We searched the PubMed database to identify relevant publications. To make the process of searching more efficient, we added PubMed filters to find clinical trials, meta-analyzes, randomized controlled trials, and systematic reviews. Additional filters included articles published after November 1st 2006, available in English. Medical subject headings (MeSH) were used to develop a literature search strategy (Moher et al., 2009; Shamseer et al., 2015) as follows: each of three synonymous phrases, i.e., (1) masticatory muscle pain, (2) masticatory myofascial pain, and (3) myofascial pain syndrome, were combined with each mental status: (a) anxiety, (b) depression, (c) mood disorders, and (d) stress-related disorders, e.g., “masticatory muscle pain anxiety,” viz. (1)+(a); “masticatory muscle pain depression,” viz. (1)+(b); “masticatory myofascial pain mood disorders,” (2)+(c), etc. In this way, we obtained 12 queries. We also screened the reference list of included studies to trace potentially relevant papers.

Three authors were involved in the literature screening procedure (MW, JS, and NG). Firstly, the titles, abstracts and full texts were screened independently by two of these authors (JS and NG). Then, the full texts of potentially suitable articles were screened for key words, such as “masticatory,” “myofascial,” “orofacial,” “facial,” “pain,” “temporomandibular,” “masseter,” “temporalis” “myogenous,” “muscle,” “anxiety,” “depression,” “stress,” and “mood,” and the articles were then evaluated for their relevance in the context of the research question. The next step of paper selection involved a final evaluation of relevance and practical validity regarding the relationship between mental status and MMP. Eventually, the three authors jointly decided whether the identified articles met the inclusion criteria. Neither of the review authors was blind to the journal title or to the study authors or institutions (Tricco et al., 2012; Shamseer et al., 2015).

After the final agreed decision, two reviewers conducted data extraction independently (JS, NG). Then, the third author (MW) checked the validity of all data extracted. The extraction process included information regarding study design, sample characteristics and size, diagnostics criteria, comparison groups, outcomes and tools used to measure those outcomes.

The studies included in our systematic review are very heterogeneous. As a consequence, performance of a meta-analysis was impossible. We conducted a “narrative, qualitative summary” as recommended (Mao et al., 2015). The quality evidence for results was assessed employing the Grading of Recommendations Assessment, Development and Evaluation working group approach (Young et al., 2012; Shamseer et al., 2015)¹. The quality evidence for each outcome was assessed as one of the following categories: very low, low, moderate or high.

According to the above search protocol, we obtained 2,275 results from searches conducted up to and including October 2016. Thirty-nine articles were included. Although, we searched for clinical trials, meta-analyzes, randomized controlled trials, and systematic reviews, we did not find such types of studies. The main reasons for exclusion were study design (review articles and not systematic reviews), studies' relationship to the therapy of TMD (not accompanied by mental status reports), and mention of the research topic, however only in the introduction or discussion. The systematic review protocol is presented as a flow-chart in Figure 1. Most studies confirmed the relationship between MMP and at least one mental state, but there were also two studies that definitely did not support any of mentioned assertions (Nilsen et al., 2008; Calixtre et al., 2014). Qualified research in the majority of cases described the co-existence of MMP and mental disorders, but did not indicate their cause and effect relationship. The percentage contribution of the particular research designs is displayed in chart form (Figure 2). Another interesting issue to mention is that the problem was associated mainly with female gender. An overview of the content of qualifying studies is presented in Table 1.

The total number of participants included in the studies ranged from 12,058 to 18. In most studies subjects were adults, mainly females, and in five studies the sample was composed only of females. (Slade et al., 2007; Nilsen et al., 2008; Vedolin et al., 2009; Nilsson and Dahlström, 2010; García-Moya et al., 2015). In 70% of studies individuals were assessed based on RDC/TMD as a diagnostic criterion. Other diagnostic criteria were Graded Chronic Pain Scale (Park et al., 2010; Velly et al., 2011), Guideline of diagnosis of TMD by the American Academy of Orofacial Pain (Kindler et al., 2012; Boggero et al., 2016), Diagnostic Criteria for FM (Nilsen et al., 2008; Pfau et al., 2009; Velly et al., 2010; Alfvén, 2012; García-Moya et al., 2015), International Classification of Headache Disorders II (Mongini et al., 2007; de Tommaso et al., 2009), International Headache Society (Glaros et al., 2007), Diagnostic and Statistical Manual of Mental Disorders-IV (Mongini et al., 2007; Vidaković et al., 2016), Craniomandibular Index (Penna et al., 2009), and Craniomandibular Index/RDC (Velly et al., 2011). In three studies only healthy subjects were included and RDC/TMD were treated as excluding criteria (Slade et al., 2007; Komiyama et al., 2008; Manfredini et al., 2011). MMP patients examined in the included studies often suffered from other concomitant disorders, such as FM (Nilsen et al., 2008; Pfau et al., 2009; Velly et al., 2010; Alfvén, 2012; Klasser et al., 2014; García-Moya et al., 2015) and headaches (Glaros et al., 2007; Mongini et al., 2007; de Tommaso et al., 2009).

