Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Psychiatry
Published in: BMC Psychiatry 1/2024

Open Access 01-12-2024 | Panic Disorder | Research

A causal relationship between panic disorder and risk of alzheimer disease: a two-sample mendelian randomization analysis

Authors: Yueqin Tian, Qiuping Ye, Jia Qiao, Lian Wang, Yong Dai, Hongmei Wen, Zulin Dou

Published in: BMC Psychiatry | Issue 1/2024

Login to get access

Abstract

Background

Observational studies have suggested a link between panic disorder (PD) and Alzheimer disease (AD). This study aimed to identify the underlying association of PD with the risk of AD using Mendelian randomization.

Methods

Genetic instrumental variables (IVs) were retrieved in the genome-wide association study between PD and AD. Then, five different models, namely inverse variance weighting (IVW), weighted median, weighted mode, MR-Egger and MR-robust adjusted profile scores (MR-RAPS), were used for MR Analysis. Finally, the heterogeneity and pleiotropy of identified IVs were verified by multiple sensitivity tests.

Results

The Cochran’s Q test based on MR Egger and IVW showed that no evidence of heterogeneity was found in the effects of instrumental variables, so a fixed-effect model was used. IVW analysis (OR 1.000479, 95% CI [1.000147056, 1.000811539], p = 0.005) indicated that PD was associated with an increased risk of AD, and a causal association existed between them. Meanwhile, weighted median (OR 1.000513373, 95% CI [1.000052145, 1.000974814], p = 0.029) and MR-RAPS (OR 1.000510118, 95% CI [1.000148046, 1.00087232], p = 0.006) also showed the similar findings. In addition, extensive sensitivity analyses confirmed the robustness and accuracy of these results.

