Interpersonal Difficulties in Eating Disorders: An Explanatory/Comprehensive Psychoneurobiological Model

Abstract

Background: Eating disorders (ED) are characterized by psychosocial dysfunctions, such as social anxiety, alexithymia and lack of assertiveness.
Objective: To propose to comprehensive integrative model including neurobiology and behavior aspects.
Method: a literature review on Medline/PubMed, SciELO and specialized texts databases were assessed against quality criteria. Core concepts were extracted and coherence was articulated.
Results: Four factors were disposed to meaning: alarm and reward system with social brain and control (inhibition/excitation) mechanisms. They were articulated in to complex psychophysiological interplay. They were associated with achieved/not achieved social behavior during development. Food intake could operate like to pathological balance to psychopathological effects
Conclusion: An explanatory/comprehensive psychoneurobiological model to understand social function in ED is proposed. This form of understanding facilitates:

Introduction

Eating disorders (ED) are associated with interpersonal difficulties (ID) which may deepen and reinforce them⁽¹⁾. Regarding this, various interpersonal profiles would predict therapeutical results⁽²⁾.
Instruments, such as the Eating Disorders Inventory, (EDI-3)⁽³⁾, evaluate the interpersonal dimension in their sub-scales:
1. Insecurity (difficulties to express personal thoughts and feelings with others, tendency to seclusion and isolation) and
2. Interpersonal alienation (disappointment, detachment, distancing and mistrust; tendency to feel trapped in relationships, unrecognized). High scores reveal stressed/insecure/disappointing/poorly rewarding/low quality social relationships. In ED, social problems, apprehensions, uncertainties and insecurity, along with usual mistrust in relationships, are part of its psychopathological and behavioral manifestations. Whether it is due to cause or effect, when the links spoil unleash or perpetuate EDs, thus significantly worsening the therapeutical correlation.

An explanatory/comprehensive model is described, including disturbances and scopes of the social dysfunction in EDs, associated to alteration of the alarm systems, social motivation brain and control prefrontal.

Method

71 articles and 12 texts available in specialized literature –from 1984 to 2020– were analyzed, by using Medline/PubMed, SciELO databases, and looking up the following key words: eating disorders, anorexia nervosa, bulimia nervosa, interpersonal problems, attachment, psychosocial functioning, and neurobiology. Other terms, such as   reward, stress and mentalizing, aimed to build the model were included.

Psychosocial Functioning in ED
Severity of ED symptoms is quite important in order to determine social functioning, especially under remission⁽⁴⁾. Co-existence of some comorbid conditions, such as social anxiety, alexithymia and lack of assertiveness, during its evolution, influence general social performance, thus hindering its progression, outcome and   forecast^{(5, 6)}.

Social Anxiety.  It is fear associated to social food intake situations before criticism, public exposure or rejection of their weight/body shape, with low self-esteem as a background, perfectionist traits and shyness⁽⁷⁾. It may turn into social phobia, although this tend to become reversed when ED is compensated. Its prevalence is significantly higher in anorexia nervosa versus control patients, reaching severe ranges or very severe ones⁽⁸⁾. It is associated to evading personality disorder, as a premorbid trait⁽⁹⁾, thus favoring, ED severity⁽¹⁰⁾.

Alexithymia.Deficientinteroceptive consciousness. Difficulties to identify, describe and discriminate feelings and body sensations, thus causing a cognitive style focused on external concrete issues, with a restricted capacity to fantasize, where physiological and behavioral responses prevail, with problems on emotional regulation⁽¹¹⁾; highly prevalent on restrictive anorectic patients⁽¹²⁾. Bulimic patients have higher difficulties to recognize feelings and anorectic patients have more problems to describe them⁽¹³⁾. In turn, parents have a high alexithymia, thus generating a family environment aimed to avoid conflicts and emotional stress, whose objective is to keep cohesion and a fake harmony⁽¹⁴⁾. The correlation between alexithymia and depression in ED is often observed. The controversy is whether alexithymia is a cause or a symptom, although its levels decrease when ED and depression⁽¹⁵⁾ improves.

Assertiveness.  Expression of independent/divergent feelings and opinions⁽¹⁶⁾.  ED improvement is associated to higher assertiveness⁽¹⁷⁾. Its deficit produces problems to state limits, to become different and be socially competent; thus submission or shyness, feelings of personal inefficacy and the need of approval by the others contribute –in a negative manner⁽¹⁶⁾. Social skills impairment leads to conflicts⁽¹⁾ and mistrust, thus creating a vicious circle between ED/effective therapeutical management⁽¹⁸⁾.

