Effects of inflammation, childhood adversity, and psychiatric symptoms on brain morphometrical phenotypes in bipolar II depression.

BACKGROUND: The neuroanatomical alteration in bipolar II depression (BDII-D) and its associations with inflammation, childhood adversity, and psychiatric symptoms are currently unclear. We hypothesize that neuroanatomical deficits will be related to higher inflammation, greater childhood adversity, and worse psychiatric symptoms in BDII-D. METHODS: Voxel- and surface-based morphometry was performed using the CAT toolbox in 150 BDII-D patients and 155 healthy controls (HCs). Partial Pearson correlations followed by multiple comparison correction was used to indicate significant relationships between neuroanatomy and inflammation, childhood adversity, and psychiatric symptoms. RESULTS: Compared with HCs, the BDII-D group demonstrated significantly smaller gray matter volumes (GMVs) in frontostriatal and fronto-cerebellar area, insula, rectus, and temporal gyrus, while significantly thinner cortices were found in frontal and temporal areas. In BDII-D, smaller GMV in the right middle frontal gyrus (MFG) was correlated with greater sexual abuse (r = -0.348, q < 0.001) while larger GMV in the right orbital MFG was correlated with greater physical neglect (r = 0.254, q = 0.03). Higher WBC count (r = -0.227, q = 0.015) and IL-6 levels (r = -0.266, q = 0.015) was associated with smaller GMVs in fronto-cerebellar area in BDII-D. Greater positive symptoms was correlated with larger GMVs of the left middle temporal pole (r = 0.245, q = 0.03). CONCLUSIONS: Neuroanatomical alterations in frontostriatal and fronto-cerebellar area, insula, rectus, temporal gyrus volumes, and frontal-temporal thickness may reflect a core pathophysiological mechanism of BDII-D, which are related to inflammation, trauma, and psychiatric symptoms in BDII-D.

Interleukin-1ß moderates the relationships between middle frontal-mACC/insular connectivity and depressive symptoms in bipolar II depression.

The functional alterations of the brain in bipolar II depression (BDII-D) and their clinical and inflammatory associations are understudied. We aim to investigate the functional brain alterations in BDII-D and their relationships with inflammation, childhood adversity, and psychiatric symptoms, and to examine the moderating effects among these factors. Using z-normalized amplitude of low-frequency fluctuation (zALFF), we assessed the whole-brain resting-state functional activity between 147 BDII-D individuals and 150 healthy controls (HCs). Differential ALFF regions were selected as seeds for functional connectivity analysis to observe brain connectivity alterations resulting from abnormal regional activity. Four inflammatory cytokines including interleukin (IL)-6, IL-1ß, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP) and five clinical scales including Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), Positive and Negative Syndrome Scale (PANSS), Columbia-Suicide Severity Rating Scale (C-SSRS), and Childhood Trauma Questionnaire (CTQ) were tested and assessed in BDII-D. Partial correlations with multiple comparison corrections identified relationships between brain function and inflammation, childhood adversity, and psychiatric symptoms. Moderation analysis was conducted based on correlation results and previous findings. Compared to HCs, BDII-D individuals displayed significantly lower zALFF in the superior and middle frontal gyri (SFG and MFG) and insula, but higher zALFF in the occipital-temporal area. Only the MFG and insula-related connectivity exhibited significant differences between groups. Within BDII-D, lower right insula zALFF value correlated with higher IL-6, CRP, and emotional adversity scores, while lower right MFG zALFF was related to higher CRP and physical abuse scores. Higher right MFG-mid-anterior cingulate cortex (mACC) connectivity was associated with higher IL-1ß. Moreover, IL-1ß moderated associations between higher right MFG-mACC/insula connectivity and greater depressive symptoms. This study reveals that abnormal functional alterations in the right MFG and right insula were associated with elevated inflammation, childhood adversity, and depressive symptoms in BDII-D. IL-1ß may moderate the relationship between MFG-related connectivity and depressive symptoms.

Linking enlarged choroid plexus with plasma analyte and structural phenotypes in clinical high risk for psychosis: A multisite neuroimaging study.

