Lecture 12a: Introduction to Clinical Neuroscience

Introduction to Clinical Neuroscience

• Overview of psychological disorders and their diagnosis

  • Disorders often require treatment and are diagnosed using the DSM (Diagnostic and Statistical Manual of Mental Disorders).

Schizophrenia

• A diverse disorder with multiple existing types and varied profiles that involves a breakdown of the effective integration of emotion, thought, and action

• Affects 1% of the population

• Symptoms: delusions, hallucinations, odd behaviour, incoherent thought, inappropriate affect

Causal Factors in Schizophrenia

• Evidence for a genetic contribution (inherit an increased risk)

• Causes:

  • Several different chromosomes implicated

  • Associated with various early insults — infections, autoimmune reactions, toxins, traumatic injury, stress

• Interference with the normal development of susceptible individuals may lead to the development of the disorder

Discovery of Antipsychotic Drugs

• Chlorpromazine: calms many agitated schizophrenics and activates many emotionally blunt schizophrenics

• Reserpine: also found to be effective but is no longer used

• Both drugs are not effective for 2-3 weeks and presents Parkinson-like motor effects

Dopamine Theory of Schizophrenia

• 1960 - link between dopamine and Parkinson’s disease established

• Antipsychotic drug side effects suggests role for dopamine — drugs work by decreasing dopamine levels; schizophrenia associated with dopamine overactivity

• Mechanisms:

  • Reserpine depletes dopamine and other monoamines by making neurotransmitter vesicles leaky

  • Amphetamines and cocaine are dopamine agonists and can produce psychosis

  • Chlorpromazine works as a dopamine antagonist by binding to and blocking dopamine receptors (first receptor blocker to be identified which changed psychopharmacology)

Effectiveness of Antipsychotics

• Generally, the higher the drug's affinity for dopamine receptors, the more effective it is in treating schizophrenia.

• Haloperidol is an exception as it and other butyro-phenones bind only to D2 receptors

Limitations of the Dopamine Theory

• Clozapine: an atypical and effective neuroleptic, acts at D1, D4, and serotonin receptors, but has only some binding to D2 receptors

• Neuroleptics act quickly at the synapse, but don’t alleviate symptoms for weeks

• Evidence suggests schizophrenia is associated with brain damage that doesn't align with dopamine theory (e.g., minimal damage to dopamine circuitry)

• Neuroleptics are only effective for some

Affective Disorders: Depression and Mania

• Affective disorders are characterized by disturbances in mood or emotion, commonly known as mood disorders.

  • Depression: Normal response to loss, becomes abnormal when it persists or has no cause

  • Mania: Overconfidence, impulsivity, distractibility, and high energy

• Statistics:

  • Unipolar affective disorder: ~5% will experience it at some point.

  • Bipolar disorder: ~1% prevalence.

Antidepressant Drugs

• Monoamine oxidase inhibitors (MAOIs)

  • e.g. Iproniazid (prevents breakdown of monoamines such as dopamine and serotonin)

• Tricyclic antidepressants

  • e.g. Imipramine (block reuptake of serotonin and norepinephrine and is safer than MAOIs)

• Selective serotonin-reuptake inhibitors (SSRIs)

  • e.g. Prozac, Paxil, Zoloft

  • No more effective than tricyclics, but side effects are few and they are effective at treating other disorders

• Selective norepinephrine-reuptake inhibitors (SNRIs)

Diathesis-Stress Model of Depression

• Diathesis refers to genetic susceptibility and combined with stress, results in depression.

• Indirect research indicates that:

  • Depressed individuals often release more stress hormones.

  • They may fail the dexamethasone suppression test, indicating impaired feedback on stress hormones.

Brain Stimulation Treatments for Depression

• A 2008 study revealed that chronic electrical stimulation near the anterior cingulate gyrus provided relief to treatment-resistant depression patients.