Accepted Manuscript

Title: Effects of anxiety and mood disorders on craving and

substance use among patients with substance use disorder: an
ecological momentary assessment study

Authors: Melina Fatseas, Fuschia Serre, Joel Swendsen, Marc

Auriacombe

PII: S0376-8716(18)30201-1
DOI: https://doi.org/10.1016/j.drugalcdep.2018.03.008
Reference: DAD 6911

To appear in: Drug and Alcohol Dependence

Received date: 31-12-2017

Revised date: 5-3-2018
Accepted date: 6-3-2018

Please cite this article as: Fatseas, Melina, Serre, Fuschia, Swendsen, Joel, Auriacombe,
Marc, Effects of anxiety and mood disorders on craving and substance use among
patients with substance use disorder: an ecological momentary assessment study.Drug
and Alcohol Dependence https://doi.org/10.1016/j.drugalcdep.2018.03.008

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 Effects of anxiety and mood disorders on craving and substance use among patients with

substance use disorder: an ecological momentary assessment study*

Melina Fatseasa,b,c, Fuschia Serrea,b,c, Joel Swendsena,d,e, Marc Auriacombe a,b,c,f #

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a
Département d'Addictologie, University of Bordeaux, CHCP, 121 rue de la Béchade,

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33076 Bordeaux Cedex, France

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b
Laboratoire de Psychiatrie / SANPSY, CNRS USR 3413, Bordeaux, France

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c
Département d'Addictologie, CH Charles Perrens and CHU de Bordeaux, Bordeaux, France
d

e
INCIA, CNRS UMR 5287, Bordeaux, France
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Ecole Pratique des Hautes Etudes, PSL, Paris, France
f
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Department of Psychiatry, Center for Studies of Addiction Perelman School of Medicine,
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University of Pennsylvania, 3400 Civic Center Blvd., Philadelphia, PA 19104, United States
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#Correspondence:
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Marc Auriacombe

Département d'Addictologie, University of Bordeaux,

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CHCP, 121 rue de la Béchade, 33076 Bordeaux Cedex, France

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Tel: +33 556 561 738

E-mail: marc.auriacombe@u-bordeaux.fr
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* Supplementary material can be found by accessing the online version of this paper at
http://dx.doi.org and by entering doi...
Highlights

 Comorbidity between psychiatric and addictive disorders is frequent.

 In comorbid mood/anxiety disorders craving remains a mediator of substance use.

 Mood/anxiety comorbid disorders are associated with higher craving intensity.

 Mood/anxiety comorbid disorders are associated with more frequent substance use.

 Mood/anxiety comorbidity increased substance use is partly independent of craving.

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Abstract

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Background. Despite recognition of the negative impact of psychiatric comorbidity on

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addictive disorders, the mechanisms underlying this association remain poorly understood.

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The present investigation applied mobile technologies to examine the effect of comorbid
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mood or anxiety disorders on craving intensity and substance use within the natural
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conditions of daily life.
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Methods. A total of 159 participants were recruited from a French outpatient addiction clinic

and completed two weeks of computerized ambulatory monitoring of daily life experiences
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using Ecological Momentary Assessment (EMA). Patients described in real-time their

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emotional states, craving intensity, and substance use. Current mood and/or anxiety disorders

were diagnosed according to DSM-IV criteria. The main substances of dependence were
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alcohol (n=48), tobacco (n=43), cannabis (n=35), or opiates (n=33).

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Results. Craving intensity strongly predicted substance use reported over subsequent hours

of the day both in groups with (OR=1.13, p=0.009, n= 95) and without (OR=1.20, p=0.002,
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n=64) current comorbid psychiatric disorders. Current comorbid mood and/or anxiety

disorders were associated with higher craving intensity (γ coef = 0.632, SE= 0.254, p=0.014)

and consequently more frequent substance use (γ coef = 0.162, SE= 0.052, p=0.003). A
portion of increased substance use associated with current mood and/or anxiety disorders was

independent of increases in craving intensity.

Conclusions: Attention to craving management is particularly important for patients with

substance use disorders and comorbid mood and/or anxiety disorders, but additional

interventions are also needed that address other mechanisms through which these disorders

lead to an increase in substance use frequency, independently from craving.

