Maternal asthma symptoms during pregnancy on child behaviour and executive function: A Bayesian phenomics approach.

OBJECTIVE: Maternal history of inflammatory conditions has been linked to offspring developmental and behavioural outcomes. This phenomenon may be explained by the maternal immune activation (MIA) hypothesis, which posits that dysregulation of the gestational immune environment affects foetal neurodevelopment. The timing of inflammation is critical. We aimed to understand maternal asthma symptoms during pregnancy, in contrast with paternal asthma symptoms during the same period, on child behaviour problems and executive function in a population-based cohort. METHODS: Data were obtained from 844 families from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort. Parent asthma symptoms during the prenatal period were reported. Asthma symptoms in children were reported longitudinally from two to five years old, while behavioural problems and executive functioning were obtained at seven years old. Parent and child measures were compared between mothers with and without prenatal asthma symptoms. Generalized linear and Bayesian phenomics models were used to determine the relation between parent or child asthma symptoms and child outcomes. RESULTS: Children of mothers with prenatal asthma symptoms had greater behavioural and executive problems than controls (Cohen's d: 0.43-0.75; all p < 0.05). This association remained after adjustments for emerging asthma symptoms during the preschool years and fathers' asthma symptoms during the prenatal period. After adjusting for dependence between child outcomes, the Bayesian phenomics model showed that maternal prenatal asthma symptoms were associated with child internalising symptoms and higher-order executive function, while child asthma symptoms were associated with executive function skills. Paternal asthma symptoms during the prenatal period were not associated with child outcomes. CONCLUSIONS: Associations between child outcomes and maternal but not paternal asthma symptoms during the prenatal period suggests a role for MIA. These findings need to be validated in larger samples, and further research may identify behavioural and cognitive profiles of children with exposure to MIA.

Systemic Diclofenac Sodium Reduces Postoperative rhBMP-2 Induced Neuroinflammation: A Rodent Model Study.

STUDY DESIGN: This is a basic science, animal research study. OBJECTIVE: This study aims to explore, in rodent models, the effectiveness of systemic nonsteroidal anti-inflammatory drugs in reducing recombinant human bone morphogenetic protein-2 (rhBMP-2) induced neuroinflammation. SUMMARY OF BACKGROUND DATA: rhBMP-2 is increasingly used to augment fusion in lumbar interbody fusion surgeries, although it can cause complications including postoperative radiculitis. MATERIALS AND METHODS: Eighteen 8-week-old Sprague-Dawley rats underwent Hargreaves testing to measure the baseline thermal withdrawal threshold before undergoing surgical intervention. The L5 nerve root was exposed and wrapped with an Absorbable Collagen Sponge containing rhBMP-2. Rats were randomized into 3 groups: (1) Low dose (LD), (2) high dose (HD) diclofenac sodium, and (3) saline, receiving daily injection treatment. Hargreaves testing was performed postoperatively on days 5 and 7. Seroma volumes were measured by aspiration and the nerve root was then harvested for hematoxylin and eosin, immunohistochemistry, Luxol Fast Blue staining, and real-time quantitative polymerase chain reaction. The Student t test was used to evaluate the statistical significance among groups. RESULTS: The intervention groups showed reduced seroma volume, and a general reduction of inflammatory markers (MMP12, MAPK6, GFAP, CD68, and IL18) compared with controls, with the reduction in MMP12 being statistically significant ( P = 0.02). Hematoxylin and eosin and immunohistochemistry of the nerve roots showed the highest macrophage density in the saline controls and the lowest in the HD group. Luxol Fast Blue staining showed the greatest extent of demyelination in the LD and saline groups. Lastly, Hargreaves testing, a functional measure of neuroinflammation, of the HD group demonstrated a minimal change in thermal withdrawal latency. In contrast, the thermal withdrawal latency of the LD and saline groups showed a statistically significant decrease of 35.2% and 28.0%, respectively ( P < 0.05). CONCLUSION: This is the first proof-of-concept study indicating that diclofenac sodium is effective in alleviating rhBMP-2-induced neuroinflammation. This can potentially impact the clinical management of rhBMP-2-induced radiculitis. It also presents a viable rodent model for evaluating the effectiveness of analgesics in reducing rhBMP-2-induced inflammation.

