Jacobs Journal of Neurology and Neuroscience

Anxiety Disorders: Definitions, Contexts, Neural Correlates And Strategic Therapy

*Giulio Perrotta
Department Of Criminal Psychology, UNIFEDER University, Italy

*Corresponding Author:
Giulio Perrotta
Department Of Criminal Psychology, UNIFEDER University, Italy

Published on: 2019-03-29


Starting from the concept of anxiety, we proceeded to separate the “physiological” form from the “pathological” forms, distinguishing between fear, anguish, panic, phobia, fear, terror and stress, all terms often confused and overlapped in the common jargon. Distinguishing the individual psychopathologies contained in DSM-V anxiety disorders, with a focus on the psychodynamic profile, the analysis focused on the neural correlates involved in anxiety disorders and on the best pharmacological and psychotherapeutic approaches chosen to treat the morbid condition, paying particular attention to the strategic model and the most important clinical techniques.


Psychology; neuroscience; anxiety; panic; terror; anxiety disorders; panic attack; panic disorder; selective mutism; phobia; agoraphobia; amygdala; prefrontal cortex; fear; anxiety; psychotherapy; psychopharmacology; benzodiazipines; antidepressants; strategic approach

Copyright: © 2019 Giulio Perrotta


The definition of anxiety is not unequivocal in the literature [1] although the descriptive characteristics are well circumscribed and easily identifiable. The American Psychiatric Association, on the definition of anxiety, describes anxi- ety as the anticipated anticipation of a future danger or negative event, accompanied by feelings of dysphoria or physical symptoms of tension. The elements exposed to risk may belong both to the internal world and to the external world [2] Similarly, in the Italian Treaty of Psychiatry, precisely in reference to the definition of anxiety, it is referred to as emotional state with an unpleasant content, associated with a condition of alarm and fear that arises in the absence of danger real and which, however, is disproportionate to any triggering stimuli [3].

However, the idea that it consists of a psychophysical state characterized by a feeling of apprehension, uncertainty, fear and alarm towards events towards which the subject feels helpless and/or is univocal helpless. It involves a psychic and somatic involvement, associating itself with biological modifications, and involving different systems, among which: neuro-transmittitorial, immune, neuroendocrine [4].

It represents an essential emotion for the correct functioning of our organism in response to external or internal stimuli, allowing a functional adaptation to environmental demands. The related manifestations of anxiety have prevalence,in the general population, of 2-4%, a value that rises to 20% in the non-psychotic psychiatric population. The feeling of anxiety, as well as, in an extremely polymorphous way, is felt by every human being, is characterized by a vague, widespread and unpleasant sense of apprehension, often accompanied by somatic symptoms autonomous species (palpitations, tachycardia, tremors, hyperhidrosis, etc.), but also from psychic symptoms and behavioral manifestations[5]. Therefore, anxiety is necessary for the development of one’s existence; it becomes the source of a morbid condi- tion if the management of it becomes uncontrollable, to the point of undergoing a negative change in one’s lifestyle.

Anxiety is innate and is part of human nature. It is the normal response of our body that prepares to face what it perceives as a danger. We have the feeling of being vulner- able, even if sometimes we do not understand for sure why. When our ancestors faced the threat of ferocious animals or hostile peoples, the changes that took place in their bodies prepared them for struggle or flight. Nowadays the dangers are of a completely different nature, but faced with a situ- ation that frightens us, or that we perceive as threatening, the same changes occur in us at the time. When anxiety is moderate it can be useful, because it puts us on the alert in the face of a difficult situation allowing us to react quickly. It can become a real problem when it is excessive compared to the situation we are facing or lasts too long, to the point that doing the simplest thing can become a huge effort [6].

Another study then focused on the identification of the main constructs that cognitive theory associates with anxiety. In detail: the psychopathological constructs of anxiety are:

  1. Disproportionate fear of harm and tendency to negative predictions or catastrophic thought, definable as the tendency on the part of the subject anxious to foresee a wider range of negative consequences than to non-anxious subjects starting from everyday situations and to conceiving the danger inherent in these negative possibilities as essentially unavoidable, irresistible and irreparable.
  2. Fear of error or pathological perfectionism, definable as the tendency to emphasize rather the errors and imperfections present in the tasks performed than the positive results, and to fear and foresee that these im- perfections inevitably lead to negative and catastrophic consequences.
  1. Intolerance of uncertainty, definable as the tendency to think of not being able to emotionally bear the fact of not knowing perfectly all the possible future scenarios and events, of not being able to bear the doubt that among the possible future events there may be some negative ones , even if this possibility is very low, or to fear that, if there are negative possibilities in a certain scenario, these will be those that inevitably or tendentially occur (of course the negative developments are then feared because of point
  2. Negative self-assessment, definable as the tendency to predict catastrophic scenarios deriving directly from a negative evaluation both of one’s own practical skills (negative performance self-assessment) and of one’s capacity for emotional self-control and recovery in situ- ations of difficulty and stress (negative self-assessment of weakness, fragility).
  3. Need for control, definable as the strenuous pursuit and search by the anxious subject of the illusion of absolute certainty that he can prevent all the negative possibilities that he himself continually feared and foreseen in rumination through continuous monitoring and manipulation some aspects and parameters of external and/ or internal reality (eg weight, food and/or fat in eating disorders, intrusive thoughts or external order in ob- sessive compulsive disorder, ). In our hypothesis, the tendency to control constitutes the above-mentioned and terminal level of the hierarchical architecture of anxiety. This means that we believe that at the bottom of every anxious state there is always ideally the final belief that things tend to go wrong and that a high de- gree of knowledge and control of reality is necessary to prevent things from going wrong. The other constructs (fear of damage, fear of error, negative self-assessment and fear of uncertainty) are subordinate and not all always present, at least from the theoretical point of view. Fear of damage and negative self-assessment are the most general ones. It is difficult to say, at present, whether they are organized hierarchically or refer to different areas. Hypothetically it could be assumed that the negative self-assessment is feared because it would lead to damage, and therefore the fear of harm is the terminal belief. Likewise, one might think that it is the negative self-assessment of the central belief that fears of harm is only a predicate. Or one might consider that the two concepts are two different dimensions of a sin- gle construct, and therefore they are mutually non-hier- archical in relation [7].

