Functional connectivity in autism spectrum disorder evaluated using rs-fMRI and DKI.

We evaluated functional connectivity (FC) in patients with adult autism spectrum disorder (ASD) using resting-state functional MRI (rs-fMRI) and diffusion kurtosis imaging (DKI). We acquired rs-fMRI data from 33 individuals with ASD and 33 healthy controls (HC) and DKI data from 18 individuals with ASD and 17 HC. ASD showed attenuated FC between the right frontal pole (FP) and the bilateral temporal fusiform cortex (TFusC) and enhanced FC between the right thalamus and the bilateral inferior division of lateral occipital cortex, and between the cerebellar vermis and the right occipital fusiform gyrus (OFusG) and the right lingual gyrus, compared with HC. ASD demonstrated increased axial kurtosis (AK) and mean kurtosis (MK) in white matter (WM) tracts, including the right anterior corona radiata (ACR), forceps minor (FM), and right superior longitudinal fasciculus (SLF). In ASD, there was also a significant negative correlation between MK and FC between the cerebellar vermis and the right OFusG in the corpus callosum, FM, right SLF and right ACR. Increased DKI metrics might represent neuroinflammation, increased complexity, or disrupted WM tissue integrity that alters long-distance connectivity. Nonetheless, protective or compensating adaptations of inflammation might lead to more abundant glial cells and cytokine activation effectively alleviating the degeneration of neurons, resulting in increased complexity. FC abnormality in ASD observed in rs-fMRI may be attributed to microstructural alterations of the commissural and long-range association tracts in WM as indicated by DKI.

Factors associated with self-perceived treatment-resistance in bipolar disorder.

Patients with bipolar disorder often report self-perceived treatment resistance. However, it is not known to what extent it is due to actual treatment resistance. The Juntendo University provides "Bipolar Disorder Treatment Rebuilding Program," in which patients with self-reported treatment resistant bipolar disorder are hospitalized for 2 weeks and undergo detailed examinations. In this study, we report our experience with the initial 43 patients hospitalized during the one and half years after the launch of the program. Among the patients who underwent full assessment, only one was regarded as having genuine treatment-resistant bipolar disorder without comorbidity. In other cases, ten were not diagnosed with bipolar disorder, 3 had organic brain diseases, 12 had comorbid mental disorders and its symptoms were regarded as treatment-resistant bipolar symptoms by the patients, and 18 did not receive adequate treatment because attendant physicians did not adhere to the treatment guidelines or patients did not adhere to the treatment because of lack of insight. The number of participants was not large, and selection bias hampered the generalization of the findings. Insight and adherence were assessed without the use of validated tools. We could not verify recovery after adequate treatment because of the limited hospitalization period. The findings suggest that most patients with self-perceived treatment-resistant bipolar disorder may not have genuine treatment-resistant bipolar disorder. These results shed light on the difficulties of public education of bipolar disorder and importance of providing appropriate services for diagnosis and treatment of bipolar disorder in the community.

Brexpiprazole-Associated Pisa Syndrome (Pleurothotonus) in a Patient With Dementia.

OBJECTIVES: The aims of the study were to report brexpiprazole-induced Pisa syndrome (PS) in a patient with Alzheimer disease and to discuss the pathophysiology and the treatment of PS. METHODS: We report a 71-year-old female patient with Alzheimer disease. After 2 months medication of brexpiprazole, she presented PS. By switching to quetiapine, the symptom was ameliorated; however, transient acute dystonia was occurred. CONCLUSIONS: Drug-induced PS may be associated with dopamine-acetylcholine imbalance. This imbalance causes the dysfunction of the cortex and basal ganglia and the dysfunction of sensory and somatosensory system. Stopping the offending drugs is a choice for the treatment of PS. This is the first report of PS-induced brexpiprazole.

Identification of 22q11.2 deletion in a patient with schizophrenia and clinically diagnosed Rubinstein-Taybi syndrome.

Background: Rubinstein-Taybi syndrome (RTS) is a rare autosomal-dominant disease. Almost all cases are sporadic and attributed to de novo variant. Psychotic symptoms in RTS are rare and have been reported in only a few published cases. On the other hand, 22q11.2 deletion syndrome is the most common chromosomal microdeletion in humans. The 22q11.2 deletion is well recognized as a risk factor for schizophrenia. Here, we present a schizophrenic psychosis case clinically diagnosed as RTS but resolved as carrying 22q11.2 deletion by genomic analysis. Case presentation: A 38-year-old Japanese male was admitted to our hospital due to psychotic symptoms. He had been diagnosed with RTS based on physical characteristics at the age of 9 months. On admission, we performed whole exome sequencing. He had no pathogenic variant in CREBBP or EP300. We detected 2.5 Mb deletion on 22q11.2 and one rare loss-of-function variant in a loss-of-function-constrained gene (MTSS1) and three rare missense variants in missense-constrained genes (CELSR3, HERC1, and TLN1). Psychotic symptoms were ameliorated by the treatment of risperidone. Conclusion: The psychiatric manifestation and genomic analysis may be a clue to detecting 22q11.2 deletion syndrome in undiagnosed patients. The reason for similarity in physical characteristics in 22q11.2 deletion syndrome and RTS remains unresolved. The 22q11.2 deletion and HERC1 contribute to the patient's phenotype.

