Personality in Chronic Headache: A Systematic Review with Meta-Analysis

Background Chronic headache (CH) is a condition that includes different subtypes of headaches and that can impair different life domains. Personality traits can play a relevant role both in the development and in coping with this medical condition. The first aim of the present study is to realize a systematic review of the personality traits associated with CH compared to healthy controls; the second objective is to carry out a quantitative meta-analysis with the studies using the same instrument to assess personality traits. Method The literature search encompassed articles published from 1988 until December 2022 on the major databases in the field of health and social sciences: PubMed, Scopus, PsychInfo, and Web of Science. Results Thirteen studies were included in the systematic review, but only three studies were deeply explored in a meta-analysis since the only ones used a common instrument for personality assessment (Minnesota Multiphasic Personality Inventory). According to the meta-analysis, different subtypes of CH patients scored higher than healthy controls on Hypochondriasis and Hysteria Scales. The systematic review showed higher levels of depressive and anxious personality dimensions and pain catastrophizing in CH compared to healthy controls. Moreover, frequent-chronic forms and medication-overuse headache were the most symptomatic and frail categories showing higher levels of dysfunctional personality traits and psychopathological symptoms. Conclusions These results seem to confirm a “neurotic profile” in patients suffering from CH. The identification of the main personality traits involved in the onset and maintenance of headache disorders represents an important objective for developing psychological interventions.


Introduction
Chronic pain (CP), defned as pain lasting more than 3 months, is a signifcant healthcare challenge with considerable economic costs and psychological burden.Prevalence rates of CP vary between 11% and 40% [1], with chronic headache (CH) representing a consistent group of afected people.Te 3rd edition of the International Classifcation of Headache Disorders (ICHD) [2] identifes diferent subtypes of chronic headache (CH), all characterized by the presence of headache on >15 days/month.Tese subtypes include chronic migraine (CM), chronic tension-type headache (CTTH), and medication-overuse headache (MOH) [2].Te prevalence in the general adult population of CM is about 2%, that of CTTH ranges from 1.7% to 2.2%, and that of MOH is 1-2% [3][4][5][6].
Te investigation of psychiatric comorbidity in headache disease dates back to the beginning of the 90s [7], with a focus on the role of anxiety and mood disorders in migraines.Te association among migraine, anxiety, and depression is strong, both in clinical and community samples [8].However, this comorbid association is not specifc to migraine, but it has been evidenced in patients with CH as well [7].Although estimates can difer, about 47% of population-based samples of people with migraine reported comorbid depression, and about 58% sufer from comorbid anxiety [9][10][11].Both these psychopathological conditions are more represented in people with CM compared to people afected by episodic forms [9,11,12].Moreover, people with episodic migraine (EM) having comorbid depression are more likely to progress to CM in the following year, thus confguring depression as a risk factor for disease synchronization [9,13].Sufering from both migraine and psychiatric disorders (i.e., anxiety and depression) denotes worsened symptomatology for each condition with greater health expenditures and medication use compared to migraineurs without psychopathological comorbidities, reduced quality of life (QoL), and increased burden and frailty associated with migraine [9,14,15].However, the specifc mechanisms and the exact direction (headache causing anxiety/depression or vice versa) of this association remain unknown.According to the biopsychosocial model of health [16,17], it exists a complex interaction between psychological, psychosocial, and biological aspects, reciprocally infuencing each other.Consequently, the expression of headache/migraine is not fxed for all suferers, as it results from the interaction of these factors, which can negatively infuence the course of the disease and enhance dysfunctional pain processing.
In this light, personality represents a relatively stable pattern of thinking, feeling, or behaving that tends to be consistent over time and across relevant situations [18].Accordingly, personality denotes the kind of adaptation the individual shows to the external environment and the related lifestyle patterns [19].Over time, many theories on personality structure have been proposed [20], and in both the clinical and reasearch area, the most widely employed are (a) the psychobiological model [21], considering seven dimensions that are novelty seeking, harm avoidance, reward dependence and persistence, self-directedness, cooperativeness, and self-transcendence, (b) the Big Five Model [22], exploring fve main dimensions that are extraversion, agreeableness, conscientiousness, negative emotionality, and openness to experience, and (c) the Eysenck's three-factor model [23], focusing on three main dimensions that are extraversion, neuroticism, and psychoticism.Tese classifcations and the other most important systems of organization of psychopathology share the model of continuity, where the pattern of infexibility, rigidity, and pervasiveness leads to shape personality traits into personality disorders [19,24].Te continuum means that at one end, there are individuals showing a good psychological functioning in every domain, and at the other end, people who respond with infexibility (in cognition, afectivity, interpersonal functioning, and impulse control levels) to the life demands.Te role of personality has been increasingly shown as infuencing the chronic progression of some disorders, and it has been linked to the clinical outcome of headache and MOH as well.Indeed, personality contributes to shape behavioural/life-style patterns that may trigger headache attacks [25].Hence, the study of the associations between personality and headache has received a growing interest in the literature over time [26][27][28].Investigations aimed to compare personality traits in subgroups with diferent headache diagnoses have highlighted that patients with chronic headache and MOH are more likely to be socially introverted compared to episodic headaches patients [29,30].In this direction, Silberstein and colleagues [27] found that migraine patients often have a higher level of neuroticism and vulnerability to negatively afect compared to controls.In the same direction, diferent studies reported that migraineurs tend to show higher scores in neuroticism than controls [19,20,31].A recent metaanalysis [20] demonstrated the existence of specifc personality traits in migraine, reporting, respectively, higher and lower levels of neuroticism and extraversion (evaluated according to the three-factor model) in migraineurs compared to controls.Moreover, higher levels of harm avoidance, persistence, and lower of self-directedness (evaluated according to the psychobiological model) emerged in migraineurs compared to controls.
Recent evidence reported that personality predicted the response to drug treatment, inasmuch as the early detection of personality characteristics could improve the management and outcome of CM [32,33].Tus, the study of personality may give new insights and ways to plan psychological interventions for headache patients and comprehend patterns driving psychiatric comorbidity.
Te principal aim of the present study is to realize a systematic review focusing on the specifc personality traits associated with CH compared to healthy controls (phase one).In this light, personality refers to enduring characteristics afecting an individual's behaviour and explaining consistencies across diferent life domains and situations.A second aim is to realize a quantitative meta-analysis with the studies that used the same instrument to assess personality (phase two).

