiftieth anniversary of the article, its cognitive value for an objective diagnosis of mental illness and the role of psychiatric hospitalization as well as the negative consequences in the form of a drastic reduction of psychiatric beds in the USA are emphasized.

Mood Stabilizers of First and Second Generation.

The topic of this narrative review is mood stabilizers. First, the author's definition of mood-stabilizing drugs is provided. Second, mood-stabilizing drugs meeting this definition that have been employed until now are described. They can be classified into two generations based on the chronology of their introduction into the psychiatric armamentarium. First-generation mood stabilizers (FGMSs), such as lithium, valproates, and carbamazepine, were introduced in the 1960s and 1970s. Second-generation mood stabilizers (SGMSs) started in 1995, with a discovery of the mood-stabilizing properties of clozapine. The SGMSs include atypical antipsychotics, such as clozapine, olanzapine, quetiapine, aripiprazole, and risperidone, as well as a new anticonvulsant drug, lamotrigine. Recently, as a candidate for SGMSs, a novel antipsychotic, lurasidone, has been suggested. Several other atypical antipsychotics, anticonvulsants, and memantine showed some usefulness in the treatment and prophylaxis of bipolar disorder; however, they do not fully meet the author's criteria for mood stabilizers. The article presents clinical experiences with mood stabilizers of the first and second generations and with "insufficient" ones. Further, current suggestions for their use in preventing recurrences of bipolar mood disorder are provided.

Application of Antipsychotic Drugs in Mood Disorders.

Since their first application in psychiatry seventy years ago, antipsychotic drugs, besides schizophrenia, have been widely used in the treatment of mood disorders. Such an application of antipsychotics is the subject of this narrative review. Antipsychotic drugs can be arbitrarily classified into three generations. First-generation antipsychotics (FGAs), such as phenothiazines and haloperidol, were mainly applied for the treatment of acute mania, as well as psychotic depression when combined with antidepressants. The second-generation, so-called atypical antipsychotics (SGAs), such as clozapine, risperidone, olanzapine, and quetiapine, have antimanic activity and are also effective for the maintenance treatment of bipolar disorder. Additionally, quetiapine exerts therapeutic action in bipolar depression. Third-generation antipsychotics (TGAs) started with aripiprazole, a partial dopamine D2 receptor agonist, followed by brexpiprazole, lurasidone, cariprazine, and lumateperone. Out of these drugs, aripiprazole and cariprazine have antimanic activity, lurasidone, cariprazine, and lumateperone exert a significant antidepressant effect on bipolar depression, while there is evidence for the efficacy of aripiprazole and lurasidone in the prevention of recurrence in bipolar disorder. Therefore, successive generations of antipsychotic drugs present a diverse spectrum for application in mood disorders. Such a pharmacological overlap in the treatment of schizophrenia and bipolar illness stands in contrast to the dichotomous Kraepelinian division of schizophrenia and mood disorders.

Updated perspectives on how and when lithium should be used in the treatment of mood disorders.

INTRODUCTION: Lithium is one of the most important drugs for the treatment of mood disorders. The appropriate guidelines can ensure that more patients benefit from its use in a personalized way. AREAS COVERED: This manuscript provides an update on the application of lithium in mood disorders, including prophylaxis of bipolar and unipolar mood disorder, treatment of acute manic and depressive episodes, augmentation of antidepressants in treatment-resistant depression, and use of lithium in pregnancy and the postpartum period. EXPERT OPINION: Lithium remains the gold standard for the prevention of recurrences in bipolar mood disorder. For long-term treatment/management of bipolar mood disorder, clinicians should also consider lithium's anti-suicidal effect. Furthermore, after prophylactic treatment, lithium may also be augmented with antidepressants in treatment-resistant depression. There have also been some demonstration of lithium having some efficacy in acute episodes of mania and bipolar depression as well as in the prophylaxis of unipolar depression.

Long-Term Lithium Therapy: Side Effects and Interactions.

Lithium remains the drug of first choice for prophylactic treatment of bipolar disorder, preventing the recurrences of manic and depressive episodes. The longitudinal experiences with lithium administration greatly exceed those with other mood stabilizers. Among the adverse side effects of lithium, renal, gastrointestinal, neurological, thyroid, metabolic, cognitive, dermatological, cardiologic, and sexual are listed. Probably, the most important negative effect of lithium, occurring mostly after 10-20 years of its administration, is interstitial nephropathy. Beneficial side-effects of long-term lithium therapy also occur such as anti-suicidal, antiviral, and anti-dementia ones. Pharmacokinetic and pharmacodynamic interactions of lithium, mostly those with other drugs, may have an impact on the success of long-term lithium treatment. This paper makes the narrative updated review of lithium-induced side-effects and interactions that may influence its prophylactic effect in bipolar disorder. Their description, mechanisms, and management strategies are provided. The papers appearing in recent years focused mainly on the long-term lithium treatment are reviewed in detail, including recent research performed at Department of Psychiatry, Poznan University of Medical Sciences, Poland. Their own observations on ultra-long lithium treatment of patients with bipolar disorder are also presented. The review can help psychiatrists to perform a successful lithium prophylaxis in bipolar patients.