BACKGROUND: Choroid plexus (ChP) enlargement exists in first-episode and chronic psychosis, but whether enlargement occurs before psychosis onset is unknown. This study investigated whether ChP volume is enlarged in individuals with clinical high-risk (CHR) for psychosis and whether these changes are related to clinical, neuroanatomical, and plasma analytes. METHODS: Clinical and neuroimaging data from the North American Prodrome Longitudinal Study 2 (NAPLS2) was used for analysis. 509 participants (169 controls, 340 CHR) were recruited. Conversion status was determined after 2-years of follow-up, with 36 psychosis converters. The lateral ventricle ChP was manually segmented from baseline scans. A subsample of 31 controls and 53 CHR had plasma analyte and neuroimaging data. RESULTS: Compared to controls, CHR (d = 0.23, p = 0.017) and non-converters (d = 0.22, p = 0.03) demonstrated higher ChP volumes, but not in converters. In CHR, greater ChP volume correlated with lower cortical (r = -0.22, p < 0.001), subcortical gray matter (r = -0.21, p < 0.001), and total white matter volume (r = -0.28,p < 0.001), as well as larger lateral ventricle volume (r = 0.63,p < 0.001). Greater ChP volume correlated with makers functionally associated with the lateral ventricle ChP in CHR [CCL1 (r = -0.30, p = 0.035), ICAM1 (r = 0.33, p = 0.02)], converters [IL1ß (r = 0.66, p = 0.004)], and non-converters [BMP6 (r = -0.96, p < 0.001), CALB1 (r = -0.98, p < 0.001), ICAM1 (r = 0.80, p = 0.003), SELE (r = 0.59, p = 0.026), SHBG (r = 0.99, p < 0.001), TNFRSF10C (r = 0.78, p = 0.001)]. CONCLUSIONS: CHR and non-converters demonstrated significantly larger ChP volumes compared to controls. Enlarged ChP was associated with neuroanatomical alterations and analyte markers functionally associated with the ChP. These findings suggest that the ChP may be a key an important biomarker in CHR.

Brain microvascular endothelial cells and blood-brain barrier dysfunction in psychotic disorders.

Although there is convergent evidence for blood-brain barrier (BBB) dysfunction and peripheral inflammation in schizophrenia (SZ) and bipolar disorder (BD), it is unknown whether BBB deficits are intrinsic to brain microvascular endothelial cells (BMECs) or arise via effects of peripheral inflammatory cytokines. We examined BMEC function using stem cell-based models to identify cellular and molecular deficits associated with BBB dysfunction in SZ and BD. Induced pluripotent stem cells (iPSCs) from 4 SZ, 4 psychotic BD and 4 healthy control (HC) subjects were differentiated into BMEC-"like" cells. Gene expression and protein levels of tight junction proteins were assessed. Transendothelial electrical resistance (TEER) and permeability were assayed to evaluate BBB function. Cytokine levels were measured from conditioned media. BMECs derived from human iPSCs in SZ and BD did not show differences in BBB integrity or permeability compared to HC BMECs. Outlier analysis using TEER revealed a BBB-deficit (n = 3) and non-deficit (n = 5) group in SZ and BD lines. Stratification based on BBB function in SZ and BD patients identified a BBB-deficit subtype with reduced barrier function, tendency for increased permeability to smaller molecules, and decreased claudin-5 (CLDN5) levels. BMECs from the BBB-deficit group show increased matrix metallopeptidase 1 (MMP1) activity, which correlated with reduced CLDN5 and worse BBB function, and was improved by tumor necrosis factor α (TNFα) and MMP1 inhibition. These results show potential deficits in BMEC-like cells in psychotic disorders that result in BBB disruption and further identify TNFα and MMP1 as promising targets for ameliorating BBB deficits.

A preliminary choroid plexus volumetric study in individuals with psychosis.