The “pathological” anxiety [8] therefore, can manifest itself in many ways:

  1. Distressing and stressful thoughts and sensations;
  2. Physical symptoms, such as cardiovascular symptoms (tachycardia, palpitations, extrasystolia, arrhythmia, pain or discomfort in the chest, hypertension or pres- sure drops, fainting), respiratory (breathlessness, chok- ing sensation, sensation of a lump in the throat, asthma), gastrointestinal (nausea, gastritis, gastroesophageal reflux, diarrhea, irritable bowel syndrome), neuromus- cular (shaking sensation tremor, stiffness, paresthesia, contractures, muscle tension, weakness and fatigue), neurological (vertigo, feeling of “empty head” or light, feeling of heeling, trembling and flushing), dermatolog- ical (hives, redness or pallor of the face, hyperhidrosis) and urinary (sudden urge to urinate and pollachiuria).
  3. Altered behaviors, such as agitation, increase/decrease appetite and avoidance of certain situations.

 In summary, when physiological anxiety becomes an abnormal reaction to a normal alarm situation, it then takes on the pathological appearance of one of the anxiety disorders described in the DSM-V and which we will see in the next section. To be straightforward, physiological anx- iety is the sensation of not being able to pass a university exam; the pathological version consists in the choice not to present ourselves at the exam session, despite the fact that there is an intense study of several months behind.

“Healthy” anxiety, however, must also be distinguished from other feelings, often confused in the common jargon in terms of terminology. We are talking about fear, anguish, phobia, panic, fear, terror and stress.

Let’s start with fear: anxiety is distinguished from fear because of the lack of a specific and recognizable stim- ulus that evokes the answer. This difference is underlined by several authors, including Nisita and Petracca, who de- scribe anxiety as an emotion that anticipates the danger in the absence of a clearly identified object” [9] defines anxiety in a timely manner as an objectless fear, and Rachman 2004, differentiates anxiety from fear, describing the former as a state of increased vigilance and the latter as a consequent emergency reaction to trigger factors. Fear can therefore be defined as that primordial feeling, present in every mam- mal, which allows automatic evaluation of a potential threat or danger so perceived, while anxiety is, instead, a more complex response system involving cognitive and emotional factors. ,behavioral and physiological. On this basis, it seems correct to state that anxiety and fear are physiological and normal responses in all individuals. Not surprisingly, sev- eral studies of cognitive neuroscience [10] have shown be- yond any doubt that anxiety states arise from an abnormal control of fear; in particular, starting from the assumption that anxiety is an adaptive state, anxiety disorders have a genetic component and that the anxious disorders are dif- ferent in intensity, time course and specific symptomatolo- gy, the researchers have concluded, also thanks to the use of images of neurovisualization (fMRI), which in the states of fear and anxiety, are called into question the neural circuits that originate in the amygdala; indeed, the activation of the amygdala was recorded in response to the presentation of a stimulus that induces fear, not consciously perceived.

Anguish is the extreme opposite of peace, the fifth extreme essence of dysfunctional anxiety, where the inva- siveness, the restlessness and the sense of catastrophe seen and perceived, from a psychodynamic point of view, from the Ego, such as to undermine the ego’s ability to control and manage the pressures of the Super-ego and the id, consisting of a painful emotional state in which there were processes of discharge, capable of creating symptoms [11]. From this description we derive the general definition, which embodies it in the sense of frustration and psychophysical malaise, a prelude to various pathologies, precisely because this condition remains for a long time, in a subtle and constant way. In the clinic, we tend to distinguish the “situational or transitory” form (due to a specific circum- stance) from the “existential or chronic” form (due to the lack of processing and maturation of the triggering condi- tion).

The phobia is the pathological condition that is gen- erated as a result of specific fear and is determined by a sit- uation that is not really dangerous (or at least less danger- ous than the subject feels); this because the phobia, unlike fear, is not proportional to the risk to which one is aware of being exposed or believed to be exposed. In essence, fear degenerates deeply, thus provoking unjustified anxiety. The phobic object that triggers the episode can be of any kind [12] among the best known and widespread [13]:

  1. Acluophobia: intense and uncontrolled fear of the dark.
  2. Ablutophobia is defined as fear of washing, bathing or coming into contact with hygien.
  3. Ailurofobia is the fear of cats.
  4. Acarophobia is defined as fear of the mites and the itch- ing they Often those suffering from this fear may have the impression that mites have infected their skin.
  5. Acluophobia or scotophobia is the fear of darkness and darkness. It is generally common in children and is related to the possible dangers it can hide.
  6. Acrophobia is defined as fear of elevated heights and places.
  7. Acousticophobia, defined as a fear of noise, generally has an infantile origin and may be linked to a very loud noise that has aroused fright.
  8. Aeroacrophobia is the fear of open and high places.
  9. Afephobia or haptofobia is a phobia that involves great discomfort and in some cases repulsion, towards physical contact (both given and received) perceived as a sort of invasion of one’s own or another intimate area.
  10.  Agoraphobia is the feeling of fear or serious discomfortthat a subject feels when he finds himself in unfamiliar environments, fearing he cannot control the situation that leads him to desire an immediate escape route to a place he considers safer. It can be associated with panic attacks.
  11. Ailurophobia or elurophobia is the irrational and persistent fear of the proximity of cats, which can often generate panic attacks. 
  12. Amaxofobia is the refusal of irrational origin to conduct a certain means of transport, due to the direct involvement or of loved ones in road accidents. It can be the cause of panic attacks and can be particularly disabling for professional and work life as it hinders travel. 
  13. Anginophobia is the fear of suffocating. 
  14. Anglophobia is the fear or the feeling of suspicion towards all that is English, in general it is the hostility expressed towards the culture and the English people. 
  15. Anthropophobia is the fear of people and social contacts.
  16. Arachnophobia is an irrational fear towards spiders, even in photos, which can manifest itself in mild form through disgust up to more serious forms such as repulsion and panic attacks with escape reactions. 
  17. Aviophobia is the fear of flying in an airplane. 
  18. Brontophobia: fear of thunder.
  19. Cinophobia: fear of dogs. 
  20. Ceraunophobia, is the fear of thunder and lightning, especially prevalent among children and pets. Even this phobia can be the cause of panic attacks and flight behavior towards places where they can hide and feel protected. 
  21. Claustrophobia is the fear of closed and restricted places like dressing rooms, elevators, underground, underground and all the narrow places where the subject is considered encircled and devoid of spatial freedom around him. It can manifest with or without panic attacks.
  22. Clinophobia is the fear of lying down and falling asleep and detaching from reality, as they fear having nightmares or bed wetting, they often remain awake and develop insomnia. Some people in this fear associate sleeping with death. 
  23. Coulrophobia corresponds to the fear of clowns and clowns, very common among children and in some cases in adolescents and adults.
  24.  Cryophobia: fear of cold, of ice.
  25.  Dysmorphophobia is the phobia that arises from an excessive concern of one’s body image and one’s outward appearance. See also somatoform disorders.
  26.  Disposophobia is an obsessive need to acquire (without using or throw away) a considerable amount of goods, even if useless, dangerous, or unhealthy. Compulsive hoarding causes impediments and significant damage to essential activities such as moving, cooking, cleaning, washing and sleeping. 
  27. Eisoptrophobia or spectrophobia is the persistent, irrational and unjustified fear of mirrors, or to be reflected in a mirror. People who suffer from this phobia feel an undue anxiety looking in the mirror, while realizing that their fears are irrational. 
  28. Emetophobia is the terror of vomiting caused basically by the inability to dominate and predict their own retching. The idea of loss of control and anxiety not to know the outcome that will have a feeling of nausea, are the basis of this phobia. It often occurs at times when it may be difficult or embarrassing to isolate oneself from people close to him (eg, at the stadium, at the cinema or more simply at a friend’s house, at work). Often a real “psychological resistance” develops to the vomit that prevents to put back even when the thing would really benefit the organism.
  29. Hemophobia is excessive repulsion for the blood. 
  30. Entomophobia or insettofobia is the abnormal and irrational fear or aversion towards insects, mites and spiders, which usually causes emotional reactions that can range from mild forms of anxiety to severe panic attacks. 
  31. Equinophobia: fear of horses. 
  32. Erythrophobia: fear of blushing in public. 
  33. Ergofobia or ergasiophobia refers to an irrational fear of work or tasks and tasks, often hiding a fear of failing in assigned tasks or socializing with colleagues, leading to experience a disproportionate anxiety about the work environment.
  34.  Fagophobia consists in the fear of swallowing. It can lead to fear of eating and subsequent malnutrition and weight loss. In milder cases one affected by phagocytic nourishes only with soft and liquid foods.
  35. Filophobia is defined as the persistent, unjustified and abnormal fear of falling in love or loving a person, although it provokes a sense of physical and moral attraction towards man or woman. 
  36. Phobophobia is a rare phobia that can be referred to as fear of fear, but also as a fear of developing a phobia. Phobophobia is related to problems of anxiety and panic attacks that are also connected with other types of phobias, such as agoraphobia. 
  37. Phonophobia is the obsessive fear of noise. Unlike hyperacusis, it has psychological causes, often in sound traumas. 
  38. Gerontophobia: intense and uncontrolled fear of getting old. 
  39. Ginophobia is an unnatural phobia of the woman. 
  40. Glossophobia: fear of public speaking. See also social phobias.
  41. Hydrophobia, is the anomalous and obsessive aversion to liquids, in particular water and also refers to a fear of swimming in deep water, or drowning. 
  42. Logophobia can be defined as the unjustified fear of words and their use. For logophobia can also be understood the fear of speaking in public.
  43.  Misophobia: fear of remaining “contaminated” through contact with foreign bodies, or through contact with other human beings. It often leads to increasing the hygiene precautions to the extent that they turn into a separate disorder (to wash their hands obsessively).
  44. Musophobia: intense and uncontrolled fear of rats. 
  45. Nomophobia refers to the uncontrolled fear of being disconnected from contact with the mobile telephone network.
  46. Ofidiophobia is the excessive and irrational fear of snakes that leads to avoid walking in the high grass or in any area where these animals can easily hide, even in the regions where the presence of any species of any species is absolutely excluded.
  47. Homophobia is fear and irrational aversion to homosexuality, which involves the presence of aversive thoughts, feelings and behavior towards gays, lesbians, bisexuals and transsexuals (called transphobia), usually resulting from prejudices and which can lead discriminating behaviors in society or in work, up to manifestations of violent aggression. 
  48. Pathophobia: intense and uncontrolled fear of diseases, of getting sick. 
  49. Pediophobia is fear, present in some children or even adults, in relation to certain dolls or puppets that are generally larger than their parents and therefore a scary enemy. 
  50. Phasmophobia is defined as the fear of ghosts and occurs in some individuals who, especially at night, find it difficult to fall asleep. 
  51. Rupophobia, is the obsessive fear of dirt that causes the subject to repeatedly accomplish the act of cleaning up on himself (for example the continuous washing of the hands) or the environment that surrounds him (for example the house). 
  52. Sessuophobia means the fear to face any action or thought related to sexuality.
  53. Siderodromophobia indicates a particular phobic condition of the train journey, which can cause panic attacks and is generally associated with claustrophobia.
  54. Sociophobia: fear of social relationships.
  55. Tafophobia is the fear of being buried alive, as a result of the erroneous observation of one’s own death, sometimes present in old people. 
  56. Tanatophobia: obsessive fear of death.
  57. Tocophobia is the fear of childbirth, usually present in the primiparous, but it can also affect a woman in the parts following the first. 
  58. Tomophobia: fear of cuts, of surgical operations. 
  59. Toxophobia: fear of being poisoned. 
  60. Urophobia is the phobia of urinating in public, in front of other people. As a result, a paruretic is unable to use exposed urinals. The most serious subjects cannot urinate even indoors, if nearby they feel the presence of other people. In other words, the paruretic, although not affected by a physiological disorder, in the presence of other people is unable to urinate.
  61. Xenophobia is the fear of what is distinct by nature, race or species. Sometimes this attitude does not stop at mere fear, but leads to a real intolerance and discrimination against the object of one’s fear.
  62. Zoophobia: fear of animals in general.