Evolutionary aspects of bipolar affective illness. / Ewolucyjne aspekty choroby afektywnej dwubiegunowej.

Bipolar affective illness (bipolar disorder - BD), also known as manic-depressive illness, is characterized by periodic opposite states of mood, activity, and motivation (mania and depression) sometimes of extreme intensity. The development and maintenance of such states in evolution can betoken a possibility of their adaptive character, enabling adaptation to an unfavorable external situation (depression) and a mobilization to using resources when available (mania). In the article, the main focus is put on the evolutionary aspect of "bipolarity" and manic/hypomanic states. Molecular-genetic studies show that in evolution, the genes connected with a predisposition to BD have been conserved. In the paper, the evolutionary adaptive concepts connected with the functioning of Homo sapiens during the middle and late Pleistocene periods were discussed as well as the "mismatch" theories associated with not befitting brain functioning to contemporary conditions. The benefits of mania and hypomania, also in the context of their link to depression were delineated, indicating their relationship to the increase in reproductive success. They result from such features of mania/hypomania as increased exploratory, psychomotor and sexual activity, and prompt risk-taking. The reproductive success can be connected with hyperthymic and cyclothymic temperaments, most frequently occurring in subjects with BD. The hyperthymic temperament often leads to increased social status and a tendency to leadership, and the cyclothymic temperament can increase creativity. Examples of the relationship between manic/hypomanic states and the phenomenon of emigration as well as the advancement of American society are provided.

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.

Expert consensus recommendations on the use of randomized clinical trials for drug approval in psychiatry- comparing trial designs.

The use of randomized clinical trials, in particular placebo-controlled trials, for drug approval, is the subject of long-standing debate in the scientific community and beyond. This study offers consensus recommendations from clinical and academic experts to guide the selection of clinical trial design in psychiatry. Forty-one highly cited clinical psychiatrists and/or researchers participated in a Delphi survey. Consensus statements were developed based on the findings of a published, peer-reviewed systematic review. Participants evaluated statements in two survey rounds, following the Delphi method. The expert panel achieved consensus on 7 of 21 recommendations regarding the use of randomized clinical trials. The endorsed recommendations were: (i) Results from placebo-controlled trials are the most reliable and (ii) are necessary despite the growing placebo-effect; (iii) it is ethical to enroll patients in placebo-arms when established treatment is available, if there is no evidence of increased health risk; (iv) There is a need to approve new drugs with the same efficacy as existing treatments, but with different side-effect profiles; (v) Non-inferiority trials incur an increased risk of approving ineffective medications; (vi) The risk of approving an ineffective drug justifies trial designs that incur higher costs, and (vii) superiority trials incur the risk of rejecting potentially efficacious treatments. The endorsed recommendations inform the choice of trial-design appropriate for approval of psychopharmacological drugs. The recommendations strongly support the use of randomized clinical trials in general, and the use of placebo-controlled trials in particular.

Higher indexes of childhood trauma in borderline personality disorder compared with bipolar disorder. / Wyzsze wskazniki traumy wczesnodzieciecej u osób z zaburzeniem osobowosci borderline w porównaniu z pacjentami z choroba afektywna dwubiegunowa.

OBJECTIVES: Comparison of the frequency of childhood traumatic events between agroup of patients with bipolar disorder (BD), borderline personality disorder (BPD) and healthy persons. METHODS: The study included 35 patients (10 male, 25 female) with BD, hospitalized in the Department of Adult Psychiatry in Poznan, the Neuropsychiatric Hospital in Koscian and the Medical Centre in Milicz, as well as 35 patients (9 male, 26 female) with BPD under the care of the Józef Babinski Hospital in Kraków. Seventy-one healthy persons (22 male, 49 female) constituted a control group. The Polish version of the Childhood Trauma Questionnaire (CTQ) was used. RESULTS: In both clinical groups, no gender differences as to the CTQ indexes were found. Patients from both groups hadmorefrequentchildhoodtraumacomparedwith controlsubjects. Patients with BPD showed significantly higher CTQ indexes than those with BD. . CONCLUSIONS: The obtained results indicate significantly more frequent experience of traumatic events in childhood in patients with BPD compared with BD. This is discussed in the context of the pathogenesis and treatment of both conditions. It is probable that in BPD childhood trauma plays the biggest role among all psychiatric disturbances.

