Psychological treatments for mental health symptoms associated with COVID-19 infection: A scoping review.

The aim of this scoping review was to synthesize published studies and ongoing clinical trials of psychological interventions for mental health problems associated with COVID-19 infection. The study protocol was developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Extension for Scoping Reviews. We conducted systematic searches for studies published or registered between January 2020 and October 2022 using eight scientific databases and clinical trial registries, which identified 40 complete published studies and 53 ongoing clinical trials. We found that most studies were randomized controlled trials (74%) while the remaining used study designs of lower methodological quality. Most studies investigated interventions for acute COVID-19 patients (74%) and others explored post-COVID conditions (PCC) or recovered patients. Cognitive and behavioral therapies were the main intervention approaches (31%), followed by multidisciplinary programs (21%) and mindfulness (17%). The most frequently evaluated outcomes were anxiety (33%), depression (26%), quality of life (13%), and insomnia (10%). No studies on youths, older people, or marginalized communities were found. These findings summarize the burgeoning research on a range of psychological interventions for individuals infected with COVID-19. However, the field is in its infancy and further research to develop an evidence base for targeted care is necessary. The gaps identified in the current study also highlight the need for more research on youths, older people, and members of marginalized communities, and PCC patients. It is important to ascertain interventions and delivery strategies that are not only effective and affordable but also allow high scalability and accessibility.

Reduced resting-state functional connectivity between insula and inferior frontal gyrus and superior temporal gyrus in hoarding disorder.

Background: Hoarding disorder (HD) is characterized by cognitive control impairments and abnormal brain activity in the insula and anterior cingulate cortex (ACC) during disposal of personal items or certain executive function tasks. However, whether there are any changes in resting-state functional connectivity of the insula and ACC remains unclear. Methods: A total of 55 subjects, including 24 patients with HD and 31 healthy controls (HCs), participated in the study. We acquired resting-state functional magnetic resonance imaging data and examined group differences in functional connectivity from the insula and ACC in whole-brain voxels. Results: In patients with HD, functional connectivity was significantly lower between the right insula and right inferior frontal gyrus (IFG) and left superior temporal gyrus (STG) compared to HCs. There was no correlation between these connectivities and HD symptoms. Conclusions: Although the clinical implication is uncertain, our results suggest that patients with HD have resting-state functional alterations between the insula and IFG and STG, corresponding with the results of previous fMRI studies. These findings provide new insight into the neurobiological basis of HD.

Association between retinopathy and risk of dementia in a general Japanese population: the Hisayama Study.

We investigated the association of retinopathy with the risk of dementia in a general older Japanese population. A total of 1709 population-based residents aged 60 years or older without dementia were followed prospectively for 10 years (2007-2017). They underwent color fundus photography in 2007. Retinopathy was graded according to the Modified Airlie House Classification. Main outcome was the Incidence of dementia. A Cox proportional hazards model was used to estimate the hazard ratios (HRs) and their 95% confidence intervals (CIs) for the risk of dementia by the presence of retinopathy. During the follow-up period, 374 participants developed all-cause dementia. The cumulative incidence of dementia was significantly higher in those with retinopathy than those without (p < 0.05). Individuals with retinopathy had significantly higher risk of developing dementia than those without after adjustment for potential confounding factors (HR 1.64, 95% CI 1.19-2.25). Regarding the components of retinopathy, the presence of microaneurysms was significantly associated with a higher multivariable-adjusted HR for incident dementia (HR 1.94, 95% CI 1.37-2.74). Our findings suggest that, in addition to systemic risk factors, retinal microvascular signs from fundus photography provide valuable information for estimating the risk of developing dementia.

Does childhood maltreatment affect hikikomori via traits of modern-type depression?

