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Accumulating evidence indicates systemic biological dysregulations in patients with psychosis that have been conceptualized as the "allostatic load" (AL) index. We aimed to investigate the AL index in 37 subjects at familial high risk of psychosis (FHRP), 42 first-episode psychosis (FEP) patients, 25 acutely relapsed schizophrenia (SCZ-AR) patients and 42 healthy controls (HCs), taking into account psychopathology and cognitive impairment. The AL index was calculated based on 15 biomarkers (cardiovascular markers, anthropometric measures, inflammatory markers, glucose homeostasis parameters, lipids and steroids). Cognition was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The AL index was significantly higher in patients with psychosis and FHR-P individuals compared to HCs. Patients with FEP and FHR-P individuals had similar AL index. Moreover, the AL index was significantly higher in SCZ-AR patients compared to other groups of participants. Higher AL index was associated with more severe general psychopathology and depressive symptoms, lower scores of attention (total score, digit span and digit coding tasks) and semantic fluency, as well as worse general functioning in patients with psychosis. There was a significant negative correlation between the AL index and the scores of attention (total score and digit coding task) in FHR-P individuals. No significant correlations between the AL index and cognition were found in HCs. Our results indicate that biological dysregulations, captured by the AL index, appear already in FHR-P individuals and progress with psychotic exacerbations. Elevated AL index might contribute to cognitive impairments in FHR-P individuals and patients with psychosis.

Schizophrenia is a chronic illness that in the majority of cases begins either in adolescence or early adulthood. It is often perceived as a severe, incurable condition with generally poor prognosis, while patients suffering from it tend to be agitated, aggressive and unpredictable in their behaviors. Growing awareness, along with gradual changes in the approach to the need for multifaceted schizophrenia therapy, as well as considerable progress in pharmacotherapy in recent years have allowed for improving the prognosis for many patients. Because of polymorphic character of the condition, many schizophrenia sub-types are identified by means of classifications of mental disorders, adjusting the criteria and descriptions to most frequently observed clinical scenarios. Clinical descriptions of schizophrenia are based on various psychopathological models, which are often multidimensional and multifactorial. They virtually always take account of the following two dimensions: negative (deficit) and positive (creative) symptoms. Contemporary approach to schizophrenia treatment assumes multidirectional therapeutic intervention aimed at achieving full remission and the patient's return to full psychosocial functioning. Long-term studies indicate that the severity of negative symptoms is the prognostic indicator of the deterioration of social and professional functioning and reduced quality of life. The following paper presents the review of concepts and research devoted to negative symptoms in schizophrenia and their treatment; in the second part, international standards and recommendations of the Polish Psychiatric Association concerning the approach to effective management of negative symptoms in schizophrenia are discussed.

Wykrycie choroby na wczesnych jej etapach jest kluczowe, ze względu na możliwość zastosowania interwencji prowadzącej do zwiększenia sukcesu w zakresie podjętego leczenia medycynie wczesne wykrycie choroby bywa kluczowe, ze względu na możliwość zastosowania interwencji jak najwcześniej, co znacznie zwiększa możliwości sukcesu w leczeniu. Profilaktyka jest adresowana do osób z tzw. grup wysokiego ryzyka. Pierwszy epizod psychozy zwykle jest poprzedzany przez rozmaite trudności w funkcjonowaniu codziennym, które ze względu na ze względu na niespecyficzność, intensywność oraz czas trwania trudno uznać za objawy jednoznacznie spełniające kryteria choroby psychicznej wg międzynarodowych klasyfikacji. Zastosowanie wczesnej interwencji np. oddziaływań psychoterapeutycznych zwłaszcza behawioralno – poznawczych (CBT) na tym etapie przypuszczalnie mogłoby zapobiec rozwojowi psychozy, bądź odroczyć jej początek. Identyfikacja potencjalnych odbiorców takiej interwencji jest jednak trudna, zwłaszcza bez odpowiednich narzędzi diagnostycznych. Metodą, która może być pomocna w codziennej praktyce klinicznej jest Ustrukturyzowany Wywiad do Badania Zespołów Ryzyka Psychozy (Structured Interview For Psychosis-Risk Syndromes – SIPS). Jest to częściowo ustrukturyzowany wywiad posiadający wysoką wartość predykcyjną, trafność oraz rzetelność pomiaru. Celem pracy jest prezentacja tłumaczenia narzędzia aktualnie poddawanego procedurze adaptacji do warunków polskiej populacji, która ostatecznie zweryfikuje jego użyteczność w praktyce klinicznej i badawczej.

Współczesne podejście do leczenia schizofrenii zakłada zastosowanie wielokierunkowej interwencji terapeutycznej koniecznej do uzyskania pełnej remisji objawów i powrotu chorego do pełnego funkcjonowania psychospołecznego. Odpowiednio dobrana i zastosowana farmakoterapia nadal pełni kluczową rolę w terapii chorych na schizofrenię. W poprzednich dekadach (od lat 50. XX wieku) stosowanie leków przeciwpsychotycznych miało na celu głównie opanowanie objawów pozytywnych (agresja, pobudzenie). Kolejne dziesięciolecia (od lat 80.) przyniosły możliwość zastosowania leków nowej generacji o mniejszych działaniach niepożądanych. Niektóre z tych leków okazały się również pomocne w łagodzeniu objawów negatywnych, co dawało niektórym chorym szansę powrotu do normalnego funkcjonowania. Nadal jednak uważa się, że pacjenci chorujący na schizofrenię z dominującymi lub przetrwałymi objawami negatywnymi stanowią największe wyzwanie terapeutyczne. Charakteryzują się gorszym przebiegiem, rokowaniem i odpowiedzią na leczenie. Ciągle potrzeba nowych, bardziej skutecznych, celowanych na te objawy interwencji terapeutycznych. Niniejsza praca przedstawia międzynarodowe standardy i rekomendacje Polskiego Towarzystwa Psychiatrycznego w podejściu do skutecznego leczenia objawów negatywnych w przebiegu schizofrenii.

In the article, the recommendations of the Polish Psychiatric Association regarding pharmacological treatment of women with bipolar disorder during pregnancy and postpartum period were presented. The issue pertains to every twentieth woman wanting to get pregnant. Before planned pregnancy, it is advisable to obtain a several-month stabilization of psychiatric state, to establish treatment with one mood-stabilizing drug (except for valproate and carbamazepine) or gradual discontinuation of drugs in case of mild course of illness and lack of recurrences in recent two years. In the first trimester of pregnancy, the dose of the mood-stabilizing drug should be reduced (lithium carbonate to 500 mg/day). Depression during pregnancy can be treated with quetiapine or lamotrigine or with antidepressant drug added to a mood-stabilizing drug. Atypical antipsychotics drugs with mood-stabilizing properties can be used in case of (hypo) manic or mixed states. Following the delivery, it is advisable to introduce a moodstabilizing drug as soon as possible to prevent postpartum psychiatric disturbances. In the treatment of postpartum depression, quetiapine can be used or an antidepressant drug added to a mood-stabilizer. Considering breastfeeding, it should be remembered that the infant/maternal ratio of serum drug concentration is low for valproate, olanzapine, quetiapine, sertraline and paroxetine, and high for lithium and lamotrigine. In the case of postpartum psychosis, a hospitalization and antipsychotic treatment are needed.