Conclusion

This investigation provides evidence of a potential causal relationship between PD and the increased risk of AD. Based on our MR results, when diagnosing and treating patients with PD, clinicians should pay more attention to their AD-related symptoms to choose therapeutic measures or minimize comorbidities. Furthermore, the development of drugs that improve both PD and AD may better treat patients with these comorbidities.
Appendix
Available only for authorised users
Literature
1.
Matthews KA, Xu W, Gaglioti AH, Holt JB, Croft JB, Mack D, et al. Racial and ethnic estimates of Alzheimer’s disease and related dementias in the United States (2015–2060) in adults aged ≥ 65 years. Alzheimers Dement. 2019;15(1):17–24.CrossRefPubMed
2.
GBD 2016 Dementia Collaborators. Global, regional, and national burden of Alzheimer’s disease and other dementias, 1990–2016: a systematic analysis for the global burden of Disease Study 2016. Lancet Neurol. 2019;18(1):88–106.CrossRef
3.
2022 Alzheimer’s disease facts and figures. Alzheimers Dement. 2022;18(4):700–89.
4.
5.
6.
7.
Silva MVF, Loures C, de Alves MG, de Souza LCV, Borges LC. Carvalho M Das G. Alzheimer’s disease: risk factors and potentially protective measures. J Biomed Sci. 2019;26(1):33.CrossRefPubMedPubMedCentral
8.
Livingston G, Sommerlad A, Orgeta V, Costafreda SG, Huntley J, Ames D, et al. Dementia prevention, intervention, and care. Lancet. 2017;390(10113):2673–734.CrossRefPubMed
9.
Gottfries CG. Recognition and management of depression in the elderly. Int Clin Psychopharmacol. 1997;12(Suppl 7):31–6.CrossRef
10.
Liu CY, Wang PN, Lin KN, Liu HC. Behavioral and psychological symptoms in Taiwanese patients with Alzheimer’s disease. Int Psychogeriatr. 2007;19(3):605–13.CrossRefPubMed
11.
12.
Kikuchi M, Komuro R, Oka H, Kidani T, Hanaoka A, Koshino Y. Panic disorder with and without agoraphobia: comorbidity within a half-year of the onset of panic disorder. Psychiatry Clin Neurosci. 2005;59(6):639–43.CrossRefPubMed
13.
Wu MH, Wang WE, Wang TN, Lin NC, Lu ML, Lui LMW, et al. Asthma and early smoking associated with high risk of panic disorder in adolescents and young adults. Soc Psychiatry Psychiatr Epidemiol. 2022;57(3):583–94.CrossRefPubMed
14.
Bienvenu OJ, Davydow DS, Kendler KS. Psychiatric diseases versus behavioral disorders and degree of genetic influence. Psychol Med. 2011;41(1):33–40.CrossRefPubMed
15.
Jimenez DA, Bond RL, Requena-Komuro MC, Sivasathiaseelan H, Marshall CR, Russell LL, et al. Altered phobic reactions in frontotemporal dementia: a behavioural and neuroanatomical analysis. Cortex. 2020;130:100–10.CrossRefPubMedPubMedCentral
16.
Segers K, Mihailescu T, Kazadi A, Benoit F, Surquin M. Takotsubo cardiomyopathy as a consequence of acute anxiety in a patient with Alzheimer’s disease associated with Lewy body disease. Psychogeriatrics. 2020;20(4):528–9.CrossRefPubMed
17.
Becker E, Orellana Rios CL, Lahmann C, Rücker G, Bauer J, Boeker M. Anxiety as a risk factor of Alzheimer’s disease and vascular dementia. Br J Psychiatry. 2018;213(5):654–60.CrossRefPubMed
18.
Gulpers BJA, Verhey FRJ, Eussen SJPM, Schram MT, de Galan BE, van Boxtel MPJ, et al. Anxiety and cognitive functioning in the Maastricht study: a cross-sectional population study. J Affect Disord. 2022;319:570–9.CrossRefPubMed
19.
Nash JR, Sargent PA, Rabiner EA, Hood SD, Argyropoulos SV, Potokar JP, et al. Serotonin 5-HT1A receptor binding in people with panic disorder: positron emission tomography study. Br J Psychiatry. 2008;193(3):229–34.CrossRefPubMed
20.
Mizukami K, Ishikawa M, Akatsu H, Abrahamson EE, Ikonomovic MD, Asada T. An immunohistochemical study of the serotonin 1A receptor in the hippocampus of subjects with Alzheimer’s disease. Neuropathology. 2011;31(5):503–9.CrossRefPubMedPubMedCentral
21.
Mattsson P, Cselényi Z, Andrée B, Borg J, Nag S, Halldin C, et al. Decreased 5-HT1A binding in mild Alzheimer’s disease-A positron emission tomography study. Synapse. 2022;76(7–8):e22235.CrossRefPubMedPubMedCentral
22.
Gladsjo JA, Rapaport MH, McKinney R, Lucas JA, Rabin A, Oliver T, et al. A neuropsychological study of panic disorder: negative findings. J Affect Disord. 1998;49(2):123–31.CrossRefPubMed
23.
24.
Lawlor DA, Harbord RM, Sterne JAC, Timpson N, Davey Smith G. Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med. 2008;27(8):1133–63.MathSciNetCrossRefPubMed
