Biological explanations for schizophrenia: genetics and neural correlates,…

The idea

Schizophrenia runs in families. Gottesman pooled twin and family data and found concordance of 48% for identical twins, 17% for fraternal twins and 9% for siblings, against roughly 1% in the population: strong heritability, but short of the 100% a purely genetic condition would give. It is polygenic; Ripke's genome study found over a hundred variations, several coding for glutamate rather than dopamine. Neural correlates are brain measures that travel with symptoms: Juckel found low ventral striatum activity tracking negative-symptom severity, Allen reduced activation in the superior temporal gyrus in patients who hallucinated. The dopamine hypothesis blames excess subcortical dopamine for positive symptoms; Davis added low prefrontal dopamine for negative ones.

What earns the marks

• Family studies show risk rising with genetic similarity: Gottesman reports about 48% concordance for monozygotic twins, 17% for dizygotic twins and 9% for siblings against about 1% population risk.
• Schizophrenia is polygenic and aetiologically heterogeneous: Ripke et al. pooled genome-wide data and identified over a hundred candidate variations, so different combinations of genes can produce the same diagnosis.
• Adoption studies such as Tienari separate genes from upbringing, and the raised risk in adopted-away children of affected mothers supports a genetic diathesis.
• Juckel et al. found low activity in the ventral striatum, part of the reward system, correlating with the severity of negative symptoms such as avolition.
• Allen et al. found lower activation in the superior temporal gyrus and anterior cingulate in patients who experienced auditory hallucinations, linking hallucination to the speech-processing areas.
• The original dopamine hypothesis: hyperdopaminergia in subcortical mesolimbic pathways is used to explain positive symptoms such as hallucinations and delusions.
• The revised hypothesis (Davis): hypodopaminergia in the prefrontal cortex accounts for negative and cognitive symptoms, so both too much and too little dopamine matter, in different places.

Common mistakes and how to put them right

• Treating concordance rates as proof of genetics.

  Put it right: If identical twins share all their genes and concordance is only about 48%, the figure itself proves the environment contributes, and the best answers say so.

• Writing "schizophrenia is caused by too much dopamine" without location.

  Put it right: The claim is excess dopamine in subcortical areas for positive symptoms and too little in the prefrontal cortex for negative symptoms; the undifferentiated version is the outdated original.

• Describing a correlate as a cause.

  Put it right: Enlarged ventricles co-occur with schizophrenia, but the illness or its medication may be causing the change, so nothing about direction of causation follows.

• Forgetting glutamate. Candidate genes and drugs such as ketamine implicate glutamate, so an answer that treats dopamine as the whole biochemistry misses an obvious AO3 point.

• Saying twins share the same environment as a throwaway line.

  Put it right: Name the confound: identical twins are treated more alike than fraternal twins, so concordance inflates heritability.

Exam tips

• For "explain what is meant by neural correlates" give the definition first (a measurement of brain structure or function that correlates with an experience), then one named example, then the symptom it tracks.
• Balance accurate explanation of genetics, neural correlates and dopamine with evaluation of correlation and causation, polygenic complexity and alternative neurochemical accounts; apply each point to any supplied scenario.
• Use the drug evidence both ways. Antipsychotics working supports dopamine, but they do not work for every patient and improvement can be slow, which weakens it.
• Avoid generic "biologically determinist" evaluation; tie it to a consequence, such as a patient being told nothing but medication will help.