Cel pracyMuzyka w życiu każdego, zwłaszcza młodego człowieka, odgrywa bardzo ważną rolę w odbiorze emocjonalnym rzeczywistości. Celem pracy było określenie znaczenia pośredniczącej roli nastroju we wpływie muzyki na odbiór emocjonalny materiału obrazowego wśród adolescentów.MetodaW badaniu eksperymentalnym uczestniczyło 388 adolescentów (13 - 15 lat). Wykorzystano pozawerbalne narzędzie do badania emocji i uwagi (The International Affective Picture System), Kartę Nastroju i Kwestionariusz dla Młodzieży. Ponadto w eksperymencie zaprezentowano utwory reprezentujące tzw. środek trzech gatunków muzycznych (hip-hop, pop i metal).WynikiWyniki wskazały, że aktualny nastrój nastolatka wyznaczał odbiór emocjonalny zdjęć. Dobry nastrój wiązał się z obniżeniem pobudzenia emocjonalnego podczas odbioru neutralnych zdjęć (po wysłuchaniu muzyki metalowej i pop) oraz wywoływał większą przyjemność z oglądania pozytywnych i neutralnych zdjęć. Oglądanie negatywnych zdjęć przy średnim i dobrym nastroju wywoływało mniejszą przyjemność niż oglądanie ich w złym nastroju. Muzyka hip-hop i zły nastrój łączyły się z większym pobudzeniem emocjonalnym przy neutralnych zdjęciach. Żaden z wyników nie wykazał zależności pomiędzy słuchaniem przez młodzież (przy gorszym nastroju) muzyki z gatunku metal czy hip-hop a pozytywnym postrzeganiem obrazów.WnioskiPrzeprowadzone badania były próbą określenia związku pomiędzy trudnymi do uchwycenia czynnikami: nastrojem, muzyką i odbiorem emocjonalnym obrazów przez młodzież w okresie adolescencji. Mimo trudności metodologicznych zależność ta została ustalona.

W artykule przedstawiono rekomendacje Polskiego Towarzystwa Psychiatrycznego dotyczące postępowania w przypadku utraty ciąży oraz niepowodzeń leczeniem niepłodności metodą in vitro. Z punktu widzenia psychologicznego utrata ciąży lub śmierć okołoporodowa jest jednym z najbardziej stresujących wydarzeń życiowych człowieka niosących za sobą ryzyko wystąpienia zaburzeń afektywnych, lękowych lub objawów zespół stresu pourazowego. Psychologowie, lekarze specjaliści i pozostały personel medyczny powinni zapewniać opiekę zintegrowaną a jednocześnie zindywidualizowaną, opartą na szacunku, empatii i kompetencji. Niezbędne etapy wsparcia kierowanego wobec pacjentki doświadczającej utraty ciąży obejmują: 1) wyczerpujące wsparcie informacyjne ze strony lekarza prowadzącego dotyczące stanu zdrowia, ewentualnych przyczyn śmierci płodu, sposobu postępowania oraz etapów indukcji porodu obumarłego płodu/ terminacji ciąży/zabiegu; 2) możliwość konsultacji psychologicznej na każdym etapie oraz 3) wyczerpujące informacje na temat obowiązującego stanu prawnego (zabezpieczenia społecznego oraz prawa pracy). Kolejne niepowodzenia podczas zapłodnienia in vitro mogą wywoływać emocjonalne konsekwencje podobne do tych, które obserwuje się po poronieniu. Frustracja trwająca zbyt długo może sprzyjać wystąpieniu objawów depresji i nasilaniu się patologicznego lęku. Przedstawiono podstawowe rekomendacje dotyczące psychoterapii i farmakoterapii w przypadku utraty ciąży czy niepowodzeń w leczeniu niepłodności metodą in vitro.

Leczenie zaburzeń depresyjnych u kobiet w wieku rozrodczym wymaga szczególnej uwagi ze względu na prawdopodobieństwo planowanej lub nieplanowanej ciąży oraz specyfikę zaburzeń nastroju związanych z okresem perinatalnym. Lekarz prowadzący leczenie depresji u kobiety w wieku rozrodczym powinien otwarcie rozmawiać z pacjentką o jej seksualności i możliwości zajścia w ciążę. Psychiatra może spotkać się z różnego rodzaju problemami jak: decyzja terapeutyczna u kobiety, która choruje na nawracającą depresję i zażywa w celach profilaktycznych lub podtrzymujących leki przeciwdepresyjne i zachodzi bądź planuje zajście w ciążę, postępowanie w przypadku wystąpienia epizodu depresyjnego u kobiety będącej już w ciąży, postępowanie w przypadku wystąpienia depresji poporodowej, leczenie przeciwdepresyjne w kontekście karmienia piersią. Rekomendacje zostały przygotowane przez grupę roboczą Polskiego Towarzystwa Psychiatrycznego w oparciu o najnowsze światowe standardy oraz opinie i konsensus ekspertów. Opisano ogólne zasady postępowania terapeutycznego z uwzględnieniem danych na temat bezpieczeństwa leków przeciwdepresyjnych.

Recent evidence indicates that the occurrence of psychiatric disorders in patients is linked to a local "sterile" inflammation of brain or due to a systemic inflammation process that affects the central nervous system. This is supported by the observation that in peripheral blood of psychotic patients are detectable several mediators and markers of inflammation as well as clinical data on correlations between systemic chronic inflammatory processes and psychiatric disorders. This may explain why some reported anti-inflammatory treatment strategies have beneficial effects on ameliorating psychotic events. In this review we will present a concept that aberrant purinergic signaling and increases in extracellular level of adenosine triphosphate (ATP) in the brain parenchyma may lead to activation of Nlrp3 inflammasome in microglia cells and as a consequence microglia released danger associated molecular pattern (DAMP) proteins activate complement cascade (ComC) in mannan binding lectin (MBL) - dependent manner. Activation of ATP-Nlrp3 inflammasome-ComC axis may also orchestrate trafficking of stem cells released from bone marrow into peripheral blood observed in psychotic patients. Based on this, the ATP-Nlrp3 inflammasome-ComC axis may become a target for new therapeutic approaches, which justifies the development and clinical application of efficient anti-inflammatory treatment strategies targeting this axis in psychiatry.

Background The aim of this study was to analyse the relationship between thyroid function and the diagnosis of metabolic syndrome (MS) and its components in schizophrenia patients to improve the overall clinical care. Methods We examined 106 schizophrenia patients (64 females and 42 males, aged 18–69 years). Sociodemographic, psychometric, anthropometric, and biochemical measures; eating habits, and the use of selected drugs were assessed during the enrolment and after 8 to 10 weeks of observation. Results An association between hyperglycaemia and hypothyroidism was observed. Compared to females, adverse metabolic profiles in male subjects were more common after follow-up, particularly in the presence of hypothyroidism. There was a significant reduction in hip circumference, blood glucose, and systolic blood pressure values after the follow-up period. Conclusions Based on hypothyroidism incidence in the studied sample and the association between thyroid-stimulating hormone (TSH) values and MS criteria, we suggest regular assessment of TSH levels in schizophrenia patients with a diagnosis of MS. Programs of MS and thyroid dysfunction prevention and treatment in schizophrenia patients should be differentiated according to gender. An indirect conclusion is that even a minute element such as conducting the interview about lifestyle may trigger patients to change their habits.