The choroid plexus (ChP) is part of the blood-cerebrospinal fluid barrier, regulating brain homeostasis and the brain's response to peripheral events. Its upregulation and enlargement are considered essential in psychosis. However, the timing of the ChP enlargement has not been established. This study introduces a novel magnetic resonance imaging-based segmentation method to examine ChP volumes in two cohorts of individuals with psychosis. The first sample consists of 41 individuals with early course psychosis (mean duration of illness = 1.78 years) and 30 healthy individuals. The second sample consists of 30 individuals with chronic psychosis (mean duration of illness = 7.96 years) and 34 healthy individuals. We utilized manual segmentation to measure ChP volumes. We applied ANCOVAs to compare normalized ChP volumes between groups and partial correlations to investigate the relationship between ChP, LV volumes, and clinical characteristics. Our segmentation demonstrated good reliability (.87). We further showed a significant ChP volume increase in early psychosis (left: p < .00010, right: p < .00010) and a significant positive correlation between higher ChP and higher LV volumes in chronic psychosis (left: r = .54, p = .0030, right: r = .68; p < .0010). Our study suggests that ChP enlargement may be a marker of acute response around disease onset. It might also play a modulatory role in the chronic enlargement of lateral ventricles, often reported in psychosis. Future longitudinal studies should investigate the dynamics of ChP enlargement as a promising marker for novel therapeutic strategies.

Peripheral inflammatory subgroup differences in anterior Default Mode network and multiplex functional network topology are associated with cognition in psychosis.

INTRODUCTION: High-inflammation subgroups of patients with psychosis demonstrate cognitive deficits and neuroanatomical alterations. Systemic inflammation assessed using IL-6 and C-reactive protein may alter functional connectivity within and between resting-state networks, but the cognitive and clinical implications of these alterations remain unknown. We aim to determine the relationships of elevated peripheral inflammation subgroups with resting-state functional networks and cognition in psychosis spectrum disorders. METHODS: Serum and resting-state fMRI were collected from psychosis probands (schizophrenia, schizoaffective, psychotic bipolar disorder) and healthy controls (HC) from the B-SNIP1 (Chicago site) study who were stratified into inflammatory subgroups based on factor and cluster analyses of 13 cytokines (HC Low n = 32, Proband Low n = 65, Proband High n = 29). Nine resting-state networks derived from independent component analysis were used to assess functional and multilayer connectivity. Inter-network connectivity was measured using Fisher z-transformation of correlation coefficients. Network organization was assessed by investigating networks of positive and negative connections separately, as well as investigating multilayer networks using both positive and negative connections. Cognition was assessed using the Brief Assessment of Cognition in Schizophrenia. Linear regressions, Spearman correlations, permutations tests and multiple comparison corrections were used for analyses in R. RESULTS: Anterior default mode network (DMNa) connectivity was significantly reduced in the Proband High compared to Proband Low (Cohen's d = -0.74, p = 0.002) and HC Low (d = -0.85, p = 0.0008) groups. Inter-network connectivity between the DMNa and the right-frontoparietal networks was lower in Proband High compared to Proband Low (d = -0.66, p = 0.004) group. Compared to Proband Low, the Proband High group had lower negative (d = 0.54, p = 0.021) and positive network (d = 0.49, p = 0.042) clustering coefficient, and lower multiplex network participation coefficient (d = -0.57, p = 0.014). Network findings in high inflammation subgroups correlate with worse verbal fluency, verbal memory, symbol coding, and overall cognition. CONCLUSION: These results expand on our understanding of the potential effects of peripheral inflammatory signatures and/or subgroups on network dysfunction in psychosis and how they relate to worse cognitive performance. Additionally, the novel multiplex approach taken in this study demonstrated how inflammation may disrupt the brain's ability to maintain healthy co-activation patterns between the resting-state networks while inhibiting certain connections between them.

Deconstructing the functional neuroanatomy of the choroid plexus: an ontogenetic perspective for studying neurodevelopmental and neuropsychiatric disorders.

