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Human Uniqueness Compared to "Great Apes": 
Absolute Difference
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Psychotic symptoms (hallucinations, delusions or thought disorder) are experienced in the course of a lifetime by approximately 2 to 3% of all human populations. They are associated with social and economic disadvantage and increased mortality. No environmental precipitant is clearly established, and there is a genetic predisposition as reflected in an approximate 10% risk to first-degree relatives.
Why are these genes not selected out of the population? The significance of the question is emphasised by the observation that the variation is associated with variations in brain structure, possibly relating to cerebral asymmetry.

The difficulty of establishing whether such symptoms occur in the great apes is that the core features are language related. Although it can be maintained that homologues in other primates might be manifest as behavioural change e.g. social withdrawal, there is no clear record of such deviations occurring in primate society with the characteristics e.g. age of onset, episodicity of psychotic illness as it occurs in human populations. One answer to the evolutionary paradox is that schizophrenia is ‘ the price that Homo sapiens pays for language ‘ with the implication that psychotic illness reflects species-specific variation relating to those aspects of brain structure that evolved at the point of origin of the species.




Timing of appearance of the difference in the Hominin Lineage as a defined date or a lineage separation event. The point in time associated with lineage separation events may change in the future as the scientific community agrees upon better time estimates. Lineage separation events are defined in 2017 as:

  • the Last Common Ancestor (LCA) of humans and old world monkeys was 25,000 - 30,000 thousand (25 - 30 million) years ago
  • the Last Common Ancestor (LCA) of humans and chimpanzees was 6,000 - 8,000 thousand (6 - 8 million) years ago
  • the emergence of the genus Homo was 2,000 thousand (2 million) years ago
  • the Last Common Ancestor (LCA) of humans and neanderthals was 500 thousand years ago
  • the common ancestor of modern humans was 100 - 300 thousand years ago

Possible Appearance: 
3,000 thousand years ago
Probable Appearance: 
150 thousand years ago
Definite Appearance: 
2 thousand years ago
Background Information: 

The psychoses (sometimes referred to as ‘functional’ to distinguish them from ‘organic’ psychoses such as dementias) constitute the core of serious mental illness, and a major unsolved medical problem. These illnesses account for significant morbidity, including loss of work capacity, and mortality, particularly from suicide, throughout the adult period of life. Treatments are limited. The phenomena of psychosis constitute a major challenge to psychiatric and evolutionary theory.   Psychotic illness is defined by the presence of hallucinations or delusions or thought disorder. Hallucinations are defined as sensory experiences for which no external cause is apparent. Delusions are defined as convictions concerning the external world held in the teeth of evidence to the contrary. A clause that specifies ’in the absence of a social group which shares the beliefs’ is sometimes added to exclude shared religious convictions that might otherwise be considered as ' delusional '. ‘Thought disorder’ is evidenced by speech that is persistently disorganised in sentence structure and comprehensibility.   The above, referred to as ' positive ' symptoms, are contrasted with negative symptoms such as flattening of affect (loss of emotional responsivity) and poverty of speech. Positive symptoms are phenomena abnormal by their presence whereas negative symptoms represent the absence of normal function. The former are more readily and reliably identified than the latter, and are therefore more significant in diagnosis, but the latter contribute substantially to the impairments, and are more closely associated with poor long-term outcome. Positive and negative symptom components have been found to be relatively independent dimensions and may have different pathophysiological bases.   A further part of the diversity associated with the psychoses is the dimension of affect, that is to say the presence of depression and elation. The traditional view, associated with Emil Kraepelin, is that there are two major categorical entities - schizophrenia on the one hand and manic-depressive illness on the other. Increasingly such a dichotomy is questioned, as indeed it was questioned by Kraepelin. Intermediate states, referred to as schizoaffective psychoses, are common. Thus we are dealing with dimensions of variation, not categories. On contemporary estimates there are five such dimensions - positive psychotic symptoms, negative symptoms, disorganisation/thought disorder, depression and elation.

The Human Difference: 

Do such conditions and such variation occur in the great apes? The question is unanswerable because the core symptoms are related to, and expressed in language. Indeed schizophrenia has been described as ‘ price that Homo sapiens pays for language ‘, with the implication that the condition is species-specific and linked to the characteristic that defines the species.
It might be maintained that such a condition in the great apes would be manifest in behaviour, e.g. as withdrawal from the social group. No such records e.g. in the Gombe National Park as evidence of spontaneous mental illness appear to have been made.

Universality in Human Populations: 

The question arises as to the nature of these dimensions. Many environmental variables have been considered as aetiological agents, but none established. On the other hand genetic factors are undoubted but at present ill defined. It appears that the variation is between individuals, and relates to the development of the nervous system. There is also evidence that the variation extends out into the general population, in other words that there are individuals who suffer from symptoms that would be described as psychotic according to the above criteria had those individuals come to the attention of psychiatric services. According to some surveys between 3 to 5% of the general population suffer from psychotic symptoms at some point in their lives. Such syndromes are less severe than those that are treated as illness but nevertheless are associated with economic and biological disadvantage of a similar nature.
The core syndromes are relatively uniform in incidence across populations. So also is a sex difference - onsets are earlier in males and outcome is generally worse than in females, illnesses in males being more likely to be characterised by negative symptoms whereas illnesses in females are more likely to be affective and delusional.
Universal incidence and age of onset, throughout the reproductive age of life, are of particular note when the phenomena of psychosis are considered in an evolutionary context. If we are dealing with variation that is genetic in origin, relates to the development of the nervous system, and is associated with the biological disadvantage (individuals with psychosis are less likely to pass on their genes than the rest of the population) we are faced with a paradox- why are the relevant genes not selected out? The fecundity disadvantage is substantial and associated with a sex difference- males are approximately 70% less likely and females 30% less likely to have children than their peers. The reason is that they are less likely to form an appropriate sexual relationship.