25.
26.
27.
Larsson SC, Woolf B, Gill D. Plasma caffeine levels and risk of Alzheimer’s Disease and Parkinson’s Disease: mendelian randomization study. Nutrients. 2022;14(9):1697.CrossRefPubMedPubMedCentral
28.
Zou XL, Wang S, Wang LY, Xiao LX, Yao TX, Zeng Y, et al. Childhood obesity and risk of stroke: a mendelian randomisation analysis. Front Genet. 2021;12:727475.CrossRefPubMedPubMedCentral
29.
1000 Genomes Project Consortium, Abecasis GR, Altshuler D, Auton A, Brooks LD, Durbin RM, et al. A map of human genome variation from population-scale sequencing. Nature. 2010;467(7319):1061–73.CrossRef
30.
Huang JY, Labrecque JA. From GWAS to PheWAS: the search for causality in big data. Lancet Digit Health. 2019;1(3):e101–3.CrossRefPubMed
31.
Burgess S, Butterworth A, Thompson SG. Mendelian randomization analysis with multiple genetic variants using summarized data. Genet Epidemiol. 2013;37(7):658–65.CrossRefPubMedPubMedCentral
32.
Bowden J, Davey Smith G, Burgess S. Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol. 2015;44(2):512–25.CrossRefPubMedPubMedCentral
33.
Bowden J, Davey Smith G, Haycock PC, Burgess S. Consistent estimation in mendelian randomization with some Invalid instruments using a weighted median estimator. Genet Epidemiol. 2016;40(4):304–14.CrossRefPubMedPubMedCentral
34.
Hartwig FP, Davey Smith G, Bowden J. Robust inference in summary data mendelian randomization via the zero modal pleiotropy assumption. Int J Epidemiol. 2017;46(6):1985–98.CrossRefPubMedPubMedCentral
35.
Zhao Q, Wang J, Hemani G, Bowden J, Small DS. Statistical inference in two-sample summary-data Mendelian randomization using robust adjusted profile score. 2019.
36.
Marie V, Chia-Yen C, Benjamin N, Ron D. Detection of widespread horizontal pleiotropy in causal relationships inferred from mendelian randomization between complex traits and diseases. Nat Genet. 2018;50(5).
37.
Burgess S, Thompson SG, CRP CHD Genetics Collaboration. Avoiding bias from weak instruments in mendelian randomization studies. Int J Epidemiol. 2011;40(3):755–64.CrossRefPubMed
38.
Hemani G, Zheng J, Elsworth B, Wade KH, Haberland V, Baird D, et al. The MR-Base platform supports systematic causal inference across the human phenome. Elife. 2018;7:e34408.CrossRefPubMedPubMedCentral
39.
Jaramillo-Jimenez A, Ying Y, Ren P, Xiao Z, Zhang Q, Wang J, et al. Prodromal Dementia with Lewy Bodies and recurrent panic attacks as the First Symptom: a Case Report. Front Neurol. 2022;13:839539.CrossRefPubMedPubMedCentral
40.
Arafuka S, Sekiguchi H, Fujishiro H, Iritani S, Torii Y, Habuchi C, et al. Late-onset panic disorder as the initial presentation in autopsy-confirmed dementia with Lewy bodies. Psychiatry Clin Neurosci. 2023;77(4):242–4.CrossRefPubMed
41.
DeLuca AK, Lenze EJ, Mulsant BH, Butters MA, Karp JF, Dew MA, et al. Comorbid anxiety disorder in late life depression: association with memory decline over four years. Int J Geriatr Psychiatry. 2005;20(9):848–54.CrossRefPubMed
42.
Perin S, Lai J, Pase M, Bransby L, Buckley R, Yassi N, et al. Elucidating the association between depression, anxiety, and cognition in middle-aged adults: application of dimensional and categorical approaches. J Affect Disord. 2022;296:559–66.CrossRefPubMed
43.
Gulpers B, Lugtenburg A, Zuidersma M, Verhey FRJ, Voshaar RCO. Anxiety disorders and figural fluency: a measure of executive function. J Affect Disord. 2018;234:38–44.CrossRefPubMed
44.
Airaksinen E, Larsson M, Forsell Y. Neuropsychological functions in anxiety disorders in population-based samples: evidence of episodic memory dysfunction. J Psychiatr Res. 2005;39(2):207–14.CrossRefPubMed
45.
Boldrini M, Del Pace L, Placidi GPA, Keilp J, Ellis SP, Signori S, et al. Selective cognitive deficits in obsessive-compulsive disorder compared to panic disorder with agoraphobia. Acta Psychiatr Scand. 2005;111(2):150–8.CrossRefPubMed
46.
Libowitz MR, Wei K, Tran T, Chu K, Moncrieffe K, Harrington MG, et al. Regional brain volumes relate to Alzheimer’s disease cerebrospinal fluid biomarkers and neuropsychometry: a cross-sectional, observational study. PLoS ONE. 2021;16(7):e0254332.CrossRefPubMedPubMedCentral
47.
Wang HY, Xu GQ, Ni MF, Zhang CH, Li XL, Chang Y, et al. Neural basis of implicit cognitive reappraisal in panic disorder: an event-related fMRI study. J Transl Med. 2021;19(1):304.CrossRefPubMedPubMedCentral
