Original Article
Psychopathology in children and adolescents with primary headaches: Categorical and dimensional approaches
Cephalalgia 33(16) 1311–1318 ! International Headache Society 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0333102413495966 cep.sagepub.com
Francesco Margari1, Elisabetta Lucarelli2, Francesco Craig2, Maria G Petruzzelli2, Paola A Lecce2 and Lucia Margari2 Abstract Background: Recurrent headache is common in childhood, but there is not a great amount of data on the associations between headaches and psychopathology in children. Objective: The aim of this study is to examine the relationships between primary headaches and psychopathology in children, using both the categorical and dimensional assessment. Methods: The sample consisted of 70 patients with primary headache compared to a matched sample of 50 healthy children. Psychiatric comorbidity was defined according to the diagnostic criteria of the Diagnostic and Statistical Manual of Disorders. Child psychopathology outcomes were assessed using child- and parent-reported standardized instruments. Results: Internalizing and externalizing problems were significantly represented among children with headaches compared to the control group, respectively 63% and 27%, without significant differences between migraine and tension-type headache children. Moreover, a total of 26% of the children with a headache reported psychiatric comorbidity such as anxiety and mood disorders. Conclusion: The dimensional approach improves accuracy in the recognition of emotional and behavioral problems compared to the categorical approach; however, the use of both of these approaches could be useful for clinical practice, treatment and research. Keywords Primary headache, children, psychiatric comorbidity, tension-type, migraine Date received: 15 March 2013; revised: 14 May 2013; accepted: 7 June 2013
Introduction Epidemiological studies conducted over the last 50 years have shown an increased incidence of primary headaches in children and adolescents, making this disease one of the most frequent reasons for child neuropsychiatric consultation (1,2). Despite the wide differences of headache prevalence in children and adolescents reported by studies, a clear and reliable estimate of the magnitude of the problem has showed that around 60% of the children are prone to headache, with attacks of variable frequency (3). The headache begins to emerge during the early years of life, but the disorder usually becomes more evident and frequent from the impact of school life, with a peak around 7 years old (4). The prevalence of primary headaches is estimated to be around 37%–51% in school-age children and adolescents around 57%–82%, with a slight predominance in females (5,6).
Children with headaches are found to have psychopathological symptoms or psychiatric disorders in clinical practice, even though this association has been mainly studied in adults (7). Only in recent years has there been an increasing interest in the field of the relationship between headaches and psychopathology in childhood and adolescence (8). The results in this regard were not unique because the studies have used 1
Psychiatry Unit, 2Child Neuropsychiatry Unit, Department of Basic Medical Sciences, Neurosciences and Sense Organs of the ‘‘Aldo Moro’’ University of Bari, Italy Corresponding author: Lucia Margari, Child Neuropsychiatry Unit, Department of Basic Medical Sciences, Neurosciences and Sense Organs of the University of Bari ‘‘Aldo Moro’’, Hospital Polyclinic of Bari, Piazza Giulio Cesare 1, Bari 70100, Italy. Email:
[email protected]
1312 different assessment methodology, with some using dimensional measures and others categorical classification of specific psychiatric disorders (9, 10). Studies using the dimensional approach reported a relationship between primary headaches and internalizing and externalizing problems in children and adolescents (11–13). Few studies have used categorical measures to investigate psychiatric comorbidity, and they reported an increased risk of affective and anxiety disorders in children with headache, compared to the control subjects (14–16). Despite the growing literature establishing associations of headaches with psychopathology, the mechanisms underlying this relationship are presently poorly understood, but this topic remains a priority for future research. The aim of this study is to examine the presence of psychopathology in a sample of children/adolescents with primary headaches compared with healthy children, using both categorical and dimensional assessment.
Cephalalgia 33(16) blurred vision, decreased visual field, phosphenes, scotoma and diplopia were conducted. In addition, the presence or absence of neurovegetative symptoms such as nausea, vomiting, pallor, feeling hot or cold, runny nose, watery eyes, mood disturbance, insomnia or deficit disorder of speech or movement were also tested. Neurological and ophthalmology examinations were performed in all patients. Finally, we evaluated the presence of precipitating factors aggravating or relieving the headache. The control group was recruited from elementary schools, middle schools and high schools in Bari. We selected a random sampling, based on the availability of parents to participate in study, that involved 50 healthy children without a history of headaches investigated using a data collection and medical history. In both groups the familiarity for psychopathology was investigated through specific questions during the anamnesis. In the headache and control group, all details of the study procedure were explained to children/adolescents and their parents and written informed consent was obtained prior to enrollment.