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Keyword: Craving; Mood disorders; Anxiety disorders; Addiction; Psychiatry; Ecological

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Momentary Assessment

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1. Introduction

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Strong comorbidity between psychiatric and addictive disorders is reported by many

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epidemiological studies (Conway et al., 2006; Merikangas et al., 1998) and this association is
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most generally associated with poorer treatment outcomes and quality of life and higher rate
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of relapse (Conway et al., 2006; Fatséas et al., 2006; Samet et al., 2013; Torrens et al., 2006).
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However, the mechanisms underlying these associations remain poorly understood,

contributing to difficulties involved in the treatment of individuals with dual disorders.

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Craving is considered as a central construct in the etiology and course of different forms of
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addiction, and it is a strong predictor of relapse and treatment outcome (Fatseas et al., 2015;

Sayette, 2016; Serre et al., 2015; Skinner and Aubin, 2010). Research using Ecological
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Momentary Assessment (EMA) to study craving and substance use episodes in daily life
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contexts has highlighted the influence of mood states in explaining variance in craving

reports (Brodbeck et al., 2014; Epstein et al., 2009; Krahn et al., 2005). A principal
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hypothesis is that negative emotional states, which are elevated among individuals with mood

or anxiety disorders, may elicit particularly strong craving episodes and as a consequence

increased relapse vulnerability. Some studies using EMA have failed to find an association

between increases in negative affect (NA) or stress and later substance use or relapse (Preston
and Epstein, 2011; Van Zundert et al., 2012), while increases in anxious and negative mood

were found to increase substance use in other studies (Buckner et al., 2015; Swendsen et al.,

2011). Substance use has also been shown to decrease NA and craving, suggesting that use

could be related to coping motives (Buckner et al., 2015). Previous EMA studies assessing

the influence of psychiatric symptoms on craving have mainly focused on only one type of

substance, or addressed only one specific psychiatric disorder, such as social anxiety and

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cannabis use (Buckner et al., 2012; Buckner et al., 2015), psychotic disorder and cannabis use

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(Kuepper et al., 2013) or PTSD and alcohol use (Kaysen et al., 2013), limiting the

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generalization of findings. Moreover, as these studies did not control for craving levels, it is

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not known how the craving-substance use association may be influenced by psychiatric

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comorbidity. The present investigation examines this issue using EMA in outpatients with
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alcohol, tobacco, cannabis or opiate dependence. The main objectives were to 1) assess the
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prospective influence of negative emotions in the prediction of subsequent craving and
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substance use in daily life; 2) estimate the potential influence of mood and anxiety disorders

on mood states, craving and substance use; and 3) examine whether psychiatric comorbidity
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influences the magnitude of the craving-substance use association.

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2. Material and Methods

This investigation is part of an EMA research program within the Addiction Aquitaine
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Cohort (ADDICTAQUI) that is aimed at understanding the determinants of substance use

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behavior among a variety of addictions as a function of individual and environmental risk

factors (Serre et al., 2012). Previous investigations of this sample have demonstrated the role
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of exposure to daily-life, person-specific cues in craving intensity and substance use (Fatseas

et al., 2015; Serre et al., 2018).

2.1. Participants
 Participants were contacted upon enrollment for substance addiction treatment in an

outpatient clinic in Bordeaux, France. Patients eligible for inclusion were those beginning

treatment and who met DSM 5 criteria for alcohol, tobacco, cannabis, or opiate use disorders,

were between 18 and 65 years of age, and did not demonstrate active psychosis or severe

cognitive impairment. Table 1 provides a description of the clinical characteristics of the

sample. Approval was obtained from the local ethics committee for clinical research. Written

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informed consent was also obtained from all participants after provision of a complete

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description of the study.

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The participants received standard comprehensive care, consisting of individual

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behavioral treatment focused on relapse prevention and psychosocial support combined when

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available with pharmacotherapy (Fatseas and Auriacombe, 2009). After establishing a quit
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date, full abstinence was encouraged as an outcome but with no negative consequences for
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the patient if he or she failed to achieve this goal.
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2.2. Procedure

The feasibility and validity of the ambulatory methodology used were recently
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demonstrated in this sample (Serre et al., 2012). In summary, EMA assessments started after
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a target-quit date that was determined with the patient's physician and corresponded to the

first day of treatment. Participants received a one-hour clinical interview to assess addiction
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severity, psychiatric comorbidity, medical disorders, and social adjustment. After a training
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session, participants were given a personal digital assistant (PDA) to carry with them for 14

days. Each PDA was programmed to administer four electronic interviews per day, between
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8:00 am and 11:00 pm. Signal times were fixed for each individual, but randomized across

participants in the sample. The signal schedule was also chosen for each participant to

accommodate their usual sleep schedule. Additional urine analysis and alcohol breath tests

were conducted as part of the general treatment protocol. Financial compensation was
provided as a function of a number of electronic interviews completed, with a maximum of

100 euros for participants who completed 75% or more of the electronic assessments.

