389

Association Between Early or

Later Onset of Substance Use

and Psychiatric Disorders

in Women

Linda B. Cottler, Ph.D.; Arbi Ben Abdallah, M.S.; and

Wilson M. Compton, M.D.

INTRODUCTION

The comorbidity of psychiatric disorders with drug addiction has

been established, but only recently has the importance of this relationship been emphasized. Rates of comorbidity vary according to factors

relevant to recall and those that are inherent in the method of assessment. Recall factors include the salience, timing, and severity of

symptoms. Assessment factors include the reliability of the diagnostic

assessment chosen, the method of data ascertainment (computer v.

paper-and-pencil), and the diagnostic system on which the assessment

is based (e.g., the various versions of the Diagnostic and Statistical Manual

of Mental Disorders, Third Edition [DSM-III]; DSM-III-R [Third Edition,

Revised], or DSM-IV [Fourth Edition] [American Psychiatric Association

1980, 1987, 1994]). Sample characteristics, such as general population

or in-treatment samples, men or women, older or younger subjects,

and ethnicity, along with other individual risk factors, have also been

shown to affect rates of comorbidity (Regier et al. 1990; Ross et al.

1988; Weissman et al. 1980; Mirin et al. 1988; Mirin and Weiss 1986;

Weiss et al. 1986; Rounsaville et al. 1982; Kosten and Rounsaville 1986;

Mirin et al. 1991; Hesselbrock et al. 1985; Khantzian and Treece 1985;

Powell et al. 1982; McLellan et al. 1983; Croughan et al. 1982; Jainchill

et al. 1986; Hasin et al. 1988; Rounsaville et al. 1991).

The Epidemiologic Catchment Area (ECA) Study found that rates

of psychiatric disorders were higher among substance users than among

nonusers for every category of DSM-III substance abuse or dependence

(Regier et al. 1990). Overall, 53 percent of persons in the ECA with

substance use disorders met the criteria for one or more psychiatric

conditions. Similarly, the National Comorbidity Survey (NCS) showed
390

that DSM-III-R psychiatric disorders are more common among substance

abusers than expected (Kessler et al. 1994). According to the NCS,

about one-half of the individuals with a past-year substance use disorder

(47 percent) had both substance abuse/dependence and another mental

disorder—more than double the rate for the overall population.

Particularly among treatment-seeking substance abusers, psychiatric

comorbidity has been found to be commonplace (Rounsaville et al.

1982; Rounsaville et al. 1991). In samples of persons seeking treatment,

rates of comorbid psychiatric diagnoses have been estimated at almost

65 percent for the past year and 78 percent over the client’s lifetime

(Ross et al. 1988). This raises the question of reasons for higher rates

of psychiatric illness among treatment-seeking substance abusers. Grant

(1997) recently showed that depression is higher among treatmentseeking substance abusers and much less pronounced among those not

seeking treatment. The causal link, if any, between drug use and a

psychiatric disorder remains murky, especially where details on the

progression from one illness to another are concerned. Furthermore,

research should be conducted to improve the recognition of the

comorbidity among abusers and to improve prevention and treatment

approaches.

Lehman and colleagues (1989) proposed several theoretical constructs: mental illness causing substance dependence, substance dependence causing a mental disorder, each diagnosis occurring independently, and both problems being caused by some common factor. For

example, posttraumatic stress disorder (PTSD) has been found to both

precede and follow substance abuse (Cottler et al. 1992). Mood and

anxiety symptoms observed in active substance users frequently improve

with abstinence (Weddington et al. 1990; Schuckit 1986; Rounsaville

et al. 1986). This implies that some cases of coexistent depression and

anxiety may be related to the use of psychoactive substances and has led

to controversy about when to start treatment for comorbid psychiatric

conditions in substance abusers. Recent evidence has supported the idea

of treating coexisting psychiatric disorders among substance abusers early

in treatment, especially in the case of coexisting depression (Nunes et al.