Cognitive deficits are widely observed in patients with psychosis and represent one of most important determinants of functional outcomes. It has been shown that patients with psychosis prefer maladaptive coping strategies over active coping styles. However, it remains unknown whether cognitive impairments are related to coping styles in psychotic disorders. Therefore, the aim of this study was to assess whether cognitive deficits observed in patients with first-episode psychosis (FEP) might impact the use of specific coping strategies. We recruited 40 FEP patients and 35 healthy controls. In our study, FEP patients were more likely to use maladaptive coping styles after adjustment for education level and medication effects. The use of maladaptive coping strategies was associated with greater impairments of visuospatial/constructional abilities and language skills in FEP patients. In addition, lower odds of using adaptive coping were related to higher levels of depressive symptoms in the group of patients. Adaptive coping was associated with better global cognitive performance in healthy controls. Our results indicate that cognitive impairments, especially worse performance of visuospatial/constructional abilities and language skills, might be related to the preference of maladaptive coping strategies. Lower odds of using adaptive coping styles might be associated with more severe depressive symptomatology. This study was funded from science budget resources granted for the years 2016-2019 (the Iuventus Plus grant awarded by the Ministry of Science and Higher Education, grant number: IP2015 052474). Scopus

Adverse childhood experiences (ACEs) might be related to cognitive impairments observed in schizophrenia spectrum disorders (SSD). However, it remains unknown what aspects of ACEs are associated with cognitive impairments in SSD. Therefore, we aimed to investigate the association between various characteristics of ACEs (age at first exposure, severity, and multiplicity) and cognition in SSD and healthy controls (HCs). We enrolled 127 individuals with SSD and 56 HCs. Cognitive performance was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The Childhood Experience of Care and Abuse Questionnaire was administered to record a history of ACEs. The following characteristics of ACEs were analyzed: multiplicity, severity, and age at first exposure. Individuals with SSD had significantly lower scores on all RBANS domains. Multiplicity and severity of ACEs were significantly higher in patients with SSD compared to HCs. In both groups, greater multiplicity of ACEs was associated with lower scores of global cognition and delayed memory. Additionally, in subjects with SSD, greater multiplicity and younger age at first exposure were associated with lower scores of attention. The present findings indicate that greater multiplicity and younger age at first exposure are the most important aspects of ACEs contributing to cognitive impairments observed in SSD. Moreover, ACEs might exert differential impact on cognition in SSD and HCs.

Early-life psychosocial stress primes a number of health risk behaviors, and contributes to the development of various mental and somatic disorders in adulthood. It has been reported that adverse childhood experiences (ACEs) and low socioeconomic status (SES) might be associated with allostatic load (AL) in adulthood. In turn, elevated AL index has been found to predict a number of unfavorable health outcomes. Therefore, we aimed to perform a systematic review of studies investigating the association of ACEs and childhood SES with AL in adult populations. Independent online searches covered the publication period up to 20th Jun 2021. A total of 27 studies were included in qualitative synthesis. The majority of eligible studies showed that ACEs (14 out of 19 studies recording ACEs, 73.7%) and low childhood SES (11 out of 12 studies recording childhood SES, 91.7%) are associated with elevated AL in adults. However, several processes were found to mediate or moderate this association. These include educational attainments, social support, health behaviors, adult stress, post-traumatic stress disorder, coping strategies and aging. Moreover, a substantial methodological heterogeneity of approaches to calculating the AL index was observed. Apart from reports from overlapping samples, none of eligible studies used the same set of biomarkers. Findings from this systematic review imply that early-life psychosocial stress might have a lasting impact on biological dysregulations captured by the AL index. Future studies need to explore whether the association between early-life stress and the AL index accounts for the development of specific health outcomes.

There is a paucity of reports examining the relationship between the integrity of the corpus callosum (CC) and different aspects of cognitive functioning in patients with first-episode (FES) and chronic schizophrenia (CS) simultaneously; furthermore, what results exist are inconclusive. We used diffusion tensor imaging tractography to investigate differences in integrity in five regions of the CC between FES, CS, and healthy controls (HC). Additionally, we analyzed correlations between these regions’ integrity and working memory, planning, and speed of processing. Eighteen patients with FES, 55 patients with CS, and 30 HC took part in the study. We assessed cognitive functions with four tasks from Measurement and Treatment Research to Improve Cognition in Schizophrenia. Patients with CS showed lower fractional anisotropy (FA) in Region 5 (statistical trend) and higher mean diffusivity (MD) in Regions 4 and 5 than HC, and patients with FES had higher MD in Region 3 (statistical trend) than HC. Both clinical groups performed worse on working memory and speed of processing tasks than HC, and patients with CS scored worse than HC on independent planning, and worse than FES and HC on dependent planning. Moreover, in patients with CS, MD in Region 3 was correlated with verbal working memory. Our results suggest that patients with FES and CS are characterized by impaired integrity of the middle and posterior CC, respectively. We confirmed that both clinical groups have cognitive impairments. Moreover, the integrity of the middle CC may influence planning in patients with CS.

This narrative review presents recent developments in virtual reality (VR)-based interventions for alcohol use disorders (AUDs). The latest advances in mental healthcare hail an imminent cyber revolution, ushering in novel treatment options, with immersive virtual technology at the very forefront of expected change. With an aim to (a) provide a background on VR use in mental healthcare of AUD patients, (b) summarize existing evidence on conventional approaches to the treatment of AUDs and a trending paradigm shift towards VR applications in their management, and (c) describe key issues and future directions in research on craving assessment and VR cue-induced therapy in AUDs, a search for experimental and meta-analytic evidence was performed in six databases: PubMed and EBSCO (Medline, ERIC, PsychINFO, Academic Search Ultimate, and Health Source: Nursing/Academic Edition). Pooled results were screened for eligibility, and relevant papers were selected for inclusion. The analysis revealed VR’s promising effects in the treatment of AUDs. Its remarkable potential to simulate cues underlying subsequent addictive behaviors makes its application in the assessment and treatment of AUDs an attractive alternative to researchers and clinicians alike. Nevertheless, more evidence is needed before virtual reality cue exposure therapy (VR-CET) can become a clinical standard of care.

Justyna Kasznia,1 Aleksandra Pytel,2 Bartłomiej Stańczykiewicz,2 Jerzy Samochowiec,3 Katarzyna Waszczuk,3 Małgorzata Kulik,4 Agnieszka Cyran,5 Błażej Misiak5 1Inpatient Psychiatric Unit, Municipal General Hospital, Ostrów Wielkopolski, Poland; 2Department of Nervous System Diseases, Wroclaw Medical University, Wroclaw, Poland; 3Department of Psychiatry, Pomeranian Medical University, Szczecin, Poland; 4Institute of Psychology, University of Szczecin, Szczecin, Poland; 5Department of Psychiatry, Division of Consultation Psychiatry and Neuroscience, Wroclaw Medical University, Wroclaw, PolandCorrespondence: Błażej MisiakDepartment of Psychiatry, Division of Consultation Psychiatry and Neuroscience, Wroclaw Medical University, Pasteura 10 Street, Wroclaw, 50-367, PolandTel +48 71 784 16 30Email blazej.misiak@umed.wroc.plPurpose: Several studies have shown that individuals with schizophrenia-spectrum disorders (SSD) employ ineffective coping styles. However, it remains unknown whether a history of adverse childhood experiences (AC Es), associated with a risk of SSD, contributes to these observations. Therefore, in this study, we aimed to investigate whether exposure to ACEs is associated with coping styles in subjects with SSD.Patients and Methods: We recruited 127 inpatients with SSD and 56 healthy controls. Coping styles and ACEs were recorded using self-reports.Results: Individuals with SSD had significantly higher use of using avoidance coping. A history of parental antipathy, physical and sexual abuse was significantly more frequent in subjects with SSD compared to controls. Subjects with SSD had significantly higher multiplicity and severity of ACEs. Individuals with SSD and a history of parental loss had significantly higher use of avoidance coping compared to controls with and without a history of parental loss. Other characteristics of ACEs (age at first exposure, severity and multiplicity) were not associated with using specific coping strategies.Conclusion: These findings imply that higher use of using avoidance coping by individuals with SSD might be related to a history of parental loss.Keywords: stress, psychosis, psychotic disorder, trauma, maltreatment

In recent years, interest has grown in measuring executive function in schizophrenia with ecological and virtual reality (VR) tools. However, there is a lack of critical analysis comparing those tools with traditional ones. This paper aims to characterize executive dysfunction in schizophrenia by comparing ecological and virtual reality assessments with traditional tools, and to describe the neurobiological and psychopathological correlates. The analysis revealed that ecological and VR tests have higher levels of verisimilitude and similar levels of veridicality compared to traditional tools. Both negative symptoms and disorganization correlate significantly with executive dysfunction as measured by traditional tools, but their relationships with measures based on ecological and VR methods are still unclear. Although there is much research on brain correlates of executive impairments in schizophrenia with traditional tools, it is uncertain if these results will be confirmed with the use of ecological and VR tools. In the diagnosis of executive dysfunction, it is important to use a variety of neuropsychological methods—especially those with confirmed ecological validity—to properly recognize the underlying characteristics of the observed deficits and to implement effective forms of therapy.

