Linking Putative Blood Somatic Mutations, Alzheimer’s & PTSD

Research Paper Title

Putative Blood Somatic Mutations in Post-Traumatic Stress Disorder-Symptomatic Soldiers: High Impact of Cytoskeletal and Inflammatory Proteins.

Background

The recently discovered autism/intellectual disability somatic mutations in postmortem brains, presenting higher frequency in Alzheimer’s disease subjects, compared with the controls. They further revealed high impact cytoskeletal gene mutations, coupled with potential cytoskeleton-targeted repair mechanisms.

The current study was aimed at further discerning if somatic mutations in brain diseases are presented only in the most affected tissue (the brain), or if blood samples phenocopy the brain, toward potential diagnostics.

Methods

Variant calling analyses on an RNA-seq database including peripheral blood samples from 85 soldiers (58 controls and 27 with symptoms of post-traumatic stress disorder, PTSD) was performed.

Results

High (e.g. protein truncating) as well as moderate impact (e.g., single amino acid change) germline and putative somatic mutations in thousands of genes were found. Further crossing the mutated genes with autism, intellectual disability, cytoskeleton, inflammation, and DNA repair databases, identified the highest number of cytoskeletal-mutated genes (187 high and 442 moderate impact). Most of the mutated genes were shared and only when crossed with the inflammation database, more putative high impact mutated genes specific to the PTSD-symptom cohorts versus the controls (14 versus 13) were revealed, highlighting tumour necrosis factor specifically in the PTSD-symptom cohorts.

Conclusions

With microtubules and neuro-immune interactions playing essential roles in brain neuroprotection and Alzheimer-related neurodegeneration, the current mutation discoveries contribute to mechanistic understanding of PTSD and brain protection, as well as provide future diagnostics toward personalised military deployment strategies and drug design.

Reference

Sragovich, S., Gershovits, M., Lam, J.C.K., Li, V.O.K. & Gozes, I. (2021) Putative Blood Somatic Mutations in Post-Traumatic Stress Disorder-Symptomatic Soldiers: High Impact of Cytoskeletal and Inflammatory Proteins. Journal of Alzheimer’s Disease. doi: 10.3233/JAD-201158. Online ahead of print.

Are Lifestyle Factors Advantageous as First-Line Interventions in Mental Health?

Research Paper Title

The Effect of Exercise on Mental Health: A Focus on Inflammatory Mechanisms.

Background

A growing body of research suggests that neuropsychiatric disorders are closely associated with a background state of chronic, low-grade inflammation.

This insight highlights that these disorders are not just localised to dysfunction within the brain, but also have a systemic aspect, which accounts for the frequent comorbid presentation of chronic inflammatory conditions and metabolic syndromes.

It is possible that a treatment resistant subgroup of neuropsychiatric patients may benefit from treatment regimens that target their associated proinflammatory state.

Lifestyle factors such as physical activity (PA) and exercise (i.e. structured PA) are known to influence mental health. In turn, mental disorders may limit health-seeking behaviours – a proposed “bidirectional relationship” that perpetuates psychopathology. PA is renowned for its positive physical, physiological and mental health benefits.

Evidence now points to inflammatory pathways as a potential mechanism for PA in improving mental illness. Relevant pathways include:

  • Modulation of immune-neuroendocrine and neurotransmitter systems;
  • The production of tissue-derived immunological factors that alter the inflammatory milieu; and
  • Neurotrophins that are critical mediators of neuroplasticity.

Methods

In this paper, the researchers focus on the role of PA in positively improving mental health through potential modulation of chronic inflammation, which is often found in individuals with mental disorders.

In a related paper by Edirappuli and colleagues (2020), they will focus on the role of nutrition (another significant lifestyle factor) on mental health.

Results

Thus, inflammation appears to be a central process underlying mental illness, which may be mitigated by lifestyle modifications.

Conclusions

Lifestyle factors are advantageous as first-line interventions due to their cost efficacy, low side-effect profile, and both preventative and therapeutic attributes.

By promoting these lifestyle modifications and addressing their limitations and barriers to their adoption, it is hoped that their preventative and remedial benefits may galvanize therapeutic progress for neuropsychiatric disorders.

Reference

Venkatesh, A., Edirappuli, S.D., Zaman, H.P. & Zaman, R. (2020) The Effect of Exercise on Mental Health: A Focus on Inflammatory Mechanisms. Psychiatira Danubina. 32(Suppl 1), pp.105-113.

What is the Effect of Nutrition on Mental HEalth?

Research Paper Title

The Effect of Nutrition on Mental Health: A Focus on Inflammatory Mechanisms.

Background

Neuropsychiatric disorders are closely associated with a persistent low-grade inflammatory state.

This suggests that the development of psychopathology is not only limited to the brain, but rather involves an additional systemic aspect, accounting for the large body of evidence demonstrating co-presentation of mental illness with chronic inflammatory conditions and metabolic syndromes.

Studies have shown that inflammatory processes underlie the development of neuropsychiatric symptoms, with recent studies revealing not only correlative, but causative relationships between the immune system and psychopathology.