Panic is an abnormal and uncontrolled reaction to an initially neutral or mildly stressful situation. If, therefore, pathological anxiety, in most cases, is due to the limits that we impose ourselves for some form of fear, and the anguish is the result of a false Self, of an identity that does not belong to us but that we consider ours and that we do not recognize as false, the panic attack is the clinical manifestation of the result of a long-standing anxiety, to which we have never left space for the elaboration and that, in a moment often of apparent banality or serenity, while the ego’s defenses are at a minimum, it hits the victim by paralyzing her. It is not by chance that the main symptoms of a panic attack,according to the DSM-5 are: palpitations, cardio palmos, or tachycardia, sweating, fine tremors or great tremors, dyspnoea or suffocation, feeling of asphyxiation (lack of air), chest pain or discomfort, abdominal discomfort, discomfort, instability, lightheaded or fainting, derealisation (feeling of unreality) or depersonalization (being detached from oneself), fear of losing control or going crazy, fear of dying, paresthesia (sensations of numbness or tingling), chills or hot flashes. From the panic attack, which single episode, however, should be distinguished the real panic disorder, or the simultaneous presence of multiple, unexpected and recurrent panic attacks and at least one of the attacks must have been preceded by the persistent worry of having other attacks or concerns about the implications of the attack or its consequences (eg, losing control, having a heart attack, “going crazy”) or significant alteration of the behavior related to the attacks. The presence or absence of agoraphobia then represents a specification.

The fear is simply: the state of mind of those who fear can occur a harmful, painful or unpleasant event. It arises when a situation that suggests a pleasant effect, joins the possibility of suffering. One is afraid when the hypothesis that the expected pleasure may not occur is considered, however the hope is still present that pleasure comes and covers the thoughts of different and painful hypotheses. It’s the case of a person who waits for the beloved/or an appointment. A minimum delay ignites the fear that the pleasure (loved one) may not arrive, together with the frustration and sorrow (pain) that will ensue. When the person arrives, a smile of contentment covers the previous fear [14]

Terror, by contrast: is even more serious than panic. In terror, the muscles are paralyzed; the fight/flight reaction is entirely inhibited. It arises in extreme danger or pain situations. It is said: “frozen/petrified” by terror. The body deactivates any sensation coming from the periphery to limit the body’s sensitivity in the agony that precedes death. It is a withdrawal inward, as in a state of shock. The breath remains paralyzed in the exhalation phase. Terror can precede fainting; in this case life is maintained by the neuro-vegetative system through unconscious processes. If the terror persists for a long period of time, the depersonalization, dissociation of the ego perceived by the bodily processes It can occur both on a conscious level and during the night hours (eg night terror). [14] And finally the stress. A term widely used in popular jargon to indicate a state of nervousness and low-level anxiety, often connected to the family or work environment. In the literature, stress is universally regarded as the nonspecific psychophysical response of the organism to every request made on it [15, 16]

Based on the duration of the stressful event it is possible to distinguish two categories of stress: if the stimulus occurs only once and has a limited duration, it is called “acute stress”; if instead the source of stress persists over time, the expression “chronic stress” is used. Furthermore, according to the nature, the stressor (stressful events) is distinguished in distress, as an event that lowers the immune defenses (correlating it to frustration and anxiety), and eustress, which is an event that fosters greater vitality.

The generally perceived symptoms depend on the triggering event but can be summarized in physical-somatic (headache, abdominal pain, muscle pain, sensory disturbances, sexual disorders), emotional (tension, anxiety, unhappiness, restlessness), behavioral (feeding impaired sleep disorders, anger, substance abuse) and cognitive impairment (memory and attention deficit, difficulty in problem solving and agitation).

Anxiety disorders. Classifications according to the DSM-V and the psychodynamic model

Anxiety can become a symptom present in numerous psychopathological disorders. In other cases, it itself becomes the predominant framework of the clinical context (eg anxiety disorders). Anxiety disorders include all those disorders that share excessive fear and anxiety character- istics; fear as an emotional response to an imminent threat, not necessarily real, while anxiety as the anticipation of an imminent or future threat. Anxiety disorders are different from each other by type, nature and symptomatology; the DSM-V lists the following specific disorders in the category under consideration:

  1. Separation anxiety disorder consists of excessive fear and anxiety concerning separation from home or from the most important figures for the child, which is im- mediately agitated and worried, experiencing a high level of anxiety and agitation, even if only mentally an- ticipating the removal from home or primary caregiv- er. A certain level of separation anxiety is healthy and is part of the normal development of children up to 6 years. A first form of separation anxiety is found around 8-10 months of life, when the baby cries and is worried about the presence of a stranger; around 18-24 months then they can experience mild levels of worry when they take their first steps towards exploring their en- vironment, frequently returning to the parent, looking for safety.
  2. Selective mutism is the inability of the child to speak and communicate effectively, in social contexts he se- lects perceived as threatening (eg school). It is not by chance that in the environments in which he experienc- es the states of well-being, serenity and safety, the child is always able to communicate and express himself Silences, however, should not be interpreted as an oppositional act: simply, the anxious state prevents the child from speaking, paralyzing him.
  3. The specific phobic disorder consists in the marked fear towards an object, a person or a specific situation and often it is a disorder in comorbidity with other pathol- ogies.
  4. The social anxiety disorder (so-called social phobia) consists in the intense and persistent fear of facing sit- uations in which one is exposed to the presence and judgment of others, for fear of being embarrassed, in- capable, ridiculous or acting in inopportune and humil- iating The immediate consequence of an exposure is a state of anxiety that in some cases can reach the intensity of a panic attack. The specific social anxiety then refers to one or two isolated situations, in which a performance or activity is generally expected while be- ing observed by others; in the case of generalized social anxiety, however, one may be afraid of meeting acquain- tances or strangers in any context, formal or informal.
  5. The panic disorder, as already analyzed above, consists in a chronicization of the single attacks, accompanied

    by the thoughts of imminence of the attack itself. It is severely disabling and often forces the subject to limit himself. It can be in comorbidity with the agoraphobic disorder that is the feeling of fear or serious discomfort that a subject feels when he finds himself in unfamiliar surroundings or in large open spaces, fearing he can- not control the situation, leading him to the need to find an immediate escape route to a place that he considers safer.

  6. Generalized anxiety disorder is characterized by symptoms of persistent, pervasive, uncontrollable and generalist anxiety, induced by the excessive preoccupation with respect to the feared event. Individuals suffering from this disorder report feelings of anxiety and apprehension that are reflected in a general inability to relax or in more specific symptoms such as muscle weakness, rumination and irritability.

