Dopamine and Psychosis Overview

Dopamine and Psychosis

• Excess dopamine binding at D2 receptors in the mesolimbic pathway is strongly associated with psychosis.
• Psychosis can be caused by various factors, not just schizophrenia.
• Schizophrenia is the most common psychotic disorder.

Dopamine Pathways in Schizophrenia

• There are four main dopamine pathways in the brain: mesolimbic, mesocortical, nigrostriatal, and tuberoinfundibular.
• The mesolimbic pathway is involved with positive symptoms of schizophrenia.
• The mesocortical pathway is involved with negative and cognitive symptoms of schizophrenia.
• The nigrostriatal pathway is involved with extrapyramidal symptoms and tardive dyskinesia.
• The tuberoinfundibular pathway is involved with hyperprolactinemia.

Mesolimbic Pathway

• The “psychotic pathway” connects the ventral tegmental area (VTA) to the nucleus accumbens (reward center).
• Implicated in motivation, pleasure, and reward.
• Excess dopamine leads to increased pleasure, reward, and motivation as well as positive symptoms of schizophrenia (hallucinations, delusions).
• Implicated in all forms of psychosis.

Mesocortical Pathway

• Connects the VTA to the prefrontal cortex (PFC).
• Reduced dopamine leads to negative symptoms of schizophrenia (flat affect, cognitive deficits, social withdrawal, executive function impairment, and difficulty with appropriate expression of emotion/cognition, and problem solving).
• Negative symptoms are associated with poorer long-term outcomes.
• Antipsychotics can worsen negative symptoms by further reducing dopamine in this pathway.

Nigrostriatal Pathway

• Connects the substantia nigra to the striatum (motor control).
• Typically unaffected in schizophrenia.
• Antipsychotics can disrupt this pathway, leading to extrapyramidal symptoms (EPS), such as tremors, rigidity, akathisia, and the “Thorazine shuffle.”
• Deficiencies of dopamine in this pathway are implicit in movement disorders like Parkinson’s Disease.

Tuberoinfundibular Pathway

• Connects the substantia nigra to the hypothalamus (prolactin production).
• Typically unaffected in schizophrenia.
• Antipsychotics can disrupt this pathway, leading to hyperprolactinemia, galactorrhea, menstrual irregularities, and difficulty conceiving.

Antipsychotic Medications

• Aim to control dopamine activity in the mesolimbic pathway while minimizing effects on other pathways.
• Newer antipsychotics are generally better at achieving this balance.

Differentiating Among Psychoses

• Psychosis is a symptom, not a diagnosis.
• Identify the type of psychosis:
  • Hallucinations are sensory perceptions without external stimuli.
    • Auditory (most common in psychotic disorders).
    • Visual (can be associated with psychotic disorders or organic conditions).
    • Tactile, olfactory, and gustatory (more likely to have organic causes).
  • Delusions are fixed, false beliefs despite evidence to the contrary or rational argument.
    • Common types: mood or atmosphere, perception, memory, ideas, and awareness.

Psychotic Disorders

• Schizophrenia: Chronic psychotic disorder with positive symptoms (hallucinations, delusions), negative symptoms, and functional impairment. Symptoms must last for at least 6 months.
• Schizoaffective Disorder: Meets criteria for both schizophrenia and a mood disorder (MDD, BPD I, BPD II).
• Schizophreniform Disorder: Symptoms of schizophrenia but for less than 6 months.
• Brief Psychotic Disorder: Psychotic symptoms lasting less than one month.
• Delusional Disorder: Persistent delusions without other psychotic symptoms.
• Substance-Induced Psychosis: Psychosis caused by substance use.
• Psychotic Disorder Due to a Medical Condition: Psychosis caused by an underlying medical condition (e.g., head injury, metabolic imbalance, organic lesion).
• Paraphrenia: Chronic psychotic disorder similar to schizophrenia but with better-preserved affect and functioning.
• Paraphrenia: Chronic psychotic disorder similar to schizophrenia but with better-preserved affect and functioning.

