Research in Psychotherapy: Psychopathology, Process and Outcome 2020; volume 23:77-87

Panic disorder: attack of fear or acute attack of solitude? Convergences

between affective neuroscience and phenomenological-Gestalt
perspective
Gianni Francesetti,1,2 Antonio Alcaro,3 Michele Settanni2
1
International Institute for Gestalt Therapy and Psychopathology - IPsiG; 2Department of Psychology, University of Turin; 3Santa Lucia
Foundation, European Centre for Brain Research, Italy

ABSTRACT
There is consensus among scientists in considering Panic Attack (PA) as an exaggerated fear response triggered by intense activation
of the amygdala and related Fear brain network. Current guidelines for treatment (e.g. National Institute for Clinical Excellence,
NICE, 2011), that are based on this view, do not achieve satisfactory results: one-third of all treated patients report persistent PAs and
other Panic Disorder (PD) symptoms, and several meta-analyses report the high likelihood of relapse. Here we review findings from
Affective Neuroscience and clinical insights from a phenomenological-Gestalt perspective, putting into question the link between PD
and activation of the Fear brain network. We propose an alternative hypothesis about PD etiology: PD is mainly connected to the

ly
Panic system, that is activated in situations of separation from affective support and overexposure to the environment. In our view, PA
can be understood as an acute attack of solitude which is not adequately recognized by the patient due to the intervention of a disso-

on
ciative component that makes it impossible to integrate all neuro-physiological responses activated by the Panic/Separation brain
system within a coherent emotional feeling. This perspective can explain many evidences that otherwise remain isolated elements
without a comprehensive frame: i.e., the association with agoraphobia, the onset of PD during adolescence and young adult life, the

e
need to be accompanied, the connection with air hunger and other respiratory anomalies, the efficacy of antidepressants and the lack
us
of activation of the Hypothalamic-Pituitary-Adrenal (HPA) axe. We discuss future steps to test this hypothesis and the consequences
for psychotherapeutic treatment.
al
Key words: Panic Disorder; Affective Neuroscience; Phenomenological-Gestalt perspective; Gestalt therapy.
ci
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acterized by recurrent panic attacks, by consequent pre-

Introduction occupations about these attacks, and then by a complex
m

According to the DSM-5 (American Psychological behavioural reorganization around such worrying. The
om

Association (APA), 2009), Panic Disorder (PD) is char- DSM-5 defines a Panic Attack (PA) as a discrete period
of intense fear or discomfort that reaches its climax rap-
idly, together with a paroxysmal increase in strong auto-
-c

nomic arousal. PAs are generally accompanied by

Correspondence: Michele Settanni, Department of Psychology,
different somatic symptoms, such as palpitations, pound-
on

University of Turin, Italy.

E-mail: [email protected] ing or accelerated heart rate, sensation of shortness of
breath or smothering (air hunger), sweating, trembling or
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Citation: Francesetti, G., Alcaro, A., & Settanni, M. (2020). Panic shaking, nausea or abdominal distress, feelings of choking
disorder: attack of fear or acute attack of solitude? Convergences be-
tween affective neuroscience and phenomenological-Gestalt per- or chest pain, dizziness, unsteadiness, light-headedness or
spective. Research in Psychotherapy: Psychopathology, Process and fainting. Moreover, PAs are also accompanied by psychic
Outcome, 23(1), 77-87. doi: 10.4081/ripppo.2020.421 symptoms such as depersonalization (being detached
from oneself), de-realization (feelings of unreality), fear
Conflict of interest: No competing financial interests exist.
of dying and fear of losing control or going crazy. In con-
Received for publication: 18 July 2019. sequence of such symptoms, panic is often characterized
Accepted for publication: 19 February 2020. by a sense of impending doom or catastrophe and a sense
of urgent need to distance oneself.
This work is licensed under a Creative Commons Attribution Non-
Commercial 4.0 License (CC BY-NC 4.0). The lifetime prevalence of PD in the population is
high (de Jonge et al., 2016; e.g. 4.7% in the US, 1.9 in
Copyright: the Author(s), 2020 Western Europe) and PD patients typically experience
©

Licensee PAGEPress, Italy

Research in Psychotherapy:
work impairment, high unemployment rates, seek medical
Psychopathology, Process and Outcome 2020; 23:77-87 treatment more frequently and have more hospitalizations
doi:10.4081/ripppo.2020.421 than people without PD (e.g. Markowitz, Weissman,
Ouellette, Lish, & Klerman, 1989). Guidelines for treat-