Interpersonal Styles in ED: Evidence
ID adversely affects self-esteem, thus encouraging search for an ideal body^{(19, 20)}. A research⁽²¹⁾ made found a correlation between interpersonal problems with nuclear ED symptoms, while incompetence to create close relationships and be assertive, discomfort involved in social anxiety, and the tendency to personal sacrifice, were positively correlated with general psychological imbalance.  
Negative/depressive affection, partially explains the correlation between ID and ED in restrictive anorectic patients, in bulimia nervosa, in binge/non-specified feeding disorders^(20-24).
ED patients, usually have a friendly, although submissive and poorly assertive interpersonal style^{(20, 25)}, thus avoiding to express their own feelings and giving priority to those of others; but bulimic patients behave with interpersonal mistrust, negative interactions and prone to conflicts⁽²⁶⁾.
An analysis of interpersonal styles in bulimic patients (warm dominant, warm submissive, cold submissive or cold dominant), related with co-morbid psychopathologies, personality traits, influences of dietary restriction and negative affectivity, proved that warm and submissive groups obtained the highest scores with adaptive personal characteristics, including kindness, extraversion and consciousness⁽²⁷⁾. An interpersonal model of binge disorders states that ID cause negative affections thus leading to binges as a confrontation strategy.
If we understand attachment as the first interpersonal development pattern, it is understood that treating stress of evitative attachment networks ID, and even, depressive symptoms up to 12 months after an intervention⁽²⁸⁾.

A Psychoneurobiological Explanatory/Comprehensive Model of ID in ED

ED and ID have some zones, circuits, neurotransmitters and functions of the nervous system that are shared with social anxiety, alexithymia and low assertiveness.
Interpersonal connections activate the nervous system before other people (Figure 1). The so-called social brain/network is connected with the alarm/reward/prefrontal control systems, thus continuously adapting and integrating signals.
Social anxiety occurs as a result of an activated/misregulated alarm system and in presence of others (imaginary or real people). Alexithymia, in turn, blocks the internal/external signals that are necessary for social adjustment, as an attempt to reduce the intensity the disturbance causes. Low assertiveness disables the expression of real intentions; therefore the necessary self-regulation of interpersonal relationships.
EDs use intake as a (wrong) homeostatic regulation, taking control of the inhibition or disinhibition system (Figure 2), thus skipping, more complex mental operations, derived from the reflexive function⁽²⁹⁾.

Social Network
Connections among mammals is given by means of empathy (emotional reading of the other) and the theory of mind (reading of intentions). The joint activity of these systems allow to bet on probabilities of meaning⁽³⁰⁾ and their equivocals⁽³¹⁾. 
Empathy is the skill to match emotional mood of others; to read their physiology and translate that into relevant information for the next action. A newly born is capable to interpret maternal signals^{(32, 33)}.   Neurobiologically, empathy lies on the following zones:
a) Subcortical: it is responsible of the emotional contagion,
b) Intermediate: basal ganglia and limbic structures involved in learning and memory, c) Cortical: reflection: emotions such as search, rage, fear, lust, care, panic or game are simple to tune by means of primary mammal circuits⁽³⁴⁾; the top-down control of the cortex-limbic system would integrate learning and cognitive regulation, to this first response⁽³⁵⁾.
The theory of mind involves the capability to forecast intentions and action, to recognize threats and act consequently, thus supporting the system of mirror neurons^{(36, 37)}.
Interpersonal interaction uses both systems, activating motor/emotional/cognitive motors, and thence, zones, strata, functions, nervous cells and their molecules.
Interpretative exchange providing continuity to interaction requires time arrangement (shifts) and space arrangements (proxemics). Repeated interactions array repetitive patterns and are organized in automated roles and rules. In order to provide contact continuity, some regulation patterns of the nervous system are laid down. Interaction creates fields of somatic tuning⁽³⁸⁾ activating networks of perception, belonging and social aversion⁽³⁹⁾, as that of mentalization⁽⁴⁰⁾, plus two groups of big networks of mirror neurons⁽³⁶⁾, overlapped with eight brain canonical brain structures: ventromedial/dorsomedial frontal cortex, anterior cingulate cortex (including subgenual/pregenual/supragenual areas), posterior cingulate, precuneus, lateral parietal cortex and hippocampus⁽⁴¹⁾. Functional magnetic resonance displays the activity during interactions in the inferior frontal/temporal median gyruses, extended to the superior/posterior temporal sulcus, the fusiform gyrus and the bilateral medial temporal gyrus, and beyond, to the temporo-parietal junction, especially the left one⁽⁴²⁾.
Early/significant interactions mark future forms of regulation as secure/insecure, according to the distance proposed by the attachment figure⁽⁴³⁾. This close/far cycle allows to develop autonomy⁽⁴⁴⁾, thus generating the (central and peripheral) neural architecture, held by the affectional bond⁽⁴⁵⁾. In this way, a relationship is a physiological modulator⁽⁴⁶⁾. From a biological standpoint, the attachment system is related with the sympathetic/parasympathetic equilibrium of the autonomous nervous system. Its peripheral neurotransmitters -adrenaline and acetylcholine- produce vascular/visceral/motor changes. The system moves in a predominant functioning/adaptive range⁽⁴⁷⁾, with a continuous reciprocal checkup using mirror neurons^{(48, 49)}.
Evidence is reported that EDs have a higher prevalence of insecure attachments⁽⁵⁰⁾, these require higher relational regulation, especially in conflict contexts⁽⁵¹⁾. Emotional regulation failures would cause failure on integration processes^{(52, 53)}, with poor self-regulation reflexive functions⁽⁵⁴⁾, thus affecting the adaptive capability to interpret internal/external mental states⁽⁵⁵⁾.

