Schizophrenia is an adult-onset disorder that can significantly disrupt the life of patients as well as their primary caregivers. Diagnosis is essentially a post-hoc assessment, but by then, neurocognitive deficits are permanent and curative treatment options to improve the quality of life of patients are more limited. Early assessment of the risk of developing schizophrenia is essential to bring in interventions to reduce the impact of these deficits.

Although the entire set of genes involved in schizophrenia has not been identified, genetic analyses indicate that some chromosomal regions show strong correlations with characteristic behavioral deficits seen in schizophrenic patients.

One early diagnostic test is the assessment of auditory inhibition to a repeated auditory stimulus. In people without schizophrenia, a particular sound is ‘heard’ when the stimulus is provided once and is manifested as the firing of neurons. However, if the same signal is provided repeatedly the response of the neurons is diminished thereby enabling people to ignore repetitive sounds or background noise. This loss of auditory inhibition has been recorded in adults suffering from schizophrenia. The diminished inhibitory response is gauged as the ratio of responses evoked by paired auditory stimuli (S2:S1).

Similar assessments were made by Hunter and colleagues (2011) on infants 0-6 months of age to attempt to understand the role of parental psychosis, maternal depression and smoking. Recordings of responses to paired auditory stimuli were made when the infants were in their active sleep, a state that is similar to REM sleep in adults.

These scientists found that children of psychotic parents displayed impaired auditory inhibition. The auditory response to the second stimulus resembled the response to the first one, indicating lack of inhibition. In contrast, infants of parents not suffering from psychoses demonstrated intact auditory inhibition in response to paired stimuli.

Other risk factors that produced similar results were incidence of maternal depression and smoking by mothers. All infants assessed in the study had similar gestational periods of 33-38 weeks which rules out delayed development as a cause for the evident responses. These results indicate that an early diagnosis of schizophrenia is possible in early infancy and may provide a good time window of 16-18 years to bring in therapeutic interventions.

Auditory responses are shown by neurons that express the alpha-7 acetylcholine receptor. Activation of this receptor by choline is responsible for development of cerebral inhibition to auditory stimuli. In another study, Ross and colleagues (2013) have investigated a dietary intervention to establish cerebral inhibition. Pregnant women were asked to consume a supplement of phosphatidylcholine throughout pregnancy as well as for three months post delivery.  Infants were also fed with this supplement for up to three months following birth. The supplement contained twice as much phosphatidylcholine as is present in normal diets.

Recordings of auditory responses of infants showed that supplementation with phosphatidylcholine helped to restore normal cerebral inhibition to auditory responses. These results show that early developmental interventions are possible to restore the normal physiological functions of neurons that express the alpha-7 acetylcholine receptor.

Interestingly, in placebo-treated individuals, infants with the CHRNA7 genotype (bearing the defective gene for the alpha-7 receptor) displayed diminished cerebral inhibition. However, in the supplementation group, infants with the same genotype showed normal cerebral auditory inhibition.

So, dietary supplements of phosphatidylcholine can restore the physiological defects that are evident in schizophrenic individuals, at least in neuronal systems that express the alpha-7 acetylcholine receptor. Together, these studies illustrate that it may be possible to bring in restorative measures to correct schizophrenia. However, long-term follow up studies are needed to understand whether these interventions can truly bring about permanent restoration of neurocognitive deficits in schizophrenic individuals.

References

Greenwood TA, Swerdlow NR, Gur RE, Cadenhead KS, Calkins ME, Dobie DJ, Freedman R, Green MF, Gur RC, Lazzeroni LC, Nuechterlein KH, Olincy A, Radant AD, Ray A, Schork NJ, Seidman LJ, Siever LJ, Silverman JM, Stone WS, Sugar CA, Tsuang DW, Tsuang MT, Turetsky BI, Light GA, & Braff DL (2013). Genome-wide linkage analyses of 12 endophenotypes for schizophrenia from the Consortium on the Genetics of Schizophrenia. The American journal of psychiatry, 170 (5), 521-32 PMID: 23511790

Hunter SK, Kisley MA, McCarthy L, Freedman R, & Ross RG (2011). Diminished cerebral inhibition in neonates associated with risk factors for schizophrenia: parental psychosis, maternal depression, and nicotine use. Schizophrenia bulletin, 37 (6), 1200-8 PMID: 20403924

Ross RG, Hunter SK, McCarthy L, Beuler J, Hutchison AK, Wagner BD, Leonard S, Stevens KE, & Freedman R (2013). Perinatal choline effects on neonatal pathophysiology related to later schizophrenia risk. The American journal of psychiatry, 170 (3), 290-8 PMID: 23318559

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