Mechanisms Responsible for the Difference: 

The problem was first clearly identified by Julian Huxley and Ernst Mayr, evolutionary theorists, who proposed that the disadvantage was balanced by a genetic advantage in terms of resistance to wound shock or stress. The problem was correctly identified, but there is no evidence to support the proposed solution. Patients who suffer from psychosis have no particular resistance to stress or injury, and the problem remains a challenge to evolutionary theory.

The significance of the central paradox is emphasised by two further findings: 1) that the spectrum of psychotic illness is similar across populations, as demonstrated in the WHO 10 country study of incidence, and 2) such illness is associated with structural change in the brain. This was first demonstrated by CT scan in 1976, and has been confirmed in many MRI scan studies and at post-mortem. There is a degree of enlargement of the ventricles with a shift upwards of the distribution relative to age matched controls without an increase in variance, a deviation being more marked in samples of individuals with illnesses described as schizophrenic than in samples including affective psychoses. Thus we are dealing with a phenomenon that is characteristic of human populations and associated with uniform changes in brain structure.

Possible Selection Processes Responsible for the Difference: 

Classical linkage and association approaches have not yielded reliable evidence for a specific predisposition to psychosis. One possible reason is that the relevant genes are many and of small effect. Against this argument is the relative uniformity of the spectrum of psychosis, age of onset and the structural change in the brain. A strong case can be made that the variation relates to phylogenetically recent and ontogenetically late aspects of brain development. It has been argued that sex chromosomal change is of particular significance in relation to speciation (Haldane’s rule states that in a hybrid cross when one sex is infertile or unviable it is the heterogametic sex ie in mammals the Y, in birds the W) and also that a genetic determinant of cerebral asymmetry is located on the X and Y chromosomes (see topic Sex Chromosome Aneuploidies). These considerations focus attention on the Xq21.3 to Yp duplication that has now been dated to 6MYA, and that has undergone subsequent change including four deletions and a paracentric inversion in the Y block. Within this homologous block two genes (TGIFLY and PABPC5Y) have been inactivated on or eliminated from the Y, leaving the third Protocadherin11XY (PCDH11XY) apparently viable and expressed from both chromosomes. The sequence has been subject to non-synonymous change with 16 amino-acid substitutions on the Y and 5 on the X. The Y sequence has now been shown to be under positive selection, and one at least of the substitutions on the X (from arginine to cysteine located on the surfac
Thus if the rule holds that speciation events are selectively associated with the sex chromosomes the Yp homologous block has the status of a ‘hominin stratum’ within which genetic change relating to species transitions has been concentrated, and the X copy of the Protocadherin11XY gene pair that has apparently responded to the changes on the Y with sequence changes of its own.
While the original duplication at 6MYA may be speculated to be related to upright walking (bi-pedalism) more recent events including the paracentric inversion are potentially relevant to the transition to modern Homo sapiens and the advent of language. Whatever these may have been they are reflected in the sequence of imperfect homologies between X and Y within this region in modern man.

Such homologies are relevant to the phenomenon of ‘meiotic suppression of unpaired chromosomes’ (MSUC) whereby an epigenetic imprint (probably through phosphorylation, methylation or acetylation of the histones that comprise the structure of the chromosome) is applied to those regions of the X and Y that fail to pair in male meiosis. Since pairing is obligatory within pseudo-autosomal region 1, but irregular (maybe 1 in 40 meioses) within the long arm pseudo-autosomal region 2 it can be seen that pairing within the only partially homologous Xq21.3/Yp11.2 region is likely to be highly stochastic. Such variable pairing will be reflected in variation in the imprint imposed on the paternal X (and perhaps also the Y) to influence expression of PCDH11X and Y in the next generation. Thus variation that surrounds the speciation characteristic is generated that is epigenetic in form. This variation is postulated to account for diversity relating to the neural organisation of language, including the predisposition to psychosis.

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  1. Genetic Markers of Human Evolution Are Enriched in Schizophrenia, Srinivasan, Saurabh, Bettella Francesco, Mattingsdal Morten, Wang Yunpeng, Witoelar Aree, Schork Andrew J., Thompson Wesley K., Zuber Verena, Winsvold Bendik S., Zwart John-Anker, et al. , Biological PsychiatryBiological Psychiatry, 08/2016, Volume 80, Issue 4, p.284 - 292, (2016)
  2. The 'big bang' theory of the origin of psychosis and the faculty of language., Crow, T. J. , Schizophr Res, 07/2008, Volume 102, Issue 1-3, p.31-52, (2008)
  3. Accelerated evolution of Protocadherin11X/Y: a candidate gene-pair for cerebral asymmetry and language., Williams, N. A., Close J. P., Giouzeli M., and Crow T. J. , Am J Med Genet B Neuropsychiatr Genet, 09/2006, Volume 141B, Issue 6, p.623-33, (2006)