- Anti-NMDA receptor antibody positivity in acute psychotic states: An exploratory study. [Journal Article]
- AJAsian J Psychiatr 2019 May 14; 43:95-98
- The glutamatergic theory of schizophrenia postulates N-methyl-D-aspartate receptor (NMDA-R) dysfunction. Anti-NMDA receptor antibodies may be present in some patients with psychosis. Fifteen patients…
The glutamatergic theory of schizophrenia postulates N-methyl-D-aspartate receptor (NMDA-R) dysfunction. Anti-NMDA receptor antibodies may be present in some patients with psychosis. Fifteen patients presenting with acute psychotic states having one additional clinical feature suggestive of autoimmune etiology were recruited. Serum antibodies against NMDA-receptor were tested at baseline and at follow-up using Indirect Immunofluorescence Technique. None of the 15 patients had positive anti-NMDA antibody at baseline or at follow-up. The study failed to detect anti-NMDA antibodies in patients with acute psychotic states with clinical suspicion of autoimmunity. This does not rule out other mechanisms of NMDA receptor dysfunction in these patients. The glutamatergic theory of schizophrenia postulates N-methyl-D-aspartate receptor (NMDA-R) dysfunction. Anti-NMDA receptor antibodies may be present in some patients with psychosis. Fifteen patients presenting with acute psychotic states having one additional clinical feature suggestive of autoimmune etiology were recruited. Serum antibodies against NMDA-receptor were tested at baseline and at follow-up using Indirect Immunofluorescence Technique. None of the 15 patients had positive anti-NMDA antibody at baseline or at follow-up. The study failed to detect anti-NMDA antibodies in patients with acute psychotic states with clinical suspicion of autoimmunity. This does not rule out other mechanisms of NMDA receptor dysfunction in these patients.
- Testing the expanded continuum hypothesis of schizophrenia and bipolar disorder. Neural and psychological evidence for shared and distinct mechanisms. [Journal Article]
- NCNeuroimage Clin 2019 May 04; 23:101854
- Despite the traditional view of Schizophrenia (SZ) and Bipolar disorder (BD) as separate diagnostic categories, the validity of such a categorical approach is challenging. In recent years, the hypoth…
Despite the traditional view of Schizophrenia (SZ) and Bipolar disorder (BD) as separate diagnostic categories, the validity of such a categorical approach is challenging. In recent years, the hypothesis of a continuum between Schizophrenia (SZ) and Bipolar disorder (BD), postulating a common pathophysiologic mechanism, has been proposed. Although appealing, this unifying hypothesis may be too simplistic when looking at cognitive and affective differences these patients display. In this paper, we aim to test an expanded version of the continuum hypothesis according to which the continuum extends over three clusters: the psychotic, the cognitive, and the affective. We applied an innovative approach known as Source-based Morphometry (SBM) to the structural images of 46 individuals diagnosed with SZ, 46 with BD and 66 healthy controls (HC). We also analyzed the psychological profiles of the three groups using cognitive, affective, and clinical tests. At a neural level, we found evidence for a shared psychotic core in a distributed network involving portions of the medial parietal and temporo-occipital areas, as well as parts of the cerebellum and the middle frontal gyrus. We also found evidence of a cognitive core more compromised in SZ, including alterations in a fronto-parietal circuit, and mild evidence of an affective core more compromised in BD, including portions of the temporal and occipital lobes, cerebellum, and frontal gyrus. Such differences were confirmed by the psychological profiles, with SZ patients more impaired in cognitive tests, while BD in affective ones. On the bases of these results we put forward an expanded view of the continuum hypothesis, according to which a common psychotic core exists between SZ and BD patients complemented by two separate cognitive and affective cores that are both impaired in the two patients' groups, although to different degrees.
