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Crosstalk between Existential Phenomenological Psychotherapy and Neuroscience in Mood and Anxiety Disorders

Psychotherapy is a comprehensive biological treatment modifying complex underlying cognitive, emotional, behavioral, and regulatory responses in the brain, leading patients with mental illness to a new interpretation of the sense of self and others. Psychotherapy is an art of science integrated with psychology and/or philosophy. Neuroscience is a multidisciplinary science of the neuron, the glial cells including oligodendrocytes, ependymal cells, and astrocytes and the neural circuits to understand learning, memory, behavior, perception, and consciousness. Both psychotherapy and neuroscience deal with the brain; nevertheless, they continue to stay polarized far. Existential phenomenological psychotherapy (EPP) has been in the forefront of meaning-centered counseling for almost a century. The phenomenological approach in psychotherapy originated in the works of Martin Heidegger, Ludwig Binswanger, Medard Boss and Viktor Frankl, and it has been committed to account for the existential possibilities and limitations of one’s life. EPP provides philosophically rich interpretations and empowers counseling techniques to assist mentally suffering individuals by finding meaning and purpose of life. The approach has proven to be effective in treating mood and anxiety disorders. This review article demonstrates the development of EPP, the therapeutic methodology, evidence-based accounts of its curative techniques, current understanding of mood and anxiety disorders in neuroscience, and a possible converging path to translate and integrate meaning-centered psychotherapy and neuroscience, concluding that the existential phenomenological approach in psychotherapy is a viable and potent alternative to the currently prevailing medication-based approaches.


