Sage Journals: Discover world-class research

Abstract

Background:

DSM-5 separates bipolar (BD) from depressive disorders, but some experts consider BD as part of a spectrum of mood disorders. The interpretation of numerous false positives of BD screened by the Mood Disorders Questionnaire (MDQ) is part of this debate. Recent study results suggest that the worsening of health-related quality of life (H-Qol) associated with MDQ positivity does not depend solely on mood disorders. This study aims to clarify whether the impairment may be due to other concomitant disorders, unrelated to mood disorders, leading to a worsening of H-Qol. Additionally, the study aims to explore if MDQ positivity itself observe clinical significance.

Design and methods:

The study involved pairs of cases (MDQ+) and controls (MDQ−) matched for sex, age, and absence of DSM-IV psychiatric comorbidity. The impact of MDQ positivity on the quality of life in a sample of MDQ+ comorbid with MDD was measured and compared to impact of MDD in other chronic disorders.

Results:

The H-Qol was significantly worse in MDQ+ than in controls (both groups without any psychiatric co-morbidity). The worsening was similar to severe chronic disorders The burden of worsening quality of life due to MDD was mild in another sample of MDQ positives with comorbid MDD.

Conclusion:

The study hypothesizes that MDQ positivity may be related to hyperactivation and dysregulation of rhythms typical of stress disorders. In fact, MDQ+ was found strongly related to sleep disturbances. Future studies could verify if a “Dysregulation of Mood, Energy, and Social Rhythms Syndrome” (DYMERS), causes worsening the H-Qol in MDQ+.

Keywords

Misdiagnosis Mood Disorder Questionnaire new syndrome Rhythms Dysregulation Screening Tool

Introduction

The last classification of the American Psychiatric Association, DSM-5, has restricted the field of bipolar disorders by separating them from depressive disorders.¹ This classification contrasts with the neo-Kraepelinian concept of a spectrum of mood disorders that includes both bipolar disorders (as more severe forms) and depressive disorders. The characterizing element of the spectrum is mania and hypomania, which, even with subthreshold manifestations, would have preceded depressive episodes often misdiagnosed as major depression. This arguing view of bipolar disorder characterized the debate following the discovery of the low accuracy of the bipolar disorder screener paper and pencil tests.² Indeed, some tools, particularly the Mood Disorder Questionnaire (MDQ), were found to identify a greater number of false positives compared to diagnoses of Bipolar Disorder conducted in clinical settings.^3,4 The low specificity was attributed to false identification, as episodes of hypomania were confounded with non-specific episodes of hyperstimulation observed in various other disorders (e.g. personality disorders, posttraumatic stress disorder, anxiety disorders, alcohol and drug use disorders, impulse control disorder, eating disorders, and attention deficit disorder). These hyperstimulation episodes were prevalent among MDQ positives even in the absence of a concurrent diagnosis of BD.⁵

This interpretation has generated several concerns among neo-Kraepelinian supporters. This is because the disorders observed among the false positives are well-established to have a strong association with bipolar disorder,^6,7 a condition that typically manifests years before anxiety and personality disorders.^7,8

If the neo-Kraepelinian perspective is accurate, the clinical consequences and impact on the quality of life related to MDQ positivity should resemble those of a “sub-threshold” disorder. Consequently, there would likely be a significant impact, even if not equivalent to that of a “full” disorder. Additionally, the impairment in quality of life would be exacerbated by the coexistence of a Major Depressive Disorder (MDD) diagnosis. As a similar condition could represent an undiagnosed “full” Bipolar II Disorder, which considerably impairs health-related quality of life.⁹ Consistent with the existing literature, it is also expected that cases of unrecognized bipolar disorder or the “conversion” of subthreshold Bipolar Disorder into “unrecognized full Bipolar Disorder” (i.e. MDQ positivity plus Major Depressive Disorder MDD) would occur at a later age compared to individuals with only MDQ positivity without full mood disorders. According to this hypothesis, the onset of a depressive episode and diagnosis of MDD would precede the onset of manic episodes (detected through MDQ positivity).¹⁰

On the other hand, if the “malaise” captured by MDQ positivity were the result of an association with frequent diagnoses of non-bipolar psychiatric disorders resulting in “false positives,” the impairment in health-related quality of life associated with MDQ positivity would be attributed to the concomitant non-bipolar disorders. However, recent research evidence challenges this assumption.¹¹

