Category: Mental Health Research

What is the Role of the Microbiota-Gut-Brain Axis in Mental Health & Medication Response?

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Research Paper Title

The Microbiota-Gut-Brain Axis in Mental Health and Medication Response: Parsing Directionality and Causality.

Abstract

There is increasing evidence for the role of the microbiome in various mental health disorders. Moreover, there has been a growing understanding of the importance of the microbiome in mediating both the efficacy and side effects of various medications, including psychotropics.

In this issue, Tomizawa and colleagues report on the effect of psychotropic drugs on the gut microbiome of 40 patients with depression and/or anxiety disorders.

In their longitudinal cohort, the authors find that antipsychotics, but not anxiolytics, decrease microbiome alpha diversity. They further find that antipsychotics dosage was negatively correlated with alpha diversity in these patients.

The health consequences of these microbiome alterations remain to be fully understood. In this commentary, the authors will discuss such findings through the lens of several recent studies on the microbiota-gut-brain axis. They also use the paper as a backdrop to discuss directionality and, by extension, causality in relation to microbiota-gut-brain-brain signalling.

Reference

Bastiaanssen, T.F.S. & Cryan, J.F. (2021) The Microbiota-Gut-Brain Axis in Mental Health and Medication Response: Parsing Directionality and Causality. The International Journal of Neuropsychopharmacology. 24(3), pp.216-220. doi: 10.1093/ijnp/pyaa088.

The Importance of International Patient-Reported Indicators in Mental Health

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Research Paper Title

Patient-reported indicators in mental health care: towards international standards among members of the OECD.

Background

Achieving people-centred health care systems requires new and innovative strategies to capture information about whether, and to what degree, health care is successful in improving health from the perspective of the patient. Patient-reported outcome measures (PROMs) and Patient-reported experience measures (PREMs) can bring some of these new insights, and are increasingly used in research, clinical care, and policymaking.

Methods

This paper reflects the ongoing discussions and findings of the OECD PaRIS Working Group on Patient-reported Indicators for Mental Health Care.

Results

The OECD has been measuring quality of care for mental health conditions over the last 14 years through the Health Care Quality and Outcomes (HCQO) programme; nonetheless, information on how persons with mental health problems value the services they receive, and impact of the services, remains limited. As of 2018, a survey from the OECD showed that only five of the twelve countries surveyed (Australia, Israel, Netherlands, Sweden, United Kingdom) reported PROMs and PREMs collection on a regular basis in mental health settings. The paper details some of the challenges specific to the collection and use of PROMs and PREMs in mental health care, and examples from countries which have implemented comprehensive programmes to gather information about PROMs and PREMs for individuals receiving mental health services.

Conclusions

Given the health and economic impact of mental ill-health across all OECD countries, there is significant value to being able to assess the quality and outcomes of care in this area using internationally-comparable measures. Continued international harmonisation of PROMs and PREMs for mental health through international coordination is a key way to facilitate the sharing of national experiences, promote the use of PROMs and PREMs, and create meaningful indicators for national and international benchmarking.

Reference

de Bienassis, K., Kristensen, S., Hewlett, E., Roe, D., Mainz, J. & Klazinga, N. (2021) Patient-reported indicators in mental health care: towards international standards among members of the OECD. International Journal for Quality in Health Care. doi: 10.1093/intqhc/mzab020.

Principles for Improving Investment in Translational Neuroscience Aimed at Psychiatric Drug Discovery

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Research Paper Title

Time to re-engage psychiatric drug discovery by strengthening confidence in preclinical psychopharmacology.

Background

There is urgent need for new medications for psychiatric disorders. Mental illness is expected to become the leading cause of disability worldwide by 2030. Yet, the last two decades have seen the pharmaceutical industry withdraw from psychiatric drug discovery after costly late-stage trial failures in which clinical efficacy predicted pre-clinically has not materialised, leading to a crisis in confidence in preclinical psychopharmacology.

Methods

Based on a review of the relevant literature, the researchers formulated some principles for improving investment in translational neuroscience aimed at psychiatric drug discovery.