Deficit syndrome (DS) is a subtype of schizophrenia characterized by primary persistent negative symptoms. The corpus callosum (CC) appears to be related to psychopathology in schizophrenia. This study assessed white matter integrity in the CC using diffusion tensor imaging (DTI) in deficit and non-deficit schizophrenia (NDS) patients. We also investigated the psychopathological dimensions of schizophrenia and their relationship to CC integrity. Fifteen DS patients, 40 NDS patients, and 30 healthy controls (HC) underwent psychiatric evaluation and neuroimaging. We divided the CC into five regions and assessed their fractional anisotropy (FA) and mean diffusivity (MD). Psychopathology was assessed with the Positive and Negative Syndrome Scale. DS patients had lower FA than NDS patients and HC, and higher MD in Region 5 of the CC than did HC. NDS patients had higher MD in Region 4 of the CC. The patient groups differed in terms of negative symptoms. After differentiating clinical groups and HC, no significant correlations were observed between DTI measures and psychopathological symptoms. Our results suggest that DS and NDS are characterized by minor impairments of the posterior CC. We confirmed that DS patients have greater negative psychopathology than NDS patients. Our results are preliminary, and further studies are needed.

Schizophrenia is a severe and disabling mental illness whose etiology still remains unclear. The available literature indicates that there exist white matter (WM) abnormalities in people with schizophrenia spectrum disorders. Recent developments in modern neuroimaging methods have enabled the identification of the structure, morphology, and function of the underlying WM fibers in vivo. The purpose of this paper is to review the existing evidence about WM abnormalities in individuals at ultra-high risk of psychosis (UHR) with the use of diffusion tensor imaging (DTI) available from the National Center for Biotechnology Information PubMed (Medline) and Health Source: Nursing/Academic Edition databases. Of 358 relevant articles identified, 25 papers published in the years 2008–2020 were ultimately included in the review. Most of them supported the presence of subtle aberrations in WM in UHR individuals, especially in the superior longitudinal fasciculus (SLF), the inferior longitudinal fasciculus (ILF), and the inferior fronto-occipital fasciculus (IFOF). These alterations may therefore be considered a promising neurobiological marker for the risk of psychosis. However, due to methodological discrepancies and the relative scarcity of evidence, further investigation is called for, especially into connectome analysis in UHR patients.

Common variations of the FKBP5 gene are implicated in psychotic disorders, by modulating the hypothalamic–pituitary–adrenal axis reactivity to stress. It has been demonstrated that some of them might moderate the effects of childhood trauma on psychosis proneness. However, these associations have not been investigated with respect to traumatic life events (TLEs). Therefore, we aimed to explore whether the FKBP5 polymorphisms moderate the effects of TLEs on the level of psychotic-like experiences (PLEs). A total of 535 non-clinical adults were approached for participation, and genotyping of six FKBP5 polymorphisms (rs3800373, rs9470080, rs4713902, rs737054, rs1360780 and rs9296158) was performed. The Prodromal Questionnaire-16 (PQ-16) and the Traumatic Events Checklist (TEC) were administered to assess PLEs and TLEs, respectively. Among the rs1360780 CC homozygotes, a history of physical abuse was associated with significantly higher PQ-16 scores. This difference was not significant in the rs1360780 T allele carriers. Similarly, a history of physical abuse was associated with significantly higher PQ-16 scores in the rs9296158 GG homozygotes but not in the rs9296158 A allele carriers. Finally, emotional neglect was related to significantly higher PQ-16 scores in the rs737054 T allele carriers but not in the rs737054 CC homozygotes. The present study indicates that variation in the FKBP5 gene might moderate the effects of lifetime traumatic events on psychosis proneness.

Impairments in cognitive functions are one of the main features of schizophrenia. A variety of factors can influence the extent of cognitive deficits. In our study, we examined the severity of cognitive deficits at different stages of the disease and the relationship between psychopathological symptoms and cognitive functions. We recruited 32 patients with first-episode psychosis (FEP), 70 with chronic schizophrenia (CS), and 39 healthy controls (HC). Psychopathological symptoms were evaluated with the Positive and Negative Syndrome Scale (PANSS) and cognitive functions were measured with the MATRICS Cognitive Consensus Battery (MCCB). Cognitive deficits were present in both FEP and CS participants. CS individuals had lower overall scores and poorer working memory; however, clinical variables appeared to play a significant role in these scores. In FEP, disorganization correlated negatively with verbal and visual learning and memory, social cognition, and overall score; negative symptoms negatively correlated with social cognition. In CS participants, disorganization correlated negatively with speed of processing, reasoning, problem solving, and overall score; negative symptoms were negatively correlated with speed of processing, visual learning, memory, and overall score; positive symptoms were negatively correlated with reasoning and problem solving. Our findings indicate that psychopathological symptoms have a significant impact on cognitive functions in FEP and CS patients.

Dysregulated cortisol responses and glucose metabolism have been reported in psychosis. We performed a random-effects meta-analysis of cortisol responses in first-episode psychosis (FEP) and psychosis risk states, taking into consideration glucose metabolism. A total of 47 studies were included. Unstimulated blood cortisol levels were significantly higher (g = 0.48, 95 %CI: 0.25–0.70, p < 0.001) in FEP, but not in psychosis risk states (g = 0.39, 95 %CI: −0.42–1.21, p = 0.342), compared to controls. Cortisol awakening response (CAR) was attenuated in FEP (g = −0.40, 95 %CI: −0.68 - −0.12, p = 0.006), but not in psychosis risk states (p = 0.433). Glucose and insulin levels were positively correlated with unstimulated blood cortisol levels in FEP. Our meta-analysis supports previous findings of elevated blood cortisol levels and attenuated CAR in FEP. Future research should focus on identifying the common denominators for alterations in stress hormones and glucose metabolism. published

There is accumulating evidence that individuals with schizophrenia show altered levels of thyroid hormones. However, a qualitative and quantitative synthesis of findings in this field has not been performed so far. Therefore, we aimed to perform a systematic review and meta-analysis of studies investigating the levels of thyroid-stimulating hormone (TSH), free thyroxine (fT4), total thyroxine (tT4), free triiodothyronine (fT3) and total triiodothyronine (tT3) in multiple-episode schizophrenia (MES) and first-episode psychosis (FEP). Electronic databases were searched from their inception until 30th May 2020 by two independent reviewers. Random-effects meta-analyses and meta-regression analyses were performed. Altogether, 19 studies were included. Persons with FEP had significantly lower TSH levels (5 studies, g = −0.26, 95%CI: −0.47 to −0.06, p = 0.013, I2 = 21.3%), higher fT4 levels (3 studies, g = 0.58, 95%CI: 0.15–1.01, p = 0.008, I2 = 64.6%) and lower tT3 levels (2 studies, g = −0.60, 95%CI: −0.82 to −0.37, p < 0.001, I2 = 0%) compared to controls. Elevated TSH levels were found in persons with MES (13 studies, g = 0.20, 95%CI: 0.02–0.39, p = 0.031, I2 = 50.0%). Our findings imply that the levels of TSH might be decreased in persons with FEP and increased in those with MES. Other alterations need to be confirmed by additional studies. These findings imply the need to monitor the levels of TSH and thyroid hormones from the onset of psychosis.

