ABO Gene is Likely a Genetic Cause of Anxiety Diagnosis

Article Information

Donna K. Hobgood*

University of Tennessee College of Medicine, Chattanooga Unit, Erlanger East Hospital, 1751 Gunbarrel Road, Chattanooga TN 37421, United States.

*Corresponding Author: Donna K. Hobgood, University of Tennessee College of Medicine, Chattanooga Unit, Erlanger East Hospital, 1751 Gunbarrel Road, Chattanooga TN 37421, United States.

Received: 30 June 2024; Accepted: 10 July 2024; Published: 17 July 2024

Citation: Donna K. Hobgood. ABO gene is likely a genetic cause of anxiety diagnosis. Journal of Psychiatry and Psychiatric Disorders. 8 (2024): 150-155.

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Abstract

Anxiety is a common and debilitating symptom without full understanding of genetic causes. ABO B allele frequency was seen associated with lower anxiety diagnosis prevalence while ABO A allele frequency with higher anxiety diagnosis prevalence in world population studies. Genetic analysis suggests that the association is causative. Dopamine beta hydroxylase (DBH) causes conversion of dopamine to norepinephrine and is related to anxiety as well as ABO blood groups through linkage disequilibrium (LD). Linkage dysequilibrium allelic analysis is consistent with ABO B in linkage with low activity DBH. High activity DB causes high norepinephrine:dopamine ratio. Anxiety diagnosis is associated with high norepinephrine. Low activity DBH causes lower norepinephrine and thus lower anxiety. Population studies were reviewed and showed lower anxiety prevalence in areas with high ABO B frequency. Mendelian randomization inferring causation from gene and proteins and diagnoses shows that ABO gene's association with anxiety diagnosis is causative since Asian populations have markedly high ABO B frequency as well as a markedly lower ABO A with essentially no ABO A2 frequency distinguishing Asia from Europe and Africa and the Middle East as well as a markedly lower anxiety diagnosis prevalence. While population stratification confounds, mendelian randomization may clarify causation instead of just association of ABO with anxiety diagnosis since DBH low activity marker rs 1611115T causes high dopamine to norepinephrine ratio and is thus a cause of lower anxiety in LD with ABO B frequency, an association with lower anxiety in population studies.

Keywords

ABO Gene Allele Frequencies; Dopamine Beta Hydroxylase; Anxiety Diagnosis; Mendelian Randomization

ABO Gene Allele Frequencies articles; Dopamine Beta Hydroxylase articles; Anxiety Diagnosis articles; Mendelian Randomization articles

Article Details

1. Introduction

ABO being the first human gene recognized has been associated with many diagnoses most notably being thrombosis risks in ABO non-O and pancreatic cancer risks in ABO non-O. [1] Anxiety and many related diagnoses have been associated with ABO but not consistently [2-6]. Dental anxiety in children was found to be lower in Indian population in ABO A groups.  ABO AB showed positive findings of Neuroticism in a Croatian study [7] and in a Pakistan study [8] and in an Iranian study. Additionally, a study done in Italy and in Boston showed ABO AB associated with Neuroticism.  But most studies reviewed showed either no significant differences in personality in ABO with anxiety related traits or did not address any anxiety dimensions of personality [9-13]. Most commonly used modern personality tests such as the Cloninger traits (Novelty-Seeking, Harm Avoidance, Reward Dependence and Persistence) and The Big Five traits (Openness, Conscientiouness, Extraversion, Agreeableness, and Neuroticism) are validated as having genetic correlates and don't  include anxiety as a personality trait. Anxiety may not be a primary and thus genetically linked personality trait like the Cloninger and the Big Five but instead may result from a combination of environmental and polygenetic multifactorial factors [14,15, 12]. While anxiety may not be a personality trait, related traits such as Neuroticism have been found in many populations to be associated with AB blood type. Using sympathetic activity prominence in anxiety related states, observations of noradrenergic pathways as well as worldwide population prevalence of anxiety diagnoses point to ABO gene as relevant to anxiety diagnoses. ABO gene perhaps through linkage disequilibrium with DBH dopamine beta hydroxylase appears to be a cause of anxiety diagnosis.

