Availability of individual proteins for quantitative analysis in postmortem brains preserved in two different brain banks.

AIM: Postmortem brain research is necessary for elucidating the pathology of schizophrenia; an increasing number of studies require a combination of suitable tissue samples preserved at multiple brain banks. In this study, we examined whether a comparative study of protein expression levels can be conducted using postmortem brain samples preserved in different facilities. METHODS: We compared the demographic factors of postmortem brain samples preserved in two institutions and measured and compared the expression levels of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and glial fibrillary acidic protein (GFAP) in the prefrontal cortex and superior temporal gyrus. GAPDH is generally used as a loading control for western blotting, and GFAP is considered as an astrocyte marker in the brain. RESULTS: We found significant differences between the two institutions in postmortem interval, age at death, and preservation time. To reduce the effects of these differences on our measurements, the parameters were set as covariates in our analyses of covariance. Subsequently, no differences in GAPDH and GFAP expression were found between institutions. CONCLUSIONS: When studies are conducted using brain samples preserved in different brain banks, differences in demographic factors should be carefully considered and taken into account by statistical methods to minimize their impact as much as possible. Since there was no significant difference in the protein expression levels of GAPDH and GFAP in either region between the two institutions that preserved the postmortem brains, we concluded that it is possible to perform protein quantitative analysis assuming that there is no effect of difference between two institutions.

Oxytocin-induced increases in cytokines and clinical effect on the core social features of autism: Analyses of RCT datasets.

Although oxytocin may provide a novel therapeutics for the core features of autism spectrum disorder (ASD), previous results regarding the efficacy of repeated or higher dose oxytocin are controversial, and the underlying mechanisms remain unclear. The current study is aimed to clarify whether repeated oxytocin alter plasma cytokine levels in relation to clinical changes of autism social core feature. Here we analyzed cytokine concentrations using comprehensive proteomics of plasmas of 207 adult males with high-functioning ASD collected from two independent multi-center large-scale randomized controlled trials (RCTs): Testing effects of 4-week intranasal administrations of TTA-121 (A novel oxytocin spray with enhanced bioavailability: 3U, 6U, 10U, or 20U/day) and placebo in the crossover discovery RCT; 48U/day Syntocinon or placebo in the parallel-group verification RCT. Among the successfully quantified 17 cytokines, 4 weeks TTA-121 6U (the peak dose for clinical effects) significantly elevated IL-7 (9.74, 95 % confidence interval [CI] 3.59 to 15.90, False discovery rate corrected P (PFDR) < 0.001), IL-9 (56.64, 20.46 to 92.82, PFDR < 0.001) and MIP-1b (18.27, 4.96 to 31.57, PFDR < 0.001) compared with placebo. Inverted U-shape dose-response relationships peaking at TTA-121 6U were consistently observed for all these cytokines (IL-7: P < 0.001; IL-9: P < 0.001; MIP-1b: P = 0.002). Increased IL-7 and IL-9 in participants with ASD after 4 weeks TTA-121 6U administration compared with placebo was verified in the confirmatory analyses in the dataset before crossover (PFDR < 0.001). Furthermore, the changes in all these cytokines during 4 weeks of TTA-121 10U administration revealed associations with changes in reciprocity score, the original primary outcome, observed during the same period (IL-7: Coefficient = -0.05, -0.10 to 0.003, P = 0.067; IL-9: -0.01, -0.02 to -0.003, P = 0.005; MIP-1b: -0.02, -0.04 to -0.007, P = 0.005). These findings provide the first evidence for a role of interaction between oxytocin and neuroinflammation in the change of ASD core social features, and support the potential role of this interaction as a novel therapeutic seed. Trial registration: UMIN000015264, NCT03466671/UMIN000031412.

Patterns of C-reactive protein trends during clozapine titration and the onset of clozapine-induced inflammation: a case series of weekly and daily C-reactive protein monitoring.