A direct link between genetic risk of bipolar disorder and MDQ scores has not been found. However, the genetics of bipolar disorder are intricate and involve multiple interactive risk factors. The absence of a direct linear relationship between genetic risk and MDQ scores does not eliminate the possibility of an association, particularly when genetic factors interact with other co-factors. Some traits of bipolar disorder, such as hyperactivity, can manifest themselves in individuals without the disorder under specific circumstances. While the presence of the “at-risk variant” in non-at-risk individuals does not rule out a potential relationship with bipolar disorder, it certainly defies a simple linear correlation. Overall, the study underscores the intricate interplay of genetic and environmental factors in bipolar disorder and related conditions, challenging straightforward diagnostic correlations and emphasizing the need for comprehensive understanding.

The purpose of this study is to investigate the clinical burden associated with MDQ positivity in terms of its impact on health-related quality of life in individuals without other psychiatric diagnoses. The hypothesis posits that if the MDQ identifies a clinically relevant and disabling condition on its own, the attributable burden will be higher. Additionally, the study aims to assess the extent to which the burden on health-related quality of life worsens in cases of comorbidity between a lifetime diagnosis of Major Depressive Disorder (MDD) and MDQ positivity.

Design and methods

Design

This is a case-control study on a database of a previous community survey. The results are then compared with similar results drawn from the same database for cases and controls or with case-control studies of non-psychiatric conditions whose controls were drawn from the same national database.

Study sample

The database of the community survey, from which was drawn the study sample, was selected after stratification by age and sex from the adult population records of urban and rural municipalities of six different Italian regions (balanced by geographical distribution and average income compared to the total of the 20 Italian regions). A detailed description of the community survey and of the 4999 selected individuals was already published.¹² For the purpose of this study we selected all individuals scoring positive on the MDQ (cases), and we excluded all the individuals who had in association a diagnosis of a psychiatric disorder. For each MDQ-positive individual selected, all MDQ-negative individuals of the same age and gender and without psychiatric DSM-IV co-morbidity. The exclusion criteria for the control sample was also to have an MDQ score of 6 or 7. For each MDQ-positive a block with all eligible controls was built and a control for each block (each case). was randomly drawn.

Study instruments

The data selected for the study refer to the following instruments: Ad-hoc form for assessing basic demographic variables; “The Advanced Neuropsychiatric Tools and Assessment Schedule” (ANTAS),¹³ a previously validated semi-structured clinical interview allowing, if administered by clinical expert interview, psychiatric diagnosis according to the DSM-IVR diagnostic system; The Mood Disorder Questionnaire (MDQ) in the Italian version¹⁴ was used, during the national survey with the purpose to assess lifetime hypomanic episodes or episodes of augmentation of energy,¹⁵ however, the present study hypothesizes that positivity of MDQ can identify a dysregulation syndrome; The Health Survey Short Form 12 item (SF−12) was used to assess the health-related quality of life according to different dimensions such as physical health and functioning, physical pain, vitality, social functioning, emotional condition, and psychosocial disability.¹⁶ The assessment period is 1 month. The higher the score on the SF-12, the better is the perception of the health-related quality of life.

Ethics

The protocol of the late National community survey was evaluated and approved by the ethical committee of the Italian National Health Institute (Rome).¹² The possibility of conducting case-control studies on the database to investigate subsequent hypotheses was foreseen in the approved protocol. Informed consent was signed by each candidate.

Statistics

The comparison between the means and standard deviations of the total scores of SF-12 in cases and controls was carried out by means of ANOVA 1 way. As mentioned in previously published articles,^17,18 the “Attributable Burden in Worsening QoL” of a given condition (in this case MDQ+) is the difference between the mean and standard deviation of a SF-12 control sample without the condition and the score of an age- and sex-matched sample with that given disorder . In this case we carried out a comparison of “Attributable Burden in Worsening QoL” of the MDQ positives with a series of impairing health and mental health condition conducted in studies on psychiatric conditions that had drawn their cases and controls from the same data and in studies on non-psychiatric condition that used the same database for controls.^17,18

