Ketamine disrupts locomotion and electrolocation in a novel model of schizophrenia, Gnathonemus petersii fish.

The present study aimed to examine a weakly electric fish Gnathonemus petersii (G. petersii) as a candidate model organism of glutamatergic theory of schizophrenia. The idea of G. petersii elevating the modeling of schizophrenia symptoms is based on the fish's electrolocation and electrocommunication abilities. Fish were exposed to the NMDA antagonist ketamine in two distinct series differing in the dose of ketamine. The main finding revealed ketamine-induced disruption of the relationship between electric signaling and behavior indicating impairment of fish navigation. Moreover, lower doses of ketamine significantly increased locomotion and erratic movement and higher doses of ketamine reduced the number of electric organ discharges indicating successful induction of positive schizophrenia-like symptoms and disruption of fish navigation. Additionally, a low dose of haloperidol was used to test the normalization of the positive symptoms to suggest a predictive validity of the model. However, although successfully induced, positive symptoms were not normalized using the low dose of haloperidol; hence, more doses of the typical antipsychotic haloperidol and probably also of a representative of atypical antipsychotic drugs need to be examined to confirm the predictive validity of the model.

Investigating the phenotypic and genetic associations between personality traits and suicidal behavior across major mental health diagnoses.

Personality traits influence risk for suicidal behavior. We examined phenotype- and genotype-level associations between the Big Five personality traits and suicidal ideation and attempt in major depressive, bipolar and schizoaffective disorder, and schizophrenia patients (N = 3012) using fixed- and random-effects inverse variance-weighted meta-analyses. Suicidal ideations were more likely to be reported by patients with higher neuroticism and lower extraversion phenotypic scores, but showed no significant association with polygenic load for these personality traits. Our findings provide new insights into the association between personality and suicidal behavior across mental illnesses and suggest that the genetic component of personality traits is unlikely to have strong causal effects on suicidal behavior.

Vascular Remodeling of Clinically Used Patches and Decellularized Pericardial Matrices Recellularized with Autologous or Allogeneic Cells in a Porcine Carotid Artery Model.

Background: Cardiovascular surgery is confronted by a lack of suitable materials for patch repair. Acellular animal tissues serve as an abundant source of promising biomaterials. The aim of our study was to explore the bio-integration of decellularized or recellularized pericardial matrices in vivo. Methods: Porcine (allograft) and ovine (heterograft, xenograft) pericardia were decellularized using 1% sodium dodecyl sulfate ((1) Allo-decel and (2) Xeno-decel). We used two cell types for pressure-stimulated recellularization in a bioreactor: autologous adipose tissue-derived stromal cells (ASCs) isolated from subcutaneous fat of pigs ((3) Allo-ASC and (4) Xeno-ASC) and allogeneic Wharton's jelly mesenchymal stem cells (WJCs) ((5) Allo-WJC and (6) Xeno-WJC). These six experimental patches were implanted in porcine carotid arteries for one month. For comparison, we also implanted six types of control patches, namely, arterial or venous autografts, expanded polytetrafluoroethylene (ePTFE Propaten® Gore®), polyethylene terephthalate (PET Vascutek®), chemically stabilized bovine pericardium (XenoSure®), and detoxified porcine pericardium (BioIntegral® NoReact®). The grafts were evaluated through the use of flowmetry, angiography, and histological examination. Results: All grafts were well-integrated and patent with no signs of thrombosis, stenosis, or aneurysm. A histological analysis revealed that the arterial autograft resembled a native artery. All other control and experimental patches developed neo-adventitial inflammation (NAI) and neo-intimal hyperplasia (NIH), and the endothelial lining was present. NAI and NIH were most prominent on XenoSure® and Xeno-decel and least prominent on NoReact®. In xenografts, the degree of NIH developed in the following order: Xeno-decel > Xeno-ASC > Xeno-WJC. NAI and patch resorption increased in Allo-ASC and Xeno-ASC and decreased in Allo-WJC and Xeno-WJC. Conclusions: In our setting, pre-implant seeding with ASC or WJC had a modest impact on vascular patch remodeling. However, ASC increased the neo-adventitial inflammatory reaction and patch resorption, suggesting accelerated remodeling. WJC mitigated this response, as well as neo-intimal hyperplasia on xenografts, suggesting immunomodulatory properties.