2.3. Clinical Measures

DSM diagnostic criteria for current psychiatric and substance use disorders were

assessed using the Mini International Neuropsychiatric Interview–Plus, that demonstrated

good interrater reliability, and adapted for DSM 5 substance use disorders (Sheehan et al.,

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1998). In this study, current psychiatric comorbidity was defined as a current diagnosis of

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DSM-IV mood disorder and/or anxiety disorder.

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2.4. EMA monitoring measures

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The EMA measures used in the current investigation have been previously validated

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in samples with substance use disorders (Johnson et al., 2009 a; Johnson et al., 2009 b; Serre
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et al., 2012).
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2.4.1. Craving and Substance Use. At each electronic interview, participants were
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asked to rate the maximum level of craving (i.e., the desire to use the substance that initiated

their treatment) that they felt since the previous assessment on a seven-point scale (1 no
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desire to 7 extreme desire). They were also asked if they had used, since the previous
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assessment, the main problematic substance that initiated their treatment, followed by

questions concerning the use of any other substance during that time period (tobacco, alcohol,
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opiates, cocaine, amphetamine, cannabis, or other substances).

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2.4.2. Negative Mood States and Event Negativity. Sad and anxious moods were

assessed by a separate 7-point Likert item that asked participants to evaluate their mood at the
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moment of the assessment. The perceived negativity of daily events was assessed by asking

participants to select the event that had the greatest impact on them since the last electronic

interview, and then to rate its negativity on a similar 7-point Likert scale. Higher scores

indicated greater sad mood, anxious mood, or event negativity.

 2.5. Statistical Analysis

Due to a restricted number of assessments occurring on the starting and ending days

of the study and their overlap with investigator contact, only field data collected between day

2 to day 13 were analyzed. Hierarchical linear and nonlinear modeling (Raudenbush et al.,

2005) was used to account for the multilevel structure of the data that involved within-person

variance in mood states, craving and substance use, as well as the between-person variance in

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clinical and sociodemographic characteristics. Missing data were handled by excluding that

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particular observation from analyses.

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The objective of examining the association of mood states and negativity of events

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with craving was achieved by random coefficient models that simultaneously included the

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intensity of mood states (sad, anxious, or event negativity) reported at any given assessment
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(T0) as predictors of craving levels at the next assessment (T1, on average four hours later),
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controlling for the status of the dependent variable (craving) at the T0 assessment. Similar
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models were used to examine the association of mood states or craving levels relative to the

subsequent use of the specific substance at the origin of addiction treatment. Analyses were
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conducted separately in the groups with and without current diagnoses of mood and/or
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anxiety disorder.

The association of current psychiatric comorbidity with craving and substance use
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was examined by means-as-outcomes models that included the current diagnosis of mood
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and/or anxiety disorder as a predictor of craving levels observed during EMA assessments, or

of the use of the specific substance at the origin of addiction treatment. These models were
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also examined separately for each substance group. Finally, the hypothesis that current

psychiatric comorbidity would influence the relationship between craving and substance use

was tested with adding the cross-level interaction of psychiatric comorbidity with craving

intensity at T0 on the prediction of substance use at T1. Additional analyses also added cross-
level interactions for substance groups with craving intensity (cannabis group used as

reference).

Sociodemographic adjustments by age and sex were included in all analyses to

provide the greatest comparability with previous investigations. Additional adjustments on

the number of years of education and employment status were included in analyses where the

current diagnosis of mood and/or anxiety disorder was tested as a predictor. Status of the

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dependent variable at T0 was included in all prospective analyses.