Results

The researchers propose the following 8 principles that could be used, in various combinations, to enhance CNS drug discovery:

  1. Consider incorporating the NIMH Research Domain Criteria (RDoC) approach;
  2. Engage the power of translational and systems neuroscience approaches;
  3. Use disease-relevant experimental perturbations;
  4. Identify molecular targets via genomic analysis and patient-derived pluripotent stem cells;
  5. Embrace holistic neuroscience: a partnership with psychoneuroimmunology;
  6. Use translational measures of neuronal activation;
  7. Validate the reproducibility of findings by independent collaboration; and
  8. Learn and reflect.

They provide recent examples of promising animal-to-human translation of drug discovery projects and highlight some that present re-purposing opportunities.

Conclusions: We hope that this review will re-awaken the pharma industry and mental health advocates to the opportunities for improving psychiatric pharmacotherapy and so restore confidence and justify re-investment in the field.

Reference

Tricklebank, M.D., Robbins, T.W., Simmons, C. & Wong, E.H.F. (2021) Time to re-engage psychiatric drug discovery by strengthening confidence in preclinical psychopharmacology. Psychopharmacology (Berl). doi: 10.1007/s00213-021-05787-x. Online ahead of print.

In Vogue: ASD

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Research Paper Title

What is Austism?

Background

The term “Autism spectrum disorder” (ASD), in vogue at present, has evolved after continual substantial developments taking place over more than a century.

ASD is a heterogeneous, multi-factorial, developmental disability in which an unusual pattern of development takes place during infant and toddler years.

As per DSM-5, Autism spectrum disorder is a combined phrase for a family of complex developmental disabilities inclusive of “Autistic Disorder, Pervasive Developmental Disorder not Otherwise Specified (PDD-NOS), and Asperger’s Disorder”.

“ASD is characterized not only by persistent impairments in reciprocal social communication and social interactions, but is also manifested by restricted, repetitive patterns of behavior, interests, or activities”.

The classical clinical signs that exist in two major domains, viz. the ‘social domain’ and the ‘behavioral domain’ for the precise diagnosis of ASD have been tabulated and major differences between DSM-5 and DSM-4 are depicted with the help of a figure in this basic review article.

A sharp rise in the incidence of ASD cases has been observed worldwide owing to various risk factors such as genetic predisposition coupled with adverse environmental conditions, gynaecological interventions, etc.

Two official manuals viz. the “Diagnostic and Statistical Manual of Mental Disorders” (DSM) (published by the American Psychiatric Association), and the “International Classification of Diseases” (ICD) (published by the World Health Organization) is being regularly updated to facilitate diagnosis of ASD.

ICD-11 guidelines being prospectively implemented with effect from January 2022 have attracted global attention.

Reference

Joon, P., Kumar, A. & Parle, M. (2021) What is Autism? Pharmacological Reports. doi: 10.1007/s43440-021-00244-0. Online ahead of print.

Anxiety Youth vs Healthy Youth: Threat-Anticipatory Psychophysiological Response Differences

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Research Paper Title

Threat-anticipatory psychophysiological response is enhanced in youth with anxiety disorders and correlates with prefrontal cortex neuroanatomy.

Background

Threat anticipation engages neural circuitry that has evolved to promote defensive behaviours; perturbations in this circuitry could generate excessive threat-anticipation response, a key characteristic of pathological anxiety. Research into such mechanisms in youth faces ethical and practical limitations. Here, the researchers use thermal stimulation to elicit pain-anticipatory psychophysiological response and map its correlates to brain structure among youth with anxiety and healthy youth.

Methods

Youth with anxiety (n = 25) and healthy youth (n = 25) completed an instructed threat-anticipation task in which cues predicted nonpainful or painful thermal stimulation; the researchers indexed psychophysiological response during the anticipation and experience of pain using skin conductance response. High-resolution brain-structure imaging data collected in another visit were available for 41 participants. Analyses tested whether the 2 groups differed in their psychophysiological cue-based pain-anticipatory and pain-experience responses. Analyses then mapped psychophysiological response magnitude to brain structure.