Associated factors of REM sleep without atonia in younger (≤ 50 years) hospitalized psychiatric patients.

BACKGROUND: Isolated REM sleep without atonia (RSWA) as a main polysomnograhic feature of REM sleep behaviour disorder (RBD) is thought to be a prodromal or subclinical state of the disease. RSWA/RBD occurence in psychiatric population is much more frequent than in general population but its associated factors are still not known. METHODS: We invited 88 psychiatry in-patients to undervent video-polysomnography. The visual scoring was focused on RSWA in submentales and flexores digitales superficiales muscles. This parametr was subsequently correlated mainly with age/gender, their medication and mental status. RESULTS: The RWSA was mostly still in normal range despite the fact, that selected psychiatry patients (≤ 50 years) were taking several classes of psychoactive medication. 3,6% had convincingly RBD, although 35.7% reported rare lifetime occurence of dream-enacting behaviour and 62.8% sporadic nightmares. We found correlation between RSWA and SNRI medication class (p = 0.015), specifically venlafaxine (p = 0.029) as well as quetiapine (p = 0.030). Another significant associated factors were current anxiety (p < 0.001) and depressive symptoms (p = 0.05), but we found no relation between RSWA and given diagnosis. CONLUCIONS: Isolated RSWA in younger psychiatry patients might be a result of multiple factors, including medication and current mental status but these factors are in most cases not sufficient to manifest RBD.

Sleep characteristics in child and adolescent offspring of parents with bipolar disorder: a case control study.

BACKGROUND: Impairment of sleep and circadian rhythm is a typical feature of bipolar disorder (BD). We carried out an exploratory cross-sectional case-control study to extend the knowledge of sleep characteristics in offspring at risk for BD. METHODS: We investigated 42 offspring of bipolar parents (OB) (mean age 12.5 ± 3.2) and 42 sex and age matched comparison offspring of healthy parents. We administered the Pediatric Sleep Questionnaire, the Morningness/Eveningness Questionnaire and The General Behavior Inventory Sleep Subscale (GBISS) to assess circadian preference, and to identify sleep impairment symptoms. In addition, the participants completed 14 days of actigraphy to characterise sleep and wake patterns. The current psychopathology profile was assessed using Kiddie Schedule for Affective Disorders and Schizophrenia. RESULTS: Prevalence of sleep disturbance symptoms was higher among OB than controls (headache after waking up, 17.9% vs. 2.4%, p = 0.03; excessive daytime sleepiness, 38.5% vs. 10.0%, p = 0.004; apparent tiredness at wake-up times, 43.6% vs. 15.0%, p = 0.007 and nightmares, 21.6% vs. 2.4%, p = 0.01), but the differences between groups were not significant after adjusting for current psychopathology. OB had higher GBISS total score (parental version, p < 0.001; self-assessment, p = 0.07) than the controls. OB had higher preference for eveningness than the controls (p = 0.047). According to the actigraphy, OB had longer sleep onset latency (p = 0.048) than the controls. CONCLUSION: Evidence suggests that the offspring of bipolar parents experience sleep disturbance symptoms, which was associated with psychopathology in this study. Prospective longitudinal sleep studies would clarify whether sleep disturbance could be a predictor of mood disorder onset in this high-risk population.

The Comparison of Effectiveness of Various Potential Predictors of Response to Treatment With SSRIs in Patients With Depressive Disorder.

The substantial non-response rate in depressive patients indicates a continuing need to identify predictors of treatment outcome. The aim of this 6-week, open-label study was (1) to compare the efficacy of a priori defined predictors: ≥20% reduction in MADRS score at week 1, ≥20% reduction in MADRS score at week 2 (RM ≥ 20% W2), decrease of cordance (RC), and increase of serum and plasma level of brain-derived neurotrophic factor at week 1; and (2) to assess whether their combination yields higher efficacy in the prediction of response to selective serotonin re-uptake inhibitors (SSRIs) than when used singly. Twenty-one patients (55%) achieved a response to SSRIs. The RM ≥20% W2 (areas under curve-AUC = 0.83) showed better predictive efficacy compared to all other predictors with the exception of RC. The identified combined model (RM ≥ 20% W2 + RC), which predicted response with an 84% accuracy (AUC = 0.92), may be a useful tool in the prediction of response to SSRIs.

Using structural MRI to identify individuals at genetic risk for bipolar disorders: a 2-cohort, machine learning study.

