exam 3 phisio - psychopathy

Trephine skull (5000 BCE)

• cut circular hole out of skull to release demons 

  • Most of early human history, psychiatric disorders were through to be supernatural (disorders due to evil spirits) 

Hippocrate (400 BCE) and Galen (2nd century CE)

• imbalance of body “humors” (fluids) 

  • Believed that psychiatric disorders were due to an imbalance of internal body humors (fluids) 

Breakthrough → mental disorders have a natural cause (not supernatural)

Psychopathology

• the scientific study of psychiatric (mental illness and disorders) 

Lunatic Asylums

solution of psychiatric disorders was to institutionalize people; lock them way and isolate them from society

St. Mary of Bethlehem (London, 1247)

•  earned nickname “Bedlam” after its horrific practices and conditions (state of uproar and confusion) 

Pitié-Salpêtrière Hospital (Paris, 1656)

• mostly for women (prostitutes, mentally ill, or just poor) prison-like conditionsand notorious for its overcrowding and inhumane treatment of patients.

Rotational Therapy

• spinning people very fast to reduce “brain congestion”

Teeth removal

• belief that mental illness was inflammation based 

  • Oral and dental infections were common → removed teeth in hopes of “curing” 

Benjamin Rush & Tranquilizing Chair

• immobilize a person in a chair to reduce blood flow with hopes of reducing psychiatric illness 

Continuous Hydrotherapy

• idea that water could ease insanity if applies to the skin

  • Effective because water could be heated or cooled 

Psychotic Disorders

schizophrenia (and many subforms), drug-induced psychosis

Affective Disorders

• major depressive disorder, bipolar disorder, premenstrual dysphoric disorder, postpartum depression conditions characterized by significant mood disturbances, including periods of extreme sadness or mania.

Anxiety Disorders

• generalized anxiety disorder, panic disorder, social anxiety disorder

• conditions characterized by excessive fear or worry, often leading to significant distress and impairment in daily functioning.

Splitting of the mind

 DOES NOT refer to multiple personalities within the same individual (dissociative personality disorder) → rather a disconnect between aspects of a single personality, thought, emotion, and behavior

 psychoses

• disturbances in thoughts and perceptions that result in a loss of touch with reality

Modern treatment

tends to consist of behavioral therapy and antipsychotic medicationto manage symptoms and improve functioning.

The spectrum of schizophrenia

• heterogeneous set of conditions that vary widely from person to person in their severity, duration, and how they present symptoms 

Positive symptoms

things that are present, but shouldn’t be

• Hallucinations: false sensory perceptions 

• Deluations: unshakable belief something that is untrue (false belief)

Negative symptoms

things that should be present, but are not

• Flattened emotions 

• Poverty of speech (lack of speaking)

• Difficulty experiencing emotions and planning 

• Lack of initiative and persistence (Lack of motivation) 

• Isolating – social withdrawal

• Anhedonia (inability to experience pleasure)

Cognitive symptoms of Schizophrenia

• Difficulty sustaining attention

• Low psychomotor speed 

• Dificenty in learning and memory 

• Poor abstract thinking 

• Poor problem solving 

• Difficulty with attention and applying information to make decisions (prefrontal cortex involved)

Catatonia

• A complex neuropsychiatric behavioral syndrome that is characterized by abnormal posturing, immobility, and withdrawal 

  • People are aware of their surrounding but do not interact with it 

• Patient may appear lifeless and exhibit posturing, muteness, staring, and immobility 

age of onset schizophrenia

20.5 is average but late 20s early 30s for women

schizophrenia prevalence

1-1.5% of the us population (3 million ppl)

genetic basis of schizophrenia

• Risk of development increase with number of genes shared by a family member with the condition 

  • General population has a 1% lifetime risk 

  • 50% shared genes with parents puts you at a 6% risk of developing

  • Monozygotic twins have 100% of the same genetic makeup but only puts the twin at a 48% risk of development  

environmental factors of schizophrenia

• People who develop schizophrenia without a family history often experienced more complications at birth (compared to neurotypicals):

  • Ex. low birth weight, prolonged labor

Can also be related to to the mothers health at time of fetal development

hunger winter ww11

Food was scarce, causing mothers to be malnourished → this resulted in a large number of the offspring to develop schizophrenia (compared to the normal population)

Seasonal effects schizophrenia

• higher number of schizophrenic births during winter months 

  • If mother becomes ill (e.g. flu) during the 2nd trimester, the offspring is more at risk to develop schizophrenia 

  • Mothers body is fighting infections → Could lead to inflammation which is detrimental to fetal development 

adolescent behavioral deficits linked to schizophrenia

• motor abnormalities, apathy, social withdrawal, attention deficits, etc. 

