Dr.
J. K. Burns
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AN EVOLUTIONARY THEORY OF SCHIZOPHRENIA: CORTICAL CONNECTIVITY, METAREPRESENTATION AND THE SOCIAL BRAIN.
Dr. Jonathan Kenneth Burns
Clinical Lecturer
Department of Psychiatry
University of Edinburgh
Morningside Park
Edinburgh
EH10 5HF
U.K.
Schizophrenia is a
universal disorder with largely genetic aetiology. A theory is proposed
that schizophrenia is a disorder of cortical and specifically fronto-temporal
connectivity that evolved in association with emerging complex neural circuitry
in human ancestors. These circuits evolved under selective pressures involving
group living, and regulate aspects of social cognition such as
metarepresentation and affective responsiveness. Evidence from various
scientific fields suggests that the evolutionary advantages conferred by these
changes rendered the hominid brain vulnerable to insults. I argue that
schizophrenia exists as a costly trade-off in the evolution of social
cognition and the creative mind.
LONG ABSTRACT
Schizophrenia is a
worldwide prevalent disorder with multifactorial but highly genetic aetiology.
Prevalence rates are approximately 1% in most societies surveyed, despite
lowered fertility in affected individuals. Thus it is argued that an
evolutionary advantage exists in genetically related unaffected relatives.
Various theories of ultimate causation of the schizophrenic genotype and Tim
Crow’s hypothesis regarding cerebral asymmetry and language are reviewed and
found wanting. In keeping with available biological and psychological evidence,
an alternative theory of the origins of this disorder is proposed.
Schizophrenia exists as a costly trade off at two stages in the evolution of
metacognition and the social brain. Paleoanthropological and comparative
primate research suggests that hominids evolved complex cortical
interconnectivity (in particular fronto-temporal circuits) in order to regulate
social cognition and the intellectual demands of group living. Ontogenetic
mechanisms underlying this cerebral adaptation rendered the hominid brain
vulnerable to genetic and environmental insults. This is the first trade off
experienced by hominid ancestors. I argue that genetic events occurring prior
to the migration of H. sapiens out of Africa 150 -100 000 years ago gave rise
to a genetic spectrum that, in it’s homozygous form resulted in the
schizophrenic phenotype, while heterozygous ‘schizotypal’ individuals possessed
cognitive advantages that enhanced their relative fitness. Thus schizophrenia
evolved as a trade off firstly in the emergence of complex social cognition and
secondly in the emergence of a phenotype that exhibited unusual creativity and
iconoclasm and may be associated with the great cultural and scientific
advances of human history.
1.
Introduction
“Reasonable people adapt themselves to the world.
Unreasonable people attempt to adapt the world to themselves.
All progress, therefore, depends on unreasonable people.”
[George Bernard Shaw]
Schizophrenia is a complex and widespread disorder, giving rise to a great burden of suffering and impairment in both patients and their families. It is human nature to seek meaning behind experiences and indeed patients with schizophrenia seek meaning in the bizarre and perplexing phenomena of their psychoses. So too, in our scientific endeavour to understand this complex disorder, it is important to undertake a search for the meaning of the existence of schizophrenia in the human species.
In recent years a number of researchers have sought to adopt an evolutionary perspective to explain the continued persistence of clearly maladaptive psychiatric disorders. In the field of schizophrenia research, Tim Crow, John Price, Anthony Stevens and others have pioneered an evolutionary approach to understanding the meaning of this distressing illness. They have asked questions about the evolutionary origins of schizophrenia and about why it is maintained in the human genome.
This paper critically assesses these models drawing on evidence from various fields including psychiatry, psychology, paleoanthropology and primatology, finds them wanting, and proposes an alternative and more integrated theory of the origins of schizophrenia that is in keeping with all the available evidence. The central argument proposed here is that schizophrenia reflects the severe end of a spectrum of disordered fronto-temporal (FT) connectivity, which is related to the evolution of metarepresentation and the ‘social brain’ in the human line. It is argued that schizophrenia exists as a costly trade-off at two stages of cognitive evolution.
I suggest that the first trade-off occurred between 16 and 2 million years ago (mya) when human ancestors evolved complex cerebral interconnectivity and specialised neural circuits in order to regulate social cognition and the intellectual demands of group living. Owing to anatomical constraints on fetal brain size, these changes necessitated the ‘infantalisation’ of the child and the prolongation of brain maturation well into adolescence. This meant that the human brain, with its complex and recently evolved circuitry, became increasingly vulnerable to both genetic and environmental developmental insults. This vulnerability was the trade-off for the advantages gained in social cognition.