The choroid plexus (CP) is a delicate and highly vascularized structure in the brain comprised of a dense network of fenestrated capillary loops that help in the synthesis, secretion and circulation of cerebrospinal fluid (CSF). This unique neuroanatomical structure is comprised of arachnoid villi stemming from frond-like surface projections-that protrude into the lumen of the four cerebral ventricles-providing a key source of nutrients to the brain parenchyma in addition to serving as a 'sink' for central nervous system metabolic waste. In fact, the functions of the CP are often described as being analogous to those of the liver and kidney. Beyond forming a barrier/interface between the blood and CSF compartments, the CP has been identified as a modulator of leukocyte trafficking, inflammation, cognition, circadian rhythm and the gut brain-axis. In recent years, advances in molecular biology techniques and neuroimaging along with the use of sophisticated animal models have played an integral role in shaping our understanding of how the CP-CSF system changes in relation to the maturation of neural circuits during critical periods of brain development. In this article we provide an ontogenetic perspective of the CP and review the experimental evidence implicating this structure in the pathophysiology of neurodevelopmental and neuropsychiatric disorders.

Brain-derived subgroups of bipolar II depression associate with inflammation and choroid plexus morphology.

AIM: Elevated inflammation and larger choroid plexus (ChP) volume has been previously identified in mood disorders. Connections between inflammation, ChP, and clinical symptoms in bipolar II depression (BDII-D) are unclear. Data-driven clustering based on neuroanatomical phenotypes may help to elucidate neurobiological associations in BDII-D. METHODS: Inflammatory cytokines, clinical symptoms, and neuroanatomical features were assessed in 150 BDII-D patients. Sixty-eight cortical surface area (SA) and 19 subcortical volumes were extracted using FreeSurfer. The ChP volume was segmented manually using 3D Slicer. Regularized canonical correlation analysis was used to identify significantly correlated components between cortical SA and subcortical volumes (excluding the ChP), followed by k-means clustering to define brain-derived subgroups of BDII-D. Low-grade inflammation was derived by averaging the standardized z scores of interleukin (IL)-6, IL-1ß, and tumor necrosis factor-α (TNF-α), which were computed to create a composite z-value score. Partial Pearson correlations followed by multiple comparison correction were conducted to explore associations between inflammation, clinical symptoms, and ChP volume. RESULTS: Subgroup I demonstrated smaller subcortical volume and cortical SA, higher inflammation, and larger ChP volume compared with subgroup II. Greater ChP volume was associated with a higher low-grade inflammation (mean r = 0.289, q = 0.003), CRP (mean r = 0.249, q = 0.007), IL-6 (left r = 0.200, q = 0.03), and TNF-α (right r = 0.226, q = 0.01), while greater IL-1ß was significantly associated with severe depressive symptoms in BDII-D (r = 0.218, q = 0.045). CONCLUSIONS: Neuroanatomically-derived subgroups of BDII-D differed in their inflammation levels and ChP volume. These findings suggest an important role of elevated peripheral inflammation and larger ChP in BDII-D.

Inflammatory Subtypes in Antipsychotic-Naïve First-Episode Schizophrenia are Associated with Altered Brain Morphology and Topological Organization.

BACKGROUND: Peripheral inflammation is implicated in schizophrenia, however, not all individuals demonstrate inflammatory alterations. Recent studies identified inflammatory subtypes in chronic psychosis with high inflammation having worse cognitive performance and displaying neuroanatomical enlargement compared to low inflammation subtypes. It is unclear if inflammatory subtypes exist earlier in the disease course, thus, we aim to identify inflammatory subtypes in antipsychotic naïve First-Episode Schizophrenia (FES). METHODS: 12 peripheral inflammatory markers, clinical, cognitive, and neuroanatomical measures were collected from a naturalistic study of antipsychotic-naïve FES patients. A combination of unsupervised principal component analysis and hierarchical clustering was used to categorize inflammatory subtypes from their cytokine data (17 FES High, 30 FES Low, and 33 healthy controls (HCs)). Linear regression analysis was used to assess subtype differences. Neuroanatomical correlations with clinical and cognitive measures were performed using partial Spearman correlations. Graph theoretical analyses were performed to assess global and local network properties across inflammatory subtypes. RESULTS: The FES High group made up 36% of the FES group and demonstrated significantly greater levels of IL1ß, IL6, IL8, and TNFα compared to FES Low, and higher levels of IL1ß and IL8 compared to HCs. FES High had greater right parahippocampal, caudal anterior cingulate, and bank superior sulcus thicknesses compared to FES Low. Compared to HCs, FES Low showed smaller bilateral amygdala volumes and widespread cortical thickness. FES High and FES Low groups demonstrated less efficient topological organization compared to HCs. Individual cytokines and/or inflammatory signatures were positively associated with cognition and symptom measures. CONCLUSIONS: Inflammatory subtypes are present in antipsychotic-naïve FES and are associated with inflammation-mediated cortical expansion. These findings support our previous findings in chronic psychosis and point towards a connection between inflammation and blood-brain barrier disruption. Thus, identifying inflammatory subtypes may provide a novel therapeutic avenue for biomarker-guided treatment involving anti-inflammatory medications.

