Brain Opioid Theory of Social Attachment Review of the Evidence for Approach Motivation to Harm

Front Psychiatry. 2019; 10: 602.

Testing a Neuro-Evolutionary Theory of Social Bonds and Habit: Methadone Associated With Lower Zipper Feet, Comfort With Closeness, and Proximity Maintenance

Received 2019 Jun iii; Accepted 2019 Jul 30.

Abstract

Prove from not-human mammals for the interest of the endogenous opioid system in prosocial behavior is reasonably extensive and robust; however, studies in humans are lacking. This study tests the neuro-evolutionary hypothesis that exogenous opiates, including morphine, heroine, and methadone, decrease separation anxiety and proximity by hijacking the neuro-peptide endogenous opioid organization modulating social bonds. Participants were 486 subjects, 43% male, with ages between 18 and 62 years (G = 26.four; SD = 9.4), divided in 3 naturalistic groups: 1: addicts in drug-free handling; 2: addicts in methadone programs; 3: normative non-clinical controls.

Instruments: 1) Adult Zipper Scale (AAS) composed of three subscales: Anxiety about being rejected (α = 0.83), Comfort with Intimacy (α = 0.68), and Comfort Depending on Others (α = 0.70). 2) Caregiving Questionnaire equanimous of four subscales: Proximity Maintenance: (α = 0.83), Sensitivity: (α = 0.76), Controlling Caregiving (α = 0.77) and Compulsive Caregiving (α = 0.68).

Results: Multivariate Assay of Co-variance (MANCOVA) models were computed; gender, historic period, and education were included in the models. Methadone patients and drug-gratis treatment addicts were equivalent and reported significantly lower Comfort Depending on Others, Comfort with Intimacy, and Caregiving Proximity. However, methadone users reported significantly lower Anxiety nearly being rejected than drug-gratuitous addicts and were equivalent to non-clinical controls. In addition, correlations between the methadone intake dose and the questionnaires' scales showed that dose was significantly and negatively correlated with Condolement with Closeness (rs = −0.36; p < 0.01) and with Caregiving Proximity (rs = −0.28; p < 0.05).

Keywords: addiction, attachment, opioids, opiates, methadone, caregiving

Introduction

Humans demand intimate relationships of great depths of emotional, psychological and physical intensity for survival, and emotional well-beingness across the life cycle. Young children exhibit intense crying when helpless, lonely, or lost, alerting caretakers to attend to their needs. Adolescents and adults look for support, emotional and sexual bonding in social interactions and relationships, without which they feel empty and alienated. Social mammals demand these affiliative interactions in lodge to get relief from negative emotions but also to become pleasure and joy (ane).

It is now widely consensual that beingness able to form positive socio-emotional bonds has implications for concrete and mental wellness as well as for greater social competence. Dysfunctional relationships, social rejection, and withdrawal are associated with a wide range of psychopathologies including drug abuse, feet, and depression (ii, 3).

Research evidence in the concluding decades showed that the need for social bonding is neurologically hard wired in socially dependent animals, including humans (iv, v). Specifically, there has been vast research on the neurochemical bases of parental and romantic social bonds focused on the neuropeptides oxytocin, vasopressin, dopamine, and serotonin (vi, 7).

Additionally, and based upon the homologies between opioid drug addiction and romantic bonding (8, 9), some authors accept pointed out the endogenous opioids as another group of neurochemical mechanism motivating parental and human relationship behavior in humans. These homologies are quite remarkable: they are both characterized by an initial strong allure (i.due east., the euphoria stage), which then decreases with exposure (i.e. the tolerance stage). After the emergence of tolerance, the system adapts to a new "fix point" whereby absence of the partner/substance leads to negative affect and distress symptoms that are similar for opiate withdrawal and for social loss (10, 11).

Several studies with rodents using self-administration showed that the lack of social bonding due to isolation enhanced the consumption of opiates (12, 13). Also, opiates and opioids have shown to be effective in reducing separation distress, in puppies, young guinea pigs, and chicks, while opiate antagonists increase vocalizations induced by separation (14).