Existential Phenomenological Psychotherapy
Phenomenology as a philosophical approach of grasping and explaining reality appeared on the European intellectual scenery some 130 years ago. Although G. W. F. Hegel already talked and wrote extensively about the "Phenomenology of Spirit" in the early 19th century, it was not until Edmund Husserl's adaptation of the term in the early 1900s that it came to gain its philosophically characteristic, nuanced meaning. Husserl, a mathematician and philosopher, was strongly influenced in the construction of his methodology by philosopher and psychologist Franz Brentano and by historian and hermeneutic philosopher Wilhelm Dilthey. From Brentano he took over arguments regarding the structure of consciousness as well as the general task of critiquing psychologism in the domain of philosophical logic, whereas from Dilthey he appropriated the "attempt to develop a more descriptive approach to the human sciences" [7]. Having carefully designed his innovative philosophical methodology, which he believed "could discover the structures common to all mental acts", he had high hopes that the systematic utilization of this methodology could turn philosophy into a "rigorous science" on par with the natural sciences. Thus, was born phenomenology, a novel philosophical approach whose concise programmatic ideal was aptly conveyed in the following famous slogan: "back to the things themselves". What does Husserl mean by "back to the things themselves"? This motto involves a call, an appeal to turn away and leave behind concepts and theories, and instead to experientially encounter all phenomena of the pure consciousness just as they present themselves, without the conceptual burden with which language and tradition weighs them down. As eminent historian of the phenomenological movement Herbert Spiegelberg noted that transcendental phenomenology attempted to reveal "the structures of pure consciousness, [which were] made accessible by a special suspension of belief in the reality of our natural and scientific world, the so-called phenomenological reduction, in which the constitution of the phenomena according to intending acts and intended contents was studied in detail" [8]. This phenomenological reduction is essential to understanding how Husserl's phenomenology was intended to operate. As Husserl explained, the main objective of phenomenology's undertaking was to intuitively discern eidetic essences that lay beyond the singular expressions of individual phenomena [9]. While descriptive phenomenology's primary goal was to "intuit, analyze, and describe the data of direct experience in a fresh and systematic manner", essential or eidetic phenomenology's responsibility was to explore "essential structures on the basis of imaginative variation of the data" [8].
The phenomenological approach had progressively become influential in psychological and psychiatric circles from the second third of the last century; especially after it successfully wed itself Dasein's-existential possibilities and limitations, initiated a prominent philosophical and literary movement that came to be called "existentialism". Among the proponents of existentialism such influential figures are customarily counted as Jean-Paul Sartre, Albert Camus, Simone de Beauvoir, Karl Jaspers, Maurice Merleau-Ponty, and so forth. Nevertheless, the rapidly growing existentialist movement of the 1940s and 1950s also began to claim an outstanding philosophical ancestry that ranged from the works of Arthur Schopenhauer to Soren Kierkegaard and from Fyodor Dostoevsky to Friedrich Nietzsche. What was common in this exceptionally diverse bunch of thinkers was the circumstance that they were all deeply intrigued by the "subjective" experiences and the inwardness of the self, at the same time looking distrustfully upon the claims for scientific hegemony of the positivist, reductionist, and objectifying approaches of the natural sciences ( Figure 2). Discovering the meaning of human existence was the first and foremost task which the existentialist thinkers set for themselves. As Wrathall and Dreyfus eloquently put it: "For existentialist thinkers, the focus is on uncovering what is unique to that individual, rather than treating her as a manifestation of a general type (…) With their focus on the individual and a denial of any meaningful sense of what constitutes an essential or absolute goal for human existence, existentialists emphasize human freedom and responsibility, and hold that the only goal consistent with that freedom and responsibility is to live authentically" [7]. When phenomenology began to merge with existentialism, first in Heidegger's, then in a prestigious line of other up-and-coming philosopher's work, the rigorousness of phenomenology and the existential concerns of existentialism generated a unique blend of philosophizing. As Spiegelberg rightly points out, this new combined approach was in palpable contrast with the methodologically less scrupulous early existentialist writings of for instance Kierkegaard or Nietzsche.
The new phenomenological-existential approach firmly maintained "that existence can be approached phenomenologically and studied as one phenomenon among others in its essential structures" [7].
Wrathall and Dreyfus add to this that since phenomenology and existentialism share many of their concerns, their joint focus tends to be on these concerns, rather than on numerous other issues that they would disagree on. "Like the phenomenology of Heidegger, Merleau-Ponty, and Sartre, existentialism as a movement starts its analysis with the existing individual -the individual engaged in a particular world with a characteristic form of life. Thus, an emphasis on the body and on the affective rather than rational side of human being are characteristic of existentialism" (Figure 3)   This is the tradition upon which existential psychiatry and psychotherapy has established its theory and practice. Existential psychotherapy is a unique approach in that it scrutinizes psychic phenomena from an existentialist point of view. This entails that existential therapists understand man not as a substantive subject that is torn from objective, "external" reality, but as a   It is important to keep in mind that existential-phenomenological psychiatry and psychotherapy were born out of the elemental dissatisfaction with the ways psychiatrists tried to cure conventionally conceived "diseases" of conventionally conceived human "subjects": for existentialists it seemed that neither of these are adequate modes of either grasping human reality or of trying to advance the well-being of the individual [11]. By the end of the 1950s, the existential approach to psychiatry and psychotherapy has arrived and started to grow in the US. Along with the so-called humanistic movement in psychology, it has gained considerable influence after a relatively brief period of time. Rollo May and Irvin D. Yalom are the most well-known and acknowledged representatives of the American school of existential therapy. Meanwhile in Great Britain, it was Ronald David Laing who first offered analyses of psychopathological and psychotherapeutic phenomena from an existential-phenomenological stance. Somewhat later several members of the British School of Existential Analysis came to reform the principles of existential therapy. Their objective was to strip the therapeutic setting from the urge to diagnose the "disease" of the client, along with the removal of the habitual pathologization of various "abnormal" psychological phenomena and the moral evaluation of medical data. Instead, they suggested that therapy should focus on the phenomenological description of the "lived world" of the patient.
Ernesto Spinelli, leading representative of the British School of Existential Analysis asserted that existential psychotherapy's "primary task is not one of seeking to direct change in the worldview of the client. Rather, existential psychotherapy's principal concerns lie with its attempts to descriptively clarify that worldview so that its explicit and implicit, sedimented dispositional stances can be re-examined inter-relationally" [12] ( Figure 5).

