Lecture 1: Introduction Neurochemical Organization of the Brain. Flashcards
What are the historical milestones in understanding the biological bases of mental disorders?
(1) Until the 20th century:
- Freud focused on neuroses and psychological explanations.
- Kraepelin: advocated for somatic (biological) bases of mental illnesses focusing on psychoses.
- No collaboration or correspondence between Freud and Kraepelin.
(2) 1950s:
- Serendipitous discovery of drugs suggesting a biological (brain) basis for mental disorders.
- Key examples: Chlorpromazine (antipsychotic), Lithium (anti-mania drug).
(3) Last 20-30 years:
- Advances in neuroimaging, neuroengineering, neurochemistry, genetics, cognitive science, and electrophysiology revolutionized understanding of mental disorders.
(4) Today: Biological psychiatry is a rapidly growing field, recognizing mental illnesses as diseases of the brain.
What are the strengths & weaknesses of DSM Classification?
(1) Strengths:
- Reliability (reliable system for diagnosing mental disorders)
(2) Weakness:
- Lack of Validity: DSM diagnoses based on clinical symptoms rather than objective laboratory measures. Due to limited understanding of the underlying causes of most mental disorders, the DSM focused on symptom clusters. Recent large-scale genetic studies do not support the discreet classification scheme used by DSM.
What is the purpose of Research Domain Criteria (RDoC)?
Aim to create a new classification system based on more foundational biological and cognitive factors, by incorporation multiple sources of information: genetics, imaging, cognitive science, and more.
5 domains
1) Negative Valence Systems (fear and anxiety)
2) Positive Valence Systems (attention and memory)
3) Cognitive systems
4) Systems for social processes
5) Arousal/regulatory systems
What is an excitatory neurotransmitter?
Excitatory neurotransmitters promote the depolarization of the postsynaptic membrane, increasing the likelihood of an action potential in the neuron, thus facilitating neural communication.
What is the role of NMDA receptors in schizophrenia and depression?
(1) NMDA Receptor Hypofunction and SCZ.
- NMDA receptor antagonists can induce psychosis and impair working memory.
- A decrease in NMDA receptor expression or reduced activity is linked to psychosis and memory impairments.
(2) NMDA Receptor and Depression:
- Ketamine acts as an antidepressant by targeting NMDA receptors.
- NMDA receptors are critical for long-term potentiation (LTP), essential for synaptic plasticity, learning, and memory formation.
What is the role of Norepinephrine? Where is it produced?
- Causes arousal and alertness/attention.
- Also involved in regulation of memory formation by emotion.
- Primary source in the locus coeruleus (in brainstem) -> plays a key role in regulating arousal, attention, stress responses, and alertness.
- Once made in LC, projects to hippocampus, basal ganglia, cortex, lateral tegmental area, spinal cord, and cerebellum.
What are the effects of stress and the types of cortisol receptors?
(1) Stress:
- Leads to heightened excitability or arousal.
- Induces perceived aversiveness.
- Produces a lack of controllability.
- Involves CRH (corticotropin-releasing hormone) and ACTH (adrenocorticotropic hormone).
(2) Cortisol receptors:
–> Mineralocorticoid receptors (MRs):
Type I, high affinity.
Activated by basal cortisol levels.
–> Glucocorticoid receptors (GRs):
Type II, low affinity.
Activated by stress-level cortisol.
What is ‘allostatic load’?
refers to the cumulative wear and tear on the body and brain that results from repeated exposure to stress or ineffective management of stress over time. It represents the physiological cost of chronic stress as the body tries to maintain allostasis—the process of achieving stability through change.
Increased risk of health issues like cardiovascular disease, diabetes, immune dysfunction, and mental health disorders (e.g., anxiety, depression).
Signs: Chronic fatigue, high blood pressure, impaired memory, and emotional dysregulation.
What are dopamine’s roles and how is it linked to specific diseases?
- Motor control: Lack of dopamine → Parkinson’s disease.
- Motivational control: Dysregulation → Drug addiction.
- Antipsychotics: Block dopamine D2 receptors.
What is the mesolimbocortical pathway, and what does it do?
- A dopaminergic pathway connecting areas involved in motivation, reward, and cognition.
- Originates in the ventral tegmental area (VTA) and projects to:
–> Mesolimbic: VTA → nucleus accumbens and limbic structures (reward, motivation, reinforcement).
–> Mesocortical: VTA → prefrontal cortex (attention, planning, executive functions). - Dysfunctions: Linked to addiction, schizophrenia, and mood disorders.
What is the role of the dopamine transporter (DAT), and how do cocaine and amphetamine affect it?
- DAT: Recycles dopamine back into presynaptic neurons.
- Cocaine: Nonselective competitive inhibitor of monoamine transporters (including DAT).
- Amphetamine: Acts as a substrate for DAT. Causes redistribution of monoamines to the cytoplasm and their release through DAT.
What are the main roles of serotonin (5-HT) in the body?
- Neurotransmitter involved in: mood regulation (feel good), sleep, appetite, cognition, memory, and vascular function.
Also, cardiovascular and respiratory activity, sleep, aggression, sexual behaviour, nutrient intake, anxiety, motor output, neuroendocrine secretion, nociception, analgesia.
What are the effects of drugs on serotonin (5-HT) and its receptors?
- Antidepressants: Drugs inhibiting serotonin transport are potent antidepressants (e.g., SSRIs).
- LSD: Activation of certain 5-HT receptors is related to hallucination effects.
Where is serotonin (5-HT) primarily produced, and how is it organized?
- Raphe Nucleus: Primary site of serotonin production.
- Divided into rostral raphe nuclei (projects to the brain) and caudal raphe nuclei (projects to the spinal cord).
- Rostral raphe:
(1) Dorsal raphe: Fine axons, rarely make synaptic contacts (more common).
(2) Median raphe: Coarse axons with synaptic specializations.
What is SERT (Serotonin Transporter), and how is it affected by SSRIs?
- Encoded by SLC6A4 on chromosome 17q.
- Two polymorphic forms:
(1) Long form: Normal function.
(2) Short form: Increases risk of depression. - SSRI (selective serotonin reuptake inhibitor) effects: Chronic SSRI exposure decreases serotonin uptake by inducing internalization and degradation of SERT proteins.
How does ecstasy cause non-vesicular release of serotonin (5-HT)?
- Normally, synaptically released 5-HT is reuptaken by SERT.
- Ecstasy’s effect: blocks VMAT, raising cytoplasmic serotonin levels. Increased cytoplasmic 5-HT reverses the presynaptic transporter direction -> non-exocytotic release of serotonin.