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3. Results

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From May 2009 to July 2013, 483 patients who sought treatment in the participating

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center met inclusion criteria for the study. Among these eligible patients, 33 % agreed to
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participate (n=159). Among participants, the average response rate to the multiple EMA
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assessments was 83.1%. The average mean intensity of craving was 3.59 and use of the main
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problematic substance was reported in 38.1 % of the EMA observations. As the day of the

study progressed, a decrease was observed in the frequency of substance use (γ=-0.017,
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SE=0.008, t=-2.120, p=0.035). Polysubstance use was also frequent over this period, with
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two-thirds of positive reports involving substances other than the substance at the origin of

treatment. In most cases, use of these additional substances involved cigarette smoking
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(96%).
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Ninety-five patients presented a current diagnosis of anxiety and/or mood disorder

(59.7 %). Table 1 provides the clinical characteristics of the sample and EMA reports.
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The association of mood states with craving intensity was examined first by including

each mood state (sad, anxious) and event negativity as predictors of craving levels for the

subsequent assessment. We tested these associations separately in the groups with and

without a current diagnosis of mood and/or anxiety disorder (Table 2). The intensity of
negative moods and event negativity perceived at any given assessment (T0) were not

associated with craving intensity at the T1 assessment occurring on average four hours later,

in either of the two groups.

Additional cross-sectional analyses revealed that mood states were strongly associated

with craving, but only in the group without a current diagnosis of mood and/or anxiety

disorder (Table S1)1. In the prospective models, when the status of the dependent variable

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(craving) at the T0 assessment was not controlled in the model, mood states at T0 remained

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unassociated with craving intensity at T1 with the exception that anxiety at T0 was associated

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with more craving at T1 in the group without current mood and/or anxiety disorder (Table

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S2)2.

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As demonstrated by Figure 1, craving assessed at T0 was associated with T1
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substance use after controlling for substance use at T0 in the group with (p=0.009, OR=1.13,

95% CI: 1.03 – 1.23) as well as without a current diagnosis of mood and/or anxiety disorder
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(p=0.002, OR=1.20, 95% CI: 1.07 – 1.34). The intensity of negative moods and event
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negativity perceived at T0 were not associated with substance use at the T1 assessment in
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either group.
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The associations of current anxiety and/or mood disorders with craving intensity,

substance use, and mood state reports during EMA monitoring are presented in Table 3. A
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diagnosis of a current mood and/or anxiety disorder was associated with higher craving
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intensity (p=0.014), more frequent substance use (p=0.003), as well as higher levels of sad

mood (p<0.001) and anxious mood (p<0.001). These comorbid disorders were not
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significantly associated with event negativity. When models were conducted separately for

each substance group, current anxiety and/or mood disorders were associated with higher

1
Supplementary material can be found by accessing the online version of this paper at http://dx.doi.org and by
entering doi : ...
2
Supplementary material can be found by accessing the online version of this paper at http://dx.doi.org and by
entering doi : ...
craving intensity in the cannabis group (γ coef = 1.956, SE= 0.471, p<0.001). A non-

significant relationship in the same direction was observed in the alcohol (γ coef = 0.519,

SE= 0.357, p=0.154), tobacco (γ coef = 0.218, SE= 0.480, p=0.651), and opiate (γ coef =

0.071, SE= 0.476, p=0.882) groups. A diagnosis of a current mood and/or anxiety disorder

was nonetheless associated with more frequent substance use in both the alcohol (γ coef

=0.886, SE= 0.391, p=0.029) and cannabis (γ coef = 2.264, SE= 0.428, p<0.001) groups,

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while not significant for the tobacco (γ coef = 0.337, SE= 0.542, p=0.538) and opiate (γ coef

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= -0.150, SE= 0.393, p=0.705) groups. Additional pairwise comparisons across substances

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confirmed that the associations between current anxiety and/or mood disorders and both

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cravings and substance use were significantly greater in the cannabis group compared to the

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opiate, tobacco and alcohol groups, as well as greater in the alcohol group compared to the
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opiate group for substance use prediction (data not shown).
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Finally, the possibility that current psychiatric comorbidity influenced the magnitude
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of the relationship between craving and later substance use was examined. The cross-level

interaction between current psychiatric comorbidity and the within-person association of

