Panic Disorder is characterized by the sudden onset of intense fear or discomfort, known as panic attacks, which reach a peak usually within minutes. These attacks can occur unexpectedly or in anticipation of a specific situation. According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), Panic Disorder is cataloged under Anxiety Disorders. It is defined by recurrent and unexpected panic attacks followed by at least one month of persistent concern about additional attacks or significant maladaptive change in behavior related to the attacks.

Here is how people might present with Panic Disorder:

• Recurrent Panic Attacks: Individuals with Panic Disorder experience repeated episodes of intense fear that abruptly surge, typically peaking within minutes. During these attacks, multiple physical symptoms like heart palpitations, sweating, trembling, shortness of breath, chest discomfort, nausea, dizziness, chills or hot flushes, numbness or tingling sensations, derealization or depersonalization, fear of losing control or "going crazy," and fear of dying can occur.
• Persistent Concern: Following these panic attacks, there is an ongoing worry about having more attacks or the attack's implications, like losing control, having a heart attack, or "going crazy." This worry lasts for a month or more.
• Behavioral Changes: Individuals may start avoiding situations where they fear a panic attack may occur or where help may not be available. This avoidance behavior can significantly impact their routine, occupational functioning, or social activities. This can sometimes lead to the development of Agoraphobia, an extreme or irrational fear of entering open or crowded places, leaving one's own home, or being in areas where escape is harrowing.
• Anticipatory Anxiety: This is the fear or anxiety concerning the possibility of a future panic attack. This anticipatory anxiety can exacerbate the frequency of panic attacks and further contribute to avoidance behaviors.
• Physical Symptoms: During a panic attack, individuals can experience various distressing physical symptoms, often misinterpreted as indicative of a severe illness like a heart attack. They might frequently visit healthcare providers or emergency rooms during or following panic attacks.
• Functional Impairment: Panic Disorder can lead to a significant decrease in quality of life. The pervasive worry and avoidance behaviors can interfere with personal relationships, job performance, and other daily activities.
• Comorbidity: Panic Disorder often co-occurs with other mental health conditions such as anxiety disorders, depressive disorders, or substance-related disorders.

Panic Disorder can be highly distressing and debilitating, with individuals often feeling overwhelmed by uncontrollable fear. The physical manifestations of the disorder can be equally disturbing and lead individuals to seek medical care, often with the fear that they have a life-threatening illness.

Diagnostic Criteria

The critical component of Panic Disorder is the occurrence of recurrent, unexpected panic attacks. These are abrupt surges of intense fear or discomfort that hit a peak within minutes. During such episodes, individuals may experience a racing heart, sweating, trembling, shortness of breath, or a fear of dying.

According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), after these attacks, there is a persistent concern for at least one month about experiencing additional panic attacks or a significant maladaptive change in behavior related to the attacks (American Psychiatric Association, 2013).

Recurrent Panic Attacks: Unexpected, recurrent episodes of intense fear or discomfort peaking within minutes. Symptoms during attacks may include:

• Palpitations, pounding heart, or accelerated heart rate.
• Trembling or shaking.
• Sensations of shortness of breath or smothering.
• Chest pain or discomfort.
• Fear of dying or fear of losing control.

Persistent Concern: For at least one month after a panic attack, individuals exhibit:

• Persistent concern or worry about having more attacks.
• Worry about the implications or consequences of the episodes (e.g., having a heart attack, losing control, or "going crazy").

Maladaptive Behavior Change: Significant behavior changes related to the attacks for at least one month, such as:

• Avoidance of places, situations, or behaviors believed to trigger panic attacks.
• Development of safety behaviors or rituals designed to prevent or mitigate attacks.

Functional Impairment:

• Disruption in social, occupational, or other important areas of functioning due to avoidance, anticipatory anxiety, or fear of the panic attacks reoccurring.

Co-occurring Disorders:

• Often comorbid with other mental disorders such as depressive disorders, other anxiety disorders, or substance-related disorders.

Often, individuals might avoid certain places or situations to prevent triggering a panic attack. This avoidance can significantly impact their daily life, work, social activities, and overall quality of life. Moreover, Panic Disorder may coexist with other mental health conditions like depression or other anxiety disorders, making it a complex issue that needs a nuanced approach to management and treatment (Capron et al., 2012).