  • Symptoms are hard to spot and often go misdiagnosed (assumed to be autism) 

  • Irrespective of whether the parent is ‘normal’ or schizophrenic

Cortical gray matter loss

1. “cerebral atrophy”) – excessive synaptic pruning in the perinatal and adolescent periods

2. Cerebral atrophy (within/ death of cortical neurons) is normal in early development → we are born with more than we need and are progressively pruned

   • Strong connections survive and integrate with the brain white weak ones die off 

   • HOWEVER pruning happens at abnormal (accelerated) rates to people with schizophrenia → they experience ~2x greater cortical neuron loss

Ventricular enlargement following gray matter loss

• Ventricles which hold cerebrospinal fluid are enlarged → likely because the significant loss of gray matter allows for more room for the ventricles to expand (less brain tissue around it) 

Disorganised hippocampus cytoarchitecture (neuron migration issues in development) 

• In neurotypical individuals hippocampal neurons have an orderly arrangement – lined up in an organized manner

• Schizophrenic individuals – there is a lack of arrangement (disorganization) → this can lead to neural connectivity issues 

  • Neurons have trouble making the right connections because they are in the wrong places → making more synaptic connections is more difficult because neurons are not in the right positions 

  • Indicates neurodevelopmental abnormalities in neuron formation, mitigation, and synaptogenesis 

Shrinking of dendritic trees leading to connectivity failures (issues with synaptogenesis)

• Shrinking of dendritic spines, usually in cortical neurons → abnormally small which suggests fewer synaptic connections 

• Related to issues in making new synaptic connections (synaptogenesis)

two-hit model

biopsychosocial interactions that show two developmental points of schizophrenia in time

early stage “first hit”

Perinatal Period

• Genetic predispositions and gene expression + Environmental insults (virus,toxins, poor nutrition, birth complications, activated immune system) 

• Result → neurodevelopmental abnormalities from conception to early adulthood including neuron formation, mitigation, synaptogenesis, pruning, apoptosis 

Latent Stage

• First Few Years of Life:

  • Early subtle signs of prediction schizophrenia including motor abnormalities, apathy, social withdrawal, deficits in attentional and information-processing tasks 

Late Stage “Second Hit”

Adolescents

• Excessive synaptic pruning in adolescence leading to abnormal neural connectivity and function + later environmental insults such as stress, substance use, and HPA axis dysfunction

• Greater impairment of cognitive function including deficits in attention, memory, executive function

• Positive symptoms including hallucinations, delusions, disorganization 

• Worsening of negative symptoms include deficits in motivation and emotion, isolation, anhedonia 

Neurodevelopment/Hypofrontality Hypothesis 

• here are defects in early brain development (particularly in the frontal cortex) → results in reduced PFC activity 

• Believe that cognitive symptoms seem PFC dependent 

• The frontal cortex is less active (hypoactivity) in individuals with schizophrenia 

  • Ex. give an executive function task to an individual believed to have schizophrenia (while in a scanner) → if they have the condition, we will see low prefrontal cortex 

• Lack of activity likely reflects lack of glutamatergic neurons

The Dopamine Hypothesis

• Schizophrenia is due to hyperactivity of dopamine circuitry (too much DA signaling)

• Evidence: drugs that enhance DA activity can produce positive symptoms of schizophrenia 

  • Ex. amphetamine psychosis → chronic heavy use can produce positive schizophrenia symptoms 

    • Causes psychotic episodes and feeling like ants are crawling on you skin (hallucinations) 

  • Results because of an access of dopamine activity 

• The first effective antipsychotic drugs are antagonists of dopamine “D2” receptors (inhibits activity) 

  • HOWEVER if schizophrenia were due to a simple overabundance of dopamine, antipsychotics would work immediately → BUT they usually take several weeks to take effect

    • This suggests more complex mechanism 

  • AND the negative and cognitive symptoms usually DO NOT improve with D2R blockade

The Glutamate Hypothesis

• Schizophrenia is due to hypoactivation of glutamate circuits (too litter GLU signaling) 

• Evidence: drugs that mimic some symptoms of schizophrenia are glutamate receptor antagonists 

  • Ex. PCP and Ketamine can create detachment and hallucinations