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01-05-2015 | Original Contribution

Multilevel analysis of ADHD, anxiety and depression symptoms aggregation in families

Authors: Daniel Segenreich, Marina Silva Paez, Maria Angélica Regalla, Dídia Fortes, Stephen V. Faraone, Joseph Sergeant, Paulo Mattos

Published in: European Child & Adolescent Psychiatry | Issue 5/2015

Abstract

A strong genetic role in the etiology of attention-deficit hyperactivity disorder (ADHD) has been demonstrated by several studies using different methodologies. Shortcomings of genetic studies often include the lack of golden standard practices for diagnosis for ADHD, the use of categorical instead of a dimensional approach, and the disregard for assortative mating phenomenon in parents. The current study aimed to overcome these shortcomings and analyze data through a novel statistical approach, using multilevel analyses with Bayesian procedures and a specific mathematical model, which takes into account data with an elevated number of zero responses (expected in samples with few or no ADHD symptoms). Correlations of parental clinical variables (ADHD, anxiety and depression) to offspring psychopathology may vary according to gender and type of symptoms. We aimed to investigate how those variables interact within each other. One hundred families, comprising a proband child or adolescent with ADHD or a typically developing child or adolescent were included and all family members (both biological parents, the proband child or adolescent and their sibling) were examined through semi-structured interviews using DSM-IV criteria. Results indicated that: (a) maternal clinical variables (ADHD, anxiety and depression) were more correlated with offspring variables than paternal ones; (b) maternal inattention (but not hyperactivity) was correlated with both inattention and hyperactivity in the offspring; (c) maternal anxiety was correlated with offspring inattention; on the other hand, maternal inattention was correlated with anxiety in the offspring. Although a family study design limits the possibility of revealing causality and cannot disentangle genetic and environmental factors, our findings suggest that ADHD, anxiety and depression are variables that correlate in families and should be addressed together. Maternal variables significantly correlated with offspring variables, but the paternal variables did not.

Klein RG, Mannuzza S, Olazagasti MA, Roizen E, Hutchison JA, Lashua EC, Castellanos FX (2012) Clinical and functional outcome of childhood attention-deficit/hyperactivity disorder 33 years later. Arch Gen Psychiatry 69(12):1295–1303PubMedCentralPubMedCrossRef

Chang Z, Lichtenstein P, Asherson PJ, Larsson H (2013) Developmental twin study attention problems: high heritabilities throughout development. JAMA Psychiatry 70(3):311–318PubMedCrossRef

Faraone SV, Perlis RH, Doyle AE, Smoller JW, Goralnick JJ, Holmgren MA, Sklar P (2005) Molecular genetics of attention-deficit/hyperactivity disorder. Biol Psychiatry 57(11):1313–1323PubMedCrossRef

Biederman J, Faraone SV, Mick E, Spencer T, Wilens T, Kiely K, Guite J, Ablon JS, Reed E, Warburton R (1995) High risk for attention deficit hyperactivity disorder among children of parents with childhood onset of the disorder: a pilot study. Am J Psychiatry 152(3):431–435PubMedCrossRef

Nigg J, Nikolas M, Burt SA (2010) Measured gene-by-environment interaction in relation to attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 49(9):863–873PubMedCentralPubMedCrossRef

Sharp D (2005) Genetic epidemiology: strengths, weaknesses, and opportunities. Lancet 366(9489):880PubMedCrossRef

Whittemore AS, Nelson LM (1999) Study design in genetic epidemiology: theoretical and practical considerations. J Natl Cancer Inst Monogr 26:61–69PubMedCrossRef

Zhao LP, Aragaki C, Hsu L, Potter J, Elston R, Malone KE, Daling JR, Prentice R (1999) Integrated designs for gene discovery and characterization. J Natl Cancer Inst Monogr 26:71–80PubMedCrossRef

Khoury MJ, Flanders WD (1995) Bias in using family history as a risk factor in case-control studies of disease. Epidemiology 6(5):511–519PubMedCrossRef

10.

Rothen S, Vandeleur CL, Lustenberger Y, Jeanprêtre N, Ayer E, Gamma F, Halfon O, Fornerod D, Ferrero F, Preisig M (2009) Parent-child agreement and prevalence estimates of diagnoses in childhood: direct interview versus family history method. Int J Methods Psychiatr Res 18(2):96–109PubMedCrossRef

11.

Brookes K, Xu X et al (2006) The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: association signals in DRD4, DAT1 and 16 other genes. Mol Psychiatry 11(10):934–953PubMedCrossRef

12.

Rommelse NN, Oosterlaan J, Buitelaar J, Faraone SV, Sergeant JA (2007) Time reproduction in children with ADHD and their nonaffected siblings. J Am Acad Child Adolesc Psychiatry 46(5):582–590PubMedCrossRef

13.

