©
Psychiatric Times. All rights reserved.
Do Lower IQ Scores Predict Schizophrenia?
by
Janet Munro, M.B.B.S., M.R.C.Psych.
Psychiatric Times 
November 2003 Vol. XX Issue 12
In the late 19th century, German psychiatrist Emil
Kraepelin, M.D., described dementia praecox, an illness of
organic origin that began during puberty (praecox) and led
to a progressive deterioration of intellectual functioning
(dementia). Eugen Bleuler, M.D., coined the term
schizophrenia to replace dementia praecox, as he observed
that some patients recovered without serious intellectual
decline and others developed the illness beyond their
adolescent years. The DSM-IV subtypes are defined by
the predominant symptomology, and intellectual function is
not a feature of current classifications. However, an
argument exists that cognitive dysfunction is the core of
the disorder and thus, schizophrenia is better characterized
by cognitive deficits than by symptoms (Elvevag and
Goldberg, 2000).
Etiology
Kraepelin and Bleuler recognized that schizophrenia often
is preceded by non-psychotic behavioral abnormalities.
Despite this recognition of premorbid abnormalities, the
relationship between the child and adult illness received
scant attention until much later.
The concept of neurodevelopmental schizophrenia proposes
that some abnormality in brain development, possibly
occurring in utero, causes delay or deviance in the
development of childhood skills, later cognitive deficits,
and behavioral and social deviance, and--at some critical
developmental point--major psychopathology and psychosis
(Murray, 1994). Critical review and evidence support this
neurodevelopmental hypothesis at all life stages (Marenco
and Weinberger, 2000).
Factors such as the lower IQ of patients with
preschizophrenia, regarded as an expression of impaired
early brain development (Murray and Lewis, 1987; Weinberger,
1987), could be controlled by genetic (Jones and Murray,
1991) or environmental (Murray et al., 1988) factors. Many
biological and non-biological environmental components have
been implicated in the etiology of schizophrenia (McDonald
and Murray, 2000; Tsuang, 2000).
Evidence suggests that a liability to schizophrenia is
genetically transmitted by a number of genes of relatively
small effect, and genes have been implicated at several
chromosomal loci (Waterwort et al., 2002). Each
susceptibility gene results in slight deviations from
normality that may be inconsequential when occurring
individually (e.g., schizotypal personality, minor cognitive
difficulties), but have more dramatic impact when inherited
in number and have devastating consequences when compounded
by environmental hazards.
If polygenic factors predominate in determining the low
premorbid IQ in schizophrenia, then arguably, patients'
relatives would also have lower IQ scores than controls.
However, if environmental factors predominate, then IQ
scores of relatives and controls would be similar. Most
studies (Egan et al., 2001; Faraone et al., 2000; Krabbendam
et al., 2001) favor the first hypothesis, although some
favor the second (Gilvarry et al., 2000). Faraone et al.
(2000) postulated that the neuropsychologic impairments in
relatives are stable traits caused by the same genes
predisposing to schizophrenia, as relatives from multiplex
families (having two or more members with schizophrenia)
have more neuropsychologic impairment than relatives from
simplex families (with just one affected member).
Development of Schizophrenia
Formal methods for assessing IQ were not available to the
earliest theorists who described schizophrenia. In more
recent years, IQ tests have provided an overall single
descriptive measure of cognitive competence that is
predictive of performance on many other neuropsychological
measures (Leckliter and Matarazzo, 1989) and provides clues
to the etiology of schizophrenia. More diverse aspects of
cognitive function are investigated by more detailed tests
(Sparrow and Davis, 2000). Patients with schizophrenia,
regardless of IQ, have different neuropsychological profiles
than controls (Kremen et al., 1998).
While a cognitive deficit is a core feature of
schizophrenia, the development of the deficit and its
relation to symptoms is not fully understood (Gold et al.,
1999). Adult patients with schizophrenia generally show a
deficit in IQ score in comparison to the normal population
(Heinrichs and Zakzanis, 1998), but at what life stage and
at what point in the process of schizophrenia does the loss
of intellectual functioning occur?
