Neurobiology of Psychological Disorders

Neurobiology of Psychological Disorders

• Diathesis-stress model: psychological disorders result from the interaction between genetic vulnerability (diathesis) and external stressors.

Heritability and Risk

• Heritability (h2) measures the extent to which genetic factors contribute to individual differences in traits.
• Genetic influences play a significant role in phenotypic variation among individuals.
• Heritability estimates the degree to which genes account for variations in traits.

Mood Disorders

Major Depressive Disorder

• Characterized by persistent feelings of sadness, emptiness, or irritability.
• High comorbidity with substance abuse.
• Stress can trigger the onset of depression, with individuals experiencing more stressful events before symptom onset.
• Depression can be reactive (triggered by negative experiences) or endogenous (without apparent external triggers).
• Biological theories involve various biomarkers, including toxic free radicals, cortisol, and epigenetics.
• Structural differences in the brain: higher activity in the amygdala, smaller size of the hippocampus, and abnormalities in Brodmann area 25 and frontopolar area 10.
• Neurotransmitter imbalances: low levels of norepinephrine and serotonin.
• Genetics play a role, with heritability estimated at 30-40% and potential links to abnormality in the 5-HTT gene.

Bipolar Disorder

• Bipolar I: involves manic episodes.
• Bipolar II: characterized by mostly depressive episodes with at least one hypomanic episode.
• Genetic factors contribute significantly, with heritability estimated at 60%.
• Biological theories involve genetic studies, neurotransmitter imbalances, and structural abnormalities in the brain, including the HPA axis and areas like the basal ganglia and cerebellum.

Biological Treatment

• Pharmaceuticals for MDEs: antidepressant medications like MAOIs, Tricyclics, SSRIs, and SSRI/SSNIs.
• Bipolar treatment: Lithium carbonate, antidepressants, and anticonvulsants.
• SSRIs and Black Box Warnings:
  • May increase suicidality, especially in children and adolescents.
  • Activating effect may lead to increased energy before mood improvement, potentially contributing to suicidality.

Alternatives to Medication

• Electroconvulsive therapy (ECT): involves passing volts through the brain to promote changes and neurotransmitter release.
• Vagus nerve stimulation and Deep Brain Stimulation (DBS) are non-pharmaceutical options for treating psychiatric disorders.

Psychedelic Treatments

• Psilocybin:
  • Shows long-lasting antidepressant effects.
  • Supportive psychotherapy combined with psilocybin may provide benefits for patients with psychiatric disorders.
• Ketamine:
  • Shows rapid improvement in depressive symptoms.
  • Approved by the FDA for treatment-resistant depression.
  • Lower BDNF levels in bipolar disorder patients may lead to reduced EGR3 levels and neuroprotection.