Increased Incidence of Stress-related Tic Habit Cough in Children During the Recent Greek Financial Crisis

Discussion

The number of children diagnosed in our specialized Unit with THC significantly increased during the 8 years of financial crisis in Greece, exceeding the incidence of previous reports (5, 11-16). Over an 18-year period, only 62 cases were reported by the Mayo Clinic (5). In 1991, Lokshin et al. analyzed 4,500 pediatric medical records and found only 9 cases of THC in a 12-year period (11). Houstek et al. reported ten cases between 1971 and 1981 (13). Likewise, Cohlan and Stone reported only 33 cases of THC in over 25 years of clinical practice (14). Later, Wolff, from the same department, described another two patients and mentioned a total of six, 4 years after the original report (15). In a study conducted in a Swedish community sample with a quite high frequency of tics, the prevalence of chronic vocal tics, including cough, was 0.3% in girls and 0.7% in boys, among children aged 7 to 15 years (16).

Since 1966, when this entity was first identified, the reported prevalence of THC has been quite low, probably because of the low medical community awareness and the lack of validated diagnostic criteria (8, 12, 25). Therefore, it was probably under-diagnosed and, hence, under-reported. Thus, a high index of suspicion of the medical personnel is an important factor for the diagnosis, as mentioned by Weinberger et al., who recently reported 140 pediatric patients with THC in the last 20 years (17). They claimed that laboratory tests were not needed to support the diagnosis and that could be based on history and observation alone. Similarly, in our study, a high awareness of this particular entity led to a diagnosis of THC based not just on the criteria shown in Table I but, mainly, on the history of repetitive coughing, ranging from several hours at a time to all day long, yet completely absent during sleep. In our series, we found a significant increase in THC cases as two thirds of them were reported in the last two years, when the stressful impact of the financial crisis was heavily felt in the Greek society. A clear increasing trend from 2.2 to 4.5 cases per year was found, represented by a much steeper slope of the increase in THC cases than that of the earlier years.

Past or current history of wheezing was not related to cough in the context of THC. Furthermore, all clinical and laboratory evaluations in this study, as in earlier ones, failed to reveal any underlying pathology. Radiologic imaging, immune studies, and pulmonary function tests were all negative. Flexible bronchoscopy, when performed, showed non-specific mucosal inflammation and EDAC during spontaneous breathing (7). Rabin et al. also noted lingual tonsils edema, impinging on the epiglottis and obliterating the vallecular space (1). These findings probably represent the consequence of aggressive, barking cough, traumatizing the mucosa, rather than its cause.

So far, five stressors have been most implicated in children’s THC, all reflecting the western modernized way of living (7, 25). In particular, peer pressure, striving for high academic achievement, learning difficulties with consequential school phobia, bullying, divorce and/or a relative’s death. In our study, learning difficulties were the major trigger. As high as 30% of children with learning disabilities have been reported to have behavioral and emotional problems such as attention deficit hyperactivity disorder, depression, anxiety, suicide ideation or substance abuse (26). Other cases experienced learning problems due to parents’ pressure for high academic achievement resulting in family quarrels, strained relationships and children with low self-confidence. Bullying at school was the second most frequent trigger and the only factor that had a close relationship with the increase in THC cases. Bullying increased significantly during the last years of the Greek financial crisis (27, 28). The prevalence of the reported bullying victimization was associated with living in a main urban center, presence of a person with a chronic illness at home, poor family economic status and increased number of adults at home. Severe forms of physical and emotional aggression have been considered as a major emotional destabilizing factor. Bullying-victims were generally aggressive, uncooperative and prone to demonstrate concurrently attention-deficit hyperactivity disorder, depression or anxiety and long-term post-traumatic stress disorders (29, 30). The present study may indicate that there is a close relationship between bullying and THC increase, which seems to be a desperate “cry” for help.