Phase One: Systematic Review and
Qualitative Meta-Analysis

Search Strategy.
To include the broadest range of relevant literature, the electronic literature search was conducted by using major databases in the feld of health and social sciences: PubMed, Scopus, PsychInfo, and Web of Science.Te search was performed using the following keywords: "chronic migraine" OR "chronic headache" OR "medication overuse headache" OR "high frequency migraine" OR "chronic tension-type headache" OR "continuous headache" OR "frequent migraine" OR "refractory headache" OR "refractory migraine" OR "persistent headache" AND personality OR temperament OR "personality disorder" OR "psychometric" OR "psychogenic" OR "psychological".Te search was limited to English-language journal articles and was adapted for each database as necessary.We limited our search to the period from 1988 to the present to include only papers with International Headache Society criteria.Moreover, we performed an additional 2 Pain Research and Management analysis of each reference list in each selected paper to ensure that all signifcant papers were included in the review (see Figure 1).Te electronic bibliographic search was conducted in December 2022.Te present review was not registered.
( Te exclusion criteria were as follows: (a) case reports, conference proceedings reviews, and studies reported in letters to the editor; (b) studies that enrolled children and adolescents; (c) studies that did not specify the selection criteria.
Study selection was performed by three independent reviewers who assessed the relevance of the studies' questions and objectives.Tis frst round of selection was based on the title, abstract, and keywords of each study.Duplicate studies were removed from the list.If the reviewers did not reach a consensus or the abstracts did not contain sufcient information, the full text was reviewed.In the second phase of the study selection process-based on the papers' full text-we tested whether the studies met the inclusion criteria.Discrepancies between reviewers were resolved by a process of discussion/consensus building by a third reviewer.When the full text was not retrievable, the study was excluded.
A standardized data extraction form was prepared, and data were inserted by the three independent reviewers in a study database.Te form included the following information: title, year of publication, numbers of patients and healthy controls, gender ratio, IHS criteria used to classify migraine, tools used in the psychometric assessment, study design, signifcant fndings, and notes and/or comments on the study fndings and/or design.

