Dopamine hypothesis + neural correlates (Biological explanation of schizophrenia)

What does the original dopamine hypothesis state?

First:

Schizophrenic individuals produce excess of dopamine, meaning a higher number are binding w/ D2 receptors → higher level of dopamine transmission → positive symptoms

Second:

Have typical dopamine levels, but excess D2 receptors → higher number of dopamine bindings to them → higher level of dopamine transmission → positive symptoms

What is evidence for the original dopamine hypothesis?

(3 to remember)

1. Anti-psychotic drugs work by inhibiting dopamine activity - block from firing → reduce positive symptoms

2. Grilly (2002) (using L-Dopa - treats Parkinson’s by increasing dopamine levels) when individuals w/o schizophrenia take large dose can develop hallucinations/delusions + small doses makes schizophrenic symptoms worse

3. Comer (2003) disturbances in dopamine process may → problems w/ attention, perception, + thought (often found in people w/ schizophrenia)

How does the revised dopamine hypothesis explain positive symptoms?

Excess dopamine in the mesolimbic pathway could explain positive symptoms (eg: hallucinations)

How does the revised dopamine hypothesis explain negative and cognitive symptoms?

Dopamine deficit in the prefrontal cortex which is responsible for thinking could explain cognitive problems + negative symptoms (eg: avolition)

What is evidence for the revised dopamine activity?

Wang + Deutch (2008) - depletion of dopamine in prefrontal cortex of rats → cognitive impairment → reversed with anti-psychotic drug

Patel (2010) – PET scans show LOWER Dopamine levels in prefrontal cortex of schizophrenic patients vs control group

Neural correlates:

What are the neural correlates that differ in Schizophrenic patients

• PFC

• Hippocampus

• Grey matter

• White Matter

Neural correlates:

How does schizophrenia differ the prefrontal cortex (PFC)?

Weinberger + Gallhofer (1997):

• Area of the brain involved in executive control (planning, reasoning, judgment) - impaired in schizophrenic patients

Neural correlates:

How does schizophrenia differ the hippocampus?

• In temporal lobe

• Conrad et al (1991) - anatomical changes in S patients

• Mukai et al (2015) - Deficits in nerve connections b/w hippocampus + PFC, correlate w/ degree of working memory impairments - central cognitive impairment in schizophrenia

Neural correlates:

How does schizophrenia differ grey matter?

• Individuals w/ schizophrenia have reduced grey matter volume (esp in temporal/frontal lobes)

• Brown et al (1986) PME found many SPs have enlarged ventricles (consequence of loss of grey matter in nearby parts of brain)

• Cannon et al (2014) - those w/ higher clinical risk + developed schizophrenia showed steeper rate of grey matter loss/expansion of ventricles vs those who didn’t develop it

Neural correlates:

How does schizophrenia differ white matter?

Du et al (2013) found reduced myelination (myelin sheath on neurons → helps insulate/strengthen signals) of white matter pathways in schizophrenic patients vs control → particularly in neural pathways b/w PFC + hippocampus

Evaluation: Supporting evidence for revised dopamine hypothesis

Patel (2010) - PET scans reveal lower dopamine levels in the prefrontal cortex → supports revised dopamine hypothesis bcs suggests it's not as simple dopamine low or high dopamine levels, but the area of the brain it occurs in

Evaluation: extrapolation w/ revised dopamine hypothesis evidence

Extrapolation (when you try generalising findings from studies on animals/computers to humans) issues in eg: Wang and Deuch (2008) (depletion of dopamine in PFC of rats) used animals → difficult to apply results to humans bcs physiologically/cognitively/anatomically different

Evaluation: alternative explanation

Family dysfunction suggests the environment/family people grow up in can cause developing schizophrenia (eg: 'double bind' theory suggests children whose parents give them contradictory messages are more likely to develop it bcs confusing interactions prevent developing internally coherent constructions of reality -> manifests as schizophrenic symptoms in long run

Evaluation: Practical application (of dopamine hypothesises)

Antipsychotics are shown to be effective in reducing dopamine by binding to D2 receptors → reduce symptoms → improve quality of life/functioning → may be well enough to return to work → economic benefits

Evaluation: reductionist

Only considers neurological/role of D in causing schizophrenia but alt explanations - like family dysfunction (eg: double bind theory), or genetic (eg: Gottesman (1991), Joseph (2004)) suggests many other factors can cause/maintain it too, so = reductionist → bad bcs suggests incomplete/incomprehensive → interactionist approach may be better