Financial difficulties emerged as a novel trigger factor during the study period. One fifth of our children with THC reported that one or both parents had lost their jobs and experienced serious financial problems. Several past publications have dealt with the influence of poverty on health status in low-income countries, but few studies have examined its influence in a rapidly declining economy in western countries (31, 32). This report enhanced previous national data dealing with children from western developed countries that experienced abrupt and serious financial constraints, which strongly influenced their mental health status (33). Our study highlights the indirect association between highly educated fathers who cope with financial problems and THC. One possible explanation could be the fact that this particular population experienced and spread more anxiety and depression. This was also reported by Barbaglia et al., who found that job loss increased the risk of any mental disorder in men (34). It seemed that highly educated parents were less able to effectively handle abrupt financial deteriorations (35). The aforementioned associations, maybe, reflect a more stressful environment in children of more educated fathers. On the other hand, poverty in childhood has been linked to emotional dysregulation throughout adulthood, and has been associated with pervasive negative physical and psychological health sequelae. Kim et al. provided evidence of prospective associations between childhood poverty at the age of 9 years and adult neural activity during effortful attempts to control negative emotions (36). The fact that exposure to poverty in early childhood has deleterious impact on brain development, restricting the ability to respond adaptively to emotional challenges in adulthood, further highlights the importance of this finding on child psychological development (37).

The present study has certain limitations. The cases described were derived from a major pediatric pulmonology center and thus, the prevalence and incidence rates were not representative of the general population. At first glance, the significant increase in incidence could be attributed to the increased awareness of the specialized medical personnel of our department. However, if this was the case, we would have expected a similar increasing trend in the incidence rates throughout the study period, a fact that was not observed. On the contrary, in the last 2 years, the incidence duplicated, suggesting additional triggers coming into play other than asthma or allergy. The identification of stressful events could not be clearly recalled in cases in which the diagnosis was delayed. The parents were asked to relate the onset of cough with a specific event retrospectively, which might have caused bias. In addition, the number of cases under study was small and thus, no clear etiologic correlation could be found between the stressors and THC. Moreover, the anxiety profile of these cases was unknown prior to the THC diagnosis, thus reported events might have acted as triggers on an unbalanced psychological background.

The mechanisms behind stress-induced THC are incompletely understood. Children, under stressful conditions, tend to reproduce a physical symptom they are familiar with, cough being the commonest during the various respiratory infections of early life (7, 24). Both the neuroendocrine and the immune systems are activated during stress as part of the adaptive response that maintains homeostasis (38-40). Stress primes neural and inflammatory processes in the brain and peripheral organs, including components of the cough reflex. In the last thirty years, ion channels of the Transient Receptor Potential (TRP) class have been implicated in the afferent sensory loop of the cough reflex and in the heightened cough sensitivity seen in disease (41). Agonists of the TRP vanilloid 1 (TRPV1) capsaicin receptor such as vanilloids and protons are amongst the most potent chemicals that cause cough. Multiple single nucleotide polymorphisms of TRPV1 gene are associated with cough sensitivity to capsaicin in healthy subjects and in cases with chronic refractory cough (42). Since it is broadly expressed in brain neurons and glia, TRPV1 acts as a regulator of neuronal activity and synaptic plasticity, through regulating long-term potentiation (LTP) and long-term depression (LTD) of synapse activity in the brain, therefore it may play a role in neurological and psychiatric disorders (43). Moreover, TPRV1 channels have been recently recognized to constitute an atypical neurotransmission system involved in functions such as addiction, anxiety, mood and cognition/learning (44, 45).

As a consequence, cough reflex is a complex neural reflex arc under both voluntary and involuntary control that is sub-served by stimulation of cough receptors in the upper and lower respiratory track. The broad knowledge is that impulses from stimulated cough receptors traverse an afferent pathway via the vagus nerve to a ‘cough center’ in the medulla oblongata (Figure 4, yellow line). The cough center generates an efferent signal that travels down the vagus, phrenic, and spinal motor nerves to expiratory muscles producing cough. However, cough is also regulated by cortical and subcortical pathways initiated by cognitive, motor and sensory neurons (46). These pathways can exert inhibitory signals suppressing cough (as during a live performance) and voluntary excitatory signals (as coughing upon request) (Figure 4, green line). Moreover, cough may be a manifestation of stress activating the fear pathway. The brain structures involved in dealing with stress and fear are the frontal cortex and the amygdala, which stimulate the stress system, including the hypothalamus, pituitary gland and adrenal cortex to release stress hormones, such as cortisol, as well as the arousal and noradrenergic centers of the autonomic nervous system in the brainstem, to release other stress hormones, such as the catecholamines (norepinephrine and epinephrine) (Figure 4, red line). Meanwhile, the activated amygdala may possibly act on the medulla oblongata via TRPV1 channels to activate the efferent limb of the cough reflex, through stimulation of the laryngeal and respiratory muscles.