Results

Youth with anxiety showed enhanced psychophysiological response specifically during anticipation of painful stimulation (b = 0.52, p = 0.003). Across the sample, the magnitude of psychophysiological anticipatory response correlated negatively with the thickness of the dorsolateral prefrontal cortex (pFWE < 0.05); psychophysiological response to the thermal stimulation correlated positively with the thickness of the posterior insula (pFWE < 0.05).

Limitations: Limitations included the modest sample size and the cross-sectional design.

Conclusions

These findings show that threat-anticipatory psychophysiological response differentiates youth with anxiety from healthy youth, and they link brain structure to psychophysiological response during pain anticipation and experience. A focus on threat anticipation in research on anxiety could delineate relevant neural circuitry.

Reference

Abend, R., Bajaj, M.A., Harrwijn, A., Matsumoto, C., Michalska, K.J., Necka, E., Palacios-Barrios, E.E., Leibenluft, E., Atlas, L.Y. & Pine, D.S. (2021) Threat-anticipatory psychophysiological response is enhanced in youth with anxiety disorders and correlates with prefrontal cortex neuroanatomy. Journal of Psychiatry & Neuroscience. 46(2):E212-E221. doi: 10.1503/jpn.200110.

The Use of Ramelteon in the the Treatment of Sleep-Related Eating Disorder & Night Eating Syndrome

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Research Paper Title

The efficacy of add-on ramelteon and subsequent dose reduction of benzodiazepine derivatives/Z-drugs for the treatment of sleep-related eating disorder and night eating syndrome: a retrospective analysis of consecutive cases.

Background

The objective of this study was to determine the efficacy of ramelteon in treating abnormal eating behaviour in cases with sleep-related eating disorder (SRED) and/or night eating syndrome (NES).

Methods

The researchers retrospectively reviewed the medical records of patients with SRED/NES at Yoyogi Sleep Disorder Centre from November 2013 to November 2018. They categorised patients as ramelteon treatment responders when the frequency of night time eating per week decreased to less than half of that before treatment.

Results

Forty-nine patients were included in the analysis. The mean frequency of eating behaviour (/week) (standard deviation) at baseline and post-ramelteon treatment was significantly different, at 5.3 (2.2) and 3.2 (3.0), respectively (p < .001). Twenty-one patients (42.9%) were classified as responders. Adverse events, all of which were mild daytime somnolence, were observed in 5 cases. There were significantly more individuals using benzodiazepine derivatives and Z-drugs (BZDs) before treatment and those with coexisting delayed sleep-wake phase disorder (DSWPD) in the responder group than in the non-responder group (p < .001 and p < .05, respectively). The mean BZD dose significantly decreased from baseline to post-ramelteon treatment within the responder group (p < .05). This trend was not observed in the non-responder group. Meanwhile, the sleep midpoint of patients with SRED/NES and DSWPD did not significantly change after treatment.

Conclusions

The results indicate that ramelteon is a candidate treatment for SRED/NES. The effects of ramelteon might have occurred primarily through the reduction of BZD rather than through the improvement of sleep-wake rhythm dysregulation.

Reference

Matsui, K., Kuriyama, K., Kobayashi, M., Inada, K., Nishimura, K. & Inoue, Y. (2021) The efficacy of add-on ramelteon and subsequent dose reduction of benzodiazepine derivatives/Z-drugs for the treatment of sleep-related eating disorder and night eating syndrome: a retrospective analysis of consecutive cases. Journal of Clinical Sleep Medicine. doi: 10.5664/jcsm.9236. Online ahead of print.

Are There Gender-Related Differences in Internet Gaming Disorder?

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Research Paper Title

Gender-related differences in frontal-parietal modular segregation and altered effective connectivity in internet gaming disorder.

Background

Although previous studies have revealed gender-related differences in executive function in internet gaming disorder (IGD), neural mechanisms underlying these processes remain unclear, especially in terms of brain networks.

Methods

Resting-state fMRI data were collected from 78 subjects with IGD (39 males, 20.8 ± 2.16 years old) and 72 with recreational game use (RGU) (39 males, 21.5 ± 2.56 years old). By utilising graph theory, the researchers calculated participation coefficients among brain network modules for all participants and analysed the diagnostic-group-by-gender interactions. They further explored possible causal relationships between networks through spectral dynamic causal modelling (spDCM) to assess differences in between-network connections.

