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Candidate Genes Involved in the Expression of Psychotic Symptoms: A Focus on Hallucinations

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The Neuroscience of Hallucinations

Abstract

Auditory hallucinations (AHs) are a possible phenotype for genetics studies. (a) AHs are a hallmark of psychosis; (b) clinically, AHs are easily identified; (c) AHs are among the symptoms most likely to be captured by neuroimaging; (d) hallucinatory dimensions have a heritability of 0.43; (d) there is evidence of genetic predisposition towards AHs in a disease called autosomal dominant partial epilepsy with auditory features (ADPEAF). Different genotypes might code different proneness to hallucinations by inducing variances in the threshold of sensory gating. We present a model with three etiopathogenic pathways for AHs in psychosis. The first one is a general vulnerability to hallucinations in any perceptual modality. This general vulnerability could be related to genes that modulate all perceptual input through the thalamus-cortical loop. The second pathway involves vulnerability to abnormal emotional responses partially regulated by genes related to serotonergic and dopaminergic neurotransmission. This pathway is related to abnormal activation of the limbic and frontal brain areas. The third pathway involves vulnerability to language disorders that could increase the ­probability of hearing voices. This vulnerability could be the result of changes or abnormal expression in the FOXP2 gene, among others. This model integrates genetic and environmental factors in the origin of AHs. And it is compatible with epidemiological and neurobiological data.

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Abbreviations

5-HT2a:

Serotonin receptor genes

5-HTTLPR:

Serotonin transporter genes

ADPEAF:

Autosomal dominant partial epilepsy with auditory features

AH:

Auditory hallucinations

CCK:

Cholecystokinin

CCK-AR:

Cholecystokinin receptor genes

COMT:

Catechol-O-methyltransferase

DAT:

Human dopamine transporter

DRD3:

Dopamine receptor genes

LGI/1:

Leucine-rich-glioma-inactived 1 gene

MRI:

Magnetic resonance imaging

PET:

Positron emission tomography

SLC6A4:

Serotonin transporter gene

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Authors and Affiliations

  1. Psychiatric Unit, Valencia University, CIBERSAM, Blasco Ibáñez 15, 46010, Valencia, Spain

    Julio Sanjuán

  2. Spanish National Network for Research in Mental Health, Valencia, Spain

    Julio Sanjuán, María Dolores Moltó & Amparo Tolosa

  3. Department of Genetics, Valencia University, Valencia, Spain

    María Dolores Moltó

  4. Department of Molecular Embryology, Institute of Anatomy and Cell Biology, University of Freiburg, Freiburg, Germany

    Amparo Tolosa

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  1. Julio Sanjuán
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  2. María Dolores Moltó
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  3. Amparo Tolosa
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Correspondence to Julio Sanjuán .

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Editors and Affiliations

  1. University Medical Centre of Lille, Pediatric Psychiatry Department, Fontan Hospital, F-59037, Lille cedex, France

    Renaud Jardri

  2. Sainte-Anne Hospital, Center for Psychiatry and Neurosciences, Université Paris Descartes, 2 ter rue d'Alesia, Paris, F-75014, France

    Arnaud Cachia

  3. University Medical Centre of Lille, Psychiatry Department, Fontan Hospital, rue Verhaeghe, Lille cedex, F-59037, France

    Pierre Thomas

  4. University Medical Centre of Lille, Functional Neurosciences & Disorders Lab, Salengro Hospital, Lille cedex, F-59037, France

    Delphine Pins

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Sanjuán, J., Moltó, M.D., Tolosa, A. (2013). Candidate Genes Involved in the Expression of Psychotic Symptoms: A Focus on Hallucinations. In: Jardri, R., Cachia, A., Thomas, P., Pins, D. (eds) The Neuroscience of Hallucinations. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4121-2_13

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