Retina as a potential biomarker in schizophrenia spectrum disorders: a systematic review and meta-analysis of optical coherence tomography and electroretinography.

INTRODUCTION: Abnormal findings on optical coherence tomography (OCT) and electroretinography (ERG) have been reported in participants with schizophrenia spectrum disorders (SSDs). This study aims to reveal the pooled standard mean difference (SMD) in retinal parameters on OCT and ERG among participants with SSDs and healthy controls and their association with demographic characteristics, clinical symptoms, smoking, diabetes mellitus, and hypertension. METHODS: Using PubMed, Scopus, Web of Science, and PSYNDEX, we searched the literature from inception to March 31, 2023, using specific search terms. This study was registered with PROSPERO (CRD4202235795) and conducted according to PRISMA 2020. RESULTS: We included 65 studies in the systematic review and 44 in the meta-analysis. Participants with SSDs showed thinning of the peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell layer- inner plexiform cell layer, and retinal thickness in all other segments of the macula. A meta-analysis of studies that excluded SSD participants with diabetes and hypertension showed no change in results, except for pRNFL inferior and nasal thickness. Furthermore, a significant difference was found in the pooled SMD of pRNFL temporal thickness between the left and right eyes. Meta-regression analysis revealed an association between retinal thinning and duration of illness, positive and negative symptoms. In OCT angiography, no differences were found in the foveal avascular zone and superficial layer foveal vessel density between SSD participants and controls. In flash ERG, the meta-analysis showed reduced amplitude of both a- and b-waves under photopic and scotopic conditions in SSD participants. Furthermore, the latency of photopic a-wave was significantly shorter in SSD participants in comparison with HCs. DISCUSSION: Considering the prior report of retinal thinning in unaffected first-degree relatives and the results of the meta-analysis, the findings suggest that retinal changes in SSDs have both trait and state aspects. Future longitudinal multimodal retinal imaging studies are needed to clarify the pathophysiological mechanisms of these changes and to clarify their utility in individual patient monitoring efforts.

Polydipsia and autistic traits in patients with schizophrenia spectrum disorders.

Introduction: Polydipsia, prevalent in 6%-20% of patients with schizophrenia, results in seclusion and prolonged hospitalization. It is also observed in autistic individuals, with previous studies reporting that autism accounted for 20% of all hospitalized patients with polydipsia. The current study investigated the association between polydipsia and autistic traits in patients with schizophrenia spectrum disorders (SSDs) based on the hypothesis that higher autistic traits would be observed in schizophrenic patients with polydipsia. Methods: In the first study (study A), the autism-spectrum quotient [(AQ); Japanese version] scores of long-stay inpatients with and without polydipsia were compared. Furthermore, the association between polydipsia and autistic traits was also examined in short-stay inpatients and outpatients with SSDs (study B). Results: Study A showed that patients with polydipsia scored significantly higher on the three AQ subscales (attention switching; communication; and imagination) compared to those without. Study B also showed that patients with polydipsia had significantly higher AQ scores overall and for several subscales compared to those without polydipsia. Binary logistic regression analysis of the combined sample showed that male gender and higher autistic traits were significant predictors of polydipsia. Discussion: The study highlights the importance of focusing on such traits to understand the pathogenesis of polydipsia in SSD patients.

Retinal layers and associated clinical factors in schizophrenia spectrum disorders: a systematic review and meta-analysis.

