Sz Dopamine

Question 1

Why is there a relationship between cannabis use and psychosis?
Regardless of the direction of the causal link, why is there a relationship in the first place common mechanisms may include dopamine dysfunction, genetic liability, brain structure abnormalities.
Dopamine

Answer 1

• One explanation that might explain link between cannabis use and risk for psychosis is as neurotransmitter systems are developing in the adolescent brain, there is a disruption of development of neurotransmitter systems, particularly dopamine, GABA and endocannabinoids (endogenous cannabinoid molecules that are involved in presynaptic transmission of gaba and dopamine).
• GABA is an inhibitory neurotransmitter that is important in a whole range of functions related to memory, mood etc.
• Secretion of GABA usually inhibits the release of dopamine from other neurons.
• Dopamine has been linked specifically to both substance use and sz and may therefore be an underlying neurobiological mechanism for the link between sz and cannabis use.

Question 2

Classic Dopamine hypothesis of Schizophrenia

Answer 2

Classic Dopamine hypothesis of Schizophrenia- states that sz is caused by overactive dopamine secretion in the brain. Dopamine is a neurotransmitter which is synthesised in nerve cells in the midbrain substantia negra and ventral tegmental areas. Dopamine if transmitted to three main areas of the brain- 1) prefrontal cortex (thinking and working memory) 2) striatum (movements) 3) limbic system (including nucleas accumbens which is the reward centre). An important function of dopamine is to enable us to anticipate behavioural and cognitive out-puts.

Question 3

Classic Dopamine hypothesis of Schizophrenia

EVIDENCE

review by Friedmann et al. (1999)]

Tallerico et al, 2001

Domyo et al, 2001

Seeman et al (2006)

Answer 3

o EVIDENCE
o review by Friedmann et al. (1999)]. D (1) receptors in the prefrontal cortex are decreased in schizophrenia patients and are unaffected by chronic treatment of typical neuroleptics.
o (Tallerico et al, 2001). In contrast, D (1)-receptors are increased in the parieto-temporal cortex in schizophrenia patients (Domyo et al, 2001). Increased D2 mRNA has been found in the frontal cortex in schizophrenia patients when compared with neuropsychiatric healthy control subjects
o Seeman et al (2006) Review papers such as that conclude that an increase in D (2)-high-receptors is a necessary basic requirement for the development of a psychosis that correlates with dopamine super-sensitivity.

However, the classic dopamine hypothesis is no longer accepted as a satisfactory explanation of Sz, as antipsychotic medication which reduces the effects of dopamine in the brain often leads to a reduction in positive symptoms, but negative symptoms tend to persist.

Question 4

This led to the reformation of the dopamine hypothesis.

Delisi et al 2006

Ghazzaoui et al 2014; Sami et al 2015

Answer 4

• This led to the reformation of the dopamine hypothesis. It is currently understood that there are two dopamine pathways in the brain which contribute to sz syptoms. It is believed that overactivity in the mesolimbic dopamine pathway leads to the positive symptoms of sz, whereas underactivity in the mesocortical dopamine pathway leads to negative and cognitive symptoms.
• Delisi et al 2006 THC and cannabinoid agonists enhance striatal and mesocorticolimbic dopamine levels and affect the maturation of the dopamine system, which directly regulates motor function, cognition, motivation, and emotional processes.
o Explains why cannabis use is associated with positive symptoms- overactive dopamine
o Also explains why effects may be transient in short term use
• However, research generally has not found that cannabis effects dopamine release in the brain immediately like other addictive substances (i.e. reviews by Ghazzaoui et al 2014; Sami et al 2015), but rather it is hypothesised that cannabis can have long lasting altering effects on dopaminergic functioning through the disruption of the endocannabinoid system in early adolescence.
• Adolescence is a critical phase for brain development, characterized by neuronal maturation and rearrangement processes.
• The endocannabinoid system plays an important role in fundamental brain developmental processes such as neuronal cell proliferation, migration and differentiation, therefore, changes in endocannabinoid activity during this specific developmental phase induced by THC might lead to subtle but lasting neurobiological changes.
• The cannabinoid systems has a dense distribution of GABAergic neurons and plays a central role in inhibiting the GABAergic neurons.
• We know that GABA secretion inhibits dopamine secrection, and overactive dopamine in the mesolimbic pathway is associated with the positive symptoms of sz. Therefore, altered endocannabinoid activity that may disrupt the inhibition of GABAergic neurons could significantly effects dopaminergic activity and thus contribute to the development of psychosis.
• The effects of early cannabis use on the development of brain functions also explain why psychotic symptoms differ according to age of onset of use, as in short term use after adolescence the disruption of neurochemical processes likely to last only until drug wears off.