Background: International guidelines for clozapine titration recommend measuring C-reactive protein (CRP) weekly for 4 weeks after clozapine initiation to prevent fatal inflammatory adverse events, including myocarditis. However, limited evidence exists regarding whether weekly CRP monitoring can prevent clozapine-induced inflammation. Aims: We examined the relationship between CRP trends and the development of clozapine-induced inflammation. We also explored the usefulness and limitations of CRP monitoring during clozapine titration. Method: This study presents 17 and 4 cases of weekly and daily CRP monitoring during clozapine initiation, respectively. Results: Among 17 patients with weekly CRP measurements, 7 had fever. Elevated CRP levels were detected before the onset of fever in two of the seven patients. Of the five remaining patients, the CRP levels on a previous test had been low; however, the fever developed suddenly. Of the 10 patients with no fever under weekly CRP monitoring, three had elevated CRP levels >3.0 mg/dL. Refraining from increasing the clozapine dose may have prevented fever in these patients. Among four patients with daily CRP measurements, two became febrile. In both cases, CRP levels increased almost simultaneously with the onset of fever. Conclusion: Weekly and daily CRP monitoring during clozapine titration is valuable for preventing clozapine-induced inflammation, assessing its severity, and guiding clozapine dose adjustments. Weekly CRP monitoring may not adequately predict clozapine-induced inflammation in some cases. Consequently, clinicians should be aware of the sudden onset of clozapine-induced inflammation, even if CRP levels are low. Daily CRP monitoring is better for detecting clozapine-induced inflammation.

Concomitant use of hydroxyzine and haloperidol did not worsen delirium in patients with cancer: A multicenter, retrospective, observational study.

OBJECTIVES: There is concern that hydroxyzine exacerbates delirium, but a recent preliminary study suggested that the combination of haloperidol and hydroxyzine was effective against delirium. This study examined whether the concomitant use of hydroxyzine and haloperidol worsened delirium in patients with cancer. METHODS: This retrospective, observational study was conducted at 2 general hospitals in Japan. The medical records of patients with cancer who received haloperidol for delirium from July to December 2020 were reviewed. The treatments for delirium included haloperidol alone or haloperidol combined with hydroxyzine. The primary outcome was the duration from the first day of haloperidol administration to the resolution of delirium, defined as its absence for 2 consecutive days. The time to delirium resolution was analyzed to compare the haloperidol group and hydroxyzine combination group using the log-rank test with the Kaplan-Meier method. Secondary outcomes were (1) the total dose of antipsychotic medications, including those other than haloperidol (measured in chlorpromazine-equivalent doses), and (2) the frequencies of detrimental incidents during delirium, specifically falls and self-removal of drip infusion lines. The unpaired t-test and Fisher's exact test were used to analyze secondary outcomes. RESULTS: Of 497 patients who received haloperidol, 118 (23.7%) also received hydroxyzine. No significant difference in time to delirium resolution was found between the haloperidol group and the hydroxyzine combination group (log-rank test, P = 0.631). No significant difference between groups was found in either chlorpromazine-equivalent doses or the frequency of detrimental incidents. SIGNIFICANCE OF RESULTS: This study showed that the concomitant use of hydroxyzine and haloperidol did not worsen delirium in patients with cancer.

Effect of concomitant use of valproic acid during clozapine initiation on clozapine-induced inflammation among Japanese patients with schizophrenia.

During clozapine initiation, titration speed and concomitant valproate administration have been reported as risk factors for clozapine-induced fever and myocarditis. We tested the risk of concomitant valproate administration by stratifying patients according to titration rate. Concomitant valproate use was only associated with increased inflammatory adverse events in the slower titration group. The frequency of inflammatory adverse events was approximately 30 % during faster titration, regardless of concomitant valproate administration. However, the faster titration group with valproate had a higher frequency of severe adverse effects such as myocarditis. Clinicians should avoid concomitant valproate administration during clozapine initiation, regardless of titration rate.

Marked alteration of phosphoinositide signaling-associated molecules in postmortem prefrontal cortex with bipolar disorder.

AIM: The etiology of bipolar disorder (BD) remains unknown; however, lipid abnormalities in BD have received increasing attention in recent years. In this study, we examined the expression levels of enzyme proteins associated with the metabolic pathway of phosphoinositides (PIs) and their downstream effectors, protein kinase B (Akt1) and glycogen synthase kinase 3ß (GSK3ß), which have been assumed to be the targets of mood stabilizers such as lithium, in the postmortem brains of patients with BD. METHODS: The protein expression levels of phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (PIP5K1C), phosphatidylinositol 4-kinase alpha (PIK4CA), phosphatase and tensin homolog deleted from chromosome 10 (PTEN), Akt1, and GSK3ß were measured using enzyme-linked immunosorbent assays and multiplex fluorescent bead-based immunoassays in the prefrontal cortex (PFC). Specifically, PTEN, Akt1, GSK3ß, and PIP5K1C were measured in seven BD patients and 48 controls. Additionally, PIK4CA was analyzed in 10 cases and 34 controls. RESULTS: PTEN expression levels were markedly decreased in the PFCs of patients with BD, whereas those of Akt and GSK3ß were prominently elevated. Moreover, patients medicated with lithium exhibited higher Akt1 expression levels and lower PTEN expression levels in comparison with the untreated group. CONCLUSION: Our results suggest that the expression levels of Akt1/GSK3ß and its upstream regulator PTEN are considerably altered.

