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New Mental Health Research: Studies Combining Analysis of Genetics, Inflammation, and MRI

By June 11, 2021No Comments

Dopaminergic organization of striatum is linked to cortical activity and brain expression of genes associated with psychiatric illness

McCutcheon RA, Brown K, Nour MM, Smith SM, Veronese M, Zelaya F, Osugo M, Jauhar S, Hallett W, Mehta MM, Howes OD. Dopaminergic organization of striatum is linked to cortical activity and brain expression of genes associated with psychiatric illness. Sci Adv. 2021 Jun 9;7(24):eabg1512. doi: 10.1126/sciadv.abg1512. PMID: 34108214.

  • “Dopamine signaling is constrained to discrete tracts yet has brain-wide effects on neural activity. The nature of this relationship between local dopamine signaling and brain-wide neuronal activity is not clearly defined and has relevance for neuropsychiatric illnesses where abnormalities of cortical activity and dopamine signaling coexist.”
  • “Using simultaneous PET-MRI in healthy volunteers, we find strong evidence that patterns of striatal dopamine signaling and cortical blood flow (an index of local neural activity) contain shared information. This shared information links amphetamine-induced changes in gradients of striatal dopamine receptor availability to changes in brain-wide blood flow and is informed by spatial patterns of gene expression enriched for genes implicated in schizophrenia, bipolar disorder, and autism spectrum disorder.”
  • “These results advance our knowledge of the relationship between cortical function and striatal dopamine, with relevance for understanding pathophysiology and treatment of diseases in which simultaneous aberrations of these systems exist.”

Circulating inflammatory markers impact cognitive functions in bipolar depression

Poletti S, Mazza MG, Calesella F, Vai B, Lorenzi C, Manfredi E, Colombo C, Zanardi R, Benedetti F. Circulating inflammatory markers impact cognitive functions in bipolar depression. J Psychiatr Res. 2021 Jun 2;140:110-116. doi: 10.1016/j.jpsychires.2021.05.071. Epub ahead of print. PMID: 34107379.

  • “Background: Cognitive impairment is a core feature of bipolar disorder, with a prevalence of about 64.4% during episodes and 57.1% in euthymia. Recent evidences suggest that cognitive deficits in BD may follow immune dysfunction and elevated levels of inflammatory cytokines have been reported during periods of depression, mania and euthymia, suggesting the presence of a chronic, low-grade inflammatory state. The aim of the study is to investigate if immune/inflammatory markers and especially chemokines associate to cognitive performances.”
  • “Methods: Seventy-six consecutively admitted inpatients with a depressive episode in course of bipolar disorder performed a neuropsychological evaluation with the Brief Assessment of Cognition in Schizophrenia and plasma blood levels of cytokines, chemokines and growth factors were analyzed with Luminex technology.”
  • “Conclusions: Our results confirm the importance of chemokines in bipolar disorder and suggest that inflammatory markers suggestive of a low-grade inflammatory state could contribute to the neurocognitive deficits observed in depressed patients.”

Associations Between Major Psychiatric Disorder Polygenic Risk Scores and Blood-Based Markers in UK Biobank

Sewell MDE, Shen X, Jiménez-Sánchez L, Edmondson-Stait AJ, Green C, Adams MJ, McIntosh AM, Lyall DM, Whalley HC, Lawrie SM. Associations Between Major Psychiatric Disorder Polygenic Risk Scores and Blood-Based Markers in UK Biobank. Brain Behav Immun. 2021 Jun 6:S0889-1591(21)00233-6. doi: 10.1016/j.bbi.2021.06.002. Epub ahead of print. PMID: 34107350.

  • “Major depressive disorder (MDD), schizophrenia (SCZ), and bipolar disorder (BD) have both shared and discrete genetic risk factors and abnormalities in blood-based measures of inflammation and blood-brain barrier (BBB) permeability. The relationships between such genetic architectures and blood-based markers are however unclear.”
  • “We investigated relationships between polygenic risk scores for these disorders and peripheral biomarkers in the UK Biobank cohort.We calculated polygenic risk scores (PRS) for samples of n = 367,329 (MDD PRS), n = 366,465 (SCZ PRS), and n = 366,383 (BD PRS) individuals from the UK Biobank cohort. We examined associations between each disorder PRS and 58 blood markers, using two generalized linear regression models: ‘minimally adjusted’ controlling for variables including age and sex, and ‘fully adjusted’ including additional lifestyle covariates such as alcohol and smoking status. In total, 15/58, 14/58 and 10/58 peripheral markers were significantly associated with MDD, SCZ and BD PRS respectively for both models. Many were disorder-specific, with 10/15 MDD PRS associations unique to MDD. Moreover, several of these disorder-specific associations for MDD and SCZ were with immune-related parameters, with mostly positive and negative associations identified for MDD and SCZ PRS respectively.
  • “This study suggests that MDD, SCZ and BD have shared and distinct peripheral markers associated with disorder-specific genetic risk. The results also implicate inflammatory dysfunction in MDD and SCZ, albeit with differences in patterns between the two conditions, and enrich our understanding of potential underlying pathophysiological mechanisms in major psychiatric disorders.

 

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