Since the year 2000, ketamine and its enantiomers have been studied for their antidepressant effects. This paper will briefly summarise the journey of ketamine from an anaesthetic to an antidepressant. The text will present the key mechanisms of its action, as well as the actions of its metabolites. The aim of this article is to describe the role of specific groups of receptors in activation of important metabolic pathways and in production of factors such as mammalian target of rapamycin kinase (mTOR) and brain-derived neurotrophic factor (BDNF), in order to comprehensively present a potential link between ketamine, ketamine's enantiomers and its metabolites with terms such as neuroplasticity and antidepressant action. Another important part of this article is a summary of arguments for and against importance of specific mechanisms of ketamine action and to compare (S) and (R)-ketamine's potential to act as an antidepressant. This article may be particularly helpful for researchers in determining further research directions and serve as a summary of the current state of knowledge regarding the mechanisms of ketamine's action and the latest therapeutic possibilities in the treatment of affective disorders.

Background:Patients with mental disorders are at increased risk of hepatitis C virus (HCV) infection, yet the prevalence of HCV among patients in Polish psychiatric ward remains unknown. Methods:A cross-sectional survey was conducted in Poland from 2021 to 2023 in psychiatric wards. Adults recently hospitalized with at least one current mental health condition were eligible and 12-897 individuals were tested for anti HCV antibodies. Patients with confirmed active HCV infection (subsequent nucleic acid testing) were offered treatment. Results:Of the 12,897 individuals who constituted the sample, 64% were male, and the median age was 45 years (interquartile range: 35-58 years). Among those subjects, 226 patients (representing 1.8% of the total) exhibited a positive HCV antibody test result, and 172 of these patients had active HCV infection (the prevalence of 1.3%). Multivariate analysis identified five risk factors for HCV infection within the investigated population: intravenous drug use (odds ratio [OR] = 9.40; 95% confidence interval [CI]: 6.12-14.44; p<0.001), diagnosed and treated liver disease (OR = 6.17; 95% CI: 4.10-9.26; p < 0.001); blood transfusions prior to 1992 (OR = 2.61; 95% CI: 1.29-5.28; p=0.008), diagnosis of mental and behavioral disorders due to psychoactive substance abuse (OR = 1.97; 95% CI: 1.34-2.91; p=0.001) and previous incarceration (OR = 1.62; 95% CI: 1.08-2.43, p=0.018). Conclusions:High prevalence of HCV infection in patients with mental health disorders and specifically in patients who used intravenous drugs suggests the importance of screening for HCV in this vulnerable population.

Major Depressive Disorder (MDD) is characterized by heterogeneous pathogenesis that extends beyond traditional monoamine deficits. A paradigm shift is recognizing neuroinflammation as a central, critical driver of both illness onset and resistance to treatment. The CXCL12/CXCR4 system is traditionally associated with immune cell trafficking, but increasing evidence reveals its powerful regulatory role in neuropsychiatric disorders. We performed a comprehensive synthesis demonstrating that CXCL12/CXCR4 axis acts as a direct molecular modulator of neurotransmission, neuroplasticity, and glial cell signaling. Specifically, this axis can modulate a multiple molecular pathways linked with the glutaminergic, GABAergic, and serotonergic systems, and mediating neuroplasticity and glial cell function. Functionally, CXCL12/CXCR4 axis has twofold character - it can strengthen neurotoxic processes through overactivation of NMDAR and excessive Ca2 + influx. On the other hand, it can also play protective role by preventing excitotoxicity, supporting neurogenesis, enhancing GABA synthesis, and dendritic spines stabilization. This review focuses on identifying potential mechanisms across in vitro, animal, and human studies to establish the CXCL12/CXCR4 axis as a powerful biomarker and, critically, an unexploited therapeutic target.

Neuroimmune dysregulation and altered pro- and anti-inflammatory signaling have been implicated in selected phenotypes of depressive and anxiety disorders. Interleukin-37 (IL-37), a member of the IL-1 family, exerts anti-inflammatory effects through extracellular signaling involving IL-18Rα and IL-1R8 and intracellular interactions with SMAD3. This scoping review mapped direct and indirect evidence concerning the relevance of IL-37 to depressive and anxiety disorders. PubMed/MEDLINE was searched through 12 July 2026, supplemented by backward citation searching and reference-list checking; evidence was charted by study type, population or model, IL-37 assessment, principal findings, and level of psychiatric relevance. Thirty-two IL-37-related sources were included. Direct psychiatric evidence comprised one small cross-sectional human study and two rodent stress-model studies, in which IL-37 was assessed as one component of broader inflammatory profiles rather than as a prespecified primary biomarker or intervention target. The remaining evidence was derived from non-psychiatric inflammatory conditions, central nervous system disease models, or mechanistic studies. These findings provide hypothesis-generating biological context but do not establish psychiatric specificity, causality, biomarker validity, or therapeutic efficacy. IL-37 should therefore be considered an exploratory research variable requiring validation in well-characterized longitudinal psychiatric cohorts using standardized assays and integrated immune profiling.