The first line of evidence for this is in ABO and DBH having shared trait research.  Some research implicates genetic causes of anxiety diagnosis. Heritability is thought to be around 50%. Many genes such as serotonin transporter have been associated with anxiety related traits but without replication  [16].   Dopamine beta hydroxylase (DBH) has been considered to relate to many behavioral effects.  A possible link of anxiety with ABO blood groups could then relate to dopamine beta hydroxylase (DBH) genetics since ABO gene is in tight linkage disequilibrium (LD) with DBH [17,18].

Based on the literature showing anxiety related sympathetic nervous system correlates, anxiety likely is higher with higher norepinephrine and the genetic cause, higher high activity DBH.  ABO A and O appear to be in LD with higher DBH, higher norepinephrine and higher anxiety, and ABO B appears in LD with lower DBH, lower norepinephrine and lower anxiety. (19,20), Studies have linked ABO A and ABO O with high DBH and high norepinephrine and adrenergic associated traits such as sensation-seeking while ABO B and low DBH and low norepinephrine are associated with traits thought to have dopamine correlates such as impulsiveness and cocaine induced psychosis, [21] Many health risks have been studied as to co-occurrence with ABO blood groups and with DBH.  As examples, ABO group B has less smoking risk than ABO groups O and A, and dopamine beta hydroxylase, DBH TT (low activity) in LD with ABO B, has less smoking risk than DBH CC [22]. This is consistent with research consensus regarding the relatively higher genetic dopamine activity patterns in non-smokers. Since ABO group B marker rs8176746 is in linkage disequilibrium with DBH, rs1611115, with consistent population frequency distributions, it is likely that the ABO blood group B association with not only smoking risk but also illnesses and personality traits may be related to linkage disequilibrium with DBH [23-27]. The second line of evidence for this lies in DBH showing association with diagnoses consistent with that of ABO.  DBH, the catecholamine enzyme that converts dopamine to norepinephrine, varies in individuals as a function of genetics. Low activity and high activity variants are described most studied being rs1611115, the locus having worldwide frequency distributions of high activity variant C at .79 and low activity variant T at .21. Associations include increased hypertension, diabetes, and myocardial infarction risk in high activity variants as well as post-traumatic stress disorder (PTSD), Inflammatory bowel disease, hypothyroid, and major depressive disorder [23-28]. Low activity DBH associated with bipolar disorder and schizophrenia in a Pakistani study and of Alzheimer's Disease in a Croatian population and obsessive-compulsive disorder in a Turkish study. Other associations with low DBH include migraine, autism, hyperthyroid, attention deficit hyperactivity disorder (ADHD). ABO research is consistent with DBH research with ABO A/O higher hypertension the most prevalent and the most replicated finding [1]. ABO gene with worldwide frequency distributions of O .63, A .21 and B .16 is known to be in tight linkage disequilibrium with DBH gene. Inspection of the LD pattern (D') between ABO and DBH shows that the pattern of D’ numbers (higher values indicating tighter linkage) with DBH allele rs1611115 and ABO alleles are consistent with literature of linkages with DBH alleles and ABO alleles as well as world population frequencies of these alleles [29].

Table 1: ABO and DBH are in linkage disequilibrium such that ABO B is linked with DBH low activity