Multivariate relationships between peripheral inflammatory marker subtypes and cognitive and brain structural measures in psychosis.

Elevations in peripheral inflammatory markers have been reported in patients with psychosis. Whether this represents an inflammatory process defined by individual or subgroups of markers is unclear. Further, relationships between peripheral inflammatory marker elevations and brain structure, cognition, and clinical features of psychosis remain unclear. We hypothesized that a pattern of plasma inflammatory markers, and an inflammatory subtype established from this pattern, would be elevated across the psychosis spectrum and associated with cognition and brain structural alterations. Clinically stable psychosis probands (Schizophrenia spectrum, n = 79; Psychotic Bipolar disorder, n = 61) and matched healthy controls (HC, n = 60) were assessed for 15 peripheral inflammatory markers, cortical thickness, subcortical volume, cognition, and symptoms. A combination of unsupervised exploratory factor analysis and hierarchical clustering was used to identify inflammation subtypes. Levels of IL6, TNFα, VEGF, and CRP were significantly higher in psychosis probands compared to HCs, and there were marker-specific differences when comparing diagnostic groups. Individual and/or inflammatory marker patterns were associated with neuroimaging, cognition, and symptom measures. A higher inflammation subgroup was defined by elevations in a group of 7 markers in 36% of Probands and 20% of HCs. Probands in the elevated inflammatory marker group performed significantly worse on cognitive measures of visuo-spatial working memory and response inhibition, displayed elevated hippocampal, amygdala, putamen and thalamus volumes, and evidence of gray matter thickening compared to the proband group with low inflammatory marker levels. These findings specify the nature of peripheral inflammatory marker alterations in psychotic disorders and establish clinical, neurocognitive and neuroanatomic associations with increased inflammatory activation in psychosis. The identification of a specific subgroup of patients with inflammatory alteration provides a potential means for targeting treatment with anti-inflammatory medications.

Retinal microvasculature and vasoreactivity changes in hypertension using optical coherence tomography-angiography.

PURPOSE: To evaluate the retinal vasculature and vasoreactivity of patients with hypertension (HTN) using spectral domain optical coherence tomography angiography (SD-OCTA). METHODS: Patients with and without a diagnosis of HTN were included in this cross-sectional observational study. All eyes were imaged with SD-OCTA using 3 mm × 3 mm and 6 mm × 6 mm centered on both the fovea and optic disk. A second 6 mm × 6 mm scan was taken after a 30 s breath-hold. Vessel density (VD), vessel skeletonized density (VSD), and fractal dimension (FD) were calculated using customized MATLAB scripts. Vessel diameter index (VDI) was obtained by taking the ratio of VD to VSD. Vasoreactivity was measured by subtracting the VD or VSD before and after breath-hold (∆VD, ∆VSD). RESULTS: Twenty-three eyes with HTN (17 patients) and 17 control eyes (15 patients) were included. In the 6 mm × 6 mm angiogram centered on fovea, the superficial capillary plexus (SCP) VD (ß = - 0.029, p = 0.012), VSD (ß = - 0.004, p = 0.043) and the choriocapillaris VD (ß = - 0.021, p = 0.030) were significantly decreased in HTN compared to control eyes. Similarly, FD was decreased in both the SCP (ß = - 0.012, p = 0.013) and choriocapillaris (ß = - 0.009, p = 0.030). In the 3 mm × 3 mm angiogram centered on optic disk, SCP VDI (ß = - 0.364, p = 0.034) was decreased. ∆VD and ∆VSD were both reduced in the DCP (ß = - 0.034, p = 0.032; ß = - 0.013, p = 0.043) and ∆VSD was elevated in the choriocapillaris of HTN eyes (ß = 0.004, p = 0.032). CONCLUSIONS: The study used SD-OCTA to show significant differences in the retinal vasculature of hypertensive patients. It was also the first to demonstrate the potential of OCT-A to investigate retinal vascular reactivity in patients with HTN.