Maternal social isolation and behavioral problems in preschool children: the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

It is essential to clarify factors associated with mental health and behavioral problems in early childhood, because children are critical stages of life for mental health. We aimed to prospectively examine the associations between maternal social isolation and behavioral problems in preschool children. We analyzed data from 5842 mother-child pairs who participated in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. The Lubben Social Network Scale-abbreviated version was used to assess social isolation (defined as scores < 12) one year after delivery. The Child Behavior Checklist 1½-5 was used to assess behavioral problems, and its subscales were used to assess internalizing and externalizing problems in children at 4 years of age. Multiple logistic regression analyses were conducted to examine the associations between social isolation and behavioral problems, after adjustment for age, education, income, work status, marital status, extraversion, neuroticism, depressive symptoms, child sex, and number of siblings. Multiple logistic regression analyses were also conducted for internalizing problems and externalizing problems. The prevalence of maternal social isolation was 25.4%. Maternal social isolation was associated with an increased risk of behavioral problems in children: the odds ratio (OR) was 1.37 (95% confidence interval [CI] 1.14-1.64). Maternal social isolation was also associated with increased risks of internalizing problems and externalizing problems in children: the ORs were 1.33 (95% CI, 1.12-1.59) and 1.40 (95% CI, 1.18-1.66), respectively. In conclusion, maternal social isolation one year after delivery was associated with behavioral problems in children at 4 years of age.

Live two-way video versus face-to-face treatment for depression, anxiety, and obsessive-compulsive disorder: A 24-week randomized controlled trial.

AIM: Live two-way video, easily accessible from home via smartphones and other devices, is becoming a new way of providing psychiatric treatment. However, lack of evidence for real-world clinical setting effectiveness hampers its approval by medical insurance in some countries. Here, we conducted the first large-scale pragmatic, randomized controlled trial to determine the effectiveness of long-term treatment for multiple psychiatric disorders via two-way video using smartphones and other devices, which are currently the primary means of telecommunication. METHODS: This randomized controlled trial compared two-way video versus face-to-face treatment for depressive disorder, anxiety disorder, and obsessive-compulsive disorder in the subacute/maintenance phase during a 24-week period. Adult patients with the above-mentioned disorders were allocated to either a two-way video group (≥50% video sessions) or a face-to-face group (100% in-person sessions) and received standard treatment covered by public medical insurance. The primary outcome was the 36-Item Short-Form Health Survey Mental Component Summary (SF-36 MCS) score. Secondary outcomes included all-cause discontinuation, working alliance, adverse events, and the severity rating scales for each disorder. RESULTS: A total of 199 patients participated in this study. After 24 weeks of treatment, two-way video treatment was found to be noninferior to face-to-face treatment regarding SF-36 MCS score (48.50 vs 46.68, respectively; p < 0.001). There were no significant differences between the groups regarding most secondary end points, including all-cause discontinuation, treatment efficacy, and satisfaction. CONCLUSION: Two-way video treatment using smartphones and other devices, was noninferior to face-to-face treatment in real-world clinical settings. Modern telemedicine, easily accessible from home, can be used as a form of health care.

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.

Slower clozapine titration is associated with delayed onset of clozapine-induced fever among Japanese patients with schizophrenia.

Clozapine-induced fever marks the beginning of its inflammatory and potentially life-threatening adverse effects, such as myocarditis. We retrospectively analyzed the correlation between clozapine titration rate and fever onset date in 254 Japanese patients, including 55 with treatment-resistant schizophrenia who developed clozapine-induced fever. Pearson's product-moment correlation indicated a significant delay in the fever onset date with slower titration. Most fever onset cases occurred within 4 weeks, even with slow titration. Therefore, clinicians should remain vigilant in monitoring clozapine-induced fever within 4 weeks of clozapine initiation, regardless of the titration rate.

Evidence for increased DNA damage repair in the postmortem brain of the high stress-response group of schizophrenia.