BACKGROUND: Brain imaging is of limited diagnostic use in psychiatry owing to clinical heterogeneity and low sensitivity/specificity of between-group neuroimaging differences. Machine learning (ML) may better translate neuroimaging to the level of individual participants. Studying unaffected offspring of parents with bipolar disorders (BD) decreases clinical heterogeneity and thus increases sensitivity for detection of biomarkers. The present study used ML to identify individuals at genetic high risk (HR) for BD based on brain structure. METHODS: We studied unaffected and affected relatives of BD probands recruited from 2 sites (Halifax, Canada, and Prague, Czech Republic). Each participant was individually matched by age and sex to controls without personal or family history of psychiatric disorders. We applied support vector machines (SVM) and Gaussian process classifiers (GPC) to structural MRI. RESULTS: We included 45 unaffected and 36 affected relatives of BD probands matched by age and sex on an individual basis to healthy controls. The SVM of white matter distinguished unaffected HR from control participants (accuracy = 68.9%, p = 0.001), with similar accuracy for the GPC (65.6%, p = 0.002) or when analyzing data from each site separately. Differentiation of the more clinically heterogeneous affected familiar group from healthy controls was less accurate (accuracy = 59.7%, p = 0.05). Machine learning applied to grey matter did not distinguish either the unaffected HR or affected familial groups from controls. The regions that most contributed to between-group discrimination included white matter of the inferior/middle frontal gyrus, inferior/middle temporal gyrus and precuneus. LIMITATIONS: Although we recruited 126 participants, ML benefits from even larger samples. CONCLUSION: Machine learning applied to white but not grey matter distinguished unaffected participants at high and low genetic risk for BD based on regions previously implicated in the pathophysiology of BD.

Sad mood induction has an opposite effect on amygdala response to emotional stimuli in euthymic patients with bipolar disorder and healthy controls.

BACKGROUND: Aberrant amygdala reactivity to affective stimuli represents a candidate factor predisposing patients with bipolar disorder (BD) to relapse, but it is unclear to what extent amygdala reactivity is state-dependent. We evaluated the modulatory influence of mood on amygdala reactivity and functional connectivity in patients with remitted BD and healthy controls. METHODS: Amygdala response to sad versus neutral faces was investigated using fMRI during periods of normal and sad mood induced by autobiographical scripts. We assessed the functional connectivity of the amygdala to characterize the influence of mood state on the network responsible for the amygdala response. RESULTS: We included 20 patients with remitted BD and 20 controls in our study. The sad and normal mood exerted opposite effects on the amygdala response to emotional faces in patients compared with controls (F1,38 = 5.85, p = 0.020). Sad mood amplified the amygdala response to sad facial stimuli in controls but attenuated the amygdala response in patients. The groups differed in functional connectivity between the amygdala and the inferior prefrontal gyrus (p ≤ 0.05, family-wise error-corrected) of ventrolateral prefrontal cortex (vlPFC) corresponding to Brodmann area 47. The sad mood challenge increased connectivity during the period of processing sad faces in patients but decreased connectivity in controls. LIMITATIONS: Limitations to our study included long-term medication use in the patient group and the fact that we mapped only depressive (not manic) reactivity. CONCLUSION: Our results support the role of the amygdala-vlPFC as the system of dysfunctional contextual affective processing in patients with BD. Opposite amygdala reactivity unmasked by the mood challenge paradigm could represent a trait marker of altered mood regulation in patients with BD.

The effectiveness of prefrontal theta cordance and early reduction of depressive symptoms in the prediction of antidepressant treatment outcome in patients with resistant depression: analysis of naturalistic data.

Current studies suggest that an early improvement of depressive symptoms and the reduction of prefrontal theta cordance value predict the subsequent response to antidepressants. The aim of our study was (1) to compare the predictive abilities of early clinical improvement defined as ≥ 20 % reduction in Montgomery and Åsberg Depression Rating Scale (MADRS) total score at week 1 and 2, and the decrease of prefrontal theta cordance at week 1 in resistant depressive patients and (2) to assess whether the combination of individual predictors yields more robust predictive power than either predictor alone. Eighty-seven subjects were treated (≥ 4 weeks) with various antidepressants chosen according to the judgment of attending psychiatrists. Areas under curve (AUC) were calculated to compare predictive effect of defined single predictors (≥ 20 % reduction in MADRS total score at week 1 and 2, and the decrease of cordance at week 1) and combined prediction models. AUCs of all three predictors were not statistically different (pair-wise comparison). The model combining all predictors yielded an AUC value 0.91 that was significantly higher than AUCs of each individual predictor. The results indicate that the combined predictor model may be a useful and clinically meaningful tool for the prediction of antidepressant response in patients with resistant depression.