Results

The study sample includes 38 pairs of cases (MDQ+) and controls (MDQ−) matched for sex (23 males), age (44.26 ± 14.08), both groups did not have DSM-IV psychiatric comorbidity diagnoses. The total score on the SF-12 scale, measuring the health-related quality of life, was higher in controls [41.65 ± 3.39vs 35.23 ± 6.35, F (1, 75 df) = 30.337, p < 0.0001]. The mean of SF-12 overall score in MDQ positives without concomitant other psychiatric conditions was similar to that of chronic mental health and non-mental health diseases (Table 1) as Wilson’s Disease,¹⁹ Carotid Atherosclerosis,²⁰ Major Depressive Disorder,²¹ Eating Disorders,¹⁵ Obsessive Compulsive Disorder,²² Post-Traumatic Stress Disorder,²³ Agoraphobia,²⁴ Solid Tumor,²⁵ and Onco-hematological tumors.²⁶ The perception of the health-related quality of life in MDQ positives without any psychiatric disorder was even worse than that observed in Celiac Disease,¹⁷ Panic Disorders,²⁷ and Simple Phobia.²⁸ Only Multiple Sclerosis¹⁸ and Fibromyalgia²⁹ were associated with a worse health-related quality of life than the MDQ positive condition free of other psychiatric disorders. Table 2 shows the demographic characteristics and the health-related quality of life (as a score of SF-12) in the eight individuals found in the database reporting MDQ positives with comorbidity with Lifetime Major Depressive Disorder. In this sample, there is a higher frequency of women than in the sample of people with MDQ positivity without diagnosis (75%vs 39.5%) and younger age (40.87 ± 13.01vs 44.26 ± 14.08; ≥50 25% vs 44.7%), however, as shown in the Table 2, the differences in all these values do not reach any statistical significance. The difference in the SF-12 score is worse in the group with concomitant diagnosis of MDD of a mean of 2.73 ± 2.44 points in the score (this measure is the attributable burden due to MDD), however even in this case, the difference between the two samples does not reach statistical significance. Table 3 shows the attributable Burden to Major Depressive Disorder in MDQ positives (as the difference in the score of health-related quality of life scale SF-12 in people with MDQ positivity without MDD and in people with MDQ positivity and MDD) and the comparison with similar measures carried out in studies using the same database for psychiatric chronic disease or case-control studies in non-psychiatric chronic disorders using the same database for the choice of controls. The impact of MDD in worsening the health-related quality of life of people with MDQ positivity tends to be the lowest compared to impact of MDD in the chronic disorders considered, however, no statistically significant differences are found except with solid tumors where the impact of comorbidity with MDD is much more impacting on the quality of life.

Table 1.

Health-related quality of life (SF-12 score) in people MDQ positives without diagnosis with other psychiatric conditions in comparison with Health-related quality of life in other chronic diseases.

Disorders	SF-12 (mean ± sd)	Attributable Burden due to Disorder	Comparison with MDQ+ without diagnosis
Celiac disease¹⁷	35.8 ± 5.7	2.4 ± 1.0 (N = 60)	df 1,97 F = 14.08 p < 0.0001
Multiple sclerosis¹⁸	29.5 ± 7.3	7.0 ± 3.5 (N = 201)	df 1,238 F = 9.937 p = 0.002
Wilson’s disease¹⁹	33.8 ± 9.0	4.4 ± 1.7 (N = 23)	df 1,60 F = 0.344 p < 0.568
Carotid atheriosclerosis²⁰	30.6 ± 8.1	6.2 ± 5.0 (N = 46)	df 1,83 F = 1.040 p = 0.311
Major depressive disorder²¹	33.8 ± 9.2	5.6 ± 3.6 (N = 37)	df 1,73 F = 2.66 p = 0.608
Eating disorders¹⁵	34.0 ± 6.2	4.4 ± 6.6 (N = 60)	df 1,97 F = 10.272 p = 0.603
Panic disorders²⁷	35.5 ± 4.6	2.9 ± 0.9 (N = 123)	df 1,160 F = 19.454 p < 0.0001
Obsessive compulsive disorder²²	35.4 ± 6.9	2.9 ± 6.0 (N = 88)	df 1,125 F = 3.709 p = 0.056
Post-traumatic stress disorder²³	36.3 ± 6.1	3.9 ± 1.0 (N = 26)	df 1,91 F = 1.388 p = 0.243
Simple phobia²⁸	35.8 ± 6.1	2.5 ± 2.4 (N = 54)	df 1,66 F = 10.016 p = 0.002
Agoraphobia²⁴	35.2 ± 7.8	3.4 ± 3.6 (N = 35)	df 1,71 F = 2.129 p = 0.149
Fibromyalgia²⁹	26.43 ± 6.04	11.02 ± 5.56 (N = 71)	df 1,108 F = 29.558 p < 0.001
Solid tumors²⁵	32.34 ± 6.764	4.67 ± 6.64 (N = 151)	df 1,188 F = 0.113 p = 0.737
Onco-hematological tumors²⁶	32.60 ± 5.43	5.44 ± 2.93	df 1,188; F = 0.113; p = 0.737
MDQ+ without diagnosis	35.23 ± 6.35	5.06 ± 5.22 (N = 38)

Table 2.