BACKGROUND: In the 1990s, the concepts of hikikomori and modern-type depression (MTD) emerged in Japan. Hikikomori is a condition of social avoidance or isolation, characterized by staying at home and being physically isolated for at least six months. MTD is characterized by depressive symptoms-mainly in stressful work or school situations during adolescence and early adulthood-which tend to rapidly reduce or disappear after leaving the stressful situation. We hypothesized that childhood maltreatment can form MTD traits that lead to hikikomori. METHODS: As a first step, we conducted a multigroup path analysis between childhood maltreatment, MTD traits, and physical isolation in the hikikomori group. This study utilized the nine-item Patient Health Questionnaire (PHQ-9), Home Environment Questionnaire (HEQ), 22-item Tarumi Modern-Type Depressive Trait Scale (TACS-22), 25-item Hikikomori Questionnaire (HQ-25), and Hamilton Depression Rating Scale (HDRS). The HQ-25 contains three factors: physical isolation, lack of socialization, and lack of emotional support. RESULTS: The hikikomori group included 92 patients and the control group comprised 137 healthy individuals. All total and subscale scores of PHQ-9, HEQ, TACS-22, HQ-25, and HDRS were significantly higher in the hikikomori group than in the control group. The risk model of childhood maltreatment for physical isolation via MTD traits obtained good fit with a goodness-of-fit index of.982. LIMITATIONS: The study's limitations were its sample selection bias, cross-sectional design, and use of self-report scales. CONCLUSIONS: Our findings support the hypothesis that childhood maltreatment is an important risk factor for hikikomori via MTD traits.

Incidence of post-COVID psychiatric disorders according to the periods of SARS-CoV-2 variant dominance: The LIFE study.

This retrospective cohort study examined the incidence of post-COVID psychiatric disorders in older adults according to hospitalization status and SARS-CoV-2 variant period in Japan. Claims data, COVID-19 case-related information, and vaccination records were obtained from three Japanese municipalities. We identified individuals aged ≥65 years who had COVID-19 or other respiratory tract infection (RTI) between March 2021 and December 2022. Participants were categorized into non-hospitalized and hospitalized patients, and the study period was divided into the Alpha (March to May 2021), Delta (June to December 2021), Omicron BA.1/BA.2 (January to June 2022), and Omicron BA.5 (July to December 2022) periods. Modified Poisson regression analyses were performed to estimate the incidence rate ratios (IRRs) for the occurrence of psychiatric disorders (organic mental disorders, psychotic disorders, mood disorders, anxiety disorders, and insomnia) three months after COVID-19 (reference: other RTI). For overall psychiatric disorders, we analyzed 19,489 non-hospitalized patients (COVID-19: 6,728, Other RTI: 12,761) and 2925 hospitalized patients (COVID-19: 1,036, Other RTI: 1889). When compared with other RTI cases, COVID-19 cases had significantly lower IRRs for overall psychiatric disorders in both non-hospitalized (IRR: 0.59, P < 0.001) and hospitalized cases (IRR: 0. 83, P = 0.045) during the Omicron BA.1/BA.2 period, but only in non-hospitalized cases (IRR: 0.45, P < 0.001) during the Omicron BA.5 period. The incidences of the individual post-COVID psychiatric disorders varied according to disorder type, hospitalization status, and SARS-CoV-2 variant period. These findings provide a foundation for further research to explore these variations and improve the provision of psychiatric care in future epidemics.

Aberrant thalamocortical connectivity and shifts between the resting state and task state in patients with schizophrenia.

Prominent pathological hypotheses for schizophrenia include auditory processing deficits and dysconnectivity within cerebral networks. However, most neuroimaging studies have focused on impairments in either resting-state or task-related functional connectivity in patients with schizophrenia. The aims of our study were to examine (1) blood oxygen level-dependent (BOLD) signals during auditory steady-state response (ASSR) tasks, (2) functional connectivity during the resting-state and ASSR tasks and (3) state shifts between the resting-state and ASSR tasks in patients with schizophrenia. To reduce the functional consequences of scanner noise, we employed resting-state and sparse sampling auditory fMRI paradigms in 25 schizophrenia patients and 25 healthy controls. Auditory stimuli were binaural click trains at frequencies of 20, 30, 40 and 80 Hz. Based on the detected ASSR-evoked BOLD signals, we examined the functional connectivity between the thalamus and bilateral auditory cortex during both the resting state and ASSR task state, as well as their alterations. The schizophrenia group exhibited significantly diminished BOLD signals in the bilateral auditory cortex and thalamus during the 80 Hz ASSR task (corrected p < 0.05). We observed a significant inverse relationship between the resting state and ASSR task state in altered functional connectivity within the thalamo-auditory network in schizophrenia patients. Specifically, our findings demonstrated stronger functional connectivity in the resting state (p < 0.004) and reduced functional connectivity during the ASSR task (p = 0.048), which was mediated by abnormal state shifts, within the schizophrenia group. These results highlight the presence of abnormal thalamocortical connectivity associated with deficits in the shift between resting and task states in patients with schizophrenia.