Additionally, information technology is now established by the concept of "social hurting" that social bonding/rejection and physical hurting share similar neuronal pathways (15). This area of enquiry suggested that responses to positive and negative events on social interactions are regulated by endogenous opioid peptides and the μ-opioid receptor, which also alleviates physical pain (16). The μ-opioid receptor (MOR) system has also been shown to interact with oxytocin and dopamine in social bonding and social reward (17, 18). This is likely explained past the adaptive value of the social attachment system, which keeps immature close to parents, and may accept evolved to enhance biological fettle in social animals (19).

Starting from this brain opioid theory of social attachment, Panksepp et al. (10,,) suggested that opiate addiction (morphine, heroin, etc.) could be neurologically motivated in part by the capacity of these drugs to reduce the pain and the lack of joy of inadequate social bonding and attachments. On the other paw, opiates' consumption reduces the drive for social interactions in animals, including humans, while pocket-size doses increase feelings of confidence and social dominance (10, 11). It is also known that the repeated utilize of opiates in its turn induces alterations in neurotransmitter and neuropeptide systems in encephalon circuits that regulate mood and bear upon (21).

The attachment theory (22, 23) has been applied widely as a theoretical framework for understanding how close interpersonal bonds tin shape both normal and abnormal evolution. According to this tradition, humans are innately equipped with behavioral systems for social attachment and caregiving, since being emotionally bonded to parents, friends, romantic partners, and providing care for dependent individuals enhanced genetic success or inclusive fettle (24).

The attachment theory tradition has provided several measurement methods such as the Developed Attachment Interview (AAI) and a series of cocky-report questionnaires, such as the Adult Attachment Scale (AAS) (25) and the Caregiving Questionnaire (26), to access individual differences in psycho-social close relationships.

Translating these notions to human habit studies, in previous works, nosotros constitute that addicts vs controls recalled a significantly greater number of traumatic events in childhood and boyhood (such as parental death, child abuse, and early separation), which are known to severely disrupt the attachment system (27). They also had higher scores on attachment Anxiety and Avoidance of close relationships, and additionally, these scores were significantly correlated with the number of traumatic family unit events in childhood and adolescence (28).

Recently, a meta-analysis found both cantankerous sectional and prospective significant correlations between zipper and (later on) substance apply, albeit both of pocket-size magnitude; these results indicate that lower attachment security is concurrent to and temporally preceded increases in substance use (29). Additionally, the report found no evidence of a moderation effect of the type of attachment measure—e.m., AAI, AAS—on the correlation between attachment and substance apply.

Although there is today a vast corporeality of studies showing a robust association between subjects with a diagnosis of drug addiction and severe problems in close relationships, at that place is non to our knowledge a comparative study betwixt addicts in opiate abstinence vs addicts consuming the opiate methadone, vs non-addicted controls. There is as well a lack of studies focusing specifically on individual differences in profiles of the caregiving system (25).

Objectives

In the present cantankerous-sectional comparative study, we aimed to exam the outcome of the opiate agonist methadone apply and dosage on measures of two behavioral systems hypothesized by Bowlby (23) to regulate close social bonds (the Attachment organization and the Caregiving system).

Hypotheses

Opiate-addicted subjects have close human relationship profiles characterized past higher avoidance of close proximity in social bonds and college attachment-related anxiety than not-clinical controls.
Methadone intake and dosage are associated with lower self-reported attachment-related anxiety and higher avoidance of proximity maintenance in shut relationships

Participants

A total of 486 subjects participated in the report; 43% were male, their age ranging from xviii to 62 years (K = 26.4; SD = 9.4). Participants were members of iii naturalistic groups: Group i: addicts in drug-free (DF) handling therapeutic communities (due north = 56); Grouping ii: addicts in MMT-Methadone maintenance handling (n = 88); Group 3: normative non-clinical controls (n = 342). The participants in group ane were residents of three therapeutic communities (TC) in Portugal that adhere strictly to total forbearance and drug-free policies, with few exceptions for a minority of patients that could not withdraw methadone (the patients taking methadone in the TC were excluded from the study statistics). Participants in group 2 were addicts in outpatient treatment and outreach programs in Lisbon, taking daily doses of methadone under medical supervision. The methadone dose ranged from 5 to 215 mg (Grand = 65.8 mg; SD = 38.6 mg); these dose values are of like range and average to other studies [e.g., Ref. (30)]. Participants in group 3 were Psychology academy students in Lisbon.