Health-related quality of life (SF-12 score) in MDQ positive individuals co-morbid with Lifetime Major Depressive Disorder.

	Sex	Age	Sf-12
1	f	21	32
2	f	23	40
3	f	34	30
4	m	43	29
5	f	45	36
6	f	47	25
7	m	53	42
8	f	61	26
Descriptive statistics	2m	40.87 ± 13.01≥50 N = 2	32.5 ± 5.87
Comparison with MDQ+ without psychiatric conditions	Chi square Yates corrected = 2.082, p = 0.149	F (1, 45 df) = 0.392, p = 0.534≥50Chi square Yates corrected = 1.362, p = 0.243	F (1, 45 df) = 1.250, p = 0.270Burden due to MDD = 2.73 ± 2.44

Table 3.

Attributable Burden to Major Depressive Disorder in MDQ positives and comparison with other psychiatric and non-psychiatric chronic disorders.

Attributable burden to major depressive disorder	Difference WithMDD-Without	One-way ANOVA F (df)	p
Solid tumors²⁵	10.1 ± 5.7	13.182 (1,158)	<0.0001
Multiple sclerosis¹⁸	2.9 ± 7.4	0.004 (1, 208)	0.948
Fibromyalgia²⁹	4.77 ± 5.76	0.975 (1,78)	0.327
Wilson disease¹⁹	3.2 ± 7.9	0.027 (1,23)	0.072
Celiac disease¹⁷	3.4 ± 5.4	0.119 (1,67)	0.732
Carotidal atherosclerosis²⁰	3.4 ± 8.2	0.052 (1,53)	0.821
MDQ positivity	2.73 ± 2.44	Pivot

Discussion

The study shows that individuals living in the community who test positive for the MDQ screening test, even in the absence of any psychiatric diagnosis, exhibit a significantly lower health-related quality of life compared to a sample of the general population with the same age and gender but negative for the MDQ. The impact of MDQ positivity (in the absence of other disorders) on worsening the quality of life was surprisingly similar to the impact seen with similar methodology and data from the same database for severe chronic disorders and diseases.^19–27 Only Multiple Sclerosis¹⁸ and Fibromyalgia²⁹ were found to have more impact on health-related quality of life than MDQ positivity even with comorbid psychiatric disorders.

This data supports the hypothesis that MDQ positivity, by itself, identifies a condition of clinical interest regardless of comorbidity with other disorders. The dimensions explored by the SF-12 (albeit from a subjective perspective) include physical health and functioning, physical pain, vitality, social functioning, emotional condition, and psychosocial disability. Therefore, these elements are not negligible on a clinical level.

Another pertinent aspect is the mean difference in SF-12 score between individuals with co-morbid MDD and positive MDQ (Mood Disorder Questionnaire) and those with positive MDQ without concomitant MDD (“attributable burden due to MDD”). This difference is not greater than that observed in most chronic psychiatric or non-psychiatric disorders when calculating the attributable burden of MDD for these conditions. Only in solid tumors is there a greater impact (“attributable burden”) of MDD on the quality of life.

It should be considered that if we accept the hypothesis that the MDQ identifies hypomania episodes, individuals diagnosed with MDD and positive MDQ could represent unrecognized cases of bipolar II disorder. The literature shows that bipolar II disorder severely compromises the quality of life even to a greater extent than bipolar I disorder.⁹

Additionally, according to the literature,¹⁰ we would expect the presence of MDD to be more common in adult/older individuals, while the trend is reversed.