DNA methylation-altered genes in the rat hippocampal neurogenic niche after continuous exposure to amorphous curcumin.

Rat offspring who are exposed to an amorphous formula of curcumin (CUR) from the embryonic stage have anti-anxiety-like behaviors, enhanced fear extinction learning, and increased synaptic plasticity in the hippocampal dentate gyrus (DG). In the present study, we investigated the links between genes with altered methylation status in the neurogenic niche and enhanced neural functions after CUR exposure. We conducted methylation and RNA sequencing analyses of the DG of CUR-exposed rat offspring on day 77 after delivery. Methylation status and transcript levels of candidate genes were validated using methylation-sensitive high-resolution melting and real-time reverse-transcription PCR, respectively. In the CUR group, we confirmed the hypermethylation and downregulation of Gpr150, Mmp23, Rprml, and Pcdh8 as well as the hypomethylation and upregulation of Ppm1j, Fam222a, and Opn3. Immunohistochemically, reprimo-like+ hilar cells and protocadherin-8+ granule cells were decreased and opsin-3+ hilar cells were increased by CUR exposure. Both reprimo-like and opsin-3 were partially expressed on subpopulations of glutamic acid decarboxylase 67+ γ-aminobutyric acid-ergic interneurons. Furthermore, the transcript levels of genes involved in protocadherin-8-mediated N-cadherin endocytosis were altered with CUR exposure; this was accompanied by Ctnnb1 and Syp upregulation and Mapk14, Map2k3, and Grip1 downregulation, suggesting that CUR-induced enhanced synaptic plasticity is associated with cell adhesion. Together, our results indicate that functionally different genes have altered methylation and expression in different neuronal populations of the hippocampal neurogenic niche, thus enhancing synaptic plasticity after CUR exposure.

Associations between COVID-19 vaccination and incident psychiatric disorders after breakthrough SARS-CoV-2 infection: The VENUS Study.

BACKGROUND: The associations between COVID-19 vaccination and post-COVID psychiatric disorders are unclear. Furthermore, it is uncertain if these associations differ depending on the dominant SARS-CoV-2 variant at the time of infection. This retrospective cohort study aimed to clarify the associations between COVID-19 vaccination and incident psychiatric disorders after breakthrough infection according to the different variant periods in Japan. METHODS: Medical claims data, COVID-19 case-related information, and vaccination records were collected from three Japanese municipalities. The study population comprised public insurance enrollees aged ≥65 years who developed COVID-19 between June 2021 and December 2022. The study exposure was each participant's vaccination status 14 days before infection, and the outcomes were the occurrence of psychiatric disorders within three months of infection. Multivariable logistic regression analyses were performed to calculate the odds ratios (ORs) and 95 % confidence intervals (CIs) of vaccination for the occurrence of psychiatric disorders. Analyses were conducted for the Delta period (June to December 2021), Omicron BA.1/BA.2 period (January to June 2022), and Omicron BA.5 period (July to December 2022). RESULTS: We analyzed 270 participants (vaccinated: 149) in the Delta period, 2,963 participants (vaccinated: 2,699) in the Omicron BA.1/BA.2 period, and 7,723 participants (vaccinated: 7,159) in the Omicron BA.5 period. During the Delta period, vaccinated participants had significantly lower odds for psychotic disorders (OR: 0.23, 95 % CI: 0.06-0.88, P = 0.032) than unvaccinated participants. During the Omicron BA.5 period, vaccinated participants had significantly lower odds for organic mental disorders (OR: 0.54, 95 % CI: 0.30-0.95, P = 0.033), psychotic disorders (OR: 0.31, 95 % CI: 0.19-0.53, P < 0.001), mood disorders (OR: 0.53, 95 % CI: 0.29-0.99, P = 0.046), and insomnia (OR: 0.48, 95 % CI: 0.32-0.72, P < 0.001) than unvaccinated participants. There were no significant differences in psychiatric disorders between the vaccinated and unvaccinated groups during the Omicron BA.1/BA.2 period. CONCLUSIONS: This is the first study to demonstrate that the associations between COVID-19 vaccination and post-COVID psychiatric disorders vary among the different variant periods. Future studies on these associations should be conducted with consideration to the prevalent circulating variants.

