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Addiction is a mental illness in which psychiatric conditions imply a prominent burden. Psychopathological symptoms in substance use disorder SUD patients are usually viewed as being assignable to the sphere of a personality trait or of comorbidity, leaving doubts about the presence of a specific psychopathology that could only be related to the toxicomanic process. Our research group at the University of Pisa has shed light on the possible definition of a specific psychopathological dimension in SUDs. In heroin use disorder patients, performing an exploratory principal component factor analysis PCA on all the 90 items included in the SCL questionnaire led to a five-factor solution. These same results were replicated by applying the PCA to another Italian sample of 1, heroin addicts entering a Therapeutic Community Treatment. Further analyses confirmed the clusters of symptoms, independently of demographic and clinical characteristics, active heroin use, lifetime psychiatric problems, kind of treatment received, and, especially, other substances used by the patient such as alcohol or cocaine. Moreover, these clusters were able to discriminate patients affected by addiction from those affected by psychiatric diseases such as major depressive disorder. Our studies seem to suggest the trait-dependent, rather than the state-dependent, nature of the introduced psychopathology dimensions of SUDs. Substance use disorder SUD individuals show an incredibly high comorbidity concomitance with mental illness, especially with anxiety, impulse control, and mood-related disorders 1 , 2. Moreover, the association with psychotic disorders is greater than what could be expected by chance 3 — The linkage between substance use abuse or dependence and mental illness is tricky. From a theoretical point of view, four possible explanations can be put forward: the first is that the manifestation of addiction may be facilitated by the presence of a mental disorder; the second is that SUDs elicit the onset of other mental disorders; the third is that the underlying causes of substance use and other psychiatric disorders may be the same; and the fourth is that factors linked to sampling, selection of instruments for diagnosis, investigation, and analysis could have led to an incorrect estimation of comorbidity. This is critical because, besides the issue of chronology in dual diagnosis which disease come first between addiction and another mental illness , the point is the need to understand the real nature of addiction by looking at the possible presence of a psychopathology that is exclusively related to the toxicomanic process. Actually, some criticism became public about the classical model of psychiatric comorbidity in the field of SUDs that leads to a high frequency of association between the two disorders. This close association raises doubts about whether the two conditions are actually independent, especially when taking into consideration the overlap between biological substrates and the neurophysiology of the psychiatric symptoms and addictive processes that are related to addiction 11 , Our V. Dole Dual Diagnosis research unit at the University of Pisa, Italy, has worked hard on this specific issue in recent years. Taking into account the ineliminable factor of uncertainty in the correct classification of symptomatology—as being intrinsic to the addictive disorder or as due to comorbidity—it seems best to try to approach the psychopathology of addicts by starting from a low inference level—rooted in the symptoms expressed by patients—rather than starting from a pre-established syndromic level such as that of DSM nosography. We started by subtyping patients, using a sample of heroin-dependent patients, and working with their responses to the Self-Report Symptom Inventory SCL survey. The choice of using heroin addicts was in line with our conviction that opiate addiction is a paradigm for the study of SUD We considered a sample consisting of 1, subjects, evaluated at their treatment entry and named agonist opioid treatment sample AOT cohort. Data were stored in the University of Pisa dataset: an anonymous database collected for research and clinical purposes. For details regarding the AOT cohort, see Maremmani et al. Using an exploratory principal component factor analysis PCA of the SCL questionnaire, a five-factor solution was found. The items that had shown the greatest loading supplied the names of the single factors. Taken together, the five factors accounted for Considering the highest z -scores obtained for each of the five SCL factors dominant SCL factor , subjects were allocated to one of the five mutually exclusive groups. These five groups were sufficiently distinct and failed to reveal any significant overlap. These feelings are frequently reported by SUD subjects at treatment entry, who talk of a feeling of being trapped in a corner, abandoned; they worry too much about difficulties, they feel guilty and report no sexual