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craving intensity and later substance use was not statistically significant (γ coef = -0.022, t=-
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0.466, p=0.642). However, when craving intensity at T0 and current psychiatric comorbidity

were included as predictors of substance use at T1 in the same model, the effect of each
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variable remained significant (for current psychiatric comorbidity: γ coef = 0.636, t=3.189,
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p=0.002, OR=1.89, 95% CI: 1.27-2.80; for craving intensity at T0: γ coef = 0.131, t=2.729,

p=0.008, OR=1.14, 95% CI: 1.04-1.25), suggesting that comorbid disorders influence the
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frequency of substance use through additional mechanisms other than craving intensity. The

cross-level interactions between substance groups and the within-person association of

craving intensity and later substance use were not statistically significant (opiates: γ coef = -

0.036, t=-0.108, p=0.740; tobacco: γ coef = -0.084, t=-0.114, p=0.461; alcohol: γ coef =
0.009, t=0.106, p=0.933; cannabis as reference group).

4. Discussion

This manuscript aimed to better understand the link between comorbid mood or

anxiety disorders and addiction. We used mobile technologies to examine the effects of mood

or anxiety disorders separately on craving intensity and substance use, as well as to

investigate whether these comorbid disorders may influence the relationship between these

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variables. The findings confirm the predictive value of craving intensity on subsequent

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substance use and relapse vulnerability as has been repeatedly observed in laboratory and

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clinical studies. This is in line with theoretical models of addiction that point out the

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relevance of craving states in the pathophysiology of substance use and relapse (Auriacombe

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et al., 2018; Fatseas et al., 2015; O'Brien, 2011; Sayette, 2016). In addition to this strong
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association, we found that a current mood and/or anxiety disorder increased craving intensity
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and thereby the risk for substance use. These findings are consistent with previous studies
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that have shown associations between depression or anxiety disorders with more substance

use and poorer treatment outcome among patients with substance addiction (Compton et al.,
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2003; Gamble et al., 2010 ). This link is also consistent with previous research indicating that
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depressive and anxiety symptoms are associated with heightened reactivity to cues and with

differential brain activity (Feldstein Ewing et al., 2010), and may be explained through
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different hypotheses. First, physiological and biological responses to stress in individuals

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with addiction seem to increase cue-induced craving and substance relapse risk (Back et al.,

2010; Fatseas et al., 2011; Sinha et al., 2011). As mood or anxiety disorders are associated
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with psychiatric distress and alterations in biological stress responses (Dedovic and Ngiam,

2015; Vreeburg et al., 2010), our findings raise the issue of whether the association between

current psychopathology and increased craving intensity may be supported in part by

underlying alterations in biological stress responses. Secondly, associated psychopathology

may increase the salience of cues with increased anticipation of reward, greater negative

reinforcement expectancies and little attention to negative consequences, that may each

enhance craving intensity and relapse risk (Pang et al., 2014; Robinson et al., 2012).

It is important to note, however, that the relationship between comorbid

psychopathology and craving or substance use was not explained by increases in negative

emotional states or perceived event negativity. In our study, no association was found for sad

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and anxious moods experienced at a given moment during the day and craving intensity over

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subsequent hours, while most previous EMA studies have reported correlations between NA,

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stress and higher craving among patients with substance addiction (for review, see (Serre et

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al., 2015)). For example, a relationship between anxiety and further craving was previously

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reported among cannabis users (Buckner et al., 2012). These discrepancies should be
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explained by the fact that initial craving levels were not controlled for. Indeed, NA should co-
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occur during craving episodes, and craving at one assessment was found predictive of higher
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negative mood at the next assessment (Buckner et al., 2012). Previous laboratory studies

nonetheless provided evidence that the experience of craving is associated with negative
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emotions as well as alterations in biological stress responses (Fatseas et al., 2011; Sinha,
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2008), and similar results were observed in the group without a current diagnosis of mood

and/or anxiety disorder in our study (Table S1)3. Based on these findings we suggest that in
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patients without current psychiatric comorbidity the negative emotions reported may be better
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explained by craving itself and its negative affect component, as craving states represent a

high-stress condition and are marked by increased emotional distress (Sinha et al., 2011).
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Interestingly, in our study, mood states were not associated with craving in the group with

current psychiatric comorbidity (Table S1)4. These findings suggest that psychiatric disorders

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Supplementary material can be found by accessing the online version of this paper at http://dx.doi.org and by
entering doi...
and their heightened negative mood states could influence substance use by mechanisms that

are partly independent of their influence on craving intensity.