Background: Schizophrenia (SZ) is a disorder diagnosed by specific symptoms and duration and is highly heterogeneous, clinically and pathologically. Although there are an increasing number of studies on the association between genetic and environmental factors in the development of SZ, the actual distribution of the population with different levels of influence of these factors has not yet been fully elucidated. In this study, we focused on stress as an environmental factor and stratified SZ based on the expression levels of stress-responsive molecules in the postmortem prefrontal cortex. Methods: We selected the following stress-responsive molecules: interleukin (IL) -1ß, IL-6, IL-10, tumor necrosis factor-α, interferon-γ, glucocorticoid receptor, brain-derived neurotrophic factor, synaptophysin, S100 calcium-binding protein B, superoxide dismutase, postsynaptic density protein 95, synuclein, apolipoprotein A1 (ApoA1), ApoA2, and solute carrier family 6 member 4. We performed RNA sequencing in the prefrontal gray matter of 25 SZ cases and 21 healthy controls and conducted a hierarchical cluster analysis of SZ based on the gene expression levels of stress-responsive molecules, which yielded two clusters. After assessing the validity of the clusters, they were designated as the high stress-response SZ group and the low stress-response SZ group, respectively. Ingenuity Pathway Analysis of differentially expressed genes (DEGs) between clusters was performed, and Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining was conducted on four cases each in the high and low stress-response SZ groups to validate DNA damage. Results: We found higher prevalence of family history of SZ in the low stress-response SZ group (0/3 vs. 5/4, p = 0.04). Pathway analysis of DEGs between clusters showed the highest enrichment for DNA double-strand break repair. TUNEL staining showed a trend toward a lower percentage of TUNEL-positive cells in the high stress-response SZ group. Conclusion: Our results suggest that there are subgroups of SZ with different degrees of stress impact. Furthermore, the pathophysiology of these subgroups may be associated with DNA damage repair. These results provide new insights into the interactions and heterogeneity between genetic and environmental factors.

Ethnicity-dependent effect of rs1799971 polymorphism on OPRM1 expression in the postmortem brain and responsiveness to antipsychotics.

Schizophrenia is associated with aberration of inhibitory neurons. Although the mu-opioid receptor (MOR) is an essential modulator of inhibitory neurons, the effect of rs1799971 polymorphism in the MOR gene on risk of schizophrenia is controversial. Moreover, the disturbance of opioids systems in patients with schizophrenia has not been fully examined. We firstly conducted preliminary meta-analyses integrating Asian and European populations separately over 12,000 subjects to assess the effect of rs1799971 on risk of schizophrenia. Based on the above result, we also investigated the effect on the expression levels of MOR mRNA in the prefrontal cortex (PFC) and caudate nucleus of 41 postmortem brains. In addition, we determined whether these levels were related to antemortem schizophrenia symptoms and pharmacotherapeutic effects. The rs1799971 G-allele reduced the risk of schizophrenia in Asian populations (OR: 0.56, 95%CI: 0.32-0.98, p = 0.042) but increased it in European populations (OR: 1.66, 95%CI: 1.08-2.56, p = 0.022). It decreased MOR mRNA levels in PFC in the Japanese population (p = 0.031). Increased MOR mRNA level in PFC correlated with higher total score of antemortem schizophrenia symptoms (p = 0.017). Furthermore, the pharmacotherapeutic effect of first-generation antipsychotics was higher for genotype AA than AG/GG of rs1799971 (p = 0.036). The rs1799971 affects risk of schizophrenia and MOR mRNA expression and the effect varies according to ethnicity. Overexpression of MOR might induce severe schizophrenia symptoms. Therefore, MOR modulation may be the key clue for treating antipsychotics-resistant schizophrenia, and genotyping rs1799971 may provide a better pharmacotherapeutic strategy.

Tohoku Medical Megabank Brain Magnetic Resonance Imaging Study: Rationale, Design, and Background.