drive. Memory impairment and compulsivity are not present in any domain. Thought disorders consist of feeling alone even at moments spent together with other individuals. This dimension can be considered on the basis of the close linkage between SUD and mental disorders, in terms of the epidemiology of the two conditions, their psychological and neurobiological background and the shared psychopathological risk factors 15 — The second domain somatization is distinguished by a number of anxious and somatic elements, which could be typical of opiate withdrawal feature. These patients complain of back pain, muscle aches, weakness and tiredness, heavy legs and arms, paresthesia, and loss of sensitivity somewhere in the body. Cold shivers and hot flushes are possible too, even stomach ache and nausea. Getting to sleep is difficult and, as a rule, when sleep comes, it is disrupted. The second dimension, resembling an opioid withdrawal condition, may be related to a request for treatment. The third factor sensitivity—psychoticism features psychoticism and sensitivity. Subjects think that people are looking at them and are talking about them, maybe organizing something against them. They think they are not respected because of their personal perspective. They believe that others do not sympathize with them or actually disapprove of their conduct. They feel uneasy or uncomfortable when they find they are being looked at by others, have to be in crowded places, or have to do things with others e. These behaviors can be considered as psychotic when patients feel sure that others influence, control, or read their thoughts. This dimension can be considered in the light of the self-medication hypothesis, due to the antipsychotic action of opioids 23 — 30 or is often related to the co-abuse of cannabis and stimulants 31 — The fourth factor panic—anxiety can be summarized as a fear of going around alone, traveling by train, bus, or subway agoraphobia , fear of feeling sick or sensations of dizziness, and episodes of critical anxiety. Generalized fear is a feature, with the need to avoid activities or places in order to prevent acute anxiety. This dimension too may be involved in the overlap between anxiety and withdrawal symptomatology, as the two conditions share physiopathological and neurobiological features 40 — The fifth factor violence—suicide includes aggressiveness against others as well as self-direct aggressiveness. Rage, anger, and smashing things up are the key components of this domain. These individuals have a habit of arguing with others and showing high energy levels, together with returning to ideas about death. There is an extreme impulsiveness, which marks out the behaviors of SUD individuals, and should be assessed in light of the shared neurobiological background the prefrontal cortex and limbic system and risk factors antisociality and drug-related lack of control 43 — The main issue related to the identification of a specific psychopathology of HUD was the need to determine whether this five-factor compound solution obtained from a sample of HUD individuals entering agonist opioid treatment was the direct outcome of the specific condition of these patients at that time requesting pharmacological treatment , or whether it subsisted independently of the request for treatment. To better understand if we were facing a trait rather than a state nature for the proposed five factorial dimensions, we looked at confounding variables such as treatment choice, active use of substance, lifetime psychiatric problems, substance chosen, and major psychiatric conditions. To do this, we used two different cohorts of patients:. To verify whether the five psychopathological dimensions identified in AOT cohort patients were in any case observable, independently of the treatment chosen, we compared the AOT cohort with heroin-dependent patients belonging to the TC cohort. The factorial analysis applied to the SCL scores of individuals with opioid use disorder at a residential TC entry led to the same five-factor solution we pointed out in heroin addicts entering an AOT. Differences were observed in the two cohorts not only at a sociodemographic level, but also at a clinical one. Turning now to sociodemographic and clinical characteristics, patients entering TC or AOT did not present differences in gender or education, but they did differ in marital status, welfare benefits, employment, age, prior treatments, and heroin addiction length. It is important to notice the differences in the settings of the two treatments: AOT is a highly standardized program, usually centering on buprenorphine or methadone maintenance, distinguished by its scientifically proven effectiveness, regulated by clear operational procedures and guidelines 55 — 57 , whereas TC is a more heterogeneous and less standardized residential program, which is subject to adaptations brought in to satisfy the needs of special populations such as adolescents, women, and people affected by psychiatric comorbidity and financial