From a strictly psychodynamic point of view, in the Freudian model, anxiety corresponds to an ego affection, which controls access to consciousness, leading to censorship and the removal of the impulse of gratification if not accepted by external reality. An instinctual desire or a removed impulse can however be expressed in the form of a symptom; then, depending on the defense mechanisms involved, the hysterical rather than the phobic symptom will be witnessed, with the compulsive symptom rather than the avoidant symptom. At a more mature (and therefore conscious) level, the anxiety that comes from the superego can be understood in terms of torments of consciousness and feelings of guilt, deriving precisely from the gap between social expectation and actual moral manifestation [17-23]

The neural correlates in anxiety disorders

The brain systems that regulate the anxious re- sponse are quite complex; among the regions that play a primary role we find the amygdala, the hippocampus and the prefrontal cortex. The amygdala is the central nucleus of the circuits of fear, as a very complex structure able to respond promptly to the danger (be it potential or real), ac- tivating a whole series of somatic responses (such as the increase in heart rate and blood pressure, up to hyperventi- lation) and emotional and behavioral reflexes (such as reaction and flight).

The circuit in question takes into account anxiety, as a physiological and functional measuring mechanism for survival and evolution; however, if the critical threshold is exceeded, anxiety turns from adaptive to maladaptive (and therefore dysfunctional), leading to a worsening of performance and reactions.

Figure 1: The relationship between anxiety level and performance.

From a neuronal point of view, the anxiety-fear circuit involves the activation of two different ways: a “short” path (short loop) and a “long” path (long loop). In the first, the sensory thalamus, which collects all the sensory perceptions of our body, transmits the stimuli to the lateral amygdaloid nucleus, which in turn transmits them back to the central nucleus. From this last part stimulation of further structures determining: the increase of the respiratory frequency (due to the stimulation of the parabrachial nucleus), the increase of the arterial pressure and of the heart rate (due to an increase in the noradrenaline release induced by stimulation of the locus ceruleus). Moreover, the activation of the gray substance and of the paraventricular nucleus of the hypothalamus will determine, respectively, the manifestation of a defensive response of “block” and the activation of the hypothalamic-pituitary-adrenal (HPA) axis with a consequent increase in the adreno-corticoid. In the “long” way, the sensory cortex, the insula and the prefrontal cortex send the signal to the lateral amygdaloid nucleus. From here the signal is sent to the brainstem and hypothalamus. Central, in this way, unlike the short one, is the activation of the prefrontal cortex whose function is to modulate anxiety [4, 23]

The thalamus performs a function of primary link between the sensory systems exteroceptive (auditory, visual, somatosensory), main afferents of the neuronal circuits that determine anxiety and fear, and the primary sensory areas of the cerebral cortex, which project the sensory input to adjacent associative areas, for integrated stimulus processing. The cortical associative areas then send projections to various brain structures, such as amygdala, entorhinal cortex, orbital-frontal cortex, and the cingulum gyrus. The visceral afferences do not converge on the thalamus and activate the locus coeruleus and the amygdala, either through direct connections, or through pathways mediated by the paragigantocellular nucleus and by the nucleus of the solitary tract.

The fear response is particularly related to three of the 13 nuclei of the amygdala: the central nucleus (CA), the lateral amygdaloid nucleus (LA) and the basal nucleus (BA). Two circuits are known: the short one (short loop) that receives the stimuli from the sensory thalamus and transmits them to the LA which, in turn, transmits them to the CA. The long circuit (long loop) instead sends signals to the LA, by the SC, insula (INS) and the prefrontal cortex. From these areas signals are sent to the brainstem (BS) and to the hypothalamus (HYP), to which the autonomic and behavioral response of fear follows. The amygdala also receives unprocessed information from the thalamus; it represents the epicenter of the events involved in the modulation of anxiety states, both in animals and in humans, with a wide spectrum of reciprocal connections with the cortical and limbic structures, implicated in the emotional, cognitive, autonomic and endocrine response to stress. The neuronal interactions between the amygdala and the other cortical and subcortical regions allow the implementation of risk reaction behaviors, dependent on multiple variables such as the individual’s biological characteristics, his temperament, previous experiences, the contingent emotional situation, etc. In this sense, the importance of the stressful load of an event is more related to the subjective evaluation of an individual than to the objective reality of the event itself [10, 24]

Furthermore: the efferent pathways of the anxiety-fear circuit trigger an autonomic response, which involves the sympathetic and parasympathetic system. The sympathetic activation, mediated by the stimulation of the hypothalamus by amygdala and locus coeruleus, determines an increase in blood pressure and heart rate, sweating, piloerection and pupillary dilatation. Para-sympathetic activation, whose main projections are represented by the vague and splanchnic nerves, mediated by the hypothalamus, the paraventricular nucleus, the amygdala and the locus coeruleus, may be linked to visceral symptoms associated with anxiety, such as disorders gastrointestinal and genito-urinary. Finally, the CNS directly and indirectly influences the immune system through complex neuroendocrine and neuro-trans-territorial interactions: the modulation of the immuno surveillance can, then, under certain conditions of intense and protracted stress exposure, determine an organ or system meiopragy, until the appearance of an organic disease [24]

Several recent researches have also shown that:

