Impact of Substance
VOL. 16, NO. 1, 1990
Abuse on the Course
and Outcome of
Schizophrenia
by Winston M. Turner and Abstract
Ming T. Tsuang
Numerous pharmacological agents
have been shown to have powerful
effects on cognitive behavior.
Schizophrenia-like reactions have
been reported in some instances.
There have also been persistent
reports of drug abuse among
psychiatric patients before and dur-
ing hospitalization. These phenom-
ena have led to speculation that
psychoactive substances are affect-
ing the course and outcome of
psychiatric illnesses, and in par-
ticular, schizophrenia. This report
first reviews the evidence for
psychotomimetic effects of various
drugs, and then focuses on reports
of the effect that substance abuse
has on the course of schizophrenia
and long-term outcome. The evi-
dence to date indicates that there is
a need for a large epidemiological
analysis of the interplay between
drug abuse and schizophrenia as
well as more intensive case studies
of afflicted individuals. This
discussion concludes with sugges-
tions for improved research
methods and two designs for future
investigations.
Previous investigations have in-
dicated that psychopathology may
increase the incidence of specific
types of drug abuse, and drug abuse
may exacerbate psychiatric distur-
bances (McLellan and Druley 1977;
Schneier and Siris 1987). Further-
more, psychoactive substances have
been implicated in the early onset of
psychosis (Breakey et al. 1974;
Tsuang et al. 1982).
Psychotomimetic Drugs
There is considerable evidence that
certain psychoactive substances can
87
mimic or aggravate psychotic symp-
toms. This has been viewed as both
a benefit (enabling researchers to
control and study psychotic
episodes) and a hindrance (con-
founding both the initial assessment
of presenting symptoms and the
course of treatment) to our under-
standing of schizophrenia. It also
raises questions about the role that
drugs may play in augmenting latent
schizophrenic disorders in sus-
ceptible individuals.
Cole and Katz (1964) examined the
psychotomimetic properties of
^-lysergic acid diethylamide (LSD),
concluding that it produces a "state
which is similar but not identical to
naturally occurring schizophrenia"
(p. 758). They discussed LSD and its
derivatives as both obstacles for
diagnosis and as therapeutic agents.
While there was initial hope that
controlled examination of psychotic
states might help to understand
those similar hallucinogenic states
found in schizophrenia, the authors
concluded that there is insufficient
evidence to support the extensive
use of the drugs, but expressed
hope that their use in carefully con-
trolled hospital settings could pro-
vide insights into the course of
schizophrenia. The work of
Janowsky and Davis (1976) provides
some justification for the use of
stimulants as psychodiagnostic
agents in view of their ability to
enhance psychotic symptoms under
controlled conditions, although
these authors also advocate more
conservative strategies for obtaining
Reprint requests should be sent to Dr.
M.T. Tsuang, Psychiatric Service (116-A),
Section on Epidemiology and Genetics,
Brockton/West Roxbury VA Medical
Center, 940 Belmont St., Brockton,
MA 02401.
88
similar information about
schizophrenic symptomatology.
An alternative approach has been
to compare the psychotic states pro-
duced by hallucinogenic drugs to
those reported by drug-free
schizophrenic patients. Bell (1965)
reviewed published reports of am-
phetamine psychosis and carefully
noted similarities and differences
between these and the subjective
reports of hallucinations given by
schizophrenic patients. The most
obvious difference involves the
duration of the hallucinations. Drug-
induced symptoms usually clear
within 10 days of withdrawal from
the drug, while schizophrenic
hallucinations usually last for
months. The quality of the halluci-
nations is also different, with visual
images dominating in the drug-
induced cases, which is not com-
mon in schizophrenia.
Stone (1973) reviewed the research
literature involving the case histories
of patients who abused drugs and
had schizophrenia. He distinguish-
ed between drug-induced drug-
aggravated psychoses and drug use
that accompanied preexisting
schizophreniform reactions. He
argued for a multidimensional
diagnostic approach to help to
distinguish among these possibili-
ties. His schema involved the
presence or absence of a series of
genetic, constitutional, organic, and
psychological factors. The pattern of
these factors indicated predisposi-
tions to adverse reactions to
stimulant drugs.