Due to the lack of previous studies comparing attachment variables on methadone users, abstinent substance abusers, and non-clinical subjects, it was impossible to rely on a reasonably expected effect size. This fact prevented us from doing an a priori power analysis to guess the minimum Due north of the sample. Hence, we used rules of pollex from the literature according to which, in a multifariousness of settings, the minimum number of subjects per variable lies in the range of 15 to 20 (31, 32). The non-clinical group subjects were role of a larger study on attachment and caregiving in academy students; for that reason, the number of subjects was substantially higher.

Groups 1 and 2 were not significantly different in gender, educational level, historic period started abusing drugs, pct of male parent, female parent, and siblings with substance abuse issues, and total number of relatives with substance abuse issues. Group 1 was slightly older than group ii, and group 3 was younger, had more years of educational activity, and contained more females than the other 2 groups (all differences p < 0.05). Table i shows the demographic characteristics of the participants. Supplementary Table i shows additional characteristics of the habit subjects. The two groups of addicts were equivalent in all variables except "Father with habit" and Methadone intake.

Table 1

Demographic characteristics of participants.

	Group
	Addicts in DF Treatment	Addicts in Metadone MT	Non-clinical
Sex (% male person)	65^a	69^b	32^c
Age	34,five^a	38,1^a	22,ane^b
Educational activity (years of)	8,9^a	8,5^a	13,1^b

Values with different messages are significantly different at p < 0.05.

Ethical Approval

All participants provided written informed consent to participate in the study. All procedures were canonical by the Research Ethics Committee of the academy (ISPA—Instituto Universitário, Lisbon, Portugal) and in accord with the ethical principles of psychologists and code of conduct of the American Psychological Association.

Instruments

Subjects completed a bombardment of 2 self-written report questionnaires. The order of the questionnaires was randomly counterbalanced:

Adult Attachment Calibration (AAS) (26) consists of eighteen items scored on a v-point Likert-type scale. Nosotros used the Portuguese version, adapted by Canavarro, Dias and Lima (33). The questionnaire contains iii subscales, each composed of half dozen items. The three subscales are Shut, DEPEND, and ANXIETY. The Close calibration measures the extent to which a person is comfy with closeness and intimacy (e.g., "I do not worry most someone getting also close to me"). The DEPEND scale measures the extent to which a person feels he/she tin depend on others to be bachelor when needed (e.g., "I know that people will be there when I need them."). The ANXIETY subscale measures the extent to which a person is worried almost being abandoned or unloved (east.g., "I do worry almost being abased".). The psychometric consistency of the scales in the nowadays study was as follows: Feet about being rejected or unloved (α = 0.83), Shut—Comfort with Closeness and Intimacy (α = 0.65) and DEPEND—Condolement Depending on others (α = .70).
Caregiving Questionnaire (ane) consists of 32 items scored on a six-point Likert scale, assessing caregiving behaviors in romantic and marital relationships. We used the Portuguese version, adapted past Torres and Oliveira (34). It is composed of iv subscales: The Proximity maintenance (or Proximity vs Altitude) subscale assesses the caste to which subjects brand themselves available to their partner when condolement is needed (e.one thousand., "When my partner seems to desire or need a hug, I'm glad to provide it"). The Sensitivity subscale assesses the caste to which subjects recognize when their partner needs back up (due east.k., "I tin can always tell when my partner needs comforting, even when south/he doesn't ask for information technology"). The Controlling subscale measures the degree to which subjects exert command to assist their partners solve problems (east.g., "I tend to be too domineering when trying to help my partner"). Finally, the Compulsive subscale measures the extent to which subjects get over-involved in their partners problems (due east.g., "I sometimes create problems by taking on my partner's troubles every bit if they were my own"). The psychometric consistency of the scales in the present study was equally follows: Proximity Maintenance: (α = 0.83), Sensitivity: (α = 0.76), Controlling Caregiving (α = 0.77), and Compulsive Caregiving (α = 0.68).