Emotional regulation
Before an alarm, two complementary forms of emotional regulation are activated. These are the relational and the self-regulation systems⁽⁵⁶⁾.
Safe attachment would be the capability to maintain welfare with/without a mother, thus generating a fluid transition between both systems, and creating a good social articulation. Dependence involves higher regulatory/emotional needs. In addition, independence involves self-regulation. In EDs, food intake would try to regulate what none of the two regulatory systems has fully achieved, or at least, not under stress events.
Alexithymic patients –incapable to recognize discomfort signals– would overcharge the system with negative affections, thus leading to dyscontrol, isolation or symbiosis, as a form of protection⁽⁵⁷⁾. Associated psychopathologies such as:   anxiety, depression, eating disorders and addictions would facilitate IDs^{(58, 59)}. 
Assertiveness reduces stress by facilitating a limit on its own⁽⁶⁰⁾. In animals, molecular studies of vasopressin/oxytocin balance prove its importance to alleviate general stress and compromise mating relationships⁽⁶¹⁾.

The Alarm System 
From an anatomical standpoint, it includes the amygdala; a broad grid of the autonomous nervous system, adrenergic and cholinergic ones, plus the neuroendocrine system of the cortisol; as well as several islets of the releasing factor of corticotrophin spread with various brain afferences. The neuroendocrine activity of the system can model the brain tissue by means of apoptosis, migrations and synaptogenesis, thus generating an effective framework in that specific context⁽⁶²⁾ and fixing an operative range, as a response to the surrounding alert needs, the epigenetic burden and the adjustment with the affective significants⁽⁶³⁾. 
Early interpersonal relationships modulate the adrenergic tone⁽⁶⁴⁾. The lack of availability, sensitivity and responsiveness, as well as affective traumas⁽⁶⁵⁾, generate phenotypes sensitive to stress that are keener to psychopathologies. Insufficient motherhood cause a relevant parental epigenetic mark⁽⁶⁶⁾.
In rats, methylation of deoxyribonucleic acid for receptors of glucocorticoids (equivalent to cortisol in humans), proves the inability to stop the hypothalamic-pituitary-adrenal axis. This sensitivity is what we find in EDs patients^{(67, 68)}.  In these patients, borderline personalities, associated to insecure attachments show impulsiveness and lack of control thus leading to ID⁽⁶⁹⁾. There is a correlation and overlap between deregulation, functioning borderline, ID and ED^{(70, 71)}.

