Category: Mental Health Research

GABA and Mental Disorders

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Research Paper Title

Development and validation of a UPLC-MS/MS method for the simultaneous determination of gamma-aminobutyric acid and glutamic acid in human plasma.

Background

Gamma-aminobutyric acid (GABA) and its precursor glutamic acid are important neurotransmitters. Both are also present in peripheral tissues and the circulation, where abnormal plasma concentrations have been linked to specific mental disorders. In addition to endogenous synthesis, GABA and glutamic acid can be obtained from dietary sources.

An increasing number of studies suggest beneficial cardio-metabolic effects of GABA intake, and therefore GABA is being marketed as a food supplement.

The need for further research into their health effects merits accurate and sensitive methods to analyse GABA and glutamic acid in plasma.

Methods

To this end, an ultra-pressure liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the quantification of GABA and glutamic acid in human plasma.

Samples were prepared by a protein precipitation step and subsequent solid phase extraction using acetonitrile.

Results

Chromatographic separation was achieved on an Acquity UPLC HSS reversed phase C18 column using gradient elution. Analytes were detected using electrospray ionisation and selective reaction monitoring. Standard curve concentrations for GABA ranged from 3.4 to 2500 ng/mL and for glutamic acid from 30.9 ng/mL to 22,500 ng/mL. Within- and between-day accuracy and precision were <10% in quality control samples at low, medium and high concentrations for both GABA and glutamic acid. GABA and glutamic acid were found to be stable in plasma after freeze-thaw cycles and up to 12 months of storage. The validated method was applied to human plasma from 17 volunteers. The observed concentrations ranged between 11.5 and 20.0 ng/ml and 2269 and 7625 ng/ml for respectively GABA and glutamic acid.

Conclusions

The reported method is well suited for the measurement of plasma GABA and glutamic acid in pre-clinical or clinical studies.

Reference

de Bie, T.H., Witkamp, R.F., Jongsma, M.A. & Balvers, M.G.J. (2021) Development and validation of a UPLC-MS/MS method for the simultaneous determination of gamma-aminobutyric acid and glutamic acid in human plasma. Journal of Chromatography. doi: 10.1016/j.jchromb.2020.122519. Online ahead of print.

Linking PTSD, Trauma, & ASD

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Research Paper Title

Heightened risk of posttraumatic stress disorder in adults with autism spectrum disorder: The role of cumulative trauma and memory deficits.

Background

Individuals with Autism Spectrum Disorder (ASD) are known to be at increased risk of exposure to traumas such as maltreatment and abuse, however less is known about possible susceptibility towards the development of Posttraumatic Stress Disorder (PTSD) and associated risk factors.

This study investigated the rates of trauma exposure and PTSD, and the role of cumulative trauma exposure and memory as risk factors for PTSD in adults who self-reported having received an ASD diagnosis, compared to a typically developing (TD) comparison group.

Methods

Questionnaires assessing self-reported frequency of trauma exposure (LEC), PTSD symptomology (PCL-S) and memory (EMQ- R and BRIEF-A) were completed online by 38 ASD adults and 44 TD adults.

Results

Rates of trauma exposure and PTSD symptomatology were significantly higher in the ASD group, compared to the TD group, with deficits in working memory and everyday memory mediating this association. Interestingly, a cumulative effect of trauma exposure on PTSD symptom severity was only found in the ASD group.

Conclusions

High rates of trauma and probable PTSD in ASD adults highlight the importance of routine screening. Cumulative trauma exposure and memory deficits may act to increase risk of PTSD in ASD; longitudinal research is called for.

Reference

Rumball, F., Brook, L., Happe, F. & Karl, A. (2021) Heightened risk of posttraumatic stress disorder in adults with autism spectrum disorder: The role of cumulative trauma and memory deficits. Research in Developmental Disabilities. doi: 10.1016/j.ridd.2020.103848. Online ahead of print.

What is the Prevalence & Risk Factors of Perinatal Depression Among Women in Rural Bihar?

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Research Paper Title

Prevalence and risk factors of perinatal depression among women in rural Bihar: A community-based cross-sectional study.

Background

Perinatal depression (PND) is one of the most common mental disorders occurring during the perinatal period among women. Few studies examined prevalence and risk factors of PND from rural settings in India. This study aimed to estimate the prevalence of perinatal depression and identify social risk factors for it among women from rural Bihar.

Methods

A cross sectional study was conducted in a community setting in rural areas of Bihar. All perinatal women were screened through a door to door survey and recruited after obtaining informed consent. A semi-structured proforma was used to collect sociodemographic characteristics and family related variables. Edinburgh postnatal depression scale (EPDS) was used to screen for perinatal depression.