Background Auricular transcutaneous vagus nerve stimulation (atVNS) has been proposed as a non-invasive neuromodulation approach for cognitive disorders, including Alzheimer's disease (AD). Sleep represents a physiological state characterized by enhanced vagal activity and memory consolidation, making it a potentially optimal window for stimulation. Objective To investigate the cognitive effects of nocturnal atVNS in individuals diagnosed with mild cognitive impairment (MCI) and AD. Methods Participants underwent nightly atVNS using a Vguard device, specifically designed for non-invasive stimulation during sleep. Cognitive performance was evaluated using four standardized neuropsychological instruments, including the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog). Results Repeated nocturnal atVNS over several months was associated with significant improvements in global cognitive function. Among the administered tests, the ADAS-Cog demonstrated the greatest sensitivity in detecting stimulation-related changes. Conclusions Nocturnal atVNS may constitute a promising therapeutic strategy for enhancing cognition in patients with MCI and AD. By leveraging sleep-related vagal activity, this approach could potentially delay or prevent the progression of MCI to AD and dementia.

BackgroundHistory of suicide attempts is one of the strongest predictors of adolescent suicide death. Our aim was to improve the comprehension of behavioral and socio-demographical characteristics of adolescent who have attempted suicide which can accelerate preventive and therapeutical measures.MethodsWe retrospectively analyzed medical data of 284 psychiatric inpatients aged 13-18. We performed an univariate and multivariate analyses for the whole group and female and male sex separately followed by a logistic regression analysis. The primary outcome measure was history of suicidal attempt (SA).Results115 out of 284 analyzed patients (40.5%) - 91 girls (subgroup 1) and 24 boys (subgroup 2) - had a history of SA. In the whole group SA was associated with female gender, cigarette smoking, nonsuicidal self-injury (NSSI) and neglect of emotional or social needs. In the subgroup of girls the most significant association was found between SA and cigarette smoking, followed by neglect of emotional and social needs, NSSI and the older age of receiving psychiatric help. In boys, the history of SA was associated with two factors: cigarette smoking and family victimization.ConclusionsThe only factor that showed significant association with SA consequently throughout all our study was cigarette smoking, which implies that in the high risk adolescents population cigarette smoking might be a more specific characteristic of the history of SA than NSSI and thus should not be neglected during first examination.

Bipolar disorder is characterized by recurrent episodes of depression, mania, hypomania, or mixed states. Early diagnosis and comprehensive treatment, including pharmacotherapy and psychosocial interactions, are associated with a more favorable prognosis. The general principles for the use of drugs in bipolar disorder in children and adolescents remain similar to those in adults. The basic drugs in bipolar disorder are mood stabilizers of the first and second generation; however, their efficacy and safety profile in children and adolescents differ from those in adults. In addition, prophylactic treatment is necessary to prevent recurrence. Lithium, aripiprazole, quetiapine, risperidone, olanzapine, asenapine, ziprasidone are recommended for the treatment of mania and mixed states. For the treatment of depressive episodes in bipolar disorder in children and adolescents, experts recommend lurasidone as monotherapy or olanzapine + fluoxetine as combination therapy. Although long-term treatment is a key aspect of bipolar disorder management in children and adolescents, consistent efficacy data are still lacking. Safety data indicate that the most commonly reported adverse reactions in children and adolescents treated with mood stabilizers are gastrointestinal and neurological adverse reactions, while the use of antipsychotics is mainly associated with weight gain and sedation.

Bipolar disorder (BD) occurring in children and adolescents may have a different clinical course than that diagnosed in adults, while there are no different criteria in the diagnostic classifications used. Among patients under 18 years of age, irritability, atypical course of depressive episodes, mixed episodes or very rapid phase change are much more frequently observed. Diagnostic difficulties are also overlapped by those resulting from the need to differentiate BD from other disorders which have their onset in childhood and adolescence; the probability of their coexistence should be considered concomitantly. This applies primarily to hyperkinetic disorders, behavioral disorders, borderline personality disorder or addiction to psychoactive substances. About 50% of patients present with symptoms of BD before the age of 18, and it takes on average 5 to 10 years from symptom onset to receive a correct diagnosis. Undiagnosed BD can have a negative impact on the development of emotional, social and cognitive competences, significantly affecting a patient's functioning into adulthood. That is why it is so important for specialists working with children and adolescents to be aware of the differences in the clinical course of BD and to make the right diagnosis, taking into account the biological, developmental and systemic context.

