The relevance of anti-N-methyl-D-aspartate receptor encephalitis for psychiatrists.

Psychiatrists are often the first to be consulted in patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. While this disease is rare, psychiatrists need to be aware of its relevant fundamental, clinical and therapeutic aspects. We begin by reviewing the connection between anti-NMDAR encephalitis and the glutamate hypothesis of schizophrenia. Next, we focus on the profile of the patient typically afflicted with this disease. Then, we tackle the limited utility of current diagnostic criteria during the early stage of the disease. After reviewing the psychiatric features, we debate the quest for finding specific psychiatric phenotypes that could facilitate early-stage diagnosis. We conclude by discussing the treatment of psychiatric symptoms and disease outcomes. As follows, this paper presents the relevance of anti-NMDAR encephalitis for psychiatrists.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an essential differential diagnosis in Psychiatry, particularly when dealing with first-episode psychosis.Psychiatrists are often the first to be consulted in patients with NMDAR encephalitis, so they need to be aware of the relevant fundamental, clinical and therapeutic aspects of this disease.

The dopamine hypothesis of autism spectrum disorder: A comprehensive analysis of the evidence.

Despite intensive research into the etiopathogenesis of autism spectrum disorder (ASD), limited progress has been achieved so far. Among the plethora of models seeking to clarify how ASD arises, a coherent dopaminergic model was lacking until recently. In 2017, we provided a theoretical framework that we designated "the dopamine hypothesis of ASD". In the meantime, numerous studies yielded empirical evidence for this model. 4 years later, we provided a second version encompassing a refined and reconceptualized framework that accounted for these novel findings. In this chapter, we will review the evidence backing the previous versions of our model and add the most recent developments to the picture. Along these lines, we intend to lay out a comprehensive analysis of the supporting evidence for the dopamine hypothesis of ASD.

The Importance of Cerebrospinal Fluid Investigation in First-episode Psychosis.

Despite being a reliable first-hand source of data on neuronal pathology, cerebrospinal fluid (CSF) analysis remains an often-overlooked evaluation method in first-episode psychosis (FEP). In this paper, we begin by discussing the current role of CSF testing during FEP evaluation in clinical practice. Given that anti-N-methyl-D-aspartate receptor encephalitis presents with a clinical picture indistinguishable from FEP in >85% of cases, we debate the importance of testing for CSF neuronal antibodies in at least a subset of patients. Then, we continue by reviewing the most important recent studies which sought to identify potential CSF biomarkers in FEP caused by a primary psychiatric disorder. By circumventing traditional psychiatric classifications, characteristic biomarker profiles have the potential to become integral components of early diagnosis, disease stratification, treatment choice, and outcome prediction. Along these lines, we aim to provide an updated perspective on the importance of CSF investigation in FEP.

The Dopamine Hypothesis of Autism Spectrum Disorder Revisited: Current Status and Future Prospects.

Autism spectrum disorder (ASD) comprises a group of neurodevelopmental disorders characterized by social deficits and stereotyped behaviors. Despite intensive research, its etiopathogenesis remains largely unclear. Although studies consistently reported dopaminergic anomalies, a coherent dopaminergic model of ASD was lacking until recently. In 2017, we provided a theoretical framework for a "dopamine hypothesis of ASD" which proposed that autistic behavior arises from a dysfunctional midbrain dopaminergic system. Namely, we hypothesized that malfunction of 2 critical circuits originating in the midbrain, that is, the mesocorticolimbic and nigrostriatal pathways, generates the core behavioral features of ASD. Moreover, we provided key predictions of our model along with testing means. Since then, a notable number of studies referenced our work and numerous others provided support for our model. To account for these developments, we review all these recent data and discuss their implications. Furthermore, in the light of these new insights, we further refine and reconceptualize our model, debating on the possibility that various etiologies of ASD converge upon a dysfunctional midbrain dopaminergic system. In addition, we discuss future prospects, providing new means of testing our hypothesis, as well as its limitations. Along these lines, we aimed to provide a model which, if confirmed, could provide a better understanding of the etiopathogenesis of ASD along with new therapeutic strategies.

Genotype-phenotype Analysis of Paraoxonase 1 in Schizophrenic Patients Treated with Atypical Antipsychotics.

OBJECTIVE: Recent studies suggest a possible involvement of low paraoxonase 1 (PON1) enzyme activities in the association between schizophrenia, treatment with atypical antipsychotics and increased cardiovascular (CVD) risk. In the present study, we aimed at investigating the PON1 status in a group of schizophrenic patients treated with either olanzapine or other antipsychotic, as compared to a group of healthy control participants. METHODS: We assessed the arylesterase (AREase) and paraoxonase (POase) activities of PON1, as well as three common polymorphisms of PON1 gene (Q192R, L55M, -108C＞T). RESULTS: We found significantly lower (-13.3%) AREase activity in schizophrenic patients, along with significantly lower (-18.2%) POase activity in olanzapine-treated patients with QQ genotype. Furthermore, we found a significant difference between groups in L55M polymorphism distribution, whereas Q192R and -108C＞T polymorphisms distributions were similar. CONCLUSION: We identified the olanzapine-treated patients with QQ genotype as having the lowest PON1 (POase) activity, providing a possible way of identifying schizophrenic patients exposed to the greatest risk of CVD.