It is also important to note that the relationship between comorbid psychopathology

and craving or substance use was not systematically found when models were examined

separately for each substance group. While current anxiety and/or mood disorders were

associated with higher craving intensity and more frequent substance use in the cannabis

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group, these effects were of smaller magnitude in other substance groups. Although we

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cannot exclude the possibility that associations observed in the entire sample were due

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mainly to the cannabis group, this finding could be partly explained by the fact the patients

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from the opiate, tobacco, and alcohol groups were more likely to receive pharmacological

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treatments for addiction (93.9%, 93.0%, and 87.5% respectively) compared to the cannabis
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group (14.3%). Such treatments may have therefore modified the occurrence of craving and
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substance use and consequently attenuated the effect of comorbid psychopathology on
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craving and substance use. Nonetheless, the substance groups when added as cross-level

interactions did not influence the within-person association of craving intensity and later
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substance use, confirming results obtained in analyses conducted separately in each substance
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group from the same sample (Serre et al., 2018).

Importantly, current mood or anxiety disorder diagnoses did not influence the
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prospective association between craving intensity and later substance use, but rather these
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comorbid disorders were associated with additional increased substance use after accounting

for their effect on craving. These findings suggest that the influence of these psychiatric
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disorders on substance use is partially independent of their influence on craving intensity.

However, the other mechanism not related to craving intensity in which current psychiatric

diagnoses are associated with more severe substance use remains to be clarified. It is possible

that individuals with mood and/or anxiety disorders want to self-medicate or regulate their
emotional distress, although motivations for use should be further assessed (Auriacombe and

Fatséas, 2007; Bolton et al., 2006). On the other hand, the relationship between

psychopathology and substance use could also be explained by other factors not evaluated in

this study, such as decision making deficits or impulsivity (Boschloo et al., 2013; Paulus and

Yu, 2012). Additional studies are therefore needed to address the mechanisms through which

depression and anxiety lead to more substance use independently of craving intensity.

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The present findings have important clinical implications. While interventions for

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individuals with substance use disorders should focus on craving reduction through

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psychosocial care and pharmacological interventions (Auriacombe et al., 2016a; Auriacombe

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et al., 2016b), previous studies have shown that the magnitude of craving responses may be

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related to a multitude of intra- and inter-individual variables (Serre et al., 2015). The present
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findings contribute to this issue by identifying individual clinical risk factors for increased
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craving intensity and further substance use and thereby should promote the systematic
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screening of co-occurring mood or anxiety disorder as well as the need for more intensive

and focused interventions based on craving reduction and management. Another notable
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finding is that psychopathology may also have a direct influence on substance use,
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independently of craving intensity. In this perspective, integrated models of intervention are

also essential for reducing substance use and improving outcomes in individuals with the dual
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disorder (Pettinati et al., 2013). Recent treatment strategies of combined medications for
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depression and alcohol addiction using anti-craving treatment have demonstrated success to

simultaneously reduce depressive symptoms and excessive drinking (Pettinati et al., 2010).
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Further research is needed to guide and optimize clinical practice and pharmacological

management of co-occurring substance use and mood/anxiety disorder.

Several limitations of this study should be considered in interpreting the findings. While a

minority (33%) of patients accepted to participate in this study, no sociodemographic or

clinical differences between eligible individuals who refused participation and those who

accepted were found (Serre et al., 2012), and the final sample was highly similar to

population of individuals seeking treatment in France or Europe at large (EMCDDA, 2015).

Furthermore, the self-report measure of craving did not assess the multidimensional feature

of this construct. Some authors have suggested the existence of different subtypes of craving

(Verheul et al., 1999), and we can hypothesize that psychopathology may affect these

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subtypes in different ways. Further EMA studies should, therefore, include multi-dimensional

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assessments of craving to address this issue. In addition, our study did not specifically

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examine the association between positive affect (PA) and craving. Some studies reported

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mixed results concerning this association that has been reported to be positive by some