How we deal with stress and certain traits of our personality can be influenced not only by psycho-social factors, but also by biological factors, including genetics. Research studies suggest that the long allele of the DRD4 gene (DRD4-7R) is associated with novelty seeking and risk taking—features potentially important for healthcare workers. The aim of this study was to assess the DRD4-7R polymorphism and its impact on propensity for risk taking and ways of coping with stress in medical professionals This preliminary study involved 82 volunteers from among active healthcare professionals, including 33 medical doctors (MDs). All participants were asked to fill out psychological questionnaires for assessment of their stress-coping strategies (Mini-COPE) and risk-taking propensity (IVE). A swab of the inside of the cheek was taken from the study participants to determine the polymorphism within the gene for the dopamine D4 receptor gene (DRD4). In our study, medical doctors (MDs) tend to have the DRD4-7R allele more often than other medical professionals. Our study also indicates that DRD4-R7 allele carriers are significantly less likely to use stimulants and other substances to help themselves with stress coping and less likely to expect emotional support. The DRD4 gene polymorphism may be important for the development of specific personality traits and ways of coping with stress. However, further research with larger numbers of participants is needed.

Leki przeciwpsychotyczne (LPP) jako grupa mimo zbliżonego efektu klinicznego, różnią się między sobą zarówno budową chemiczną, właściwościami farmakodynamicznymi i farmakokinetycznymi, jak również możliwymi działaniami niepożądanymi ich stosowania. Przy doborze odpowiedniego leczenia dla pacjenta lekarz powinien kierować się nie tylko oczekiwanym efektem terapeutycznym, ale także zważać na możliwe skutki uboczne, zwłaszcza u pacjentów obciążonych dodatkowymi schorzeniami somatycznymi. Prawie wszystkie, z wyjątkiem niedostępnej w Polsce pimawanseryny, zarejestrowane aktualnie LPP są antagonistami receptorów D2. Leki II generacji dodatkowo wywierają istotny wpływ na przekaźnictwo serotoninergiczne, przede wszystkim blokując receptory 5HT2a. Z kolei nowoczesne leki przeciwpsychotyczne III generacji oprócz antagonizmu w stosunku do receptorów D2 wykazują również częściowy agonizm względem receptorów dopaminergicznych, co pozwala modulować przekaźnictwo dopaminergiczne. Celem niniejszej pracy jest przedstawienie wskazówek dotyczących doboru leków przeciwpsychotycznych (LPP) w leczeniu pacjentów psychiatrycznych ze współwystępującymi schorzeniami somatycznymi (część pierwsza zaleceń dotyczy zespołu metabolicznego, hiperprolaktynemii oraz schorzeń kardiologicznych.), w oparciu o ryzyko możliwych działań niepożądanych związanych ze stosowaniem LPP.

Dobór odpowiedniego leczenia psychiatrycznego może stanowić wyzwanie. Jest on szczególnie trudny w grupie pacjentów obciążonych a priori poważnymi schorzeniami somatycznymi tj. niewydolność nerek lub wątroby, schorzenia neurologiczne czy jaskra. Gdy zachodzi zasadność stosowania leków przeciwpsychotycznych, oprócz odpowiedniego profilu działania klinicznego, należy także zwracać uwagę na inne cechy danego leku takie jak: jego właściwości farmakodynamiczne i farmakokinetyczne oraz możliwe działania niepożądane. Prawie wszystkie, z wyjątkiem pimawanseryny (niedostępna w Polsce), obecnie zarejestrowane leki przeciwpsychotyczne są antagonistami receptora D2. Leki drugiej generacji dodatkowo wywierają istotny wpływ na przekaźnictwo serotoninergiczne, głównie poprzez blokowanie receptorów 5HT2a. Z kolei nowoczesne leki przeciwpsychotyczne trzeciej generacji, oprócz antagonizmu wobec receptorów D2, wykazują również częściowy agonizm wobec receptorów dopaminergicznych, co pozwala na modulację przekaźnictwa dopaminergicznego. Ten profil oddziaływań wpływać może na rodzaj działań niepożądanych. Celem niniejszej pracy jest przedstawienie praktycznych zaleceń dotyczących bezpieczeństwa stosowania leków przeciwpsychotycznych (LPP) w grupach pacjentów obciążonych często spotykanymi w praktyce klinicznej schorzeniami somatycznych tj. niewydolność nerek, schorzenia neurologiczne, w tym choroba Parkinsona i padaczka, niewydolność wątroby, rozrost gruczołu krokowego oraz jaskra. Praca stanowi kontynuację zaleceń dotyczących stosowania neuroleptyków u pacjentów z chorobami somatycznymi