difficulties 58 — The TC individuals selected for the study were recruited from TCs set up in 8 different Italian regions. These TCs tended to differ from one another in the services they offered pharmacological, including opioid agonist treatment, psychiatric social psychological and also educational, rehabilitative, work training, and so on , in the population target e. We verified whether any differences emerged between the five SCL dimensions previously identified through the application of PCA in comparing heroin-addicted patients who had already been detoxified DTX with those who were not yet detoxified NDTX from heroin at the time of entering a Therapeutic Community Treatment. Detoxified patients were defined as those who reported having already been detoxified and not requiring agonist opioid treatment during the first month of TC treatment. Looking at the five-factor solution, the greatest difference was found in the case of the somatic dimension, which was, in fact, the only dimension that successfully discriminated between the two groups of patients. To explore the possible impact of comorbid psychiatric conditions on the five psychopathological dimensions set out above, we verified whether heroin-addicted individuals with PC-HA or those without NPC-HA known lifetime psychiatric problems showed any differences in these five domains. We considered PC-HA patients on the basis of the previous presence of a psychiatric diagnosis, suicide attempts, psychiatric hospitalization, and psychiatric welfare benefits at treatment entry or psychiatric treatment prescription while in a therapeutic community. Conversely, older age, longer history of heroin dependence, being female, and general pattern of discriminated social status were associated with a higher proportion of heroin addicts marked out by their more severe psychopathology PC-HA. According to multivariate analysis, none of the other three domains were able to predict the allocation of subjects to the NPC-HA or PC-HA group, so their persistence as components of the SCLdefined structure of opioid use disorder may be considered independent of the presence of lifetime psychiatric problems We decided to explore the specific burden arising from the substance of abuse in identifying the psychopathological structure. We considered subjects affected by cocaine, alcohol, and heroin dependence according to a diagnosis based on clinical judgment, availability of the SCL questionnaire, and an age of 18 years old or more, leading to the selection of a sample of 2, individuals Patients with heroin, alcohol, or cocaine dependence showed differences in most of the demographic characteristics considered: differences emerged in the frequency of male gender, age of subject, living conditions, and marital status. Alcohol dependents were older, and they tended to live alone more often than heroin or cocaine dependents; heroin dependents were more frequently single and less frequently male than cocaine-dependent ones. In subjects with primary opioid dependence, those with cocaine as secondary substance of abuse showed a lower educational level than those who had alcohol as secondary substance of abuse, and in their group, the level of unemployment had to be calculated at a higher level than those who had any other secondary substance of abuse. The further logistic regression analyzing cocaine versus alcohol as primary substance of abuse did not detect any significant association between the five domains and the primary substance of abuse. No statistically significant differences were observed between the three groups in any of the five SCL-based psychopathological domains. Considering major psychiatric diagnosis, it is important to demonstrate that these five dimensions were able to differentiate SUD patients from other psychiatric patients. If our five dimensions are directly correlated with heroin SUD, we would expect to find a higher prevalence of these dimensions in heroin-addicted SUD patients than in MD ones. Heroin SUD patients present a lower level of severity of psychopathological symptoms in general and a lesser severity of current symptoms with respect to MD subjects. Although differences in age, gender, and severity of psychopathological symptoms were observed, according to SCL criteria, the best predictor of being a heroin-addicted SUD subject remains a prominent psychopathology. The results of our studies open the way forward to the possible identification of a specific psychopathology of heroin addiction and addiction per se. These five-factor dimensions appear to be different from the dimensions that are related to mental illness patients and remain stable no matter which confounding factors are considered, among those that are most pertinent when we are dealing with addicted patients. When the choice of treatment is considered, the model of SCL used by us showed the same five-factor solution for both TC and AOT groups of individuals. This result should be interpreted after taking into consideration the fact that AOT