Schizophrenia

Schizophrenia:

Psychopathology:

Study of mental disorders such as progression, diagnosis, treatment.
This broad discipline draws on research from numerous areas like psychology, biochemistry, pharmacology, psychiatry, neurology, and endocrinology.

APA dictionary of Psychology:

The scientific exploration of abnormal mental states.
The discipline that assesses and makes sense of abnormal human subjectivity.

Limitations and challenges:

Measurements and categorization issues
Norms and neurodiversity (what is normal)
Blurry boundaries (do disorders fit into neat categories?)
Mental health vs medical conditions: fundamental differences

ICD-11

Diagnostic framework

Traditional categorical approach

Diagnostic tools: DSM-5 & ICD
Disorders are “present or absent”, not “continous”
Disorders are classified by discrete categories
Assuming you either meet criteria or don't, does not account for symptom severity or spectrum based disorders.

Key components:

Characteristic symptoms
Social/ occupational dysfunction
Duration of symptoms.

Emerging Dimensional approach:

Research framework, not a diagnostic tool
RDoC
^^organizes psychopathology by domains of functions, not disorders (negative valence, positive valence, cognitive systems, social processes, arousal/regulatory systems, sensorimotor systems)

Key principles:

Conceptualized mental illness as a brain disorder
Emphasized biomedical explanations
Moves away from descriptive diagnostic systems (DSM-5)

1 in 4 2022, psychopathology is common

Nearly one in five U.S. adults lives with a mental illness (44.7 million in 2016). Among adults aged 18 or older in 2022, 23.1% (or 59.3 million people) had any mental illness (AMI) in the past year.

Faces of Schizophrenia you may know:

John Nash
Pink Floyd
Eduard Einstein
Vincent Van Gogh

How common is Schizo?

Affects 20 million people worldwide
3 million cases in the U.S

Misconceptions vs reality:

Schizo is often stigmatized as being linked to danger or “criminal insanity”
Scientific evidence does not support the idea that individuals with schizo are inherently violent.
exceptions:

Substance abuse: individuals with schizo who abuse drugs have a slightly higher risk or violent offenses.

Childhood conduct problems: those with a history of conduct disorder in childhood are more likely to commit violent crimes.

What is schizophrenia?

3 symptom categories:

Positive deviant symptoms::

Hallucinations
Delusions
Disorganized speech

Negative deficit symptoms:

“Flat affect” means reduced expression of emotions via facial expression or voice tone.
Reduced feelings of pleasure
Difficulty beginning or sustaining activities
Reduced speaking

Cognitive symptoms:

Working memory deficits (Problems with “working memory” (the ability to use information immediately after learning it)
Trouble focusing
Poor executive function
Bizarre behavior

DSM-5: at least one positive symptom and two (total) symptoms for a significant portion of time during a one month period

Development of Schizo:

Diagnosed in the late teens year to early thirties
Tend to emerge earlier in males than females
Genetics (can run in the family, no single gene causes the disorder)
Environment (interactions between genetic risk and individuals environment)
Prenatal viral infection, maternal stress, hypoxia, childhood trauma, urban living cannabis use during adolescence)

Neural features that we see in schizo

Disorganized Hippocampal Formation:

Alterations and dysfunction in the hippocampal structure may play a role in symptom manifestation

Enlarged ventricles

Structural brain damage, enlargements of lateral and third ventricles

Higher rate of gray matter loss — decreased frontal lobe activation.

Adolescents with schizo show a higher average annual loss of gray matter and decreased frontal lobe activity compared to normal adolescents.

Dopamine dysregulation, and glutamate abnormalities

Antipsychotic drugs:

Medication required institutionalization for mental illness

Impact on institutionalization:

Antipsychotic medications have significantly reduced the need for institutionalization for mental illness.

Mechanism of Action:

Primary action on dopamine signaling (neuroleptics), which was identified in the 1960s
The 1970 brought the discovery of dopamine receptors, revealing that higher D2 receptor affinity correlates with clinical efficacy of antipsychotic medications.

Importance of Atypical antipsychotics:

2nd generation antipsychotic target serotonin as well as dopamine receptors, which presents a multi-faceted approach to treatment.

Model of Aberrant Salience:

Proposes that psychotic symptoms first emerge when chaotic brain dopamine transmission leads to a shift in a stimuli significance.
Focuses more on stimuli that would normally be considered irrelevant.

The mechanism:

Delusions may stem from altered dopamine pathways that shift emotional and reward significance, thereby enhancing perceived threats and altering attention.
Too much dopamine = irrelevant cues feel meaningful
Too little dopamine = important cues feel less relevant
hallucinations= sensory experiences given too much salience
delusions= attempts to explain abnormal salience

Animal models of Schizo

Neurodevelopmental models: inducing changes in brain development during gestation or perinatal periods
Pharmacological models: creating drug- induced psychosis using substances like PCP,LSD and amphetamines
Genetic manipulation technique: manipulating genetic expression to stimulate schizo in animal studies
Prepulse inhibition (PPI): common behavioral test used to examine sensory processing deficits

PPI reflected ability to filter sensory information
schizophrenia= reduced ppi= impaired sensory gating

Focus on Positive Symptoms: most studies primarily target positive symptoms; addressing how to model negative symptoms like flat affect remains a challenge

Translational considerations:

1st drug prozemene