Psilocybin disrupts sensory and higher order cognitive processing but not pre-attentive cognitive processing-study on P300 and mismatch negativity in healthy volunteers.

RATIONALE: Disruption of auditory event-related evoked potentials (ERPs) P300 and mismatch negativity (MMN), electrophysiological markers of attentive and pre-attentive cognitive processing, is repeatedly described in psychosis and schizophrenia. Similar findings were observed in a glutamatergic model of psychosis, but the role of serotonergic 5-HT2A receptors in information processing is less clear. OBJECTIVES: We studied ERPs in a serotonergic model of psychosis, induced by psilocybin, a psychedelic with 5-HT2A/C agonistic properties, in healthy volunteers. METHODS: Twenty subjects (10M/10F) were given 0.26 mg/kg of psilocybin orally in a placebo-controlled, double-blind, cross-over design. ERPs (P300, MMN) were registered during the peak of intoxication. Correlations between measured electrophysiological variables and psilocin serum levels and neuropsychological effects were also analyzed. RESULTS: Psilocybin induced robust psychedelic effects and psychotic-like symptoms, decreased P300 amplitude (p = 0.009) but did not affect the MMN. Psilocybin's disruptive effect on P300 correlated with the intensity of the psychedelic state, which was dependent on the psilocin serum levels. We also observed a decrease in N100 amplitude (p = 0.039) in the P300 paradigm and a negative correlation between P300 and MMN amplitude (p = 0.014). CONCLUSIONS: Even though pre-attentive cognition (MMN) was not affected, processing at the early perceptual level (N100) and in higher-order cognition (P300) was significantly disrupted by psilocybin. Our results have implications for the role of 5-HT2A receptors in altered information processing in psychosis and schizophrenia.

Role of Glutamatergic System in Obsessive-Compulsive Disorder with Possible Therapeutic Implications.

Obsessive-compulsive disorder (OCD) is a chronic psychiatric illness and 1 of the most common anxiety disorders with the prevalence of 3%. Although its pathogenesis remains unclear, the traditional model focused on alternations in the serotonin system. Selective serotonin reuptake inhibitors provide the most effective treatment; however, as much as 40-60% of patients do not respond to antidepressants therapy. Thus, attention has shifted towards other neurotransmitter systems and related neuroanatomical structures. Recently, there is extensive evidence showing a key role of glutamate pathways abnormalities within the cortico-striatal-thalamo-cortical circuitry and temporal lobes in OCD pathogenesis. In this review, we link together the existent neuroanatomical, neurophysiological, and neuropsychological evidence to argue for potential benefits of adjuvant treatment with glutamatergic agents, especially memantine. By a targeted de-excitation effect on the glutamatergic system in the temporal lobes and connected brain regions, memantine might further alleviate OCD symptoms. This effect should be even more pronounced in certain subtypes of patients with specific cognitive deficits and maladaptive compensatory memory processes (e.g., checkers).

Prediction of treatment response and the effect of independent component neurofeedback in obsessive-compulsive disorder: a randomized, sham-controlled, double-blind study.

AIMS: The goal of this study was to assess the effect of independent component neurofeedback (NFB) on EEG and clinical symptoms in patients with obsessive-compulsive disorder (OCD). Subsequently, we explored predictors of treatment response and EEG correlates of clinical symptoms. METHODS: In a randomized, double-blind, parallel design, 20 inpatients with OCD underwent 25 sessions of NFB or sham feedback (SFB). NFB aimed at reducing EEG activity in an independent component previously reported abnormal in this diagnosis. Resting-state EEG recorded before and after the treatment was analyzed to assess its posttreatment changes, relationships with clinical symptoms and treatment response. RESULTS: Overall, clinical improvement in OCD patients was not accompanied by EEG change as assessed by standardized low-resolution electromagnetic tomography and normative independent component analysis. Pre- to posttreatment comparison of the trained component and frequency did not yield significant results; however, in the NFB group, the nominal values at the downtrained frequency were lower after treatment. The NFB group showed significantly higher percentage reduction of compulsions compared to the SFB group (p = 0.015). Pretreatment higher amount of delta (1-6 Hz) and low alpha oscillations as well as a lower amount of high beta activity predicted a worse treatment outcome. Source localization of these delta and high beta oscillations corresponded with previous EEG resting-state findings in OCD patients compared to healthy controls. CONCLUSION: Independent component NFB in OCD proved useful in percentage improvement of compulsions. Based on our correlation analyses, we hypothesize that we targeted a network related to treatment resistance.