Transcranial direct current stimulation (tDCS) in the treatment of neuropsychiatric symptoms of long COVID.

The study aimed to assess the efficacy of transcranial direct current stimulation (tDCS) in the treatment of neuropsychiatric (NP) symptoms of the post-acute sequelae of SARS-CoV-2 infection (PASC), known as the long COVID. A double-blind, randomized, sham-controlled study compared the efficacy and safety of prefrontal cortex active tDCS to sham-tDCS in treating NP-PASC. Patients diagnosed with NP-PASC, with a Fatigue Impact Scale (FIS) score ≥ 40, were eligible for the study. Twenty tDCS sessions were administered within four weeks, with continuous, end-of-treatment, and follow-up measurements. The primary outcome was a change in the FIS at the end-of-treatment, analyzed in the intention-to-treat population. Data from 33 patients assigned to active (n = 16) or sham-tDCS (n = 17) were analyzed. After the treatment, a decrease in the FIS score was more pronounced in the sham than in the active group, yet the intergroup difference was insignificant (11.7 [95% CI -11.1 to 34.5], p = 0.6). Furthermore, no significant intergroup differences were observed regarding anxiety, depression, quality of life, and cognitive performance. The small cohort sample, differences in baseline FIS scores between groups (non-stratified randomization), or chosen stimulation parameters may have influenced our findings. However, it might also be possible that the expected mechanism of action of tDCS is insufficient to treat these conditions.

Right ventrolateral and left dorsolateral 10 Hz transcranial magnetic stimulation as an add-on treatment for bipolar I and II depression: a double-blind, randomised, three-arm, sham-controlled study.

OBJECTIVES: Despite the clinical importance of bipolar depression (BDE), effective treatment options are still limited. Transcranial magnetic stimulation (rTMS) has proven of moderate efficacy in major depression, but the evidence remains inconclusive for BDE. METHODS: A 4-week, double-blind, randomised, parallel-group, sham-controlled study (trial ID ISRCTN77188420) explored the benefits of 10 Hz MRI-guided right ventrolateral (RVL) rTMS and left dorsolateral (LDL) rTMS as add-on treatments for BDE. Outcome measures included changes in the Montgomery-Åsberg Depression Rating Scale (MADRS) score, self-assessment, response and remission rates, and side effects. RESULTS: Sixty patients were randomly assigned to study groups, and forty-six completed the double-blind phase. The mean change from baseline to Week 4 in MADRS was greater in both active groups compared to the sham, yet differences did not achieve significance (RVL vs sham: -4.50, 95%CI -10.63 to 1.64, p = 0.3; LDL vs sham: -4.07, 95%CI -10.24 to 2.10, p = 0.4). None of the other outcome measures yielded significant results. CONCLUSIONS: While not demonstrating the superiority of either 10 Hz rTMS over sham, with the limited sample size, we can not rule out a moderate yet clinically meaningful effect. Further well-powered studies are essential to elucidate the role of rTMS in managing BDE.

External Support of Autologous Internal Jugular Vein Grafts with FRAME Mesh in a Porcine Carotid Artery Model.