Negrete et al. (1986) reported an
enhancement of psychotic symp-
toms (delusional and hallucinatory
activity) among schizophrenic pa-
tients who use marijuana. The
authors suggested that the observed
effects may be due to (1) an exacer-
bation of psychotic symptoms, (2) a
secondary toxic psychosis superim-
posed on the schizophrenic state, or
(3) a diminution of the effectiveness
of the antipsychotic medication that
the patients were taking. Once
again, the data were insufficient to
differentiate between these alter-
native mechanisms.
O'Brien et al. (1984) reported high
frequencies of psychiatric diagnoses
among opioid users in treatment,
but relatively low levels of psychosis
or schizophrenia. McLellan et al.
(1979) found psychosis was much
more prominent among stimulant
users.
Although alcohol is apparently not
the drug of choice among schizo-
phrenic patients, its ready availabili-
ty and licit status make it a fre-
quently abused substance. Schuckit
(1983) noted that primary alcoholism
can mimic most psychotic disorders,
and secondary alcohol abuse can ac-
centuate psychotic symptoms. He
advocated for routine psychiatric
assessments of all alcoholism pa-
tients and, conversely, alcoholism
screens for all psychiatric
admissions.
Drugs as Precipitants of
Psychosis
Investigations of the co-occurrence
of drug abuse and schizophrenia
should determine the specific
substances being abused, as well as
the quantity and frequency of abuse.
That history must then be temporal-
ly related to the course of the
psychotic illness. This procedure is
essential for determining whether
the observed substance abuse
among schizophrenic patients (1)
precedes the onset of psychopath-
ology and is therefore either a
precipitant or a cause; (2) follows the
onset of symptoms and may repre-
SCHIZOPHRENIA BULLETIN
sent an attempt to self-medicate or
ameliorate symptoms; or (3) merely
accompanies the disorder and is not
directly related to the clinical path-
ology, though it could still affect the
course of the illness. Relatively few
studies have adequately addressed
this problem. Previous findings are
equivocal, providing some evidence
to support each of the three
hypotheses.
Researchers have stressed the in-
creased vulnerability of drug
abusers to psychotic episodes. For
instance, Hensala et al. (1967) in-
vestigated the role of LSD in trigger-
ing psychotic episodes and hospital-
izations. They examined a broad
spectrum of variables, including
demographic characteristics, family
history, and psychosocial adjust-
ment as well as drug involvement.
They concluded that in only 25 per-
cent of the cases investigated was
LSD directly related to the index
hospitalization. In the remaining
cases, poor premorbid adjustment,
high-risk family history, and exten-
sive substance abuse were associ-
ated with an increased risk for
hospitalization.
Breakey et al. (1974) investigated
the drug usage and premorbid per-
sonality of hospitalized schizo-
phrenic patients and reported that
those who used drugs had a signifi-
cantly earlier age of onset of symp-
toms. Furthermore, they were more
likely to be free of personality
disorders before their psychosis
than were the nondrug-using
psychotic subjects. They concluded
that the drugs had a precipitating
role among individuals who were
"somewhat less constitutionally
vulnerable" to schizophrenia
(p. 260). Similarly, Tsuang et al.
(1982) reported a significantly earlier
onset of psychiatric illness and first
psychiatric hospitalizations among
VOL. 16, NO. 1, 1990
long-term drug-abusing psychotic
patients when compared to non-
drug-abusing schizophrenic or
atypical schizophrenic patients.
Bowers and colleagues (Glass and
Bowers 1970; Bowers 1972, 1977;
Bowers and Swigar 1983; Bowers
and Wing 1983) also investigated the
premorbid personality traits and
family history of long-term hallu-
cinogenic drug users who suffer
from chronic psychotic episodes.
They concluded that susceptibility to
drug-induced psychosis is frequent-
ly associated with an early develop-
ment that is relatively free of
personality disturbance (Glass and
Bowers 1970; Bowers 1972), but is
more likely to be characterized by a
reluctance to deal with life stresses
(Glass and Bowers 1970). They fur-
ther noted a genetic predisposition,
characterized by increased rates of
parental psychiatric disorders
(Bowers 1977; Bowers and Swigar
1983). The relationship between
male susceptibility to drug-induced
psychosis and parental history of
psychiatric disorders was found to
be reciprocal, such that those "with
a positive family history appear
capable of becoming psychotic in
association with relatively small
amounts of hallucinogen use"
(Bowers and Swigar 1983, p. 95). An
extensive study by Vardy and Kay
(1983) found essentially no dif-
ferences in premorbid personality
among victims of LSD psychosis,
but extensive family histories of
psychosis (13.5 percent), suicides (77
percent), and alcoholism (30.8
percent).