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investigators (Delfino et al., 2001; Dunbar et al., 2010) and negative by others. Interestingly,
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PA was found related to cannabis use, but not after controlling for NA (Buckner et al., 2013).
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That failure to control for NA may at least partially explain some of the mixed findings

regarding PA’s relation to craving/substance use from other EMA studies. Our EMA
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evaluation of emotions was based on the circumplex model of emotions, considering PA and
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NA as opposite ends on the same dimension (Russell, 1980). Further studies should,
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therefore, examine PA as an independent predictor of craving and substance use. Another

limitation of this study is that signal schedules were fixed per individual. However, in a
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validation study of this same sample, activity and environmental categories examined did not
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vary by study duration, suggesting that reactivity or practice effects were negligible (Serre et

al., 2012). Finally, this study focused on a group of patients with different forms of addiction.
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While previous analyses revealed no influence of substance group on the prospective link

between craving and substance use (Fatseas et al., 2015), in the present study the relationship

between psychopathology and craving or substance use was not systematically found

statistically when models were examined separately for each substance group. The possibility
cannot be excluded that anxiety/mood disorders and mood states could be differentially

associated with craving and use according to the type and pharmacological effects of each

substance.

5. Conclusions

The present findings add to the growing literature demonstrating that craving is a

major mediator of substance use in individuals with substance use disorders. While the

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findings clarify that mood and anxiety disorders are associated with greater craving intensity

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and, therefore, influence substance use frequency, these forms of comorbidity also increase

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the probability of substance use through mechanisms other than craving intensity. These

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findings argue for the development of integrated dual disorder treatment programs for

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patients who request treatment for substance use disorders and meet criteria for mood or
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anxiety disorders.
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Authors Disclosures
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Role of Funding Source

This work was supported by a Research Grant PHRC (2006-2014) from the French Ministry
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of Health, Research Grant AAP-Recherche-CRA (20091301018) from the Aquitaine

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Regional Council and French Government Addiction Agency MILDT grant 2010 to MA

French National Research Agency PRA-CNRS-CHU-Bordeaux award (2008-2010) to MF,

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and CNRS ATIP award to JS. The funding sponsors had no role in the design and conduct of
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the study, in the collection, analysis, and interpretation of the data, or in the preparation,

review, or approval of the manuscript. The researchers confirm their independence from
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funders and sponsors. All authors report no competing interests.

Contributors

MA and JS had full access to all of the data in the study and take responsibility for the

integrity of the data and the accuracy of the data analysis. MA was the overall principal
investigator of the study, obtained funding and access to participants. JS obtained funding

and supervised data collected using mobile technologies. MA, JS and MF developed the

study design and methods. FS and MF participated in patient recruitment and data collection.

MF, FS, MA and JS undertook analysis and interpretation of data and the drafting of the

manuscript. MF, FS, MA and JS, undertook the critical revision of the manuscript for

important intellectual content. All authors have reviewed and approved the current version of

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the manuscript.

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Conflicts of Interests

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No conflict declared.

SC
Acknowledgments

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The authors express their thanks to all participants for their contribution and are grateful to

the participants’ treating addiction physicians for their collaboration: Dr. Jacques Dubernet,
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MD, Dr. Saman Sarram, MD, Dr. Audrey Guerin-Vossart, MD, Dr. Yannick Saura, MD, Dr.
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Christelle Donon, MD, Dr. Bérengère Gelot, MD, Dr. Cécile Gazel, MD.
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Figures
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Figure Legend
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Figure 1.

Caption: Substance use reported at any assessment (T1) as a function of craving intensity
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reported at the previous assessment (T0), adjusting for age, sex, number of years of

education, employment status.

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Legend:

With current mood/anxiety disorders (n = 95)

Without current mood/anxiety disorders (n = 64)
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Figure 1.
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Table 1. Characteristics of the final sample and description of daily life variables according to current comorbid psychiatric disorders.
Without Current Mood With Current Mood and/or

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and/or Anxiety disorder Anxiety disorder

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(N= 64) (N= 95)

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Min Max % n Mean SD % n Mean SD p*
Sample characteristics
Sex (female)
ED 37.5 24 29.5 28 0.290
Main problematic substance use 0.245
-alcohol 28.1 18 31.6 30
PT
-tobacco 29.7 19 25.3 24
-cannabis 15.6 10 26.3 25
-opiates 26.6 17 16.8 16
E

Employed 67.2 43 49.5 46 0.028

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Age 19 65 35.0 10.7 37.8 10.9 0.108

Education (years) 7 25 12.9 2.9 12.0 2.7 0.030
§
Addiction severity
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Number of years of use 1 56 13.9 11.9 15.8 11.0 0.309