Some components of the cognitive deficit are present
during childhood (Jones et al., 1994), with IQ deficits
reported as early as 7 years of age (Goldstein et al.,
2000). Children who develop schizophrenia typically have
lower IQ scores premorbidly (by one-third to one-half a
standard deviation) than unaffected children (David, 1998;
Davidson et al., 1999).
Substantial cognitive deficits exist early in the course
of schizophrenia (Hoff et al., 1992; Mohamed et al., 1999),
with first-episode patients demonstrating similar
impairments to patients with established schizophrenia
(Addington and Addington, 2002). More controversial are the
issues of the intransience of IQ over time and at which
point any drop in IQ occurs. The stability of broad
cognitive deficits after the onset of schizophrenia is
confirmed in a review that concludes that cognitive deficits
are relatively stable over long periods and there is no
support for a longitudinal decline (Rund, 1998). Gold et al.
(1999) and Hoff et al. (1999) reported that over the first
five years of illness, cognitive function does not
deteriorate. Russell et al. (1997) found no significant
differences between the child and adult IQ scores at 19-year
follow-up of a cohort with schizophrenia. Other studies of
adult patients have found an intellectual decline from
premorbid performance (David, 1998; Kremen et al., 1998;
Sheitman et al., 2000). It is difficult to execute studies
that provide a definitive answer to this question; the tools
used to measure or estimate premorbid IQ are imperfect and
the timing and setting of the psychological testing critical
(Russell et al., 2000; Sheitman et al., 2000). While
Sheitman et al. (2000) reported a decline in intellectual
function, premorbid test scores were highly predictive of
postmorbid functioning. In a heterogeneous disorder of
multifactorial etiology, it could be argued that a uniform
deterioration in intellectual functioning is surprising and
possibly explained by inconsistencies in the measurement of
premorbid IQ. The decline in IQ of patients with
childhood-onset schizophrenia during adolescence reflects an
inability to acquire new information, as opposed to a
dementia (Bedwell et al., 1999).
Cosway et al. (2000) reported that the development of
psychotic symptoms is preceded by a decline in IQ. Fuller et
al. (2002) reported that deterioration in scholastic
performance occurs at ages 13 and 16 and "may be a precursor
to the cognitive impairment seen during the first episode of
illness." Meltzer et al. (1999) reported that any decline in
cognition occurs during the prodromal period, the first
psychotic episode or both.
Outcome
The age of onset of schizophrenia is usually but not
always reported as being positively associated with IQ
(Aylward et al., 1984; Gilvarry et al., 2000; Johnstone et
al., 1995). Aylward et al. (1984) reviewed the literature
investigating the relationship between IQ and outcome and
reported a consistent relationship between higher IQ and
positive outcome: measured by incidence of remission, length
of hospitalization, psychiatric ratings and social outcome.
More recently, chronic cognitive impairment was reported to
be strongly predictive of poor social functioning in
schizophrenia (Liddle, 2000) and low IQ predictive of poor
outcome (Roff, 2001). However, broader cognitive measures
have been found to be independent of severity of the
disorder and symptom presentation (Seaton et al., 1999).
If pre-psychotic abnormalities in schizophrenia were the
manifestations of the disease itself, then severe
abnormalities would predict a severe disease, which would
predict a poor outcome. On the other hand, if pre-psychotic
abnormalities are merely markers of vulnerability to
schizophrenia, then severe vulnerability could result in a
mild disease and have little relationship to outcome. Munro
et al. (2000) undertook an explorative long-term follow-up
study of 51 subjects referred to child or adolescent
psychiatric services and subsequently treated for
schizophrenia in adulthood. These patients had a childhood
IQ assessment and were followed up for a mean of 21 years
after presentation. Childhood IQ was strongly predictive of
social outcome and mental health service utilization but not
clinical symptoms. No other factors (age at onset, sex,
obstetric complications, family history) predicted outcome.
The impact of IQ on outcome could be explained by the
assumption that in domains where the subject has some
control living independently, or having a relationship or
job a higher IQ results in a higher level of functioning.