Treatment-resistant depression (TRD), defined as the failure to achieve adequate response to at least two antidepressant trials, affects 20-30% of patients with major depressive disorder and poses substantial personal and socioeconomic burdens. This review aimed to synthesize current knowledge on the genetic, epigenetic, and neurobiological underpinnings of TRD to understand its pathophysiology better and inform future treatment strategies. A systematic search identified relevant studies focusing on genetic predispositions, epigenetic modifications, structural and functional brain alterations, the role of chronic inflammation, and deficits in neuroplasticity and neurogenesis associated with TRD. Findings highlight the involvement of polymorphisms in genes regulating neurotransmission, neuroplasticity, and stress response, though replication across studies remains inconsistent. Genome-wide association studies suggest polygenic contributions but are limited by small sample sizes and heterogeneous definitions of TRD. Emerging evidence points to aberrant DNA methylation, histone modifications, and dysregulated non-coding RNAs as potential mediators of treatment resistance. Neuroimaging studies reveal TRD-specific patterns, particularly altered default mode network connectivity and white matter disruptions, supporting its distinction as a subtype of depression. Collectively, the evidence underscores TRD as a multifactorial condition shaped by genetic and neurobiological factors, while emphasizing the need for standardized definitions, larger cohorts, and longitudinal designs to advance the field.

Nutritional psychiatry is a promising approach to mental health, yet translating research into clinical practice remains a challenge. This article underscores the importance of implementation science in closing the gap between evidence and real-world application. Current barriers include the entrenched focus on pharmacological treatments, inadequate integration of nutritional interventions into established care models, and limited clinician training in nutrition. To address these issues, we suggest incorporating dietitians or nutritionists into mental health teams, educating case managers on nutritional interventions, and expanding interdisciplinary collaboration. Additionally, investing in comprehensive training programs for clinicians and leveraging emerging technologies can help facilitate this integration. By embracing these strategies, nutritional psychiatry can be more effectively implemented into routine mental health care, offering a more holistic and patient-centered approach. Implementation science is key to overcoming these barriers and advancing mental health treatment, leading to improved outcomes and enhanced well-being for patients. [ Psychiatr Ann . 2025;55(2):e46–e50.]

Introduction: Mental disorders are an increasingly common phenomenon in the Polish population. Medical students are at high risk of developing mental disorders. Aim of the research: To investigate the prevalence of mental disorders among medical university students, the level of stress, the use of psychotherapy, and the use of psychiatric medications. Material and methods: The study was conducted using an original survey, which was distributed among students from the first to the sixth year of the Medical University between February 20 and March 8, 2024. Students received a survey consisting of 22 questions in their university email inbox. Results: 1132 students participated in the study. A mental disorder was diagnosed in 28.6% of the respondents. The most common disorder was depression, diagnosed in 16.52% of students, followed by anxiety disorders, which were diagnosed in 15.02% of respondents. 60.1% of students with diagnosed mental disorders took psychiatric medications, and 66% used psychotherapy. Among students, the most frequently indicated level of stress on a daily basis was medium, followed by high. Conclusions: The prevalence of mental disorders among medical students is higher than in the general population. The most common mental disorder is depression. The most commonly taken psychiatric drug is sertraline. Medical students face high levels of stress on a daily basis.