Studies differed in psychometric assessment tools. In all, about 20 different inventories were used to evaluate the mental status of studied individuals. The most common were Hospital Anxiety and Depression Scale, Symptom Check List 90/-R, Beck Depression Inventory, State-Trait Anxiety Inventory, Hamilton Depression and Anxiety Rating Scales, Symptom Check List 25—Depression Scale. Seventy-nine percent of studies concerned depression, 42% anxiety, 29% mood disorders, and 21% stress-related disorders. Other considered mental states were somatization, catastrophizing, sleep disturbances, phobia, paranoia, psychoticism, and hostility.

We finally included 38 papers, of which prospective cohort studies were found to be the most common research design. In addition, we considered prospective cohort studies to be the most reliable type of included research. However, there were also many cross-sectional studies. This type of study explores relationships occurring only at one point in time in the appropriate population; thus, no causal relationship can be established.

The quality of the evidence is presented in Table 2 as overall GRADE score for each primary outcome. Due to the study design (only observational studies, not randomized control trials or systematic reviews) the initial GRADE score of included studies was decreased¹. Other common causes of score reduction included limited generalizability of the reported results, quality flaws and clinical heterogeneity between studies. Eventually, none of the outcome evidence was judged as high quality.

Many research teams have tried to establish whether there is an association between anxiety and pain location (Mongini et al., 2007; Nifosì et al., 2007; Kindler et al., 2012; Klasser et al., 2014). Mongini et al. (2007) found that the prevalence of anxiety was higher in patients with myogenous pain than in those with arthrogenous TMD and neuropathic pain. Researchers concluded that, regardless of the pain localization, anxiety and depression independently increased the likelihood of greater muscle tenderness. Nifosì et al. (2007) reported similar findings. However, comparisons of patients divided in a twofold manner contributed to variations in results. Firstly, the group with a myofascial component scored higher on anxiety, paranoia, psychoticism, hostility subscales, and the global severity index than the group with only articular pain. Then, a similar comparison of the three TMD subgroups separately, i.e., (1) with muscle disorders (2) with painful joint disorder and (3) mixed, found no significant differences. Subjects with muscle involvement presented significantly more frequently with a positive psychiatric history and greater lifetime use of psychotropic drugs than did the other patients. Unfortunately, in both studies there was no healthy control group. Among studies comparing patients suffering from MFP with healthy controls (Galli et al., 2009; Pfau et al., 2009; Pizolato et al., 2013; Nadendla et al., 2014) or the general population (Giannakopoulos et al., 2010), there seems to be no certain convergence between the findings. Some of these studies (Manfredini et al., 2009; Pizolato et al., 2013; Nadendla et al., 2014) showed that patients with MFP scored higher on anxiety than healthy controls. However, there have been investigations (Pfau et al., 2009; Giannakopoulos et al., 2010) that do not support this result. Another two findings that did not show any relation between anxiety and MMF (Vedolin et al., 2009; Calixtre et al., 2014) were conducted among young adults. The first study investigated clinical symptoms and jaw functionality in 19 college students with TMD (Calixtre et al., 2014). The second study assessed the pressure pain threshold of masticatory muscles and the level of pain in 29 female dental students suffering from MMF compared to 16 asymptomatic controls (García-Moya et al., 2015).

There have also been studies relevant to anxiety, MMF and comorbid conditions such as FM (de Tommaso et al., 2009; García-Moya et al., 2015). According to García-Moya et al. (2015), the palpation pain of the masseter was significantly greater in FM patients and the pain intensity and state anxiety was correlated only among FM sufferers. Notwithstanding this fact, no significant differences in anxiety were observed between FM and control group. Unfortunately, the study sample size was limited. de Tommaso et al. showed a comorbidity of FM in tension-type headache (de Tommaso et al., 2009). The total tenderness score was higher in FM patients. FM patients (especially tension-type headache sufferers) scored significantly higher in terms of anxiety and depression.