However, new research evidence may suggest a new interpretation of clinical means of MDQ false positives. A recent study has determined that based on genetic profiling, MDQ “false positives” were closely associated with anxiety disorders and PTSD genetic determinants, and that there wasn’t a linear correlation between the genetic risk of bipolar disorder and the MDQ score.³⁰ The same research also demonstrated a close association between MDQ positivity and insomnia.³⁰

However, the genetics of bipolar disorder are complex, and the concomitance of different interactive genetic risk factors cannot be excluded.³¹ The absence of a linear relationship cannot exclude an association that could exist but be mild if this genetic factor interacts with concomitant co-factors. In fact, some elements, such as the attitude of hyperactivity, typical of bipolar disorder, can be found in people who do not suffer from this disorder in specific conditions of conflict or social danger,³² and a high frequency of a genetic variant (the allele RS1006737 of the CACNA1C gene considered a risk factor for bipolar disorder) was found in elderly people with hyperactivity/novelty-seeking traits but who are perfectly socially integrated and without any psychiatric diagnosis.^33–35

In this framework, even admitting that the presence of the “at-risk variant” may be found also in the not-at-risk subgroup, this cannot cancel a possible BD-genetic variant association relationship but certainly cannot justify a linear correlation. An indirect confirmation of a possible interaction between other risk factors than the genetic variant RS1006737 of the CACNA1C gene comes from a study that had to compare the score of MDQ and the presence of the above-cited genetic variant as screeners of BD, against a diagnosis of bipolar disorder carried out by clinicians as the Gold Standard.³⁶

Both screeners exhibited a certain accuracy against the Gold Standard, albeit insufficient for practical use (excellent specificity for the MDQ, good sensitivity for gene testing). However, the unexpected and apparently contradictory finding was that the two screeners showed very low reliability between them, measured independently of the Gold Standard.³⁶

Considering the close association of sleep disturbances with MDQ positivity,³⁰ it was hypothesized that the hyperactivation identified by the MDQ could be related not only to a manic/hypomanic episode but also to the hyperactivation typical of certain stress disorders known to be linked to sleep disorders.³⁷ A similar hypothesis made the phenomenon of moderate accuracy of the MDQ and gene test plausible (which, we reiterate, was identified even in healthy hyper-exploratory elderly individuals) regarding bipolar disorder, as well as the low reliability between the two tests (MDQ and gene). In other words, if the activation identified by the MDQ was a trigger (not exclusive to BD) and gene positivity a predisposition (non-pathogenic in itself), a similar hypothesis made plausible the phenomenon of moderate accuracy for both the MDQ and the gene test in diagnosing bipolar disorder, along with low reliability between the two tests (as if the MDQ and gene could identify two different components).

On the other hand, a subsequent study demonstrated that the presence of MDQ positivity significantly worsened the quality of life, regardless of the presence of a bipolar episode or comorbidity with a bipolar diagnosis. This was evident by comparing the scores on the SF-12 scale of health-related quality of life from a sample of positive MDQs from a database of the general population (excluding those with comorbidity for bipolar disorder) and a sample matched by gender, age, and the co-presence of psychiatric disorders other than mood disorders. Furthermore, the difference between the two samples remained substantial even after the age of 50, when a late diagnosis of bipolar disorder became increasingly unlikely, thus reducing the risk of false negatives.

Considering the clinical consistency of the condition (i.e. the significant deterioration in associated quality of life), the co-occurrence of sleep disturbances, and the possibility that the hyperactivation investigated by the questionnaire could potentially identify not only manic episodes but also stress-induced hyperactivation, the “heuristic” hypothesis emerged that MDQ positivity could identify a “Dysregulation of Mood, Energy, and Social Rhythms Syndrome” (DYMERS). This syndrome appears to play a crucial role in the worsening of chronic conditions and represents a specific picture related to stress, as well as the relevance of social rhythms in stress prevention. Discussions have started concerning stress during the Covid pandemic and specifically during the lockdown periods.^38–40

In conclusion, the results suggest the hypothesis that the positivity of the MDQ may have captured a hyperactivity syndrome.

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This publication was carried out as part of the resource-funded research project: P.O.R. SARDEGNA F.S.E. 2014-2020 - Asse III “Istruzione e Formazione, Obiettivo Tematico: 10, Obiettivo Specifico: 10.5, Azione dell’accordo di Partenariato:10.5.12 “Avviso di chiamata per il finanziamento di Progetti di ricerca – Anno 2017, and Fondazione di Sardegna, Italy.

ORCID iDs

Goce Kalcev

Cesar Ivan Aviles Gonzalez

Giulia Cossu

References

American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th, text rev ed. Arlington, VA: American Psychiatric Association, 2022.