Functional near-infrared spectroscopy of medical students answering various item types.

Background: Traditionally, the effect of assessment item types including true/false questions (TFQs), multiple-choice questions (MCQs), short answer questions (SAQs), and case scenario questions (CSQs) is examined through psychometric qualities or student interviews. However, brain activity while answering such questions or items remains unknown. Functional near-infrared spectroscopy (fNIRS) can be used to safely measure cerebral cortex hemodynamic response during various tasks. Hence, this fNIRS study aimed to determine differences in frontotemporal cortex activity as medical students answered TFQs, MCQs, SAQs, and CSQs. Methods: In total, 24 medical students (13 males and 11 females) were recruited in this study during their mid-psychiatry posting. Oxy-hemoglobin and deoxy-hemoglobin levels in the frontal and temporal regions were measured with a 52-channel fNIRS system. Participants answered 9-18 trials under each of the four types of tasks that were based on their psychiatry curriculum during fNIRS measurements. The area under the oxy-hemoglobin curve (AUC) for each participant and each item type was derived. Repeated measures ANOVA with post-hoc Bonferroni-corrected pairwise comparisons were used to determine differences in oxy-hemoglobin AUC between TFQs, MCQs, SAQs, and CSQs. Results: Oxy-hemoglobin AUC was highest during the CSQs, followed by SAQs, MCQs, and TFQs in both the frontal and temporal regions. Statistically significant differences between different types of items were observed in oxy-hemoglobin AUC of the frontal region (p ≤ 0.001). Oxy-hemoglobin AUC in the frontal region was significantly higher during the CSQs than TFQ (p = 0.005) and during the SAQ than TFQ (p = 0.025). Although the percentage of correct responses was significantly lower in MCQ than in the other item types, there was no correlation between the percentage of correct response and oxy-hemoglobin AUC in both regions for all four item types (p > 0.05). Conclusion: CSQs and SAQs elicited greater hemodynamic response than MCQs and TFQs in the prefrontal cortex of medical students. This suggests that more cognitive skills may be required to answer CSQs and SAQs.

Functional Near-Infrared Spectroscopy of English-Speaking Adults With Attention-Deficit/Hyperactivity Disorder During a Verbal Fluency Task.

OBJECTIVE: Functional near-infrared spectroscopy (fNIRS) provides direct and quantitative assessment of cortical hemodynamic response. It has been used to identify neurophysiological alterations in medication-naïve adults with attention-deficit/hyperactivity disorder (ADHD). Hence, this study aimed to distinguish both medication-naïve and medicated adults with ADHD from healthy controls (HC). METHOD: 75 HCs, 75 medication-naïve, and 45 medicated patients took part in this study. fNIRS signals during a verbal fluency task (VFT) were acquired using a 52-channel system and relative oxy-hemoglobin changes in the prefrontal cortex were quantified. RESULTS: Prefrontal cortex hemodynamic response was lower in patients than HCs (p ≤ ≤.001). Medication-naïve and medicated patients did not differ in hemodynamic response or symptom severity (p > .05). fNIRS measurements were not associated with any clinical variables (p > .05). 75.8% patients and 76% HCs were correctly classified using hemodynamic response. CONCLUSION: fNIRS may be a potential diagnostic tool for adult ADHD. These findings need to be replicated in larger validation studies.

Premenopausal Singaporean Women Suffering from Major Depressive Disorder Treated with Selective Serotonin Reuptake Inhibitors Had Similar Bone Mineral Density as Compared with Healthy Controls.