  1. The amygdala plays a fundamental role in emotions. Its functional coupling with the hippocampus and the ventromedial prefrontal cortex extending to a portion of the anterior cingulate cortex (ACC) is implicated in anxiogenesis and regulation of the hypothalamic-pituitary-adrenal (HPA) system. However, it is not clear how functional connectivity centered on the amygdala (FC) influences the concentrations of anxiety and cortisol in everyday life. Here, we investigate the relationship between daily cortisol concentrations (dCOR) and amygdala-centered HR during emotional processing in forty-one healthy humans. FC analyzes revealed that a higher dCOR predicts strengthened amygdala-centered FC with the hippocampus and cerebellum, but inhibited FC with supramarginal rupture and a perigenal part of ACC (pgACC) during face processing fearful (compared to neutral faces). In particular, the strength of the amygdala-hippocampus FC mediated the positive relationship between cortisol and anxiety, particularly when the effect of amygdala-pgACC FC was considered, a presumptive neural indicator of emotional control. Individuals with reduced connectivity between amygdala and pgACC during fear-related processing may be more vulnerable to anxiogenesis as it relates to higher circulating levels of cortisol in everyday life. The individual functional models of amygdala-hippocampus-pgACC connectivity could provide a key to understanding the complicated link between cortisol and anxiety-related behaviors [25] 
  2. Individuals with anxiety disorders show deficits in the discrimination between an idea that predicts an adverse result and a sure stimulus that provides for the absence of that result. This impairment has been linked to a spontaneous increase in fear after extinction; however it is not known whether there is a link between discrimination and the return of fear in a new context (i.e. the renewal of the context). It is also unknown if the impaired discrimination mediates the relationship between stroke anxiety and spontaneous recovery or context renewal. The present study used a differential fear conditioning paradigm to examine the relationships between stroke anxiety, discriminant learning, spontaneous recovery and context renewal in healthy volunteers. Learning of fear was assessed using continuous assessments of US expectation and subjective assessments of fear. Discrimination mediated the relationships between stroke anxiety and spontaneous recovery and context renewal in such a way that high trait anxiety was associated with weaker discrimination, which in turn was associated with an increase in fear in the test phases. The results are discussed in terms of genesis and maintenance of anxiety disorders (Staples-Bradley et al., 2018); the molecular processes that establish the memory of fear are complex and involve a combination of genetic and epigenetic influences. The dysregulation of these processes can manifest itself in humans as a range of anxiety disorders related to fear such as post-traumatic stress disorder (PTSD). In the present study, immunohistochemistry for acetyl H3, H4, c-fos, CBP (CREB binding protein) in the prefrontal infralimbic cortex (IL-PFC) and prelimbal prefrontal cortex (PL-PFC) of mPFC (medial prefrontal cortex) and basal Amygdala ( BA), lateral amygdala (LA), centrolateral amygdala (CeL), centromedial amygdala (CeM) of the amygdala was performed to link the region-specific histone acetylation to the learning of fear and extinction. It has been found that the PL-PFC and IL-PFC together with the sub-regions of the amygdala have responded differently to learning and extinction of fear. After learning of fear, the expression of c-fos and CBP and the acetylation of H3 and H4 increased in BA, LA, CeM and CeL and PL-PFC but not in IL-PFC compared to naive control. Likewise, after learning the extinction, the expression of c-fos and CBP is increased in BA, LA, CeL and IL-PFC but not in PL-PFC and CeM compared to the naive control and the conditioned group. However, acetylation of H3 increased both in IL and in PL compared to H4, which increased only in IL-PFC after extinction learning. Overall, the specific activation of the region in the amygdala and in the PFC after learning of fear and extinction, as evident from c-fos activation, has parallel H3/H4 acetylation in these regions. These results suggest that histone differential acetylation in PFC and amygdala subcores following learning and fear extinction may be associated with region-specific changes in the neuronal activation model resulting in greater fear/less fear [26] 
  3. The polymorphisms of the OT receptor gene (OXTR) have been implicated in gene-environment interactions with style of attachment and child maltreatment and to influence clinical outcomes, including the intensity of SAD and limbic reactivity. The DNA methylation patterns of epigenetic OXTRs emerged as a link between categorical SAD, dimensional, neuroendocrinological and neuroimaging correlations, highlighting them as potential peripheral surrogates of the central oxytocinergic tone. A pathophysiological structure of OT is proposed that integrates the dynamic nature of epigenetic biomarkers and the synthesized genetic and peripheral evidence. Finally, we emphasize the opportunities and challenges of OT as a key node in the social interaction network and we fear learning in social contexts. Coinciding with multi-level surveys incorporating a dimensional understanding of social belonging and avoidance in anxiety spectrum disorders, these concepts will help promote research for diagnostic, state, and OT response biomarkers advancing towards indicated preventive interventions and personalized treatment approaches [27] 
  4. Pathological concern is a characteristic feature of generalized anxiety disorder (GAD) associated with dysfunctional emotional processing. The ventromedial prefrontal cortex (vmPFC) is involved in the regulation of these processes, but the link between the vmPFC and pathological blood responses v. Adaptive concern has not yet been examined. Objectives To study the association between concern and vmPFC activity evoked by the elaboration of the learned signs of security and threat. In total, 27 non-paramedical patients with GAD and 56 healthy controls (HC) underwent a differential fear conditioning paradigm during functional magnetic resonance imaging. Compared to HC, the GAD group demonstrated reduced activation of vmPFCs to safety signals and no differentiation of security threat processing. This response was positively correlated with the severity of the concern in GAD, while the same variables showed a negative and weak correlation in HC. The poor differentiation of the safety threat of vmPFC could characterize the GAD and its particular association with the concerns of the GAD suggests a qualitative difference based on the neuron between the health and pathological pathologies [28]

Pharmacological and psychotherapeutic therapy for the resolution of anxiety disorders.Focus on the strategic approach 

Anxious forms, in the first instance, are treated with psychotherapy. The most used approach is undoubtedly the cognitive-behavioral one, even if the protocol foreseen for the specific case is not always perfectly adapted to the patient, thus risking an incomplete resolution of the problems described in the anamnesis or worse a slippage of the object towards another object, as it often happens for the treatment of specific phobias. The list is therefore subject to continuous variations. However, it has been noted, in various researches [10,28] that psychotherapeutic treatment, if associated with pharmacological therapy, increases the chances of maintaining the desired result longer and faster, practicing distinct distinctions; in fact: 

  1. The drugs of first choice, because they are more effective and well tolerated, are the antidepressants (in particular, the specific inhibitors of the reassortment of serotonin); 
  2. For simple phobias, it is not recommended to combine the pharmacological product with psychotherapy, while for more complex and complex phobias and obsessive compulsive disorder, it is also possible to combine an antidepressant referred to in point a);
  3. Benzodiazipines are used to deal more strongly with anxiety, especially the generalized form, but often they depress cognitive functions and create physical and psychic dependence. For this reason, these categories of psychiatric drugs are considered second choice, since they are effective from the first dose (unlike the antidepressants that need before giving the expected effects of an initial period of administration equal to some weeks), because of secondary effects from keep in serious consideration.