No association between glutathione-synthesis-related genes and Japanese schizophrenia.

AIMS: Schizophrenia is a major psychiatric disorder with complex genetic, environmental, and psychological causes, and oxidative stress may be involved in the pathogenesis of the disease. Glutathione (GSH), one of the main cellular non-protein antioxidants and redox regulators, and altered GSH levels have been reported in various regions in patients with schizophrenia. Three enzymes are responsible for GSH synthesis: glutamate cysteine ligase modifier (GCLM), glutamate cysteine ligase catalytic subunit (GCLC), and glutathione synthetase (GSS). Previously, positive associations between GCLM and schizophrenia were reported in Europeans, but not in the Japanese population. Thus, in this study, we investigated the association between the GSH synthesis genes (GCLM, GCLC, and GSS) and schizophrenia in Japanese individuals. METHODS: Seventeen single-nucleotide polymorphisms (SNP) in GCLM, GCLC, and GSS were genotyped in 358 patients with schizophrenia and in 359 controls. RESULTS: No SNP showed a significant association between their allelic or genotypic frequencies and schizophrenia. Case-control haplotype association analysis using windows of two or three SNP showed no significant associations with schizophrenia. The case-control haplotype analyses based on the ascertained linkage disequilibrium blocks also showed no significant associations in any genes with schizophrenia. CONCLUSIONS: The three primary GSH synthesis genes do not have an apparent degree of association with schizophrenia in the Japanese population.

Acquisition of multiple prior distributions in tactile temporal order judgment.

The Bayesian estimation theory proposes that the brain acquires the prior distribution of a task and integrates it with sensory signals to minimize the effect of sensory noise. Psychophysical studies have demonstrated that our brain actually implements Bayesian estimation in a variety of sensory-motor tasks. However, these studies only imposed one prior distribution on participants within a task period. In this study, we investigated the conditions that enable the acquisition of multiple prior distributions in temporal order judgment of two tactile stimuli across the hands. In Experiment 1, stimulation intervals were randomly selected from one of two prior distributions (biased to right hand earlier and biased to left hand earlier) in association with color cues (green and red, respectively). Although the acquisition of the two priors was not enabled by the color cues alone, it was significant when participants shifted their gaze (above or below) in response to the color cues. However, the acquisition of multiple priors was not significant when participants moved their mouths (opened or closed). In Experiment 2, the spatial cues (above and below) were used to identify which eye position or retinal cue position was crucial for the eye-movement-dependent acquisition of multiple priors in Experiment 1. The acquisition of the two priors was significant when participants moved their gaze to the cues (i.e., the cue positions on the retina were constant across the priors), as well as when participants did not shift their gazes (i.e., the cue positions on the retina changed according to the priors). Thus, both eye and retinal cue positions were effective in acquiring multiple priors. Based on previous neurophysiological reports, we discuss possible neural correlates that contribute to the acquisition of multiple priors.

No genetic association between the SLC1A2 gene and Japanese patients with schizophrenia.

Glutamatergic dysfunction may be a pathophysiological feature in the brains of schizophrenic patients. In addition to glutamate receptors, excitatory amino acid transporters (EAATs) have received much attention because they directly affect glutamatergic neurotransmission by excluding excessive glutamate from the synaptic cleft. Among these, EAAT2 (also known as solute carrier family 1, member 2; SLC1A2) has been widely studied in schizophrenia pathophysiology. During the last decade, we reported significant decreases in EAAT2 mRNA expression in the prefrontal cortex and parahippocampal gyrus in postmortem schizophrenic brains. Previously, a haplotype association between SLC1A2 and Japanese patients with schizophrenia was reported. In this study, we reinvestigated the association between SLC1A2 and schizophrenia by performing a case-control association study with twice as many subjects (401 cases and 407 controls) as compared to a previous study, and especially focused on the region where a previous association with schizophrenia had been shown. Our current results failed to show any significant association with schizophrenia in individual single nucleotide polymorphisms (SNPs), two- and three-SNP-based haplotypes, or with possible pairwise haplotype analysis. SCL1A2 appears not to be a genetic risk factor for schizophrenia.