- Appetite regulating hormones in first-episode psychosis: A systematic review and meta-analysis. [Review]
- NBNeurosci Biobehav Rev 2019 May 20
- We aimed to perform a systematic review and meta-analysis of appetite regulating hormones in patients with first-episode psychosis (FEP). Meta-analyses were conducted using random-effects models with…
We aimed to perform a systematic review and meta-analysis of appetite regulating hormones in patients with first-episode psychosis (FEP). Meta-analyses were conducted using random-effects models with Hedges' g as the effect size estimate. We identified 31 eligible studies, investigating the levels of 7 appetite regulating hormones (adiponectin, insulin, leptin, ghrelin, orexin, resistin and visfatin) in 1792 FEP patients and 1364 controls. The insulin levels in FEP patients were higher than in controls (g = 0.34, 95%CI: 0.19 - 0.49, p < 0.001), even considering only antipsychotic-naïve patients (g = 0.39, 95%CI: 0.12 - 0.66, p = 0.005). The severity of negative symptoms was positively associated with the effect size estimates (β = 0.08, 95%CI: 0.01 - 0.16, p = 0.030). Moreover, we found lower levels of leptin in antipsychotic-naïve FEP patients (g = -0.62, 95%CI: -1.11 - 0.12, p = 0.015). Impaired appetite regulation, in terms of elevated insulin levels and decreased leptin levels, occurs in early psychosis, before antipsychotic treatment. Hyperinsulinemia might be related to negative symptoms.
- Metformin reverses the schizophrenia-like behaviors induced by MK-801 in rats. [Journal Article]
- BRBrain Res 2019 May 20
- Schizophrenia is known to be a complex and disabling psychiatric disorder. Dopamine receptor antagonists have a significant therapeutic effect in improving the positive symptoms that are associated w…
Schizophrenia is known to be a complex and disabling psychiatric disorder. Dopamine receptor antagonists have a significant therapeutic effect in improving the positive symptoms that are associated with the illness. Therefore, dopamine receptor antagonists are commonly used in the treatment of schizophrenia; however, they do not achieve satisfactory results in improving negative symptoms and cognitive impairment. Metformin, widely known as an antidiabetic drug, has been found to enhance spatial memory formation and improve anxiety-like behaviors in rodents. Metformin's neuroprotective effect has been well documented in several neurological disorders including Alzheimer's disease, Parkinson's disease, strokes, Huntington's disease, and seizures. In the present study, we used a rat model to explore the effect of metformin on schizophrenia-like behaviors induced by MK-801 (dizocilpine), an N-methyl-D-aspartate (NMDA) receptor antagonist. We found that the pre-pulse inhibition (PPI) deficit caused by MK-801 could be alleviated by metformin. The hyperlocomotion in the open field test induced by chronic treatment of MK-801 was reversed by administration of metformin. Metformin has no effect on the baseline level of anxiety in normal naive rats, while metformin could relieve the anxiety-like behaviors in MK-801-treatment rats, though this effect is not reaching a significant level. Additionally, metformin could significantly ameliorate working memory impairments induced by MK-801. Moreover, the increased level of phosphorylation of Akt and GSK3β in the frontal cortex induced by MK-801 was normalized by metformin. In conclusion, our results demonstrate that metformin improved schizophrenia-like symptoms in rats, and is therefore a potential agent for the treatment of schizophrenia.
- Observed psychopathology in offspring of parents with major depressive disorder, bipolar disorder and schizophrenia. [Journal Article]
- PMPsychol Med 2019 May 23; :1-7
- CONCLUSIONS: Our results suggest that externalizing problems and cognitive and language difficulties may represent a general manifestation of familial risk for mood and psychotic disorders, while anxiety may be a specific marker of liability for mood disorders. Observer assessment may improve early identification of risk and selection of youth who may benefit from targeted prevention.