The association between selective serotonin reuptake inhibitor (SSRI) treatment and lower bone mineral density (BMD) remains controversial, and further research is required. This study aimed to compare the BMD, levels of bone formation and bone metabolism markers in medicated premenopausal Singaporean women with major depressive disorder (MDD) and matched healthy controls. We examined 45 women with MDD who received SSRI treatment (mean age: 37.64 ± 7) and 45 healthy controls (mean age: 38.1 ± 9.2). BMD at the lumbar spine, total hip and femoral neck were measured using dual-energy X-ray absorptiometry. We also measured bone formation markers, procollagen type 1 N-terminal propeptide (P1NP) and bone metabolism markers, osteoprotegerin (OPG) and receptor activator of nuclear factor-kappa-Β ligand (RANKL). There were no significant differences in the mean BMD in the lumbar spine (healthy controls: 1.04 ± 0.173 vs. MDD patients: 1.024 ± 0.145, p = 0.617, left hip (healthy controls: 0.823 ± 0.117 vs. MDD patients: 0.861 ± 0.146, p = 0.181) and right hip (healthy controls: 0.843 ± 0.117 vs. MDD patients: 0.85 ± 0.135, p = 0.784) between healthy controls and medicated patients with MDD. There were no significant differences in median P1NP (healthy controls: 35.9 vs. MDD patients: 37.3, p = 0.635), OPG (healthy controls: 2.6 vs. MDD patients: 2.7, p = 0.545), RANKL (healthy controls: 23.4 vs. MDD patients: 2178.93, p = 0.279) and RANKL/OPG ratio (healthy controls: 4.1 vs. MDD patients: 741.4, p = 0.279) between healthy controls and medicated patients with MDD. Chronic SSRI treatment might not be associated with low BMD in premenopausal Singaporean women who suffered from MDD. This finding may help female patients with MDD make an informed decision when considering the risks and benefits of SSRI treatment.

Functional near-infrared spectroscopy during the verbal fluency task of English-Speaking adults with mood disorders: A preliminary study.

Functional near-infrared spectroscopy (fNIRS) provides a direct and objective assessment of cerebral cortex function. It may be used to determine neurophysiological differences between psychiatric disorders with overlapping symptoms, such as major depressive disorder (MDD) and bipolar disorder (BD). Therefore, this preliminary study aimed to compare fNIRS signals during the verbal fluency task (VFT) of English-speaking healthy controls (HC), patients with MDD and patients with BD. Fifteen HCs, 15 patients with MDD and 15 patients with BD were recruited. Groups were matched for age, gender, ethnicity and education. Relative oxy-haemoglobin and deoxy-haemoglobin changes in the frontotemporal cortex was monitored with a 52-channel fNIRS system. Integral values of the frontal and temporal regions were derived as a measure cortical haemodynamic response magnitude. Both patient groups had lower frontal and temporal region integral values than HCs, and patients with MDD had lower frontal region integral value than patients with BD. Moreover, patients could be differentiated from HCs using the frontal and temporal integral values, and patient groups could be differentiated using the frontal region integral values. VFT performance, clinical history and symptom severity were not associated with integral values. These results suggest that prefrontal cortex haemodynamic dysfunction occurs in mood disorders, and it is more extensive in MDD than BD. The fNIRS-VFT paradigm may be a potential tool for differentiating MDD from BD in clinical settings, and these findings need to be verified in a larger sample of English-speaking patients with mood disorders.

Attitudes toward COVID-19 vaccination and willingness to pay: comparison of people with and without mental disorders in China.

BACKGROUND: Acceptance and willingness to pay for the COVID-19 vaccine are unknown. AIMS: We compared attitudes toward COVID-19 vaccination in people suffering from depression or anxiety disorder and people without mental disorders, and their willingness to pay for it. METHOD: Adults with depression or anxiety disorder (n = 79) and healthy controls (n = 134) living in Chongqing, China, completed a cross-sectional study between 13 and 26 January 2021. We used a validated survey to assess eight aspects related to attitudes toward the COVID-19 vaccines. Psychiatric symptoms were assessed by the 21-item Depression, Anxiety and Stress Scale. RESULTS: Seventy-six people with depression or anxiety disorder (96.2%) and 134 healthy controls (100%) reported willingness to receive the COVID-19 vaccine. A significantly higher proportion of people with depression or anxiety disorder (64.5%) were more willing to pay for the COVID-19 vaccine than healthy controls (38.1%) (P ≤ 0.001). After multivariate adjustment, severity of depression and anxiety was significantly associated with willingness to pay for COVID-19 vaccination among psychiatric patients (P = 0.048). Non-healthcare workers (P = 0.039), health insurance (P = 0.003), living with children (P = 0.006) and internalised stigma (P = 0.002) were significant factors associated with willingness to pay for COVID-19 vaccine in healthy controls. CONCLUSIONS: To conclude, psychiatric patients in Chongqing, China, showed high acceptance and willingness to pay for the COVID-19 vaccine. Factors associated with willingness to pay for the COVID-19 vaccine differed between psychiatric patients and healthy controls.