However, IQ did not predict outcome in terms of psychiatric
morbidity, indicating that a higher IQ does not protect
against psychiatric symptoms. The findings are compatible
with the theory that the pre-psychotic abnormalities are the
manifestations of the illness itself.
Poor motivation or negative symptoms occurring in chronic
schizophrenia are not the major causal factors of the
neurocognitive deficits, but they may impact assessment.
There is a relationship between low premorbid IQ and a
preponderance of negative symptoms (Andreasen and Olsen,
1982; Tamminga et al., 1998). Voruganti et al. (1997)
reported that patients with predominantly negative symptoms
exhibit more severe neurocognitive deficits. Low IQ may be a
confounding variable in the reporting of positive symptoms
(Nelson et al., 1990).
Within the population there is an essentially normal
distribution of IQ, which has a role in determining an
individual's outcome. In normal subjects, IQ is under a high
degree of polygenic control (Plomin, 1994), so family
members tend to have similar IQ. Environmental factors also
play a role in determining IQ. Individuals born prematurely,
of low birth weight or with other obstetric hazards have
lower IQ than the general population (Litt et al., 1995;
Pharoah et al., 1994; Waber and McCormick, 1995). Obstetric
complications may contribute to the low premorbid IQ in
schizophrenia (Gilvarry et al., 2000). The relationship
between IQ, schizophrenia and outcome is undoubtedly
complex. However, if patients with low IQ are destined to
achieve the worst social prognosis and be the most
service-dependent, then resources, support and education can
be diverted to optimize outcome. Future studies
investigating IQ as a prognostic indicator should
distinguish between clinical and non-clinical outcomes and
consider the role of low IQ in symptom ratings and the
impact of specific cognitive deficits on different areas of
functioning (Dickinson and Coursey, 2002). Other factors
contributing to overall intellectual impairment and
cognitive function, for example, atypical antipsychotics
(Fujii et al., 1997; Good et al., 2002; Velligan and
Bow-Thomas, 1999) and the duration of untreated psychosis
(Amminger et al., 2002) should also be considered.
Dr. Munro is a clinical research psychiatrist in
the institute of psychiatry at King's College Hospital in
London.
References
Addington J, Addington D (2002), Cognitive functioning in
first-episode schizophrenia. J Psychiatry Neurosci
27(3):188-192.
Amminger GP, Edwards J, Brewer WJ et al. (2002), Duration
of untreated psychosis and cognitive deterioration in
first-episode schizophrenia. Schizophr Res
54(3):223-230.
Andreasen N, Olsen S (1982), Negative v positive
schizophrenia. Definition and validation. Arch Gen
Psychiatry 39(7):789-794.
Aylward E, Walker E, Bettes B (1984), Intelligence in
schizophrenia: meta-analysis of the research. Schizophr Bull
10(3):430-459.
Bedwell JS, Keller B, Smith AK et al. (1999), Why does
postpsychotic IQ decline in childhood-onset schizophrenia?
Am J Psychiatry 156(12):1996-1997.
Cosway R, Byrne M, Clafferty R et al. (2000),
Neuropsychological change in young people at high risk for
schizophrenia: results from the first two neuropsychological
assessments of the Edinburgh High Risk Study. Psychol Med
30(5):1111-1121.
David A (1998), Schizophrenia and intellectual decline.
Am J Psychiatry 155(11):1634-1635; author reply 1636-1637
[letter].
Davidson M, Reichenberg A, Rabinowitz J et al. (1999),
Behavioral and intellectual markers for schizophrenia in
apparently healthy male adolescents. Am J Psychiatry
156(9):1328-1335 [see comments].
Dickinson D, Coursey RD (2002), Independence and overlap
among neurocognitive correlates of community functioning in
schizophrenia. Schizophr Res 56(1-2):161-170.
Egan MF, Goldberg TE, Gscheidle T et al. (2001), Relative
risk for cognitive impairments in siblings of patients with
schizophrenia. Biol Psychiatry 50(2):98-107.
Elvevag B, Goldberg TE (2000), Cognitive impairment in
schizophrenia is the core of the disorder. Crit Rev
Neurobiol 14(1):1-21.
