lecture: 13.3 schitzophrenia

Symptoms of schizophrenia

Positive (something extra being added)symptoms: 

Presence of unusual behaviors, in excess of typical functioning 

• Though disorders delusions 

• Hallucinations 

 

Negative symptoms: 

Absence or decrease in some typical behaviors 

• Social withdrawal, lack of affect, and reduced motivation 

Cognitive symptoms: 

Cognitive deficits, such as , difficulty sustaining attention, low psychomotor speed, deficits in learning and memory, poor abstract thinking, poor problem solving 

Age of onset of psychotic symptoms: 

• Between early adolescence and early adulthood peaking at age of 20-25 and more common in males than females 

Examples of schizophrenia symptoms: 

Positive: 

Hallucinations 

Disordered thoughts 

Delusions 

• Persecution

• Grandeur 

• Control 

Negative: 

• Flat affect 

• Poverty of speech 

• Lack of initiative and persistence 

• Anhedonia 

• Social withdrawal 

Cognitive: 

• Difficulty in sustaining attention 

• Low psychomotor speed 

• Deficits in learning/memory 

• Poor abstract thinking 

• Poor problem solving 

Genetic factors: 

• Twin and adoption studies indicate the heritability of schizophrenia 

• Higher rates in monochorionic monozygotic twins 

• No “schizophrenia gene” but some associated with them 

Schizophrenia: 

Mutations: mutation of the DISC1 gene 

Paternal age: 

• Children of older fathers are at increased risk 

• Increase likelihood of mutation 

Epigenetics

Environmental contributions: 

Associated factors: 

• Season of birth (late winter/ early spring) 

• Viral epidemics 

• Vitamin D deficiency 

• Population density 

• Substance abuse 

• Protective factors: limited evidence 

Obstetric complications: 

• Prenatal malnutrition and stress 

• Complications of pregnancy 

• Toxemia 

• Abnormal fetal development 

• Labor and delivery complications 

Brain anomalies: ventricular size 

• People with schizophrenia have increased ventricle size 

Cerebral gray matter: 

• Decreased gray matter in people with schizophrenia 

• MRI scans demonstrate the loss of brain volume in a patient with schizophrenia over 10 years. Notice the enlargement of the lateral; ventricles (dark region in the center of the brain)
  
  

Dopamine and positive symptoms: 

• Dopamine hypothesis: positive symptoms of schizophrenia are caused by hyperactivity of dopaminergic synapses in the mesolimbic pathway 

• Drugs activating as agonists produce and reinforce positive symptoms 

• Some studies show those diagnosed with schizophrenia release excessive dopamine, brains may contain more dopamine receptors. 

Mesolimbic dopamine pathway: 

• Overactivity of the mesolimbic pathway leads to positive symptoms 

• Mesocortical pathway dysfunction leads to negative and cognitive symptoms

Mesolimbic pathway and treatment side effects: 

Long term drug treatment of schizophrenia: 

• Typical antipsychotics block dopamine activity 

• Parkisonian symptoms ‘

• Tardive dyslexia: repetitive involuntary movements 

Mesocortical DA pathway: Negative and cognitive symptoms

Hypofrontality: 

• Believes to be responsible for negative symptoms 

• May also be responsible for hyperactivity in the mesolimbic pathways related to positive symptoms 

Role of Glutamate: 

• Decreased glutamate activity (resulting in hypofrontality) may contribute to negative and positive symptoms 

• Chronic low doses of glutamate antagonist drugs produce negative and cognitive symptoms 

Mesocortical DA pathway

Negative and cognitive symptoms

Developmental changes

• DISC1 gene mutation connected to schizophrenia 

• Abnormalities in the pyramidal neurons in the PFC 

Atypical antipsychotics: 

Increase DA activity in the PFC and reduce it in the mesolimbic system 

• aripiprazole : parietal agonist at DA receptors  

Role of DISC1 in schizophrenia 

• Abnormalities after puberty lead to behavioral abnormalities 

Role of D2 receptors

• increased availability of D2 leads to decrease in inhibitory neurotransmitter expression