Existential Psychotherapy's Approach to Treating Mood and Anxiety Disorders
The aim of existential analysis is to guide a person towards experiencing their life authentically and freely. This is done through practical methods that help an individual to live with `inner consent', or the ability to affirm what he or she is doing [13].
As Viktor Frankl, the founder of the Vienna School of Existential Analysis maintained, existential analysis is the search for meaning: the meaning of a given individual's unique existence with its goals and values, amidst its limitations and situatedness [14]. However, this approach to the human psyche comprises other essential facets as well that point beyond a mere psychological analysis of contingent factors. Frankl claimed that "existential analysis is (…) not only the Existential Pscyhotherapy • Existential Psychotherapy (1980) explication of ontic existence, but also the ontological explication of what existence is. In this sense, existential analysis is the attempt at a psychotherapeutic anthropology, an anthropology that precedes all psychotherapy, not only logotherapy." The establishment of such an anthropology is the ultimate goal of existential psychology and psychiatry as a theory of the human psyche and its dysfunctions. It is exceedingly important to clarify such an anthropology, because, as Frankl goes on to explain: "every psychotherapy plays itself out against an a priori horizon. There is always an anthropological conception at its foundation, no matter how little aware of this the psychotherapy may be" [14].
Frankl, an Austrian-born Holocaust survivor believed that the root cause of the majority of our psychological problems was a general feeling of meaninglessness: an "existential vacuum" which leads one to despair and believe that life no longer has any meaning [14]. Therefore, the goal of his therapeutic approach is to assist rediscovering meaning in one's life (logotherapy: meaning therapy).
One might wonder why meaning appears crucial for psychiatry and psychopathology. The answer lies in the fact that mental health and the perceived meaningfulness of personal existence seem to be Regarding some of the concrete techniques that existential-phenomenological psychotherapy routinely employs to treat mental disorders, the following two are of special interest: paradoxical intention and dereflection [14]. Frankl argued that both with anxiety disorders and with obsessive-compulsive disorders, the technique of paradoxical intention can be effectively utilized. As he wrote, "we define paradoxical intention in the following way: the patient will be directed to wish (in the case of anxiety neuroses) or to resolve to do (in the case of compulsive neuroses) precisely that which the patient fears so much" [14]. In other words, paradoxical intention is a technique whereby the individual resolves themselves to opt for an attitude that is diametrically opposed to that which they would originally want to adopt as a "natural" reaction to their perceived psychological difficulty. For example, if one is pathologically anxious and is terrified to experience a panic attack when they need to speak in front of an audience (glossophobia), then Frankl would suggest that instead of trying to avoid the anxiety-inducing thoughts, on the contrary, they should engage these troubling thoughts head-on and even exaggerate them. As Vos elucidates, "paradoxical intentions are based on the assumption that individuals can choose the stance they take towards their psychological difficulties and that their symptoms are exacerbated by avoiding problems or feeling saddened or anxious. Frankl invited clients to deliberate practice or exaggerate a neurotic habit or thought, so that they stopped fighting and instead identified and undermined their problems. This technique has proven to be particularly effective in anxiety disorders [16]. recommend that the patient be encouraged 'not to engage in sex, but rather to acquiesce to fragmentary acts of tenderness, like a mutual sexual foreplay" [14]. Consequently, the drawing away of the attention from the perceived problem-sexual impotence-and thus from the self towards the other person-by giving tenderness and caring, as well as by other gentle forms of mutual pleasuring-the psychological block can be gradually lifted, and the sexual functioning can become once again normal.

Clinical Evidence
The EPP is practiced as a MCP in general. MCP has proved its efficacy against depressive and anxiety symptoms in patients with a wide range of diseases from psychiatric disorders,  [25].
The result may reinforce the evidence of the efficacy and determine the cost-benefit ration of MCGP. Furthermore, an open trial study reported the preliminary results that meaning-centered grief therapy for parents who lost a child to cancer presented improvements in prolonged grief, sense of meaning, depression, haplessness, continuing bonds with their child, posttraumatic growth, positive affect, and quality of life. The treatment gains were maintained or improved after three months [26]. The meaning-centered intervention was shown to provide perceived benefits to palliative care nurses who faced recurrent burden, but improvement of spiritual and emotional quality of life remains unclear [27].

