Clinical Psychology - Carlsson et al. 2000

Issues with the DA hypothesis

• DA dysfunction cannot be the only explanation as some individuals have normal DA levels

• DA could be a result of stress

• Most current research only looks at Sudden Onset Schiz

• Anti-psychotic drugs that only reduce DA don’t suit everyone

3 Aims

1. To show the current view of the DA hypothesis

2. To look at other neurotransmitters + psychosis, not just DA

3. To use this understanding to produce better anti-psychotics, with fewer side effects

Why is the DA hypothesis too simplistic?

Other neurotransmitters involved in Schizophrenia

• Noradrenaline

• Serotonin

• Acetylcholine

• Glutamate

• GABA

Evidence for the role of Glutamate

One study found that PCP blocks glutamate receptors (blocks NDMA (antagonist)) → causes psychosis e.g hallucination

2 experimental models of schizophrenia

Hyperdopaminergia = too much Dopamine

Hypoglutamatergia = too little Glutamate

Some drugs only impact one, others impact multiple

• Clozapine works on Serotonin, so maybe we should have drugs that impact Glutamate

Literature review of research

• Sources investigating neurochemical levels in patients

• Studies into drugs known to induce sympt of psychosis

• Evidence from brain scans to support DA related to psychosis

  • Abi-Dargham et al. 1998

  • Brier et al. 1997

• Studies on use recreational drugs that induce psychosis

  • Amphetamines (inc. DA)

  • Phencyclidine (PCP)

Are drugs that only act on DA still valuable?

How to improve?

Yes, but it wold be est to stabalise DA levels without lowering too much

Would be beneficial to have drugs that affect multiple neurotransmitters, not just DA (Serotonin + Glutamate)

Conclusions

• Sub-populations of individuals with schiz - may be different causes within those populations

• More research needed into the role of Glutamat, Neuropeptides, GABA and Acetylcholine

• Just too much DA / too little glutamate causing schiz

• Instead the 2 interact → too little glutamate = causing too much dopamine

• More research needed to increase understanding