BACKGROUND: Autologous vein grafts are widely used for bypass procedures in cardiovascular surgery. However, these grafts are susceptible to failure due to vein graft disease. Our study aimed to evaluate the impact of the latest-generation FRAME external support on vein graft remodeling in a preclinical model. METHODS: We performed autologous internal jugular vein interposition grafting in porcine carotid arteries for one month. Four grafts were supported with a FRAME mesh, while seven unsupported grafts served as controls. The conduits were examined through flowmetry, angiography, macroscopy, and microscopy. RESULTS: The one-month patency rate of FRAME-supported grafts was 100% (4/4), whereas that of unsupported controls was 43% (3/7, Log-rank p = 0.071). On explant angiography, FRAME grafts exhibited significantly more areas with no or mild stenosis (9/12) compared to control grafts (3/21, p = 0.0009). Blood flow at explantation was higher in the FRAME grafts (145 ± 51 mL/min) than in the controls (46 ± 85 mL/min, p = 0.066). Area and thickness of neo-intimal hyperplasia (NIH) at proximal anastomoses were similar for the FRAME and the control groups: 5.79 ± 1.38 versus 6.94 ± 1.10 mm2, respectively (p = 0.558) and 480 ± 95 vs. 587 ± 52 µm2/µm, respectively (p = 0.401). However, in the midgraft portions, the NIH area and thickness were significantly lower in the FRAME group than in the control group: 3.73 ± 0.64 vs. 6.27 ± 0.64 mm2, respectively (p = 0.022) and 258 ± 49 vs. 518 ± 36 µm2/µm, respectively (p = 0.0002). CONCLUSIONS: In our porcine model, the external mesh FRAME improved the patency of vein-to-carotid artery grafts and protected them from stenosis, particularly in the mid regions. The midgraft neo-intimal hyperplasia was two-fold thinner in the meshed grafts than in the controls.

Individualized rTMS neuronavigated according to regional brain metabolism ((18)FGD PET) has better treatment effects on auditory hallucinations than standard positioning of rTMS: a double-blind, sham-controlled study.

Low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) of the left temporo-parietal cortex (LTPC) has been proposed as a useful therapeutic method for auditory hallucinations (AHs). Stereotactic neuronavigation enables the magnetic coil to be targeted according to the individual parameters obtained from neuroimaging. Individualized rTMS neuronavigated according to 18-fluorodeoxyglucose positron emission tomography ((18)FDG PET) allows us to focus the coil explicitly on a given area with detected maxima of specific abnormalities, thus presuming a higher therapeutic effect of the method. The objective of this study is to test clinical efficacy of neuronavigated LF-rTMS administered according to the local maxima of (18)FDG PET uptake of LTPC and to compare it with treatment effects of standard and sham rTMS. In a double-blind, sham-controlled design, patients with AHs underwent a 10-day series of LF-rTMS using (1) (18)FDG PET-guided "neuronavigation," (2) "standard" anatomically guided positioning, and (3) sham coil. The effect of different rTMS conditions was assessed by the Auditory Hallucinations Rating Scale (AHRS) and the Positive and Negative Syndrome Scale (PANSS). Fifteen patients were randomized to a treatment sequence and ten of them completed all three treatment conditions. The intention-to-treat analysis of AHRS score change revealed superiority of the (18)FDG PET-guided rTMS over both the standard and the sham rTMS. The analyses of the PANSS scores failed to detect significant difference among the treatments. Our data showed acute efficacy of (18)FDG PET-guided rTMS in the treatment of AHs. Neuronavigated rTMS was found to be more effective than standard, anatomically guided rTMS.

Relationship of ketamine's antidepressant and psychotomimetic effects in unipolar depression.

OBJECTIVES: Ketamine and other NMDA (N-methyl-D-aspartate) antagonists produce fast-acting antidepressant-like effects, although the underlying mechanism is unclear. Furthermore, high affinity NMDA antagonists such as ketamine are associated with psychotomimetic effects. To date the link between the antidepressant and psychotomimetic effects of ketamine has not been explored. We examined the relationship between the antidepressant and psychotomimetic effects of a single ketamine infusion in subjects diagnosed with major depressive disorder. METHODS: In a double-blind, cross-over, placebo-controlled, two weeks clinical trial we studied the effects of ketamine (0.54 mg/kg within 30 min) in a group of 27 hospitalized depressive patients. RESULTS: Higher intensity of psychotomimetic symptoms, measured using BPRS, during ketamine administration correlated with alleviation in mood ratings during the following week with maximum on day seven. Ketamine was superior to placebo in all visits (day 1, 4, and 7) assessed by MADRS with effect size (Cohen´s d) of 0.62, 0.57, and 0.44 respectively. There was no significant correlation between ketamine and nor-ketamine plasma levels and MADRS score change at any study time point. CONCLUSION: The substantial relationship between ketamine's antidepressant and psychotomimetic effects was found. This relationship could be mediated by the initial steps of ketamine's action, trough NMDA receptors, shared by both ketamine's clinical effects.

Antidepressant monotherapy compared with combinations of antidepressants in the treatment of resistant depressive patients: a randomized, open-label study.

