BACKGROUND AND HYPOTHESIS: Schizophrenia is associated with altered energy metabolism, but the cause and potential impact of these metabolic changes remain unknown. 22q11.2 deletion syndrome (22q11.2DS) represents a genetic risk factor for schizophrenia, which is associated with the loss of several genes involved in mitochondrial physiology. Here we examine how the haploinsufficiency of these genes could contribute to the emergence of schizophrenia in 22q11.2DS. STUDY DESIGN: We characterize changes in neuronal mitochondrial function caused by haploinsufficiency of mitochondria-associated genes within the 22q11.2 region (PRODH, MRPL40, TANGO2, ZDHHC8, SLC25A1, TXNRD2, UFD1, and DGCR8). For that purpose, we combine data from 22q11.2DS carriers and schizophrenia patients, in vivo (animal models) and in vitro (induced pluripotent stem cells, IPSCs) studies. We also review the current knowledge about seven non-coding microRNA molecules located in the 22q11.2 region that may be indirectly involved in energy metabolism by acting as regulatory factors. STUDY RESULTS: We found that the haploinsufficiency of genes of interest is mainly associated with increased oxidative stress, altered energy metabolism, and calcium homeostasis in animal models. Studies on IPSCs from 22q11.2DS carriers corroborate findings of deficits in the brain energy metabolism, implying a causal role between impaired mitochondrial function and the development of schizophrenia in 22q11.2DS. CONCLUSIONS: The haploinsufficiency of genes within the 22q11.2 region leads to multifaceted mitochondrial dysfunction with consequences to neuronal function, viability, and wiring. Overlap between in vitro and in vivo studies implies a causal role between impaired mitochondrial function and the development of schizophrenia in 22q11.2DS.

• MeSH
• DiGeorgeův syndrom * genetika   MeSH
• lidé MeSH
• mikro RNA * metabolismus   MeSH
• mitochondrie genetika   metabolismus   MeSH
• proteiny vázající RNA metabolismus   MeSH
• ribonukleoproteiny metabolismus   MeSH
• ribozomální proteiny metabolismus   MeSH
• schizofrenie * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Astrocytes are the most abundant cell type in the human brain and are important regulators of several critical cellular functions, including synaptic transmission. Although astrocytes are known to play a central role in the etiology and pathophysiology of schizophrenia, little is known about their potential involvement in clinical response to the antipsychotic clozapine. Moreover, astrocytes display a remarkable degree of morphological diversity, but the potential contribution of astrocytic subtypes to disease biology and drug response has received little attention. Here, we used state-of-the-art human induced pluripotent stem cell (hiPSC) technology to derive a morphological subtype of astrocytes from healthy individuals and individuals with schizophrenia, including responders and nonresponders to clozapine. Using functional assays and transcriptional profiling, we identified a distinct gene expression signature highly specific to schizophrenia as shown by disease association analysis of more than 10 000 diseases. We further found reduced levels of both glutamate and the NMDA receptor coagonist d-serine in subtype astrocytes derived from schizophrenia patients, and that exposure to clozapine only rescued this deficiency in cells from clozapine responders, providing further evidence that d-serine in particular, and NMDA receptor-mediated glutamatergic neurotransmission in general, could play an important role in disease pathophysiology and clozapine action. Our study represents a first attempt to explore the potential contribution of astrocyte diversity to schizophrenia pathophysiology using a human cellular model. Our findings suggest that specialized subtypes of astrocytes could be important modulators of disease pathophysiology and clinical drug response, and warrant further investigations.