Motivation and Reward System 
Related with the interest (reward anticipation) and the search for pleasure sources, subjects, substances, food, significant objects may be a reason of search.
The reward system works in the zones of the sustancia nigra, striatum, nucleus accumbens, ventral tegmental area and it preferably uses dopamine as a neurotransmitter, which is released in the ventral tegmental area. Positive satisfying sensing occurs in the D2 receptors of the nucleus accumbens. Release of opioids by the ventral striatum and the prefrontal cortex, make contact to become a positive and satisfying issue. In this sense, the positive regulation of the receptors DA1 would be crucial to maintain and active social link⁽⁷²⁾.
The reward system is stimulated when pleasure is anticipated. There are differences among anorectic and bulimic patients, when they see/imagine food, according to the functional magnetic resonance⁽⁷³⁾. In anorexia nervosa, the activation of the dopaminergic systems increases cortical top-down circuits and –in some cases- the amygdala, associating feeding stimuli to fear⁽⁷⁴⁾.
Deregulation of the reward system has been interpreted, according to the following parameters^(75-77) 
a) Theory of the hyper-responsiveness: about reactiveness before food intake.
b) Theory of the sensitization: on reactivity before dense food intake.
c) Theory of the reward deficit: increasing intake until activation of the reward system.
d) Theory of the susceptibility to rewards: it explains that both, genetic factors (receptor D1), as well as the environment (anticipation of the presence of a warm mother), change sensitivity of the striatal activation 
e) Theory of the deficient inhibitory control: according which, the reward system would be released from the cortical circuit.

Control Systems
The need to generate accurate /quick/adaptive responses maintaining mutuality and, in turn, maintaining the limits of the subject, with no need to use violence to get it, is a learned/modifiable/adaptable plastic function.
The prefrontal cortex receives information from all other cortex (associative/sensory/parietal/occipital/temporal), insula, amygdala, basal ganglia.  By means of the executive functions, it refines impulsive responses. This process allows comparing, comprehending, project, control emotional experiences and subsequent actions, apart from delaying gratification. From an anatomical standpoint, the prefrontal cortex is divided into regions:
a) Orbitofrontal region: it is related with adaptive planning,
b) Medial region: it includes control of attention and regions,
c) Ventromedial region: it involves social conducts, attention and planning,
d) Dorsolateral region: it activates the working memory, reasoning, capability to understand, to plan and make conduct decisions⁽⁵⁷⁾. 
Executive functions manage the information inhibiting/exciting/integrating memories, thus making decisions and adapting. Development of feeding inhibitory control can fail in adolescent obesity. Mammal’s neo-cortex has a balanced inhibitory/excitatory neural population, dynamically interacting. It represents –approximately- 20% of the total. This is an essential aspect for neuro-development, adaptation and control of cortical plasticity. Among the known excitatory/inhibitory inter-neurons are somatostatin, parvalbumin and vasoactive intestinal peptide. The somatostatin inter-neurons are located inside the cortical networks, thus integrating sensory/unimodal/multimodal information, involved in inhibitory/disinhibitory circuits. In this way, it is part of the plasticity, depending on experiences. From a molecular stand point gamma-aminobutyric acid is the main inhibitory neurotransmitter required to control synaptic excitation/inhibition and neural oscillation^{(78, 79)}.

Discussion

EDs are characterized by high levels of fear to eating, interacting, criticism and change. Alexithymia and low assertiveness would be insufficient defensive responses that would act as a cause, or effect or appear along with the feeding symptoms, thus generating various ID levels. The more difficulties in their relationships, the worse the ED forecast becomes⁽²⁶⁾.
When presenting the psychoneurobiological explanation/comprehension model of ID in ED, the information available has been organized and collected into a simple management structure, aimed to favor facilitation of clinical decision-making. The model allows to think –from encompassing perspective– ED events, their transitions, risks and forecast; as well as the moment of the development, the pathological setting and overlapping of other mental disorders, mainly, anxiety, depression and psychosis. IDs are linked to the alarm and motivation systems, and are subject to control by the EDs, that have been arranged bound to topics related with weight and body image, thus including the idea of the critical other who threatens welfare. Examples of how to use this model and how to provide therapeutical solutions would be thinking about:
1. Binge as a facilitation of the dopaminergic pathways that are independent from the cortical control, once they are stimulated. This could happen, especially in addiction to substances, such as sugar and fat. After that, dyscontrol sensations would trigger social rejection and isolation; 
2. Depression associated to ED, as the fatigue of the alarm and motivation systems, that have been extremely stimulated during a quick loss of weight, that because of  attention fatigue, reduce empathy and the social interpretative capabilities; 
3. Restriction and food intake rejection, as a need of increase control aimed to rule the alarm system, thus reducing contact with food;
4. Isolation or social rejection as a way to reduce excitation of the nervous system;
5. Thought focalization in just one objective (to lose weight), as a way to keep attention and planning, keeping the representation process of others out⁽⁸⁰⁾.
Social interaction continues neurobiologically under study, and there is a wide spread over the zones involved. Among the explored areas, some are shared with EDs; for instance, failures in executive functions could affect interpersonal relationships, thus activating rigidity and the perfectionism. These conditions could be associated to social anxiety⁽⁷⁹⁾.
As a conclusion, an explanatory/comprehensive model is presented for ID, in ED, based on psychoneurobiological evidence available for social interactions (social network). This network is connected with the alarm/motivation/control systems. The four systems are altered in EDs, in various manners and intensity, thus generating a wide variety of clinical symptoms and risks indexes in those pathologies. The described model could help to comprehend and interpret the results obtained in recent research, as well as support clinical management and more accurate therapeutical decision-making.