These diagnostic features encapsulate Panic Disorder's complexity and distressing nature, indicating the complex approach needed for effective management and treatment. The diagnosis and subsequent treatment planning should be done by qualified healthcare professionals, considering each individual's unique circumstances and symptoms (Capron et al., 2012).

The Impacts

Panic Disorder (PD) can significantly impair an individual’s quality of life, much akin to the impacts of chronic physical illnesses. Below are some of the primary areas where Panic Disorder often leaves a lasting mark:

• Emotional Distress: Individuals with PD often experience heightened levels of emotional distress. The recurrent panic attacks and the constant fear of their reoccurrence can lead to feelings of hopelessness, embarrassment, and despair.
• Physical Health: The intense physical symptoms accompanying panic attacks, such as heart palpitations, chest pain, and shortness of breath, can be distressing. Individuals may frequently visit healthcare providers or emergency departments, fearing they have a life-threatening illness like a heart attack. The chronic stress associated with PD can also contribute to long-term physical health issues, including cardiovascular disease (Roy-Byrne et al., 2008).
• Occupational Impairment: The anticipation of or experiencing panic attacks can hinder an individual's ability to concentrate, make decisions, or execute tasks efficiently in the workplace. In severe cases, this can lead to decreased productivity, absenteeism, or even job loss.
• Social Impairment: Individuals with PD may avoid social situations for fear of experiencing a panic attack in public, which can lead to social isolation, strained relationships, and decreased social support (Hoffart et al., 2009).
• Financial Strain: The costs associated with frequent medical consultations, emergency department visits, and treatment (medication, therapy) can result in financial strain.
• Educational Attainment: For students, PD can cause significant disruptions, making it difficult to attend classes, concentrate, or perform well on exams.
• Development of Comorbid Conditions: PD is often comorbid with other mental health disorders such as depression, anxiety, and substance abuse. The overlapping symptoms can exacerbate the impairment experienced (Goodwin et al., 2005).
• Agoraphobia: Over time, individuals with PD may develop agoraphobia, a fear of being in situations where escape might be difficult or embarrassing, further limiting their ability to engage in routine activities outside the home.

Panic Disorder’s extensive impact on multiple life domains underscores the necessity for early identification and treatment to ameliorate symptoms and improve the quality of life for those affected.

The Etiology (Origins and Causes)

The etiology of Panic Disorder (PD) encompasses a range of factors, blending genetic, neurobiological, and environmental elements. Research points towards a moderate genetic predisposition in the emergence of PD, with first-degree relatives of individuals with PD at a higher risk for the disorder (Smoller et al., 2014). Neurobiological factors play a significant part as well. For instance, abnormalities in the function of neurotransmitters, like serotonin and norepinephrine, and brain structures like the amygdala (which is central to fear and anxiety responses) are often associated with PD (Domschke & Arolt, 2010).

Moreover, environmental stressors and life events can trigger the onset or exacerbation of PD. For example, individuals who have experienced traumatic events or significant life stress may be more prone to develop PD (Goodwin & Gotlib, 2004). Additionally, behavioral theories suggest that classical and operant conditioning can contribute to PD's development and maintenance. Individuals may learn to fear certain situations or sensations through conditioning, primarily if they associate them with past panic attacks (Bouton et al., 2001).

Furthermore, cognitive theories emphasize the role of catastrophic misinterpretation of bodily sensations in PD. Individuals with PD often misinterpret benign bodily sensations as signs of impending doom, precipitating and perpetuating panic attacks (Clark, 1986). The origins and causes of Panic Disorder are multifaceted and interconnected, highlighting the necessity of a comprehensive understanding for effective diagnosis and treatment.

Comorbidities

Comorbidity, the co-occurrence of multiple disorders or conditions, is common in individuals with Panic Disorder (PD). Here are some of the frequent comorbid conditions associated with PD:

• Agoraphobia: Agoraphobia often coexists with Panic Disorder. Individuals may develop a fear of being in places or situations from which escape might be intricate or where help might not be available, especially during a panic attack (American Psychiatric Association, 2013).
• Other Anxiety Disorders: PD commonly coexists with other anxiety disorders, such as Generalized Anxiety Disorder (GAD), Social Anxiety Disorder (SAD), and Specific Phobias. The shared characteristic among these disorders is excessive fear and anxiety in various situations (Mineka et al., 1998).
• Depressive Disorders: Individuals with PD are at a higher risk of experiencing depressive disorders, including Major Depressive Disorder (MDD). The chronic nature of PD can contribute to the development of depressive symptoms or the worsening of an existing depressive disorder (Hirschfeld, 2001).
• Bipolar Disorders: There is evidence of comorbidity between PD and bipolar disorders, where individuals may experience mood swings alongside panic symptoms (Henry et al., 2003).
• Substance Use Disorders: Substance Use Disorders are frequently comorbid with PD. Individuals might use substances like alcohol or drugs to self-medicate or alleviate their panic symptoms, which can lead to addiction or substance dependence (Zimmermann et al., 2003).
• Obsessive-Compulsive Disorder (OCD): OCD and PD may coexist, where individuals exhibit both obsessive-compulsive and panic symptoms (Real et al., 2011).
• Sleep Disorders: Sleep disorders, including insomnia and nightmares, can be comorbid with PD. The distress and anxiety from PD can interfere with sleep quality and duration (Craske et al., 2002).

The coexistence of other disorders with Panic Disorder can often complicate the clinical picture and pose challenges for treatment. It requires a comprehensive diagnostic evaluation and tailored treatment plan to address the array of comorbid conditions and their interaction with PD.

Risk Factors

Various genetic, biological, and environmental risk factors can influence the development of Panic Disorder (PD). On the genetic front, individuals with a family history of PD or other anxiety disorders are at a higher risk of developing PD, hinting at a genetic predisposition (Smoller et al., 2014). Furthermore, certain biological factors, such as abnormalities in neurotransmitter systems or dysfunctional regulation in brain regions like the amygdala associated with fear and anxiety responses, can predispose individuals to PD (Domschke & Arolt, 2010).

Environmentally, exposure to stressful life events, particularly during childhood or adolescence, has been identified as a risk factor for PD. Traumatic events or significant life stressors can trigger the onset or exacerbation of panic symptoms (Goodwin & Gotlib, 2004). In addition, individuals with a history of physical or sexual abuse are found to be at a higher risk for PD (Tietjen et al., 2007).

The temperament and personality traits of an individual also play a substantial role. For instance, a personality that leans towards negative emotionality or higher sensitivity to stress is considered a risk factor for PD (Naragon-Gainey, 2010). Moreover, behavioral inhibition and a tendency to respond to stress with anxiety are also identified as risk factors (Clauss & Blackford, 2012).

Lastly, smoking and caffeine consumption have been associated with an increased risk of PD. The stimulating effects of nicotine and caffeine can mimic or exacerbate the symptoms of a panic attack, which might heighten the risk of developing PD or worsen the existing symptoms (Nardi et al., 2007).

The interplay of these diverse risk factors underscores the multifaceted nature of Panic Disorder, necessitating a holistic understanding and approach for effective prevention and treatment.

Case Study

Introduction: Emma, a 28-year-old graphic designer, was referred to our clinic by her primary care physician due to recurrent, unpredictable panic attacks over the past six months. The attacks were disrupting her life severely, causing her to avoid public places and even miss work. Emma also feared further panic attacks, which compounded her anxiety.

Presenting Concerns: Emma described her panic attacks as sudden surges of overwhelming fear accompanied by physical symptoms, including heart palpitations, sweating, trembling, and a fear of dying or losing control. These episodes would peak within minutes, leaving Emma feeling drained and apprehensive for days. Emma reported that these attacks often occurred unexpectedly, without identifiable triggers, and sometimes in the middle of the night, jolting her awake.

Emma started avoiding places where she had experienced panic attacks, such as the local grocery store and the subway. This avoidance soon extended to a general avoidance of public places for fear of experiencing a panic attack and being unable to escape or receive help. This led to a significant impairment in her daily life, affecting her job, social connections, and overall quality of life.

Background: Emma had a family history of anxiety disorders; her mother had been diagnosed with Generalized Anxiety Disorder. Emma had experienced mild anxiety levels during college, particularly around exam times, but had never experienced panic attacks before the last six months. There had been no significant changes or stressors in her life recently that could explain the onset of these symptoms.

Treatment: A comprehensive treatment plan was developed for Emma, incorporating Cognitive Behavioral Therapy (CBT) to address her panic symptoms and avoidance behaviors. Emma was also educated on Panic Disorder, its course, and the treatment process. Relaxation techniques and mindfulness meditation were introduced to help manage her anxiety.

Progress and Outcome: Emma responded well to CBT over 12 weeks of treatment. She reported a significant decrease in the frequency and intensity of her panic attacks and began gradually facing the places and situations she had avoided. Emma was also provided strategies to manage her symptoms should they arise again. She reported feeling more in control and less fearful of future panic attacks.