Carta

Angst

Screening for bipolar disorders: A public health issue. J Affect Disord 2016; 205: 139–143.

Zimmerman

Galione

JN.

Screening for bipolar disorder with the Mood Disorders Questionnaire: a review. Harv Rev Psychiatry 2011; 19(5): 219–228.

Zimmerman

Galione

Ruggero

, et al. Screening for bipolar disorder and finding borderline personality disorder. J Clin Psychiatry 2010; 71(9): 1212–1217.

Zimmerman

Galione

Chelminski

, et al. Psychiatric diagnoses in patients who screen positive on the Mood Disorder Questionnaire: Implications for using the scale as a case-finding instrument for bipolar disorder. Psychiatry Res 2011; 185(3): 444–449.

Quarantini

Miranda-Scippa

Nery-Fernandes

, et al. The impact of comorbid posttraumatic stress disorder on bipolar disorder patients. J Affect Disord 2010; 123(1-3): 71–76.

Friborg

Martinsen

Martinussen

, et al. Comorbidity of personality disorders in mood disorders: a meta-analytic review of 122 studies from 1988 to 2010. J Affect Disord 2014; 152–154: 1–11.

Nabavi

Mitchell

Nutt

A lifetime prevalence of comorbidity between bipolar affective disorder and anxiety disorders: a meta-analysis of 52 interview-based studies of psychiatric population. EBioMedicine 2015; 2(10): 1405–1419.

Maina

Albert

Bellodi

, et al. Health-related quality of life in euthymic bipolar disorder patients: differences between bipolar I and II subtypes. J Clin Psychiatry 2007; 68(2): 207–212.

10.

Kapczinski

Montezano

de Azevedo Cardoso

Latent bipolar disorder. Lancet 2023; 401(10394): 2109.

11.

Carta

Kalcev

Fornaro

, et al. Does screening for bipolar disorders identify a “Dysregulation of Mood, Energy, and Social Rhythms Syndrome” (DYMERS)? A heuristic working hypothesis. J Clin Med 2023; 12: 5162.

12.

Carta

Aguglia

Balestrieri

, et al. The lifetime prevalence of bipolar disorders and the use of antidepressant drugs in bipolar depression in Italy. J Affect Disord 2012; 136(3): 775–780.

13.

Carta

Aguglia

Bocchetta

, et al. The use of antidepressant drugs and the lifetime prevalence of major depressive disorders in Italy. Clin Pract Epidemol Ment Health 2010; 6: 94–100.

14.

Hardoy

Cadeddu

Murru

, et al. Validation of the Italian version of the “Mood Disorder Questionnaire” for the screening of bipolar disorders. Clin Pract Epidemol Ment Health 2005; 1: 8.

15.

Carta

Preti

Moro

, et al. Eating disorders as a public health issue: prevalence and attributable impairment of quality of life in an Italian community sample. Int Rev Psychiatry 2014; 26(4): 486–492.

16.

Ware

Jr Kosinski

Keller

SD.

A 12-item short-form health survey: construction of scales and preliminary tests of reliability and validity. Med Care 1996; 34: 220–233.

17.

Carta

Conti

Lecca

, et al. The burden of depressive and bipolar disorders in celiac disease. Clin Pract Epidemol Ment Health 2015; 11: 180–185.

18.

Carta

Moro

Lorefice

, et al. Multiple sclerosis and bipolar disorders: the burden of comorbidity and its consequences on quality of life. J Affect Disord 2014; 167: 192–197.

19.

G. Carta

Mura

Sorbello

, et al. Quality of life and psychiatric symptoms in Wilson's disease: the relevance of bipolar disorders. Clin Pract Epidemol Ment Health 2012; 8: 102–109.

20.

Lecca

Saba

Sanfilippo

, et al. Quality of life in carotid atherosclerosis: the role of co-morbid mood disorders. Clin Pract Epidemol Ment Health 2016; 12: 1–8.

21.

Carta

Tondo

Balestrieri

, et al. Sub-threshold depression and antidepressants use in a community sample: searching anxiety and finding bipolar disorder. BMC Psychiatry 2011; 11: 164.

22.

Carta

Fineberg

Moro

, et al. The burden of comorbidity between bipolar spectrum and obsessive-compulsive disorder in an Italian Community Survey. Front Psychiatry 2020; 11: 188.

23.