References

1. Hartmann A, Zeeck A, Barrett M. Interpersonal problems in eating disorders Int J Eat Disord 2010; 43(7):619-27. doi: 10.1002/eat.20747.
2. Ung E, Erichsen C, Poulsen S. The association between interpersonal problems and treatment outcome in patients with eating disorders. J Eat Disord 2017; 5: 53. doi: 10.1186/s40337-017-0179-6. 
3. Garner D. Eating disorder inventory-3. Professional manual. Lutz FL: Psychological Assessment Resources Inc, 2004.
4. Rymaszewska J. The social functioning of individuals with various psychiatric disorders. Psychiatr Pol 2007; 41(1): 39-51.<br>
5. Behar R.   Funcionamiento psicosocial en los trastornos de la conducta alimentaria: Ansiedad social, alexitimia y falta de asertividad. Rev Mex de Trastor Aliment 2010; 1: 90-101.
6. Behar R. Expresión emocional en los trastornos de la conducta alimentaria: Alexitimia y asertividad. Rev Chil Neuro-Psiquiat 2011;  49 (4): 338-346.<br>
7. Franca S, D&rsquo;ivernois J, Marchand C, Haenni C, Ybarra J, Golay A. Evaluation of nutritional education using concept mapping. Patient Educ Couns 2004; 52: 183-92.
8. Behar R, Iglesias B, Barahona M,  Casanova D. (2007).Trastorno depresivo, ansiedad social y su prevalencia en trastornos de la conducta alimentaria. Rev Chil Neuro-Psiquiat 2007; 45(3): 211-220.
9. Sipos V, Schweiger U, Renneberg B. Anxious (avoidant) personality disorder. MMW Fortschr Med 2006; 148(8):32, 34-5.
10. Behar R. Trastornos de personalidad y trastornos de la conducta alimentaria. En: Behar R, Figueroa G, editores. Trastornos de la conducta alimentaria. Segunda Edición. Santiago de Chile: Mediterráneo, 2010.p. 95-120.
11. Taylor G, Bagby R. An overview of the alexithymia construct. In: Bar-On R,   Parker J, editors.  Handbook of emotional intelligence. San Francisco: Jossey-Bass; 2000.p.40-67.
12. Bourke P, Taylor G, Parker J, Bagby R. Alexithymia in women with anorexia nervosa. A preliminary investigation. Br J Psychiatry 1992; 161: 240-243.
13. Speranza M, Corcos M, Loas G, Stephan P, Guilbaud O, Perez-Diaz F, <em>et al</em>.   Depressive personality dimensions and alexithymia in eating disorders. Psychiatry Res 2005; 135 (2): 153-163.
14. Onnis L, Di Genaro A. Alexitimia: Una revisión crítica. Medicina Psicosomática 1987; 32: 45-64.
15. Behar R. Alexitimia, depresión y trastornos de la conducta alimentaria. Trastor Ánimo 2009; 5(1): 19-27.
16. Behar R. Trastornos de la conducta alimentaria: Clínica y epidemiología. En: Behar R, Figueroa G, editores.  Trastornos de la conducta alimentaria. Segunda Edición. Santiago de Chile: Mediterráneo, 2010. p. 121-47.
17. Behar R, Manzo R, Casanova D. Trastornos de la conducta alimentaria y asertividad. Rev Med Chile 2006; 134: 294-301.
18. Jones A, Lindekilde N, Lübeck M, Clausen L. The association between interpersonal problems and treatment outcome in the eating disorders: A systematic review. Nord J Psychiatry 2015; 69(8): 563-73. doi: 10.3109/08039488.2015.1019924. 
19. Lampard A, Byrne S, McLean N. Does self-esteem mediate the relationship between interpersonal problems and symptoms of disordenetwork eating? Eur Eat Disord Rev 2011; 19(5):454-8.
20. Ivanova I, Tasca G, Proulx G, Bissasda H. Contribution of interpersonal problems to eating disorder psychopathology via negative affect in treatment-seeking men and women: Testing the validity of the interpersonal model in an understudied population.  Clin Psychol Psychother 2017; 24(4):952-964. doi: 10.1002/cpp.2060. 