Aims: Recent studies have provided evidence that interactions between variation in dopaminergic genes and stressful experiences might impact risk of psychosis. However, it remains unknown whether these interactions impact the development of subclinical symptoms, including psychotic‐like experiences (PLEs). In this study, we aimed to test the effects of interactions between variation in dopaminergic genes and traumatic life events (TLEs) on a severity of PLEs. Methods: We assessed TLEs, cognitive biases, PLEs as well as the catechol‐O‐methyltransferase (COMT) rs4680 and the dopamine D2 receptor (DRD2) rs6277 gene polymorphisms in 445 university students at three urban areas. Results: There was a significant effect of the interaction between the COMT rs4680 and a history of any type of TLEs on a severity of PLEs. Among the COMT rs4680 Met allele carriers, a severity of PLEs was higher in individuals with a history of any type of TLEs. Further stratification of the sample revealed that this effect appears only in the group of participants with a high level of cognitive biases. The DRD2 rs6277 C allele was independently associated with a higher level of PLEs. Conclusions: Our results indicate that decreased dopamine catabolism related to the COMT gene polymorphism might increase psychosis proneness in individuals with a history of TLEs and high levels of cognitive biases. Variation in the DRD2 gene might exert independent effects on psychosis proneness. These findings imply that there are various levels of complexity in the models of interactions between genetic and environmental factors explaining the mechanisms underlying psychosis proneness.

Background The COVID-19 pandemic caused an unprecedented worldwide crisis affecting several sectors, including health, social care, economy and society at large. The World Health Organisation has emphasized that mental health care should be considered as one of the core sectors within the overall COVID-19 health response. By March 2020, recommendations for the organization of mental health services across Europe have been developed by several national and international mental health professional associations. Methods The European Psychiatric Association (EPA) surveyed a large European sample of psychiatrists, namely the EPA Ambassadors, on their clinical experience of the impact of COVID-19 pandemic on the treatment of psychiatric patients during the month of April 2020 in order to: a) identify and report the views and experiences of European psychiatrists; and b) represent and share these results with mental health policy makers at European level. Based on the recommendations issued by national psychiatric associations and on the results of our survey, we identified important organisational aspects of mental health care during the peak of the first wave of the COVID-19. Results While most of the recommendations followed the same principles, significant differences between countries emerged in service delivery, mainly relating to referrals to outpatients and for inpatient admission, assessments and treatment for people with mental disorders. Compared to previous months, the mean number of patients treated by psychiatrists in outpatient settings halved in April 2020. In the same period, the number of mentally ill patients tested for, or developing, COVID-19 was low. In most of countries, traditional face-to-face visits were replaced by online remote consultations. Conclusions Based on our findings we recommend: 1) to implement professional guidelines into practice and harmonize psychiatric clinical practice across Europe; 2) to monitor the treatment outcomes of patients with COVID-19 and pre-existing mental disorders; 3) to keep psychiatric services active by using all available options (for example telepsychiatry); 4) to increase communication and cooperation between different health care providers., European Psychiatric Association, The work was funded by the European Psychiatric Association.

Due to poor eating habits, insufficient physical activity, and nicotine use, schizophrenia patients are at increased risk of lifestyle diseases. Factors contributing to unhealthy behaviors include lower socioeconomic status and level of education as well as social isolation. Schizophrenia manifestations such as amotivation, apathy, and cognitive deficits can further hinder development of proper health habits. The aim of this study was to assess the possible association between lifestyle-related choices and schizophrenia symptoms severity. This observational study enrolled 106 patients with schizophrenia (42 Males/64 Females), 18–69 years (mean: 41.89 ± 9.7 years). Mean duration of schizophrenia was 14.61 ± 9.7 years. Multiple significant correlations were found between patients’ lifestyle and their biochemical laboratory parameters (lipid profile and fasting glucose). Most importantly, a significant link emerged between presented habits and schizophrenia symptom severity. There were also significant gender differences in the intake of sweets and sweet beverages. Quite unexpectedly, a behavioral shift towards more healthy lifestyle choices was observed after completion of questionnaires on lifestyle and health habits. There are clear benefits to systematic provision of educational interventions concerning physical activity and proper eating habits to schizophrenia patients. These simple preventive measures could significantly improve both mental and physical health outcomes in schizophrenia patient populations.

Patients with schizophrenia spectrum disorders have a reduced life expectancy, which is largely the consequence of a high co-occurrence of cardiovascular diseases. To date, several intrinsic and environmental factors underlying this phenomenon have been found. However, the association with psychosocial stress has not been extensively addressed. In this study, we tested the relationship between a history of adverse childhood experiences (ACEs), lifetime stressors, perceived stress and metabolic parameters in patients with schizophrenia spectrum disorders and in healthy controls. The participants included 85 inpatients with schizophrenia spectrum disorders and 56 healthy controls. Serum levels of glucose, insulin, low- and high-density lipoproteins (LDL and HDL), triglycerides, total cholesterol and high-sensitivity C-reactive protein (hsCRP) were determined. After adjustment for potential confounding factors, patients had significantly higher levels of glucose (F = 4.856, p = 0.030), triglycerides (F = 4.720, p = 0.032) and hsCRP (F = 7.499, p = 0.007) as well as significantly lower levels of HDL (F = 5.300, p = 0.023) compared to healthy controls. There were also significant effects of interactions between diagnosis and a history of ACEs on the levels of insulin (F = 4.497, p = 0.036) and homeostatic model assessment of insulin resistance (HOMA-IR) (F = 3.987, p = 0.048). More specifically, the levels of insulin and HOMA-IR were significantly higher in the subgroup of patients with schizophrenia spectrum disorders and a positive history of ACEs compared to other subgroups of participants. No significant associations between lifetime stressors and perceived stress with metabolic parameters were found. Our findings indicate that a history of ACEs might be associated with insulin resistance in patients with schizophrenia spectrum disorders. Therapeutic strategies targeting early-life stress should be considered with early interventions that aim to manage cardiometabolic comorbidity in patients with schizophrenia spectrum disorders.

© The Author(s), 2020. Published by Cambridge University Press on behalf of the European Psychiatric Association. This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited., Background: Compulsory admission procedures of patients with mental disorders vary between countries in Europe. The Ethics Committee of the European Psychiatric Association (EPA) launched a survey on involuntary admission procedures of patients with mental disorders in 40 countries to gather information from all National Psychiatric Associations that are members of the EPA to develop recommendations for improving involuntary admission processes and promote voluntary care. Methods: The survey focused on legislation of involuntary admissions and key actors involved in the admission procedure as well as most common reasons for involuntary admissions. Results: We analyzed the survey categorical data in themes, which highlight that both medical and legal actors are involved in involuntary admission procedures. Conclusions: We conclude that legal reasons for compulsory admission should be reworded in order to remove stigmatization of the patient, that raising awareness about involuntary admission procedures and patient rights with both patients and family advocacy groups is paramount, that communication about procedures should be widely available in lay-language for the general population, and that training sessions and guidance should be available for legal and medical practitioners. Finally, people working in the field need to be constantly aware about the ethical challenges surrounding compulsory admissions.

Despite the well-established roles of B-vitamins and their deficiencies in health and disease, there is growing evidence indicating a key role of those nutrients in functions of the central nervous system and in psychopathology. Clinical data indicate the substantial role of B-vitamins in various psychiatric disorders, including major depression, bipolar disorder, schizophrenia, autism, and dementia, including Alzheimer's and Parkinson's diseases. As enzymatic cofactors, B-vitamins are involved in many physiological processes such as the metabolism of glucose, fatty acids and amino acids, metabolism of tryptophan in the kynurenine pathway, homocysteine metabolism, synthesis and metabolism of various neurotransmitters and neurohormones including serotonin, dopamine, adrenaline, acetylcholine, GABA, glutamate, D-serine, glycine, histamine and melatonin. Those vitamins are highly involved in brain energetic metabolism and respiration at the cellular level. They have a broad range of anti-inflammatory, immunomodulatory, antioxidant and neuroprotective properties. Furthermore, some of those vitamins are involved in the regulation of permeability of the intestinal and blood-brain barriers. Despite the fact that a substantial amount of the above vitamins is acquired from various dietary sources, deficiencies are not uncommon, and it is estimated that micronutrient deficiencies affect about two billion people worldwide. The majority of gut-resident microbes and the broad range of bacteria available in fermented food, express genetic machinery enabling the synthesis and metabolism of B-vitamins and, consequently, intestinal microbiota and fermented food rich in probiotic bacteria are essential sources of B-vitamins for humans. All in all, there is growing evidence that intestinal bacteria-derived vitamins play a significant role in physiology and that dysregulation of the "microbiota-vitamins frontier" is related to various disorders. In this review, we will discuss the role of vitamins in mental health and explore the perspectives and potential of how gut microbiota-derived vitamins could contribute to mental health and psychiatric treatment.