• MeSH
• antipsychotika farmakologie   MeSH
• astrocyty metabolismus   MeSH
• dospělí MeSH
• indukované pluripotentní kmenové buňky MeSH
• klozapin farmakologie   MeSH
• kyselina glutamová metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• schizofrenie farmakoterapie   metabolismus   MeSH
• serin metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Obesity is highly prevalent in schizophrenia, with implications for psychiatric prognosis, possibly through links between obesity and brain structure. In this longitudinal study in first episode of psychosis (FEP), we used machine learning and structural magnetic resonance imaging (MRI) to study the impact of psychotic illness and obesity on brain ageing/neuroprogression shortly after illness onset. METHODS: We acquired 2 prospective MRI scans on average 1.61 years apart in 183 FEP and 155 control individuals. We used a machine learning model trained on an independent sample of 504 controls to estimate the individual brain ages of study participants and calculated BrainAGE by subtracting chronological from the estimated brain age. RESULTS: Individuals with FEP had a higher initial BrainAGE than controls (3.39 ± 6.36 vs 1.72 ± 5.56 years; β = 1.68, t(336) = 2.59, P = .01), but similar annual rates of brain ageing over time (1.28 ± 2.40 vs 1.07±1.74 estimated years/actual year; t(333) = 0.93, P = .18). Across both cohorts, greater baseline body mass index (BMI) predicted faster brain ageing (β = 0.08, t(333) = 2.59, P = .01). For each additional BMI point, the brain aged by an additional month per year. Worsening of functioning over time (Global Assessment of Functioning; β = -0.04, t(164) = -2.48, P = .01) and increases especially in negative symptoms on the Positive and Negative Syndrome Scale (β = 0.11, t(175) = 3.11, P = .002) were associated with faster brain ageing in FEP. CONCLUSIONS: Brain alterations in psychosis are manifest already during the first episode and over time get worse in those with worsening clinical outcomes or higher baseline BMI. As baseline BMI predicted faster brain ageing, obesity may represent a modifiable risk factor in FEP that is linked with psychiatric outcomes via effects on brain structure.

• MeSH
• dospělí MeSH
• index tělesné hmotnosti MeSH
• lidé MeSH
• longitudinální studie MeSH
• magnetická rezonanční tomografie MeSH
• mladiství MeSH
• mladý dospělý MeSH
• obezita komplikace   diagnostické zobrazování   patologie   patofyziologie   MeSH
• předčasné stárnutí diagnostické zobrazování   etiologie   patologie   patofyziologie   MeSH
• progrese nemoci * MeSH
• psychotické poruchy diagnostické zobrazování   patologie   patofyziologie   MeSH
• rizikové faktory MeSH
• strojové učení * MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The recent renaissance of psychedelic science has reignited interest in the similarity of drug-induced experiences to those more commonly observed in psychiatric contexts such as the schizophrenia-spectrum. This report from a multidisciplinary working group of the International Consortium on Hallucinations Research (ICHR) addresses this issue, putting special emphasis on hallucinatory experiences. We review evidence collected at different scales of understanding, from pharmacology to brain-imaging, phenomenology and anthropology, highlighting similarities and differences between hallucinations under psychedelics and in the schizophrenia-spectrum disorders. Finally, we attempt to integrate these findings using computational approaches and conclude with recommendations for future research.

• MeSH
• halucinace chemicky indukované   diagnostické zobrazování   etiologie   patofyziologie   MeSH
• halucinogeny škodlivé účinky   MeSH
• lidé MeSH
• nervová síť diagnostické zobrazování   účinky léků   patofyziologie   MeSH
• schizofrenie komplikace   diagnostické zobrazování   patofyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• srovnávací studie MeSH

Background: The greater presence of neurodevelopmental antecedants may differentiate schizophrenia from bipolar disorders (BD). Machine learning/pattern recognition allows us to estimate the biological age of the brain from structural magnetic resonance imaging scans (MRI). The discrepancy between brain and chronological age could contribute to early detection and differentiation of BD and schizophrenia. Methods: We estimated brain age in 2 studies focusing on early stages of schizophrenia or BD. In the first study, we recruited 43 participants with first episode of schizophrenia-spectrum disorders (FES) and 43 controls. In the second study, we included 96 offspring of bipolar parents (48 unaffected, 48 affected) and 60 controls. We used relevance vector regression trained on an independent sample of 504 controls to estimate the brain age of study participants from structural MRI. We calculated the brain-age gap estimate (BrainAGE) score by subtracting the chronological age from the brain age. Results: Participants with FES had higher BrainAGE scores than controls (F(1, 83) = 8.79, corrected P = .008, Cohen's d = 0.64). Their brain age was on average 2.64 ± 4.15 years greater than their chronological age (matched t(42) = 4.36, P < .001). In contrast, participants at risk or in the early stages of BD showed comparable BrainAGE scores to controls (F(2,149) = 1.04, corrected P = .70, η2 = 0.01) and comparable brain and chronological age. Conclusions: Early stages of schizophrenia, but not early stages of BD, were associated with advanced BrainAGE scores. Participants with FES showed neurostructural alterations, which made their brains appear 2.64 years older than their chronological age. BrainAGE scores could aid in early differential diagnosis between BD and schizophrenia.