Introduction to Dissociation

• Dissociation is a disconnection between a person’s thoughts, memories, feelings, or sense of self.
• Everyone dissociates sometimes. It is not a disorder unless it disrupts social or occupational function.
• Normal vs. abnormal dissociation:
  • Everyday examples (daydreaming, highway hypnosis).
  • Therapeutic uses (hypnosis).
  • Dissociation as a coping mechanism (trauma, accidents, crime victim).

Characteristics of Dissociative Disorder

• Abrupt onset and offset.
• Positive and negative disruptions:
  • Positive: Experiences that shouldn’t be there (e.g., feeling detached from your body).
  • Negative: Lack of experiences that should be there (e.g., memory loss).
• Triggered by psychological conflict or trauma.
• Impaired functioning or distress.

Types of Dissociative Disorders

• Depersonalization/Derealization Disorder:
  • Depersonalization: Detachment from oneself (physical, cognitive, or emotional self).
  • Derealization: Feeling that surroundings are unreal or that people around them are not real people.
  • Begins in early childhood - almost always before age 16.
• Dissociative Amnesia:
  • Inability to recall important personal information, usually related to trauma.
  • Begins suddenly and often precipitated by severe stress.
  • Types:
    • Localized: No recall for events within a particular time frame.
    • Selective: Certain portions of time are lost.
    • Generalized: All experiences of the lifetime are forgotten.
    • Continuous: Loss of all memory from a certain time to the present.
    • Systematized: Loss of certain classes of information (e.g., everything about work).
• Dissociative Fugue:
  • Sudden, unexpected travel away from home with amnesia for identity.
  • May assume a new identity.
  • Severe stressor -> sx commonly lasts a few hours or days.
  • Recovery is sudden.
• Dissociative Identity Disorder (DID):
  • Formerly known as multiple personality disorder.
  • Presence of two or more distinct personalities with unique attributes (mood, perception, recall, control of thought and behavior).
  • Often associated with severe childhood trauma.
  • Each identity has unique characteristics (names, age, gender).
  • Significant gaps in memory and personal information.
  • Identity switching triggered by stress.

Somatic Symptom and Related Disorders

• Somatic Symptom Disorder:
  • Distressing physical symptoms with no identifiable medical cause.
  • Common symptoms: pain, shortness of breath, palpitations, abdominal problems.
  • Sx DO NOT respond to treatment that are usually effective.
• Conversion Disorder:
  • Altered voluntary motor or sensory function with no neurological explanation.
  • Examples: Blindness, paralysis, seizures, deafness, diplopia, hallucinations, paralysis, dysphagia.
  • Symptoms do not conform to anatomical patterns.
• Illness Anxiety Disorder:
  • “Hypochondriac”.
  • Healthy people with a serious fear of a life-threatening illness.
  • Needs repeated reassurance.
  • Preoccupation with having or acquiring a serious illness.
  • High anxiety about health, even with minimal or no symptoms.
• Psychological Factors Affecting Other Medical Conditions:
  • Mental health conditions (e.g., depression, anxiety) impacting physical health.
  • Examples: Depression worsening chronic pain, and hallucinations interfering with treatment adherence.

Factitious Disorder

• Factitious Disorder Imposed on Self (Munchausen’s Syndrome):
  • Deceptive falsification of physical or psychological symptoms for the purpose of assuming the sick role.
  • Often have coincident personality disorders.
  • May undergo unnecessary medical procedures.
• Factitious Disorder Imposed on Another (Munchausen’s Syndrome by Proxy):
  • Falsification of symptoms in another person, typically a child, for the purpose of gaining attention or sympathy.
  • Not too concerned when given bad news.
  • Sx do not make sense.
  • Typical tx do not work.
  • Death rate = 10%.

Malingering

• Intentional fabrication or exaggeration of symptoms for external gain (e.g., financial compensation, avoiding work, drugs).
• VERY difficult to detect.