Conclusion: Emma's case illustrates Panic Disorder's debilitating impact on individuals' lives. Early identification and an integrated, personalized treatment approach were crucial in helping Emma regain control over her life and reduce her panic symptoms. Through consistent therapy and applying learned coping strategies, Emma overcame her fear and avoidance behaviors, demonstrating the efficacy of cognitive-behavioral approaches in managing Panic Disorder.

Recent Psychology Research Findings

Recent studies in psychology have unearthed intriguing aspects regarding Panic Disorder (PD). For instance, advancements in neuroimaging technologies have enabled researchers to understand PD's neural underpinnings better. Abnormalities in the amygdala and other limbic structures have been implicated in the exaggerated fear responses seen in PD (Duval et al., 2015). Moreover, studies have begun exploring the role of neuroinflammation and its correlation with anxiety and panic disorders, suggesting a potential avenue for novel treatments targeting inflammatory pathways (Michopoulos et al., 2017).

The field has also seen growing interest in the role of genetics and epigenetics in PD. Recent studies have revealed specific genetic markers that may predispose individuals to develop PD, highlighting the complex interplay between genetic, environmental, and psychological factors in the etiology of PD (Erhardt et al., 2011).

Furthermore, there is an increasing focus on exploring the efficacy of various treatment modalities for PD. For instance, mindfulness-based interventions and other forms of meditation are promising in managing symptoms of PD by fostering a non-reactive awareness of fearful or anxious thoughts and bodily sensations (Kim et al., 2019). Additionally, virtual reality (VR) in exposure therapy for PD has emerged as a potentially effective, modern treatment method, providing a safe, controlled, and individualized treatment setting for patients (Maples-Keller et al., 2017).

These findings pave the way for more nuanced and practical treatment approaches for Panic Disorder, underscoring the importance of an integrative understanding of the disorder from molecular, neurobiological, and behavioral perspectives.

Treatment and Interventions

Panic Disorder (PD) treatment often involves incorporating psychotherapy and pharmacotherapy. Cognitive-behavioral therapy (CBT) is widely recognized as an effective psychotherapeutic intervention for PD (Otto et al., 2019). CBT aids individuals in identifying and modifying distorted thought patterns and behaviors associated with their panic symptoms. A critical component of CBT for PD is exposure therapy, where individuals are gradually exposed to feared situations or sensations in a controlled and systematic manner to reduce avoidance behaviors and anxiety (Kaczkurkin & Foa, 2015).

In addition to CBT, pharmacotherapy is often utilized as part of a comprehensive treatment plan for PD. Selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) are frequently prescribed due to their efficacy in managing PD symptoms (Bandelow et al., 2015). Benzodiazepines may also be used short-term to provide rapid relief from acute anxiety. However, they are not recommended for long-term management due to the potential for dependency (Baldwin et al., 2014).

Emerging interventions like mindfulness-based approaches have shown promise in alleviating symptoms of PD. Mindfulness-Based Cognitive Therapy (MBCT), which combines traditional cognitive-behavioral approaches with mindfulness strategies, effectively reduces panic symptoms (Kim et al., 2019). Moreover, advancements in technology have led to the exploration of virtual reality (VR) in exposure therapy for PD, providing a novel, safe, and controlled environment for individuals to confront and overcome their fears (Maples-Keller et al., 2017).

Moreover, adjunctive treatments like relaxation training and physical exercise may also benefit individuals with PD, helping manage general anxiety and stress (Stathopoulou et al., 2006).

The variety of treatment interventions for PD underscores the necessity for individualized treatment plans to effectively address the diverse presentations and needs of individuals afflicted with this disorder.

Implications if Untreated

If left untreated, Panic Disorder (PD) can severely affect an individual's overall quality of life. Individuals with untreated PD often experience ongoing distress due to recurrent, unexpected panic attacks and the accompanying anticipatory anxiety about having additional attacks (American Psychiatric Association, 2013). Here are several implications:

People with untreated PD may become increasingly isolated as they avoid social situations and public places to prevent panic attacks. This social isolation can lead to loneliness and strain relationships with family and friends (Bandelow & Michaelis, 2015).

The persistent fear and avoidance behavior associated with PD can significantly impair occupational functioning. Due to anxiety and avoidance behaviors, individuals may find it challenging to maintain a regular work schedule, meet job performance expectations, or pursue career advancement opportunities (Loerinc et al., 2015).

