Theme 3: when things go wrong in the
brain
Type Notes
Due @April 7, 2025
Status Done
Chapter 4: How Synaptic Neurotransmission Mediates
Emotional Disorders
Several general concepts relating to how psychiatric disorders are thought to be associated with
modifications in synaptic neurotransmission
Molecular Neurobiology and Psychiatric Disorders
The formulation of psychiatric disorders involves the integration of at least four elements:
1. Genetic vulnerability
2. Life event stressors
3. Personality, coping skills, and social support
4. Other environmental influences (incl. viruses, toxins, and diseases)
Genetic vulnerability
Not inherited disorders, but inherited vulnerabilities
Current view ⇒ multiple sites in DNA within the genome must interact to produce most of the
causation of a psychiatric illness
Multiple genes acting additievly/synergistically across development
Heterogenity = different families may have different sets of abnormal genes for the same illness
Life Events (the two-hit hypothesis)
Two-hit hypothesis = in order to manifest an overt psychiatric disorder, one must not only sustain
the first hit but one must also sustain a second hit
First hit ⇒ genetic vulnerability
Second hit ⇒ environmental stressors
Implication: one doesn’t inherit th eillness, but the potential
Some mental disorders, such as schizophrenia or bipolar illness, may have a higher chance of
being expressed in vulnerable individuals as compared with disorders such as depression, anxiety,
Theme 3: when things go wrong in the brain 1
, or obsessive-compulsive disorder, which may more frequently lie dormant in the vulnerable
individual
Childhood development, Personality, Coping skills, and Social support
Early life experienes influence:
coping skills
personality traits (genetic + environmental origins)
Personality and coping skills filter the effects of like stressors on one’s genetic vulernabilities
Good coping ⇒ blunts stressor effects
Poor coping ⇒ magnifies or recruits new stressors
It’s a combination of personality traits + severity of stressors + genome type
More genetically determined disorders (e.g. schizophrenia) requrie only minor stressors to
manifest
Some stressors coud be so severe that even a normal robust genome might break down to cause a
mental disorder
Theme 3: when things go wrong in the brain 2
, Other environmental influences
Viruses, toxins, and diseases can interact with genes to activate vulnerabilities
Neuronal Plasticity and Psychiatric Disorders
Neurodevelopmental Disorders
Proper brain function requires:
correct neuron selection
proper migration
accurate synapse formation
Disorders like epilepsy and schizophrenia may arise from abnormal migration or synapse formation
Theme 3: when things go wrong in the brain 3
, Migration
Neuron selection
Correct synapse formation
Wrong synapse formation
Failure of neuronal migrations could be caued by genes giving the wrong directions
Causes of abnormal development:
inherited errors
prenatal exposure to drugs, alcohol, or radiation
Neurodegenerative disorders and neurotrophic growth factors
An undeveloped neuron may fail to develop during childhood
Brain disorders can also occur if normal healthy synapses are inappropriately interupted late in life
a mild form of this may occur in “normal aging”, but can be reduced with training the brain
Theme 3: when things go wrong in the brain 4
brain
Type Notes
Due @April 7, 2025
Status Done
Chapter 4: How Synaptic Neurotransmission Mediates
Emotional Disorders
Several general concepts relating to how psychiatric disorders are thought to be associated with
modifications in synaptic neurotransmission
Molecular Neurobiology and Psychiatric Disorders
The formulation of psychiatric disorders involves the integration of at least four elements:
1. Genetic vulnerability
2. Life event stressors
3. Personality, coping skills, and social support
4. Other environmental influences (incl. viruses, toxins, and diseases)
Genetic vulnerability
Not inherited disorders, but inherited vulnerabilities
Current view ⇒ multiple sites in DNA within the genome must interact to produce most of the
causation of a psychiatric illness
Multiple genes acting additievly/synergistically across development
Heterogenity = different families may have different sets of abnormal genes for the same illness
Life Events (the two-hit hypothesis)
Two-hit hypothesis = in order to manifest an overt psychiatric disorder, one must not only sustain
the first hit but one must also sustain a second hit
First hit ⇒ genetic vulnerability
Second hit ⇒ environmental stressors
Implication: one doesn’t inherit th eillness, but the potential
Some mental disorders, such as schizophrenia or bipolar illness, may have a higher chance of
being expressed in vulnerable individuals as compared with disorders such as depression, anxiety,
Theme 3: when things go wrong in the brain 1
, or obsessive-compulsive disorder, which may more frequently lie dormant in the vulnerable
individual
Childhood development, Personality, Coping skills, and Social support
Early life experienes influence:
coping skills
personality traits (genetic + environmental origins)
Personality and coping skills filter the effects of like stressors on one’s genetic vulernabilities
Good coping ⇒ blunts stressor effects
Poor coping ⇒ magnifies or recruits new stressors
It’s a combination of personality traits + severity of stressors + genome type
More genetically determined disorders (e.g. schizophrenia) requrie only minor stressors to
manifest
Some stressors coud be so severe that even a normal robust genome might break down to cause a
mental disorder
Theme 3: when things go wrong in the brain 2
, Other environmental influences
Viruses, toxins, and diseases can interact with genes to activate vulnerabilities
Neuronal Plasticity and Psychiatric Disorders
Neurodevelopmental Disorders
Proper brain function requires:
correct neuron selection
proper migration
accurate synapse formation
Disorders like epilepsy and schizophrenia may arise from abnormal migration or synapse formation
Theme 3: when things go wrong in the brain 3
, Migration
Neuron selection
Correct synapse formation
Wrong synapse formation
Failure of neuronal migrations could be caued by genes giving the wrong directions
Causes of abnormal development:
inherited errors
prenatal exposure to drugs, alcohol, or radiation
Neurodegenerative disorders and neurotrophic growth factors
An undeveloped neuron may fail to develop during childhood
Brain disorders can also occur if normal healthy synapses are inappropriately interupted late in life
a mild form of this may occur in “normal aging”, but can be reduced with training the brain
Theme 3: when things go wrong in the brain 4