21. Lo Coco G, Mannino G, Salerno L, Oieni V, Di Fratello C, Profita G, <em>et al</em>. The Italian version of the Inventory of Interpersonal Problems (IIP-32): Psychometric properties and factor structure in clinical and non-clinical groups. Front Psychol 2018; 341. doi: 10.3389/fpsyg.2018.00341. 
22. Ivanova I, Tasca G, Proulx G, Bissada H. Does the interpersonal model apply across eating disorder diagnostic groups? A structural equation modelling approach. Compr Psychiatry 2015; 63:80-7. doi: 10.1016/j.comppsych.2015.08.009. 
23. Ivanova I, Tasca G, Hammond N, Balfour L, Ritchie K, Koszycki D<em>,  et al</em>.   Negative affect mediates the relationship between interpersonal problems and binge-eating disorder symptoms and psychopathology in a clinical sample: A test of the interpersonal model. Eur Eat Disord Rev 2015 23,(2):133-8. doi: 10.1002/erv.2344.
24. Ansell E, Grilo C, White M. Examining the interpersonal model of binge eating and loss of control over eating in women. Int J Eat Disord 2012; 45(1):43-50. doi: 10.1002/eat.20897.
25. Raykos B, McEvoy P, Carter O, Fursland A, Nathan P. Interpersonal problems across restrictive and binge-purge samples: Data from a community-based eating disorders clinic. Eat Behav 2014; 15(3):449-52. doi: 10.1016/j.eatbeh.2014.06.008. 
26. Arcelus J, Haslam M, Farrow C, Meyer C. The role of interpersonal functioning in the maintenance of eating psychopathology: A systematic review and testable model. Clin Psychol Rev 2013; 33(1):156-67. doi: 10.1016/j.cpr.2012.10.009. 
27. Ambwani S, Hopwood C. The utility of considering interpersonal problems in the assessment of bulimic features. Eat  Behav 2009; 10(4): 247-53. doi: 10.1016/j.eatbeh.2009.07.007.  
28. Maxwell H, Tasca G, Ritchie K, Balfour L, Bissada H. Change in attachment insecurity is related to improved outcomes 1-year post group therapy in women with binge eating disorder. Psychother (Chic) 2014; 51 (1): 57-65. doi: 10.1037/a0031100. 
29. Fonagy P, Allison E. (2012). What is mentalization? The concept and its foundations in developmental research. In: Midgley N, Vrouva I, editors. Minding the child: Mentalization-based interventions with children, young people and their families. Hove: Routledge; 2012.p. 11-34.
30. Cordella P.   ¿Qué es semiosis?. Rev  GPU 2014; 10: 390-394.
31. Porcelli S, van Der Wee N, van der Werff S, Aghajani M, Glennon J, van Heukelum S, <em>et al</em>. Social brain, social dysfunction and social withdrawal. Neurosci Biobehav Rev 2019; 97: 10-33.
32. Beebe B, Rustin J, Sorter D, Knoblauch S. An expanded view of inter-subjectivity in infancy and its application to psychoanalysis.&nbsp;Psychoanal  Dial  2003; 13(6): 805-841.
33. Glocer Fiorini L. Intersubjectivity, otherness, and thirdness: A necessary relationship. Int J Psychoanal 2016; 97(4): 1095-1104.
34. Panksepp J. The basic emotional circuits of mammalian brains: Do animals have affective lives?. Neurosci Biobehav Rev 2011; 35(9): 1791-1804.
35. Panksepp J. Toward a cross-species understanding of empathy. Trends Neurosci 2013; 36(8): 489-496.
36. Rizzolatti G, Craighero L. The mirror neuron system. Annu Rev Neurosci 2004; 27:169-192.
37. Siegal M, Varley R. Neural systems involved in 'theory of mind'. Nat Rev Neurosci 2002; 3(6): 463-471.
38. Cordella P. Campos de sintonía somática durante el desarrollo infantil. Rev Chil  Pediatr 2009; 80(5): 407-419.
39. Bickart KC, Dickerson BC, Barrett LF. The amygdala as a hub in brain networks that support social life. Neuropsychologia 2014;  63: 235-248.
40. Frith C, Frith U.  The neural basis of mentalizing. Neuron 2006; 50(4): 531-534.