Lifestyle factors such as diet and exercise may influence psychopathology, and this may occur via a bidirectional relationship.

Mental illness may prevent health-seeking behaviours such as failing to maintain a balanced diet, whilst adopting a ‘healthy’ diet rich in fruits, vegetables and fish alongside nutritional supplementation correlates with a reduction in psychiatric symptoms in patients.

Obesity and the gut microbiome have proven to be further factors which play an important role in inflammatory signalling and the development of psychiatric symptoms.

In a related paper the authors focus on the role of exercise (another significant lifestyle factor) on mental health (Venkatesh et al. 2020).

Conclusions

Lifestyle modifications which target diet and nutrition may prove therapeutically beneficial for many patients, especially in treatment-resistant subgroups.

The current evidence base provides equivocal evidence, however future studies will prove significant, as this is a highly attractive therapeutic avenue, due to its cost efficacy, low side effect profile and preventative potential.

By promoting lifestyle changes and addressing the limitations and barriers to adoption, these therapies may prove revolutionary for mental health conditions.

Reference

Edirappuli, S.D., Venkatesh, A. & Zaman, R. (2020) The Effect of Nutrition on Mental Health: A Focus on Inflammatory Mechanisms. Psychiatria Danubina. 32(Suppl 1), pp.114-120.

Should We Target Inflammation, The Gut Microbiome, and Mitochondrial Dysfunction in Combat PTSD-Metabolism?

Research Paper Title

Novel Pharmacological Targets for Combat PTSD-Metabolism, Inflammation, The Gut Microbiome, and Mitochondrial Dysfunction

Background

Current pharmacological treatments of post-traumatic stress disorder (PTSD) have limited efficacy.

Although the diagnosis is based on psychopathological criteria, it is frequently accompanied by somatic comorbidities and perhaps “accelerated biological ageing,” suggesting widespread physical concomitants.

Such physiological comorbidities may affect core PTSD symptoms but are rarely the focus of therapeutic trials.

Methods

To elucidate the potential involvement of metabolism, inflammation, and mitochondrial function in PTSD, the researchers integrate findings and mechanistic models from the DOD-sponsored “Systems Biology of PTSD Study” with previous data on these topics.

Results

Data implicate inter-linked dysregulations in metabolism, inflammation, mitochondrial function, and perhaps the gut microbiome in PTSD.

Several inadequately tested targets of pharmacological intervention are proposed, including insulin sensitisers, lipid regulators, anti-inflammatories, and mitochondrial biogenesis modulators.

Conclusions

Systemic pathologies that are intricately involved in brain functioning and behaviour may not only contribute to somatic comorbidities in PTSD, but may represent novel targets for treating core psychiatric symptoms.

Reference

Bersani, F.S., Mellon, S.H., Lindqvist, D., Kang, J.I., Rampersaud, R., Somvanshi, P.R., Doyle, F.J., Hammamieh, R., Jett, M., Yehuda, R., Marmar, C.R. & Wolkowitz, O.M. (2020) Novel Pharmacological Targets for Combat PTSD-Metabolism, Inflammation, The Gut Microbiome, and Mitochondrial Dysfunction

Examining the Role the Inflammatory Process & Immune System Play in Mental Disorder

Research Paper Title

Inflammatory Response and Treatment-Resistant Mental Disorders: Should Immunotherapy Be Added to Pharmacotherapy?

Abstract

Treatment resistance continues to challenge and frustrate mental health clinicians and provoke psychiatric researchers to seek additional explanatory theories for psychopathology.

Because the inflammatory process activates symptoms of depression, anxiety, and psychosis, it is a reasonable route to follow for primary and/or indirect contribution to mental disorders.

The current article reviews the research literature regarding the role the inflammatory process and immune system play in mental disorders as well as novel treatments under investigation for resistant depression, anxiety, substance use, and psychotic disorders.

Reference

Limandri, B.J. (2020) Inflammatory Response and Treatment-Resistant Mental Disorders: Should Immunotherapy Be Added to Pharmacotherapy? Journal of Psychosocial Nursing and Mental Health Services. 58(1), pp.11-16. doi: 10.3928/02793695-20191218-03.

Inflammatory Response & Treatment-Resistant Mental Disorders

Research Paper Title

Inflammatory Response and Treatment-Resistant Mental Disorders: Should Immunotherapy Be Added to Pharmacotherapy?

Abstract

Treatment resistance continues to challenge and frustrate mental health clinicians and provoke psychiatric researchers to seek additional explanatory theories for psychopathology.

Because the inflammatory process activates symptoms of depression, anxiety, and psychosis, it is a reasonable route to follow for primary and/or indirect contribution to mental disorders.

The current article reviews the research literature regarding the role the inflammatory process and immune system play in mental disorders as well as novel treatments under investigation for resistant depression, anxiety, substance use, and psychotic disorders.

Reference

Limandri, B.J. (2020) Inflammatory Response and Treatment-Resistant Mental Disorders: Should Immunotherapy Be Added to Pharmacotherapy? Journal of Psychosocial Nursing and Mental Health Services. 58(1), pp.11-16. doi: 10.3928/02793695-20191218-03.