The addicted subjects further completed the section D of Portuguese ASI-6 (Addiction Severity Index, Version half-dozen) by a clinical psychologist fellow member of the research team in order to check if all them had heroin as a drug of addiction, which was the case.

Information Assay Plan

All statistics were performed using the IBM SPSS Statistics package Version 21.0. Preliminary inspection of the data showed that the AAS and Caregiving questionnaires' scales were usually distributed, while the methadone intake variable significantly differed from the normal distribution.

Start, we performed Pearson correlations between all questionnaire scales in written report, in gild to test for theoretically coinciding associations between zipper and caregiving constructs, and to detect potential multicollinearity (which was not nowadays: all correlation coefficients were below .50). 2nd, in order to exam for differences betwixt the three groups, ii Multivariate Analysis of Co-variance (MANCOVA) models were computed, one with the AAS and one with the Caregiving scales as dependent variables; the 3 groups of subjects were included as the independent variable. The variables Sexual activity, Age, and Instruction were also included in the models as covariates to statistically control for the demographic differences between the three groups.

Finally, nosotros tested the association betwixt methadone dosage in milligrams and all the questionnaire scales using Spearman non-parametric correlations since methadone dosage had a non-normal distribution.

Results

The intercorrelation matrix, presented in Supplementary Table 2 , shows theoretically congruent significant correlations between the constructs of attachment and caregiving.

Ii MANCOVA models were computed, 1 with the AAS scales equally dependent variables and the other with the Caregiving scales as dependent variables. In both models, the three groups of subjects were the levels of the contained variable, and the variables Sex, Historic period, and Education were included in both models. All MANCOVA assumptions were tested and met past the data except the equality of variances, which were significantly different in the AAS Capacity to be Close scale (F = 3.45; p = 0.004) and the Caregiving Controlling calibration (F = 2.90; p = 0.013). For this reason, nosotros performed the MANCOVAs using a bootstrap method (35) with the number of samples = 1,000, available in the SPSS bundle. In both models, multivariate tests showed significant effects of the group variable merely, no significant primary furnishings of the demographic variables, and no interaction effects betwixt the variables in the model. Table ii shows the mean differences for each group on all the questionnaires' scales, the value of F statistic, and contrasts for both models.

Table 2

MANCOVA models' results and differences between groups on Zipper and Caregiving variables.

	Addicts in DF Treatment	Addicts in Metadone MT	Non-clinical Subjects	F_ii.451	p	Partial Eta Squared
Model i: AAS
Anxiety about rejection	3.42^a (0.83)	2.39^b (0.76)	2.44^b (0.78)	29.91	0.000	0.116
Capacity to be Close	iii.03^a (0.51)	2.88^a (0.68)	3.68^b (0.49)	18.77	0.000	0.076
Condolement Depending on others	2.82^a (0.58)	2.72^a (0.66)	3.19^b (0.57)	7.68	0.001	0.033
Model 2: CAREGIVING
4. Proximity maintenance	three.91^a (0.65)	3.95^a (0.99)	iv.81^b (0.88)	six.68	0.001	0.029
5. Sensitivity	3,65^a (0.65)	3.86^a (0.98)	4.32^b (0.73)	5.47	0.005	0.024
vi. Controlling Caregiving	3.97^a (0.66)	3.61^a (ane.01)	2.88^b (0.82)	21.83	0.000	0.090
7. Compulsive Caregiving	3.65^a (0.75)	3.41^a (0.97)	3.nineteen^b (0.76)	3.53	0.030	0.016

As can exist seen in Table 2 , the Methadone intakers and Drug-free handling addicts were statistically equivalent on all questionnaire scales, except for the AAS scale "Anxiety about being rejected or unloved": in this calibration, the Methadone MT subjects had significantly lower scores than drug-free addicts and were equivalent to not-clinical controls.