Drug Abuse at Time of
Admission
A number of authors have examined
the rates of use and abuse observed
at the time of hospital admissions.
Crowley et al. (1974) found that
more than one-third of a sample of
admissions to an adult psychiatric
unit of a university hospital reported
drug abuse problems, while nearly
one-half had psychoactive drugs in
their urine at the time of admission.
Within their small sample (n = 50),
the schizophrenic patients (22 per-
cent) had relatively low rates of drug
use. Similarly, Fisher et al. (1975)
reported that one-third of their
psychiatric hospital admissions
(diagnoses not reported) acknowl-
edged previous drug use, and ap-
proximately half of the admitted
drug users were currently abusing
illicit drugs.
Richard et al. (1985) found a
relatively low (11 percent) rate of
drug use just before hospitalization,
similar to the 8 percent found by
Crowley et al. (1974). Contrary to the
findings of Crowley et al., Richard et
al. reported that their schizophrenic
patients acknowledged drug use
significantly more often than did
their nonschizophrenic patients.
Cohen and Klein (1970) examined
the drug usage and diagnoses of
young (under 25 years old) psychi-
atric admissions and found that 26
percent of the moderate drug users,
but only 5 percent of the extreme
drug users, had a schizophrenic
diagnosis.
These data indicate significant
rates of drug usage among schizo-
phrenic patients before their admis-
sion to treatment, but not necessar-
ily at a rate exceeding that found
among other diagnostic categories.
While most of these studies acknowl-
edge an apparent interaction between
drug abuse and psychosis, none
succeeded in clarifying the relation-
ship between drug use and the
89
onset of psychotic symptoms.
Drug Abuse Among Hospital-
ized Psychiatric Patients
Substance abuse is widespread
among psychiatrically impaired in-
dividuals. Those psychotic patients
who are also addicted to drugs pre-
sent a unique challenge to treatment
facilities, and many receive treat-
ment for one or the other disorder,
but rarely do both conditions receive
specialized services (Pinsker 1983).
While the rate of abuse among
schizophrenic patients appears to be
similar to that found among patients
with other diagnoses, the specific
drugs of choice have been shown to
differ by diagnosis. The interaction
of drug abuse and schizophrenia is
poorly understood, although
numerous authors have called for
more research investigations of dual-
diagnosis patients.
McLellan et al. (1978) found that
nearly 60 percent of patients inter-
viewed acknowledged use of
alcohol, drugs, or both while in the
hospital. Similarly, Alterman et al.
(1980, 1981, 1982) found that a
substantial number of patients had a
history of drug abuse, and over half
of them had used drugs in the
hospital. Alcohol abuse appeared to
be more prevalent among hospital-
ized patients with a diagnosis of
paranoid schizophrenia than among
patients with other diagnoses.
Hasin et al. (1985) examined rates
of alcohol and drug abuse among a
large sample (n = 835) of inpatient
subjects with affective disorders.
Using relatively conservative ratings,
they found nearly 23 percent of the
subjects to have serious alcohol
dependence problems, and 9 per-
cent to have serious drug problems
during their current affective
90
episode. Unfortunately, their data
did not differentiate rates among
schizophrenic patients.
Substance abuse has also been
noted as a problem among psychi-
atric patients within rehabilitation
treatment settings. Straussman
(1985) noted significant alcohol
problems among members of a
psychosocial club, over half (7 of 13)
of whom had schizophrenia. In a
therapeutic community, where the
most common presenting problem
was personality disorders, drug
abuse was also found in 67 percent
of admissions (Jainchill et al. 1986).
Similarly, Lett (1987) reported high
rates of drug abuse among schizo-
phrenic patients in inpatient as well
as psychiatric rehabilitation facilities.
Substances Abused by
Schizophrenic Patients
The co-occurrence of substance
abuse and mental illness has been
well documented, but relatively few
authors have focused specifically on
schizophrenic patients. Freed (1975)
conducted a comprehensive review
of the early literature on alcoholism
and schizophrenia, and found few
conclusive research findings despite
the high co-occurrence of the two
disorders. Among his findings was
evidence that "alcoholism masks
schizophrenia rather than vice
versa" (p. 855), that alcohol abuse is
more likely to follow the onset of
schizophrenic symptoms than to
precede them, and "a not insignifi-
cant proportion of schizophrenics
are intemperate and. . . many
alcoholics suffer an underlying
schizophrenia" (p. 856).