Neuroscience of Mood Disorders
Recent advance in neuroimaging technology has facilitated the investigation of brain structure and function. Among magnetic resonance imaging, computed tomography, and positron emission tomography, functional MRI (fMRI) provides information on the properties of functional connectivity (FC). Resting-state fMRI investigates the behavioral characteristics such as psychological states, sustained attention, personality, temperament traits, creative ability, and cognitive ability including working memory and motor performance [29][30][31][32]. Furthermore, the patterns of resting-state fMRI are correlated with specific symptoms and respond to treatment [33,34]. Analytical methods of resting-state network connectivity include seed-based analysis, the amplitude of low-frequency fluctuation (ALFF) and fractional ALFF techniques, regional homogeneity (ReHo), independent component analysis (ICA), and graph theory.

The default mode network
The default mode network (DMN) is a network of interacting brain regions which shows synchronized activation and deactivation during tasks [35]. DMN includes the medial prefrontal cortices (mPFC), the posterior cingulate cortex (PCC), precuneus, inferior parietal lobule, lateral temporal cortex, and hippocampal formation [36,37]. DMN activity is associated with internal processes including self-referential thinking, autobiographical memory, or thinking about the future [38][39][40]. The DMN is divided into an anterior subdivision centered in the mPFC and a posterior subdivision centered in the PCC. The anterior DMN is more related to self-referential processing, emotion regulation through its strong connections with limbic areas. The posterior DMN are associated with consciousness and memory processing through its connection with hippocampal formation [41,42] (Figure 6). A relative increase in DMN connectivity and significant ReHo reduction were observed in the posterior DMN in patients with late-life depression (LLD) [43][44][45][46]. ICA studies revealed an increased connectivity within the anterior DMN of patients with depression compared to healthy controls [47].
The dissociation between the anterior and posterior DMN subdivisions was observed in patients with major depressive disorder [48]. Antidepressant treatment restored FC abnormality in the posterior DMN but did not correct the FC abnormality in the anterior DMN. Network homogeneity was increased in the anterior DMN but decreased in the posterior DMN [49]. Seed-based analysis using mPFC showed the dissociation between the anterior and posterior DMN and increased connectivity between the anterior DMN and the salience network (SN) in depression [50,51].
Decreased PCC connectivity and increased connectivity in the anterior DMN were observed in depressive patients without medication and 12-weeks treatment of paroxetine partially restored the decreased connectivity [52]. The executive control network (ECN) plays an important role in the integration of sensory and memory information, the regulation of cognition and behavior, and the process of working memory [54]. The ECN consists of the dorsolateral prefrontal cortex (dlPFC), medial frontal cortex, lateral parietal cortex, cerebellum, and supplementary motor area [55]. Changes of the ECN were reported in ageing and in patients with LLD, mild cognitive impairment, Alzheimer's disease, and Parkinson's disease [56][57][58][59][60] (Figure 6).
Disruptions of the ECN were reported in non-demented elders with LLD [61][62][63]. Seed-based analyses using the dlPFC showed decreased FC in the frontoparietal areas in patients with LLD and current depression [64]. Seed-based analyses the cerebellum presented decreased FC in ECN nodes in dlPFC and the parietal cortex and DMN nodes [65,66]. ICA analysis reported decreased FC in the dlPFC and superior frontal areas, which is consistent with other resting-state fMRI studies with ReHo and ALFF [45,[67][68][69]. Decreased FC in the frontal-parietal cortex was also reported in LLD remitters 3 months after remission [70]. Alteration of the ECN was associated with susceptibility to distraction, difficulty to sustain attention, in multi-tasking, and organizational skills, and concrete thinking [71]. The FC between the dlPFC and other bilateral regions was negatively associated with executive function in patients with LLD [72]. Furthermore, the levels of functional disability were positively correlated with executive dysfunction in LLD [73,74]. Low and slow response to antidepressants and relapse were correlated with deficits in word-list generation and response inhibition which are governed in executive function network [75,76]. In addition, dissociation between the posterior DMN and ECN was also reported in patients with LLD and current depression [77].