Previous studies have reported on the relationship between gut microbiota and major depressive disorder (MDD). However, there remain gaps in literature concerning the role of the intestinal barrier and microflora in the pathogenesis of depression. This study analyzes the potential causative relationship between gut microbiota and inflammatory and gut integrity markers and clinical symptoms in inpatients with depressive episodes. Sixteen inpatients (50% females) being treated with escitalopram (5–20 mg daily) in standardized conditions were included in the study. The composition of fecal microbiota was evaluated at baseline and endpoint using 16S rRNA sequencing. A significant correlation between depression severity was found, as measured with HDRS24 (Hamilton Depression Rating Scale-24 item), and the following abundance in bacteria: positive correlation with Paraprevotella (r = 0.80, q = 0.012), strong, negative correlations with Clostridiales (r = −0.70, q = 0.016), Clostridia (r = −0.71, q = 0.026), Firmicutes (r = −0.67. q = 0.032), and the RF32 order (r = −0.70, p = 0.016) in the Alphaproteobacteria (r = −0.66, q = 0.031). After six weeks of treatment, clinical outcomes were found to have a negative correlation with levels of plasma intestinal fatty acid-binding protein (IFABP) at the beginning of the study. Still they had a positive correlation with changes in fecal calprotectin during hospitalization. In conclusion, gut microbiota was associated with the severity of depressive symptoms. However, these findings do not serve as predictors of symptomatic improvement during antidepressant treatment in inpatient treatment for MDD. In turn, intestinal integrity and inflammation markers were associated with the response to treatment of patients with MDD and symptom severity. Additional studies are needed to confirm and extend these findings.

Diffusion tensor imaging (DTI) is an imaging technique that uses magnetic resonance. It measures the diffusion of water molecules in tissues, which can occur either without restriction (i.e., in an isotropic manner) or limited by some obstacles, such as cell membranes (i.e., in an anisotropic manner). Diffusion is most often measured in terms of, inter alia, fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD). DTI allows us to reconstruct, visualize, and evaluate certain qualities of white matter. To date, many studies have sought to associate various changes in the distribution of diffusion within the brain with mental diseases and disorders. A better understanding of white matter integrity disorders can help us recognize the causes of diseases, as well as help create objective methods of psychiatric diagnosis, identify biomarkers of mental illness, and improve pharmacotherapy. The aim of this work is to present the characteristics of DTI as well as current research on its use in schizophrenia, affective disorders, and other mental disorders.

Progress in medical science has allowed the discovery of many factors affecting the pathogenesis of bipolar disorder, and among the most recent research directions are found regenerative and inflammatory processes. The role of regenerative processes remains particularly poorly explored, but available data encourage further research, which may explain the pathogenesis of bipolar disorder (BD). The aim of this study was to evaluate the mobilization of stem cells into peripheral blood, in patients with bipolar disorder during stable phase, not treated with lithium salts. The study included 30 unrelated individuals with the diagnosis of bipolar disorder, with disease duration of at least 10 years, not treated with lithium salts for at least five years prior to the study. The control group consisted of 30 healthy subjects, matched for age, sex, body mass index (BMI), origin, socio-demographic factors and nicotine use. Blood samples underwent cytometric analyses to assess concentrations of: Very Small Embryonic Like (VSEL) CD34+, VSEL AC133+, HSC CD34+, HSC AC133+. There were no significant differences in stem cell levels between patients with BD and healthy controls. However, the level of VSEL cells AC133 + was significantly higher in type I BD patients compared to healthy controls. Our results indicate a disturbance in regenerative processes in patients with bipolar disorder.

It has been proposed that type 2 diabetes and schizophrenia-spectrum disorders share overlapping genetic backgrounds. Therefore, we aimed to perform a systematic review and meta-analysis of studies comparing fasting levels of glucose and insulin, the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), glucose levels during the oral glucose tolerance test (OGTT) and the levels of glycated hemoglobin (HbA1c) in unaffected first-degree relatives of patients with schizophrenia and controls. Online searches covered the publication period from database inception until May 8th 2020. Meta-analyses were performed using random-effects models with Hedges' g as the effect size estimate. Out of 2556 records identified, 12 studies representing 672 relatives of schizophrenia patients and 6446 controls were found to be eligible. There were no significant differences in fasting levels of glucose (g = 0.54, 95%CI = -0.26 to 1.35, p = 0.188) and insulin (g = 0.07, 95%CI = -0.14 to 0.29, p = 0.491), HOMA-IR (g = 0.12, 95%CI = -0.19 to 0.43, p = 0.433), and the levels of HbA1c (g = 0.38, 95%CI = -0.02 to 0.77, p = 0.061) between relatives of schizophrenia patients and controls. Two studies demonstrated significantly higher 2-hour glucose levels during OGTT in relatives of patients with schizophrenia (g = 0.90, 95%CI = 0.49 to 1.31, p 0.001). Our findings do not support the hypothesis that familial liability to psychosis is related to altered fasting parameters of glucose homeostasis. However, this population might show impaired glucose tolerance. More studies are needed to confirm these observations.

The article presents update of the 2013 Guidelines of the Pharmacotherapy Section of the Polish Society for Research on Addictions (PTBU) and the Psychopharmacology Section of the Polish Psychiatric Association (PTP) on long-term pharmacotherapy aimed at maintaining abstinence or reducing alcohol intake in adult alcohol-dependent patients. Apart from practical guidelines for long-term pharmacotherapy of alcohol dependence, the authors present the areas of uncertainty, which still require further studies and scientific debate.

Human endogenous retroviruses (HERV) have been widely associated with schizophrenia etiology. Aberrant epigenetic processes may play a role in the etiology of schizophrenia. In this study, we tested whether schizophrenia patients at different stages of illness might present alterations in the levels of HERV-K methylation. We recruited 49 first-episode schizophrenia (FES) patients with 47 age- and sex-matched healthy controls (HCs), and 100 multi-episode schizophrenia (MES) patients with 50 age- and sex-matched HCs. Based on the Schedule for Deficit Schizophrenia, patients with MES were also divided into two subgroups: deficit (D-SCZ) and non-deficit schizophrenia (ND-SCZ). DNA methylation levels of HERV-K sequences were examined in peripheral blood leukocytes. We found significantly lower levels of HERV-K methylation in FES patients compared to HCs. Patients with MES and matched HCs had similar levels of HERV-K methylation. There was a significant positive correlation between chlorpromazine equivalent dosage and HERV-K methylation levels in MES patients, but not in FES individuals. No significant differences in HERV-K methylation levels between D-SCZ and ND-SCZ as well as HCs were found. Our results indicate lower HERV-K methylation levels at early stages of schizophrenia. This difference might normalize with subsequent exacerbations of schizophrenia, likely due to the effects of antipsychotics.