Cognitive behavioral therapy (TCC) is based on the assumption that our thoughts (and not external events) influence the way we feel; therefore, they determine our emotions not the situations but as we interpret and perceive the same. All modern cognitive theories assume that human experience is internalized and stored in memory in an organized manner. According to this perspective, anxious people have internalized certain cognitive patterns concerning the potential danger of certain situations with respect to their coping skills. The goal of TCC in the treatment of anxiety disorders is to identify and correct dysfunctional thoughts and beliefs, changing the behavior that causes the discomfort, also taking into account the factors of maintenance of these disorders, namely: avoidance of the feared object or situation; b) the continuation of the underlying problem; c) the automatic shift of attention to one’s anxious state (the reflection on ...), which produces a second-order anxiety. The TCC, however, provides several tasks, including: a) learn to recognize when you feel anxiety and how it manifests at the body level; b) to learn coping skills and relaxation techniques to deal with anxiety and panic; c) to face the feared situations (in imagination and in reality). Among the various techniques we mention: a) the “exposure”, implying precisely the gradual or drastic exposure of the person to feared situations and objects, allowing the person to feel more and more in charge of the situation through the ability to manage and lower anxiety levels; b) “systematic desensitization”, with which the situations considered as anxiety are progressively faced, according to a model constructed in three phases (learning of relaxation techniques, creation of a hierarchy of disturbing situations, active intervention).

A related model is the social learning of Bandura’s anxiety, according to which the basic mechanism that produces anxiety is the lack of self-efficacy beliefs in the individual. The cognitive model then expands the conditioning paradigm by suggesting that the initial automatic association between traumatic experiences and the specific object or situation results in the formation of patterns related to the danger. These then influence the anticipations of catastrophic ruin every time the individual confronts the feared object or situation. While the first versions of the cognitive and cognitive-behavioral model focused on conscious cognitions, now the most recent hypotheses focused on unconscious cognitive patterns, thus approaching the psychoanalytic, especially the more recent, which has shifted the focus away from the conflict to the unconscious representations of the Self, and of the Self in relation to the other, as the main determinants of conscious thought and behavior [29]

Also other approaches can then help for the resolution of anxiety disorders.

The experiential approach focuses on the emotions and the Greenberg model, linked to the concept of emotional patterns: An analysis of the content of such catastrophic conflicts shows that they reflect more broadly existential crises: the inevitability the loss, the experience of a separate consciousness that is often associated with the fear of being alone, the weight of individual responsibility, awareness and acceptance of one’s death, the need to balance our actions and expressiveness than the socio-cultural demands, the need to go through the painful process of deciding how much freedom, autonomy and novelty we need in our experience of comfort, security and protection. Each of these problems is involved in the struggle for self-esteem, and this battle necessarily involves the experience of demeaning emotions, such as humiliation, guilt, shame, anger. Depression is lurking. The experiential perspective is the one that most has to say about the role of emotions in the development and maintenance of disorders. This view differs from all others in the assumption that emotions are sources of biologically adaptive information that individuals ignore at their own risk. The problems derive from the learning of erroneous cognitions regarding emotional expression, which, as felt as dangerous or useless, is not followed [30].

The approach of the Self, according to Wolfe’s approach. In an anxious individual anxiety is felt as a basic threat to deep beliefs about the Self. This experience of self-impairment is characterized by a variety of states, which include a sense of loss of control, lack of security and impotence, and which push the individual to believe that he is unable to avoid a traumatic experience, or extremely painful, or humiliating. When people are in the middle of this experience they automatically shift their attention from the direct experience of anxiety to the thought of being anxious and this inevitably increases the level of anxiety. When, as happens in therapy, people manage to stay in touch with their immediate anxious experience, they understand that the experience of self-impairment represents a feared confrontation with a terribly painful self-perception. And it is only through this exploration of the implicit meaning of anxiety that lasting healing can take place. Wolfe indicates five types of wounds of the Self, corresponding to five types of strongly anxious painful perceptions of self: a) the biologically vulnerable Self (fear of extreme vulnerability to diseases or physical impediments); b) the inadequate or incapable Self (fear of situations reminiscent of past failures of a performance); c) the shameful, imperfect, humbled self; d) the dissatisfied or isolated Self; e) the Conflict or confused Self (often a difficulty in recognizing one’s needs or a conflict between the basic needs of the individual and his values). There are many sources of wounds of the Self, most of which are interconnected: traumatic experiences, ideas of shame or humiliation, betrayals by other significant, emotional diseducation, ineffective responses to life’s existential data. Anxiety disorders are maintained by numerous factors, most of which have to do with protecting oneself from the atrociously painful perception of the self. Instead of confronting openly with the wounds of the Self, anxious people generally implement these three strategies to keep them hidden: reflection on the state of anxiety and on potential catastrophes, avoidance of anxiogenic situations, negative circles of interpersonal behavior (those who see themselves negatively involve so that others reinforce this idea). These strategies result in a temporary reduction in anxiety but at the high price of reinforcing the maladaptive beliefs of one’s inability to manage the feared situations. The three fundamental elements of anxiety disorders are therefore: 1) immediate experience of anxiety; 2) the automatic shift of attention to one’s anxious state (to reflect on), which produces second-order anxiety; 3) a tacit perception of self, but painful [31]

The emotional approach, linked to Bowlby’s thinking, is based on the concept of attachment. The child preserves and classifies the facts and emotions he feels on the basis of the decoding, or interpretation, of which the parent provides them. When parents give him a distorted codification of facts and emotions that is, not corresponding to the actual emotion that the child feels, it follows for him the impossibility to accept all the experiences that on the conscious level When we cannot use our emotions, there is a risk of psychopathological implications. The memories of the responses coming from the attachment figures are incorporated into cognitive structures that will constitute the convictions and expectations of the child and then of the adult each time they are in difficult conditions [32, 33].