[Research in Psychotherapy: Psychopathology, Process and Outcome 2020; 23:421] [page 77]
 Article

ment have been published by major health institute world- 2018). Gestalt psychotherapy is a phenomenological ap-
wide (e.g. NICE, 2011) and they are based on the phar- proach that explores the processes of experiences as they
macological, psychological and combined treatments. The emerge in the therapeutic meeting. It focuses on both the
recommended treatment options have a significant evi- patient’s and the therapist’s subjective experience and on
dence base: psychological therapy, medication and self- the processes of co-creation in the therapeutic situation.
help have all been shown to be effective. As regards Gestalt Therapy is an experiential, existential and rela-
pharmacological treatment the elective drugs are antide- tional approach that gives value to the mutual bodily
pressants, even if APA proposes benzodiazepines as com- processes of affective co-regulation between the patient
plementary medications for specific situations (APA, and the therapist (Perls, Hefferline, & Goodman, 1951;
2009). In particular, on the basis of numerous randomized Jacobs & Hycner, 2009; Philippson, 2009; Spagnuolo
controlled trials, APA recommends the use of a Selective Lobb, 2013; Robine, 2016; Bloom, 2009; Bloom, 2019;
Serotonin Reuptake Inhibitor (SSRI), Serotonin-Norepi- Francesetti, 2019a; 2019b; Francesetti & Griffero, 2019).
nephrine Reuptake Inhibitor (SNRI), Tricyclic Antide- Both the Affective Neuroscience and phenomenological-
pressant (TCA), or Cognitive-Behavioural Therapy Gestalt approach share the relevance given to subjective
(CBT) as the initial treatment for panic disorder. experience and, more specifically, to emotional feelings,
As regards psychological approaches meta-analyses that are considered the fundamental core of all mental
indicate that, although CBT shows the largest evidence processes (Alcaro, Carta, & Panksepp, 2017). Moreover,
base, other approaches have also showed significant pos- as we will briefly show in the following pages, they also
itive short-term effects (e.g., psychodynamic therapies) share a common view on PD that differs from the domi-

ly
(APA, 2009; Furukawa, Watanabe, & Churchill, 2006). nant perspective, giving the emotional experience of being
Despite the availability of guidelines indicating effec- abandoned/left alone a central role in the manifestation

on
tive pharmacological, psychological and combined treat- and in the etiology of PAs.
ments, about one-third of all PD patients after treatment
Is panic an intense attack of fear?

e
report persistent panic attacks and other PD symptoms,
and several meta-analyses agree on highlighting the high
likelihood of relapse in patients treated both using drugs
us
Current approaches usually consider panic attack as
an exaggerated and inappropriate fear response (Clark,
or via psychosocial interventions, or with combined (med- 1986; Casey, Oei, & Newcombe, 2004) triggered by in-
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ications and therapy) approaches (Batelaan et al, 2017; tense activation of the amygdala and the related Fear brain
Nardi et al., 2016). These unsatisfactory outcomes with
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network2 (McNally, Otto, Yap, Pollack, & Hornig, 1999;

respect to stability of therapy effects indicate the need for Windmann, 1998; Gorman, Kent, Sullivan, & Coplan,
er

further theoretical investigation into the etiology of the 2000; LeDoux, 2015; Hamm et al., 2016). According to
disorder that in turn could lead to the development of this perspective, current psychotherapeutic interventions
m

more effective, especially on the long-term, therapeutic (especially CBT) are aimed at reducing the patient’s fear
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approaches. Therefore, the aim of this study is to present (and anxiety) sensitivity, by de-conditioning procedures,
converging findings about PD origin and treatment com- correcting maladaptive thoughts, improving self-esteem,
ing from two different fields, Affective Neuroscience and etc. (Barlow, Gorman, Shear, & Woods, 2000; Gallagher
-c

a phenomenological-Gestalt approach, and to propose an et al., 2013; Yang, Kircher, & Straube, 2014).
alternative hypothesis about the PD etiology and possible However, although psychotherapeutic treatments that
on

effective treatment.1 focus exclusively on FEAR de-sensitization are very effec-

Affective Neuroscience is a discipline founded by
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Jaak Panksepp (1998) and is now very popular among

clinical psychologists and psychiatrists for its contribution
to understanding human psychopathology and in devel-
The first idea of writing this paper came up in October 2016, during
oping new therapeutic strategies to mental disorders
1

the Conference of the FIAP (Italian Federation of the Associations of

(Panksepp, 2004; Panksepp & Biven, 2012). Combining Psychotherapy). In that occasion Jaak Panksepp and author discussed
animal and human experimental investigations, Panksepp their perspectives on panic disorder and decided to develop further their
and his collaborators identified the existence of seven convergences. Very sadly Panksepp passed away in April 2017, so we
couldn’t write this paper together, but the inspiration of it comes from
basic Emotional Systems in the brain of mammals that that first meeting. We want to acknowledge his contribution to this paper
play a central role in the organization of human personal- and to express our gratitude to him.
ity (Davis & Panksepp, 2011; Panksepp & Biven, 2012; 2
Being the most studied brain circuitry of the mammalian brain, the
Fear system is mainly located within central and lateral amygdala,
Montag et al., 2016).
medial hypothalamus and dorsal periacqueductal gray, and uses
The phenomenological approach to psychopathology glutamate, cholecystokinin, corticotropin releasing factor, and diazepam
carefully explores the patient’s subjective experience, the binding inhibitor as the main neurotransmitters/neuromodulators of its
ways in which it emerges and is constituted (Jaspers, intrinsic network (Panksepp & Biven, 2012; LeDoux, 2015). It is also
well known that both pharmacological and psychotherapeutic
1963; Minkowski, 1927; Binswanger, 1963; Borgna, interventions reduce anxiety, phobias and other fear-dependent
1988; Francesetti, Gecele, & Roubal, 2013; Zahavi, symptoms, by reducing neural excitability within the Fear brain system.