Sancassiani

Carmassi

Romano

, et al. Impairment of quality of life associated with lifetime diagnosis of post-traumatic stress disorder in women - A National Survey in Italy. Clin Pract Epidemol Ment Health 2019; 15: 38–43.

24.

Preti

Piras

Cossu

, et al. The burden of agoraphobia in worsening quality of life in a community survey in Italy. Psychiatry Investig 2021; 18(4): 277–283.

25.

Lindert

Sancassiani

Massa

, et al. An overview of the international literature on health-related quality of life, mental health and psychosocial issues in people with cancer. Clin Pract Epidemol Ment Health 2021; 17(1): 253–256.

26.

La Nasa

Caocci

Morelli

, et al. Health related quality of life in patients with Onco-hematological diseases. Clin Pract Epidemol Ment Health 2020; 16: 174–179.

27.

Carta

Moro

Aguglia

, et al. The attributable burden of panic disorder in the impairment of quality of life in a national survey in Italy. Int J Soc Psychiatr 2015; 61(7): 693–699.

28.

Sancassiani

Romano

Balestrieri

, et al. The prevalence of specific phobia by age in an Italian nationwide survey: How much does it affect the quality of life? Clin Pract Epidemol Ment Health 2019; 15: 30–37.

29.

Carta

Moro

Pinna

, et al. The impact of fibromyalgia syndrome and the role of comorbidity with mood and post-traumatic stress disorder in worsening the quality of life. Int J Soc Psychiatr 2018; 64(7): 647–655.

30.

Mundy

Hübel

Adey

, et al. Genetic examination of the Mood Disorder Questionnaire and its relationship with bipolar disorder. Am J Med Genet B 2023; 192: 147–160.

31.

Kalcev

Preti

Scano

, et al. Insight into susceptibility genes associated with bipolar disorder: A systematic review. Eur Rev Med Pharmacol Sci 2021; 25(18): 5701–5724.

32.

Carta

Nardi

Pinna

, et al. Multidisciplinary contributions towards an evolutive interpretation of bipolar disorders: could it be the pathological drift of a potentially adaptive condition? Braz J Psychiatry. Epub ahead of print 12 June 2023. DOI: 10.47626/1516-4446-2023-3154

33.

Carta

Kalcev

Scano

, et al. Is bipolar disorder the consequence of a genetic weakness or not having correctly used a potential adaptive condition? Brain Sci 2022; 13(1): 16.

34.

Kalcev

Cossu

Preti

, et al. Development and validation of the questionnaire for adaptive hyperactivity and goal achievement (AHGA). Clin Pract Epidemiol Ment Health 2023; 19: e174501792303281.

35.

Kalcev

Scano

Orrù

, et al. Is a genetic variant associated with bipolar disorder frequent in people without bipolar disorder but with characteristics of hyperactivity and novelty seeking? Clin Pract Epidemiol Ment Health 2023; 19: e174501792303280.

36.

Carta

Kalcev

Scano

, et al. Screening, genetic variants, and bipolar disorders. Clin Pract 2023; 13(4): 853–862.

37.

Lou

Wang

, et al. Hyper-activation of mPFC underlies specific traumatic stress-induced sleep-wake EEG disturbances. Front Neurosci 2020; 14: 883.

38.

Carta

Ouali

Perra

, et al. Living with bipolar disorder in the time of Covid-19: biorhythms during the severe lockdown in Cagliari, Italy, and the moderate lockdown in Tunis, Tunisia. Front Psychiatry 2021; 12: 634765.

39.

Okechukwu

Griffiths

Carta

, et al. Biological and practical considerations regarding circadian rhythm and mental health relationships among nurses working night shifts: a narrative review and recommendations. Riv Psichiatr 2022; 57(2): 67–79.

40.

Carta

Fornaro

Minerba

, et al. Previous functional social and behavioral rhythms affect resilience to COVID-19-related stress among old adults. J Public Health Res 2022; 11(2): 2768.

The impact of MDQ positivity on quality of life impairment: Does it support the hypothesis of “Dysregulation of Mood,Energy,and Social Rhythms Syndrome” (DYMERS)?

Abstract

Background:

Design and methods:

Results:

Conclusion:

Keywords

Introduction

Design and methods

Design

Study sample

Study instruments

Ethics

Statistics

Results

Discussion

Footnotes

Declaration of conflicting interests

Funding

ORCID iDs

References