Development of depression assessment tools using humanoid robots -Can tele-operated robots talk with depressive persons like humans?

BACKGROUND: Depression is a common mental disorder and causes significant social loss. Early intervention for depression is important. Nonetheless, depressed patients tend to conceal their symptoms from others based on shame and stigma, thus hesitate to visit psychiatrists especially during early phase. We hypothesize that application of humanoid robots would be a novel solution. Depressed patients may feel more comfortable talking with such robots than humans. METHODS: We recruited 13 patients with major depressive disorder (MDD) and 27 healthy volunteers as controls. Participants took both tele-operated humanoid robot and human interviews to evaluate severity of depression using the Hamilton Depression Rating Scale (HDRS). In addition, participants completed a self-administered questionnaire asking about their impressions of the robot interview. RESULTS: Confidence interval and t-test analysis have revealed that the HDRS scores are equally reliable between robot and human interviews. No significant differences were observed between the two interviews regarding "nervousness about the interview" and "hesitancy to talk about depressed moods and suicidal ideation." Compared to human interviews, robot interviews yielded significantly lower scores on shame-related factors especially among patients with MDD. LIMITATION: Small sample size, and the evaluator is male only. CONCLUSIONS: This is the first report to show the reliability of tele-operated humanoid robot interviews for assessment of depression. Robot interviews are potentially equally reliable as human interviews. Robot interviews are suggested to be more appropriate in assessing shame-related suppressed emotions and hidden thoughts of depressed patients in clinical practice, which may reduce the stigma associated with depression.

Risks of dementia in a general Japanese older population with preserved ratio impaired spirometry: The Hisayama Study.

BACKGROUND: Studies on the association between preserved ratio impaired spirometry (PRISm) and dementia are limited. Indeed, PRISm has often been overlooked or ignored as an index of lung function impairment. Therefore, we investigated the association of PRISm with the risk for the development of dementia in an older Japanese population. METHODS: A total of 1202 community-dwelling, older Japanese participants aged ≥65 years without dementia were followed up for a median of 5.0 years. Participants were categorized by spirometry as follows: normal spirometry (FEV1/FVC ≥0.70 and FEV1 ≥80% predicted), PRISm (≥0.70 and <80%), airflow limitation (AFL) Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 (<0.70 and ≥80%), and AFL GOLD 2 to 4 (<0.70 and <80%). Hazard ratios (HRs) and their 95% confidence intervals (CIs) were computed using a Cox proportional hazards model. RESULTS: During the follow-up period, 122 participants developed dementia. The age- and sex-adjusted incidences of dementia in the participants with normal spirometry, PRISm, AFL GOLD 1, and AFL GOLD 2 to 4 were 20.5, 37.0, 18.4, and 28.6 per 1000 person-years, respectively. Participants with PRISm had a higher risk of dementia (HR 2.04 [95%CI, 1.19-3.49]) than those with normal spirometry after adjusting for confounders. Moreover, both reduced FEV1% predicted values and FVC% predicted values were associated with the risk for dementia. CONCLUSION: PRISm was associated with an increased risk of dementia in a general older Japanese population.

Abnormal phase entrainment of low- and high-gamma-band auditory steady-state responses in schizophrenia.