[page 78] [Research in Psychotherapy: Psychopathology, Process and Outcome 2020; 23:421]
 Panic disorder: attack of fear or acute attack of solitude?

tive in correcting rapidly some secondary manifestation of 1997). They are not able to mentalize these bodily signals
PD, such as the spiralling increase in anxiety after the first as feelings connected to the need for another who enters
episode, they do not guarantee good outcomes over the long in an affective co-regulation of this strong discomfort
term (Bakker, 2001; Durham et al., 2005). Moreover, since (Shore, 2003). These feelings are not mentalized as lone-
the work of Donald Klein in the early 60s, it is well known liness at the beginning and they emerge only during the
that the benzodiazepine-type antianxiety agents (Librium, process of therapy.3 To consider panic disorder as a com-
Valium, etc.) have little effect on the incidence of panic, plex clinical experience implying an unmentalized soli-
while antidepressants are more effective in quelling such tude is the thesis of this paper. It is supported by some
attacks (Klein & Fink, 1962). These evidences bring into research and clinical findings and it can orient the thera-
question the conviction that panic is simply an excessive peutic interventions with this population.
and uncontrolled fear reaction.
Other doubts come from the evidence that panic at- Panic and the experience of being overexposed without
tacks differ from Cannon’s emergency fear response affective mediation
(Cannon, 1920) and Selye’s General Alarm Syndrome The etymology of ‘panic’ refers to Greek mythology:
(Selye, 1956) in two important psycho-physiological as- to Pan, the god half man and half goat. According to
pects. First of all, panic is characterized by the promi- Greek tradition, Pan lives in wild places and forests and
nence of intense air hunger, that rarely occurs in acute, he causes terror to lonely wayfarer. He is also responsible
external-danger initiated fear (Klein, 1993; Preter & for nightmares that suddenly wake the sleepers during the
Klein, 1998). Moreover, contrary to fear, panic is accom- night. His history is very interesting: Pan’s mother, when

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panied by the lack (possibly suppression) of Hypothala- pregnant, went alone into the forest in order to give birth
mic-Pituitary-Adrenal (HPA) activation. Indeed,

on
to her baby. But when she did so, and was about to take
tachycardia and other forms of psychophysiological acti- him in her arms, she saw that he was a monster, half a
vation during panic are produced by vagal (parasympa- baby and half a goat. Terrified, she ran away and left the

e
thetic) withdrawal rather than sympathetic arousal (Preter new-born Pan alone in the forest, exposed to the world
& Klein, 2008).
In accordance with such evidence, the exploration of
us
without the necessary mediation of his mother and of a
shelter (Homeric Hymn 19 to Pan).
patients’ experience through a phenomenological-Gestalt The link that the mythology establishes between terror
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analysis (Francesetti, 2007; Francesetti et al., 2013) indi- and loneliness has surprising similarities with clinical and
cates that fear - even though overwhelming and predom-
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epidemiological evidence. In their clinical study with hos-

inating in patient’s narratives - is not the first event in the pitalized agoraphobics, Klein and Flink (1962) showed
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acute attack. Indeed, the very moment of the attack is that patients suffering from PD reported severe early sep-
characterized by the actual experience of dying or of be- aration anxiety that often-prevented school attendance in
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coming crazy, perceived as a bodily discomfort; then - im- childhood. This result was replicated by specific longitu-
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mediately after - the fear of death or the fear of craziness dinal studies of the same individuals confirming the rela-
emerges. After the first attack, these fears, and the fear of tionship between PD (and agoraphobia) and childhood
other attacks, become the main narrative. But patients say Separation Anxiety Disorder (SAD) (Klein 1993, 1995;
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that during the attack the experience is actually of dying Kossowsky et al., 2013). Moreover, recent twin studies
or of becoming crazy, and then they become terrified by also demonstrated a common genetic diathesis for child-
on