Low Retinal Dehydrogenase 1 (RALDH1) Level in Prepubertal Boys with Autism Spectrum Disorder: A Possible Link to Dopamine Dysfunction?

OBJECTIVE: Retinal dehydrogenase 1 (RALDH1) is a cytosolic enzyme which acts both as a source of retinoic acid (RA) and as a detoxification enzyme. RALDH1 has key functions in the midbrain dopaminergic system, which influences motivation, cognition, and social behavior. Since dopamine has been increasingly linked to autism spectrum disorder (ASD), we asked whether RALDH1 could contribute to the autistic phenotype. Therefore, we investigated for the first time the levels of RALDH1 in autistic patients. To further assess the detoxification function of RALDH1, we also explored 4-hydroxynonenal protein adducts (4-HNE PAs) and reduced glutathione (GSH) levels. Moreover, considering the effect of testosterone on RALDH1 expression, we measured the second to fourth digit ratio (2D:4D ratio) for both hands, which reflects exposure to prenatal testosterone. METHODS: Male patients with ASD (n=18; age, 62.9±4.3 months) and healthy controls (n=13; age, 78.1±4.9 months) were examined. Erythrocyte RALDH1, serum 4-HNE PAs and erythrocyte GSH levels were measured using colorimetric assays, and digit lengths were measured using digital calipers. RESULTS: We found significantly lower (-42.9%) RALDH1 levels in autistic patients as compared to controls (p=0.032). However, there was no difference in 4-HNE PAs levels (p=0.368), GSH levels (p=0.586), or 2D:4D ratios (p=0.246 in the left hand, p=0.584 in the right hand) between healthy controls and autistic subjects. CONCLUSION: We concluded that a subset of autistic patients had a low RALDH1 level. These results suggest that low RALDH1 levels could contribute to the autistic phenotype by reflecting a dopaminergic dysfunction.

A Dopamine Hypothesis of Autism Spectrum Disorder.

Autism spectrum disorder (ASD) comprises a group of neurodevelopmental disorders characterized by social deficits and stereotyped behaviors. While several theories have emerged, the pathogenesis of ASD remains unknown. Although studies report dopamine signaling abnormalities in autistic patients, a coherent dopamine hypothesis which could link neurobiology to behavior in ASD is currently lacking. In this paper, we present such a hypothesis by proposing that autistic behavior arises from dysfunctions in the midbrain dopaminergic system. We hypothesize that a dysfunction of the mesocorticolimbic circuit leads to social deficits, while a dysfunction of the nigrostriatal circuit leads to stereotyped behaviors. Furthermore, we discuss 2 key predictions of our hypothesis, with emphasis on clinical and therapeutic aspects. First, we argue that dopaminergic dysfunctions in the same circuits should associate with autistic-like behavior in nonautistic subjects. Concerning this, we discuss the case of PANDAS (pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections) which displays behaviors similar to those of ASD, presumed to arise from dopaminergic dysfunctions. Second, we argue that providing dopamine modulators to autistic subjects should lead to a behavioral improvement. Regarding this, we present clinical studies of dopamine antagonists which seem to have improving effects on autistic behavior. Furthermore, we explore the means of testing our hypothesis by using neuroreceptor imaging, which could provide comprehensive evidence for dopamine signaling dysfunctions in autistic subjects. Lastly, we discuss the limitations of our hypothesis. Along these lines, we aim to provide a dopaminergic model of ASD which might lead to a better understanding of the ASD pathogenesis.

From molecules to behavior: An integrative theory of autism spectrum disorder.

Autism spectrum disorder (ASD) comprises a group of neurodevelopmental disorders for which various theories have been proposed. Each theory brings valuable insights and has experimental evidence backing it, yet none provides an overarching explanation for each of the pathological aspects involved in ASD. Here we present an integrative theory of ASD, centered on a sequence of events spanning from the molecular to the behavioral level. We propose that an abnormality in the interplay between retinoic acid and sex hormones predisposes an individual to specific molecular malfunctions. In turn, this molecular syndrome generates an altered brain connectivity between the cerebellum, the midbrain dopaminergic areas, and the prefrontal cortex. Lastly, this disconnection would generate specific behavioral traits traditionally involved in ASD. Therefore, this paper represents a step forward in unifying different levels of pathological features into novel integrated testable hypotheses.