Antiviral, immunomodulatory, and neuroprotective effect of lithium.

Currently, in psychiatry, lithium is a drug of choice as a mood stabilizer in the maintenance treatment of bipolar disorder for the prevention of manic and depressive recurrences. The second most important psychiatric use of lithium is probably increasing the efficacy of antidepressants in treatment-resistant depression. In addition to its mood-stabilizing properties, lithium exerts antisuicidal, antiviral, immunomodulatory, and neuroprotective effects. The goal of the review is to describe the experimental and clinical studies on the last three properties of lithium. Antiviral effects of lithium pertain mostly to DNA viruses, especially herpes viruses. The therapeutic effects of lithium in systemic and topical administration on labial and genital herpes were demonstrated in clinical studies. There is also some evidence, mostly in experimental studies, that lithium possesses antiviral activity against RNA viruses, including coronaviruses. The immunomodulatory effect of lithium can mitigate "low-grade inflammatory" conditions in bipolar illness. The neuroprotective properties of lithium make this ion a plausible candidate for the prevention and treatment of neurodegenerative disorders. A favorable effect of lithium was shown in experimental models of neurodegenerative disorders. On the clinical level, some preventive action against dementia and moderately therapeutic activity in Alzheimer's disease, and mild cognitive impairment were observed. Despite promising results of lithium obtained in animal models of Huntington's disease and amyotrophic lateral sclerosis, they have not been confirmed in clinical studies. A suggestion for common mechanisms of antiviral, immunomodulatory, and neuroprotective effects of lithium is advanced.

Speech Understanding in Manic and Depressive Episodes of Mood Disorders.

OBJECTIVE: The aim of this study was to assess the perception of speech in adverse acoustic conditions during manic and depressive episodes of mood disorders. METHODS: Forty-three patients with bipolar disorder (mania, N=20; depression, N=23) and 32 patients with unipolar depression were included for analyses. Thirty-five participants served as the control group. The study of speech understanding was carried out using the Polish Sentence Matrix Test, allowing for the determination of the speech reception threshold (SRT). The test was performed in the clinical groups both during an acute episode and remission; during remission, patients underwent audiometric evaluation. RESULTS: Compared with control subjects, patients with mood disorders had worse speech understanding (higher SRT), regardless of the episode or remission. A manic episode in the course of bipolar disorder was not associated with worse speech understanding compared with remission of mania. However, an episode of depression in the course of both bipolar disorder and unipolar depression was associated with worse speech understanding compared with remission of depression. In bipolar depression, this correlated with age, duration of the disorder, number of episodes, and number of hospitalizations, as well as in remission with age and duration of illness. In unipolar depression, poor speech understanding was more severe in individuals with hearing impairment. CONCLUSIONS: These findings revealed that patients with mood disorders had impaired speech understanding, even while in remission, and manic episodes in the course of bipolar disorder were not associated with impaired speech understanding compared with mania remission.

Dysfunction of the Purinergic System in Bipolar Disorder.

OBJECTIVE: To verify the purinergic hypothesis of bipolar disorder (BD), we assessed the concentration of various components of the purinergic system in manic and depressed bipolar patients. METHODS: Sixty-two patients (19 male and 43 female), aged 22-69 (49 ± 14) years, with BD were studied. Twenty-three patients (9 male and 14 female) were assessed during a manic episode and subsequent remission, and 39 patients (10 male and 29 female) were investigated in a depressive episode and the following remission. Twenty-two healthy subjects (8 male and 14 female), aged 19-70 (41 ± 14) years, served as the control group (CG). The severity of symptoms was evaluated using the Hamilton Depression Rating Scale (HDRS) and the Young Mania Rating Scale (YMRS). The concentrations of uric acid (UA) were estimated by the uricase-based method, whereas xanthine dehydrogenase (XDH), adenosine (Ado), and adenosine deaminase (ADA) by ELISA. RESULTS: The mean score in the acute episode was 32 ± 8 points in the YMRS for mania and 31 ± 8 in the HDRS for depression. UA levels were significantly higher in female bipolar patients compared to the females in the CG. The concentrations of XDH, Ado, and ADA were significantly lower in bipolar patients both during an acute episode and remission compared to CG. CONCLUSIONS: A significant dysfunction of the purinergic system in patients with BD was observed. In most instances, the disturbances were not different in the acute episode than in remission what qualifies them as trait dependent. The results may confirm the role of the purinergic system in the pathogenesis of BD.