Zaburzenia afektywne dwubiegunowe (ChAD) występujące u dzieci i młodzieży mogą mieć inny przebieg kliniczny niż te diagnozowane u dorosłych przy jednoczesnym braku odmiennych kryteriów w stosowanych klasyfikacjach diagnostycznych. Wśród pacjentów poniżej 18 roku życia znacznie częściej obserwuje się drażliwość, atypowy przebieg epizodu depresji, epizody mieszane czy bardzo szybką zmiana faz. Na trudności diagnostyczne nakładają się także te wynikające z konieczność różnicowania ChAD z innymi zaburzeniami rozpoczynającymi się w okresie dziecięco-młodzieżowym z jednoczesnym uwzględnieniem możliwości ich współwystępowania. Dotyczy to głównie zaburzeń hiperkinetycznych, zachowania, osobowości borderline czy uzależnienia od substancji psychoaktywnych. Około 50% pacjentów prezentuje objawy ChAD przed 18 rokiem życia, a średni czas od ich pojawienia się do postawienia właściwej diagnozy wynosi 5-10 lat. Nierozpoznane ChAD mogą mieć negatywny wpływ na rozwój kompetencji emocjonalnych, społecznych i poznawczych co istotnie wpływa na funkcjonowanie pacjenta także w życiu dorosłym. Dlatego tak ważne jest aby specjaliści pracujący z dziećmi i młodzieżą byli świadomi odmienność przebiegu klinicznego ChAD i potrafili postawić właściwą diagnozę z uwzględnieniem kontekstu biologicznego, rozwojowego i systemowego.

Altered immune system activity is one of the common pathomechanisms of depressive disorders and cancer. The aim of this study is to evaluate level of selected elements of the kynurenine pathway in groups of depressed and oncological patients. The study included 156 individuals, aged 19-65 years (M = 43.46, SD = 13.99), divided into three groups, namely depressive disorders (DD), oncology patients (OG), and a comparison group of healthy subjects (CG). A sociodemographic questionnaire and the Hamilton Depression Rating Scale (HDRS) were used in the study to assess the intensity of depressive symptoms. Level of TDO2, L-KYN, HK, AA and QA was significantly higher in patients from OG and DD groups than in the comparison group. TDO2 level in the OG group was positively correlated with the severity of depressive symptoms. When the OG and DD groups were analyzed together, level of TDO2, 3-HKYN, AA, QA correlated positively with the severity of depressive symptoms. Thus, kynurenine pathway might play an integral role in the pathogenesis of depression.

Depressive disorders are a growing problem worldwide. They are also characterized by high comorbidity, including from the circle of dermatological diseases. Autoimmune diseases seem to be particularly correlated with depressive comorbidity, raising the question of their possible common pathomechanism. The PubMed database was searched, focusing on results published after 2016. A particular reciprocal correlation of depressive disorders with psoriasis, atopic dermatitis, alopecia areata, impetigo, lupus and systemic scleroderma was found. One possible explanation for the co-occurrence of the above diseases is that the inflammatory theory may be applicable to depression, the various elements of which also apply to autoimmune diseases.

Since the 1950s, there have been rapid developments in psychiatric pharmacotherapy, resulting not only in more effective treatment of patients, but also in improvements in minimizing adverse effects of therapy. Modern third-generation antipsychotics, in addition to antagonism toward D2 receptors, also exhibit partial agonism toward dopamine receptors. Such a mechanism of action is intended to regulate dopaminergic transmission - inhibit (antagonism) it in pathways where it is excessive (excessive transmission in the mesolimbic pathway in psychotic patients, excessive transmission in the tuberoinfundibular pathway in patients with hyperprolactinemia) and stimulate (agonism) it in pathways where it is too low (mesocortical pathway). This has a beneficial effect on both the reduction of adverse symptoms and the negative, affective and cognitive symptoms of patients suffering from schizophrenia. The purpose of this review article is to present the most important clinical aspects of the use of dopamine D2 receptor partial agonists in the treatment of schizophrenia, using brexpiprazole as an example, and to define the profile of patients to whom this drug could be dedicated - based on recent studies.

The Polish standard of treatment with racemic ketamine for patients with depressive disorders was developed by a Working Group appointed by the National Consultant in the field of psychiatry. Despite the wide range of available medications, as many as one-third of depressed patients do not respond to standard antidepressant treatment, raising the need for an ongoing search for new effective and safe therapies. In recent years, the possible role of overactivity of the glutamatergic system in the etiopathogenesis of depression has again attracted the attention of many experts. The possibility of using substances with a modulating effect on the glutamatergic system in the treatment of depressive disorders has been postulated, among others, the long-known anesthetic ketamine, which is a noncompetitive NMDA receptor antagonist. This paper summarizes the results of studies on the efficacy and safety of racemic ketamine (administered intravenously) in the treatment of patients with depressive symptoms in the course of both unipolar and bipolar affective disorder, and, meeting the expectations of many practicing psychiatrists wishing to broaden the range of therapies offered to their patients, presents recommendations on indications, contraindications, precautions and the treatment regimen itself with intravenous ketamine for patients with mood disorders.