Results

Compared to males with RGU, males with IGD demonstrated reduced modular segregation of the frontal-parietal network (FPN). Male IGD subjects also showed increased connections between the FPN and cingulo-opercular network (CON); however, these differences were not found in female subjects. Further spDCM analysis indicated that the causal influence from CON to FPN in male IGD subjects was enhanced relative to that of RGU males, while this influence was relatively reduced in females with IGD.

Conclusions

These results suggest poor modular segmentation of the FPN and abnormal FPN/CON connections in males with IGD, suggesting a mechanism for male vulnerability to IGD. An increased “bottom-up” effect from the CON to FPN in male IGD subjects could reflect dysfunction between the brain networks. Different mechanisms may underlie in IGD, suggesting that different interventions may be optimal in males and females with IGD.

Reference

Zeng, N., Wang, M., Zheng, H., Zhang, J., Dong, H., Potenza, M.N. & Dong, G-H. (2021) Gender-related differences in frontal-parietal modular segregation and altered effective connectivity in internet gaming disorder. Journal of Behavioural Addictions. doi: 10.1556/2006.2021.00015. Online ahead of print.

Are Those With Serious Mental Illness More or Less Likely to Receive Cancer Screening?

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Research Paper Title

Cancer Screening Among Adults With and Without Serious Mental Illness: A Mixed Methods Study.

Background

Persons with serious mental illness (SMI) die 10-20 years earlier than the general population; cancer is the second leading cause of death. Differences in cancer screening between SMI and the general population are not well understood.

Therefore the aim of this study was to describe receipt of cancer screening among individuals with versus without SMI and to explore clinicians’ perceptions around cancer screening for people with SMI.

Methods

Mixed-methods study using 2010-2017 MarketScan commercial insurance administrative claims data and semi-structured clinician interviews. In the quantitative analyses, we used multivariate logistic regression analyses to calculate the likelihood of receiving cervical, breast, colorectal, or prostate cancer screening among people with versus without SMI, defined as schizophrenia or bipolar disorder. We conducted semi-structured interviews with 17 primary care physicians and 15 psychiatrists. Interview transcripts were coded using a hybrid deductive/inductive approach.

Results

Relative to those without SMI, individuals with SMI were less likely to receive screening for cervical cancer [adjusted odds ratio (aOR): 0.80; 95% confidence interval (CI): 0.80-0.81], breast cancer (aOR: 0.79; 95% CI: 0.78-0.80), colorectal cancer (aOR: 0.90; 95% CI: 0.89-0.91), and prostate cancer (aOR: 0.85; 95% CI: 0.84-0.87). Clinicians identified 5 themes that may help explain the lower rates of cancer screening in persons with SMI: access to care, available support, prioritization of other issues, communication, and patient concerns.

Conclusions

People with SMI were less likely to receive 4 common types of cancer screening. Improving cancer screening rates in the SMI population will likely require a multidisciplinary approach to overcome barriers to screening.

Reference

Murphy, K.A., Stone, E.M., Presskreischer, R., McGinty, E.E., Daumit, G.L. & Pollack, C.E. (2021) Cancer Screening Among Adults With and Without Serious Mental Illness: A Mixed Methods Study. Medical Care. 59(4), pp.327-333. doi: 10.1097/MLR.0000000000001499.

Do High Levels of Physical Activity in Acute Anorexia Nervosa Associate with Worse Clinical Outcomes at Admission?

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Research Paper Title

High levels of physical activity in female adolescents with anorexia nervosa: medical and psychopathological correlates.

Background

While overexercise is commonly described in patients who experience anorexia nervosa (AN), it represents a condition still underestimated, especially in the paediatric population.

Methods

The present study aims at assessing the possible associations between levels of physical activity (PA) and clinical features, endocrinological data and psychopathological traits in a sample of 244 female adolescents hospitalised for AN subdivided into two groups according to PA levels (high PA vs. no/low PA). The two groups were compared through multivariate analyses, while multiple regression analysis was conducted to determine whether physical activity predict specific outcomes.