• MeSH
• bipolární porucha diagnostické zobrazování   MeSH
• diferenciální diagnóza MeSH
• dospělí MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• psychotické poruchy diagnostické zobrazování   MeSH
• riziko MeSH
• schizofrenie diagnostické zobrazování   MeSH
• strojové učení * MeSH
• věkové faktory MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

BACKGROUND: The phenomenology of the clinical symptoms indicates that disturbance of the sense of self be a core marker of schizophrenia. AIMS: To compare neural activity related to the self/other-agency judgment in patients with first-episode schizophrenia-spectrum disorders (FES, n = 35) and healthy controls (HC, n = 35). METHOD: A functional magnetic resonance imaging (fMRI) using motor task with temporal distortion of the visual feedback was employed. A task-related functional connectivity was analyzed with the use of independent component analysis (ICA). RESULTS: (1) During self-agency experience, FES showed a deficit in cortical activation in medial frontal gyrus (BA 10) and posterior cingulate gyrus, (BA 31; P < .05, Family-Wise Error [FWE] corrected). (2) Pooled-sample task-related ICA revealed that the self/other-agency judgment was dependent upon anti-correlated default mode and central-executive networks (DMN/CEN) dynamic switching. This antagonistic mechanism was substantially impaired in FES during the task. DISCUSSION: During self-agency experience, FES demonstrate deficit in engagement of cortical midline structures along with substantial attenuation of anti-correlated DMN/CEN activity underlying normal self/other-agency discriminative processes.

• MeSH
• cingulární gyrus patofyziologie   MeSH
• dospělí MeSH
• konektom metody   MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• nervová síť patofyziologie   MeSH
• percepční poruchy etiologie   patofyziologie   MeSH
• pohybová aktivita MeSH
• prefrontální mozková kůra patofyziologie   MeSH
• psychomotorický výkon MeSH
• schizofrenie komplikace   patofyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Abnormalities in both time processing and dopamine (DA) neurotransmission have been observed in schizophrenia. Time processing seems to be linked to DA neurotransmission. The cognitive dysmetria hypothesis postulates that psychosis might be a manifestation of the loss of coordination of mental processes due to impaired timing. The objective of the present study was to analyze timing abilities and their corresponding functional neuroanatomy in schizophrenia. We performed a functional magnetic resonance imaging (fMRI) study using a predictive motor timing paradigm in 28 schizophrenia patients and 27 matched healthy controls (HC). The schizophrenia patients showed accelerated time processing compared to HC; the amount of the acceleration positively correlated with the degree of positive psychotic symptoms and negatively correlated with antipsychotic dose. This dysfunctional predictive timing was associated with BOLD signal activity alterations in several brain networks, especially those previously described as timing networks (basal ganglia, cerebellum, SMA, and insula) and reward networks (hippocampus, amygdala, and NAcc). BOLD signal activity in the cerebellar vermis was negatively associated with accelerated time processing. Several lines of evidence suggest a direct link between DA transmission and the cerebellar vermis that could explain their relevance for the neurobiology of schizophrenia.