this. As an evidence of this sequence, we can observe that hood separation anxiety disorder and adult onset panic at-
patients go to the emergency room or to the general prac- tacks (Robertson-Nay et al., 2012).
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titioner in order to treat the acute physical symptomatol- Since the work of Klein and Fink, the hypothesis of a
ogy and not to a psychologist in order to seek help for connection between PD and separation distress received
their fear. In this perspective, the fear is the major over- some attention and it has been eventually confirmed by
whelming event in the phenomenology of the panic dis- successive research studies (e.g. Raskin, Peeke, Dickman
order, but it is secondary to the experience of dying or of & Pinsker, 1982; Rizq, 2002). Epidemiological studies
becoming crazy, emerging as a bodily discomfort in the show that panic disorder’s onset occurs from adolescence
panic attack. This phenomenological observation is in line up to age 35 (DSM 5). This phase of life is characterized
with the literature indicating that interoceptive awareness by the processes of separation from the familiar belong-
is central in these patients (Craig, 2003): they are contin-
uously detecting the variability of each situation accord-
ing to a bodily centred system of orientation (Lorenzini
& Sassaroli, 1987; Guidano, 1991; Arciero and Bondolfi,
2009). These patients are able to mentalize fear - to rec- 3
A phenomenological inquiry requires an intersubjective exploration
ognize and express it - but they are not able to mentalize that is not only intended to describe what is already present as a first
narrative, but also to support the emergence of what is implied in the
the bodily signals indicating the lack of affective media- considered experience. Indeed, by definition, a phenomenon is what
tion in a situation of overexposure (Fonagy & Target, appears when we stay, pause and wait close to it (Giorgi, 2009).

[Research in Psychotherapy: Psychopathology, Process and Outcome 2020; 23:421] [page 79]
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ing, the movement towards the world and towards an in- It has also been suggested by cognitive models that
creasing autonomy. Moreover, the onset of PD in adults PD is related to a conflict between two opposite tenden-
is often preceded by actual separation, loss, bereavement, cies, the need for affective proximity and the refusal to be
or other events implying emotional or physical separation constricted within enduring bonds (Lorenzini & Sassaroli
from a significant figure4 (Roy-Byrne, Geraci, & Uhde, 1987; Guidano, 1991; Macaurelle, 2003). In accordance
1986; Jacobs et al., 1990; Faravelli & Pallanti, 1989; with this idea, PD’s onset is sometimes related to the be-
Kaunonen, Paivi, Paunonen, & Erjanti, 2000; Klein, 1993; ginning of a marriage, indicating that such an important
Venturello, Barzega, Maina, & Bogetto, 2002; Milrod, life change may activate the anxiety of being restricted
Leon, & Shear, 2004). (Macaurelle, 2003). However, it is also plausible that the
The phenomenological-Gestalt exploration confirms marriage also implies the experience of separation from
that at the onset of panic disorder there is typically a sig- previous familiar bonds, as well as from a lifestyle centred
nificant passage of separation that is usually underesti- on autonomy and individual freedom (see paragraph 5).
mated by patients: ‘I went to the university and I left my Moreover, the phenomenological inquiry reveals that the
group of friends’; ‘I moved to work in another city and reluctance to be restricted within enduring bonds is usu-
my girlfriend stopped the relationship with me’; ‘I got a ally better represented in conscious thoughts of patients,
new and better position in the company and I went to live while the anxiety of solitude is usually underestimated or
by myself’; ‘I finished university, I started to work and neglected altogether (paragraph 5). This evidence indi-
my sister went to study abroad’. When these changes are cates that PD symptoms, especially bodily symptoms,
explored, we found the experience of feeling more ex- may represent an alternative (somatic) way of expressing

ly
posed to the world, outside the familiar environment, with a refused emotional experience that plays a central role in
less mediation offered by the previous belongings and re- the actual subjective conflict.

on
lationships. Bereavement seems to be a condition of vul- These elements bring us to the conclusion that to con-
nerability to panic disorder when the person who is lost sider the panic simply as an attack of fear does not take
into account a number of important clinical elements. It

e
was a significant one in the process of mediation between
the patient and their environment. A patient says ‘My seems more accurate to consider panic disorder as a com-
us
grandmother died one year before the first panic attack. I plex clinical situation that emerges from the experience
didn’t pay attention to this, I was already living quite far of feeling too exposed to the world without a sufficient
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relational protection that provides a mediation with the
from her, she had her life and I had mine. But now I un-
world. The fear comes just after the very immediate ex-
derstand something different: I grew up with her, since
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perience of dying or becoming crazy, in a moment of

my parents were divorced and were busy at work. She was
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overexposure and then it is mainly generated by the fear

my protection in my life. Now I can feel the pain and sad-
that the acute attack can happen again. Dying or becoming
ness, I miss her tremendously’.
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crazy are the two existential situations of radical separa-

The connection between panic and the loneliness of
tion from belonging to the human community.
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being overexposed to the environment provides meaning

From these considerations, we propose considering
to at least four elements of the disorder, which might oth-
panic disorder as a kind of separation anxiety rather than
erwise be difficult to understand: the experience of suffo-
a generic fear, and in this frame as an acute attack of soli-
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cating, agoraphobia, the difficulty in being alone

tude. Let’s go now to discuss some neurological data and
(expressed also by the need to be accompanied and the
on

then we will connect them to clinical experiences.