Results

No significant differences were found between the two groups in terms of last Body Mass Index (BMI) before illness, BMI at admission and disease duration, while a difference emerged in delta BMI(rapidity of weight loss), significantly higher in high-PA group (p = 0.021). Significant differences were observed in Free triiodothyronine- (p < 0.001), Free thyroxine (p = 0.046), Follicle-stimulating hormone (p = 0.019), Luteinising hormone (p = 0.002) levels, with values remarkably lower in high-PA group. Concerning psychopathological scales, the high-PA group showed worst Children’s Global Assessment Scale (CGAS) scores (p = 0.035). Regression analyses revealed that higher PA predicts higher delta BMI (p = 0.021), presence of amenorrhea (p = 0.003), lower heart rate (p = 0.012), lower thyroid (Free triiodothyronine p < 0.001, Free thyroxine p = 0.029) and gynaecological hormones’ levels (Follicle-stimulating hormone p = 0.023, Luteinising hormone p = 0.003, 17-Beta estradiol p = 0.041). Concerning psychiatric measures, HPA predicts worst scores at CGAS (p = 0.019), and at scales for evaluation of alexithymia (p = 0.028) and depression (p = 0.004).

Conclusions

Results suggest that high levels of physical activity in acute AN associate with worst clinical conditions at admission, especially in terms of endocrinological and medical features.

Reference

Riva, A., Falbo, M., Passoni, P., Polizzi, S., Cattoni, A. & Nacinovich, R. (2021) High levels of physical activity in female adolescents with anorexia nervosa: medical and psychopathological correlates. Eating and Weight Disorders. doi: 10.1007/s40519-021-01126-3. Online ahead of print.

Reviewing the Understanding of the Treatment Guidelines for Schizophrenia & Major Depressive Disorder

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Research Paper Title

Improvements in the degree of understanding of the treatment guidelines for schizophrenia and major depressive disorder in a nationwide dissemination and implementation study.

Background

To implement clinical practice guidelines (CPGs), it is necessary for psychiatrists to deepen their understanding of the CPGs. The Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE) project is a nationwide dissemination and implementation study of two sets of CPGs for schizophrenia and major depressive disorder (MDD).

Methods

A total of 413 psychiatrists (n = 212 in 2016; n = 201 in 2017) learned the two CPGs in the education program of the EGUIDE project, and clinical knowledge of these CPGs was evaluated at baseline and after the programs. To improve the correct answer rate for clinical knowledge after the programs, we revised the lecture materials associated with items that had a low correct answer rate in 2016 and used the revised lecture materials with the CPGs in 2017. The rates of correct answers after the programmes between the 2016 and 2017 groups were compared.

Results

The correct answer rate of one item on the schizophrenia CPG and one item on the MDD CPG tended to be improved (S-D5 and D-C6) and that of one on the MDD CPG was significantly improved (D-D3, P = 0.0008) in the 2017 group compared to those in the 2016 group.

Conclusions

The researchers reported improvements in clinical knowledge of CPGs after the EGUIDE program in the 2017 group following revision of the lecture materials based on results from the 2016 group. These attempts to improve the degree of understanding of CPGs may facilitate the successful dissemination and implementation of psychiatric guidelines in everyday practice.

Reference

Numata, S., Nakataki, M., Hasegawa, N., Takaesu, Y., Takeshima, M., Onitsuka, T., Nakamura, T., Edagawa, R., do, H., Miura, K., Matsumoto, J., Yasui-Fiurukori, N., Kishimoto, T., Hori, H., Tsuboi, T., Yasuda, Y., Furihata, R., Muraoka, H., Ochi, S., Nagasawa, T., Kyou, Y., Murata, A., Katsumoto, E., Ohi, K., Hishimoto, A., Inada, K., Watanabe, K. & Hashimoto, R. (2021) Improvements in the degree of understanding the treatment guidelines for schizophrenia and major depressive disorder in a nationwide dissemination and implementation study. Neuropsychopharmacology Reports. doi: 10.1002/npr2.12173. Online ahead of print.