The Tohoku Medical Megabank Brain Magnetic Resonance Imaging Study (TMM Brain MRI Study) was established to collect multimodal information through neuroimaging and neuropsychological assessments to evaluate the cognitive function and mental health of residents who experienced the Great East Japan Earthquake (GEJE) and associated tsunami. The study also aimed to promote advances in personalized healthcare and medicine related to mental health and cognitive function among the general population. We recruited participants for the first (baseline) survey starting in July 2014, enrolling individuals who were participating in either the TMM Community-Based Cohort Study (TMM CommCohort Study) or the TMM Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study). We collected multiple magnetic resonance imaging (MRI) sequences, including 3D T1-weighted sequences, magnetic resonance angiography (MRA), diffusion tensor imaging (DTI), pseudo-continuous arterial spin labeling (pCASL), and three-dimensional fluid-attenuated inversion recovery (FLAIR) sequences. To assess neuropsychological status, we used both questionnaire- and interview-based rating scales. The former assessments included the Tri-axial Coping Scale, Impact of Event Scale in Japanese, Profile of Mood States, and 15-item Depression, Anxiety, and Stress Scale, whereas the latter assessments included the Mini-Mental State Examination, Japanese version. A total of 12,164 individuals were recruited for the first (baseline) survey, including those unable to complete all assessments. In parallel, we returned the MRI results to the participants and subsequently shared the MRI data through the TMM Biobank. At present, the second (first follow-up) survey of the study started in October 2019 is underway. In this study, we established a large and comprehensive database that included robust neuroimaging data as well as psychological and cognitive assessment data. In combination with genomic and omics data already contained in the TMM Biobank database, these data could provide new insights into the relationships of pathological processes with neuropsychological disorders, including age-related cognitive impairment.

The influence of tissue pH and RNA integrity number on gene expression of human postmortem brain.

Background: Evaluating and controlling confounders are necessary when investigating molecular pathogenesis using human postmortem brain tissue. Particularly, tissue pH and RNA integrity number (RIN) are valuable indicators for controlling confounders. However, the influences of these indicators on the expression of each gene in postmortem brain have not been fully investigated. Therefore, we aimed to assess these effects on gene expressions of human brain samples. Methods: We isolated total RNA from occipital lobes of 13 patients with schizophrenia and measured the RIN and tissue pH. Gene expression was analyzed and gene sets affected by tissue pH and RIN were identified. Moreover, we examined the functions of these genes by enrichment analysis and upstream regulator analysis. Results: We identified 2,043 genes (24.7%) whose expressions were highly correlated with pH; 3,004 genes (36.3%) whose expressions were highly correlated with RIN; and 1,293 genes (15.6%) whose expressions were highly correlated with both pH and RIN. Genes commonly affected by tissue pH and RIN were highly associated with energy production and the immune system. In addition, genes uniquely affected by tissue pH were highly associated with the cell cycle, whereas those uniquely affected by RIN were highly associated with RNA processing. Conclusion: The current study elucidated the influence of pH and RIN on gene expression profiling and identified gene sets whose expressions were affected by tissue pH or RIN. These findings would be helpful in the control of confounders for future postmortem brain studies.

Benefits of Working from Home During the COVID-19 Pandemic for Undiagnosed Workers with Attention-Deficit/Hyperactivity Disorder Symptoms.

Purpose: Our previous study suggested that working conditions might impact work productivity amid the COVID-19 pandemic. This study aimed to investigate the association between working from home (WFH) and depressive symptoms, work productivity, and quality of life (QOL), in undiagnosed workers with attention-deficit/hyperactivity disorder (ADHD) symptoms during the COVID-19 pandemic. Methods: During the pandemic, the survey was conducted among eligible workers with (N = 904) and without (N = 900) ADHD symptoms based on the Adult ADHD Self-Report Scale [ASRS]. Each group was further stratified by working conditions (full working on-site [FWOS], hybrid, full WFH [FWFH]). Two-way ANOVA was performed to investigate the impact of WFH on depressive symptoms (Patient Health Questionnaire [PHQ-9] score), work productivity (Work Productivity and Activity Impairment scale [WPAI] scores), and QOL (EuroQol 5-Dimensions 5-Levels [EQ-5D-5L] score). The Tukey-Kramer test was used to assess differences between the stratified subgroups. Poisson and multiple regression analyses were also performed to assess the factors associated with these outcomes. Results: Other than PHQ-9 score between FWOS and hybrid work in workers with ADHD symptoms (p < 0.05), no significant differences were observed in outcomes among the working condition subgroups in both workers with and without ADHD symptoms. In workers with ADHD symptoms, hybrid work and FWFH were significantly associated with a lower PHQ-9 score (hybrid, p < 0.001; FWFH, p < 0.05) but neither were significantly associated with WPAI score nor EQ-5D-5L. Annual income and discretionary work were significantly associated with a lower PHQ-9 score and a higher EQ-5D-5L score in workers with ADHD symptoms. Job type (manufacture/construction) was significantly associated with a lower presenteeism score. Conclusion: WFH (hybrid and FWFH) may be associated with lower depressive symptoms compared with FWOS in undiagnosed workers with ADHD symptoms. The findings may be useful when considering suitable working environments for workers especially with ADHD symptoms.

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.