BMS 200: Schizophrenia and Migraines Quiz

BMS 200: Schizophrenia, Migraines & Microbiome

• Course focuses on schizophrenia, migraines, and the microbiome.

Outcomes

• Students will describe the epidemiology and clinical features of schizophrenia.
• The dopaminergic hypothesis of schizophrenia and the role of inflammation in its pathophysiology will be discussed.
• The evidence linking inflammation and the gut microbiome to migraine pathophysiology will be detailed.

Common Psychiatric Presentations: Delusion

• A delusion is a clearly false belief indicative of an abnormality in thought content.
• Cultural or religious background, and intelligence level cannot explain the belief.
• The belief persists despite evidence to the contrary.
• Delusions can be caused by various factors, including mental, neurological, or medical disorders.
• Examples include schizophrenia, substance use, bipolar disorder, major depressive disorder, delirium, and dementia.

Definition for Hallucination

• A hallucination is a sensory perception in the absence of a corresponding external stimulus.
• Hallucinations occur in the sensory domain (e.g., visual, auditory, tactile).
• Vivid and clear without voluntary control.
• Hallucinations can occur with or without insight, and are not always related to mental illness—they can occur as part of grief or adjustment disorders.

Schizophrenia – DSM V Criteria (Simplified)

• Two (or more) of the following symptoms are present. At least one must be delusions, hallucinations or disorganized speech.
• Delusions
• Hallucinations
• Disorganized speech (e.g., frequent derailment or incoherence).
• Grossly disorganized or catatonic behavior
• Negative symptoms (e.g., diminished emotional expression or avolition).
• Continuous symptoms for at least 6 months, and one month active symptoms.
• Level of functioning in work, school, relationships, or self-care is markedly decreased.
• Cannot be attributed to another condition.

Schizophrenia - Definitions: Disorganized Speech and Thoughts

• Disorganized Speech/Thought: characterized by derailment, poverty of speech, tangentiality, lack of logical connection, perseveration, neologisms, thought blocking, clanging, and echolalia, these are part of a phenomenon known as "thought disorders".
• Catatonia: Disorganized behavior can be related to schizophrenia. It involves psychomotor disturbances such as stupor, rigidity, strange postures ("waxy flexibility"), excessive activity, echolalia, and echopraxia.
• Derailment (Loose Associations): Shifting abruptly between unrelated topics in speech, making it difficult to follow. Lack of connection or logic.
• Poverty of Speech: Reduced quantity or content of speech. Brief, monosyllabic responses, and lack of detail.
• Tangentiality: Responding to a question with a totally or partially irrelevant answer or completely unrelated ideas.
• Lack of Logic/Illogical Thinking: Conclusions or statements that don't logically follow.

Schizophrenia - Definitions: Neologism, Thought Blocking, Clanging, Echolalia

• Neologism: Creation of new, nonsensical words.
• Thought Blocking: Sudden interruptions of thought.
• Clanging: Focusing on the phonetic aspects of words (rhyming, alliteration).
• Echolalia: Repetition of words or phrases from another speaker without understanding.

Schizophrenia - Disorganized Behavior

• Involves a significant disruption in the ability to perform daily activities.
• Incoherent Behavior: Bizarre, nonsensical actions, such as inappropriately dressing (e.g., heavy coats in hot weather), aimless wandering, difficulty initiating tasks, or completing tasks.
• Inappropriate Emotional Responses: Laughing or crying at inappropriate times, unpredictable behavior, or sudden shifts in mood.
• Difficulty in Planning or Sequencing: Difficulty in tasks like meal preparation or personal hygiene due to cognitive impairment.

Schizophrenia - Catatonia

• A complex psychomotor syndrome characterized by abnormal movements, behaviors, and reactions.
• Motor Immobility: Reduced or complete lack of voluntary movement.
• Stupor: Profound unresponsiveness to stimuli.
• Rigidity: Muscular stiffness that prevents movement.
• Strange Postures (Catalepsy): Unusual, often uncomfortable or bizarre postures that are maintained.
• Excessive Motor Activity: Excessive, purposeless activity not influenced by external stimuli, impulsivity

Schizophrenia – Negative Symptoms

• Communication: Limited speech, minimal responses, pauses.
• Emotion/Affect: Reduced range of emotional experiences, blunted expressions, monotonous speech.
• Social Activity: Few friends, minimal desire for social interactions.
• Motivation: Little motivation to engage in daily activities. Decreased interest in hobbies, grooming, and self-care.
• Psychomotor Activity: Slowed movements, fewer expressive gestures.