OBJECTIVE: This randomized, 6-week, open-label study compared efficacy of CAD and antidepressant monotherapies (ADM) that had been chosen according to clinical judgment of the attending psychiatrist. METHODS: A total of 60 inpatients (intent-to-treat analysis) with depressive disorder (≥ 1 unsuccessful antidepressant treatment) were randomly assigned to the interventions. The responders who completed the acute phase of study, were evaluated for relapse within 2 months of follow-up treatment. The primary outcome measure was change in the Montgomery-Åsberg Depression Rating Scale (MADRS) and response was defined as a ≥ 50% reduction of MADRS score. RESULTS: Mean changes in total MADRS score from baseline to week 6 for patients in both treatment modalities were not different (ADM = 13.2 ± 8.6 points; CAD = 14.5 ± 9.5 points; P = 0.58). The analysis of covariance performed for significantly higher value of imipramine equivalent dose in CAD group showed only a non-significant between-group difference for total MADRS change (P = 0.17). There were also no differences between groups in response rate (ADM = 48%; CAD = 58%) and number of drop-outs in acute treatment as well as proportion of responders' relapses in the follow-up. CONCLUSION: Both treatment modalities produced clinically relevant reduction of depressive symptomatology in acute treatment of patients with resistant depression and their effect was comparable.

The effect of low-frequency rTMS on auditory hallucinations, EEG source localization and functional connectivity in schizophrenia.

BACKGROUND: Low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) diminishes auditory hallucinations (AHs). The aims of our study were a) to assess the efficacy of LF-rTMS in a randomized, sham-controlled double-blind alignment, b) to identify the electrophysiological changes accompanying the LF-rTMS, and c) to identify the influence of LF-rTMS on brain functional connectivity (FC). METHODS: Nineteen schizophrenia patients with antipsychotic-resistant AHs were randomized to either active (n = 10) or sham (n = 9) LF-rTMS administered over the left temporo-parietal region for ten days. The clinical effect was assessed by the Auditory Hallucination Rating Scale (AHRS). The localization of the differences in electrical activity was identified by standardized low resolution brain electromagnetic tomography (sLORETA) and FC was measured by lagged phase synchronization. RESULTS: AHRS scores were significantly improved for patients receiving active rTMS compared to the sham (median reduction: 40 % vs 12 %; p = 0.01). sLORETA revealed a decrease of alpha-2, beta-1,-2 bands in the left hemisphere in the active group. Active rTMS led to a decrease of the lagged phase connectivity in beta bands originating in areas close to the site of stimulation, and to a prevailing increase of alpha-2 FC. No significant differences in current density or FC were observed in the sham group. LIMITATIONS: Limitations to our study included the small group sizes, and the disability of LORETA to assess subcortical neuronal activity. CONCLUSIONS: LF-rTMS attenuated AHs and induced a decrease of higher frequency bands on the left hemisphere. The FC changes support the assumption that LF-rTMS is linked to the modulation of cortico-cortical coupling.

Underlying pharmacological mechanisms of psilocin-induced broadband desynchronization and disconnection of EEG in rats.

Introduction: Psilocybin is one of the most extensively studied psychedelic drugs with a broad therapeutic potential. Despite the fact that its psychoactivity is mainly attributed to the agonism at 5-HT2A receptors, it has high binding affinity also to 5-HT2C and 5-HT1A receptors and indirectly modulates the dopaminergic system. Psilocybin and its active metabolite psilocin, as well as other serotonergic psychedelics, induce broadband desynchronization and disconnection in EEG in humans as well as in animals. The contribution of serotonergic and dopaminergic mechanisms underlying these changes is not clear. The present study thus aims to elucidate the pharmacological mechanisms underlying psilocin-induced broadband desynchronization and disconnection in an animal model. Methods: Selective antagonists of serotonin receptors (5-HT1A WAY100635, 5-HT2A MDL100907, 5-HT2C SB242084) and antipsychotics haloperidol, a D2 antagonist, and clozapine, a mixed D2 and 5-HT receptor antagonist, were used in order to clarify the underlying pharmacology. Results: Psilocin-induced broadband decrease in the mean absolute EEG power was normalized by all antagonists and antipsychotics used within the frequency range 1-25 Hz; however, decreases in 25-40 Hz were influenced only by clozapine. Psilocin-induced decrease in global functional connectivity and, specifically, fronto-temporal disconnection were reversed by the 5-HT2A antagonist while other drugs had no effect. Discussion: These findings suggest the involvement of all three serotonergic receptors studied as well as the role of dopaminergic mechanisms in power spectra/current density with only the 5-HT2A receptor being effective in both studied metrics. This opens an important discussion on the role of other than 5-HT2A-dependent mechanisms underlying the neurobiology of psychedelics.