- Monitoring and improving antipsychotic adherence in outpatient forensic diversion programs. [Journal Article]
- CSCNS Spectr 2019 May 23; :1-9
- Outpatient diversion programs present an opportunity for severely mentally ill defendants to receive psychiatric treatment and have alleged offenses dismissed by the court. Moreover, the successful c…
Outpatient diversion programs present an opportunity for severely mentally ill defendants to receive psychiatric treatment and have alleged offenses dismissed by the court. Moreover, the successful completion of pretrial diversion is associated with fewer post-program arrest and jail days. The target patient population for such programs is typically people with schizophrenia spectrum disorders, but the care of such patients in outpatient settings presents challenges for monitoring treatment fidelity, specifically antipsychotic adherence, as low adherence rates are associated with increased rates of recidivism. Presented here is a review of evidence-based strategies that must be employed to track antipsychotic adherence in outpatient diversion programs, including pill counts, use of long-acting injectable antipsychotics, and determination of plasma antipsychotic levels to assess adherence and the adequacy of antipsychotic treatment. Antipsychotic therapy remains the foundation of schizophrenia treatment, but only through the use of all available modalities can clinicians maximize the odds that schizophrenia patients in pretrial diversion maintain psychiatric stability and successfully complete mental health court mandates.
- Quality of Life in Schizophrenia: A Meta-Analysis of Comparative Studies. [Journal Article]
- PQPsychiatr Q 2019 May 22
- Studies and findings regarding the impact of schizophrenia on quality of life (QOL) has been highly variable. This meta-analysis compared QOL between schizophrenia subjects and healthy controls with …
Studies and findings regarding the impact of schizophrenia on quality of life (QOL) has been highly variable. This meta-analysis compared QOL between schizophrenia subjects and healthy controls with a focus on standardized measures. A systematic literature search was conducted through Pubmed, PsycINFO, EMBASE, Cochrane Library and Web of Science databases. Only studies using the World Health Organization Quality of Life (WHOQOL) or its brief version or the Short Form-36 Health Survey (SF-36) were included. Fifteen case-control studies with 2195 schizophrenia subjects and 1508 healthy controls were included in this meta-analysis. The WHOQOL/WHOQOL-BREF score was significantly lower in physical health (SMD = -1.80, 95% CI: -2.31 to -1.28, P < 0.001), psychological health (SMD = -1.28, 95% CI: -1.72 to -0.83, P < 0.001), social relationships (SMD = -1.60, 95% CI: -2.05 to -1.15, P < 0.001), and environment domains (SMD = -0.98, 95% CI: -1.38 to -0.59, P < 0.001) in schizophrenia subjects compared to controls. The SF-36 score was significantly lower in both physical (SMD = -1.09, 95% CI: -1.41 to -0.76, P < 0.001 and mental health domains (SMD = -2.08, 95% CI: -3.58 to -0.59, P = 0.006) in schizophrenia subjects than in controls. Subgroup and meta-regression analyses found that age, male gender, illness duration and income have significant moderating effects on QOL. The meta-analysis of studies with standardized measures confirmed that QOL in schizophrenia subjects is significantly lower than healthy controls. Effective interventions should be developed to improve QOL for this population.