1993, 1994; Batki et al. 1987; Woody et al. 1982; Dorus et al. 1989;

Mason and Kocsis 1991) and perhaps anxiety disorders as well (Kranzler

et al. 1994; Malcolm et al. 1992). Underrecognition of symptoms

continues to be one of the major problems that has occurred in both

understanding and treating these conditions.
391

Despite the proliferation of papers linking psychiatric disorders with

substance abuse, the extent of this association among women has not

been fully addressed in the literature (Alexander 1996). Studies from

Brooner and colleagues (1997) emphasize the importance of providing

therapeutic interventions that address the psychiatric comorbidity.

Using behavioral interventions in conjunction with pharmacotherapy

may significantly improve the outcomes for patients with comorbid

psychiatric disorders.

In the past several years attention has been placed on subtypes of

alcoholics. Babor and colleagues (1992) identified two distinct types of

alcoholics who differ with respect to a variety of defining characteristics,

including age of onset—those who are characterized by later onset, with

less severe dependence and fewer alcohol-related problems, and those

who are characterized by early onset, with greater severity of dependence

and more extreme alcohol-related problems. These subtypes of alcoholics have been identified among both men and women.

The study described in this chapter advances the knowledge of the

comorbidity literature by addressing the consequences of substance abuse

among both treated and untreated users, by deleting the confounder of

gender to focus only on women, and by stratifying the sample by early or

late onset of substance abuse.

METHODS

Sample

The women included in these analyses were drawn from two separate NIDA-funded studies of illicit substance users in the St. Louis area

with varying substance use patterns and severity of problems. The

studies were conducted from 1990 to 1994. The first sample (n=204)

came from the Substance Abuse and Risk for AIDS (SARA) study, a

longitudinal study of substance abusers who had recently been admitted

to treatment or who resided in one of two shelters for women and who

were reforming prostitutes or were in recovery from substance abuse

(Cottler et al. 1991). The second sample (n=134) was obtained from

the Efforts to Reduce the Spread of AIDS (ERSA) study (Cottler et al.

1993, pp. 205-218; Cottler et al. 1995, pp. 233-248). This longitudinal

demonstration study sought to improve drug abuse treatment in the most

vulnerable, high-risk areas of St. Louis. ERSA subjects were obtained
392

through street outreach and thus represent out-of-treatment substance

abusers. The followup rate for both studies was in excess of 90 percent;

in fact, ERSA achieved a 96.6 percent followup at 18 months (Cottler

et al. 1996). The samples were pooled to increase the ability to detect

differences; pooling was possible because the two studies used nearly

identical diagnostic assessments. There was no overlap in subjects across

the two studies, a total of 338 women.

Interview

Respondents were questioned in person by interviewers who had

undergone extensive training on administration of the interviews and

on study protocols. The informed consent procedure, cleared by both

the Washington University Institutional Review Board and the State

of Missouri Department of Drug and Alcohol Abuse, advised potential

respondents of the confidentiality of their responses. Participation was

further protected by a NIDA Certificate of Confidentiality.

The interview included an assessment of substance abuse and

dependence for alcohol, amphetamines, cannabis, cocaine, hallucinogens, inhalants, opiates, PCP (phencyclidine), sedatives, and tobacco.

The SARA study used the American Psychiatric Association’s Diagnostic Interview Schedule (DIS, Version III-R); the ERSA study used the

World Health Organization’s Composite International Diagnostic

Interview-Substance Abuse Module (CIDI-SAM). The differences

between these instruments are minimal. The CIDI-SAM elicits information about specific withdrawal symptoms as well as the psychological,

physical, and social consequences of drug use; the DIS obtains the same

information in a briefer form. Because these assessments are from the

same family of instruments (Cottler and Compton 1993) and the core

components are identical, they are compatible for analyses. Histories

of lifetime psychiatric symptoms were obtained by the DIS, with the

following sections included: depressive disorders, generalized anxiety,

panic, phobic disorders, antisocial personality disorder (ASPD), PTSD,

and pathological gambling.