Faraone SV, Seidman LJ, Kremen WS et al. (2000),
Neuropsychologic functioning among the nonpsychotic
relatives of schizophrenic patients: the effect of genetic
loading. Biol Psychiatry 48(2):120-126.
Fujii DE, Ahmed I, Jokumsen M, Compton JM (1997), The
effects of clozapine on cognitive functioning in
treatment-resistant schizophrenic patients. J
Neuropsychiatry Clin Neurosci 9(2):240-245.
Fuller R, Nopoulos P, Arndt S et al. (2002), Longitudinal
assessment of premorbid cognitive functioning in patients
with schizophrenia through examination of standardized
scholastic test performance. Am J Psychiatry
159(7):1183-1189.
Gilvarry C, Takei N, Russell A et al. (2000), Premorbid
IQ in patients with functional psychosis and their
first-degree relatives. Schizophr Res 41(3):417-429.
Gold S, Arndt S, Nopoulos P et al. (1999), Longitudinal
study of cognitive function in first-episode and
recent-onset schizophrenia. Am J Psychiatry
156(9):1342-1348.
Goldstein JM, Seidman LJ, Buka SL et al. (2000), Impact
of genetic vulnerability and hypoxia on overall intelligence
by age 7 in offspring at high risk for schizophrenia
compared with affective psychoses. Schizophr Bull
26(2):323-334.
Good KP, Kiss I, Buiteman C et al. (2002), Improvement in
cognitive functioning in patients with first-episode
psychosis during treatment with quetiapine: an interim
analysis. Br J Psychiatry Suppl 43:s45-s49.
Heinrichs RW, Zakzanis KK (1998), Neurocognitive deficit
in schizophrenia: a quantitative review of the evidence.
Neuropsychology 12(3):426-445.
Hoff AL, Riordan H, O'Donnell DW et al. (1992),
Neuropsychological functioning of first-episode
schizophreniform patients. Am J Psychiatry
149(7):898-903.
Hoff AL, Sakuma M, Wieneke M et al. (1999), Longitudinal
neuropsychological follow-up study of patients with
first-episode schizophrenia. Am J Psychiatry
156(9):1336-1341.
Johnstone EC, Frith CD, Lang FH, Owens DG (1995),
Determinants of the extremes of outcome in schizophrenia. Br
J Psychiatry 167(5):604-609.
Jones PB, Guth C, Lewis SW, Murray RM (1994), Low
intelligence and poor educational achievement precede early
onset schizophrenic psychosis. In: The Neuropsychology of
Schizophrenia, David AS, Cutting JC, eds. London: Psychology
Press, pp131-144.
Jones P, Murray RM (1991), The genetics of schizophrenia
is the genetics of neurodevelopment. Br J Psychiatry
158:615-623.
Krabbendam L, Marcelis M, Delespaul P et al. (2001),
Single or multiple familial cognitive risk factors in
schizophrenia? Am J Med Genet 105(2):183-188.
Kremen WS, Buka SL, Seidman LJ et al. (1998), IQ decline
during childhood and adult psychotic symptoms in a community
sample: a 19-year longitudinal study. Am J Psychiatry
155(5):672-677.
Leckliter IN, Matarazzo JD (1989), The influence of age,
education, IQ, gender, and alcohol abuse on Halstead-Reitan
Neuropsychological Test Battery performance. J Clin Psychol
45(4):484-512.
Liddle PF (2000), Cognitive impairment in schizophrenia:
its impact on social functioning. Acta Psychiatr Scand Suppl
400:11-16.
Litt R, Joseph A, Gale R (1995), Six year
neurodevelopmental follow-up of very low birthweight
children. Isr J Med Sci 31(5):303-308 [see comment].
Marenco S, Weinberger DR (2000), The neurodevelopmental
hypothesis of schizophrenia: following a trail of evidence
from cradle to grave. Dev Psychopathol 12(3):501-527.
McDonald C, Murray RM (2000), Early and late
environmental risk factors for schizophrenia. Brain Res
Brain Res Rev 31(2-3):130-137.