Introduction The co-existence of schizophrenia and metabolic syndrome is a widely described phenomenon that contributes to the worse functioning of patients in everyday life. A relatively new area of research is the relationship between metabolic syndrome (MS) and cognitive function in patients with schizophrenia. The aim of the study was to verify the relationship between the presence of metabolic syndrome and cognitive function of patients with schizophrenia and to assess the possibility of changing cognitive function by introducing appropriate dietary intervention. Materials and Methods The study involved 87 individuals diagnosed with schizophrenia according to ICD-10 criteria, aged 19 to 67 years (M = 41.67; SD = 11.87). Patients were in the remission phase of schizophrenia, all using antipsychotics for pharmacological treatment. From a group of 83 patients with schizophrenia and diagnosed metabolic syndrome (according to IDF criteria) 30 patients were randomly assigned to an experimental group—with dietary intervention, 29 patients—to group without dietary intervention, 24 patients with schizophrenia without metabolic syndrome was a comparison group. All groups were evaluated for cognitive function using Stroop Test, Trail Making Test (TMT), Verbal Fluency Test, Digit Span Backwards Test. In the experimental group a dietary intervention was applied, which was to provide the examined person with a 7-day dietary plan with reduced calorie content, in compliance with the Mediterranean diet. Results After the dietary intervention there was a significant improvement in the number of errors made in the third Stroop Test (p

Cel pracyCelem przedstawionego badania było wykazanie związku pomiędzy wybranymi polimorfizmami genu receptora dopaminy DRD2 a uzależnieniem od narkotyków.MetodaW badaniu zrekrutowano 100 osób uzależnionych od narkotyków, leczonych w stacjonarnych ośrodkach leczenia uzależnień na terenie Polski. Uczestnicy zostali przebadani z zastosowaniem ustrukturyzowanego wywiadu klinicznego SSAGA celem opisania obrazu klinicznego. W drugiej części, przebadano uczestników z zastosowaniem narzędzi psychometrycznych oceniających wybrane cechy psychopatologiczne. Od każdego z uczestników pobrano krew celem izolacji DNA, z którego oznaczono następujące polimorfizmy SNP genu DRD2: Tag 1D (rs1800498), Tag 1B (rs 1079597), rs 1076560.WynikiW badaniu asocjacyjnym wykazano związek polimorfizmu Tag D1 z uzależnieniem od narkotyków, gdzie wariant alleliczny T pojawiał się częściej w grupie badanej w stosunku do grupy kontrolnej. Związek ten okazał się jeszcze silniejszy w podgrupach pacjentów uzależnionych od przetworów konopi indyjskich i opiatów.WnioskiPrzekaźnictwo dopaminergiczne odgrywa kluczową rolę w neurobiologicznym podłożu uzależnień. Polimorfizmy SNP położone w niekodowanych obszarach genu DRD2, wykazują związek z uzależnieniem. Wpływ tych polimorfizmów na funkcję wybranego receptora, odbywa się poprzez zjawisko “splicing'u”.

Dysregulation of innate and adaptive immunity is increasingly being recognized as one of core characteristics of schizophrenia pathophysiology. Several studies have revealed that patients with schizophrenia present various alterations in the levels of distinct leukocyte subpopulations. However, studies addressing this point have provided mixed results. Therefore, in this study we translated a computational deconvolution algorithm in order to estimate counts of distinct leukocyte subpopulations in peripheral blood of patients with schizophrenia. Our analysis was based on publicly available data from peripheral blood DNA methylation profiling in 711 schizophrenia patients and 713 healthy controls (2 independent samples). In both datasets, there were significantly lower levels of CD8 and NK cells together with significantly higher levels of granulocytes. However, the levels of CD8 cells were insignificant after controlling for age and sex differences in one dataset. Our results indicate that patients with schizophrenia present innate immunity dysregulation in terms of NK cells depletion and increased levels of granulocytes. Longitudinal studies of various clinical subgroups of schizophrenia patients are required in order to disentangle whether our findings reflect trait- or state-dependent alterations.

Parenting style is one of the exogenous factors, participating both in the etiology of psychopathology and in the healthy development of a child. Four main parenting styles, investigated so far, which evoke researchers interest most frequently, are: authoritative, authoritarian, permissive (liberal) loving and permissive uninvolved style. Research conducted in different countries has allowed us to describe connections between applying particular upbringing models and the occurrence of depression, eating disorders, addictions or violence. It has been evidenced that liberal- unloving parenting style, based on little control, and lack of emotional support, is positively associated with aggressive behavior. Parenting models based on excessive control and emotional coldness increase the risk of depression and substance abuse in children and adolescent, whereas authoritative parenting style applied by both parents minimalizes the risk of depression, suicidal tendencies and is also negatively correlated with substance abuse, bulimia and anorexia nervosa. Scientific reports indicate cross-cultural differences in young people’s perception of their parent’s style. For example, uninvolved parenting style was associated with higher depressiveness in Asian females than in African-American. Our paper presents a review of investigations on parenting styles and their results, conducted in different times and often in different cultures. The presented data allows us to formulate general conclusions and recommendations concerning parenting methods which may minimize the risk of psychopathology in youth. Authoritative style, consisting in high control combined with expression of emotional warmth, seems to be the most advantageous for the child’s development.

Polymorphisms in immune-inflammatory response genes are believed to impact schizophrenia susceptibility. However, it remains unknown whether immunogenetic factors play a role in the etiology of deficit schizophrenia (D-SCZ). Therefore, we genotyped four polymorphisms in genes encoding two immune system regulatory proteins (CTLA-4 rs231775 and CD28 rs3116496), interleukin-6 (IL6 rs1800795) and transforming growth factor-β (TGFB1 rs1800470) in 513 schizophrenia patients and 374 controls. The CD28 rs3116496-CC genotype and C-allele were significantly more frequent in the whole group of patients and D-SCZ patients compared to controls. Our results indicate that the CD28 rs3116496 polymorphism might impact the risk of schizophrenia, especially D-SCZ.

Background The aim of this article was to perform a systematic review of studies investigating the association between peripheral levels of cytokines and C-reactive protein (CRP), cytokine gene polymorphisms and cognition in patients with schizophrenia and bipolar disorder (BD). Methods The following databases: PubMed, CINAHL Complete, Academic Search Complete, ERIC and Health Source: Nursing/Academic Edition databases were searched according to the PRISMA guidelines. We included studies that investigated the association between peripheral levels of CRP and cytokines, cytokine gene polymorphisms and cognitive performance in schizophrenia and/or BD patients. Subsequently, quality assessment of eligible publications was performed. Results were synthesized by discussing main findings around correlations between inflammatory markers and cognition. Results Most consistent results indicate worse cognitive performance in schizophrenia patients with higher CRP levels. Less consistent evidence suggests better cognitive functioning of schizophrenia patients with higher levels of tumour necrosis factor-α (TNF-α). Evidence for the involvement of other cytokines in cognitive impairment in patients with schizophrenia is less convincing due to discordant results or scarcity of studies. Due to low number of studies, it is difficult to draw conclusions on the involvement of CRP and cytokine alterations in the development of cognitive deficits in BD. Single studies suggest the role of CRP, interleukin(IL)-1 receptor antagonist, IL-6 and TNF-α with its receptors in the development of cognitive impairment in BD. Conclusions Peripheral inflammation might be related to cognitive deficits in schizophrenia and BD. Unequivocal conclusions cannot be made due to methodological heterogeneity and low number of studies investigating particular cytokines.

The robustness of stem cells is one of the major factors that directly impacts life quality and life span. Evidence has accumulated that changes in the stem cell compartment affect human mental health and serve as an indicator of psychiatric problems. It is well known that stem cells continuously replace differentiated cells and tissues that are used up during life, although this replacement occurs at a different pace in the various organs. However, the participation of local neural stem cells in regeneration of the central nervous system is controversial. It is known that low numbers of stem cells circulate continuously in peripheral blood (PB) and lymph and undergo a circadian rhythm in their PB level, with the peak occurring early in the morning and the nadir at night, and recent evidence suggests that the number and pattern of circulating stem cells in PB changes in psychotic disorders. On the other hand, progress in the creation of induced pluripotent stem cells (iPSCs) from patient somatic cells provides valuable tools with which to study changes in gene expression in psychotic patients. We will discuss the various potential sources of stem cells that are currently employed in regenerative medicine and the mechanisms that explain some of their beneficial effects as well as the emerging problems with stem cell therapies. However, the main question remains: Will it be possible in the future to modulate the stem cell compartment to reverse psychiatric problems?