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Figure 4.

Cough reflex pathways. Psychophysiology of cough is shown through the interactions of cough reflex with the cortex and subcortex. A) Cough reflex pathway (yellow areas and lines): impulses from stimulated cough receptors traverse an afferent signal via the vagus nerve to the cough center in the medulla oblongata and generate an efferent signal that travels down the vagus, phrenic and spinal motor nerves to muscles of expiration producing cough. B) Cortical and subcortical pathway (green areas and lines): cough can also be regulated by cortical and subcortical pathways initiated by cognitive, motor or sensory neurons. C) Stress and limbic pathways (red areas and lines): Frontal cortex and amygdala, the brain structures that are involved in dealing with stress and fear, stimulate the thalamus, pituitary and adrenal cortex to release stress hormone such as glucocorticoids and catecholamines. Meanwhile, the amygdala act on the medulla oblongata and the efferent limb of cough reflex, stimulating the laryngeal and respiratory muscles.

The range of cortical control falls within limits determined by involuntary self-regulatory physiologic mechanisms and vice versa, as involuntary cough can be suppressed voluntarily, while both can be modified by Pavlovian (classical) and operant conditioning procedures (47). Classical conditioning is an established method of learning, whereby a conditioned stimulus is paired with an unconditioned one. For example, a child with learning difficulties feels uncomfortable and initially starts coughing during class. Later, however, the child would cough whenever a stimulus reminds him/her of school, such as the sound of the alarm clock in the morning or the school bus bell. On the other hand, operant conditioning is a type of learning in which the strength of a behavior is modified by the behavior’s consequences, such as a reward or punishment, for instance, a child coughing may be picked up earlier from school.

Taking advantage of the direct influence and the physiologic correlation between the higher cortical areas and the lower cough reflex center, manipulation of the higher brain has been used therapeutically to suppress anxiety. Behavioral therapy has been recognized as an effective way of altering emotions in anxiety-related disorders (48). The premise behind behavioral therapy is that the unwanted behavior that was involuntarily used for a secondary gain can be un-learned. The goal is to help the child learn new, positive and distractional behaviors, which minimize or eliminate stress. The therapist teaches the child specific cognitive behavioral techniques, such as repeating positive statements, performing relaxed breathing, drinking water, registering of “cough attacks” in a calendar and escaping from or coping with a stressful activity. It should be noted that the mere reassurance that there is no serious underlying organic pathology, usually liberates the child and relieves the parents (49). When the possible stressful trigger factors are pointed out and the proper advice is followed, the psychological pressure and the cough substantially decrease, usually without recurrence. The prompt and favorable response to cognitive behavioral therapy in children further supports the diagnosis of THC (8, 10). Another proposed effective therapeutic intervention in children is the Suggestion Therapy (24, 50). On rare occasions, when family history is positive for serious psychiatric disorders, appropriate medication may be used.

In conclusion, the incidence of THC has significantly increased in recent years, reflecting the adverse consequences of modern life style, negatively affecting the health status of children. Family financial problems were found to be a new stressor for THC, but bullying seemed to be the only factor that had a close relationship with its increase, both demanding reforms in public health policy and practice. The findings of this study suggest that clinicians’ awareness of the condition is the key to diagnosis and efforts should be made to recognize THC early. The sound knowledge of the clinical criteria may discern between organic, tic and ‘somatized’ respiratory symptoms in everyday practice, thus minimizing unnecessary diagnostic procedures on one hand, and the administration of ineffective, potentially harmful, therapeutic interventions, on the other. The psychophysiological mechanisms behind stress-induced THC may involve interactions among the higher cortical areas, the amygdala and the cough reflex center, thus explaining the successful therapeutic intervention achieved by cognitive behavioral therapy. Prompt and proper diagnosis as well as psychological support of children with THC will relieve the high pressure exerted on affected families.