MoodDisorder17

Genetics of Mood Disorders

Overview

• Mood disorders such as bipolar disorder and major depressive disorder (MDD) have a strong genetic component.

• Insights into genetic variants underlying mood disorders can help improve treatment options.

Heritability of Psychiatric Disorders (Page 2)

• High heritability estimates for various psychiatric conditions including:

  • Bipolar Disorder

  • Schizophrenia

  • Major Depressive Disorder

  • Other conditions such as substance use disorders and anxiety disorders.

• Graphical representation indicates the relative heritability of these disorders.

Human Karyotype (Page 3)

• Karyotype shows chromosomes: 22 pairs of autosomes and sex chromosomes (XX for females, XY for males).

• Findings can assist in understanding chromosomal disorders and array comparative genomic hybridization results.

SNP Analysis (Page 4)

• Single Nucleotide Polymorphism (SNP) differences analyzed between DNA from individuals (e.g., C/T polymorphism).

• The SNP variations may have significant implications for mood disorders genetics.

Genome-Wide Association Studies (GWAS) (Page 5)

• Association plots conducted to identify genetic loci linked to mood disorder traits.

• Specific SNPs associated with neuroticism and extraversion show variances, reflective of genetic influences on psychiatric conditions.

Cross-Disorder Genetic Effects (Page 6-8)

Summary of Findings

• Genetic studies highlight overlapping variants across disorders such as:

  • Autism Spectrum Disorder (ASD)

  • Attention Deficit-Hyperactivity Disorder (ADHD)

  • Bipolar Disorder

  • Major Depressive Disorder

  • Schizophrenia

• Variants on chromosomes 3p21 and 10q24 were notable, indicating shared genetic underpinnings.

Research Methodology (Page 6)

• Analyzed SNP data from 33,332 cases and 27,888 controls of European ancestry.

• Utilized multinomial logistic regression to explore genotype-phenotype relationships.

• Conducted pathway analyses to elucidate biological correlations.

Specific Genetic Variants

• Variants identified were associated with various disorders and included genes such as:

  • CACNA1C and CACNB2 - L-type calcium channel subunits associated with mood disorders.

• Polygenic risk scores indicated diagnostic specificity across mood disorders.

GLUTAMATERGIC SYSTEM in Mood Disorders (Page 10-11)

Genetic Studies

• The glutamatergic system's role in BD and MDD is significant for understanding treatment pathways.

• Glutamate-related genes are linked to mood disorders, with implications for treatment resistance.

Target Genes of Interest

• GRIA3, GRIK2, GRIK4, GRM7: associations with suicidal ideation and treatment response.

• Gene involvement varies, with stronger links to bipolar disorder compared to MDD.

Integrative Pathophysiology Concepts (Page 13)

• Allostatic Load: describes the body's cumulative burden of chronic stress, impacting mood disorder development.

  • Healthy state: Low load leads to normal activity and neuroplasticity.

  • Mood Disorder state: High allostatic load results in persistent neurotoxicity and energetic imbalance.

Experimental Designs and Data (Page 14)

Panicker and Non-Panicker Group Analysis

• Investigation of brain activation differences in response to CCK-4 injections in panic states, focusing on the amygdala.

• Findings suggest significant insights into the neurophysiological responses underlying panic disorders.