INTRODUCTION: The retina shares structural and functional similarities with the brain. Furthermore, structural changes in the retina have been observed in patients with schizophrenia spectrum disorders (SSDs). This systematic review and meta-analysis investigated retinal abnormalities and their association with clinical factors for SSD. METHODS: Studies related to retinal layers in SSD patients were retrieved from PubMed, Scopus, Web of Science, Cochrane Controlled Register of Trials, International Clinical Trials Registry Platform, and PSYNDEX databases from inception to March 31, 2021. We screened and assessed the eligibility of the identified studies. EZR ver.1.54 and the metafor package in R were used for the meta-analysis and a random-effects or fixed-effects model was used to report standardized mean differences (SMDs). RESULTS: Twenty-three studies (2079 eyes of patients and 1571 eyes of controls) were included in the systematic review and meta-analysis. The average peripapillary retinal nerve fiber layer (pRNFL) thickness, average macular thickness (MT), and macular ganglion cell layer-inner plexiform layer (GCL-IPL) thickness were significantly lower in patients than in controls (n = 14, 6, and 3, respectively; SMD = -0.33, -0.49, and -0.43, respectively). Patients also had significantly reduced macular volume (MV) compared to controls (n = 7; SMD = -0.53). The optic cup volume (OCV) was significantly larger in patients than in controls (n = 3; SMD = 0.28). The meta-regression analysis indicated an association between several clinical factors, such as duration of illness and the effect size of the pRNFL, macular GCL-IPL, MT, and MV. CONCLUSION: Thinning of the pRNFL, macular GCL-IPL, MT, and MV and enlargement of the OCV in SSD were observed. Retinal abnormalities may be applicable as state/trait markers in SSDs. The accumulated evidence was mainly cross-sectional and requires verification by longitudinal studies to characterize the relationship between OCT findings and clinical factors.

Mediating effects of self-stigma and depression on the association between autistic symptoms and recovery in patients with schizophrenia-spectrum disorders: a cross-sectional study.

BACKGROUND: Several studies have indicated that self-stigma is associated with depressive symptoms and could be a barrier to recovery in patients with schizophrenia-spectrum disorders. More recently, an association between autistic symptoms and self-stigma was found in schizophrenia-spectrum patients. This study aimed to investigate the association between self-stigma, autistic and depressive symptoms, and recovery in patients with schizophrenia. METHODS: In total, 105 participants were evaluated using the Autism Spectrum Quotient, the Internalized Stigma of Mental Illness Scale, the Quick Inventory of Depressive Symptomatology, and the Recovery Assessment Scale to investigate autistic symptoms, self-stigma, depressive symptoms, and recovery, respectively. The relationship between self-stigma, autistic symptoms, depressive symptoms, and recovery was assessed using structural equation modeling analysis. RESULTS: Impaired attention switching, one symptom of autism, was found to positively affect stereotype endorsement, which negatively influenced recovery through depressive symptoms. Moreover, problems with communication skills negatively affected recovery through depressive symptoms. Concerning self-stigma, stereotype endorsement and perceived discrimination had a negative effect on recovery through depressive symptoms, whereas stigma resistance had a direct negative effect on recovery. CONCLUSIONS: This study may provide meaningful insight into the psychological structure of recovery and could inform effective interventions for patients with schizophrenia-spectrum disorders. This was a cross-sectionally designed study; therefore, further longitudinal studies are needed to identify the causal relationships between self-stigma, autistic and depressive symptoms, and recovery.

Association Between OLIG2 Gene SNP rs1059004 and Negative Self-Schema Constructing Trait Factors Underlying Susceptibility to Depression.

Recent evidence has indicated that the disruption of oligodendrocytes may be involved in the pathogenesis of depression. Genetic factors are likely to affect trait factors, such as characteristics, rather than state factors, such as depressive symptoms. Previously, a negative self-schema had been proposed as the major characteristic of constructing trait factors underlying susceptibility to depression. Thus, the association between a negative self-schema and the functional single nucleotide polymorphism (SNP) rs1059004 in the OLIG2 gene, which influences OLIG2 gene expression, white matter integrity, and cerebral blood flow, was evaluated. A total of 546 healthy subjects were subjected to genotype and psychological evaluation using the Beck Depression Inventory-II (BDI-II) and the Brief Core Schema Scale (BCSS). The rs1059004 SNP was found to be associated with the self-schema subscales of the BCSS and scores on the BDI-II in an allele dose-dependent manner, and to have a predictive impact on depressive symptoms via a negative-self schema. The results suggest the involvement of a genetic factor regulating oligodendrocyte function in generating a negative-self schema as a trait factor underlying susceptibility to depression.