patients are better equipped to handle the features of violence and suicide, as well as showing a positive effect on somatic dimensions that may be closely related to withdrawal symptoms Considering now other confounding factors, it is comprehensible that patients who still have a job are at their first request for treatment, are distinguished by a short addiction history, and are therefore likely to select a less stringent treatment program, such as AOT, which will lead to treatment having lower repercussions on their daily life. The SCL items included in this dimension correspond to a number of somatic complaints e. In fact, the lower score shown by NDTX subjects for the somatic dimension can plausibly be attributed to the low or zero level of tolerance they show to opioids. Regarding the lower psychopathological severity shown by DTX patients in the other four SCLbased psychopathological dimensions, besides the effect of the anti-withdrawal treatment, which should never be overlooked 65 , 66 , it might result from the interruption of a disruptive addiction-related lifestyle, with its influences on the usual affective and cognitive parameters of patients, as well as from the changes in expectations arising from the implementation of a detoxification program. This explanation is consistent with our findings on the easier resolution of the physiological symptoms of withdrawal compared with the psychological ones. One particularly instructive example is anxiety, which, together with other affective components of the withdrawal condition—those related to the reduction of dopamine tone and to the activation of the stress system—tends to persist longer after the interruption of heroin use 67 — In this case too, however, the alternative possibility—that patients who have been less severely damaged on psychological and psychiatric grounds may have found it easier to interrupt heroin use before entering TC—should also be kept in mind throughout treatment. One possible explanation takes into account the high percentage of somatic symptomatology that is observed both in the general psychiatric population 79 — 81 and in the dual diagnosis addict population 72 , 82 , The involvement of these brain regions has been observed in neuroimaging studies — , such as those linked to the exploratory circumstances of decision-making or other neuropsychological assignments carried out by chronic SUD individuals 44 , 99 , , Surely, substance of abuse works on different neuronal systems, nearly all of them leading back to the DA-ergic and opiate systems. In aiming to explain addiction per se , it was important to exclude another confounding factor—none other than the specific substance of abuse: heroin, cocaine, or alcohol, leading to the consideration that this structure is largely independent of the specific drug used. In considering the frequency of the five predominant psychopathological dimensions in patients with primary opioid dependence, the use of alcohol or cocaine as secondary substance of abuse does not lead to any significant difference; thus, the use of these additional substances appears to have no significant impact on these dimensions. As regards psychiatric severity, considering the full sample, the SCL average scores seem to follow a decreasing order in four of the five psychopathological dimensions, with patients who have primary alcohol dependence showing the highest and those with cocaine dependence the lowest severity. Conversely, when considering the somatic symptoms related to the SCL questionnaire, only mild somatic symptoms, or none at all, are associated with cocaine dependence 14 , These two forms of SUD are associated with a high odds ratio for the presence of anxiety disorders, given that anxiety is considered an important element in the toxicomanic progression from use to dependence 1 , , It should be remembered that anxiety is a frequent consequence of cocaine use or intoxication, and also that in alcohol dependence anxiety emerges as a component of withdrawal. Moreover, we should take into account that alcohol withdrawal-related anxiety, unlike most of the other physical symptoms accompanying withdrawal, may last for months , Persistent changes in the GABA and NMDA circuits associated with the development of tolerance and withdrawal could be at the basis of the long-lasting nature of anxiety-related symptoms 41 , Finally, we defined the capability of this five-factor solution to differentiate between HUD and MD patients. Some of the differences that have been found are, of course, related to the pathophysiological course of the illness. In fact, while addiction tends to have an earlier onset 11 , , the depressive episodes that are clearly expressed occur more and more frequently as time goes by, especially the reactive ones that are due to stressful events encountered in life HUD patients are more frequently males than MD patients. In particular, women are twice as likely as men to be depressed, while men tend to present a higher risk of substance and alcohol