The salience network
The SN detects and filters salient stimuli and recruits relevant functional networks [78]. The SN is responsible for detecting and incorporating sensory and emotional stimuli, allocating attention, switching inward and outward cognition. The SN is located in the ventral anterior insula and includes nodes in the amygdala, hypothalamus, ventral striatum, and thalamus [79]. The ventral components play a role in emotional control, while the dorsal components play a role in cognitive control [80]. Cognitive tasks activate the dorsal components including the dorsal anterior cingulate cortex and the right anterior insula. During cognitive tasks, the SN engages ECN and disengages DMN, but vice versa in rest [80][81][82]. Dissociation between the ECN and SN is correlated with cognitive task performance [83] (Figure 6).
Decreased FC from the amygdala to the hippocampus was observed in patients with depression and individuals at high risk of depression [84,85]. Disrupted pattern of SN connectivity was reported in depression, especially in the insula and amygdala [86]. Elevated connectivity was found between the insula and DMN in patients with LLD [87]. Seed-based analysis using the amygdala as a seed region was positively associated with increased amygdala FC with DMN nodes and long-term negative emotions [88]. Increased FC between the SN and DMN is considered to predispose individuals to depression but decreased FC between the amygdala and precuneus was reported in patients with depression [62,89,90]. Decreased negative FC between the ECN and the SN was associated with cognitive impairment and severity of depression in patients with LLD.
Disrupted standard SN pattern was associated with a worse treatment response [91].
Mood disorders, anxiety disorders, and posttraumatic stress disorder (PTSD) share neurobiologically common characteristics in task-related fMRI. A meta-analysis was conducted by articles studying stereotactic coordinates of whole-brain-based activation in task-related fMRI between adult patients and controls. Patients with mood disorders, anxiety disorders, or PTSD shared abnormalities in convergence of task-related brain activity in regions associated with inhibitory control and salience processing. Patients who suffered from mood and anxiety disorders presented abnormally lower activity in the inferior prefrontal and parietal cortex, the insula and the putamen. The regions are responsible for cognitive and motional control, and inhibition of and switching to new metal activities. The patients also showed higher activity in the anterior cingulate cortex, the left amygdala, and the thalamus which process emotional thoughts and feelings [92].

Other relevant biomarkers and therapeutic targets
Besides the large-scale brain network, endogenous metabolites, neuropeptides, receptor agonist, their synthetic analogues, plasma proteins, and lipids are under extensive study in search of biomarkers and novel drugs for mood disorders [93][94][95][96]. Normal human brain functions are maintained in balance of 80% of excitatory neuronal and 20% of inhibitory neuronal activities. The  cognitive disturbance, and social behavior and a microbiota composition was proposed to be potential biomarkers and targets [100,101].
Profiles of longitudinal plasma samples were proposed to be a potential predictive biomarker for the treatment of depression [102]. Nutraceuticals were proposed for the treatment of metabolic dysfunction in ageing neurodegenerative diseases [103]. In addition to biomolecules, any measurable indicators are entitled for risk, diagnosis, prognosis, and prognostic biomarkers and interventional targets. Depression was found a risk factor for Alzheimer's disease and dementia.
Dyslipidemia treatment reduced the risk of development of dementia in diabetics [104]. The presence of depressive symptom following acute stroke or transient ischemic attack increased mortality and disability within 12-months period, suggesting that depression is a prognostic biomarker in cerebral ischemia [105]. Therefore, the treatment of depression is a crucial measure to avoid the development of comorbid condition and psychotherapy is certainly able to contribute to prevention of disease progression and complication for better quality of life. In addition, depression is a measurable psychobehavioral component of dementia, which can be ameliorated by animal-assisted and pet-robot interventions in patients with dementia [106] (Figure 7).

Conflicts of Interest:
The authors declare no conflict of interest.