Stratification of Sample

For these analyses women were divided into early and later substance use groups, according to the age of onset of the first drug use
393

TABLE 1. Stratification of SARA/ERSA drug-using women (n=338)

Age of

Onset Restricted

of Any Age of Onset

Other Drug Use Onset Cluster Onset

Cocaine Opiates Drugs Number Percent (Years) (Years) Years Index*

+ + +/– 156 46 15.7 20.1 4.4 Early

+ – +/– 127 38 18.8 25.4 6.6 Later

– + +/– 24 7 18.0 21.8 3.8 Later

– – + 31 9 17.4 17.9 0.5 Early

*Considers cluster and onset age

KEY: SARA/ERSA=Substance Abuse and Risk for AIDS/Efforts to Reduce the Spread of

AIDS

(alcohol and tobacco excluded) and the onset cluster years. Age of onset

refers to the age at which a respondent first used an illicit drug, as reported on the SAM/DIS. Onset cluster years refers to the span of years in

which an individual’s drug repertoire began. In addition, a second ageof-onset term, the restricted age of onset, is used to indicate this age of

onset limited to the first use of cocaine or opiates or “other drugs” if

cocaine/opiates were not used. On the basis of these combined data,

the sample was grouped into onset indexes of either “early” or “later”

drug use.

As shown in table 1, 84 percent of the sample reported using cocaine, with or without other drugs; 53 percent reported using opiates,

with or without other drugs; and 9 percent reported using drugs other

than cocaine/opiates. On the basis of the grouping criteria described

above, 55 percent of the sample were characterized as early users and the

remaining 45 percent as later users. Early users included 46 percent of

the sample whose drug use started, on average, by 15.7 years of age—the

earliest age of onset of the four groups shown in table 1. These same

women had used cocaine or opiates by age 20.1 for an average onset

cluster span of 4.4 years. Early users also consisted of women who did

not use cocaine or opiates but whose onset span for other drugs was

short (within 6 months). Women characterized as later users included

those who used other drugs with cocaine or opiates, those who did not

use their first drug until at least 18 years of age, and those whose onset

span was longer than the others.

Sample Size

Substance Used
394

Analyses

The authors performed analyses using SAS version 6.12. For categorical data, chi-squared tests were employed. Student’s t-tests were

used to compare means.

RESULTS

Demographics

As shown in table 2, the mean age of all women in the sample was

31.9 years (standard deviation [SD]=6 years). Of this sample, 67 percent were African-American, 14 percent were married at the time of the

interview, 77 percent had one or more children, 45 percent had attained

less than a high school education, 70 percent were unemployed, and

52 percent lived in their own houses or apartments. The early users

were differentiated from the later users by age, racial mix, and current

living arrangement. Specifically, the early users were slightly older

than the later users at the time of the interview (33.0 years v. 30.5 years,

SD=6 years) and were more likely to be racially diverse (53 percent v.

83 percent African-Americans) and living in their own houses or

apartments (59 percent v. 43 percent). With these exceptions, the two

groups were comparable in their sociodemographic characteristics.

Patterns of Substance Use

The use of all substances except alcohol, cocaine, and PCP was

found to be statistically more prevalent among early users than among

later users. As seen in table 3, for more than half of the drug categories,

the rates among early users were more than double those of the later

group. Although not shown in the table, injection drug use was more

than three times as prevalent among early users as among later users

(68 percent v. 22 percent).

Although rates of use were higher among early users than among

later users, there was no difference among the various drugs in rates of

dependence between the two groups, except for alcohol, in which case

early users were more likely to be dependent (table 3). Furthermore,

as shown in table 4, women categorized as early users were more likely

to have experienced consequences of use of any drug from 2 to 4 years

earlier than women categorized as later users (average age 22.4 years for
395

TABLE 2. Sociodemographic characteristics of SARA/ERSA drug-using

women

Sample Size (N=338) Substance Use Status

Early Users Later Users

Characteristics Number Percent (N=187) (N=151)

Mean age in years (SD) 31.9 (6) 33.0 (6) 30.5* (6)