Methods Subjects
Assessment
The sample consisted of 70 patients consecutively referred to the Child Neuropsychiatry Unit, Department of Basic Medical Sciences, Neurosciences and Sense Organs of the ‘‘Aldo Moro’’ University of Bari, in the period between November 2011 and January 2013. The patients were eligible if they met the following criteria: diagnosis of primary headaches in accordance with the criteria of the International Classification of Headache Disorders, second edition (ICHD-II) (16) and any symptomatic and prophylactic therapy for headaches. The diagnostic assessment involved the anamnesis, clinical observation, neuropsychological evaluation, routine laboratory tests and instrumental tests including electroencephalography (EEG) and electrocardiography (ECG). Brain magnetic resonance imaging (MRI) was performed in only some of the patients when indicated for clinical reasons. The Pediatric Migraine Disability Assessment Scale (Ped-MIDAS) (17) was conducted to calculate the level of disability associated with the pain of the patients. The assessment focused on the headache onset, duration, total number of attacks at the time of the visit, the frequency (daily, weekly, monthly) of attacks over the past six months, the average duration of attacks, the intensity of pain, the localization, the site of emergence and spread. Before, during or after the migraine attack, tests for phonophobia, tinnitus and dizziness, and visual symptoms including photophobia,
The evaluation of psychopathology was performed with both categorical and dimensional approaches. The categorical assessment of the psychiatric comorbidity was defined according to diagnostic criteria of the Diagnostic and Statistical Manual of Disorders, fourth edition text revision (DSM-IV-TR) (18). The diagnosis was formulated by a child and adolescent neuropsychiatrist on the basis of interviews with the children/adolescents and their families, medical history and clinical observation. The dimensional assessment included the administration of clinical standardized interviews and scales such as the Child Behavior Checklist (CBCL/1.5– 5, CBCL/6–18) and Youth Self-Report (YSR/11–18) (19); the Screen for Child Anxiety Related Disorders (SCARED) (20); the Children’s Depression Inventory (CDI) (21); and Conner’s Parent Rating Scale-Revised (CPRS-R) (22). The CBCL is a questionnaire completed by the parents that assesses emotional and behavioral problems of children and adolescents. The questionnaire consists of two parts, ‘‘powers’’ (business, social and school) and ‘‘emotional and behavioral problems,’’ identifying two types of problems: ‘‘internalizing’’ symptoms included in the subscales of anxiety, depression, social withdrawal and somatic complaints, and ‘‘externalizing’’ with manifestations of aggression and antisocial behavior. The SCARED is a self-administered questionnaire consisting of 41 questions about feelings of anxiety during the last three months. A score equal to or
1313
Margari et al. greater than 39 is considered indicative of clinical impairment. The CDI is a self-assessment scale derived from the Beck scale, and assesses the severity of depressive symptoms during the previous two weeks in children between 7 and 17 years. A 19-point cut-off indicates the ideal threshold discriminating children at risk of depression from the nondepressed children. The CPRS-R is a self-administered questionnaire composed of 80 questions based on behavioral problems during the last month, in a group where the ages range from 3 to 17 years. Scores equal to or greater than 65 are considered indicative of clinical impairment.
between 4 and 17 years old (11.05 2.7), matched to age (p ¼ 0.458) and gender (p ¼ 0.439). In the control group, family history was present for the following diseases: headaches in 14 patients (28%), mood disorder in four patients (8%) and anxiety disorder in one patient (2%). The analysis of the neuropsychiatric family history revealed a statistically significant difference between children with headaches and the control group for anxiety disorders (p ¼ .005, OR 9.28) headache (p ¼ .000, OR 2.85) and epilepsy (p ¼ .034) (Table 1).