• MeSH
• dospělí MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mapování mozku MeSH
• mozek patofyziologie   MeSH
• nervová síť patofyziologie   MeSH
• pohybová aktivita fyziologie   MeSH
• schizofrenie patofyziologie   MeSH
• vermis cerebelli patofyziologie   MeSH
• vnímání času fyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: There is evidence of a positive association between insight and depression among patients with schizophrenia. Self-stigma was shown to play a mediating role in this association. We attempted to broaden this concept by investigating insight as a potential moderator of the association between depressive symptoms amongst people with schizophrenia and stigmatizing views towards people with mental disorders in their close social environment. METHOD: In the initial sample of 120 pairs, data were gathered from 96 patients with a diagnosis of "paranoid schizophrenia" and 96 of their nearest relatives (80% response rate). In this cross-sectional study data were collected by clinical interview using the following questionnaires: "The Scale to Assess Unawareness of Mental Disorder," "Calgary Depression Scale for Schizophrenia," and "Brief Psychiatric Rating Scale." The stigmatizing views of patients' nearest relatives towards people with mental disorders were assessed with the "Mental Health in Public Conscience" scale. RESULTS: Among patients with schizophrenia depressive symptom severity was positively associated with the intensity of nearest relatives' stigmatizing beliefs ("Nonbiological vision of mental illness," τ = 0.24; P < .001). The association was moderated by the level of patients' awareness of presence of mental disorder while controlling for age, sex, duration of illness and psychopathological symptoms. CONCLUSIONS: The results support the hypothesis that the positive association between patients' depression and their nearest relatives' stigmatizing views is moderated by patients' insight. Directions for further research and practical implications are discussed.

• MeSH
• deprese psychologie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• paranoidní schizofrenie psychologie   MeSH
• pilotní projekty MeSH
• průřezové studie MeSH
• rodina psychologie   MeSH
• schizofrenie (psychologie) * MeSH
• společenské stigma * MeSH
• uvědomování si fyziologie   MeSH
• zdraví - znalosti, postoje, praxe * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

It has been shown that learning a new skill leads to structural changes in the brain. However, it is unclear whether it is the acquisition or continuous practicing of the skill that causes this effect and whether brain connectivity of patients with schizophrenia can benefit from such practice. We examined the effect of 6 months exercise on a stationary bicycle on the brain in patients with schizophrenia and healthy controls. Biking is an endemic skill in the Netherlands and thus offers an ideal situation to disentangle the effects of learning vs practice. The 33 participating patients with schizophrenia and 48 healthy individuals were assigned to either one of two conditions, ie, physical exercise or life-as-usual, balanced for diagnosis. Diffusion tensor imaging brain scans were made prior to and after intervention. We demonstrate that irrespective of diagnosis regular physical exercise of an overlearned skill, such as bicycling, significantly increases the integrity, especially of motor functioning related, white matter fiber tracts whereas life-as-usual leads to a decrease in fiber integrity. Our findings imply that exercise of an overlearned physical skill improves brain connectivity in patients and healthy individuals. This has important implications for understanding the effect of fitness programs on the brain in both healthy subjects and patients with schizophrenia. Moreover, the outcome may even apply to the nonphysical realm.

• MeSH
• bílá hmota anatomie a histologie   patologie   MeSH
• cyklistika fyziologie   MeSH
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• následné studie MeSH
• schizofrenie patologie   terapie   MeSH
• terapie cvičením metody   MeSH
• výsledek terapie MeSH
• zobrazování difuzních tenzorů MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

Although latent infection with Toxoplasma gondii is among the most prevalent of human infections, it has been generally assumed that, except for congenital transmission, it is asymptomatic. The demonstration that latent Toxoplasma infections can alter behavior in rodents has led to a reconsideration of this assumption. When infected human adults were compared with uninfected adults on personality questionnaires or on a panel of behavioral tests, several differences were found. Other studies have demonstrated reduced psychomotor performance in affected individuals. Possible mechanisms by which T. gondii may affect human behavior include its effect on dopamine and on testosterone.

• MeSH
• Catellův osobnostní dotazník 16PF MeSH
• chronická nemoc MeSH
• dospělí MeSH
• financování organizované MeSH
• lidé MeSH
• mozková toxoplazmóza diagnóza   imunologie   parazitologie   psychologie   MeSH
• protilátky protozoální krev   MeSH
• psychomotorický výkon fyziologie   MeSH
• reakční čas MeSH
• schizofrenie (psychologie) MeSH
• schizofrenie diagnóza   imunologie   parazitologie   MeSH
• těhotenství MeSH
• Toxoplasma imunologie   MeSH
• věkové faktory MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Geografické názvy
• Česká republika MeSH