Percent Percent

Age

24 years or younger 34 10 7 13

25-34 years 180 53 45 64*

35 years or older 124 37 48 23*

Ethnicity

African-American 225 67 53 83

Other 113 33 47 17†

Marital status

Currently married 49 14 17 11

Not married 289 86 83 89

Children

No children 77 23 22 24

One or more children 261 77 78 76

Education level

Less than high school 153 45 44 47

High school or more 185 55 56 53

Employment status

Unemployed 237 70 66 75

Employed 100 30 34 25

Current living arrangements

In own house or apartment 174 52 59 43

Someone else‘s house/ 162 48 41 57*

 shelter/street

*p 0.01

†0.01<p 0.05

KEY: SARA/ERSA=Substance Abuse and Risk for AIDS/Efforts to Reduce the Spread of

AIDS; SD=standard deviation
396

TABLE 3. Substance use and dependence among SARA/ERSA drugusing women (percent)

Early Users Later Users

(N=187) (N=15) p

Drugs Use Dependence* Use Dependence* Use Dependence*

Alcohol 81 62 74 40 NS 0.001

Cannabis 91 33 73 25 0.001 NS

Amphetamines 60 41 27 27 0.001 NS

Sedatives 66 34 21 25 0.001 NS

Cocaine 83 73 84 77 NS NS

Opiates 83 58 16 71 0.001 NS

PCP 22 34 16 46 NS NS

Hallucinogens 39 14 9 8 0.001 NS

Inhalants 10 22 1 50 0.001 NS

*DSM-III-R dependence, lifetime

KEY: SARA/ERSA=Substance Abuse and Risk for AIDS/Efforts to Reduce the Spread

of AIDS; NS=not significant; PCP=phencyclidine

TABLE 4. Progression of symptoms of drug dependence among

SARA/ERSA drug-using women

Mean Age at Onset of Symptoms

Early Users Later Users

Symptom (N=187) (N=151) p

Consumption greater/longer than intended 21.9 24.8 0.0007

Persistent desire/unsuccessful efforts to 22.5 25.6 0.0001

 cut down

Excessive time spent using/getting/recovering 20.9 24.2 0.0001

 from effects

Use with increased risk of injury 20.2 23.5 0.0002

Given up/reduced important activities 23.7 27.2 0.0001

Continued use despite social/psychiatric/ 20.6 23.1 0.0008

 physical problem

Marked tolerance 23.1 26.1 0.0007

Withdrawal 24.3 25.9 0.0669

Use to avoid/relieve withdrawal 24.2 26.8 0.0163

KEY: SARA/ERSA=Substance Abuse and Risk for AIDS/Efforts to Reduce the Spread of

AIDS
397

early users and 25.2 years for later users). For all symptoms, the differences between the two groups were statistically significant; for all but

two symptoms, withdrawal and withdrawal avoidance, these differences

were significant at the 0.01 level.

Psychiatric Comorbidity

The primary focus of this chapter is the comorbidity of psychiatric

disorders with substance use and dependence. A substantial proportion

of the women in this sample met the criteria for these disorders, as

shown in table 5. The most commonly identified disorder in both

groups was phobic disorder, followed by depression, ASPD, and

PTSD. Women who were early users were more likely than later

users to meet the criteria for any one of these diagnoses, except for

generalized anxiety and pathological gambling. Of the coexisting

diagnoses found to be statistically significant, ASPD and depression

had the most significant difference in rates of occurrence between the

two groups (ASPD=30 percent early v. 15 percent later, p=0.001;

depression=33 percent early v. 15 percent later, p=0.001).

ASPD and Depression

The next analysis describes the lifetime co-occurrence of ASPD and

depression. As shown in figure 1, early users were more likely than later

users to have histories of comorbid ASPD and depression (10 percent v.