Data analysis
A total of 44 children (63%) with primary headaches showed internalizing problems, 19 patients (27%) showed externalizing problems and 20 patients (29%) did not show psychopathology problems. A simultaneous presence of internalizing and externalizing problems was shown in 7% of patients. In the control group, six children (12%) reported internalizing problems, six children (12%) reported externalizing problems and 38 children (76%) did not report psychopathological problems. A simultaneous presence of internalizing and externalizing problems was shown in 3% of children of the control group. The finding reveals a statistically significant difference between patients affected by primary headaches and the control group in internalizing problems (OR: 14.6, 95% CI: 3.6–83.0, p ¼ 0.001) and externalizing problems (OR: 12.9, 95% CI: 1.6–573.5, p ¼ 0.003). In children with TTH, 16
All demographic and clinical variables were subjected to statistical analysis. Descriptive analysis was conducted for socio-demographics featuring two samples. To compare age and gender between the headache and control group, we used respectively Student’s t tests and Fisher’s exact test. The chi-square independence (2) was used to examine the difference of psychopathology in a sample of children/adolescents with primary headaches compared with healthy children/adolescents. In addition, to investigate the relation of psychopathology with severity of headache, frequency of attacks, and sleep disturbance, the chi-square test was performed. Where possible, it was calculated with odds ratio (OR) with 95% confidence intervals (95% CI). Statistical significance was considered for p values 0.05. We used the statistical program Statistical Package for Social Science 20.
Results The sample consisted of 70 patients, 42 (60%) females and 28 (40%) males between the ages of 3 and 17 (10.47 2.7). Forty-two patients (60%) received a diagnosis of migraine, and 28 patients (40%) were suffering from a tension-type headache (TTH). The average age for the headache onset was 8 years old. No patient showed a neurological deficit or routine laboratory abnormalities and brain MRIs were normal in all patients. In the headache children, family history was present for the following diseases: headaches in 56 patients (80%), anxiety disorders in 13 patients (18.5%), mood disorder in 12 patients (17%), epilepsy in six patients (8.5%) and schizophrenia in one patient (1%). The family history of neuropsychiatric disorders was higher in the subjects with migraine (24%) compared to the TTH patients (11%), but there was not a statistically significant difference (p ¼ 0.3, OR 1.70). The control group consisted of 50 healthy children, 20 (40%) females and 30 (60%) males with ages ranging
CBCL
Table 1. Socio-demographic characteristics and family history of neuropsychiatric disorders.
Sex N (%) Male Female Age Diagnosis Migraine Tensive NP family history Headache Anxiety Mood Epilepsy Schizophrenia Total
Headache N ¼ 70
Control N ¼ 50
28 (40%) 42 (60%) 10.47 2.7
30 (60%) 20 (40%) 11.05 2.7
.439 — — .458
42 (60%) 28 (40%)
— —
— —
56 (80%) 13 (18.5%) 12 (17%) 6 (8.5%) 1 64 (91%)
14 (28%) 1 (2%) 4 (8%) 0 0 19 (38%)
.005a .000a .1 .034 — .0001a
NP: neuropsychiatric. ap < .005.
p
1314 patients (57%) showed internalizing problems and seven patients (25%) showed externalizing problems. In children with migraine, 28 patients (67%) showed internalizing problems and 12 patients (28%) showed externalizing problems. Internalizing problems were more frequent in migraine patients compared to the TTH patients with a statistically significant difference (p ¼ 0.002). No statistically significant difference was found in externalizing problems (p ¼ 0.4) between migraine and TTH children. Analyzing the relation of psychopathology with severity of headache, frequency of attacks and sleep disturbance, we found a statistically significant difference between psychopathology (internalizing and externalizing symptoms) in severity of headache (p ¼ 0.004) and frequency of attacks (p ¼ 0.031), but no statistically significant difference in sleep disturbance was found. Children with internalizing symptoms were mainly distributed in the group with mild severity and with weekly frequency, children with externalizing symptoms were mainly distributed in the group with moderate severity and with monthly frequency, and children without psychopathology were mainly distributed in the group with high severity and with daily frequency.
SCARED Seventeen patients (24%) with primary headaches showed anxiety disorder, and no child in the control group exceeded the cut-off for anxiety disorder. A statistically significant difference between patients affected by primary headaches and the control group was found (p < 0.001). Children with anxiety symptoms reported more sleep disturbance (p ¼ 0.012) compared to children without anxiety symptoms. No statistically significant difference in severity of headache and frequency of attack were found.