Altered cerebral perfusion in bipolar disorder: A pCASL MRI study.

BACKGROUND: Neurovascular abnormalities are relevant to the pathophysiology of bipolar disorder (BD), which can be assessed using cerebral blood flow (CBF) imaging. CBF alterations have been identified in BD, but studies to date have been small and inconclusive. We aimed to determine cortical gray matter CBF (GM-CBF) differences between BD and healthy controls (HC) and to identify relationships between CBF and clinical or cognitive measures. METHODS: Cortical GM-CBF maps were generated using Pseudo-Continuous Arterial Spin Labeling (pCASL) for 109 participants (BD, n = 61; HC, n = 48). We used SnPM13 to perform non-parametric voxel-wise two-sample t-tests comparing CBF between groups. We performed multiple linear regression to relate GM-CBF with clinical and cognitive measures. Analysis was adjusted for multiple comparisons with 10,000 permutations. Significance was set at a voxel level threshold of P < .001 followed by AlphaSim cluster-wise correction of P < .05. RESULTS: Compared to HCs, BD patients had greater GM-CBF in the left lateral occipital cortex, superior division and lower CBF in the right lateral occipital, angular and middle temporal gyrus. Greater GM-CBF in the left lateral occipital cortex correlated with worse working memory, verbal memory, attention and speed of processing. We found using voxel-wise regression that decreased gray matter CBF in the bilateral thalamus and cerebellum, and increased right fronto-limbic CBF were associated with worse working memory. No clusters were associated with clinical variables after FDR correction. CONCLUSIONS: Cortical GM-CBF alterations are seen in BD and may be related to cognitive function, which suggest neurovascular unit dysfunction as a possible pathophysiologic mechanism.

Trajectory of neurological examination abnormalities in antipsychotic-naïve first-episode psychosis population: a 1 year follow-up study.

BACKGROUND: Neurological Examination Abnormalities (NES) are quantified by measuring subtle, partially localizable (cerebello-thalamo-prefrontal cortical circuit) and heritable neurological signs comprising sensory integration, motor coordination and complex motor sequencing that are associated with first-episode psychosis (FEP). A few studies have evaluated NES longitudinally and as a predictor for diagnostic and response classification, but these studies have been confounded, underpowered and divergent. We examined (1) baseline and longitudinal NES differences between diagnostic and year 1 response groups; (2) if NES predicts diagnostic and response groups and (3) relationships between clinical variables and NES measures in antipsychotic-naïve FEP. METHODS: NES and clinical measures were obtained for FEP-schizophrenia (FEP-SZ, n = 232), FEP non-schizophrenia (FEP-NSZ, n = 117) and healthy controls (HC, n = 204). Response groups with >25% improvement in average year 1 positive and negative symptomatology scores were classified as responsive (n = 97) and <25% improvement as non-responsive (n = 95). Analysis of covariance, NES trajectory analysis and logistic regression models assessed diagnostic and response group differences. Baseline and longitudinal NES relationships with clinical variables were performed with Spearman correlations. Data were adjusted for age, sex, race, socioeconomic status and handedness. RESULTS: Cognitive perceptual (COGPER) score was better than repetitive motor (REPMOT) at differentiating FEP-SZ from FEP-NSZ and distinguishing responders from non-responders. We identified significant group-specific associations between COGPER and worse GAF, positive and negative symptomatology and some of these findings persisted at 1-year assessment. CONCLUSION: NES are an easy to administer, bedside-elicited, endophenotypic measure and could be a cost-effective clinical tool in antipsychotic-naïve FEP.

Neuroscience in pictures:1. History of psychiatric neuroscience.