Latent toxoplasmosis reduces gray matter density in schizophrenia but not in controls: voxel-based-morphometry (VBM) study.

OBJECTIVES: To address the role of latent T. gondii infection in schizophrenia we studied the influence of latent toxoplasmosis on brain morphology. METHODS: An optimized voxel-based morphometry of magnetic resonance imaging was analyzed by analysis of variance with diagnosis and seropositivity as factors in 44 schizophrenic patients (12 T. gondii positive) and 56 controls (13 T. gondii positive). RESULTS: Grey matter (GM) volume was reduced in schizophrenia patients compared with controls in the cortical regions, hippocampus and in the caudate. In the schizophrenia sample we found a significant reduction of GM volume in T. gondii positive comparing with T. gondii-negative patients bilaterally in the caudate, median cingulate, thalamus and occipital cortex and in the left cerebellar hemispheres. T. gondii-positive and -negative controls did not differ in any cluster. Among participants seropositive to T. gondii the reduction of GM in the schizophrenia subjects was located in the same regions when comparing the entire sample (11,660 over-threshold voxels (P ≤ 0.05, FWR corrected). The differences between T. gondii-negative patients and controls consisted only of 289 voxels in temporal regions. CONCLUSIONS: Our study is the first to document that latent toxoplasmosis reduces GM in schizophrenia but not in controls.

Electroencephalographic spectral and coherence analysis of ketamine in rats: correlation with behavioral effects and pharmacokinetics.

AIMS: This study was designed to evaluate the changes in EEG power spectra and EEG coherence in a ketamine model of psychosis in rats. Analyses of behavioral measurements--locomotion and sensorimotor gating--and the pharmacokinetics of ketamine and norketamine were also conducted. METHODS: Ketamine and norketamine levels in rat sera and brains were analyzed by gas chromatography-mass spectrometry after ketamine 30 mg/kg (i.p.). Ketamine 9 and 30 mg/kg (i.p.) were used in the behavioral and EEG experiments. Locomotor effects in an open field test and deficits in prepulse inhibition of acoustic startle reaction (PPI ASR) were evaluated in the behavioral experiments. EEG signals were simultaneously recorded from 12 implanted active electrodes; subsequently, an EEG power spectral and coherence analysis was performed. RESULTS: Ketamine had a rapid penetration into the brain; the peak concentrations of the drug were reached within 15 min after administration. Ketamine induced marked hyperlocomotion and deficits in the PPI ASR. EEG spectral analysis mainly showed increases in EEG power as well as coherence. These were most robust at 10-15 min after the administration and influenced all parts of the spectrum with ketamine 30 mg/kg. CONCLUSIONS: Ketamine at behaviorally active doses induces a robust increase in EEG power spectra and coherence. The maximum levels of change correlated with the kinetics of ketamine.

Augmentation of antidepressants with bright light therapy in patients with comorbid depression and borderline personality disorder.

BACKGROUND: Borderline personality disorder (BPD) is typically characterized by instability and impaired behaviour, affectivity, interpersonal relations and lifestyle. The most common condition comorbid with BPD is a depressive episode. Depression is associated with severe disturbance of the circadian rhythms. This is apparent in depressive patients with BPD. Both sleep and diurnal rhythms are disturbed and the symptoms fluctuate. Bright light may be an effective in treatment of seasonal affective disorder, circadian sleep disorder and jet lag. It also improves sleep-wake patterns and behavioural disorders in hospitalized patients with Alzheimer's disease. Several studies have suggested antidepressant effects of phototherapy in non-seasonal depressive episodes. The treatment of comorbid depressive disorder and borderline personality disorder (BPD) is usually reported to be less successful than the treatment of patients without personality disorder. Studies describing the use of bright light in depressed patients with comorbid BPD have not been published so far. METHOD: The aim of this open study was to assess the effectiveness of a 6-week combined therapy with the application of bright light (10,000 lux, 6:30 to 7:30 a.m. for 6 weeks) added to SSRIs in drug-resistant depressed patients with comorbid BPD who did not respond with improvement to 6-week administration of antidepressants. The study comprised 13 female patients who met the ICD-10 diagnostic criteria for research and the DSM-IV-TR diagnostic criteria for major depression. The participants were regularly evaluated using the CGI, HAMD and MADRS scales and the BDI and BDI self-report inventories. RESULTS: According to all the assessment instruments, the application of bright white light leads to a significant improvement. However, the results must be interpreted with caution due to the open nature of the study.