Schizophrenia is a heterogeneous group of disorders with common symptoms of auditory hallucinations, paranoid delusions, and cognitive disorder. It is fairly common affecting 1% of the population. The heritability rate for identical twins is about 80%. No one gene causes the condition; rather the risk is compiled from the addition of many genes. But environmental factors, notably cannabis and amphetamine abuse, also strongly contribute.
The risk that is inherited is a diffuse functional hypo-connection of the frontal lobe from other areas of the brain. The same hypo-connection can be found in family members not suffering from schizophrenia. This underlying developmental disability seems to be the cause of some of the cognitive difficulties that are present in schizophrenia. The main areas of hypo-connection are:
-frontal lobe to anterior capsule (activity in the anterior capsule counters obsessional thinking)
– frontal lobe to thalamus (the thalamus relays and sorts pertinent sensory information)
– frontal lobe to parietal lobe
– frontal lobe to occipital lobe
There is also hypo-connection between the left and right brain via the corpus callosum. ( One theory of the origins of Schizophrenia is that it is a consequence of left hemisphere specialisation for language in humans).
Within the frontal lobe itself there are areas of increased connectivity in the dorso-lateral prefrontal cortex and the medial prefrontal cortex which correlate with delusional symptoms. They are caused by overactivity of dopamine neurons which change the balance between excitatory/inhibitory activity in the cortices. This results in an erroneous importance being given to random or irrelevant events – hence the evolution of the delusional system. Anti-psychotic drugs modulate dopamine overactivity.
A similar thing happens in the auditory cortex where again the excitatory/inhibitory balance is shifted leading to oversensitivity of the cortical cells and a tendency to hear “non-stimuli”. Hence the origins of auditory hallucinations.
Fornito, A et al “Schizophrenia Neuroimaging and Connectomics”‘ in Neuroimage vol 64 (2012) pp 2296-2314
Klass, S et al “Translational Perspectives for Computational Neuroimaging” in Neuron vol 87 (2015) pp716-729.