limitations in movements) and the moment of the onset.
The first element will be discussed in the next paragraph The Panic/Separation System
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since it is directly connected to the neurological pathways

implicated in panic. The second, agoraphobia (from Panksepp’s neuro-ethological studies have demon-
Greek, agorà: square, and phobia: fear), is very often as- strated that mammals are provided with two separated brain
sociated with panic: being in the middle of a square is the alarm systems (Panksepp & Biven, 2012). The first, that
iconic situation of being overexposed to the world without has been called the Fear System, is activated by the percep-
enough mediation. The third, the need to be accompanied, tion of an external threat. The other, that has been called
sometime so strong that it makes it impossible to move the Panic/Separation system, is maximally activated when
from home autonomously, is the expression of the need the individual is separated from a fundamental social/af-
for a mediation between the patient and the world in order fective support, such as when young pups are distanced
not to be alone and overexposed. The fourth element is from their mother, and driven to active protest, such as cry-
the moment of onset of PD: adolescence and young adult ing in humans and distress vocalizations in other mammals
life. This phase is characterized by a movement of sepa-
ration from the safer familiar context towards the outside
world, with the risk of feeling overexposed to the envi-
It has also been shown that the presence of separation anxiety in
ronment (the movement from Oikos to Polis, Francesetti,
4

adults influences panic symptom severity and impairments in the quality

2007; Francesetti et al., 2013). of life (Pini et al., 2014).

[page 80] [Research in Psychotherapy: Psychopathology, Process and Outcome 2020; 23:421]
 Panic disorder: attack of fear or acute attack of solitude?

(Nelson & Panksepp, 1988; Panksepp, 1998). The separa- The connection between panic and suffocation re-
tion alarm signal serves as a biologic leash for the increas- ceived an important confirmation by the evidence that a
ingly mobile, but helpless infant who continually checks dysfunction in the endogenous opioid system may explain
for the mother’s presence, becomes acutely distressed on the respiratory anomalies in panic disorder patients8
discovering her absence, and immediately attempts to elicit (Preter & Klein, 2008). Moreover, it has been evidenced
retrieval by crying.5 However, if the caregiver does not
come back, the separation calls gradually stop and the in-
fant enters into an inhibitory behavioural state characterized
by retirement and isolation from the external world
Specifically, the separation call, intended to maintain mother-
(Bowlby, 1969). At the subjective level, while the first
5

offspring contact, has been suggested to be the most ancient form of

phase (protest) is accompanied by feelings of intense dis- mammal communication (Battaglia, 2015). The emergence of a
comfort, the second phase (despair) is characterized by the Panic/Separation Distress emotional drive, together with Care/nursing and
feeling of sadness (Bowlby, 1969; Panksepp, 1998). Play, marked the emergence of mammals from mammal-like reptiles, and
led to the evolution of complex social and cognitive skills, as well as to
The Panic/Separation System is characterized by neu- the emergence of the distinctively mammalian brain structures of the
roanatomical and neurochemical pathways distinct from cingulate cortex and the so-called thalamo-cingulate division (MacLean,
the Fear system. If the Fear system is mainly centered on 1985; Panksepp, 1998). As noted by Battaglia, «the advent of greater brain
the amygdala, medial hypothalamus and dorsal periacque- cellular mass—like that associated with the emergence of the
neopallium—allowed paleomammals to attain greater brain plasticity and
ductal gray, the Panic System is mainly located within the extend the array of learning capacities, which are in turn basic ingredients
anterior cingulate, the bed nucleus of the stria terminalis, of individual variation in behavior. All forms of learning, however, require

ly
the dorso-medial thalamus, the preoptic area, and the pe- time for practicing, as practice implies errors, and correction and
riacqueductal gray.6 Being the key neuromodulators of

on
consolidation of newly acquired skills. In a growing child this generates
dependence on parental care in order to ensure safety, nourishment, and
socio-affiliative interactions, endogenous opioids, oxy- protection. It can thus be expected that the wider the array and plasticity
tocin, and prolactin are the main neurochemicals of the of behavioral repertoire in a species, the longer the time needed for

e
Panic system (Panksepp & Biven, 2012; Nelson & learning and practicing, and the more protracted the dependence on
Panksepp, 1998). In particular, the endogenous opioid
system seems to indicate a main role, since animal studies
usparental care. […] The progressive extension of a period of dependence
from maternal care that can be attributed to an increasingly complex, and
thus immature, brain at birth, probably prepared the ground for the
have revealed that the administration of opioids is the development and maintenance of SA as an element of reciprocal
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most powerful inhibitor of distress vocalizations elicited regulation of the infant-mother bond, and a moderator between the child’s
cycles of exploration of the environment, learning, and safe return to the
by young pups when they have been separated from their
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mother» (from Battaglia, 2015).