Introduction: Gamma-band oscillatory deficits have attracted considerable attention as promising biomarkers of schizophrenia (SZ). Notably, a reduced auditory steady-state response (ASSR) in the low gamma band (40 Hz) is widely recognized as a robust finding among SZ patients. However, a comprehensive investigation into the potential utility of the high-gamma-band ASSR in detecting altered neural oscillations in SZ has not yet been conducted. Methods: The present study aimed to assess the ASSR using magnetoencephalography (MEG) data obtained during steady-state stimuli at frequencies of 20, 30, 40, and 80 Hz from 23 SZ patients and 21 healthy controls (HCs). To evaluate the ASSR, we examined the evoked power and phase-locking factor (PLF) in the time-frequency domain for both the primary and secondary auditory cortices. Furthermore, we calculated the phase-locking angle (PLA) to examine oscillatory phase lead or delay in SZ patients. Taking advantage of the high spatial resolution of MEG, we also focused on the hemispheric laterality of low- and high-gamma-band ASSR deficits in SZ. Results: We found abnormal phase delay in the 40 Hz ASSR within the bilateral auditory cortex of SZ patients. Regarding the 80 Hz ASSR, our investigation identified an aberrant phase lead in the left secondary auditory cortex in SZ, accompanied by reduced evoked power in both auditory cortices. Discussion: Given that abnormal phase lead on 80 Hz ASSR exhibited the highest discriminative power between HC and SZ, we propose that the examination of PLA in the 80 Hz ASSR holds significant promise as a robust candidate for identifying neurophysiological endophenotypes associated with SZ. Furthermore, the left-hemisphere phase lead observed in the deficits of 80 Hz PLA aligns with numerous prior studies, which have consistently proposed that SZ is characterized by left-lateralized brain dysfunctions.

Decision-making deficits in obsessive-compulsive disorder are associated with abnormality of recency and response consistency parameter in prospect valence learning model.

Background: Patients with obsessive-compulsive disorder (OCD) have deficits in decision-making in the Iowa Gambling Task (IGT). However, no study has investigated the parameters of the prospect valence learning (PVL) model in the IGT for OCD. Aims: This study aimed to investigate deficits in decision-making in OCD using the PVL model and identify whether the parameters of the PVL model were associated with obsessive-compulsive severity. Methods: Forty-seven medication-free patients with OCD were compared with 47 healthy controls (HCs). Decision-making was measured using the total net and block net scores of the IGT. A PVL model with a decay-reinforcement learning rule (PVL-DecayRI) was used to investigate the parameters of the model. Correlation analysis was conducted between each parameter of the PVL-DecayRL and obsessive-compulsive symptoms. Results: The total net score of patients with OCD was significantly lower than that of the HCs. The block net scores of the OCD group did not differ across the five blocks, whereas in the HCs, the fifth block net score was significantly higher than the block net scores of the first and second blocks. The values of the recency and response consistency parameters of the PVL-DecayRI in patients with OCD were significantly lower than those in HCs. The recency parameter positively correlated with the Y-BOCS obsessive score. Meanwhile, there was no correlation between consistency parameter values and symptom severity in OCD. Conclusion: Our detailed analysis of the decision-making deficit in OCD suggests that the most recent outcome has a small influence on the expectancy of prospect valence, as indicated by the lower recency parameter, and is characterized by more impulsive choices, as indicated by the lower consistency parameter.

Angiogenic and inflammatory responses in human induced microglia-like (iMG) cells from patients with Moyamoya disease.

Angiogenic factors associated with Moyamoya disease (MMD) are overexpressed in M2 polarized microglia in ischemic stroke, suggesting that microglia may be involved in the pathophysiology of MMD; however, existing approaches are not applicable to explore this hypothesis. Herein we applied blood induced microglial-like (iMG) cells. We recruited 25 adult patients with MMD and 24 healthy volunteers. Patients with MMD were subdivided into progressive (N = 7) or stable (N = 18) group whether novel symptoms or radiographic advancement of Suzuki stage within 1 year was observed or not. We produced 3 types of iMG cells; resting, M1-, and M2-induced cells from monocytes, then RNA sequencing followed by GO and KEGG pathway enrichment analysis and qPCR assay were performed. RNA sequencing of M2-induced iMG cells revealed that 600 genes were significantly upregulated (338) or downregulated (262) in patients with MMD. Inflammation and immune-related factors and angiogenesis-related factors were specifically associated with MMD in GO analysis. qPCR for MMP9, VEGFA, and TGFB1 expression validated these findings. This study is the first to demonstrate that M2 microglia may be involved in the angiogenic process of MMD. The iMG technique provides a promising approach to explore the bioactivity of microglia in cerebrovascular diseases.