The second trade-off occurred approximately 150-100 000 years ago when a genetic mutation resulted in aberrant connectivity in these FT circuits. The exact mechanism responsible at the phenotypic level is debateable and will be discussed in this paper. It is argued that the expression of this genetic change is variable in different individuals and that ‘milder’ expression proved to be adaptive in the environment of evolutionary adaptedness (EEA). Therefore the schizophrenic genotype was retained in the human genome. Hence the disorder we call schizophrenia emerged as a trade-off for the advantages gained by some individuals in the schizotypal spectrum (ie. individuals who share some of the clinical features of schizophrenia such as magical and referential thinking, but never have overt psychosis.)
2. Evolutionary origins of the schizophrenic
genotype
The WHO has undertaken a number of important cross-cultural studies of the epidemiology of schizophrenia. The International Pilot Study of Schizophrenia, conducted in nine countries (World Health Organization 1973) and a later larger study (Sartorius et al 1986) demonstrated remarkable consistency in the prevalence and the core symptoms of the disorder. One of their ‘first-rank’ findings was that the evidence points to a significant genetic component in the transmission of schizophrenia (Jablensky 1988). Other evidence suggests that this is a polygenetic disorder (Kendler et al 2000).
The fact that this disorder is found universally implies that the schizophrenic genotype dates to at least 150-100 000 years ago when the migration of Homo erectus out of Africa occurred (Crow 1995a). A less parsimonious theory would have to argue that there was parallel evolution in geographically separate populations. This is unlikely. There are at least some historical references to schizophrenia-like illnesses in early Islamic, Ayurvedic and Classic societies (Gottesman 1991;Youssef & Youssef 1996) but these obviously post-date the development of written records.
It is a well-accepted fact that schizophrenics have lower fertility (Larson & Nyman 1973) and increased early mortality (Brown 1997). Therefore the disorder is maladaptive and, according to the laws of natural selection (Darwin 1859), should have disappeared from the gene pool long ago. The constant prevalence of core features therefore implies that there is some adaptive advantage conferred by one of two genetic mechanisms: 1) the ‘pleiotropy hypothesis’ - that the gene or genes for the trait/disorder is/are linked to other genes which confer an advantage; or 2) the same genes that cause disorder in some individuals have advantages in others (Cartwright 2001). This might involve either a different combination of genes or different gene expression. The example of sickle cell anaemia is commonly cited where homozygous expression of the genetic defect results in the disease and heterozygous expression confers resistance to malaria. The latter mechanism is preferred again for parsimonious reasons for the purposes of this discussion of schizophrenia.
Tim Crow has proposed that psychotic illness should be viewed as lying on a “continuum of variation” (Crow 1998a;Crow 1995a). It seems that there may be at least two dimensions to this spectrum – one stretching from schizophrenia to the affective psychoses and the other from disorder to trait to ‘normality’. Evidence from neuroimaging and neuropsychology studies suggest that schizotypal people have milder but similar deficits to schizophrenic patients (Buchsbaum et al 1997b;Buchsbaum et al 1997a;Cadenhead et al 1999;Dickey et al 2002). That these deficits are also found in relatives of patients with schizophrenia suggests a genetic cause (Lawrie et al 2001;Byrne et al 1999). This supports the idea of a genetic continuum. Thus those individuals in the spectrum, representing perhaps different expressions or combinations of genes - those individuals we might describe as schizotypal or schizoid for example - could have mild and adaptive traits that were selected for during the EEA. Support for this notion of enhanced fitness in ‘carriers’ comes from recent research by Avila and colleagues that demonstrates an increased number of children in first degree relatives of schizophrenic individuals (Avila et al 2001).
This leads one to considering the ultimate causation of the schizotypal genotype. The focus of most psychiatric research is on proximal causation (e.g. neurotransmitter activity). A number of theories have been proposed over the last 30 years regarding the possible adaptive advantages conferred by the schizophrenic genotype. These include: that the genotype confers some physiological advantage on the individual such as resistance to infection (Carter & Watts 1971) – but there is no evidence for this; that the advantage lies in some aspect of social interaction (Kuttner et al 1967), specifically that the genotype mediates ‘territoriality’ and therefore the survival of the family unit (Kellett 1973); that there is variability in multiple genes that control social skills and personality traits (Farley 1992;Farley 1976); and/or that the genotype is linked with ‘sociality versus asociality’ in the preservation of the individual (Allen & Sarich 1988).