CDI Six patients (9%) with primary headaches showed depressive disorder; in the control group no child presented depressive disorder. A statistically significant difference between patients affected by primary headaches and the control group was found (p ¼ 0.004). No statistically significant differences between children with and without depressive symptoms in severity of headache, frequency of attacks, and sleep disturbance were found.
CPRS-R Thirty-four patients (49%) were in the normal range, 15 patients (21%) were in the clinical range for anxiety and
Cephalalgia 33(16) somatization disorders, and 26 patients (37%) were in the clinical range for inattention and hyperactivity disorders. In the control group 44 children (88%) were in the normal range and six children (12%) were in the clinical range for inattentive/hyperactivity disorder. The finding reveals a statistically significant difference between patients affected by primary headache and control groups for anxiety and somatization disorders (p ¼ 0.001) and inattentive/hyperactivity disorder (OR: 4.1, 95% CI: 1.21–16.22, p ¼ 0.01). We found a statistically significant difference in severity of headache (p ¼ 0.005), but no statistically significant differences in frequency of attack and sleep disturbance were found. Patients with anxiety and somatization disorders were mainly distributed in the group with moderate severity of headache, patients with inattentive/ hyperactivity disorders were mainly distributed in the group with high severity, and children without psychopathology were mainly distributed in the group with moderate severity. The prevalence of psychiatric disorders and psychopathologies is shown in Table 2 and the relationship between psychopathology with severity of headache, frequency of attacks and sleep disturbance in Table 3. Psychiatric comorbidity, diagnosed according to the criteria of the DSM-IV-TR, was found in 18 patients (26%), in particular 16 patients (23%) reported anxiety disorders and two patients (3%) mood disorders. Anxiety disorders were represented by generalized anxiety in 14 patients (20%) and separation anxiety in two patients (3%). Patients with mood disorders reported a major depressive episode in one patient (1.4%) and a
Table 2. Prevalence of psychiatric disorders and psychopathologies in the groups.
CBCL Internalizing Externalizing SCARED CDI CPRS-R Anxiety Inattentive/restless DSM-IV diagnosis Anxiety disorders Mood disorders
Headache Number (%)
Control Number (%)
p 2
44 (63%) 19 (27%) 17 (24%) 6 (9%)
6 (12%) 6 (12%) 0 0
.000a .003a .000 .004a
15 (21%) 26 (37%)
0 6 (12%)
.001a .01a
16 (23%) 2 (3%)
0 0
.001a .126
CBCL: Child Behavior Checklist; SCARED: Screen for Child Anxiety Related Disorders; CDI: Children Depression Inventory; CPRS-R: Conner’s Parent Rating Scale-Revised; DSM-IV: Diagnostic and Statistical Manual of Disorders, fourth edition. ap < .005.
1315
Margari et al. dysthymic disorder in one patient (1.4%). No psychiatric disorders were reveled in the control group. The finding showed a statistically significant difference between patients with headache and control group in anxiety disorders (p < 0.001); no statistically significant difference was found in mood disorders (p ¼.126). In children with TTH, 11 patients (16%) reported anxiety disorders and two patients (3%) showed mood disorders. In children with migraine, five patients (7%) showed anxiety disorder. Psychiatric comorbidity was higher in children with TTH compared to children with migraine, but no statistically significant difference was found.