ABO allele

ABO blood group

D’ LD with DBH

rs8176746T

ABO B

32

rs512770A

ABO O

40

rs8176704G

ABO A or O

31

rs495828G

ABO A or O

77

rs1752337T

ABO A or O

81

rs9411493A

ABO A

43

rs7025162C

ABO O

82

rs624960T

ABO O

80

rs4962043C

ABO O

37

rs8176743C

ABO  O

32

rs8176693C

ABO O

32

rs8176672C

ABO O

32

rs8176668A

ABO O

33

rs 651007C

ABO O

79

rs479459G

ABO B

79

rs7030248G

ABO O

30

rs558240G

ABO O

40

rs11244065C

ABO O

83

rs532207A

ABO O

80

rs561585A

ABO O

80

rs17150319C

ABO O

66

DBH and ABO role in anxiety is supported by personality trait research and genetic correlations.  Anxiety would intuitively include such traits as Cloninger traits of Persistence trait and high Reward Dependence based on intensity of emotions present in anxiety states and would be likely associated with higher norepinephrine state and thus higher ABO A and DBH high activity.  For comparison, ABO blood group B’s has been found to be associated with high tough-mindedness (thought related to high unemotionality) and low Reward Dependence (thought related to level of engagement propencity) including subtraits of low attachment, low dependence, low openness to warm communication, low persistence, low pain perception [30,31]. The association of ABO B with low DBH via LD with ABO B supports ABO B’s association with traits of impulsiveness, low extraversion and low sensation-seeking and low persistence [21, 32-35].  Persistence trait has been linked with dopamine transporters and receptors (36,37) so since DBH determines the ratio of dopamine to norepinephrine, DBH would be  related to Persistence trait via dopamine and norepinephrine activities. Dopamine and norepinephrine activities are also implicated in Impulsiveness trait via its association with DBH.  Because of the relationship of dopamine and norepinephrine activity to motivation and Aggression (38) DBH allele specificity would then stratify Impulsive action (aggression) vs Persistent action (aggression) such that low activity DBH allele would be associated with Impulsiveness of action and the high activity DBH allele would be associated with Persistence of action. The linkage with dopamine activity to Persistence has been demonstrated by studies which show that for dopamine transporter (DAT), alleles of high dopamine affinity are linked to higher Persistence trait, thus implicating decreased dopaminergic neurotransmission in Persistence trait expression. (39-41) Many studies are consistent with Persistence trait’s connection with relatively low dopamine transmission either from high DBH or from high dopamine transporters and from low avidity or low numbers of dopamine receptors. A study in Japan did demonstrate Persistence trait associated with ABO A and with high DBH [42]. Review of research in PubMed and google scholar site population prevalence of anxiety diagnosis  association with ABO allele frequencies.  Anxiety diagnosis and ABO blood groups were compared using population studies and ABO allele frequencies from standard registries.  Anxiety may be a complex state with environmental and polygenetic underpennings.  So, comparing genetic associations to anxiety diagnosis among populations may be prone to confounding from population stratification. An approach to the problem of population stratification was addressed be using Mendelian Randomization, inferring causation starting from association by assessing allelic links with both an illness in a population and with a known physiologic cause of the illness.  Mendelian Randomization is a standard model that has been employed to understand many genetic effects including inference that folate metabolic defects is a cause of neural tube defects.

Populations representing areas having available anxiety diagnosis frequencies with available data on ABO allele frequencies were reviewed.  Compared to Western European and Middle Eastern populations, ABO A and especially ABOA2 is of lower frequency in Asia while ABO B is of high frequency.  Using Mendelian Randomization model, ABO A allele is associated with both high DBH thus high norepinephrine/dopamine ratio and with higher anxiety population prevalence, supporting a conclusion that ABO A especially ABOA2 allele with highest world frequencies in Western Europe and the Middle East is a cause of higher anxiety. Also, ABO B by Mendelian Randomization is associated with both low DBH and thus low norepinephrine/dopamine ratio and with low anxiety population prevalence, supporting a conclusion that ABO B is a cause of low anxiety.  Thus Asia having both high ABO B and low A especially A2 frequencies has lower anxiety population prevalence [43]. Tables 2, 3, Figure 1, 2

Table 2:  Anxiety population prevalence and ABO gene table ordered by increasing Anxiety diagnosis population prevalence

Population

Anxiety/1000

ABO O

ABO A

ABO B

China

28

55

24

21

Pakistan

28

60

20

20

Hong Kong

28

60

19

21

Croatia

32

62

25

13

Sudan

44

70

15

15

Hispanic

45

75

22

3

African Amer

54

70

18

12

Kuwait

60

55

28

17

Palestine

60

60

24

16

Saudi Arabia

60

60

28

12

Spain

62

60

34

6

Netherlands

64

65

29

6

Germany

64

64

28

8

White Amer

64

65

28

7

Table 3:  Anxiety diagnosis population prevalence and ABO gene table ordered by increasing frequency rs1611115C, high activity DBH

Population

Anxiety/1000

ABO O

ABO A

ABO B

Hispanic

45

75

22

3

Kuwait

60

55

28

17

Palestine

60

60

24

16

Saudi Arabia

60

60

28

12

Netherlands

64

65

29

6

Croatia

32

62

25

13

Germany

64

64

28

8

China

28

55

24

21

Pakistan

28

60

20

20

Hong Kong

28

60

19

21

White Ameri

64

65

28

7

Spain

62

60

34

6

African Ameri

54

70

18

12

Sudan

44

70

15

15

fortune-biomass-feedstock

Figure 1: Series 3-Anxiety diagnosis in world populations (1-14) in order on increasing prevalence and Series 1-ABO O, Series 2-ABO A and Series 4-ABO B allele frequencies