Schneier and Siris (1987) provided
a more recent review of drug abuse
patterns among schizophrenic pa-
tients. They concluded that drug
choices cited in 18 articles they
reviewed were not random. Schizo-
phrenic patients appeared to prefer
stimulants and hallucinogens, and
to use less alcohol and fewer
sedative-hypnotics than did other
psychiatric patients. The authors
noted that the choice of stimulants is
counter-intuitive since schizophrenic
patients suffer from an agitated
mental state. They speculated that if
the schizophrenic patients were at-
tempting to self-medicate their
symptoms, hypnotics or sedatives
would seem to have been more ef-
fective. The authors concluded that
the potential benefits of stimulant
use could be relief of negative symp-
toms, counteracting side effects of
their neuroleptic medications, or
both. They further speculated that
the drugs of choice may be related
to the subtype of schizophrenia or
severity of symptoms, although no
studies have directly addressed that
possibility to date.
McLellan and Druley (1977)
reported high rates of drug prob-
lems among schizophrenic patients
(48 percent of paranoid patients and
43 percent of chronic patients), with
alcohol being the drug of choice
among 31 percent of the sample.
Similarly, Alterman et al. (1980)
reported that 50 percent of their
schizophrenic sample who had a
secondary alcoholism diagnosis con-
tinued to consume alcohol in the
hospital.
In contrast, Rimmer and Jacobson
(1977) encountered no greater rates
of alcoholism among schizophrenic
patients and their relatives than
among the general population.
Richard et al. (1985) also found
relatively low rates of drug abuse (21
percent) in their sample. OTarrell et
al. (1983) examined addictive behav-
iors in hospitalized male veterans
and found lower rates of alcohol
SCHIZOPHRENIA BULLETIN
abuse among schizophrenic patients
than among all other psychiatric pa-
tients. Tsuang et al. (1982) compared
substance abuse, along with other
variables, among schizophrenic and
nonschizophrenic patients and
found more hallucinogen use but
less sedative-hypnotic use in
schizophrenic patients and no dif-
ferences in the use of alcohol.
Although there is considerable
disagreement about which drugs are
most abused by schizophrenic pa-
tients, what emerges from these
studies is confirmation that the co-
occurrence of substance abuse and
schizophrenia is widespread. More-
over, most authors recognized their
inability to delineate the temporal
relationship between the drug abuse
and the onset of the psychotic
symptoms. An understanding of that
relationship is essential to determin-
ing the interaction of drug abuse
and the onset of schizophrenia.
The Impact of Drugs on the
Outcome of Schizophrenia
Some authors have examined the
short-term impact of prior drug
abuse on schizophrenic patients'
outcome by examining hospitaliza-
tion records. Alterman et al. (1981,
1982) found drug-abusing hospital-
ized psychiatric patients (some of
whom had schizophrenia) to have
poorer attitudes toward treatment.
Tsuang et al. (1982) examined the
relationship of the duration of drug
abuse (short vs. long) to length of
hospitalization, length of pharma-
cotherapy, and discharge disposition
and found those with shorter drug
histories showed less pathology on
all three measures. Miller and
Tanenbaum (1989) examined several
measures of hospital outcome
(length of stay, time before first pass,
VOL. 16, NO. 1, 1990
neuroleptic dosage, incidence of
sign-out letters and medication
refusals, seclusion imposition, and
discharge status) for a small sample
(n = 55) of male schizophrenic pa-
tients. Over one-half (55 percent)
had abused drugs before admission.
The only measure that was signifi-
cantly different between the two
groups was a higher rate of dis-
charge against medical advice for
the drug-abusing schizophrenic
patients.
Other authors have conducted
long-term followup studies docu-
menting social-vocational adjust-
ment and rehospitalizations of drug-
abusing schizophrenic patients.
McLellan et al. (1979) reported one
of the few followup studies con-
ducted on drug abusers. Their sub-
jects (n = 51) were selected from a
drug-abuse population on the basis
of having 6 consecutive years of
admissions to a Veterans Admini-
stration (VA) hospital after the index
admission. The results revealed that
although they all had low symptom
levels when first admitted, over one-
half of the stimulant users (6 of 11)
subsequently developed psychosis
and 5 were hospitalized for the
disorder. The authors acknowledged
that the subjects who chose stimu-
lants may have had some prior sub-
threshold vulnerability, but the data
did not allow confirmation or refuta-
tion of that possibility. This study il-
lustrates the strength of prospective
analyses and emphasizes the need
to document the temporal pattern of
the psychotic symptoms and the
substance abuse, as well as, to the
extent possible, the effect of premor-
bid personality.