mother (Nelson & Panksepp, 1988).
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6
In accordance with the neuroanatomical distinction between fear
The Panic/Separation brain system controls a series of and Panic brain circuitries, the analysis of neurologic patients
neurophysiologic and neuroendocrine responses that demonstrated that individuals with lesions of the amygdala show a
m

marked absence of fear during exposure to fear-provoking stimuli and

modify the internal state of the body, such as respiration, do not condition to aversive stimuli. However, they show common panic
om

heartbeat, pain sensitivity, etc. This fact may explain why reactions when they are experimentally exposed to anoxic conditions,
panic attacks are characterized by physical symptoms, suggesting that amygdalocentric Fear system is not necessary to trigger
a panic attack (Feinstein et al., 2013).
acute and inexplicable, that interrupt the continuity of
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Indeed, experimental studies have also shown that the panic attack
usual experience and are experienced as a catastrophic
7

can be reliably incited in laboratory settings by specific chemical

event (dying or losing one’s mind).
on

challenges, using intravenous lactate infusion and carbon dioxide

Of all the many kinds of somatic manifestations that inhalation (Liebowitz et al., 1984, Gorman et al., 1984, Papp, Klein,
Gorman, 1993; Klein, 1993). However, while normal controls or patients
characterize PAs, those associated with the experience of
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with other anxiety disorders rarely show such reactivity (i.e., progress to
air-hunger and suffocation are probably the most frequent a full- blown panic attack), higher concentrations of inhaled CO2 are
and intense. Interestingly, physiological investigations re- highly aversive and can produce respiratory panic symptomatology in a
vealed that one prominent characteristic of the panic at- dose-dependent fashion (Griez et al., 2007; Esquivel et al., 2010; Leibold
et al., 2013). Beck et al. (1999; 2000) showed that panic patients respond
tack and subthreshold panic-related anxiety is respiratory with increased panic symptoms not only to CO2 inhalation, but also to
dysregulation and chaotic breathing, while air hunger and normocapnic hypoxia. This makes it possible to integrate separation
chronic sighing outside of the acute attack are hallmarks anxiety disorder, CO2 and lactate hypersensitivity, and a range of
of panic (Klein, 1993; Preter & Klein, 2008). Moreover, respiratory phenomena and pathology with Panic Disorder.
Indeed, naloxone infusion (ranging from an initial 0.5mg/kg to a
panic disorder patients show an excessive reactivity to
8

maximum of 2mg/kg) followed by lactate (N+L), caused significant tidal

blind hypercapnic and/or hypoxic conditions7 (Griez, Co- volume increments similar to those observed during clinical and lactate
lasanti, van Diest, Salamon, & Schruers 2007; Esquivel, induced panic attacks in 8 of 12 normal subjects, supporting the
hypothesis that opioidergic deficiency might be necessary for lactate to
Schruers, Maddock Colasanti, & Griez, 2010; Leibold et produce a marked increase in tidal volume in normal subjects (Sinha,
al., 2013; Beck, Shipherd, & Read, 1999; Beck, Shipherd, Goetz, & Klein, 2007). Moreover, «normal subjects, usually relatively
& Ohtake, 2000). All such evidence suggested the hypoth- insensitive to the tidal volume effects of lactate infusion, [...] given opioid
esis that panic attacks may be interpreted as a “false suf- antagonist pretreatment, developed tidal volume and respiratory rate
increments resembling those occurring in both spontaneous clinical panic
focation alarm signal” and that PD patients suffer from a attacks and in panic patients who panic during lactate infusions» (Preter
chronic Suffocation anxiety (Klein, 1993). et al., 2011).

[Research in Psychotherapy: Psychopathology, Process and Outcome 2020; 23:421] [page 81]
 Article

that separations and losses (i.e. parental death, parental tional style, not inclined to ask for help and to rely upon
separation or divorce) affect the functionality of the en- others, hardly able to express their affective needs
dogenous opioid system, and the deficit of the opioid sys- (Francesetti, 2007; Francesetti et al., 2013). This rela-
tem may explain separation anxiety, respiratory anomalies tional style makes the disorder even more upsetting since
and panic disorder9 (Preter et al., 2011). the patient is unaccustomed to the need for help and sup-
Finally, the evidence showing that the endogenous port. The mentalisation of the need for support and close-
opioid system of the brain co-regulates breathing as well ness, even if it is strongly present, is difficult and people
as separation/distress behaviours fits with the neuro-evo- suffering from panic disorder tend not to behave very co-
lutionary hypothesis formulated by Stephen Porges (2007; operatively.
2011), who underlined the function of the cranial nerves If PD patients suffer from an emotional dissociation
and muscles for expressing separation distress vocaliza- and tend to be alexithymic, the feeling of imminent death
tions evolved from the primitive gill arches that extract or breakdown may be viewed as the expression of a so-
oxygen from water (Porges, 2007). matic activation that overwhelms the containment capac-
ity of the subject (Strubbe & Vanheule, 2014) and that is
Panic and dissociation then experienced in an “unmentalized” and somatoform
condition (Busch & Sandberg, 2014). Indeed, if the
If suffocation and other bodily symptoms of panic at-
Panic/Separation system activates a series of neurophys-
tacks may be explained by the neurophysiologic responses
iologic and neuroendocrine responses that modify respi-
induced by the Panic/Separation brain system, it remains
ration, heart beating, pain sensitivity, etc., the failure in
to be explained why PD patients do not recognize that