- An update on genetic frontotemporal dementia. [Journal Article]
- JNJ Neurol 2019 May 22
- Frontotemporal dementia (FTD) is a highly heritable group of neurodegenerative disorders, with around 30% of patients having a strong family history. The majority of that heritability is accounted fo…
Frontotemporal dementia (FTD) is a highly heritable group of neurodegenerative disorders, with around 30% of patients having a strong family history. The majority of that heritability is accounted for by autosomal dominant mutations in the chromosome 9 open reading frame 72 (C9orf72), progranulin (GRN), and microtubule-associated protein tau (MAPT) genes, with mutations more rarely seen in a number of other genes. This review will discuss the recent updates in the field of genetic FTD. Age at symptom onset in genetic FTD is variable with recently identified genetic modifiers including TMEM106B (in GRN carriers particularly) and a polymorphism at a locus containing two overlapping genes LOC101929163 and C6orf10 (in C9orf72 carriers). Behavioural variant FTD (bvFTD) is the most common diagnosis in each of the genetic groups, although in C9orf72 carriers amyotrophic lateral sclerosis either alone, or with bvFTD, is also common. An atypical neuropsychiatric presentation is also seen in C9orf72 carriers and family members of carriers are at greater risk of psychiatric disorders including schizophrenia and autistic spectrum disorders. Large natural history studies of presymptomatic genetic FTD are now underway both in Europe/Canada (GENFI-the Genetic FTD Initiative) and in the US (ARTFL/LEFFTDS study), collaborating together under the banner of the FTD Prevention Initiative (FPI). These studies are taking forward the validation of cognitive, imaging and fluid biomarkers that aim to robustly measure disease onset, staging and progression in genetic FTD. Grey matter changes on MRI and hypometabolism on FDG-PET are seen at least 10 years before symptom onset with white matter abnormalities seen earlier, but the pattern and exact timing of changes differ between different genetic groups. In contrast, tau PET has yet to show promise in genetic FTD. Three key fluid biomarkers have been identified so far that are likely to be helpful in clinical trials-CSF or blood neurofilament light chain levels (in all groups), CSF or blood progranulin levels (in GRN carriers) and CSF poly(GP) dipeptide repeat protein levels (in C9orf72 carriers). Increased knowledge about genetic FTD has led to more clinical presymptomatic genetic testing but this has not yet been mirrored in the development of either an accepted FTD-specific testing protocol or provision of appropriate psychological support mechanisms for those living through the at-risk phase. This will become even more relevant as disease-modifying therapy trials start in each of the genetic groups over the next few years.
- Phosphodiesterase 10A levels are related to striatal function in schizophrenia: a combined positron emission tomography and functional magnetic resonance imaging study. [Journal Article]
- EAEur Arch Psychiatry Clin Neurosci 2019 May 22
- Pharmacological inhibition of phosphodiesterase 10A (PDE10A) is being investigated as a treatment option in schizophrenia. PDE10A acts postsynaptically on striatal dopamine signaling by regulating ne…
Pharmacological inhibition of phosphodiesterase 10A (PDE10A) is being investigated as a treatment option in schizophrenia. PDE10A acts postsynaptically on striatal dopamine signaling by regulating neuronal excitability through its inhibition of cyclic adenosine monophosphate (cAMP), and we recently found it to be reduced in schizophrenia compared to controls. Here, this finding of reduced PDE10A in schizophrenia was followed up in the same sample to investigate the effect of reduced striatal PDE10A on the neural and behavioral function of striatal and downstream basal ganglia regions. A positron emission tomography (PET) scan with the PDE10A ligand [11C]Lu AE92686 was performed, followed by a 6 min resting-state magnetic resonance imaging (MRI) scan in ten patients with schizophrenia. To assess the relationship between striatal function and neurophysiological and behavioral functioning, salience processing was assessed using a mismatch negativity paradigm, an auditory event-related electroencephalographic measure, episodic memory was assessed using the Rey auditory verbal learning test (RAVLT) and executive functioning using trail-making test B. Reduced striatal PDE10A was associated with increased amplitude of low-frequency fluctuations (ALFF) within the putamen and substantia nigra, respectively. Higher ALFF in the substantia nigra, in turn, was associated with lower episodic memory performance. The findings are in line with a role for PDE10A in striatal functioning, and suggest that reduced striatal PDE10A may contribute to cognitive symptoms in schizophrenia.
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- Mindfulness-Based Social Cognition Training (SocialMind) for People With Psychosis: A Feasibility Trial. [Journal Article]
- FPFront Psychiatry 2019; 10:299
- CONCLUSIONS: This is the first implementation of SocialMind, which is the first mindfulness-based social cognition training. It is well tolerated by participants with schizophrenia spectrum disorders, and a further randomized controlled trial is proposed for people who have suffered their first episode of psychosis within the past 5 years. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03434405.