But without doubt, the most complete is the short strategic approach. The strategic therapist has the task of developing a series of intervention strategies capable of producing effective, rapid and resolutive changes to theproblem that afflicts the patient. From the focus of the strategic, suggestive and persuasive Chinese art to modern times, with Bateson, Watzlawick and other researchers from the Mental Research Institute (known as the “Palo Alto School”) and in Italy, with Nardone and Petruccelli, the approach strategic has found its space ever more dominant in the psychological landscape. Assuming that the individual should not be considered, but all the context and relationships that bind the patient to all the components of his mental and social universe, there is no objective reality and pathologies are the manifestation of discomfort, the result of attempted solutions rigidly applied. An attempted solution that does not work, if repeated, does not solve the problem but complicates it, eg avoidance of the anxiogenic situation in phobic disorder. It is therefore necessary to block the attempted ineffective and pathological solutions and to stimulate the experiences that change the perception of the problem. The intervention that leads to change is the provoking of concrete perceptive experiences that put the person in a position to try something different in relation to the reality to be changed. Strategic therapy is not a superficial and symptomatic therapy but a radical intervention, as it aims at restructuring the ways through which each one organizes the reality that then undergoes. Therapeutic attention is focused on: a) how the person, and the people around her, have tried unsuccessfully to solve the problem, or the attempted solutions that feed the problem; b) to ask oneself not the why but how it is maintained and how to change the negative experience in positive. In the hypothesis of anxiety disorders, the suggested therapeutic strategies concern: a) give a task that distracts, exposing however to the situation avoided The strategic approach then proceeds by agreed objectives, pursues results and solutions and adapts perfectly to the patient, without fixed or rigid schemes, elevating the word spearhead of the therapist’s tools, also thanks to the choice of the use of the criteria strategic operations, i.e. the logic of paradox, contradiction and belief. The approach in question, using these logics, allows you to quickly interrupt the vicious circles by offering the patient the most effective maneuver (with respect to the result) and more efficient (with respect to time and cost/ benefit). On the other hand, given the results, the advantages of this approach cannot be questioned: the safety of the results; the effectiveness obtained in a short time; the use of tools, guidelines and protocols already successfully tested; the positive modification of the patient’s way of feeling the world; the stability of positive results over time. [34]


The most decisive treatment for anxiety disorders is identified in the combination between the profiles linked to the psychotherapeutic approach and to the pharmacological one. Compared to the first element, the short-term strategic approach seems to be the best in terms of healing, as it provides the tools necessary for its resolution, drawing on the cognitive-behavioral protocols extended with the strategic techniques of the Palo Alto school and the systemic-relational school. Compared to the second element, on the other hand, it certainly appears useful in two precise hypotheses: 1) when the symptomatology is so invalidating as to prevent the patient from orienting himself favorably towards psychotherapeutic therapy; 2) when the word approach alone is not sufficient to teach the patient the best management of his disorder, perhaps in the presence of a biological or family vulnerability.


  1.  Rachman S. (2004), L’ansia. Roma: Laterza Editori.
  2. American Psychiatric Association (1994), cit. in: Franceschina E., Sanavio E., Sica C., “I disturbi d’ansia”. In: Galeazzi A., Meazzini P. (A cura di) Mente e comportamento. Trattato italiano di psicoterapia cognitivo-comportamentale. Giunti Editore, Milano, 2004.
  3. Perugi G, Toni C, L’ansia. In: Cassano G.B. (A cura di) “Affettività”. In: Cassano G., Pancheri P., Pavan L., Pazzagli A., Ravizza L., Rossi R., Smeraldi E., Volterra V., Trattato italiano di psichiatria. Seconda Edizione – Edizione elettronica, Masson, Milano, 2002. 
  4. Guccione, F. (2018), I circuiti dell’ansia. Tratto da.
  5. Damiani, A. (2018), L’ansia.
  6. Lavaggi, M. (2018), I disturbi d’ansia.
  7. Sassaroli S, Ruggiero GM. I costrutti dell’ansia: obbligo di controllo, perfezionismo patologico, pensiero catastrofico, autovalutazione negativa e intolleranza dell’incertezza. Studi Cognitivi, Milano. In Psicoterapia Cognitiva e Comportamentale 2002;8: n. 1. 
  8. Massaro F. (2011), Quando il corpo va in ansia: i sintomi fisici dei disturbi d’ansia. 
  9. Colombo G. “Disturbi dell’affettività e dei sentimenti”. In: Colombo G., Manuale di Psicopatologia Generale. Cleup, Padova, 2001.
  10. Kandle E. R. (2018), Principi di neuroscienze. IV ed., Bologna: Casa Editrice Ambrosiana, Zanichelli.
  11. Freud S. (1925), Inibizione, sintomo e angoscia. Torino: Bollati Boringhieri. 
  12. Lauri S. (2018), Le fobie specifiche. 
  13. Algeri D. (2018), Fobie e monofobie: il trattamento con la terapia breve strategico.
  14. Aruta C. La paura.2018. 
  15. Selye H. (1974). Stress without distress. J. B. Lippincott, Philadelphia. 
  16. Selye H. (1976). Stress in health and disease. Butterworth’s, reading, Massachusetts.
  17. Freud S. (1899), L’interpretazione dei sogni. In Opere. 
  18. Freud S. (1901), Psicopatologie della vita quotidiana. In Opere. 
  19.  Freud S. (1905), Tre saggi sulla sessualità. In Opere. 
  20. Freud S. (1914), Introduzione al narcisismo. In Opere.
  21. Freud S. (1920), Al di là del principio di piacere. In Opere.
  22. Freud S. (1921), Psicologia delle masse e analisi dell’Io. In Opere. 
  23. Freud S. (1923), L’Io e l’Es. In Opere.
  24. Torta R, Caldera P, (2008) “Che cos’è l’ansia: basi biologiche e correlazioni cliniche”, Pacini ed., Pisa. 
  25. Hakamata e coll. Amygdala-centred functional connectivity affects daily cortisol concentrations: a putative link with anxiety. Abstract. Sci Rep 2017; 7(1):8313. 
  26. Siddiqui e coll. Enhanced Histone Acetylation in the Infralimbic Prefrontal Cortex is Associated with Fear Extinction. Abstract. Cell Mol Neurobiol 2017; 37(7):1287- 1301.
  27. Gottschalk-Domschke. Oxytocin and Anxiety Disorders. Abstract. Curr Top Behav Neurosci 2017. 
  28. Via e coll. Ventromedial prefrontal cortex activity and pathological worry in generalised anxiety disorder. Abstract. Br J Psychiatry 2018;1-7.
  29. Bandura A. (1996), Il senso di autoefficacia, Torino: Erikson.
  30. Greenberg L, Paivio S. (2000), Lavorare con le emozioni in psicoterapia integrata, Roma: Sovera.
  31. Wolfe B.E. (2007), Trattamenti integrati per disturbi d’ansia. Roma: Sovera.
  32.  Bowlby J. (1989), Una base sicura. Milano: Raffaello Cortina Editore.
  33.  Holmes, J. (1994), La Teoria dell’attaccamento. Milano: Raffaello Cortina Editore.
  34.  Nardone, G. (1993), Paura, panico, fobie. Firenze: Ponte alle Grazie.