Finally, we tested the association between methadone dosage in milligrams and all the questionnaire scales using Spearman non-parametric correlations.

Results showed that dose was significantly and negatively correlated with AAS Condolement with Closeness (r_s = –0.36; p < 0.01) and with Caregiving Proximity (r_southward = –0.28; p < 0.05). There were no meaning correlations with any of the other scales. These are presented in Figures 1 and 2 . These results show that increasing methadone doses were associated with macerated capacity for, and diminished condolement with, emotional and concrete closeness with partners.

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Scatterplot of Correlation betwixt methadone dose and Capacity to be Close.

An external file that holds a picture, illustration, etc. Object name is fpsyt-10-00602-g002.jpg

Scatterplot of Correlation between methadone dose and Caregiving Proximity.

Word

The results of our written report show support for the neuro-evolutionary theory of social bonds and addiction [also known equally Encephalon Opioid Theory of Social Attachment (BOTSA)] (4), co-ordinate to which exogenous opiates decrease separation feet and proximity maintenance in humans, as in beast models, by hijacking the neuro-peptide endogenous opioid system modulating social bonds (12).

In our sample, both groups of drug addicts—more than 95% reported the opiate heroin as their main addiction—showed lower levels of adaptive profiles of attachment and caregiving compared with non-clinical controls. This consequence is coinciding with more than than xx cross-sectional studies, which have reported that equally zipper security decreases, substance use increases (29). Similarly to these previous studies, in the present study, the estimated upshot sizes were in the pocket-sized-to-medium range (the Partial Eta Squared ranged from 0.016 to 0.116).

Nosotros had the possibility of comparing two groups of subjects with equivalent histories of opiate addictions: ane—addicts currently in abstinence of opiates and ii—methadone intakers. Methadone is a synthetic opioid that acts on the same opioid receptors equally morphine and heroin. It is commonly used to treat opiate addictions, especially habit to heroin, and has been considered by some as the "aureate standard" for treating opiate addiction (36). The abstinent drug addicts were inpatients at therapeutic communities' residential treatment with strict forbearance rules for all drugs including alcohol, undergoing regular urine analyses to detect drugs. For this reason, we can accept a high caste of conviction that they were really abstinent of opioids. In this way, we had the opportunity to compare in a quasi-experimental style, the effect of an opiate drug on self-reported psychological states related to intimate social bonds and zipper.

Results showed that the methadone users reported significantly less feelings of attachment anxiety, i.e., feet near being abandoned or unloved, than their abstinent counterparts. Furthermore, this association had the stonger effect size of all questionnaire scales (Partial Eta Squared = 0.116), which represents a medium size effect. This result is coinciding with experimental work on animal models, which showed that opiate agonists decreased appreciable signs of anxiety due to separation and isolation (xiv, 37). In a range of mammals, including rats, mice, chicks, sheep, guinea pigs, dogs, non-homo primates, and humans, separation from the mother leads the young to emit distress vocalizations. In that location is considerable evidence from a range of species that assistants of morphine reduces these vocalizations, while the opioid antagonist naloxone increases them (4). The fact that in our study the methadone intakers were statistically equivalent to the abstemious addicts, except for the lower score of AAS separation anxiety, gives the states some grounds to advise a possible homology with the opioid-mediated separation distress paradigm in animate being models.

Additionally, nosotros were able to correlate methadone dosage with the attachment and caregiving scales, inside the methadone intakers group. Results showed that higher methadone dosage was associated with lower levels of Caregiving Proximity and Comfort with Closeness. The Caregiving Proximity maintenance subscale is a measure of the caste to which subjects make themselves available to their partners when condolement is needed and, hence, is an important part of parental-similar behaviors. The negative correlation with methadone dosage is congruent with previous beast studies showing that morphine significantly impairs parental behavior such as retrieving, grouping, licking, and nursing the young, while naloxone, an opiate antagonist, restores it (38). Opiates, in particular mu-receptor ligands, disrupt maternal behavior in a very selective, naloxone-reversible fashion (39). Additionally, the negative correlation of Condolement with closeness suggests that methadone might decrease the rewarding aspect of concrete contact characteristic of parental and affiliative behaviors, a phenomenon that was previously suggested for other opiates (xl). These results with the notion that patients maintained on opioids relate autistically (e.grand., "with coldness in homo interactions and gaze avoidance) which are reversed by detoxification from opioids" (41).