X= populations in order of increasing anxiety prevalence per 1000

Y=1 blue ABO O , 2 red ABO A, 3 green anxiety dx prevalence per 1000 population, 4 purple ABO B

fortune-biomass-feedstock

Figure 2: Series 3 Anxiety diagnosis in world populations (1-14) in order on increasing DBH high activity (rs1611115C) and Series 1-ABO O, Series 2-ABO A and Series 4-ABO B allele frequencies

Table 2 and Figure 1 show population 1-14 in order of increasing anxiety population prevalence illustrating that ABO O shows less correlation with anxiety while ABO A shows positive correlation and ABO B shows negative correlation with anxiety diagnosis. Table 3 and Figure 2 show populations 1-14 in order of increasing frequency of rs1611115C DBH high activity thus allowing some sense of how ABO gene alleles for O, A and B vary when ordered by or controlled for linked DBH high activity allele.

Figure 2 illustrates that when DBH 1611115 C high activity is controlled for ABO A is  seen as varying directly with anxiety diagnosis prevalence  and ABO B is seen as varying indirectly with anxiety diagnosis prevalence.  This would indicate the central relationship between ABO gene even more than DBH and anxiety diagnosis prevalence in populations worldwide.  DBH 1611115 C individuals with ABO A and B and not so much ABO O seems more related to anxiety diagnosis.  Additionally based on populations with high ABO A2 having much higher anxiety diagnosis than populations with high ABO A1 one suspects ABO A2 to be the driver of ABO A and anxiety diagnosis correlation.

2. Discussion

Understanding the related genetics leads to improved screening for anxiety diagnosis allowing targeting of interventions best suited to the individual, thus furthering personalized medicine. And since self-knowledge would further healing, this hypothesis advances that goal.

Limitations drawing inferences from population studies of anxiety diagnosis include variations in how the anxiety diagnosis is made that would impact prevalence rates in populations studied.  Other relevant considerations include cultural inputs on anxiety prevalence as to what level of anxiety symptoms is considered pathological.  Additionally, Resource availability and other social determinants of health vary within and between populations.  Consensus seems to be that low resource availability may not increase prevalence of anxiety diagnosis as much as disparities among the population in resource availability [43]. So, advancing understanding of genetics of anxiety such as this hypothesis would be meaningful to the individual and to society.

For the individual, anxiety genetics may associate with many health-related issues.  High anxiety correlates with emotional and circulatory illnesses [25] while low anxiety correlates with outcomes of low alertness and low attention such as accidents [44, 24]. At the level of society, there may be geopolitical differences that could be attributable to genetic differences in propensity to anxiety.  Areas of conflict are associated with higher anxiety prevalence long-term [45]. Anxiety is a leading cause of morbidity in both males and females, but population studies show that the male: female ratio of diagnosis of anxiety disorder is 0.46 from either environmental and or genetic inputs [45]. It is associated with higher mortality rates, loss in ability to participate in the workforce, in community organizations, and in interpersonal relationships.  Pharmacologic treatment and counseling are mainstays of treatment, but progress depends on elucidating physiologic and genetic causes. Understanding physiology of anxiety is work in progress.  This review uses Mendelian Randomization to show that ABO blood group A is likely a cause of anxiety symptoms and that ABO B is a likely a cause of low anxiety.  While we treat individuals, knowing the context of the prevalence of a diagnosis in a population has meaning.  And knowing the causes of symptoms can facilitate screening strategies.  In the setting of anxiety symptoms, ABO blood group testing being widely available in populations may prove helpful in screening for genetic etiologies of anxiety diagnosis.

 

3. Conclusion

ABO blood groups through linkage disequilibrium with dopamine beta hydroxylase appears to be a cause of anxiety diagnosis.  Large-scale testing populations for correlations between ABO phenotype and anxiety diagnosis is feasible, but ABO genotype would also be necessary since ABO A subtype A2 in populations appears to be more related to anxiety diagnosis than ABO A1. Verification of this hypothesis would serve to further knowledge of genes and their effects and thus lead to better treatments for anxiety.  And just as important, this hypothesis would allow better insight for the individual to understand who he is and what it is that makes him feel and think as he does.