abuse disorders — In this way, we were also able to test the importance of differences in age and gender in limiting the importance of the psychopathological symptoms. Of fact of particular interest is that in differentiating heroin SUD from MD patients, the quality of the psychopathology encountered is more important than the severity of symptoms. Looking at this in a quantitative way, MD patients have a more severe psychopathology overall, but, from a qualitative perspective, four out of the five specific dimensions in the five-factor solution for psychopathology differentiate heroin addicts from depressed subjects. As regards the Panic—Anxiety dimension, it is important to consider the involvement of a specific cerebral circuit—the LC noradrenergic system—in the affective and physiological changes seen in heroin addiction, especially those due to withdrawal and protracted withdrawal, as well as those found in Anxiety disorders 84 — The inability of this dimension to differentiate between heroin-addicted SUD and MD patients may be related to the transnosographic nature of anxiety-related symptoms, which may be considered rather common features both of addictive and depressive disorders. We found that in heroin SUD patients, depressive symptomatology remains the most important and frequent psychopathological aspect of heroin SUD. Moreover, this symptomatology is less closely related to suicidal ideation than in depressed patients. It mainly reflects a depressive dimension distinguished by depressed mood, feelings of uselessness, being trapped in a corner, sad, abandoned, with no interest or goal, and unreasonably consumed by difficulties as well as feelings of guilt and experiencing a low or zero sexual drive. These symptoms identify an overall condition of depression, but it is critical to understand which kind of depression we are looking at. Depression can be due to the use of substances e. Hypothetically, and this is our view, a specific depression peculiar to heroin addiction may come to be recognized as a component of its own psychopathological structure. It is not surprising that somatic symptoms can differentiate heroin-addicted SUD patients. This is in line with heroin addiction withdrawal symptoms that are linked with anxiety. More frequently, heroin SUD patients showed prominent sensitivity—psychoticism symptoms. In addition, we have demonstrated that, taken together, the sensitivity and psychoticism dimensions were linked with younger heroin SUD patients, whereas older subjects who had HUD showed higher values for the somatization and worthlessness-being trapped symptomatology Finally, it seems of particular interest that MD patients were distinguished by suicide ideation, which, in heroin SUD patients, constitutes a dimension unrelated to the depressive one. In general, guilt and suicidality are a psychopathological substrate that is typical of a depressive state. In heroin SUD patients, their guilt appears to be more strongly linked with feelings of being trapped and with a consequent sense of worthlessness. SCL questionnaire was used to highlight the psychiatric and psychological profiles of individuals belonging to both samples. Symptoms were collected on subjective perceptions self-administration. In any case, having a self-driven questioner makes it possible to investigate symptoms from a dimensional perspective instead of using a group of several interviewers—a feature that inevitably leads lead to a non-uniform interviewer-related objective rating. It must, surely, be taken into account that some individuals may hide some symptoms, either voluntarily or involuntarily. Using questionnaires to check the tendency of patients to lie is bound to function as a factor that helps to ensure the fairness of our data. The individuals involved in our study were without any formal psychiatric diagnosis. It is important to know that in Italy a diagnosis is formulated at a late stage of treatment, either in addiction facilities or local units. The impact of psychiatric problems cannot be discriminated by using the SCL questionnaire, and, surely, we cannot say whether or how strongly the profiles identified may correlate with a specific diagnostic criterion. Of course, a formal and objective psychiatric diagnosis would have to distinguish between subjects who have and those who do not have a significant psychiatric condition. Another limitation in using the SCL scale is that it was administered at treatment entry only; the selection of one single time means highlighting only that specific moment in the life of a heroin addict; we certainly know that some symptoms may vary in accordance with the different stages of the disease, whereas some may improve or at least be reduced in their intensity due to a specific kind of treatment leading to a sort of underweighting or overweighting within our sample. Moreover, the TC cohort and the OAT sample show differences in several factors especially age and length of drug dependence. First, diagnosis in the two samples was