Risk of Bias.
Quality assessment of each study included in the systematic review was evaluated according to the Newcastle-Ottawa Scale (NOS) for case-control studies method that is based on a 9-star model [34].Studies scoring above the median NOS value were considered as high quality (low risk of bias), and those scoring below the median value were considered as low quality (high risk of bias) [35].Tree judges (SB, FG, and AR) independently extracted the information from all eligible reports useful to meet the above inclusion criteria.
Six studies obtained a median NOS value of 5, fve studies were above it, and two were below the median value (Table 2).Tus, fve studies were quoted as having high quality (low risk of bias) according to the NOS method (see Table 2).

Studies Selection.
Tree studies assessed personality according to the MMPI.Galli et al. [40] and Sances et al. [39] assessed personality by using the MMPI on MOH patients, whereas Aguirre et al. [36] used it on CTTH patients, which were considered as reference groups and compared with healthy controls.Furthermore, Galli et al. [40] included also a group of substance addicts, which was excluded from the analysis (see Table 2).

Statistical
Analysis.Data were analysed using R 4.0.2.We computed the efect sizes (ES) from considered studies, according to means and standard deviations, using Cohen's d approach.Negative values indicated that headache had lower scores than controls in the considered outcome.Conventionally, it is considered that a value of Cohen's d < 0.20 indicates a small efect size (ES)=0.5, a medium ES, and >0.80, a large ES.For each efect size, we computed 95% CI, variance, standard error, and statistical signifcance.Te random-efects model was used since it allows accounting for diferent sources of variation among studies in a conservative way.Statistical heterogeneity was assessed with Q and I 2 .A signifcant Q value represents a lack of homogeneity of fndings among studies, whereas I 2 allows estimating the proportion of observed variance refecting real diferences in ES.I 2 is used, which usually is considered as a value of low (25%), moderate (50%), and high (75%) heterogeneity.Q has small statistical power in small meta-analysis, whereas I 2 is independent of the number of studies.Te heterogeneity among considered studies is partially tackled by the choice of the randomefects model.Trough the funnel plot and Egger's performed whenever possible (with reference to the small number of studies in the analysis), the publication bias was estimated.

Personality Profle according to MMPI: Clinical Scale.
Forest plots for MMPI clinical scales are reported in Table 3.