Association Between Autistic Symptoms and Self-Stigma in Patients with Schizophrenia Spectrum Disorders.

PURPOSE: Self-stigma negatively influences self-esteem, quality of life, self-efficacy, treatment adherence, and recovery in psychiatric patients. By revealing personality traits that influence self-stigma, we can gain useful knowledge for the management of self-stigma. A previous meta-analysis indicated that patients with schizophrenia have higher scores on the Autism-Spectrum Quotient (AQ) than healthy controls. However, the relationship between autistic symptoms and self-stigma in patients with schizophrenia spectrum disorders remains unclear. Therefore, the present study aimed to reveal the association between autistic symptoms and self-stigma in patients with schizophrenia spectrum disorders. PATIENTS AND METHODS: We recruited 127 patients with schizophrenia spectrum disorders (schizophrenia, schizoaffective disorder, and delusional disorder). We assessed participants' self-stigma and autistic symptoms using the Internalized Stigma for Mental Illness (ISMI) scale and the Autism-Spectrum Quotient (AQ), respectively. The differences in the scores of ISMI and AQ according to patient characteristics were investigated. Multiple regression analysis controlling for age and gender was performed to determine the relationship between the total scores on the AQ and IMSI scale. RESULTS: Female patients showed a higher level of self-stigma than males. Unmarried patients showed a significantly higher score on the AQ than married patients. Multiple regression analysis adjusted for age and gender indicated that the total score on AQ might be a predictor of the overall rating on ISMI in patients with schizophrenia spectrum disorders. CONCLUSION: This study is the first to reveal the association between autistic symptoms and self-stigma in patients with schizophrenia spectrum disorders. Our results highlight the importance of considering autistic symptoms in the assessment and management of self-stigma in patients with schizophrenia spectrum disorders.

The Impact of Health Consciousness on the Association Between Walking Durations and Mental Health Conditions After a Disaster: a Cross-Sectional Study.

BACKGROUND: In communities affected by a disaster, walking can be a feasible form of physical exercise to improve physical and mental health conditions. However, there is limited evidence to support relationships between walking habits and mental health conditions in post-disaster settings. Cross-sectional epidemiological data obtained from a questionnaire survey (conducted in October 2017) of a community affected by the 2011 Great East Japan Earthquake (GEJE) was analyzed to evaluate the relationships. METHODS: Participants included individuals over 20 years of age (N = 718) from Shichigahama town in Miyagi prefecture, whose houses were significantly damaged by the GEJE. Their mental health conditions were assessed by the Kessler Psychological Distress Scale (K6), the Center for Epidemiologic Studies Depression Scale (CES-D), and the Impact of Event Scale-Revised (IES-R). Additionally, the questionnaire asked the participants spent duration walking on average and their walking purpose by the following items: (1) longer than 60 min per day, (2) between 30 and 60 min per day, or (3) less than 30 min per day, and whether they walked to maintain healthy living habits (health-conscious walkers) or merely for transportation without considering health consequences (non-health-conscious walkers). These information and mental health indicators were analyzed using analysis of covariance (ANCOVA). RESULTS: Among the three walking duration groups of health-conscious walkers, there were significant differences in CES-D and K6 scores (p = 0.01 and p = 0.04), but not in IES-R scores, considering age, gender, and alcohol drinking habits as covariates. CES-D score was significantly higher among short walkers (p = 0.004). Among the three walking duration groups of non-health-conscious walkers, there were significant differences in avoidance symptoms, the subdomain of IES-R (p = 0.01), but not in CES-D, K6, and total IES-R scores, considering the variants. CONCLUSION: Our study suggests that walking durations may positively affect mood, but not PTSR, only when walking is performed with the purpose of maintaining healthy living habits. Walking durations were negatively associated with avoidance symptoms among non-health-conscious walkers in the community affected by the GEJE, indicating that the disaster may have had a long-lasting impact on walking habits.

Ethnicity-Dependent Effects of Schizophrenia Risk Variants of the OLIG2 Gene on OLIG2 Transcription and White Matter Integrity.