The absence of significant correlation between higher methadone doses and lower attachment anxiety might at first sight be seen every bit counter-intuitive and contradicting the other results. However the mean value of AAS-Anxiety in the MMT group was below the total sample hateful (as the non-clinical subjects), which reduces statistical variance and may contribute to a non-significant correlation. On the other hand, information technology is besides likely that methadone can reduce zipper-anxiety/separation distress at low doses, and hence, increasing the dosage does not have a proportional effect due to a ceiling outcome. Indeed, it has been reported in psychiatric patients that "opiates at low doses can powerfully counteract feelings of social loss and despair" (p. 645) (12), in rodents "low doses of morphine inhibit separation distress of infants" (4), every bit well as low doses of opiates (down to 0.5 mg/kg) can reduce motivation to social contact (40). These results converge with previous literature suggesting that provision of exogenous opioids, such as methadone, may have meaning long-term consequences of degrading the endogenous opioid system such equally avoidance of social interactions "that are non currently deemed for in medical practice" (41).

It is worth noting that as in previous studies, the obtained issue sizes were in the modest-to-medium range. This fact is congruent with the notion that opiate drugs' abuse/addiction is a multifactorial phenomenona with a great number of both genetical and environmental determinants. For this reason, issue sizes for specific biopsychosocial take a chance factors may often sally equally small in magnitude (29, 42). Another possible reason for the pocket-size upshot sizes is that there might exist moderators of the zipper–drug abuse association at several levels of analysis (biological, genetic, psycho-social, geographical, macro-social). Notwithstanding, in this study, we did non observe pregnant interactions betwixt gender, education or age and drug corruption status. A meta-analysis by Fairbairn et al. (29) tested a large number of potential moderators (historic period, gender, racial composition, geographic region, substance use blueprint, attachment figure, zipper measures, and others) and found merely age to be a moderator in prospective studies but non in cantankerous-sectional studies, like the present one. We demand more multilevel studies that can accost the interactions between genetic, epigenetic, neurobiological factors, and experiences of psychosocial and relationship arduousness at several stages of development, to reframe our understanding of how attachment/shut human relationship variables are moderated by other phenomena in the development, severity, and maintenance of addiction (43).

The present study has a number of limitations. First, the ones which are typical of cross-sectional correlational and quasi-experimental designs: it is not possible to determine or infer directional causality from the data. Additionally, the employ of self-report questionnaires to measure zipper-theory constructs has its own limitations and has drawn criticism: on the one manus, some of the psychological processes are supposed to take place implicitly or unconsciously and, hence, cannot be measured by explicit self-study measures; on the other mitt, previous research showed that the correlations between implicit measures of zipper such as in-depth interviews and self-report questionnaires are typically low (44). Furthermore, it is possible that respondents dispense some of their answers, either in a conscious or unconscious way. Yet, the meta-analysis by Fairbairn et al. (29) did not constitute any significant influence of the different attachment measures (i.eastward., implicit measures such equally the AAI and explicit measures such equally the AAS questionnaire) on the results, which gives u.s. some reassurance that the present results may be robust.

Information Availability

The datasets generated for this study are available on asking to the corresponding author.

Ideals Statement

The studies involving human participants were reviewed and approved past ISPA-IU: Comité de Ética exercise Centro de Investigação. The patients/participants provided their written informed consent to participate in this study.

Writer Contributions

The author confirms being the sole contributor of this work and has canonical information technology for publication.

Funding

This enquiry was funded by grants from the Foundation for Science and Technology of Portugal: UID/PSI/04810/2019.

Conflict of Interest Statement

The author declares that the research was conducted in the absenteeism of whatsoever commercial or financial relationships that could exist construed as a potential conflict of interest.

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