Comparison of Brain Activation Patterns during Olfactory Stimuli between Recovered COVID-19 Patients and Healthy Controls: A Functional Near-Infrared Spectroscopy (fNIRS) Study.

Impaired sense of smell occurs in a fraction of patients with COVID-19 infection, but its effect on cerebral activity is unknown. Thus, this case report investigated the effect of COVID-19 infection on frontotemporal cortex activity during olfactory stimuli. In this preliminary study, patients who recovered from COVID-19 infection (n = 6) and healthy controls who never contracted COVID-19 (n = 6) were recruited. Relative changes in frontotemporal cortex oxy-hemoglobin during olfactory stimuli was acquired using functional near-infrared spectroscopy (fNIRS). The area under curve (AUC) of oxy-hemoglobin for the time interval 5 s before and 15 s after olfactory stimuli was derived. In addition, olfactory function was assessed using the Sniffin' Sticks 12-identification test (SIT-12). Patients had lower SIT-12 scores than healthy controls (p = 0.026), but there were no differences in oxy-hemoglobin AUC between healthy controls and patients (p > 0.05). This suggests that past COVID-19 infection may not affect frontotemporal cortex function, and these preliminary results need to be verified in larger samples.

Hemodynamic Response to Three Types of Urban Spaces before and after Lockdown during the COVID-19 Pandemic.

(1) Background: Prolonged lockdowns with stay-at-home orders have been introduced in many countries since the outbreak of the COVID-19 pandemic. They have caused a drastic change in the everyday lives of people living in urbanized areas, and are considered to contribute to a modified perception of the public space. As research related to the impact of COVID-19 restrictions on mental health and well-being emerges, the associated longitudinal changes of brain hemodynamics in healthy adults remain largely unknown. (2) Methods: this study examined the hemodynamic activation patterns of the prefrontal and occipital cortices of 12 participants (5 male, Mage = 47.80, SDage = 17.79, range 25 to 74, and 7 female, Mage = 39.00, SDage = 18.18, range 21 to 65) passively viewing videos from three urban sites in Singapore (Urban Park, Neighborhood Landscape and City Center) at two different time points-T1, before the COVID-19 pandemic and T2, soon after the lockdown was over. (3) Results: We observed a significant and marginally significant decrease in average oxyhemoglobin (Oxy-Hb) over time for each of the visual conditions. For both green spaces (Urban Park and Neighborhood Landscape), the decrease was in the visual cortex, while for the City Center with no green elements, the marginal decrease was observed in the visual cortex and the frontal eye fields. (4) Conclusions: The results suggest that the COVID-19-related lockdown experienced by urban inhabitants may have contributed to decreased brain hemodynamics, which are further related to a heightened risk of mental health disorders, such as depression or a decline in cognitive functions. Moreover, the busy City Center scenes induced a hemodynamic pattern associated with stress and anxiety, while urban green spaces did not cause such an effect. Urban green scenes can be an important factor to offset the negative neuropsychological impact of busy urban environments post-pandemic.

Cortical haemodynamic response during the verbal fluency task in patients with bipolar disorder and borderline personality disorder: a preliminary functional near-infrared spectroscopy study.