Schizophrenia: Onset, Pathogenesis, and Cognitive Symptoms

• Onset typically occurs between puberty and the third decade.
• Pathogenesis is not fully understood, but dysregulation in dopaminergic systems is implicated in positive symptoms such as psychosis.
• Neurological basis for cognitive symptoms is poorly understood.
• Cognitive symptoms include problems with working memory, attention, executive functions (organization), social cognition (understanding cues).

Dopamine and Schizophrenia

• There is hyper-responsiveness of the dopaminergic system in schizophrenia.
• Antipsychotic drugs block dopamine receptors (D2).
• Dopamine-increasing drugs (e.g., L-dopa, amphetamines) worsen psychosis.
• GABA interneurons are last to develop, vulnerable to developmental insults, highly susceptible to damage from oxidative stress and glutamatergic drive particularly early postnatal.

Dopaminergic System

• A complex network of neurons in the brain that use dopamine as a neurotransmitter.
• The main dopaminergic areas include the ventral tegmental area (VTA), and substantia nigra.
• These areas project to various brain regions, influencing different functions like motivation, motor control, and executive functions.
• Dopamine is released in a tonic (steady) and phasic (transient) fashion. Tonic firing is decreased in stress responses, while phasic firing is stronger with interesting/acute stressors.

Inflammation and Schizophrenia

• General inflammation may be linked to schizophrenia.
• Elevations in pro-inflammatory cytokines (e.g., TNF-alpha, IL-6, IL-1beta) during psychosis often normalize with antipsychotic treatment.
• Pro-inflammatory cytokines can lead to kynurenic acid production, which blocks NMDA receptors.
• Activation of microglia and cognitive dysfunction and grey matter volume loss.

Migraine – Pathophysiology

• The key pathway for migraine pain involves the trigeminal nerve's connection to the meninges.
• Important modulation of neurotransmitters plays a role, including those from the brainstem nuclei.
• Problems with modulation of pain sensation are implicated as a cause.
• Vascular dilation and constriction (vasomotion) may play a role.

Migraine – Pathophysiology (Medications)

• Medications acting on the central pathway include 5-HT1 receptors important in the trigeminal nucleus and thalamus and serotonin (using "-triptans" and/or CGRP).

Migraine, Pathophysiology – (Theories)

• The best-accepted theory for Migraines is a neurovascular one, involving primary neural dysfunction leading to "spreading depression," a wave of neural excitability that spreads through the cortex and activates the trigeminal complex, leading to vascular pain.

Central Sensitization

• Pro-inflammatory cytokines release nerve growth factor (NGF).
• NGF increases brain-derived neurotrophic factor (BDNF) from C fibers.
• This increases the excitability of "pro-pain" dorsal horn networks and C fibre transmission.

Neurogenic Inflammation

• Action potentials can move in both directions along pain fibres.
• Substances released from C fibers, like substance P and CGRP, can cause neurogenic inflammation by causing mast cell degranulation, vasodilation, and edema.

Migraines & Gut Microbiome

• Eradication of H. pylori may improve migraine symptoms.
• H. pylori triggers the release of CGRP, possibly increasing nerve sensitization.
• Irritable bowel syndrome (IBS) is more common in migraine sufferers (increased risk 40-80%).
• Food intolerances can trigger both IBS and migraine episodes.
• Pharmaceuticals that modulate serotonin receptors are effective in both IBS and migraines.

Possible Mechanisms (Gut Microbiome & Migraines)

• Pro-inflammatory cytokines (IL-1beta, IL-6, IL-8, TNF-alpha, IFN) are increased in migraine sufferers, and likely involved.
• Dysbiosis (imbalance in gut microbiome) may lead to increased gut permeability and subsequent LPS leakage.

References

• Specific references provided, encompassing articles, research papers, and relevant studies.