Conflicts of interest

None

Acknowledgements

None

References

  1. Liumbruno GM, Franchini M. Beyond immunohaematology: the role of the ABO blood group in human diseases. Blood Transfus 11 (2013): 491-499.
  2. Kanazawa, M. Relationship between ABO Blood Type and Personality in a Large-scale Survey in Japan. Int J Psychol Behav Sci 11 (2021): 6-12.
  3. Song C, Leng J, Wang L, et al. ABO blood types and postpartum depression among Chinese women: A prospective cohort study in Tianjin, China. Women & Health 58 (2018): 685-698.
  4. Rihmer Z, Arató M. ABO blood groups in manic-depressive patients. Journal of Affective 3 (1998): 1-7.
  5. Gupta S. Blood groups and personality characteristics. Personality and individual differences 11(1990): 317-218
  6. Ghouri RN, Ehtisham M, Jawed S. A comparative study of Emotional Quotient with relation to Blood Groups among medical students of Punjab. Journal of Rawalpindi Medical College 26 (2022).
  7. Pisk SV, Vuk T, Ivezic E, et al., ABO blood groups and psychiatric disorders: a Croatian study. Blood Transfus 17 (2019): 66-71.
  8. Mustafa K, Khan SH, Javed F, et al., Is your blood grouping associated with personality and intelligence?. Biomedica38 (2022): 167-172.
  9. Rinieris, PM GN, Stefanis CN. Neuroticism and ABO blood types. Acta Psychiatrica Scandinavica 61 (1980):  473-476.
  10. Rinieris PM, Stefanis C, Rabavilas A. Obsessional Personality Traits and ABO Blood Types Neuropsychobiology 6 (1980): 128-131.
  11. Wu,K, Lindsted KD., Lee JW. Blood type and the five factors of personality in Asia. Personality and individual differences 38 (2005): 797-808.
  12. Cramer KM, & Imaike E. Personality, blood type, and the five-factor model. Personality and individual differences,;32 (2002): 621-626.
  13. McKeon JP, & McColl D. ABO blood groups in obsessional illness-state and trait. Acta 65 (1982): 74-78.
  14. Cloninger CR, Svrakic DM, Przybeck TR. A psychobiological model of temperament and character. Arch Gen Psychiatry 50 (1993): 975-990.
  15. Keller MC, Coventry WL, Heath AC, et al., Widespread evidence for non-Additive genetic variation in Cloninger's and Eysenck's personality dimensions using a twin plus sibling design. Behav Genet 35 (2005): 707-721
  16. Reimold M, Knobel A, Rapp MA, et al. Central serotonin transporter levels are associated with stress hormone response and anxiety. Psychopharmacology (Berl) 213 (2011): 563-572.
  17. Chen Y, Wen G, Rao F, et al., Human dopamine beta-hydroxylase (DBH) regulatory polymorphism that influences enzymatic activity, autonomic function, and blood pressure. J Hypertens 28 (2010): 76-86.
  18. Asamoah A, Wilson AF, Elston RC, et al., Segregation and linkage analyses of dopamine beta-hydroxylase activity in a six-generation pedigree. Am J Med Genet 27 (1987): 613-621.
  19. McCall JD, Al-Hasani R, Siuda ER, et al., CRH engagement of the locus coeruleus noradrenergic system mediates stress-induced anxiety Neuron, 2015.
  20. Tanaka M, Yoshida M, Emoto H, et al., Noradrenaline systems in the hypothalamus, amygdala and locus coeruleus are involved in the provocation of anxiety: basic studies. European journal of pharmacology (2000)
  21. Hess C, Reif A, Strobel A, et al., A functional dopaminebeta-hydroxylase gene promoter polymorphism is associated with impulsive personality styles, but not with affective disorders. J. Neurol Transm 116 (2009):121- 130.
  22. Freire MTMV, Marques FZC, Hutz MH, et al., Polymorphisms in the DBH and DRD2 gene regions and smoking behavior. European Archives of Psychiatry and Clinical Neuroscience 256 (2006): 93-97.
  23. Zhang H, Cotecchia S, Thomas SA, et al., Gene deletion of dopamine beta-hydroxylase and alpha1-adrenoceptors demonstrates involvement of catecholamines in vascular remodeling. Am J Physiol Heart Circ Physiol 287 (2004): H2106-2114.