inevitably differentiated; considering the DSM-based criteria applied in the OAT sample and the clinically based criteria used in the TC sample, bias should be allowed for. On the other hand, one cannot exclude either the opposite situation in which individuals in the TC sample did not fully reflect the DSM diagnostic criteria. One consequence is that the magnitude of the measures of association used in our study could be underestimated or overestimated. Our studies shed light on a specific aggregation of psychopathological symptoms in cases of HUD—a fact that strengthens the feasibility of the five-factor solution. It is now possible to say that these aggregations of symptoms are stable regardless of demographic and clinical characteristics, kind of treatment chosen, active involvement in substance use, lifetime psychiatric problems, and the substance chosen. These results pave the way to the delineation of a trait nature in place of a state nature in the perception of the structure of these five-factor psychopathological dimensions of heroin addicts. Moreover, the results shown by implementing a rigorous comparison of different substances of abuse allow us to define addiction as a unitary condition. AM and IM drafted the strategy of the review and the present manuscript. SB and LR critically revised the article. All the authors read and approved the final manuscript. The other authors declare no conflict of interest. The sponsors had no role in the study design, in the collection, analysis or interpretation of data, in writing the manuscript, or in the decision to submit the manuscript for publication. The authors thank Anthony Johnson for the language revision. Region of Piedmont provided additional funding. No other financial support was requested for the study other than internal funds. Comorbidity of mental disorders with alcohol and other drug abuse. JAMA 19 —8. Results from the National Comorbidity Survey. Arch Gen Psychiatry 51 1 :8— Substance abuse and psychopathology: a diagnostic screening of Italian narcotic addicts. 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Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher. Top bar navigation. About us About us. Sections Sections. About journal About journal. Article types Author guidelines Editor guidelines Publishing fees Submission checklist Contact editorial office. Psychiatry , 27 April Angelo G. Introduction Substance use disorder SUD individuals show an incredibly high comorbidity concomitance with mental illness, especially with anxiety, impulse control, and mood-related disorders 1 , 2. Exploratory Factor Analysis on SCL Questionnaires of Heroin Use Disorder HUD Individuals Entering Agonist Opioid Treatment: Identification of Dominant Factors Taking into account the ineliminable factor of uncertainty in the correct classification of symptomatology—as being intrinsic to the addictive disorder or as due to comorbidity—it seems best to try to approach the psychopathology of addicts by starting from a low inference level—rooted in the symptoms expressed by patients—rather than starting from a pre-established syndromic level such as that of DSM nosography. Stability of the Psychopathological Profile of Heroin Addiction The main issue related to the identification of a specific psychopathology of HUD was the need to determine whether this five-factor compound solution obtained from a sample of HUD individuals entering agonist opioid treatment was the direct outcome of the specific condition of these patients at that time requesting pharmacological treatment , or whether it subsisted independently of the request for treatment. The Inquiry Became Independent of the Presence of Lifetime Psychiatric Problems To explore the possible impact of comorbid psychiatric conditions on the five psychopathological dimensions set out above, we verified whether heroin-addicted individuals with PC-HA or those without NPC-HA known lifetime psychiatric problems showed any differences in these five domains. The Inquiry Became Independent of the Choice of Substance Used Heroin versus Cocaine versus Alcohol We decided to explore the specific burden arising from the substance of abuse in identifying the psychopathological structure. Differentiation from Specific Psychiatric Psychopathological Dimensions \[Major Depression MD \] Considering major psychiatric diagnosis, it is important to demonstrate that these five dimensions were able to differentiate SUD patients from other psychiatric patients. Discussion The results of our studies open the way forward to the possible identification of a specific psychopathology of heroin addiction and addiction per se. Limitations SCL questionnaire was used to highlight the psychiatric and psychological profiles of individuals belonging to both samples. Conclusion Our studies shed light on a specific aggregation of psychopathological symptoms in cases of HUD—a fact that strengthens the feasibility of the five-factor solution. References 1.

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