Hippocampal volumes in bipolar disorders: opposing effects of illness burden and lithium treatment.

OBJECTIVE: Hippocampal volume decrease associated with illness burden is among the most replicated findings in unipolar depression. The absence of hippocampal volume changes in most studies of individuals with bipolar disorder (BD) may reflect neuroprotective effects of lithium (Li). METHODS: We recruited 17 BD patients from specialized Li clinics, with at least two years of regularly monitored Li treatment (Li group), and compared them to 12 BD participants with < 3 months of lifetime Li exposure and no Li treatment within two years prior to the scanning (non-Li group) and 11 healthy controls. All BD patients had at least 10 years of illness and five episodes. We also recruited 13 Li-naïve, young BD participants (15-30 years of age) and 18 sex- and age-matched healthy controls. We compared hippocampal volumes obtained from 1.5-T magnetic resonance imaging (MRI) scans using optimized voxel-based morphometry with small volume correction. RESULTS: The non-Li group had smaller left hippocampal volumes than controls (corrected p < 0.05), with a trend for lower volumes than the Li group (corrected p < 0.1), which did not differ from controls. Young, Li-naïve BD patients close to the typical age of onset had comparable hippocampal volumes to controls. CONCLUSIONS: Whereas patients with limited lifetime Li exposure had significantly lower hippocampal volumes than controls, patients with comparable illness burden, but with over two years of Li treatment, or young Li-naïve BD patients, showed hippocampal volumes comparable to controls. These results provide indirect support for neuroprotective effects of Li and negative effects of illness burden on hippocampal volumes in bipolar disorders.

Family therapy in the Czech Republic.

Political, economic and cultural transformations in the Czech Republic after 1989 were reflected in a number of demographic indicators, including those that characterize family behaviour. The main features of these changes are declining birth and marriage rates, postponement of first marriage and first birth ages, and a growing proportion of children born outside of marriage. These changes are comparable to those that have taken place in western Europe since the 1960s; however, some of them are abrupt and cause rapid shift in the family structure. Over the last two decades, significant changes have also occurred in the organization of family therapy. Earlier less coordinated activities underwent institutionalization, and guidelines for training and supervision were established. Family therapy in the Czech Republic is covered by a national organization, the Society of Family Therapy (SOFT). Standards of training and supervision correspond to European standards. The problem remains the lack of support for family therapy from state institutions, especially in the health service. There are only a few healthcare facilities providing family therapy for the treatment of psychiatric disorders or chronic somatic diseases. The capacity of these centres is substantially inadequate.

Increased interleukin-6 and tumor necrosis factor alpha in first episode schizophrenia patients versus healthy controls.

BACKGROUND: Inflammatory immune processes have been clearly implicated in the etiopathology of schizophrenia. There are, however, only limited data dealing with immune parameters in the first episode patients with schizophrenia and the course of these parameters during treatment. SUBJECTS AND METHODS: The presented study compared plasma levels of interleukin (IL)-6, IL-8, IL-10 and TNF-alpha in 25 patients with the first episode of schizophrenia with the minimal exposition of antipsychotics before and after treatment and with age and sex matched group of healthy volunteers. Changes in plasma cytokine levels were investigated after 4 weeks of treatment in relationship with the therapeutic outcome. RESULTS: Our results show significantly increased plasma levels of IL-6 (p≤0.001) and TNF-alpha (p≤0.001) in patients at the admission in comparison with healthy volunteers. After 4 weeks of the treatment the PANSS score decreased (p≤0.001), concurrently the plasma level of IL-6 decreased and TNF-alpha did not show any decrease after treatment. The patients' posttreatment and healthy control group comparison showed higher plasma levels of TNF-alpha (p=0.008) and marginally elevated plasma level of IL-6 (p=0.046) in the posttreatment group. Plasma levels of IL-8 and IL-10 did not show any significant differences. CONCLUSIONS: Our study validated the presence of the proinflammatory state in the first episode of schizophrenia. IL-6 may be considered as a state marker for acute exacerbations and TNF-alpha may be a trait marker of schizophrenia.