Results

A total of 564 perinatal women were recruited into the study. The estimated prevalence of PND was 23.9 % (95 % CI: 20.6,27.6). Multivariate analysis showed perinatal depression was associated with physical illness in the mother, previous history of abortion, poor financial status and ill-treatment by in-laws.

Conclusions

Prevalence of perinatal depression among women is high in rural settings of North India. A multitude of factors ranging from physical, obstetric, economic and family related confer a high risk for PND. Comprehensive interventions are needed to address these risk factors of perinatal depression.

Reference

Raghavan, V., Khan, H.A., Seshu, U., Rai, S.P., Durairaj, J., Aarthi, G., Sangeetha, C., John, S. & Thara, R. (2021) Prevalence and risk factors of perinatal depression among women in rural Bihar: A community-based cross-sectional study. Asian Journal of Psychiatry. doi: 10.1016/j.ajp.2021.102552. Online ahead of print.

Is the Mental Wellbeing of Doctors Becoming an Increasing Concern?

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Research Paper Title

Depressive symptoms in residents of a tertiary training hospital in Malaysia: The prevalence and associated factors.

Background

The mental wellbeing of doctors is becoming an increasing concern in the world today.

In Malaysia, residency is a challenging period in a doctor’s life, with many changes professionally and possibly in their personal lives as well.

This study aims to determine the prevalence of depressive symptoms and the socio-demographic correlates among residents in a tertiary training hospital in Malaysia.

It is a cross sectional study and all residents were approached to participate in the study.

Methods

The instruments used were a socio-demographic questionnaire and the Patient Health Questionnaire 9 (PHQ-9).

Chi-square test was used to explore the association between the socio-demographic correlates, and those that were found to have significant associations were further tested using multivariate logistic regression.

Results

The prevalence of depression among residents was 25.1 %. Longer working hours, missing meals, and working in Department of Surgery and Department of Anaesthesia was significantly positively associated while having protected study time, CME/lectures, leisure/hobbies and exercise were negatively associated with depression.

The Department of Rehabilitation Medicine had a significantly negative association with depression. After logistic regression, longer working hours and a lack of protected study time was significantly associated with depression in the respective departments.

Conclusions

In summary, the prevalence of depression among residents is high and is associated with longer working hours, missing meals and a lack of protected study time are significantly associated with depression.

Remedial steps should be taken to improve the mental health among residents.

Reference

Nair, N., Ng, C.G. & Sulaiman, A.H. (2021) Depressive symptoms in residents of a tertiary training hospital in Malaysia: The prevalence and associated factors. Asian Journal of Psychiatry. doi: 10.1016/j.ajp.2021.102548. Online ahead of print.

Neighbourhood & Mental Health During Covid-19: Any Link?

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Research Paper Title

Examine the associations between perceived neighbourhood conditions, physical activity, and mental health during the COVID-19 pandemic.

Background

This study examined how neighbourhood conditions changed and how neighbourhood conditions were associated with physical activity and mental health during the COVID-19 pandemic among Americans.

Methods

The major outcomes were stratified by the neighbourhood’s poverty and regression models were used to assess the associations between neighbourhood conditions and their change during the pandemic and the outcomes of physical activity and mental health.

Results

The results show that low-poverty neighbourhoods had more health-promoting neighbourhood conditions before the outbreak and more positive changes during the outbreak. Health-promoting neighbourhood conditions were associated with higher physical activity and moderate physical activity and lack of negative neighbourhood conditions such as crime/violence and traffic were associated with a lower risk of mental health problems including loneliness, depression, and anxiety. Mental health problems were also significantly associated with the COVID-19 infection and death and household income level.

Conclusions

The findings suggest that it is plausible that the disparities of physical activity and mental health by neighbourhood exacerbate due to the pandemic and people who are living in socioeconomically disadvantaged neighbourhoods bear increasingly disproportionate burden.

Reference

Yang, Y. & Xiang, X. (2021) Examine the associations between perceived neighborhood conditions, physical activity, and mental health during the COVID-19 pandemic. Health & Place. doi: 10.1016/j.healthplace.2021.102505. Online ahead of print.

Identifying Two Novel Distinct Epigenetic Biotypes for PTSD

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Research Paper Title

Epigenetic biotypes of post-traumatic stress disorder in war-zone exposed veteran and active duty males.

Background

Post-traumatic stress disorder (PTSD) is a heterogeneous condition evidenced by the absence of objective physiological measurements applicable to all who meet the criteria for the disorder as well as divergent responses to treatments.