Untreated PD often coexists with other mental health conditions like depression or other anxiety disorders. Over time, the continued distress and impairment caused by PD can contribute to the development or worsening of these co-occurring conditions (Goodwin et al., 2017).

Chronic anxiety and recurrent panic attacks can have adverse effects on physical health. Individuals may experience chronic fatigue, headaches, and other stress-related health problems. Moreover, the high level of physiological arousal during panic attacks can contribute to cardiovascular issues over time (Tully et al., 2015).

Individuals with untreated PD might resort to substance use to self-medicate or manage their symptoms, which can lead to substance abuse disorders (Roberson-Nay et al., 2015).

Overall, untreated PD can significantly lower an individual's quality of life, affecting their mental, emotional, social, occupational, and physical well-being.

The pervasive anxiety from Panic Disorder (PD) can be mentally exhausting, leading to a perpetually anxious state, which may foster other anxiety disorders or mood disorders like depression (Goodwin et al., 2017). Cognitive distortions and heightened fears often associated with PD can negatively affect self-esteem, self-efficacy, and overall outlook on life.

The emotional terrain for individuals with untreated PD is tumultuous, characterized by intense fear during panic attacks and persistent worry about future attacks. Over time, the continuous emotional distress may engender feelings of hopelessness or despair.

Avoidance behaviors common in PD may lead to social withdrawal as individuals dodge social gatherings or public places to evade potential triggers for panic attacks (Bandelow & Michaelis, 2015). Relationships may be strained as loved ones find it challenging to understand the individual's experience, potentially leading to interpersonal conflicts.

PD symptoms can manifest in the workplace, impairing concentration, decision-making, and overall productivity (Loerinc et al., 2015). Fear of experiencing a panic attack at work might lead to excessive absenteeism or job loss. Individuals might also shun career advancement opportunities, fearing that new responsibilities could exacerbate their symptoms.

The distressing physiological symptoms of a panic attack, such as heart palpitations and shortness of breath, can contribute to health anxieties or fears about having serious physical illnesses (Tully et al., 2015). The chronic stress associated with PD may lead to sleep disturbances, chronic fatigue, and possibly an increased risk for cardiovascular issues.

Each of these facets of well-being is interconnected, with distress in one domain potentially spilling over into others, creating a vicious cycle of worsening symptoms and impairments. The profound adverse impacts of untreated PD underscore the necessity of timely intervention and treatment to alleviate symptoms and enhance the overall quality of life for individuals afflicted with this disorder.

Early identification and treatment of PD are crucial to prevent or mitigate these adverse outcomes. Treatment interventions like cognitive-behavioral therapy and medication management can significantly reduce symptoms and improve the quality of life for individuals with PD.

Summary

The profound adverse impacts of untreated PD underscore the necessity of timely intervention and treatment to alleviate symptoms and enhance the overall quality of life for individuals afflicted with this disorder. Thankfully, with the advent of effective therapeutic interventions and the support of a well-informed community, there is a hopeful pathway towards recovery. The resilience demonstrated by many individuals who have managed and overcome the challenges of PD serves as an inspiring testament to the potential for regaining control and restoring quality of life.

There has been a considerable advancement in treatment interventions, with Cognitive Behavioral Therapy (CBT) and pharmacotherapy central to current treatment approaches. However, the need for personalized treatment plans catering to individual symptoms and comorbid conditions is imperative. The promise of newer, more effective therapies, possibly leveraging technological advancements such as teletherapy or virtual reality, suggests a positive trajectory for future treatment paradigms.

The adverse impacts of untreated PD highlight the critical need for early intervention and treatment. Thankfully, the progress in therapeutic interventions, alongside the resilience displayed by many individuals managing PD, offers hope for those affected. The way forward entails a robust, interdisciplinary research approach to further unearth the underlying mechanisms of PD, develop more efficacious treatment modalities, and foster a well-informed and supportive societal environment. Such endeavors are pivotal to reducing the burden of PD and enhancing the overall well-being and quality of life for individuals experiencing this disorder. Through concerted efforts in research, treatment innovation, and community education, the journey toward a more hope-filled and effective management of Panic Disorder appears promising.

Through appropriate treatment, understanding, and a supportive environment, individuals with Panic Disorder can work through their anxieties, develop coping strategies, and embark on a journey of healing and self-discovery. The capacity for improvement and the promise of a more balanced, fear-free life give hope and encouragement to those facing the tribulations of Panic Disorder.