  24. Miyata S, Nagata H, Yamao S, et al., Dopamine-beta-hydroxylase activities in serum and cerebrospinal fluid of aged and demented patients. J Neurol Sci 63 (1984): 403-409.
  25. Kanda T, Gotoh F, Yamamoto M, et al., Serum dopamine beta-hydroxylase activity in acute stroke. Stroke 10 (1979): 168-173.
  26. El-Ferzli,GT, Dreher M, Patel rp, et al., ABO Blood Group Is Associated with Response to Inhaled Nitric Oxide in Neonates with Respiratory Failure. Plos One (2012).
  27. Tanaka T, Nakagawa T, Tamai H. Plasma dopamine beta-hydroxylase activity and thyroid suppressibility in Graves' disease. Metabolism 28 (1979): 828-830.
  28. OMIM Onine Mendelian Inheritance in Man last assessed (2024).
  29. e! Ensembl assessed (2024).
  30. Granot M. Personality traits associated with perception of noxious stimuli in women with vulvar vestibulitis syndrome. J Pain 6 (2005): 168-173.
  31. Pud D, Eisenberg E, Sprecher E, et al., The Tridimensional personality theory and pain: harm avoidance and reward dependence traits correlate with pain perception in healthy volunteers. Eur J Pain 2004; 8 (2004): 31-38.
  32. Perris C, Jacobsson L, von Knorring L, et al., Enzymes related to biogenic amine metabolism and personality characteristics in depressed patients. Acta Psychiatr Scand 1980; 61 (1980): 477-484.
  33. Hashmi AN, Ahmed Dharejo R, Zubair UB, et al., Association of dopamine β-hydroxylase polymorphism rs1611115 and serum levels with psychiatric disorders in Pakistani population. International Journal of Neuroscience (2022): 1-9.
  34. La Grange L, Jones TD, Erb L, et al., Alcohol consumption: biochemical and personality correlates in a college student population. Addict Behav 20 (1995): 93-103.
  35. Roy A, Brockington K. Plasma dopamine beta hydroxylase in depressed patients and controls. Neuropsychobiology 18 (1987): 57-59.
  36. Szekely A, Ronai Z, Nemoda Z, et al., Human personality dimensions of persistence and harm avoidance associated with DRD4 and 5-HTTLPR polymorphisms. Am J Med Genet B Neuropsychiatr Genet 126B (2004):106.
  37. Czermak C, Lehofer M, Renger H. Dopamine receptor D3 mRNA expression in human lymphocytes is negatively correlated with the personality trait of persistence. J Neuroimmunol 150 (2004): 145-149.
  38. McDermott R, Tingley D, Cowden J, et al., Monoamine oxidase A gene (MAOA) predicts behavioral aggression following provocation by The National Academy of Sciences of the USA (2009): 2118 -2123
  39. Kazantseva AV, Gaysina DA, Malykh SB, et al., Role of dopamine transporter gene (DAT1) polymorphisms in personality traits variation. Russian journal of genetics 45 (2009): 974-980.
  40. Schosser A, Fuchs K, Scharl T, et al., Interaction between serotonin 5-HT2A receptor gene and dopamine transporter (DAT1) gene polymorphisms influences personality trait of persistence in Austrian Caucasians. The World Journal of Biological Psychiatry 2010; 11 (2010): 417-424.
  41. Ebstein RP, Levine J, Geller V, et al., Dopamine D4 receptor and serotonin transporter promoter in the determination of neonatal temperament. Molecular psychiatry 3 (1998): 238-246.
  42. Tsuchimine S, Saruwatari J, Kaneda A, et al., ABO blood type and personality traits in healthy Japanese subjects. PloS one 10 (2015): e0126983.
  43. Baxter AJ, Scott KM, Vos T, et al., Global prevalence of anxiety disorders: a systematic review and meta-regression. Psychological medicine (2013).
  44. Shalev N, Vangkilde S, Neville MJ, et al., Dissociable Catecholaminergic Modulation of Visual Attention: Differential Effects of Catechol-O-Methyltransferase and Dopamine Beta-Hydroxylase Genes on Visual Attention,Neuroscience 412 (2019): 175-189
  45. Baxter AJ, Vos T, Scott KM, et al. The regional distribution of anxiety disorders: implications for the Global Burden of Disease Study, 2010. Int J Methods Psychiatr Res 23 (2014): 422-438.

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