41. Thomas  B, Krienen F, Sepulcre J, Sabuncu M, Lashkari D, Hollinshead M, <em>et al</em>. The organization of the human cerebral cortex estimated by intrinsic functional connectivity. J Neurophysiol 2011; 106(3): 1125-1165.
42. Thye M, Murdaugh D, Kana R.  Brain mechanisms underlying reading the mind from eyes, voice, and actions. Neuroscience 2018; 374: 172-186.
43. Holmes J. John Bowlby and attachment theory. London: Routledge, 2014.
44. Cordella P. Apego, vínculo y desarrollo cerebral. Rev  GPU 2010; 6: 6(3).
45. Sravanti L. Nurture the nature. Indian J Psychiatry 2017; 59(3): 385. doi: 10.4103/psychiatry.
46. Hofer M. Relationships as regulators: A psychobiologic perspective on bereavement. Psychosom Med 1984; 46(3): 183-197. 
47. Kozlowska K, Walker P, McLean L, Carrive P. Fear and the defence cascade: Clinical involvestions and management. Harv Rev Psychiatry 2015; 23(4): 263.
48. Ferri F, Frassinetti F, Ardizzi M, Costantini M,  Gallthat V. A sensorimotor network for the bodily self. J Cognitive Neurosci 2012; 24(7): 1584-1595.
49. Rolls E.  Functions of the anterior insula in taste, autonomic, and related functions. Brain Cogn  2016; 110: 4-19.  
50. Pace C, Guiducci V, Cavanna D. Attachment in eating-disordenetwork outpatients with and without borderline personality disorder. J Health Psychol 2017; 22(14): 1808-1818.
51. Peris T, Miklowitz D.  Parental expressed emotion and youth psychopathology: New directions for an old construct. Child Psychiatry Hum Dev 2015; 46(6): 863-873.
52. Ainsworth M. D. S. Attachment as related to mother-infant interaction. In:   Rosenblatt J,   Hinde R, Beer C,   Busnel M, editors. Advances in the study of behaviour.  New York: Academic Press; 1979.p. 1–51.
53. Farina B, Liotti M, Imperatori C. The role of attachment trauma and disintegrative pathogenic processes in the traumatic-dissociative dimension. Front Psychol 2019; 10: 933.
54. Fonagy P. Affect regulation, mentalization and the development of the self. Routledge, London, 2018.
55. Allen J, Fonagy P, editores.   The Handbook of Mentalization-based Treatment. Sussex: John Wiley &amp; Sons; 2006.
56. Schore J,  Schore A.  Modern attachment theory: The central role of affect regulation in development and treatment. Clin Soc Work J 2008; 36(1): 9-20.
57. Perez-Rodriguez M, Bulbena-Cabré A, Nia A, Zipursky G, Goodman M, New A.  The neurobiology of borderline personality disorder. Psychiatr Clin 2018; 41(4): 633-650.
58. Lenzo V, Barberis N, Cannavò M, Filastro A, Verrastro V, Quattropani M.  The relationship between alexithymia, defence mechanisms, eating disorders, anxiety and depression. Riv Psichiatr 2020; 55(1): 24-30.
59. Giles S, Hughes E, Fuller?Tyszkiewicz M, Krug I. The cognitive?interpersonal model of disordenetwork eating: A test of the mediating role of alexithymia. Eur Eat Disord Rev, 2020. https://doi.org/10.1002/erv.2720
60. Girard J., Wright A, Beeney J, Lazarus S, Scott L, Stepp S, <em>et al</em>. Interpersonal problems across levels of the psychopathology hierarchy. Compr Psychiat 2017; 79: 53-69.
61. Schneiderman I, Zagoory-Sharon O, Leckman J, Feldman R. Oxytocin during the initial stages of romantic attachment: Relations to couples&rsquo; interactive reciprocity. Psychoneuroendocrinology 2012; 37(8): 1277-1285.
62. Tost H, Champagne F, Meyer-Lindenberg A.   Environmental influence in the brain, human welfare and mental health. Nat Neurosci 2015; 18(10): 1421-1431. https://doi.org/10.1038/nn.4108