Previous studies have indicated associations between several OLIG2 gene single-nucleotide polymorphisms (SNPs) and susceptibility to schizophrenia among Caucasians. Consistent with these findings, postmortem brain and diffusion tensor imaging studies have indicated that the schizophrenia-risk-associated allele (A) in the OLIG2 SNP rs1059004 predicts lower OLIG2 gene expression in the dorsolateral prefrontal cortex (DLPFC) of schizophrenia patients and reduced white matter (WM) integrity of the corona radiata in normal brains among Caucasians. In an effort to replicate the association between this variant and WM integrity among healthy Japanese, we found that the number of A alleles was positively correlated with WM integrity in some fiber tracts, including the right posterior limb of the internal capsule, and with mean blood flow in a widespread area, including the inferior frontal operculum, orbital area, and triangular gyrus. Because the A allele affected WM integrity in opposite directions in Japanese and Caucasians, we investigated a possible association between the OLIG2 gene SNPs and the expression level of OLIG2 transcripts in postmortem DLPFCs. We evaluated rs1059004 and additional SNPs in the 5' upstream and 3' downstream regions of rs1059004 to cover the broader region of the OLIG2 gene. The 2 SNPs (rs1059004 and rs9653711) had opposite effects on OLIG2 gene expression in the DLPFC in Japanese and Caucasians. These findings suggest ethnicity-dependent opposite effects of OLIG2 gene SNPs on WM integrity and OLIG2 gene expression in the brain, which may partially explain the failures in replicating associations between genetic variants and psychiatric phenotypes among ethnicities.

Possible multiple system atrophy with predominant parkinsonism in a patient with chronic schizophrenia: a case report.

BACKGROUND: Multiple system atrophy (MSA) is an adult-onset, rare, and progressive neurodegenerative disorder characterized by a varying combination of autonomic failure, cerebellar ataxia, and parkinsonism. MSA is categorized as MSA-P with predominant parkinsonism, and as MSA-C with predominant cerebellar features. The prevalence of MSA has been reported to be between 1.86 and 4.9 cases per 100,000 individuals. In contrast, approximately 1% of the population is affected by schizophrenia during their lifetime; therefore, MSA-P comorbidity is very rare in schizophrenic patients. However, when the exacerbation or progression of parkinsonism occurs in patients with schizophrenia treated with antipsychotics, it is necessary to consider rare neurodegenerative disorders, including MSA-P, in the differential diagnosis of parkinsonism. CASE PRESENTATION: A 60-year-old female patient with chronic schizophrenia developed possible MSA-P. She had been treated mainly with typical antipsychotics, and presented with urinary incontinence, nocturnal polyuria, and dysarthria around 2011. In 2014, she developed worsening parkinsonian symptoms and autonomic dysfunction. Although her antipsychotic medication was switched to an atypical antipsychotic and the dose reduced, her parkinsonism was not improved. In 2015, modified electroconvulsive therapy produced slight improvements in the symptoms; however, she shortly returned to her symptomatic state. A combination of cardiac 123I-meta-iodobenzylguanidine scintigraphy and 123I-FP-CIT single-photon emission computed tomography imaging, in addition to brain magnetic resonance imaging findings, helped to discriminate MSA-P from other sources of parkinsonism. L-dopa had been prescribed, but she responded poorly and died in the spring of 2016. CONCLUSIONS: This case report highlights the importance of considering MSA-P in the differential diagnosis for parkinsonism in a patient being treated with antipsychotics for chronic schizophrenia. MSA-P should be considered in patients presenting with worsening and progressing parkinsonism, especially when accompanied by autonomic dysfunction or cerebellar ataxia. Although a definite diagnosis of MSA-P requires autopsy confirmation, a combination of brain magnetic resonance imaging and nuclear medicine scans may help to differentiate suspected MSA-P from the other parkinsonian syndromes. This case also demonstrates that MSA with parkinsonism that is poorly responsive to L-dopa may improve shortly after modified electroconvulsive therapy without worsening psychiatric symptoms.