In the followup study of drug
abusers by Bowers (1977) cited
earlier, he successfully recontacted
15 formerly hospitalized patients
who suffered from psychotic reac-
tions to illicit drug use. His findings
indicated that of the patients who
were assessed, approximately half
did well and half did poorly. He also
noted that the extent of premorbid
drug involvement did not relate to
outcome. Vardy and Kay (1983) also
followed up their LSD-psychosis
subjects and found similar rates of
rehospitalization (52.4 percent) to
those of the schizophrenic com-
parison group (47.6 percent).
Perkins et al. (1986) recontacted
the previously hospitalized drug-
abusing/psychotic patients who
were originally studied by Tsuang et
al. (1982) and found, after 10 years,
that those who had more serious
psychotic symptoms at their index
hospitalization did more poorly than
those who had drug reactions with
psychotic features. Specifically, the
more chronically psychotic former
drug abusers were less likely to be
employed and had more frequent
hospital admissions than those with
psychotic reactions of short dura-
tion. The gross measures of
temporal interaction of substance
abuse (long vs. short) and psycho-
pathology in this study did not
allow the investigators to perform a
more detailed analysis of their
interdependence.
McLellan et al. (1983) conducted a
6-month followup of alcoholics and
drug addicts who had been enrolled
in rehabilitation programs. Those
patients who presented with more
severe psychiatric impairment failed
to improve, while those who were
less impaired all showed consider-
able improvement.
Large scale followup studies on
drug abusers are rare, and practical-
ly nonexistent among schizophrenic
substance abusers. There is a clear
need for an investigation involving
comprehensive assessments of pre-
morbid personality, family history of
psychopathology, and drug use
habits of schizophrenic subjects at
91
the time of their admission. This
cohort needs to be monitored in the
hospital and then followed for
several years.
Future Directions in Research
It is evident from the preceding
review that substance abuse may
profoundly affect the course and
outcome of schizophrenia. It is also
evident that many questions remain
unanswered about (1) the precip-
itating role of drugs in the develop-
ment of schizophrenia, (2) specific
drug/schizophrenia dose-response
interactions, and (3) the long-term
prognosis for schizophrenic patients
who also abuse drugs.
As several authors noted in the
research discussed above, drugs can
mimic or augment the psychotic
symptoms found among psychiatric
patients. This fact underscores the
need to obtain differential diagnoses
for all patients who present with
psychotic features. Gold and Dackis
(1986) advocate routine drug screens
in all new patients, and especially in
instances of psychosis of sudden
onset. More involved assays of
blood and urine are indicated when
there is suspicion that specific sub-
stances are being abused. Ingram
(1985) echoed the need for careful
diagnosis, given the propensity of
hallucinogenic drugs to mimic
schizophrenia. As has been noted
above, he asserted a need for careful
premorbid personality assessment
as well as a careful history of drug
usage. Pinsker (1983) advocated the
use of the schizophreniform diag-
nosis for all cases in which sub-
stance abuse is a contributing cause
of the observed symptoms. He also
indicated that treatment objectives
need to be oriented to the primary
diagnosis, be it schizophrenia or
substance abuse.
92
Alterman et al. (1984) compared
three diagnostic schemesthe
Research Diagnostic Criteria (RDC;
Spitzer et al. 1978), the Renard
Diagnostic Interview (Helzer et al.
1981), and DSM-III (American
Psychiatric Association 1980)with
the diagnosis of schizophrenia and
alcoholism that their VA patients
had received at the time of their ad-
mission. They were able to confirm
most of the diagnoses using the
alternative diagnostic systems. The
value of the structured diagnostic
systems was their potential to dif-
ferentiate the temporal relationship
between the two presenting diag-
noses (alcoholism and schizophre-
nia). They found that the age of
onset of schizophrenic symptoms
among the drug-abuse/schizophrenia
group was significantly earlier than
that of the schizophrenia only
group, despite similarities in the
nature and number of symptoms ex-
hibited by each group. These impor-
tant findings need to be replicated
with a larger sample and more
careful documentation of early
childhood development.