63. Cassiers L, Sabbe B, Schmaal L, Veltman D, Penninx B,  Van Den Eede F.   Structural and functional brain abnormalities associated with exposure to different childhood trauma subtypes: A systematic review of neuroimaging findings. Front Psychiatry 2018; 9: 329.
64. Pratt M, Apter-Levi Y, Vakart A, Kanat-Maymon Y, Zagoory-Sharon O, Feldma R. Mother-child adrenocortical synchrony: Moderation by dyadic relational behaviour. Horm Behav 2017; 89: 167-175. https://doi. org/10.1016/j.yhbeh.2017.01.003 
65. Taylor G. Symbolism, symbolization, and trauma in psychosomatic theory. In:   Aisenstein M, Rappoport de Aisemberg E, editors.  Psychosomatics today. London: Routledge; 2018.p. 181-199.
66. Meaney M, Ferguson-Smith A.  Epigenetic regulation of the neural transcriptome: The meaning of the marks. Nat Neurosci  2010; 13(11): 1313-1318.
67. Zachrisson H, Skårderud F. Feelings of insecurity: Review of attachment and eating disorders. Eur Eat Disord Rev 2010; 18: 97-106. 10.1002/erv.999.
68. Yilmaz Z, Hardaway J, Bulik, C. Genetics and epigenetics of eating disorders. Advances in genomics and genetics 2015; 5: 131-150.
69. Fernando S, Beblo T, Schlosser N, Terfehr K, Otte C, Löwe B, <em>et al</em>. Associations of childhood trauma with hypothalamic-pituitary-adrenal function in borderline personality disorder and major depression. Psychoneuroendocrino 2012; 37(10): 1659-1668.
70. De Paoli T, Fuller-Tyszkiewicz M, Huang C, Krug I.  A network analysis of borderline personality disorder symptoms and disordenetwork eating.   J Clin Psychol 2020;  76(2): 787-800. DOI: 10.1002/jclp.22916
71. Ripoll L, Snyder R, Steele H, Siever L.  The neurobiology of empathy in borderline personality disorder. Curr Psychiatry Rep 2013; 15(3): 344.
72. Lahousen T, Unterrainer H, Kapfhammer H.  Psychobiology of attachment and trauma—some general remarks from a clinical perspective. Front Psychiatry 2019; 10. 10.3389/fpsyt.2019.00914
73. Monteleone A, Castellini G, Volpe U, Ricca V, Lelli L, Monteleone P, <em>et al</em>. Neuroendocrinology and brain imaging of reward in eating disorders: A possible key to the treatment of anorexia nervosa and bulimia nervosa. Prog Neuropsychopharmacol Biol Psychiatry 2018; 80: 132-142.
74. Simon J, Stopyra M, Friederich H.  Neural processing of disorder-related stimuli in patients with anorexia nervosa: A narrative review of brain imaging studies. J Clin Med 2019; 8(7): 1047.
75. Devoto F, Zapparoli L, Bonandrini R, Berlingeri M, Ferrulli A, Luzi L, <em>et al</em>.   Hungry brains: A meta-analytical review of brain activation imaging studies on food perception and appetite in obthat individuals. Neurosci Biobehav Rev 2018; 94: 271-285.
76. Richards J, Vásquez A, Von Rhein D, van der Meer D, Franke B, Hoekstra P, <em>et al</em>. Adolescent behavioural and neural reward sensitivity: A test of the differential susceptibility theory. Transl  Psychiatry 2016; 6(4): 771-771.
77. Turton R, Nazar B, Burgess E, Lawrence N, Cardi V, Treasure J, <em>et al</em>. To go or not to go: A proof of concept study testing food?specific inhibition training for women with eating and weight disorders. Eur Eat Disord Rev 2018; 26(1): 11-21.
78. Yang Y, Shields G,    Guo C,   Liu Y. Executive function performance in obesity and overweight individuals: A meta-analysis and review. Neurosci Biobehav Rev 2018;  84:225-244. doi: 10.1016/j.neubiorev.2017.11.020
79. Arlt J, Yiu A, Eneva K, Dryman M, Heimberg R, Chen E.   Contributions of cognitive inflexibility to eating disorder and social anxiety symptoms. Eat Behav 2016; 21: 30-32.
80. Steinglass J, Berner L, Attia E. Cognitive neuroscience of eating disorders. Psychiatr Clin 2019; 42(1): 75-91.