Stevens and Price have argued in their two books, Evolutionary Psychiatry and Prophets, Cults and Madness, for a “group-splitting hypothesis” of schizophrenia (Stevens & Price 1996;Stevens & Price 2000). In the ancestral environment a group would reach a critical size at which it began to outgrow its resources. At this point a schizotypal individual, having undergone a “mazeway resynthesis” and spurred on by his or her iconoclastic ideas and possible ‘voices of the gods’ (Jaynes 2000), would offer a vision of a new and better ‘promised land’ to those who would follow. The shaman of traditional cultures such as the Inuit may be a more recent example of this type of character. The power of the schizotype was such that followers would enter his/her ‘delusional’ world (or at least go along with it) and the group would split. The converted and their leader would either stay and enter into a genocidal conflict for resources with the ‘outgroup’ or set off on a migration, dispersing our ancestors across the planet. Thus the particular personality and behaviour of the schizotype proved adaptive for the group, according to these authors. They cite a number of clearly schizotypal but also paranoid and psychopathic cult leaders such as David Koresh, Jim Jones and Adolf Hitler as examples of this phenomenon in recent times (Storr 1997), and interestingly note that both Koresh and Jones fathered many children – suggesting increased fitness as a result of their schizotypal personalities. The eventual failure of these modern gurus may reflect greater social intolerance and censure relative to the EEA. Emmanuelle Peters has studied members of a number of religious cults in Britain and discovered a high level of near-psychotic delusional beliefs (Peters et al 1999). This suggests that schizotypal traits flourish in cults or that schizotypes flock to them and it may also support the notion that in the ancestral environment, where ‘cults’ may have had a greater impact on society, these traits may have played a very significant role in the splitting and dispersal of people.
Finally, many writers and thinkers, both in remote and recent times, have linked ‘madness’ to creativity, genius and religiosity. John Dryden wrote:
“Great wits are sure to madness near alli’d
And thin partitions do their bounds divide.”
Karlsson demonstrated an increased incidence of psychotic illnesses including schizophrenia in a cohort of particularly gifted artists, philosophers and politicians (Karlsson 1973;Karlsson 1984;Karlsson 2001). The Nobel Laureate, John Nash springs to mind as a contemporary example, while an attempted reading of Ullyses by James Joyce must raise some questions as to the mental state of this great author. Jamison has pointed out the high incidence of mood disorders in creative individuals such as Schumann, Shelley, Byron and Van Gogh (Jamison 1993;Jamison 1995), while Baron-Cohen and colleagues, in a fascinating study conducted recently at Cambridge University (UK) have demonstrated higher than expected scores for Asperger syndrome/ high-functioning autism among scientists and mathematicians (Baron-Cohen et al 2001). Others who have written about the association between mental illness and creativity/genius include Parfitt (Parfitt 1956), Maudsley (Maudsley 1908), Post (Post 1994), O’Reilly (O'Reilly et al 2001), Nettle (Nettle 2001) and Horrobin (Horrobin 2001;Horrobin 1998).
In attempting to summarise all of these theories about ultimate causation and the schizophrenic genotype, two central themes emerge. The first is that of the social role of the schizotype. It seems that in one way or another the schizotype, by virtue of his/her particular personality structure, is thought to perform the social function of ‘spacing’ individuals – that is, facilitating and maintaining distance between individuals and between groups. The second theme is that of unusual and perhaps iconoclastic giftedness, without which culture may never have evolved and science and art may never have existed.
Obviously all of this is speculative and limited by its untestable nature but I would contend that there is worth in such speculation, for it challenges our current thinking and may expand our areas of scientific enquiry. Indeed, the creativity in science is in developing ingenious methods of testing what superficially appears unamenable to empirical investigation.
In summary then: those on the continuum with a partial or schizotypal genotype may be adaptively advantaged and responsible for maintaining the genes in the human gene pool; while those with a fuller expression or combination of genes and/or environmental triggers (drugs, life events, head trauma, etc.) may develop schizophrenia. This hypothesis would explain the apparent variability in the clinical presentation of schizophrenia and ‘schizophrenia-spectrum disorders’ (SSD, i.e. a spectrum of clinical presentations that share some features of schizophrenia but insufficient for a diagnosis, and may or may not manifest other symptoms e.g. affective or autistic). Predictions one might make therefore are: 1) that schizotypy/SSD is more common than schizophrenia; 2) that it is especially evident in geniuses; and 3) that it is especially evident in eccentric ‘outcasts’ of society. It is also important to consider that schizotypy may well have been particularly adaptive during the EEA and have lost some of its impact in this very different modern world.
3. What is the schizophrenic phenotype?
Several authors have attempted to address the question of what evolutionary mechanisms might account for the anatomical and cognitive findings in schizophrenia. Tim Crow has pioneered this quest, arguing that schizophrenia results from the evolution of brain asymmetry and specialisation of the language area on the left side (Crow 1997a;Crow 1995a;Crow 1991). The schizophrenia gene is XY-linked and is propagated by sexual selection (Crow 1993). He identifies the corpus callosum as the primary site of pathology (Crow 1997b;Crow 1998b).
While agreeing with Crow that an evolutionary perspective is essential in trying to understand this most human of disorders, I argue that FT dysconnectivity is better supported, relating it to the evolution of metarepresentation and social cognition and subject to the selection pressures of group living.
3.1. A disorder
of metarepresentation
The concept of a ‘Theory of Mind’ (ToM) has become increasingly popular in attempting to describe the cognitive deficits in schizophrenia. The term was first used in association with autism, where the inability of these individuals to attribute mental states to others and to “mind-read” was described as an abnormal or absent ToM