Posterior cingulate cortex spontaneous activity associated with motor response inhibition in patients with obsessive-compulsive disorder: A resting-state fMRI study.

Recent evidence suggests that broad brain regions, not limited to the fronto-striato-thalamo-cortical circuit, play an important role in motor response inhibition. However, it is still unclear which specific key brain region is responsible for impaired motor response inhibition observed in obsessive-compulsive disorder (OCD). We calculated the fractional amplitude of low-frequency fluctuations (fALFF) and measured response inhibition ability using the stop-signal task in 41 medication-free patients with OCD and 49 healthy control (HC) participants. We explored the brain region that shows different association between the fALFF and the ability of motor response inhibition. Significant differences in fALFF associated with the ability of motor response inhibition were identified in dorsal posterior cingulate cortex (PCC). There was a positive correlation between increased fALFF in the dorsal PCC and impaired motor response inhibition in OCD. In the HC group, there was a negative correlation between the two variables. Our results suggest that the magnitude of resting-state blood oxygen level-dependent oscillation of the dorsal PCC is a key brain region for the underlying mechanisms of impaired motor response inhibition in OCD. Future studies should examine whether this characteristic of dorsal PCC affects other large-scale networks responsible for motor response inhibition of OCD.

The functional connectome in obsessive-compulsive disorder: resting-state mega-analysis and machine learning classification for the ENIGMA-OCD consortium.

Current knowledge about functional connectivity in obsessive-compulsive disorder (OCD) is based on small-scale studies, limiting the generalizability of results. Moreover, the majority of studies have focused only on predefined regions or functional networks rather than connectivity throughout the entire brain. Here, we investigated differences in resting-state functional connectivity between OCD patients and healthy controls (HC) using mega-analysis of data from 1024 OCD patients and 1028 HC from 28 independent samples of the ENIGMA-OCD consortium. We assessed group differences in whole-brain functional connectivity at both the regional and network level, and investigated whether functional connectivity could serve as biomarker to identify patient status at the individual level using machine learning analysis. The mega-analyses revealed widespread abnormalities in functional connectivity in OCD, with global hypo-connectivity (Cohen's d: -0.27 to -0.13) and few hyper-connections, mainly with the thalamus (Cohen's d: 0.19 to 0.22). Most hypo-connections were located within the sensorimotor network and no fronto-striatal abnormalities were found. Overall, classification performances were poor, with area-under-the-receiver-operating-characteristic curve (AUC) scores ranging between 0.567 and 0.673, with better classification for medicated (AUC = 0.702) than unmedicated (AUC = 0.608) patients versus healthy controls. These findings provide partial support for existing pathophysiological models of OCD and highlight the important role of the sensorimotor network in OCD. However, resting-state connectivity does not so far provide an accurate biomarker for identifying patients at the individual level.

Gyrification of the medial and lateral orbitofrontal cortex in first-degree relatives of patients with obsessive-compulsive disorder.

Gyrification patterns reflect early neurodevelopment and could be highly heritable. While some discrepant results have been reported, the most consistent finding was that patients with obsessive-compulsive disorder showed altered gyrification patterns in the orbitofrontal cortex. Nevertheless, no study has investigated the alterations in gyrification in unaffected first-degree relatives of patients with obsessive-compulsive disorder. We measured local gyrification by the FreeSurfer software in 23 unaffected first-degree relatives of patients with obsessive-compulsive disorder and 52 healthy control participants. We explored differences in the local gyrification index using vertex-wise whole-brain analysis and a region of interest-based approach in the medial and lateral orbitofrontal cortex. There was no significant difference in the local gyrification index between the 2 groups in the vertex-wise whole-brain analysis. Region of interest analyses showed that, compared with healthy controls, first-degree relatives showed significantly reduced local gyrification index in the left medial and lateral orbitofrontal cortex. A negative correlation was observed between the reduced local gyrification index in lateral orbitofrontal cortex and the subclinical anxiety scores of first-degree relatives. Our results showed that first-degree relatives of patients with obsessive-compulsive disorder had an altered local gyrification index in the orbitofrontal cortex. Especially, reduced local gyrification index in lateral orbitofrontal cortex associated with subclinical anxiety symptom could be a potential neurodevelopmental marker for the illness onset.