Discussion Children with primary headaches have an increased risk for emotional and behavioral problems, as epidemiological and clinical studies have showed. However, psychopathological manifestations in headaches have been studied more in adults and much less in children (8), although children with headaches are frequently found to have psychopathological symptoms or psychiatric disorders in clinical practice. On the other hand, psychopathology in children differs from adults in many ways (23). First, the assessment of psychopathology comorbidity in children and adolescents requires multiple sources of information, such as parents, teachers and children themselves, but often the modest agreement found among sources makes the diagnosis of
children difficult. Moreover, another salient difference is that the expression of psychopathology in children often influences the overall development progress. In fact, the assessment of psychopathology in the developmental age must take into account age-related changes, because a behavior that is considered pathological at one age may be considered normal at another age and vice versa. The first edition of the International Classification of Headache Disorders (24) reported that psycho-social stress, anxiety and depression might be the probable leading cause of TTH; these factors were not mentioned in migraine. In the second edition of the ICHD (2004) (16) no causal link between psychological factors and TTH or migraine was described, but a new category named ‘‘headache attributed to psychiatric disorders’’ was introduced in the appendix without a definition of the specific clinical characteristics of the disorder. In the criteria for the diagnosis of ‘‘headache attributed to psychiatric disorders,’’ the headache must occur exclusively during the course of the psychiatric disorders. In the classification it is emphasized that the introduction of this type of headache has the aim of facilitating the research regarding the relationships between specific psychopathology and headache. Studies that have assessed psychopathology in children with headache have varied in the definition of clinical problems, with some using more dimensional measures and others using categorical classifications. However, the majority of studies assessing psychopathological symptoms in
Table 3. Relation between psychopathology with frequency of attacks, severity of pain, and sleep/wake disturbances. Severity
CBCL Internalizing Externalizing Absent SCARED Anxiety Absent CDI Depressive Absent CPRS-R Anxiety Inattention and hyperactivity Absent
Frequency
Sleep/wake Disturbances
Mild
Moderate
High
p
Daily
Weekly
Monthly
p
Presence
Absence
p
33% 3% 0
20% 18% 16%
10% 6% 13%
.004a — —
8% 4% 14%
30% 12% 13%
24% 11% 2%
.031a — —
35% 17% 20%
27% 10% 9%
.081 — —
3% 14%
17% 34%
4% 28%
.3 —
4% 23%
10% 36%
10% 17%
.29
14% 66%
10% 10%
.012a
0 19%
7% 47%
2% 25%
.286 —
2% 26%
4% 41%
3% 24%
.825 —
9% 71%
0% 20%
.2
0 9% 5%
14% 10% 30%
7% 18% 7%
.005a — —
8% 10% 10%
11% 17% 15%
2% 10% 17%
.210 — —
19% 29% 28%
2% 8% 14%
.08 — —
CBCL: Child Behavior Checklist; SCARED: Screen for Child Anxiety Related Disorders; CDI: Children Depression Inventory; CPRS-R: Conner’s Parent Rating Scale-Revised. ap < .005.
1316 children with headache have used dimensional measures, usually supported by psychodiagnostic tools such as the CBCL. These studies found that children with headache compared to healthy children reported a greater presence of emotional and behavioral problems, including internalizing symptoms (somatic complaints, anxiety and depression) and externalizing symptoms (hyperactivity, aggressive behavior and conduct problems) (11,12,25). In agreement with these studies, we also found a higher prevalence of internalizing and externalizing disorders in children with primary headaches compared to the healthy subjects. Some studies have shown higher psychopathology symptoms in migraine children compared to subjects with TTH, with a prevalence of internalizing problems (26,27); other authors have found increased psychopathology symptoms, both internalizing and externalizing, in children with TTH compared to children with migraine (11). Bag et al. found a high presence of psychological symptoms, particularly depression, anxiety and hostility, in subjects with headaches compared with the control group, but the authors did not find significant differences between migraine and TTH children (27). Recently, Balottin et al., in a quantitative meta-analysis of studies that have investigated the psychopathological symptoms in children with headache, found that migraine patients reported more psychopathological problems, both internalizing and externalizing, compared to the healthy controls, while patients with TTH had more psychopathological problems, only in the internalizing symptoms area, compared to the controls (8). Our study showed a statistically significant difference of internalizing problems in migraine children compared to subjects with TTH, while no difference was found for externalizing problems. However, the association between each type of primary headache and psychopathology symptoms remains a controversy. Few studies have used categorical measures to investigate psychiatric comorbidity in children with headache, and these studies were performed in patients with migraine. Some authors reported an increased risk of affective and anxiety disorders in children with migraine, compared to the control subjects, with a higher frequency of major depression disorder or bipolar disorder (14,15). Pakalnis et al. found that oppositional defiant disorder and ADHD were found more frequently in headache children than in healthy children (28). Costello et al. analyzed children with psychiatric disorders (depression, anxiety, somatization) and identified a presence of headaches in 20.5% of the subjects versus 9.2% of pre-adolescents without psychiatric diagnosis, with a higher prevalence in females, indicating the presence of more intense and frequent headaches in cases where there were depression symptoms (29). Breslau et al. demonstrated in adults a