TABLE 5. Psychiatric comorbidity among SARA/ERSA drug-using

women (percent)

Early Users Later Users

Disorder (N=187) (N=151) p

Phobia 45 32 0.014

Panic 6 1 0.049

Generalized anxiety 8 6 NS

Posttraumatic stress disorder* 20 8 0.052

Major depression 33 15 0.001

Antisocial personality disorder 30 15 0.001

Pathological gambling 3 3 NS

*Among ERSA subjects only

KEY: SARA/ERSA=Substance Abuse and Risk for AIDS/Efforts to Reduce the Spread

of AIDS; NS=not significant
398

FIGURE 1. Comorbidity of antisocial personality disorder and

depression among SARA/ERSA drug-using women

KEY: SARA/ERSA=Substance Abuse and Risk for AIDS/Efforts to Reduce the Spread

of AIDS

4 percent). Early users were also more likely to have higher rates of

each diagnosis separately (depression=23 percent v. 11 percent; ASPD=

21 percent v. 11 percent).

With regard to the most severe symptoms of depression, a large

proportion of these women reported thoughts of death, wanting to die,

thoughts of suicide, and attempting suicide (table 6), indicating a
399

TABLE 6. Characteristics of depression among SARA/ERSA drug-using

women (percent)

Early Users Later Users

Characteristic (N=187) (N=151)

Thoughts of death 55 46

Felt like dying 42 36

Thoughts of suicide 50 42

Attempted suicide 34 28

KEY: SARA/ERSA=Substance Abuse and Risk for AIDS/Efforts to Reduce the Spread of

AIDS

TABLE 7. Specific DSM-III-R antisocial personality symptoms among

SARA/ERSA drug-using women (percent)

Early Users Later Users

Symptoms (N=187) (N=151)

Inability to sustain consistent work behavior 71 72

Failure to conform to social norms of legal behavior 89 83

Irritable and aggressive behavior 74 63*

Repeated failure to honor financial obligations 43 38

Failure to plan ahead or impulsive behavior 37 39

No regard for truth 53 50

Recklessness regarding one’s own or another’s personal safety 36 26†

Inability to function as a responsible parent or guardian 30 34

Failure to sustain a monogamous relationship 10 7

Lack of remorse for hurting or stealing 42 23†

*0.01<p 0.05, relative to Early Users group

†p=0.001, relative to Early Users group

KEY: DSM-III-R=Diagnostic and Statistical Manual of Mental Disorders, Third Edition,

Revised; SARA/ERSA=Substance Abuse and Risk for AIDS/Efforts to Reduce the

Spread of AIDS

severity of illness that is of considerable concern. Although these high

rates did not differ significantly between the groups, early users were

more likely to report each of these symptoms. Differences between the

two groups in specified adult antisocial behaviors are shown in table 7.

The most commonly reported behaviors among the early users were

failure to conform to social norms, irritability and aggressivity, and

inability to sustain consistent work behavior. Three behaviors discriminated between the two groups: irritability and aggressivity, recklessness

regarding one’s own or another’s safety, and lack of remorse.
400

To understand more about the relationship between early drug use

and comorbid ASPD and depression, the authors evaluated the age of

onset of these two disorders in relation to the age of onset of drug use

and found that ASPD and depression were temporally subsequent to first

use of any drug. As shown in table 8, on average, drug use among the

early users preceded adult antisocial behavior by 1.6 years, whereas the

later users seemed to meet criteria for ASPD at the same time as their

drug use initiation. Onset of depression, on the other hand, was reported from more than 3 to more than 5 years after the initiation of

drug use, indicating that drug use is a strong risk factor for depression

in both groups.

DISCUSSION

The authors studied the early and later onset of drug use in a sample

of both in-treatment and out-of-treatment female drug users and found

that the use of virtually all substances was more prevalent among early

users than among later users. In fact, for almost all drugs, the rates of

drug use among early users were more than double those of the later

users. However, except for alcohol, the greater rates of use were not

associated with a difference in rates of dependence between the two

groups. Furthermore, women categorized as early users were more likely

to have experienced consequences of any drug from 2 to 4 years earlier

than women categorized as later users.