BACKGROUND: Functional near-infrared spectroscopy (fNIRS) is an emerging neuroimaging modality that provides a direct and quantitative assessment of cortical haemodynamic response during a cognitive task. It may be used to identify neurophysiological differences between psychiatric disorders with overlapping symptoms, such as bipolar disorder (BD) and borderline personality disorder (BPD). Hence, this preliminary study aimed to compare the cerebral haemodynamic function of healthy controls (HC), patients with BD and patients with BPD. METHODS: Twenty-seven participants (9 HCs, 9 patients with BD and 9 patients with BPD) matched for age, gender, ethnicity and education were recruited. Relative oxy-haemoglobin and deoxy-haemoglobin changes in the frontotemporal cortex was monitored with a 52-channel fNIRS system during a verbal fluency task (VFT). VFT performance, clinical history and symptom severity were also noted. RESULTS: Compared to HCs, both patient groups had lower mean oxy-haemoglobin in the frontotemporal cortex during the VFT. Moreover, mean oxy-haemoglobin in the left inferior frontal region is markedly lower in patients with BPD compared to patients with BD. Task performance, clinical history and symptom severity were not associated with mean oxy-haemoglobin levels. CONCLUSIONS: Prefrontal cortex activity is disrupted in patients with BD and BPD, but it is more extensive in BPD. These results provide further neurophysiological evidence for the separation of BPD from the bipolar spectrum. fNIRS could be a potential tool for assessing the frontal lobe function of patients who present with symptoms that are common to BD and BPD.

Brief Relaxation Practice Induces Significantly More Prefrontal Cortex Activation during Arithmetic Tasks Comparing to Viewing Greenery Images as Revealed by Functional Near-Infrared Spectroscopy (fNIRS).

BACKGROUND: There is little understanding on how brief relaxation practice and viewing greenery images would affect brain responses during cognitive tasks. In the present study, we examined the variation in brain activation of the prefrontal cortex during arithmetic tasks before and after viewing greenery images, brief relaxation practice, and control task using functional near-infrared spectroscopy (fNIRS). METHOD: This randomized controlled study examined the activation patterns of the prefrontal cortex (PFC) in three groups of research participants who were exposed to viewing greenery images (n = 10), brief relaxation practice (n = 10), and control task (n = 11). The activation pattern of the PFC was measured pre- and post-intervention using a portable fNIRS device and reported as mean total oxygenated hemoglobin (HbO µm). Primary outcome of the study is the difference in HbO µm between post- and pre-intervention readings during a cognitive task that required the research participants to perform arithmetic calculation. RESULTS: In terms of intervention-related differences, there was significant difference in average HbO µm when performing arithmetic tasks before and after brief relaxation practice (p < 0.05). There were significant increases in average HbO µm in the right frontopolar cortex (p = 0.029), the left frontopolar cortex (p = 0.01), and the left orbitofrontal cortex (p = 0.033) during arithmetic tasks after brief relaxation practice. In contrast, there were no significant differences in average HbO µm when performing arithmetic tasks before and after viewing greenery images (p > 0.05) and the control task (p > 0.05). CONCLUSION: Our preliminary findings show that brief relaxation practice but not viewing greenery images led to significant frontal lobe activation during arithmetic tasks. The present study demonstrated, for the first time, that there was an increase in activation in neuroanatomical areas including the combined effort of allocation of attentional resources, exploration, and memory performance after the brief relaxation practice. Our findings suggest the possibility that the right frontopolar cortex, the left frontopolar cortex, and the left orbitofrontal cortex may be specifically associated with the benefits of brief relaxation on the brain.

Validating a functional near-infrared spectroscopy diagnostic paradigm for Major Depressive Disorder.

