Neurobiology of mental disorders

In general

• Changes in the brain signal transmission are essential in the development of mental disorders

• genetic effects, effect of stress (environmental factors) and effect of disturbed chronobiology) - it is proposed that the bases of biological changes (plasticity, connections) are changes in neurotransmission, signal transduction and information storage and processing

Examples of mental disorder and their neurobiological etiopathogenesis

1. Depression

• Monoamine hypothesis
  • Most antidepressants work by inhibiting the reuptake of monoamines (e.g., serotonin, noradrenaline, dopamine), indicating that a lack of monoamines plays a major role in the pathophysiology of depression (and other mood disorders). MAO-A activity and density of adrenergic transporters are included in the pathophysiology → regulation of serotonin and norepinephrine levels in the brain -
• More recent hypothesis (low yield for examination)
  • Neurotrophic hypothesis of depression: CREB (cAMP response element binding protein) is one intracellular target of long-term antidepressant treatment and BDNF (brain-derived neurotrophic factor) is one target gene of CREB
  • Inflammatory and neurodegenerative hypothesis of depression: Depression is associated with both inflammatory processes, as well as neurodegeneration and reduced neurogenesis

2. Bipolar disease

• hypothesis of mitochondrial dysfunction
• calcium and mitochondrial dysfunction hypothesis
• corresponds to the neurotrophic hypothesis → role of calcium in singaling pathway in synaptic plasticity regulation

3. Schizophrenia

• Dopamine hypothessis
  • Dopamine excess in the mesolimbic pathway
  • Dopamine reduction in the frontocortical pathway
• Glutamate hypothesis
  • developmental anomaly of glutamate synapse -> secondary dopaminergic dysfunction
  • NMDA antagonists mimic some positive and negative symptoms as seen in schizophrenia
  • likely both hypothesis (glumate and dopaminergic abnormalities) are implicated in that disease