ly
integrating such changes within a coherent and recogniz-
they are suffering from separation distress. Indeed, PD pa-
able subjective emotional state may lead to the experience

on
tients usually do not report feelings of social or affective
of a catastrophic and unintelligible somatic breakdown.
discomfort, and they do not recognize any psychological
cause or meaning for their attacks.
Some clinical evidence

e
In order to answer that question, it is important to con- us
sider that there is a distinction between the functional emo- As we observed before, during the panic attack the ex-
tion state (‘the emotion state’) and its conscious experience perience is not the fear of dying but the actual experience
(‘the experience of the emotion’) (Adolphs, 2017). Even if of dying. This experience causes the fear of dying and the
al

emotion states, emotion experiences, and emotion concepts medical feedback usually confirms that ‘it is only fear,
ci

usually occur together in healthy adult humans, they can you are not dying’. However, for the patient to reach the
also be dissociated. In our view, this kind of dissociation understanding that it is fear usually takes some time and
er

could be present in PD patients, who could experience sep- elaboration: at that point the patient can say ‘I know that
I am not dying, it is my attack, it is fear, I know it’. This
m

aration distress as an emotion state, without experiencing

it in a conscious way. In line with this view, recent experi- awareness usually comes later and brings a significant
om

mental studies have shown that PD patients often report clinical relief (Rovetto, 2003; Francesetti, 2007).
childhood traumatic experiences (Zou et al., 2016), that Returning to therapy and exploration, gradually an-
lead to a pathological form of dissociation in adulthood other emotional dimension emerges: the feeling of lone-
-c

(Majohr et al., 2011). As a consequence, adult PD patients liness (Meltzer et al., 2013). These feelings usually are
tend to be alexithymic, having difficulty in realizing, rec- not easily accessible and it takes some time before we can
on

ognizing, discriminating, and expressing emotional feelings meet them. Often, for a long time, the patient doesn’t feel
(Cox, Swinson, Shulman, & Bourdeau, 1995; Iancu, Dan- that loneliness is a relevant feeling in their life and the
N

non, Poreh, Lepkifker, & Grunhaus. 2001; Marchesi, Fontò, therapist is the only one who feels it, as a feeling of being
Balista, Cimmino, & Maggini, 2005; Cucchi et al., 2012; alone without being able to give sense to it. The kind of
Izci et al., 2014). Moreover, they also tend to be less coop- solitude that the patient gradually discovers is quite spe-
erative and confident with other people (Wachleski et al., cific: the experience of being alone, overexposed to the
2008; Izci et al., 2014). Also related to this point, it is worth world, without a sufficient protective mediation. In the
noting that literature findings support the connection be- words of a patient, deeply touched by this discovery: ‘I
tween separation anxiety experienced at early age and the discovered that the point is not that I am scared of dying.
development of difficulties in recognizing (being aware of)
affective states (e.g., Mason, Tyson, Jones and Potts, 2005;
Joukamaa, et al. 2003) and that alexithymic traits have been
found to be more pronounced in individuals who reported 9
The role of endogenous opioid in panic disorder and suffocation
more severe symptoms of separation anxiety during child- alarm receive a confirmation in animal studies (Moreira et al., 2013).
hood (Troisi, D’Argenio, Peracchio, & Petti, 2001). Graeff (2012), studying an animal model of panic disorder found that
In accordance with such scientific evidence, clinical the inhibitory action of serotonin is connected with activation of
endogenous opioids in the periaqueductal gray (PAG). Schenberg and
observation shows that patients suffering from PD typi- colleagues (Schimitel et al., 2012) suggest «[the PAG] harbors an
cally present a highly autonomous and independent rela- anoxia-sensitive suffocation alarm system».

[page 82] [Research in Psychotherapy: Psychopathology, Process and Outcome 2020; 23:421]
 Panic disorder: attack of fear or acute attack of solitude?

The point is that I am so alone that I could die. Even from this theme are often dissociated, the therapist can be
forever having been alone in my life.’ the first, for some considerable time, to feel, recognize
Usually, the emotions that emerge along with the dis- and legitimate them during the sessions;
covery of the solitude are sadness and anger: ‘I feel a sad- – Even though the onset of the PD is usually experi-
ness that I didn’t know I have, I don’t know why I am enced without any connection to life events, it is usu-
crying, nothing really serious happened...’; ‘Now I realize ally connected to separation processes, typically a life
that I have always been alone, it is sad... I don’t know how passage towards more autonomy (during adolescence
it was possible for me not to feel it...’; ‘I remember now or young adult life) or a loss of somebody relevant in
how good I was at school… I was just a little girl but I mediating between the patient and the world;
never cried when I had to leave my parents for some days – Even though patients ask to regain their autonomy rap-
during the outdoor activities. Many children were crying, idly, they should be supported to move towards the ex-
but I never did. For my teacher, I was a model for all of perience of relational belonging more than – or along
them. Now, remembering that, I am crying... it is so with – a movement towards independence. The thera-
sad...’; ‘Why did I have to be so good? Why couldn’t I peutic relationship can be an affective mediation be-
cry like the others? Of course, I couldn’t: my mother tween the patient and the world and the therapeutic
would have been even colder than usual and would have belonging can be one of the most healing experiences
humiliated me, and my father would have agreed with her. for these patients.
Now I am very angry’. A crucial phenomenon is that the We could wonder why, despite the impressive number
emergence of loneliness is a difficult passage, which re- of clues in research and in clinical work, PD has been con-