Two studies investigated relationships between masticatory muscle activity according to anxiety using electromyography (EMG) (Komiyama et al., 2008; Manfredini et al., 2011) and aimed to clarify how psychological aspects affect masticatory muscles activity. Manfredini et al. (2011) reported that an above median value for the temperamental anxiety score, depression and anger was correlated to EMG-assessed non-functional nocturnal masticatory activity. Unfortunately, the study was conducted on an insufficiently representative sample and sleep-related EMG recordings were performed only once. Also, Komiyama et al. (2008) showed that anxiety impacts on the reflexes and pain reactions associated with masticatory muscles.

Two investigations presented that salivary cortisol level was related to anxiety scores among MMF patients, but without any dependences among healthy controls. Galli et al. (2009) showed that after administration of dexamethasone patients with chronic myogenous TMD exhibited enhanced and persisting suppression of cortisol levels. Their psychological evaluation revealed that they scored significantly higher in terms of depression, anxiety, physical and mental fatigue. Nadendla et al. (2014) found that awakening salivary cortisol levels and anxiety scores were significantly greater among patients with MFP (without any other joint symptoms).

Many researchers have attempted to establish whether depression episodes influence pain location (Reissmann et al., 2008; Manfredini et al., 2009; Giannakopoulos et al., 2010; Park et al., 2010; Kim et al., 2012; Klasser et al., 2014; Boggero et al., 2016). Most of these have found that patients with muscle disorders have significantly higher depression scores (Manfredini et al., 2009; Park et al., 2010; Kim et al., 2012; Klasser et al., 2014; Boggero et al., 2016). Klasser et al. (2014) showed that patients with myogenous TMD more often reported not only depression, but also anxiety, psychiatric treatment, phobias and severe headaches than arthrogenous TMD. In this study, the psychosocial assessment of the sample was based on a dichotomous medical questionnaire and there was no verification of the accuracy of self-reported co-existing conditions. The absence of healthy controls and a reliable psychometric inventory make comparisons with other studies difficult. Similar findings were reported by Giannakopoulos et al. (2010), who established that patients with MFP were significantly more depressed than patients with joint pain. However, some researchers have not found any significant relationships between depression and muscle pain when comparing three groups of patients suffering from (1) muscle disorder, (2) arthralgia and/or osteoarthritis, and (3) both (Reissmann et al., 2008; Manfredini et al., 2009; Guarda-Nardini et al., 2012). Unfortunately in all these studies, there were no controls to compare with.

Depression was often considered the main factor to be reported in the included studies; however, other factors defined as secondary outcomes were also investigated. Some researchers have studied somatization along with depression (Park et al., 2010; Guarda-Nardini et al., 2012; Kindler et al., 2012; Shedden Mora et al., 2012; Yachida et al., 2012; Cioffi et al., 2014; Mladenović et al., 2014). Mladenović et al. (2014) investigated psychological and dentition-related aspects of TMD in class III patients referred for orthognathic surgery and showed that MFP was related to higher grades of depression and somatization (Mladenović et al., 2014). Similar findings were reported by Shedden Mora et al. (2012), who recorded nocturnal masseter activity and found that in MFP patients one component of nocturnal masseter activity, namely burst per episode, was related to general somatic complaints, TMD related symptoms, pain intensity, depression, and stress level. Patients with MFP were nearly four times more likely to have a psychiatric disorder than healthy controls. Also, Cioffi et al. (2014) found an increased incidence of episodes of depression and somatization in patients with orofacial pain. Catastrophizing was also considered as an issue accompanying MMP. Velly et al. (2010, 2011) found a positive correlation between the intensification of pain symptoms in the 18 months and catastrophizing or depression. One study mentioned post-traumatic stress disorder (Vidaković et al., 2016). This described a higher appearance of MFP syndrome among Croatian soldiers who had taken an active part in war. Fifty-nine percent of the respondents had MFP syndrome, which more often concerned patients with severe and moderate depression.