An additional factor of great im-
portance is the determination of
family history of psychopathology.
Tsuang et al. (1982) emphasized the
importance of careful assessment of
premorbid personality as well as
family history variables when
diagnosing psychosis among drug
abusers. Their evidence indicated
that drug abusers with chronic
psychotic symptoms were more like-
ly to have a positive family history
of psychosis and affective disorders
as well as poorer premorbid per-
sonalities than did drug abusers
with more acute psychoses.
Two research designs that might
further our understanding of the im-
pact of drug abuse on the course
and outcome of schizophrenia are
described below. The first approach
is a large epidemiological analysis to
ascertain prevalence rates of each
disorder separately, as well as the
rates of co-occurrence, paired with
an assessment of psychiatric service
utilization at several later intervals.
The second design involves a pro-
spective analysis with extensive
history taking and longitudinal
followup.
A Prevalence Study. A multistage
strategy is needed, involving a large
nationally representative initial sam-
ple of noninstitutionalized subjects
who are old enough to have been
exposed to the risk of developing
substance dependence. The results
of the Epidemiologic Catchment
Area program (Robins et al. 1984),
which used the Diagnostic Interview
Schedule (DIS; Robins et al. 1985),
provided reasonable estimates of
prevalence. The lifetime prevalence
rate for serious drug abuse was
found to be approximately 11 per-
cent in the 18- to 44-year age range,
and nearly 2 percent for schizo-
phrenia (Robins et al. 1984).
A survey package containing a
self-administered diagnostic instru-
ment such as the DIS, and a com-
prehensive drug use questionnaire
such as the Youth Survey Question-
naire (YSQ; World Health Organiza-
tion 1980) should be used to assess
probable psychiatric disturbance.
Relevant information on risk and
protective factors needs to be obtain-
ed, as does specific differentiation of
quantities and frequencies of abuse
of various drug types. The YSQ con-
tains three sections: demographic
items, questions concerning the fre-
quency and age of first use of 13
types of drugs, and two items
assessing the honesty with which
questions are answered.
The sample obtained from the
initial mailing (stage 1) should be
SCHIZOPHRENIA BULLETIN
matched on age, sex, race, and
socioeconomic status with an equal-
ly sized sample of nondrug users
who are free of apparent psycho-
pathology. All of those screened
positive for drug abuse and
dependence, and those screened
positive for potential mental illness,
as well as the sample of those
screened negative for both dis-
orders, should then be contacted by
telephone in stage 2. The structured
telephone interviews should use in-
struments such as the Structured
Clinical Interview for DSM-III-R
(SCID; Spitzer et al. 1986) to elicit
relevant information to confirm a
diagnosis of substance dependence
and/or abuse. The rate of comor-
bidity within this sample is an em-
pirical question.
Stage 3 of this study should in-
volve recontacting the identified
cohorts annually over a 5-year
period to track subsequent drug
abuse and psychiatric disturbances
using similar instruments.
If we assume that a final sample of
3,000 drug abusers and 500 schizo-
phrenic patients is needed to allow
for attrition over the subsequent
years of followup (stage 3), and if we
further assume that only about 65
percent of those who are originally
screened (stage 1) will be successful-
ly contacted by telephone (stage 2),
it will be necessary to have 10,000 in-
dividuals screened positive from the
general mail survey (stage 1). If we
also assume an 80-percent response
rate to the first stage survey, and
prevalence rates similar to those
found by Robins et al. (1984), over
50,000 individuals will need to be
canvassed in the initial stage of this
study.
A Hospitalization Study. The
primary issue to be considered in
this design involves careful differen-
tial diagnosis of both the drug and
VOL. 16, NO. 1, 1990
the psychotic condition. Other
issues of concern include (1) the
temporal relationship between drug
use and the onset of schizophrenic
symptoms, (2) the quantity and fre-
quency of drug(s) consumed, (3) a
careful assessment of the premorbid
personality, and (4) the family
history of somatic and psychiatric
disabilities (including substance
abuse). The final issue is the out-
come of these subjects over time.
The complexity of this issue,
resulting from the large number of
drugs being abused and the great
potential for interaction among
dosage, frequency, and subsequent
psychopathology, requires that a
very large sample of affected in-
dividuals be obtained. Consequent-
ly, schizophrenic admissions will be
needed from multiple psychiatric
facilities around the country. It will
be essential to obtain unambiguous
differential diagnoses of both the
presenting psychosis and the cur-
rent drug involvement.