Our understanding of the brain basis of mental illness has evolved over three and half millennia. Early insights into the role of the brain in relation to the mind faded during the middle ages as mental illness became the province of religion, spirituality, and philosophy. Psychiatry became a medical discipline again as medical and scientific thinking evolved during the 17th century. However, progress in neuroscience and astute clinical observations were punctuated by setbacks due to lingering dualism, reductionistic thinking, and dogma. Accelerating neuroscience discoveries and methodological innovations are beginning to bring neuroscience and psychiatry closer than ever as we begin the 21st century, This pictorial article seeks to briefly highlight this journey for an early trainee in psychiatry and related professions in mind.

Overlap between ophthalmology and psychiatry - A narrative review focused on congenital and inherited conditions.

A number of congenital and inherited diseases present with both ocular and psychiatric features. The genetic inheritance and phenotypic variants play a key role in disease severity. Early recognition of the signs and symptoms of those disorders is critical to earlier intervention and improved prognosis. Typically, the associations between these two medical subspecialties of ophthalmology and psychiatry are poorly understood by most practitioners so we hope to provide a narrative review to improve the identification and management of these disorders. We conducted a comprehensive review of the literature detailing the diseases with ophthalmic and psychiatric overlap that were more widely represented in the literature. Herein, we describe the clinical features, pathophysiology, molecular biology, diagnostic tests, and the most recent approaches for the treatment of these diseases. Recent studies have combined technologies for ocular and brain imaging such as optical coherence tomography (OCT) and functional imaging with genetic testing to identify the genetic basis for eye-brain connections. Additional work is needed to further explore these potential biomarkers. Overall, accurate, efficient, widely distributed and non-invasive tests that can help with early recognition of these diseases will improve the management of these patients using a multidisciplinary approach.

Lesion network guided delta frequency neuromodulation improves cognition in patients with psychosis spectrum disorders: A pilot study.

BACKGROUND: Transcranial electric stimulation (tES) may improve cognition in psychosis spectrum disorders. However, few studies have used novel tES approaches, such as high definition tES (HD-tES) to target specific brain circuits. Recently, the extrastriate visual cortex (V5/MT) has been causally linked to visual hallucinations through lesion network mapping and this may be a promising approach for improving cognition. OBJECTIVE: We aim to determine if causal lesion network guided HD-tES to V5/MT improves cognitive performance as measured by the Brief Assessment of Cognition in Schizophrenia (BACS). METHODS: A single-blind pilot study with a within-subjects crossover design was performed to characterize the effect of cathodal HD-transcranial direct current stimulation (tDCS) and 2 Hz HD-transcranial alternating current stimulation (tACS) on cognition. Enrolled patients received 20 mins of HD-tES twice daily for 5 consecutive days applied bilaterally to V5/MT with a washout between conditions. BACS assessments were performed at baseline, day-5, and 1-month. RESULTS: 6 participants with psychosis spectrum disorder were enrolled. 6 individuals received cathodal HD-tDCS. 4 individuals received 2 Hz HD-tACS. HD-tACS resulted in significant (p < 0.1 baseline to 1-month improvements for Digit Sequencing, Verbal Fluency, and Tower of London. HD-tDCS did not result in significant improvement on any task. CONCLUSIONS: HD-tACS targeting V5/MT may be a promising treatment to improve cognitive abilities in individuals with psychosis. By promoting delta oscillations, tACS may enhance cortico-cortico communications across brain networks to improve verbal working memory, processing speed, and executive function. Large-scale investigations are needed to replicate these results.

Neuroscience in pictures: 2. Sleep, wakefulness, and mental state biology.

Sleep is a vital restorative process that has occupied our curiosity for millennia. Despite our longstanding research efforts, the biology of sleep and its connection to mental states remains enigmatic. Unsurprisingly, sleep and wakefulness, the fundamental processes between which our mental states oscillate, are inseparable from our physical and mental health. Thus, clinical consideration of sleep impairments warrants a transdiagnostic approach whilst appropriately acknowledging that certain individual disorders (e.g. depression, schizophrenia) may have somewhat distinct sleep disturbances. Moreover, our knowledge of the anatomy and physiology of sleep regulation-albeit limited-forms the foundation for current treatments for sleep difficulties. This pictorial article overviews the core concepts and future of sleep neuroscience and mental state biology for trainees and practitioners in psychiatry and related professions.