[Natori EI project: the early intervention project for psychiatric disorders by the Miyagi Psychiatric Center].

Attempts to promote early intervention (EI) for psychiatric disorders are becoming accepted worldwide. Although several attempts at EI have begun in Japan, this movement is still limited, and the development of concrete EI services suited to individual regions is required. At the Miyagi Psychiatric Center, the "Natori EI project" is being carried out with the aim of improving the mental health of young people. This project involves three activities: consultation and mental health promotion in high schools, specialized outpatient clinics for young people, and psychosocial intervention for first-episode psychosis. There are many difficulties in building a system to support this kind of EI within the framework of the conventional medical care system; it is necessary to sort out issues such as collaboration with government and educational institutions, sharing the basic principle of EI, medical economic problems, ensuring manpower, and staff training system.

Construction of a remote radiotherapy planning system.

BACKGROUND: We constructed a remote radiotherapy planning system, and we examined the usefulness of and faults in our system in this study. METHODS: Two identical radiotherapy planning systems, one installed at our institution and the other installed at an affiliated hospital, were used for radiotherapy planning. The two systems were connected by a wide area network (WAN), using a leased line. Beam data for the linear accelerator at the affiliated hospital were installed in the two systems. During the period from December 2001 to December 2002, 43 remote radiotherapy plans were made using this system. RESULTS: Data were transmitted using a file transfer protocol (FTP) software program. The 43 radiotherapy plans examined in this study consisted of 13 ordinary radiotherapy plans, 28 radiotherapy plans sent to provide assistance for medical residents, and 2 radiotherapy plans for emergency cases. There were ten minor planning changes made in radiotherapy plans sent to provide assistance for medical residents. CONCLUSION: Our remote radiotherapy planning system based on WAN using a leased line is useful for remote radiotherapy, with advantages for both radiation oncologists and medical residents.

Long-term outcome of breast-conserving therapy for breast cancer.

PURPOSE: We present a retrospective analysis of long-term therapeutic results for patients treated in our institution to evaluate the efficacy of breast-conserving therapy (BCT). PATIENTS AND METHODS: The study population was 99 patients (102 breasts) with stage 0, I, and II breast cancer who underwent breast conservation therapy between April 1990 and November 1997. The entire breast was irradiated to a median dose of 50 Gy (range, 50-60 Gy) in 25-30 fractions. An additional 10 Gy in five fractions with 6-12 MeV electrons was given to 23 breasts (23%) with positive surgical margins. RESULTS: The 5-/10-year overall survival, cause-specific survival, relapse-free rate, local recurrence, and regional recurrence rates were 94.6/93.3%, 95.7/94.5%, 88.2/77.5%, 4.2/8.5%, and 2.0/6.3%, respectively. In both uni- and multivariate analyses, age < 40 years was a significant prognostic factor for local recurrence. No severe morbidity was observed. CONCLUSION: The long-term clinical outcome of BCT for early breast carcinoma patients in our department was favorable. Patient age <40 was the most important factor associated with an increased risk of local recurrence in the ipsilateral breast.

Results of radiation therapy for uterine cervical cancer using high dose rate remote after loading system.

In Japan, radiotherapy with high dose rate remote after loading system (HDR-RALS) for intracavitary brachytherapy is the standard treatment for more than 30 years. This report showed the usefulness of HDR-RALS for uterine cervical cancer. From 1980 through 1999, 442 patients with uterine cervical cancers (stage I: 66, stage II: 161, stage III: 165, stage IV: 50) were treated. Radiotherapy was performed both external teletherapy and HDR-RALS. Overall survival rate at 5 years was 60.2%. The 5-year actuarial incidence of all complications was 16.4%. The 5-year actuarial incidence of all complications in cases treated with the sum doses of whole pelvic irradiation (without central shield) and RALS up to 49 Gy, 50 to 59 Gy or larger doses were 7.5%, 11.0% and 25.2%, respectively. Radiation therapy using HDR-RALS was very effective. While the dose of whole pelvic irradiation was increased, the actuarial incidence of all complications was increased.