Cephalalgia 33(16) bidirectional association in which major depression increased the risk for migraine and the migraine increased the risk for major depression (30). In addition, psychiatric disorders, represented by affective and anxiety disorders, were mainly present in children with chronic headache (31). In our study we used both dimensional and categorical assessment. Internalizing symptoms were detected in 63% of the patients compared to 12% of the control group; externalizing symptoms were present in 27% of the patients compared to 12% of the control group. According to the criteria of DSM-IV-TR, we found the presence of anxiety disorders in 23% of the patients and mood disorder in 3% of the patients without statistically significant difference between migraine and TTH. No psychiatric disorders were revealed in the control group. This study showed that internalizing disorders in few cases met the criteria for a categorical diagnosis of anxiety and mood disorders, while the externalizing symptoms were not enough to meet the criteria for a categorical diagnosis in any cases. This means that the dimensional approach improves accuracy in the recognition of emotional and behavioral problems compared to the categorical approach. In fact, dimensional tools allow the identification of problems that may be neglected by the categorical approach. However, through the use of CBCL, caution must be applied in the interpretation of internalizing symptoms in children with headache, because the scale assesses somatic symptoms, including headache and vomiting, which cannot be excluded from the scoring of internalizing symptoms. Nevertheless, the finding underlines the impact that the use of dimensional diagnosis would have on research and clinical practice. Categorical measures are used to determine if sufficient criteria are present to suggest a specific psychiatric disorder. Researchers usually take the categorical approach into consideration in order to have understandable outcome measures and to consider eligibility for clinical trials. However, several authors have emphasized common limitations of the categorical approach that include: relationship between diagnostic categories, heterogeneity, diagnostic overlap and the lack of a clear boundary between normality and abnormality. In this view, the ICHD-II category of headache attributed to specific psychiatric disorders is limiting because the headache appears to be exclusively a symptom of a psychiatric disorder. Therefore, an adequate investigation of the relationship between the two disorders in terms of comorbidities is not discussed. On the other hand, these considerations regarding the categorical and dimensional approach could contribute to a better understanding of the underlying causal mechanisms in relationship between headaches and psychopathology that are not currently well known, and the
1317
Margari et al. studies in this regard have so far mainly focused on migraine. Migraine is a complex, polygenic and multifactorial disease, wherein genetics and biology interact with environmental factors (32). In the current study, the occurrence of headaches, anxiety disorders and epilepsy in family history (Table 1) strongly suggests a common genetic predisposition among these diseases. On the other hand, the statistical analysis of our data showed that headache children without psychopathology, investigated with the CBCL, are distributed mainly in the group with high gravity and daily frequency of headache. In addition, using the CPRS-R, headache children without psychopathology are distributed mainly in the group with moderate severity. Moreover, using the SCARED and CDI, no statistically significant difference in severity of headache and frequency of attack were found in children with anxiety and depressive symptoms. These findings suggest that psychopathological symptoms are not directly correlated to headache. Recent evidence reported that noradrenergic, serotoninergic and dopaminergic systems are involved in migraine (33,34); furthermore, it is known that the dysregulation of serotoninergic, noradrenergic and dopaminergic systems may also play a role in emotional and behavior disorders
(35,36). This suggests that the relationship between migraine and psychopathology may be due to a shared neurotransmitter system involvement. For this reason, further research is needed to determine the homogeneous symptoms of psychopathology profiles in order to define pathophysiological mechanisms common with primary headaches and not only in a context of categorical psychiatric diagnosis that seems to be less suitable in children. In conclusion, the higher prevalence of psychopathology problems detected with dimensional measures emphasizes the need for cognitive, emotional and behavioral assessment in clinical practice to improve planning of treatment that should not be restricted only to headache but must also include the resolution of psychopathology symptoms. Moreover, the investigation of psychopathology profiles in headache children, using dimensional approaches, could offer evidence to better understand the mechanisms underlying the cause-and-effect relationship between headaches and psychopathology. Many unanswered questions remain on the nature of the relationship between headaches and psychopathology, but the use of a dimensional approach could be useful for clinical practice, treatment and research.
Clinical implications . Children with headaches are found to have psychopathological problems in clinical practice. . Explore relationships between primary headaches and psychopathology in children. . Categorical and dimensional assessment. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Conflict of interest None declared.
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