Age of substance use onset 9 49 21.2 7.2 22.1 8.9 0.505
Number of previous treatment 0 51 2.1 0.6 1.5 0.5 0.398
MINI current diagnosis (DSM-IV)
Mood disorder - - 64.2 61
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Major depression 57.0 59
Bipolar Disorder I 16.1 15

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Bipolar Disorder II 8.5 8

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Anxiety disorder - - 78.9 75
Social phobia 20.6 19

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Panic disorder 9.7 9

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Agoraphobia 30.4 28
Generalized anxiety disorder 51.1 47
Post-traumatic stress disorder
ED 15.4 14
Obsessive-compulsive disorder 7.6 7
EPT
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Table 1 (continued)
Without Current Mood With Current Mood

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and/or Anxiety disorder and/or Anxiety disorder

N
(N= 64) (N= 95)
Min Max % n Mean SD % n Mean SD p*

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MINI current diagnosis (DSM-5)

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Tobacco Use Disorder 79.4 50 81.5 75 0.738
Alcohol Use Disorder 35.9 23 45.2 42 0.248
ED
Cannabis Use Disorder
Cocaine Use Disorder
26.6
0
17
0
41.9
7.5
39
7
0.048
0.025
Opiate Use Disorder 26.6 17 1.4 18 0.286
PT

EMA reports # 2435 observations 3810 observations

Main problematic substance use 0 1 25.6 649 46.4 1768 0.001
Others’ substance use
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0 1 63.2 1603 65.5 2490 0,596

Craving intensity 1 7 3.16 2.09 3.87 2.06 0.013
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Sad mood intensity 1 7 3.33 1.20 3.94 1.30 <0.001

Anxious mood intensity 1 7 3.26 1.15 3.92 1.56 <0.001
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Event negativity 1 7 3.56 1.61 3.94 1.64 0.014

Notes: *Comparison of patients with vs. patients without current mood and/or anxiety disorder. ANOVA and chi-square tests were used to compare
quantitative and qualitative variables. For EMA variables, multiple comparisons were performed by HLM means-as-outcomes models, with current
diagnosis of mood and/or anxiety disorder as predictor of EMA reports.
#
Frequencies, percentages and means are based on the total number of valid electronic interviews over the assessment period.
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§
For the specific substance at the origin of addiction treatment (alcohol, tobacco, cannabis or opiates)

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N
A
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ED
E PT
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 Table 2. Prospective associations between mood states and event negativity with later
craving intensity and substance use.
Without Current Mood and/or With Current Mood and/or

Predictor (T0) Outcome (T1) Anxiety disorder (N= 64) Anxiety disorder (N= 95)

Coef SE df T-ratio Coef SE df T-ratio

Sad mood Craving 0.025 0.068 61 0.374 -0.129 0.066 92 -1.938

Anxious mood Craving 0.062 0.058 61 1.056 0.003 0.052 92 0.056

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Negativity of events Craving 0.031 0.054 61 0.564 -0.013 0.039 92 -0.332

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Sad mood Substance Use 0.026 0.049 61 0.531 -0.070 0.075 92 -0.935

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Anxious mood Substance Use 0.061 0.044 61 1.393 -0.025 0.050 92 -0.502

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Event negativity Substance Use 0.025 0.035 61 0.709 -0.003 0.050 92 -0.052

Craving Substance Use 0.183 0.056 61 3.256** 0.118 0.044 92 2.683**

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**p<0.01; adjusted for age, sex, status of the dependent variable at T0. Substance use refers
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to the use of the main problematic substance (alcohol, tobacco, cannabis or opiates).
A
M
ED
E PT
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 Table 3. Current comorbid mood and/or anxiety disorders as predictors of craving, substance
use, negativity of events and mood states (N=159).

Predictor Outcome γ Coef SE df T-ratio

Current mood and/or anxiety disorder Craving 0.632 0.254 153 2.482*

Current mood and/or anxiety disorder Substance use 0.162 0.052 153 3.089**

Current mood and/or anxiety disorder Sad mood 0.585 0.112 153 5.202***

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Current mood and/or anxiety disorder Anxious mood 0.644 0.139 153 4.645***

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Current mood and/or anxiety disorder Event negativity 0.253 0.142 153 1.778

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*p<0.05, **p<0.01, ***p<0.001; adjusted for age, sex, number of years of education,

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employment status. Substance use refers to the use of the main problematic substance
(alcohol, tobacco, cannabis or opiates).

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N
A
M
ED
E PT
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A