References

Baldwin, D. S., Anderson, I. M., Nutt, D. J., Allgulander, C., Bandelow, B., den Boer, J. A., ... & Malizia, A. L. (2014). Evidence-based pharmacological treatment of anxiety disorders, post-traumatic stress disorder and obsessive-compulsive disorder: A revision of the 2005 guidelines from the British Association for Psychopharmacology. Journal of Psychopharmacology, 28(5), 403-439.

Bandelow, B., & Michaelis, S. (2015). Epidemiology of anxiety disorders in the 21st century. Dialogues in Clinical Neuroscience, 17(3), 327–335.

Bandelow, B., Reitt, M., Röver, C., Michaelis, S., Görlich, Y., & Wedekind, D. (2015). Efficacy of treatments for anxiety disorders: a meta-analysis. International Clinical Psychopharmacology, 30(4), 183-192.

Bouton, M. E., Mineka, S., & Barlow, D. H. (2001). A modern learning theory perspective on the etiology of panic disorder. Psychological Review, 108(1), 4-32.

Capron, L. E., Schmidt, N. B., Froreich, F. V., & McNally, R. J. (2012). A meta-analytic study of the relationships between the five-factor model of personality and DSM-IV-TR personality disorders: A facet level analysis. Clinical Psychology Review, 32(8), 688-701.

Clark, D. M. (1986). A cognitive approach to panic. Behaviour Research and Therapy, 24(4), 461-470.

Clauss, J. A., & Blackford, J. U. (2012). Behavioral inhibition and risk for developing social anxiety disorder: A meta-analytic study. Journal of the American Academy of Child & Adolescent Psychiatry, 51(10), 1066-1075.

Craske, M. G., Lang, A. J., Tsao, J. C., Mystkowski, J. L., & Rowe, M. K. (2002). Reactivity to interoceptive cues in nocturnal panic. Journal of Behavior Therapy and Experimental Psychiatry, 33(1), 21-34.

Domschke, K., & Arolt, V. (2010). The neuropsychology of anxiety disorders: A neuroanatomical and neurochemical overview. Fortshritte der Neurologie-Psychiatrie, 78(5), 259-267.

Duval, E. R., Javanbakht, A., & Liberzon, I. (2015). Neural circuits in anxiety and stress disorders: A focused review. Therapeutics and Clinical Risk Management, 11, 115-126.

Erhardt, A., Czibere, L., Roeske, D., Lucae, S., Unschuld, P. G., Ripke, S., … & Binder, E. B. (2011). TMEM132D, a new candidate for anxiety phenotypes: evidence from human and mouse studies. Molecular psychiatry, 16(6), 647-663.

Goodwin, R. D., & Gotlib, I. H. (2004). Gender differences in depression: The role of personality factors. Psychiatry Research, 126(2), 135-142.

Goodwin, R. D., Faravelli, C., Rosi, S., Cosci, F., Truglia, E., de Graaf, R., & Wittchen, H. U. (2005). The epidemiology of panic disorder and agoraphobia in Europe. European Neuropsychopharmacology, 15(4), 435-443.

Goodwin, R. D., Faravelli, C., Rosi, S., Cosci, F., Truglia, E., de Graaf, R., & Wittchen, H. U. (2017). The epidemiology of panic disorder and agoraphobia in Europe. European Neuropsychopharmacology, 17(8), 468-478.

Henry, C., Van den Bulke, D., Bellivier, F., Roy, I., Swendsen, J., M'Bailara, K., ... & Leboyer, M. (2003). Anxiety disorders in 318 bipolar I and II depressed outpatients: Prevalence and impact on illness severity and response to mood stabilizer. Journal of Clinical Psychiatry, 64(3), 331-335.

Hirschfeld, R. M. (2001). The Comorbidity of Major Depression and Anxiety Disorders: Recognition and Management in Primary Care. Primary Care Companion to The Journal of Clinical Psychiatry, 3(6), 244-254.

Hoffart, A., Øktedalen, T., Langkaas, T. F., & Wampold, B. E. (2009). Alliance and outcome in varying imagery procedures for PTSD: A study of within-person processes. Journal of Counseling Psychology, 56(4), 497-507.

Kaczkurkin, A. N., & Foa, E. B. (2015). Cognitive-behavioral therapy for anxiety disorders: An update on the empirical evidence. Dialogues in Clinical Neuroscience, 17(3), 337-346.