ly
quires time and relational support: at the beginning of the sidered for decades to be an acute attack of fear without
therapy the solitude is not only not perceived, but there is recognizing the experience of loneliness that we claim to

on
a kind of affective distance or reactivity to it, as if it is a be crucial in this disorder. This is probably connected to
dissociated area of experience. Only gradually and the patient’s dissociation that protects the feeling of lone-

e
through a careful therapeutic exploration can the patient liness from being perceived and that also influences the
feel, recognize, legitimate and finally mentalize it: ‘I therapist during the meeting (Francesetti, 2015; 2019a;
us
never thought that I could feel any kind of solitude, I have 2019c; Roubal, 2019; Stern, 2015). Furthermore, we sug-
always been a point of reference to my friends, the person gest that it can also be connected to a wider dissociation
al
to rely upon... Until the panic, I was autonomous, but af- characterizing our social field. Loneliness seems to be a
terwards I couldn’t move without somebody being with central element in our Western societies, but, even though
ci

me... but I didn’t understand that yet. Now, finally, I feel central, it is not fully integrated in our culture (Lasch,
er

that I need the closeness and the hug of somebody... It 1978; Bauman, 2002; Cacioppo & Patrick, 2008; Rosa,
costs me a great deal to admit this, even though I don’t 2010; Bollas, 2018). Often, it is considered to be the ex-
m

know why...’. perience of people who are not sufficiently integrated into
society, the losers.
om

The curious forgetfulness of loneliness in PD could be

Conclusions the result of both an individual pressure (a dissociated
-c

feeling in the personal biography) and of a social pressure

On the basis of research and clinical explorations, we
(a dissociated need for relational and intimate bonds), in
propose to consider the PD a complex clinical situation
on

which both the therapist and the patient are deeply in-
that emerges from an experience of dissociated and un-
volved. This hypothesis is compatible with cross-cultural
metallized loneliness, similar to separation distress and
N

and epidemiological research, that highlighted the pres-

characterized by an overexposure to the world without af-
ence of relevant differences in the prevalence rates of PD
fective mediation. The alarm signal recruited by the
in different countries (e.g. Kessler et al., 2007), finding
Panic/Separation system is not subjectively recognized
quite a strong positive link between societal values such
and mentalized by PD patients and consequently is ex-
as affective autonomy and the rates and lifetime risk of
pressed in a somatic form. Psychotherapeutic interven-
PD (Heim, Wegmann, & Maercker, 2017). The myth of
tions should gradually help the patient to increase their
Pan seems to provide a narrative frame to an experience
awareness of the hidden emotional drive expressed by
that expresses both an individual and a social condition:
PAs and to recognize the importance of relational and af-
a dissociated solitude and the need for a relational bond.
fective bounds for their mental wellbeing.
The fear, in this perspective, can be understood as the ex-
This perspective has some relevant implications for
pression of an acute attack of solitude.
psychotherapy:
– Even though the fear is the overwhelming and daz-
Future steps
zling emotion in the patient’s experience, the themes
connected to solitude and to overexposure to the world In order to explore the relationships between unmen-
should be gradually and carefully considered and ex- talized loneliness and PD further empirical studies are
plored. Since the feelings and emotions connected to needed. Our research group plan to put the hypothesis of

[Research in Psychotherapy: Psychopathology, Process and Outcome 2020; 23:421] [page 83]
 Article

a causal connection between unmentalized loneliness and profiles influence response to a hypoxic challenge in patients
PD to a test, by studying different interrelated phenom- with panic disorder? A preliminary report. Psychosom Med
ena. First, we aim at testing if there are significant dif- 62(5):678-83.
ferences between perceived levels of affective autonomy, Binswanger, L. (1963). Being in the World. New York: Basic
Books.
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Bloom D. (2009). The Phenomenological Method of Gestalt
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treatment, following the conclusion of therapy. In addi- Gestalt Therapy. Gestalt Rev 13(3):277-95.
tion, we aim at improving our knowledge of the direct Bloom D. (2019). Afterword. Neither from the “Inside” Looking
antecedents of PD onset. It is already known that the “Out” nor from the “Outside” Looking “In”. In: Francesetti
onset of PD is often preceded by life events such as grief, G., Griffero T., eds. Psychopathology and Atmospheres. Nei-
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