The new area of research in psychiatric disorders is concerned with abnormal regeneration processes. The role of brain neurogenesis has been studied for decades. New discoveries, concerned with the pluripotency of VSEL cells and the role of factors involved in stem cell trafficking in peripheral blood create hope that it will be possible to develop a better understanding of the processes of neuroregeneration/neurodegeneration. There is an ongoing research investigating concentrations of: sphingosine -1-phosphate, SDF-1, elements of complement cascade, and stem cells in peripheral blood, including their possible connection to psychiatric disorders. Collected data, suggesting an abnormal course of regeneration processes in psychiatric disorders, raises hope of finding new potential markers of psychosis and anxiety disorders.

Background We investigated the effect of long-term lithium treatment on very-small embryonic-like stem cells (VSELs) and the mRNA expression of pluripotency and glial markers, in peripheral blood, in patients with bipolar disorder (BD). Methods Fifteen BD patients (aged 53 ± 7 years) not treated with lithium, with duration of illness > 10 years, 15 BD patients (aged 55 ± 6 years) treated with lithium for 8–40 years (mean 16 years) and 15 control subjects (aged 50 ± 5 years) were included. The number of VSELs was measured by flow cytometric analysis. Assessment of the mRNA levels of pluripotency markers (Oct-4, Sox 2 and Nanog) and glial markers (glial fibrillary acidic protein - GFAP, Olig1 and Olig2) was performed, using the Real-time quantitative reverse transcription PCR. Results In BD patients not taking lithium, the number of VSELs was significantly higher than in control subjects and correlated with the duration of illness. The expression of pluripotency markers was significantly higher than in the controls and correlated with the number of VSELs. The mRNA levels of the Olig1 and Olig 2 were higher than in the controls and those of the GFAP were higher than in patients receiving lithium. In lithium-treated BD patients the number of VSELs was similar to controls and correlated negatively with the duration of lithium treatment and serum lithium concentration. The mRNA levels of Oct-4, Sox-2, GFAP and Olig1 were not different from controls. The mRNA expression of Nanog was significantly higher and correlated with the number of VSELs. The mRNA expression of Olig 2 was higher than in the BD patients not taking lithium. Conclusion Long-term treatment with lithium may suppress the activation of regenerative processes by reducing the number of VSELs circulating in PB. These cells, in BD patients not treated with lithium, may provide a new potential biological marker of the illness and its clinical progress. The higher expression of peripheral mRNA markers in BD patients may involve ongoing inflammatory process, compensatory mechanisms and regenerative responses. Long-term lithium treatment may attenuate these mechanisms, especially in relation to the transcription factors Oct-4, Sox-2, GFAP and Olig1.

Schizophrenia is a chronic mental illness of unknown etiology. A growing and compelling body of evidence implicates immunologic dysfunction as the key element in its pathomechanism. Cytokines, whose altered levels have been increasingly reported in various patient populations, are the major mediators involved in the coordination of the immune system. The available literature reports both elevated levels of proinflammatory as well as reduced levels of anti-inflammatory cytokines, and their effects on clinical status and neuroimaging changes. There is evidence of at least a partial genetic basis for the association between cytokine alterations and schizophrenia. Two other factors implicated in its development include early childhood trauma and disturbances in the gut microbiome. Moreover, its various subtypes, characterized by individual symptom severity and course, such as deficit schizophrenia, seem to differ in terms of changes in peripheral cytokine levels. While the use of a systematic review methodology could be difficult due to the breadth and diversity of the issues covered in this review, the applied narrative approach allows for a more holistic presentation. The aim of this narrative review was to present up-to-date evidence on cytokine dysregulation in schizophrenia, its effect on the psychopathological presentation, and links with antipsychotic medication. We also attempted to summarize its postulated underpinnings, including early childhood trauma and gut microbiome disturbances, and propose trait and state markers of schizophrenia.

Dysregulation of epigenetic processes might account for alterations of the hypothalamic-pituitary-adrenal axis observed in patients with schizophrenia. Therefore, in this study, we aimed to investigate methylation of the glucocorticoid receptor (NR3C1) gene in patients with schizophrenia-spectrum disorders, individuals at familial high risk of schizophrenia (FHR-P), and healthy controls with respect to clinical manifestation and a history of psychosocial stressors.We recruited 40 first-episode psychosis patients, 45 acutely relapsed schizophrenia (SCZ-AR) patients, 39 FHR-P individuals, and 56 healthy controls. The level of methylation at 9 CpG sites of the NR3C1 gene was determined using pyrosequencing.The level of NR3C1 methylation was significantly lower in first-episode psychosis patients and significantly higher in SCZ-AR patients compared with other subgroups of participants. Individuals with FHR-P and healthy controls had similar levels of NR3C1 methylation. A history of adverse childhood experiences was associated with significantly lower NR3C1 methylation in all subgroups of participants. Higher methylation of the NR3C1 gene was related to worse performance of attention and immediate memory as well as lower level of general functioning in patients with psychosis.Patients with schizophrenia-spectrum disorders show altered levels of NR3C1 methylation that are significantly lower in first-episode psychosis patients and significantly higher in SCZ-AR patients. Higher methylation of the NR3C1 gene might be related to cognitive impairment observed in this clinical population. The association between a history of adverse childhood experiences and lower NR3C1 methylation is not specific to patients with psychosis. Longitudinal studies are needed to establish causal mechanisms underlying these observations.

Previous findings revealed high correlations between serum/plasma and saliva levetiracetam concentrations, indicating saliva as an alternative matrix for monitoring levetiracetam therapy. Levetiracetam concentration in the hair, which could reflect long-term drug exposure and patients' compliance, has not been systematically tested, as yet. The aim of this study was to determine the correlation between plasma, saliva, and hair levetiracetam concentrations in 47 patients with epilepsy.Plasma, saliva, and hair levetiracetam concentrations were measured by liquid chromatography-tandem mass spectrometry with positive ionization.Levetiracetam saliva and plasma concentrations were highly correlated (r = 0.93). Plasma concentrations were not influenced by sex, age, and other concomitant antiepileptic drugs. Levetiracetam hair concentrations correlated with plasma concentrations (r = 0.36) but not daily dose (mg/kg). Drug hair concentrations were not influenced by hair color or treatment (dyed).The results tend to indicate that saliva may be a reliable alternative to plasma for monitoring levetiracetam concentrations. Levetiracetam can also be detected in human hair.

Background Dysfunction of the glutamatergic system has been implicated in alcohol addiction; however, the molecular underpinnings of this phenomenon are still poorly understood. In the current study we have investigated the possible function of matrix metalloproteinase-9 (MMP-9) in alcohol addiction because this protein has recently emerged as an important regulator of excitatory synaptic plasticity. Methods For long-term studies of alcohol drinking in mice we used IntelliCages. Dendritic spines were analyzed using Diolistic staining with DiI. Whole-cell patch clamp was used to assess silent synapses. Motivation for alcohol in human subjects was assessed on the basis of a Semi-Structured Assessment for the Genetics of Alcoholism interview. Results Mice devoid of MMP-9 (MMP-9 knockout) drank as much alcohol as wild-type animals; however, they were impaired in alcohol seeking during the motivation test and withdrawal. The deficit could be rescued by overexpression of exogenous MMP-9 in the central nucleus of the amygdala (CeA). Furthermore, the impaired alcohol seeking was associated with structural alterations of dendritic spines in the CeA and, moreover, whole-cell patch clamp analysis of the basal amygdala to CeA projections showed that alcohol consumption and withdrawal were associated with generation of silent synapses. These plastic changes were impaired in MMP-9 knockout mice. Finally, C/T polymorphism of MMP-9 gene at position –1562, which upregulates MMP-9 expression, correlated with increased motivation for alcohol in alcoholics. Conclusions In aggregate, our results indicate a novel mechanism of alcohol craving that involves MMP-9–dependent synaptic plasticity in CeA.