In some studies, researchers have used EMG to find correlations between muscle activity and depression (Ivkovic et al., 2008; Yachida et al., 2012). Ivkovic et al. conducted a study whose aim was to evaluate the long-term effects of antidepressant therapy on chronic pain and related disability, and masseter silent periods in psychiatric depressive patients with TMD (Ivkovic et al., 2008). The study showed lower occurrence of muscular TMD subtype and chronic muscle pain in patients on antidepressant therapy protocols. Also, Yachida et al. compared the EMG activity of masseter muscles during sleep in patients with orofacial pain and in a control group and found a positive correlation between increased myogenic activity of facial muscles and depression (Yachida et al., 2012).

Along with mood disorders, research teams have studied sleep disturbances and their influence on participants' habitual life (Shibuya et al., 2009; Buenaver et al., 2012). Shibuya et al. (2009) reported that in patients with MFP a depressive mood was common and this aggravated occlusal discomfort and sleep complaints. Buenaver et al. (2012) reported similar findings. Pain catastrophizing, defined as a “negative cognitive-affective response to pain involving rumination, helplessness, and magnification,” was strongly correlated with increased levels of pain severity and sleep disturbances. Other scientists have also studied muscle pain as a possible result of mood disorders. Pfau et al. investigated psychological parameters among TMD myogenic patients, FM patients and healthy controls (Pfau et al., 2009). Higher levels of pain, catastrophizing, disability index (but not anxiety and depression) were found in TMD patients compared to healthy individuals. Nilsson and Dahlström (2010) found that there were no differences in fatigue, emotional distress, cognitive symptoms, or somatic symptoms between patients with different TMD diagnoses. Nonetheless, the psychometric scale scores were significantly higher among TMD patients than in controls.

Some researchers investigated the impact of emotional distress on pain sensitivity and muscle tenderness (Slade et al., 2007; Vedolin et al., 2009; Alfvén, 2012). According to Slade et al. (2007), stress, and also depression and mood disorders were associated with pain sensitivity and were qualified as risk factors of TMD. Vedolin et al. (2009) reported that during stressful periods, the pressure pain thresholds of masticatory muscles in MFP subjects were significantly lower than in controls. Notwithstanding the fact, that both groups were equally anxious and depressed, the MFP individuals had lower pain tolerance. Scientists have reasoned that the external stressor, that is academic examination, had a potential influence on masticatory muscle tenderness. A study conducted among children experiencing psychosomatic pain showed that there was a specific pattern of stress tender points, different from that found in FM sufferers (Alfvén, 2012). A stress tender point localized near the muscle-tendon junction in the temporal region was found only in patients suffering from prolonged stress.

Glaros et al. raised the problem of headache and TMD overlap (Glaros et al., 2007). Participants suffering from headache were significantly more likely to be diagnosed as having MFP, more tension in the jaw, face, head, and stress than those in the non-headache control group.

There was one study employing a salivary cortisol level assay (Nilsson and Dahlström, 2010). It was reported that there were no differences in awakening salivary cortisol levels between TMD patients and the healthy control group and the same held for cortisol levels and emotional distress. Nonetheless, the psychometric scale scores were significantly higher among TMD patients than in controls. An important drawback of the study is the single collection of salvia samples.

The studies included in our systematic review are very heterogeneous. Inconsistences arising from many sources greatly impeded systematic comparisons; thus, we conducted a “narrative, qualitative summary,” as is recommended (Shamseer et al., 2015). Discrepancies related to differences in primary diagnostic criteria employed in the studies were relatively slight, but even if the diagnostic criteria were similar, the structure of comparison groups differed considerably. Some researchers divided their subjects into two (e.g., with myogenous and arthrogenous TMD; Klasser et al., 2014), three (e.g., with MFP, with joint pain and mixed; Park et al., 2010) or even four groups, when the control group was included (Giannakopoulos et al., 2010). Next, they differed in psychometric assessment tools. In all, about 20 different inventories were used to evaluate the mental status of studied individuals. Finally, the studies often differed in their design, sample strength, age and health status of enrolled participants. Thus, the evidence cannot be considered as definitively confirming a cause-and-effect relationship. However the coexistence of anxiety, depression, mood and stress-related disorders among the MMP patients, which is an indisputable scientific fact, must be taken into consideration. Clinicians' improved knowledge and awareness of this multifaceted problem would facilitate an appropriate approach to patients and the making of accurate therapeutic decisions.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.