Implementing Technologies to Enhance Coordinated Specialty Care Framework: Implementation Outcomes From a Development and Usability Study.

BACKGROUND: Coordinated specialty care (CSC) has demonstrated efficacy in improving outcomes in individuals at clinical high risk for psychosis and individuals with first-episode psychosis. Given the limitations of scalability and staffing needs, the augmentation of services using digital mental health interventions (DMHIs) may be explored to help support CSC service delivery. OBJECTIVE: In this study, we aimed to understand the methods to implement and support technology in routine CSC and offered insights from a quality improvement study assessing the implementation outcomes of DMHIs in CSC. METHODS: Patients and clinicians including psychiatrists, therapists, and supported education and employment specialists from a clinical-high-risk-for-psychosis clinic (Center for Early Detection Assessment and Response to Risk [CEDAR]) and a first-episode-psychosis clinic (Advancing Services for Psychosis Integration and Recovery [ASPIRE]) participated in a quality improvement project exploring the feasibility of DMHIs following the Access, Alignment, Connection, Care, and Scalability framework to implement mindLAMP, a flexible and evidenced-based DMHI. Digital navigators were used at each site to assist clinicians and patients in implementing mindLAMP. To explore the differences in implementation outcomes associated with the app format, a menu-style format was delivered at CEDAR, and a modular approach was used at ASPIRE. Qualitative baseline and follow-up data were collected to assess the specific implementation outcomes. RESULTS: In total, 5 patients (ASPIRE: n=3, 60%; CEDAR: n=2, 40%) were included: 3 (60%) White individuals, 2 (40%) male and 2 (40%) female patients, and 1 (20%) transgender man, with a mean age of 19.6 (SD 2.05) years. Implementation outcome data revealed that patients and clinicians demonstrated high accessibility, acceptability, interest, and belief in the sustainability of DMHIs. Clinicians and patients presented a wide range of interest in unique use cases of DMHI in CSC and expressed variable feasibility and appropriateness associated with nuanced barriers and needs. In addition, the results suggest that adoption, penetration, feasibility, and appropriateness outcomes were moderate and might continue to be explored and targeted. CONCLUSIONS: Implementation outcomes from this project suggest the need for a patient- and clinician-centered approach that is guided by digital navigators and provides versatility, autonomy, and structure. Leveraging these insights has the potential to build on growing research regarding the need for versatility, autonomy, digital navigator support, and structured applications. We anticipate that by continuing to research and improve implementation barriers impeding the adoption and penetration of DMHIs in CSC, accessibility and uptake of DMHIs will improve, therefore connecting patients to the demonstrated benefits of technology-augmented care.

Manual Segmentation of the Human Choroid Plexus Using Brain MRI.

The choroid plexus has been implicated in neurodevelopment and a range of brain disorders. Evidence demonstrates that the choroid plexus is critical for brain maturation, immune/ inflammatory regulation, and behavioral/cognitive functioning. However, current automated neuroimaging segmentation tools are poor at accurately and reliably segmenting the lateral ventricle choroid plexus. Furthermore, there is no existing tool that segments the choroid plexus located in the third and fourth ventricles of the brain. Thus, a protocol delineating how to segment the choroid plexus in the lateral, third, and fourth ventricle is needed to increase the reliability and replicability of studies examining the choroid plexus in neurodevelopmental and brain disorders. This protocol provides detailed steps to create separately labeled files in 3D Slicer for the choroid plexus based on DICOM or NIFTI images. The choroid plexus will be manually segmented using the axial, sagittal, and coronal planes of T1w images making sure to exclude voxels from gray or white matter structures bordering the ventricles. Windowing will be adjusted to assist in the localization of the choroid plexus and its anatomical boundaries. Methods for assessing accuracy and reliability will be demonstrated as part of this protocol. Gold standard segmentation of the choroid plexus using manual delineations can be used to develop better and more reliable automated segmentation tools that can be openly shared to elucidate changes in the choroid plexus across the lifespan and within various brain disorders.