Reduced haemodynamic response in the frontotemporal cortices of patients with major depressive disorder (MDD) has been demonstrated using functional near-infrared spectroscopy (fNIRS). Most notably, changes in cortical oxy-haemoglobin during a Japanese phonetic fluency task can differentiate psychiatric patients from healthy controls (HC). However, this paradigm has not been validated in the English language. Therefore, the present work aimed to distinguish patients with MDD from HCs, using haemodynamic response measured during an English letter fluency task. One hundred and five HCs and 105 patients with MDD took part in this study. NIRS signals during the verbal fluency task (VFT) was acquired using a 52-channel system, and changes in oxy-haemoglobin in the frontal and temporal regions were quantified. Depression severity, psychosocial functioning, pharmacotherapy and psychiatric history were noted. Patients with MDD had smaller changes in oxy-haemoglobin in the frontal and temporal cortices than HCs. In both regions of interest, oxy-haemoglobin was not associated with any of the clinical variables studied. 75.2% and 76.5% of patients with MDD were correctly classified using frontal and temporal region oxy-haemoglobin, respectively. Haemodynamic response measured by fNIRS during an English letter fluency task is a promising biomarker for MDD.

Locating the Site of Neuropathic Pain In Vivo Using MMP-12-Targeted Magnetic Nanoparticles.

Neuropathic pain remains underrecognised and ineffectively treated in chronic pain sufferers. Consequently, their quality of life is considerably reduced, and substantial healthcare costs are incurred. The anatomical location of pain must be identified for definitive diagnosis, but current neuropsychological tools cannot do so. Matrix metalloproteinases (MMP) are thought to maintain peripheral neuroinflammation, and MMP-12 is elevated particularly in such pathological conditions. Magnetic resonance imaging (MRI) of the peripheral nervous system has made headway, owing to its high-contrast resolution and multiplanar features. We sought to improve MRI specificity of neural lesions, by constructing an MMP-12-targeted magnetic iron oxide nanoparticle (IONP). Its in vivo efficiency was evaluated in a rodent model of neuropathic pain, where the left lumbar 5 (L5) spinal nerve was tightly ligated. Spinal nerve ligation (SNL) successfully induced mechanical allodynia, and thermal hyperalgesia, in the left hind paw throughout the study duration. These neuropathy characteristics were absent in animals that underwent sham surgery. MMP-12 upregulation with concomitant macrophage infiltration, demyelination, and elastin fibre loss was observed at the site of ligation. This was not observed in spinal nerves contralateral and ipsilateral to the ligated spinal nerve or uninjured left L5 spinal nerves. The synthesised MMP-12-targeted magnetic IONP was stable and nontoxic in vitro. It was administered onto the left L5 spinal nerve by intrathecal injection, and decreased magnetic resonance (MR) signal was observed at the site of ligation. Histology analysis confirmed the presence of iron in ligated spinal nerves, whereas iron was not detected in uninjured left L5 spinal nerves. Therefore, MMP-12 is a potential biomarker of neuropathic pain. Its detection in vivo, using IONP-enhanced MRI, may be further developed as a tool for neuropathic pain diagnosis and management.

Factors Associated with the Risk of Developing Coronary Artery Disease in Medicated Patients with Major Depressive Disorder.

Background: The aim of this study was to identify factors associated with high Framingham Risk Score (FRS) in medicated patients with major depressive disorder (MDD). Methods: We examined 61 medicated patients with MDD (mean age 37.77 ± 7.67, 90.2% women) and 43 non-depressed controls (mean age 38.26 ± 9.20, 90.7% women). We administered the Hamilton Depression Rating Scale (HAM-D) and measured systolic blood pressure (SBP), diastolic BP (DBP), mean arterial BP (MAP), pulse wave velocity (PWV), intima-media thickness (IMT), interleukin-6 (IL-6) and triglycerides. Results: We found that medicated patients with MDD had significantly higher levels of HAM-D score (p < 0.01), SBP (p = 0.015), MAP (p = 0.037), IL-6 level (p = 0.007), as compared with controls. Medicated patients who remained moderately to severely depressed showed significantly higher SBP (p = 0.049), DBP (p = 0.009), MAP (p = 0.024), IL-6 level (p = 0.019), left PWV (p = 0.004) and average PWV (p = 0.026) than those with mild depression. Multivariate regression showed that the interaction effect between HAM-D score and triglyceride level (p = 0.018) was significantly associated with FRS in medicated patients with MDD. Conclusions: This study highlights that the interaction effect of the severity of depression and the triglyceride level, was a modifiable factor positively associated with high FRS.