Methods

This study capitalised on biological diversity observed within the PTSD group observed following epigenome-wide analysis of a well-characterised Discovery cohort (N = 166) consisting of 83 male combat exposed veterans with PTSD, and 83 combat veterans without PTSD in order to identify patterns that might distinguish subtypes.

Results

Computational analysis of DNA methylation (DNAm) profiles identified two PTSD biotypes within the PTSD+ group, G1 and G2, associated with 34 clinical features that are associated with PTSD and PTSD comorbidities.

The G2 biotype was associated with an increased PTSD risk and had higher polygenic risk scores and a greater methylation compared to the G1 biotype and healthy controls.

The findings were validated at a 3-year follow-up (N = 59) of the same individuals as well as in two independent, veteran cohorts (N = 54 and N = 38), and an active duty cohort (N = 133).

In some cases, for example Dopamine-PKA-CREB and GABA-PKC-CREB signalling pathways, the biotypes were oppositely dysregulated, suggesting that the biotypes were not simply a function of a dimensional relationship with symptom severity, but may represent distinct biological risk profiles underpinning PTSD.

Conclusions

The identification of two novel distinct epigenetic biotypes for PTSD may have future utility in understanding biological and clinical heterogeneity in PTSD and potential applications in risk assessment for active duty military personnel under non-clinician-administered settings, and improvement of PTSD diagnostic markers.

Reference

Yang, R., Gautam, A., Getnet, D., Daigle, B.J., Miller, S., Misganaw, B., Dean, K.R., Kumar, R., Muhie, S., Wang, K., Lee, I., Abu-Amara, D., Flory, J.D., PTSD Systems Biology Consortium, Hood, L., Wolkowitz, O.M., Mellon, S.H., Doyle 3rd, F.J., Yehuda, R., Marmar, C.R., Ressler, K.J., Hammamieh, R. & Jett, M. (2020) Epigenetic biotypes of post-traumatic stress disorder in war-zone exposed veteran and active duty males. Molecular Psychiatry. doi: 10.1038/s41380-020-00966-2. Online ahead of print.

What is the Impact of Shame in Body-Focused Repetitive Behaviours & Binge Eating?

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Research Paper Title

“Shame on you”: The impact of shame in body-focused repetitive behaviours and binge eating.

Background

Body-focused repetitive behaviours (BFRBs), such as hair-pulling, skin-picking, and nail-biting, have been associated with difficulties in emotion regulation.

Studies have suggested that aversive emotions are important triggers for impulsive behaviours such as BFRBs and binge eating.

In particular, shame has been hypothesized to be a key emotion before and after these behaviours, but no experimental studies yet have investigated its impact on BFRBs.

The researchers aimed to evaluate the role of shame in BFRB and binge eating episodes and the presence of shame following these behaviours.

Methods

Eighteen women with BFRBs, 18 with binge eating, and 18 community controls participated in the study.

Results

Results showed that an experimental shame condition triggered more shame in the binge eating and BFRB groups than in the control group.

In addition, the shame induced condition increased the urge to engage in BFRBs, but not in binge eating.

Conclusions

Results showed that participants from the BFRB and the binge eating groups reported more shame after engaging in their pathological behaviours compared to following the neutral condition.

Future studies should replicate these findings with larger samples and different shame-inducing conditions.

Reference

Houazene, S., Leclerc, J.B., O’Connor, K. & Aardema, F. (2021) “Shame on you”: The impact of shame in body-focused repetitive behaviors and binge eating. Behaviour Research and Therapy. doi: 10.1016/j.brat.2021.103804. Online ahead of print.

Does the OCI-4 Show Promise as an Ultra-Brief Screening Tool for Identifying likely OCD?

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Research Paper Title

The OCI-4: An ultra-brief screening scale for obsessive-compulsive disorder.

Background

Obsessive-compulsive disorder (OCD) is a prevalent and burdensome condition that is typically assessed using in-depth interviews or lengthy self-report measures. Accordingly, routine screening in busy non-mental health settings is impractical, and OCD is often under- (or mis-) recognised.

Methods

The researchers evaluated an ultra-brief version of a widely used self-report measure, the Obsessive-Compulsive Inventory-Revised (OCI-R), which may be employed as a routine screener for OCD.

A total of 1,087 adults diagnosed with OCD, 1,306 unselected adults from the community, and 423 adults with anxiety related disorders completed the OCI-R along with measures of anxiety and mood.

Analyses were conducted to reduce the number of items and examine evidence for sensitivity and specificity to OCD clinical status, test-retest reliability, sensitivity to treatment, and convergent and discriminant validity.

Results

Four items that optimally assess different dimensions of OCD (washing, checking, ordering, obsessing) were identified. Psychometric evaluation revealed good to excellent test-retest reliability, validity, prediction of clinical OCD status, and sensitivity to treatment.