48.
Trzesniak C, Uchida RR, Araújo D, Guimarães FS, Freitas-Ferrari MC, Filho AS, et al. (1)H magnetic resonance spectroscopy imaging of the hippocampus in patients with panic disorder. Psychiatry Res. 2010;182(3):261–5.CrossRefPubMed
49.
Dresler T, Guhn A, Tupak SV, Ehlis A-C, Herrmann MJ, Fallgatter AJ, et al. Revise the revised? New dimensions of the neuroanatomical hypothesis of panic disorder. J Neural Transm (Vienna). 2013;120(1):3–29.CrossRefPubMed
50.
den Heijer T, Geerlings MI, Hoebeek FE, Hofman A, Koudstaal PJ, Breteler MMB. Use of hippocampal and amygdalar volumes on magnetic resonance imaging to predict dementia in cognitively intact elderly people. Arch Gen Psychiatry. 2006;63(1):57–62.CrossRef
51.
Chen K, Palagashvili T, Hsu W, Chen Y, Tabakoff B, Hong F, et al. Brain injury and inflammation genes common to a number of neurological diseases and the genes involved in the genesis of GABAnergic neurons are altered in monoamine oxidase B knockout mice. Brain Res. 2022;1774:147724.CrossRefPubMed
52.
Canet G, Hernandez C, Zussy C, Chevallier N, Desrumaux C, Givalois L. Is AD a stress-related disorder? Focus on the HPA Axis and its promising therapeutic targets. Front Aging Neurosci. 2019;11:269.CrossRefPubMedPubMedCentral
53.
Pietrzak RH, Laws SM, Lim YY, Bender SJ, Porter T, Doecke J, et al. Plasma cortisol, brain Amyloid-β, and Cognitive decline in preclinical Alzheimer’s disease: a 6-Year prospective cohort study. Biol Psychiatry Cogn Neurosci Neuroimaging. 2017;2(1):45–52.PubMed
54.
Fiksdal A, Hanlin L, Kuras Y, Gianferante D, Chen X, Thoma MV, et al. Associations between symptoms of depression and anxiety and cortisol responses to and recovery from acute stress. Psychoneuroendocrinology. 2019;102:44–52.CrossRefPubMed
55.
Mantella RC, Butters MA, Amico JA, Mazumdar S, Rollman BL, Begley AE, et al. Salivary cortisol is associated with diagnosis and severity of late-life generalized anxiety disorder. Psychoneuroendocrinology. 2008;33(6):773–81.CrossRefPubMedPubMedCentral
56.
Furtado M, Katzman MA. Neuroinflammatory pathways in anxiety, posttraumatic stress, and obsessive compulsive disorders. Psychiatry Res. 2015;229(1):37–48.CrossRefPubMed
57.
Lambiase MJ, Kubzansky LD, Thurston RC. Prospective study of anxiety and incident stroke. Stroke. 2014;45(2):438–43.CrossRefPubMed
58.
Teixeira AL, Barbosa IG, Diniz BS, Kummer A. Circulating levels of brain-derived neurotrophic factor: correlation with mood, cognition and motor function. Biomark Med. 2010;4(6):871–87.CrossRefPubMed
59.
de Bruijn RFAG, Direk N, Mirza SS, Hofman A, Koudstaal PJ, Tiemeier H, et al. Anxiety is not associated with the risk of dementia or cognitive decline: the Rotterdam Study. Am J Geriatr Psychiatry. 2014;22(12):1382–90.CrossRefPubMed
60.
Pierce BL, Burgess S. Efficient design for mendelian randomization studies: subsample and 2-sample instrumental variable estimators. Am J Epidemiol. 2013;178(7):1177–84.CrossRefPubMedPubMedCentral
Metadata
Title
A causal relationship between panic disorder and risk of alzheimer disease: a two-sample mendelian randomization analysis
Authors
Yueqin Tian
Qiuping Ye
Jia Qiao
Lian Wang
Yong Dai
Hongmei Wen
Zulin Dou
Publication date
01-12-2024
Publisher
BioMed Central
Keyword
Panic Disorder
Published in
BMC Psychiatry / Issue 1/2024
Electronic ISSN: 1471-244X
DOI
https://doi.org/10.1186/s12888-024-05624-3

Other articles of this Issue 1/2024

BMC Psychiatry 1/2024 Go to the issue

Research

Potential of niacin skin flush response in adolescent depression identification and severity assessment: a case-control study

Study Protocol

The short- and longer-term effects of brief behavioral parent training versus care as usual in children with behavioral difficulties: study protocol for a randomized controlled trial

Research

Spanish validation of the short version of the racing and crowded thoughts questionnaire (RCTQ-13)

Research

Changes in mental health services in response to the COVID-19 pandemic in high-income countries: a rapid review

Research

Depressive symptoms and visual attention to others’ eyes in healthy individuals

Research

Development of stigma scale for women with mental illness in perinatal period, validity and reliability study