Except for generalized anxiety and pathological gambling, early

users were more likely than later users to meet the criteria for any given

one of the diagnoses. Of those diagnoses assessed and found to be

statistically significant, ASPD and depression varied the most between

the two groups. These findings are unique in that they focus on the

TABLE 8. Age of onset of depression or antisocial personality

disorder in relation to drug use

Mean Age at Onset

Early Users Later Users

Disorder (N=187) (N=151) p

Depression 20.7 24.5 0.006

Adult antisocial behaviors 17.6 18.9 0.013

Drug use 16.0 18.7 0.001
401

presence of these two disorders. Early users were more likely than later

users to have histories of comorbid ASPD and depression. They were

also more likely to have higher rates of each diagnosis separately. In

fact, a large proportion of this sample, regardless of age of onset of

substance use, indicated an intensity of depressive illness that in itself

is of considerable concern. In addition, women who began to use drugs

earlier were more likely to be irritable and aggressive, reckless regarding

their own or another’s safety, and lacking remorse for their behavior.

Finally, early users were found to have ASPD sequelae to drug use.

Later users met the criteria for ASPD shortly after drug use initiation,

suggesting that their ASPD behaviors might have led them to use drugs

or that their drug use was just beginning to cause antisocial behaviors.

Drug use was a strong risk factor for depression in both the early and

later use groups.

These findings may be limited by the nature of comorbidity research

in general, where multiple conditions must be considered. There are

issues regarding the assessment, recall, hierarchies of diagnoses, misclassification bias, and nosologies that might complicate interpretation

of these results. For example, although it might be argued that data

collected by nonclinicians might be less valid than data collected by

clinicians, this study minimized this risk by using well-trained nonclinicians who demonstrated a high level of expertise. Comorbidity research

might also be limited by the possibility of selective recall bias. If there

were selective recall for events, it could affect recall of either psychiatric

symptoms or substance use. In this study, any recall bias probably

affected measures for both psychiatric symptoms and substance use

in the same direction for early and later users, because early users also

reported early onset of psychiatric symptoms and later users reported

later onset of psychiatric symptoms. Also, because neither study focused

on determining the association between early and later onset of use,

the respondents and interviewers could not have known of this postdata-collection hypothesis.

Arguments against a misclassification bias include the compatibility

of these results with those of Brooner and colleagues (1997). With the

identical number of women in the authors’ studies (n=338)—a coincidence—the authors found the prevalence of psychiatric disorders, as

assessed with a different structured interview, to be comparable, especially for depression and ASPD.
402

CONCLUSION

These findings, which are generalizable to female drug abusers both

in and out of treatment, indicate that women who begin to use drugs at

later ages are not much better off than women who begin to use drugs at

earlier ages. The later users showed psychiatric profiles that were similar

to those of the early users—who themselves showed considerable signs

of impairment. These findings suggest that starting drug use at a later

age does not reduce the harm of drugs; it only delays its onset. Once

drugs are used, the symptoms are not far behind.

These findings, which emphasize that early drug users experience

problems from drugs earlier in their lives than later drug users, should

influence policy decisions regarding the availability of early treatment

and intervention for women who use drugs. They should also highlight

the need for special treatment focusing on the comorbid conditions of

depression and antisocial behaviors among female substance abusers.

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ACKNOWLEDGMENTS

This work was supported by National Institute of Mental Health

training grant MH-17104, NIDA grant DA-00209 (Dr. Compton),

and expired NIDA-funded data collection grants DA-05619 and DA06163.

AUTHORS

Linda B. Cottler, Ph.D.

Associate Professor of Epidemiology in Psychiatry

(314) 286-2266 (Tel)

(314) 286-2265 (Fax)

cottler@epi.wustl.edu (E-mail)
406

Arbi Ben Abdallah, M.S.

Statistical Data Analyst

(314) 286-2269 (Tel)

(314) 286-2265 (Fax)

aba@epi.wustl.edu (E-mail)

Wilson M. Compton, M.D.

Assistant Professor of Psychiatry

(314) 286-2260 (Tel)

(314) 286-2265 (Fax)

compton@epi.wustl.edu (E-mail)

Department of Psychiatry

Washington University School of Medicine

40 North Kingshighway Boulevard, Suite 4

St. Louis, MO 63108