Discussion
Te present study focused on the investigation of personality traits that characterized patients sufering from CH compared to healthy controls.Tirteen studies were included in the systematic review, and three of them were explored in a meta-analysis, since in these studies, the same personality   Te criterion is refected in the study.* * Two stars were assigned when the control was matched not only for age and gender.
12 Pain Research and Management   Pain Research and Management inventory has been employed: the MMPI.As regards the studies included in the meta-analysis [36,39,40], all reported that the CH patients scored higher than healthy controls in hypochondriasis and hysteria [46,47].Since the CH patients evaluated in the three studies sufered from MOH or CTTH, it is possible to hypothesize that these personality traits are common to diferent categories of CH patients.Tis result appears to be coherent with those of previous studies on the evaluation of personality traits in headache patients through the use of MMPI that highlighted the presence of a "neurotic profle" [46,47].According to this profle, headache patients are characterized by high levels of depression, hypochondria, and hysteria [29,39,48].
In our meta-analysis, higher levels of depression emerged only in two studies: Sances et al. [39] and Aguirre et al. [36].However, depression, though evaluated through diferent tools, is highly represented in this clinical population (see Table 1).In Rausa et al. [46], the "neurotic triad" emerged only in patients with psychiatric comorbidity, while patients without psychiatric comorbidity displayed a high score only in the hypochondriasis subscale, indicating high concerns for their health status as the most central personality trait.However, the presence of the "neurotic profle" in CH [39,40] has been considered a reaction to the chronic pain rather than a specifc personality trait characterizing headache patients [49].In this direction, hypochondriasis, characterized by a preoccupation of having a serious illness based on misrepresentation of bodily sensation persisting to reassurance [50], appeared to be commonly associated with somatization, chronic pain, and the severity of pain [50].
On the contrary, clinical and control subjects constantly did not report any diference in hypomania and psychopathic deviation.It can be hypothesized that these traits could be more relevant in people sufering from mental health problems, as they can predispose individuals to develop other disorders, instead of somatic problems such as headache.In this direction, headache patients showed a level of functioning comparable to those of healthy controls.
Moreover, only Aguirre et al. [36] found diferences between clinical and control subjects as regards Social Introversion Scores.It should be noted that Aguirre et al. [36] explored personality traits in CTTH, whereas Galli et al. [40] and Sances et al. [39] in MOH.Terefore, it may be hypothesized that the social introversion could be a peculiar trait of CTTH.Specifcally, tension-type forms seem to originate in emotional difculties and stressful conditions, as may be the social circumstances; thus, individuals sufering from these forms may be more likely to avoid the situation that may provoke tension and headache thus resulting in more social introversion.Moreover, this seems to be in line with Barton-Donovan and Blanchard's [51] results that reported a higher score of social introversion in CH patients compared to less severe migraine forms.
In conclusion, the studies included in the meta-analysis [36,39,40] seem to defne CH patients' personalities as characterized by neurotic concern over bodily functioning, hysteria, and/or physical complaints.Shyness and tendency to withdraw from social contacts and responsibilities characterize CTTH patients.
All the studies that investigated depressive and anxious personality traits constantly found higher scores in clinical groups compared to healthy controls [19,37,[41][42][43][44][45].Tis seems to highlight that the headache clinical population is characterized by a reduced hope in the future and general dissatisfaction with one's life, as well as the tendency to perceive things as threatening where others might not.Tese fndings appeared to be in line with the broader literature reporting high levels of depression and anxiety in this clinical population as principal psychological comorbidities [52,53].
A further personality trait investigated in headache patients is the pain catastrophizing [41,42,45] being characterized by exaggerated and negative cognitive and emotional schema brought to bear during actual or anticipated painful stimulation, the tendency to magnify or exaggerate the threat value or seriousness of pain sensations, and helplessness and ruminative thinking about pain.High levels of pain catastrophizing in headache patients and catastrophizing about consequences of somatic symptoms seem to afect headache pain intensity also [54].
As regards diferences between subcategories of patients, it should be noted that MOH patients seem to be the most pathological/frail ones with scores constantly higher than migraine and TTH in hypochondriasis, health concerns, depression, hysteria, pain catastrophizing, neuroticism as the tendency to frequently experience negative emotions, and anxiety and afect regulation disorders (see Table 1).Moreover, MOH patients reported lower levels of openness, agreeableness, and consciousness that are generally considered functional personality traits (see Table 1).Such a "more complicated" characterization of MOH patients is in line with previous studies [33,[55][56][57] showing the causative role of psychological and psychosocial aspects in the development and perpetuation of this condition.
Consistent with previous fndings, patients sufering from frequent or chronic forms of both migraines and TTH resulted characterized by higher levels of dysfunctional traits and symptoms than episodic forms [51].
Te present investigation should be interpreted in the light of some limitations.First, the diferent instruments used for assessing personality traits and dimensions.Tis clinical heterogeneity made it difcult to draw frm conclusions; however, all studies included validated measures of personality; thus, a scientifc criterion has been respected.A further limit is in the sample size of the studies since some of them included a limited clinical sample (n ≤ 65 participants) whereas others included a control group with a lower number of individuals compared to clinical subjects or vice versa.A third limit regards the gender, as unfortunately, data were not constantly available for men and women separately.Lastly, the cross-sectional nature of the studies does not allow us to draw conclusion on the direction of the association that emerged since it is not possible to conclude whether some personality traits play a role in the development of headache disorders or the prolonged pathological condition causes some changes in personality as a maladjustment to pain.Longitudinal studies are needed to draw frm conclusions on the role of personality in the evolution 16 Pain Research and Management and outcome of headache disorders.In addition, it should be considered that although, to date, there are a large number of works devoted to the investigation of personality in headache, only a small number of these have used validated diagnostic criteria and assessment tools.Consequently, more methodological rigor would be needed in the future so as to obtain comparable data.
4.1.Conclusions.In conclusion, the results of this literature review with meta-analysis provide evidence supporting that MOH and CTTH are characterized by higher levels of dysfunctional personality traits and psychopathological symptoms.Insufcient evidence was available for CM.Te principal personality traits involved in the onset are identifed, and the maintenance of headache disorders seems to be important for the disease in order to develop specifc psychological intervention programs positively infuencing the health status of headache suferers and improving their quality of life.

Table 3 :
Forest plot for clinical scales of the Minnesota Multiphasic Personality Inventory (MMPI) for chronic headache patients (case) and controls.

Table 1 :
Characteristics of primary studies included in the meta-analysis.

Table 2 :
Risk of bias of the included studies.