It can be anticipated that at least
one-third of the admissions will
have abused drugs at some time
before their admission. If a final
sample of 3,000 schizophrenic pa-
tients with a confirmed history of
drug abuse is needed, and is to be
matched with an equal sample of
nondrug-abusing schizophrenic pa-
tients as a comparison group, ap-
proximately 10,000 admissions will
need to be screened.
Several structured diagnostic inter-
views have been developed to aid in
this process. For instance, Hasin and
Grant (1987) have compared the
relative effectiveness and reliability
of the RDC with the Schedule of Af-
fective Disorders and Schizophrenia
(SADS; Endicott and Spitzer 1978)
and the DIS. They found high
reliability for substance abuse
diagnoses, but less agreement on
antisocial personality disorders. The
SCID provides a highly reliable
diagnostic confirmation and can be
administered by trained lay
interviewers.
The assessment of prior substance
abuse behavior and the onset of per-
sonality deterioration would be
greatly enhanced by the use of a col-
lateral informant. The collateral
could be a spouse, roommate, close
friend, sibling, or parent. The tem-
poral pattern of substance abuse and
psychotic symptoms could be deter-
mined with modifications to the
Time-Line Follow-Back Drinking
Behavior Interview (Sobell et al.
1979). The Time-Line method an-
chors specified target behaviors to
holidays, birthdays, and other
significant life events, thereby great-
ly increasing the reliability of the
subjects' recollections. Comparison
of the subjects' recollections of
events with those of the collaterals
will also increase the accuracy of
these reports.
An assessment of the extent of the
history of both somatic and psychi-
atric disturbances among first- and
second-degree relatives is also
essential. Family history of alcoho-
lism has been reliably recorded
using the Family Tree Questionnaire
for Assessing Family History of
Drinking Problems (Mann et al.
1985). Once again, this instrument
could be easily modified to capture
broader medical histories for family
members.
An essential element of this
project would be to follow patients
who screen positive for both schizo-
phrenia and substance abuse, and
compare their course of treatment
and outcome with the nondrug-
abusing schizophrenic comparison
group. The large sample size would
93
also make further analysis of treat-
ment course and outcome possible
by, in addition to the type of drug
abused and the quantity and fre-
quency of the abuse, family history
and premorbid personality factors.
Conclusions
It is evident from the previous
discussion that the impact of
substance abuse on the course and
outcome of schizophrenia remains
largely undefined. There is some
evidence that drugs tend to hasten
the age of onset of psychosis, but it
is unclear whether the effect is to
precipitate latent or subliminal
psychotic behavior or to initiate
psychosis in subjects who would not
have had an episode absent their
drug abuse. Drug abuse just before
hospitalization and during hospitali-
zation is fairly common, and the
drugs of choice do not appear to be
random, but it has yet to be deter-
mined whether the specific benefits
the schizophrenic patients are
receiving from the drugs differ from
those experienced by nonschizo-
phrenic individuals. The relation-
ship between characteristics of drug
abuse (drug type, quantity and
frequency of drug abuse) and the
degree of psychopathology, manifes-
tations of disease, and long-term
outcome has yet to be addressed.
Finally, drugs may be precipitating
relapse and subsequent rehospital-
izations among schizophrenic pa-
tients who are in remission.
The volume and complexity of
the issues that remain unresolved
must be addressed in a comprehen-
sive and systematic manner. Two
large-scale research efforts are
outlined which could begin to pro-
vide some of the answers to these
questions.
94
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Acknowledgments
This project was supported in part
by USPHS grants R01 AA-07555
from the National Institute on
Alcohol Abuse and Alcoholism and
R37 MH-43518 and R01 MH-44277
from the National Institute of Mental
Health.
The Authors
Winston M. Turner, Ph.D., is Scien-
tific Director, Family History and
Alcoholism Project, Psychiatry
Service (151-D) Brockton/West Rox-
bury Veterans Administration
Medical Center, Brockton, MA.
Ming T. Tsuang, M.D., Ph.D., is Pro-
fessor of Psychiatry and Director of
Psychiatric Epidemiology, Harvard
School of Medicine and Public
Health, and Chief of Psychiatry,
Brockton/West Roxbury Veterans Ad-
ministration Medical Center,
Brockton, MA.