Conclusions

A 4-item version of the OCI-R, called the OCI-4, shows promise as an ultra-brief screening tool for identifying likely OCD in settings where in-depth assessment is impractical. Patients with a positive screen may be referred for further evaluation and appropriate treatment.

Reference

Abramovitch, A., Abramovitchm J.S. & McKay, D. (2021) The OCI-4: An ultra-brief screening scale for obsessive-compulsive disorder. Journal of Anxiety Disorder. doi: 10.1016/j.janxdis.2021.102354. Online ahead of print.

Schizophrenia & Smoking Traits

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Research Paper Title

Colocalisation of association signals at nicotinic acetylcholine receptor genes between schizophrenia and smoking traits.

Background

Epidemiological data suggest that smoking may be a risk factor for schizophrenia (SCZ), but more evidence is needed. Two regions coding nicotinic acetylcholine receptor (nAchR) subunits, atCHRNA2 and the CHRNA5/A3/B4 cluster, were associated with SCZ in genome-wide association studies (GWAS). Additionally, a signal at CHRNA4 is near significance. CHRNA2 was also associated with cannabis use disorder (CUD). These regions were also associated with smoking behaviours. If tobacco is a risk factor, the GWAS signals at smoking behaviours and SCZ have to be due to the same causal variants, i.e. they have to colocalise, although colocalisation does not necessarily imply causality. Here, we present colocalisation analysis at these loci between SCZ and smoking behaviours.

Methods

The Bayesian approach implemented in coloc was used to check for posterior probability of colocalisation versus independent signals at the three loci with some evidence of association with SCZ and smoking behaviours, using GWAS summary statistics. Colocalisation was also assessed for positive control traits and CUD. Three different sensibility analyses were used to confirm the results. A visualisation tool, LocusCompare, was used to facilitate interpretation of the coloc results.

Results

Evidence for colocalisation of GWAS signals between SCZ and smoking behaviours was found for CHRNA2. Evidence for independent causal variants was found for the other two loci. CUD GWAS signal at CHRNA2 colocalises with SCZ and smoking behaviours.

Conclusions

Overall, the results indicate that the association between some nAchR subunit genes and SCZ cannot be solely explained by their effect on smoking behaviours.

Reference

Al-Soufi, L. & Costas, J. (2021) Colocalization of association signals at nicotinic acetylcholine receptor genes between schizophrenia and smoking traits. Drug and Alcohol Dependence. doi: 10.1016/j.drugalcdep.2021.108517. Online ahead of print.

Does Lack of a Consistent Definition Hinder Treatment for Clozapine-Resistant Schizophrenia Patients?

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Research Paper Title

Characteristics and definitions of ultra-treatment-resistant schizophrenia – A systematic review and meta-analysis.

Background

The aim of this systematic review and meta-analysis was to characterise ultra-treatment-resistant Schizophrenia also known as clozapine-resistant schizophrenia (CRS) patients across clozapine combination and augmentation trials through demographic and clinical baseline data. Furthermore, the researchers investigated the variability and consistency in CRS definitions between studies.

Methods

Systematic searches of articles indexed in PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL) and PsycINFO were conducted in March 2020. 1541 randomised and non-randomised clinical trials investigating pharmacological and non-pharmacological clozapine add-on strategies were screened and a total of 71 studies were included. The primary outcome was the overall symptom score at baseline, measured with Positive and Negative Syndrome Scale (PANSS) total or Brief Psychiatric Rating Scale (BPRS) total scores.

Results

Data from 2731 patients were extracted. Patients were overall moderately ill with a mean PANSS total score at baseline of 79.16 (±7.52), a mean duration of illness of 14.64 (±4.14) years with a mean clozapine dose of 436.94 (±87.47) mg/day. Illness severity data were relatively homogenous among patients independently of the augmentation strategy involved, although stark geographical differences were found. Overall, studies showed a large heterogeneity of CRS definitions and insufficient guidelines implementation.

Conclusions

This first meta-analysis characterising CRS patients and comparing CRS definitions revealed a lack of consistent implementation of a CRS definition from guidelines into clinical trials, compromising the replicability of the results and their applicability in clinical practice. The researchers offer a new score modelled on a best practice definition to help future trials increase their reliability.

Reference

Campana, M., Falkai, P., Siskind, D., Hasan, A. & Wagner, E. (2021) Characteristics and definitions of ultra-treatment-resistant schizophrenia – A systematic review and meta-analysis. Schizophrenia Research. 228, pp.218-226. doi: 10.1016/j.schres.2020.12.002. Online ahead of print.