Meltzer HY, Park S, Kessler R (1999), Cognition,
schizophrenia, and the atypical antipsychotic drugs. Proc
Natl Acad Sci U S A 96(24):13591-13593 [comment].
Mohamed S, Paulsen JS, O'Leary D et al. (1999),
Generalized cognitive deficits in schizophrenia: a study of
first-episode patients. Arch Gen Psychiatry 56(8):749-754.
Munro JC, Russell AJ, Murray RM et al. (2002), IQ in
childhood psychiatric attendees predicts outcome of later
schizophrenia at 21 year follow-up. Acta Psychiatr Scand
106(2)139-142.
Murray RM (1994), Neurodevelopmental schizophrenia: the
rediscovery of dementia praecox. Br J Psychiatry Suppl
25:6-12.
Murray RM, Lewis SW (1987), Is schizophrenia a
neurodevelopmental disorder? Br Med J (Clin Res Ed)
295(6600):681-682.
Murray RM, Lewis SW, Owens MJ (1988), The
neurodevelopmental origins of dementia praecox. In:
Schizophrenia: The Major Issues, Bebbington P, McGuffin P,
eds. Oxford, U.K.: Heinemann.
Nelson HE, Pantelis C, Carruthers K et al. (1990),
Cognitive functioning and symptomatology in chronic
schizophrenia. Psychol Med 20(2):357-365.
Pharoah PO, Stevenson CJ, Cooke RW, Stevenson RC (1994),
Clinical and subclinical deficits at 8 years in a
geographically defined cohort of low birthweight infants.
Arch Dis Child 70(4):264-270.
Plomin R (1994), Genetics and Experience: The Interplay
Between Nature and Nurture. Thousand Oaks, Calif.: Sage
Publications.
Roff JD (2001), Comparison of childhood problem behaviors
in boys with subsequent schizophrenic, antisocial, and good
adult outcomes. Psychol Rep 89(3):633-640.
Rund BR (1998), A review of longitudinal studies of
cognitive functions in schizophrenia patients. Schizophr
Bull 24(3):425-435.
Russell AJ, Munro JC, Jones PB et al. (1997),
Schizophrenia and the myth of intellectual decline. Am J
Psychiatry 154(5):635-639 [see comments].
Russell AJ, Munro J, Jones PB et al. (2000), The National
Adult Reading Test as a measure of premorbid IQ in
schizophrenia. Br J Clin Psychol 39(pt 3):297-305.
Seaton BE, Allen DN, Goldstein G et al. (1999), Relations
between cognitive and symptom profile heterogeneity in
schizophrenia. J Nerv Ment Dis 187(7):414-419.
Sheitman BB, Murray MG, Snyder JA et al. (2000), IQ
scores of treatment-resistant schizophrenia patients before
and after the onset of the illness. Schizophr Res
4(2-3)6:203-207.
Sparrow SS, Davis SM (2000), Recent advances in the
assessment of intelligence and cognition. J Child Psychol
Psychiatry 41(1):117-131.
Tamminga CA, Buchanan RW, Gold JM (1998), The role of
negative symptoms and cognitive dysfunction in schizophrenia
outcome. Int Clin Psychopharmacol 13(suppl 3):S21-S26.
Tsuang M (2000), Schizophrenia: genes and environment.
Biol Psychiatry 47(3):210-220.
Velligan DI, Bow-Thomas CC (1999), Executive function in
schizophrenia. Semin Clin Neuropsychiatry 4(1):24-33.
Voruganti LN, Heslegrave RJ, Awad AG (1997),
Neurocognitive correlates of positive and negative syndromes
in schizophrenia. Can J Psychiatry 42(10):1066-1071 [see
comment].
Waber DP, McCormick MC (1995), Late neuropsychological
outcomes in preterm infants of normal IQ: selective
vulnerability of the visual system. J Pediatr Psychol
20(6):721-735.
Waterwort DM, Bassett AS, Brzustowicz LM (2002), Recent
advances in the genetics of schizophrenia. Cell Mol Life Sci
59(2):331-348.
Weinberger DR (1987), Implications of normal brain
development for the pathogenesis of schizophrenia. Arch Gen
Psychiatry 44(7):660-669.