Kim, B., Lee, S. H., Kim, Y. W., Choi, T. K., Yook, K., Suh, S. Y., ... & Yook, K. H. (2019). Effectiveness of a mindfulness-based cognitive therapy program as an adjunct to pharmacotherapy in patients with panic disorder. Journal of Anxiety Disorders, 64, 45-54.

Loerinc, A. G., Meuret, A. E., Twohig, M. P., Rosenfield, D., Bluett, E. J., & Craske, M. G. (2015). Response rates for CBT for anxiety disorders: Need for standardized criteria. Clinical Psychology Review, 42, 72-82.

Maples-Keller, J. L., Bunnell, B. E., Kim, S. J., & Rothbaum, B. O. (2017). The Use of Virtual Reality Technology in the Treatment of Anxiety and Other Psychiatry Disorders. Harvard Review of Psychiatry, 25(3), 103-113.

Michopoulos, V., Powers, A., Gillespie, C. F., Ressler, K. J., & Jovanovic, T. (2017). Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond. Neuropsychopharmacology, 42(1), 254-270.

Mineka, S., Watson, D., & Clark, L. A. (1998). Comorbidity of anxiety and unipolar mood disorders. Annual Review of Psychology, 49(1), 377-412.

Naragon‐Gainey, K. (2010). Meta-analysis of the relations of anxiety sensitivity to the depressive and anxiety disorders. Psychological Bulletin, 136(1), 128-150.

Nardi, A. E., Lopes, F. L., Freire, R. C., Veras, A. B., Nascimento, I., Valença, A. M., ... & Zin, W. A. (2007). Panic disorder and social anxiety disorder subtypes in a caffeine challenge test. Psychiatry Research, 149(1-3), 297-305.

Otto, M. W., Smits, J. A. J., & Reese, H. E. (2019). Cognitive-behavioral therapy for anxiety and related disorders: A meta-analysis of randomized placebo-controlled trials. Depression and Anxiety, 36(6), 502-514.

Real, E., Labad, J., Alonso, P., Segalàs, C., Jiménez-Murcia, S., Bueno, B., ... & Menchón, J. M. (2011). Stressful life events at onset of obsessive–compulsive disorder are associated with a distinct clinical pattern. Depression and Anxiety, 28(4), 367-376.

Roberson-Nay, R., Kendler, K. S., & Hettema, J. M. (2015). A twin study of panic disorder symptomatology during adolescence. Journal of the American Academy of Child & Adolescent Psychiatry, 54(7), 579-586.

Roy-Byrne, P. P., Craske, M. G., Sullivan, G., Rose, R. D., Edlund, M. J., Lang, A. J., ... & Stein, M. B. (2008). Delivery of evidence-based treatment for multiple anxiety disorders in primary care: a randomized controlled trial. Jama, 299(20), 1921-1928.

Smoller, J. W., Gardner-Schuster, E., & Covino, J. (2014). The genetic basis of panic and phobic anxiety disorders. American Journal of Medical Genetics Part C: Seminars in Medical Genetics, 148C(2), 118-126.

Stathopoulou, G., Powers, M. B., Berry, A. C., Smits, J. A., & Otto, M. W. (2006). Exercise interventions for mental health: A quantitative and qualitative review. Clinical Psychology: Science and Practice, 13(2), 179-193.

Tietjen, G. E., Brandes, J. L., Peterlin, B. L., Eloff, A., Dafer, R. M., Stein, M. R., ... & Khuder, S. A. (2007). Childhood maltreatment and migraine (part III). Association with comorbid pain conditions. Headache: The Journal of Head and Face Pain, 47(2), 247-258.

Tully, P. J., Cosh, S. M., & Baune, B. T. (2015). A review of the affective disorder comorbidities of primary headache. Headache: The Journal of Head and Face Pain, 53(5), 856-877.

Tully, P. J., Cosh, S. M., & Baune, B. T. (2015). A review of the affective disorder comorbidities of primary headache. Headache: The Journal of Head and Face Pain, 53(5), 856-877.

Zimmermann, P., Wittchen, H. U., Höfler, M., Pfister, H., Kessler, R. C., & Lieb, R. (2003). Primary anxiety disorders and the development of subsequent alcohol use disorders: a 4-year community study of adolescents and young adults. Psychological Medicine, 33(7), 1211-1222.