Larsson H, Anckarsater H, Rastam M, Chang Z, Lichtenstein P (2012) Childhood attention-deficit hyperactivity disorder as an extreme of a continuous trait: a quantitative genetic study of 8,500 twin pairs. J Child Psychol Psychiatry 53(1):73–80PubMedCrossRef

14.

Souza I, Pinheiro MA, Denardin D, Mattos P, Rohde LA (2004) Attention-deficit/hyperactivity disorder and comorbidity in Brazil: comparisons between two referred samples. Eur Child Adolesc Psychiatry 13(4):243–248PubMedCrossRef

15.

Sciberras E, Lycett K, Efron D, Mensah F, Gerner B, Hiscock H (2014) Anxiety in children with attention-deficit/hyperactivity disorder. Pediatrics. 2014 Apr 21. [Epub ahead of print]

16.

Roy A, Oldehinkel AJ, Verhulst FC, Ormel J, Hartman CA (2014) Anxiety and disruptive behavior mediate pathways from attention-deficit/hyperactivity disorder to depression. J Clin Psychiatry 75(2):e108–e113PubMedCrossRef

17.

Yüce M, Zoroglu SS, Ceylan MF, Kandemir H, Karabekiroglu K (2013) Psychiatric comorbidity distribution and diversities in children and adolescents with attention deficit/hyperactivity disorder: a study from Turkey. Neuropsychiatr Dis Treat 9:1791–1799PubMedCentralPubMedCrossRef

18.

Piñeiro-Dieguez B, Balanzá-Martínez V, García-García P, Soler-López B (2014) Psychiatric comorbidity at the time of diagnosis in adults With ADHD: the CAT study. J Atten Disord. Jan 24. [Epub ahead of print]

19.

Segenreich D, Fortes D, Coutinho G, Pastura G, Mattos P (2009) Anxiety and depression in parents of a Brazilian non-clinical sample of attention-deficit/hyperactivity disorder (ADHD) students. Braz J Med Biol Res 42(5):465–469PubMedCrossRef

20.

Goos LM, Ezzatian P, Schachar R (2007) Parent-of-origin effects in attention-deficit hyperactivity disorder. Psychiatry Res 149(1–3):1–9PubMedCrossRef

21.

van Steijn DJ, Richards JS, Oerlemans AM, de Ruiter SW, van Aken MA, Franke B, Buitelaar JK, Rommelse NN (2012) The co-occurrence of autism spectrum disorder and attention-deficit/hyperactivity disorder symptoms in parents of children with ASD or ASD with ADHD. J Child Psychol Psychiatry 53(9):954–963PubMedCrossRef

22.

Merikangas KR (1982) Assortative mating for psychiatric disorders and psychological traits. Arch Gen Psychiatry 39(10):1173–1180PubMedCrossRef

23.

Cartwright KL, Bitsakou P, Daley D, Gramzow RH, Psychogiou L, Simonoff E, Thompson MJ, Sonuga-Barke EJ (2011) Disentangling child and family influences on maternal expressed emotion toward children with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 50(10):1042–1053PubMedCrossRef

24.

Knouse LE, Mitchell JT, Brown LH, Silvia PJ, Kane MJ, Myin-Germeys I, Kwapil TR (2008) The expression of adult ADHD symptoms in daily life: an application of experience sampling methodology. J Atten Disord 11(6):652–663PubMedCrossRef

25.

van Ewijk H, Heslenfeld DJ, Luman M, Rommelse NN, Hartman CA, Hoekstra P, Franke B, Buitelaar J, Oosterlaan J (2014) Visuospatial working memory in ADHD patients, unaffected siblings, and healthy controls. J Attent Disord 18(4):369–378CrossRef

26.

Rapport MD, Stoner G, DuPaul GJ, Kelly KL, Tucker SB, Schoeler T (1988) Attention deficit disorder and methylphenidate: a multilevel analysis of dose-response effects on children’s impulsivity across settings. J Am Acad Child Adolesc Psychiatry 27(1):60–69PubMedCrossRef

27.

Gordóvil-Merino Al, Guàrdia-Olmos J, Peró-Cebollero M, de la Fuente-Solanas EI (2010) Classical and Bayesian estimation in the logistic regression model applied to diagnosis of child attention deficit hyperactivity disorder. Psychol Rep 106(2):519–533PubMedCrossRef

28.

Erskine HE, Ferrari AJ, Nelson P, Polanczyk GV, Flaxman AD, Vos T, Whiteford HA, Scott JG (2013) Epidemiological modelling of attention-deficit/hyperactivity disorder and conduct disorder for the Global Burden of Disease Study. J Child Psychol Psychiatry 54(12):1263–1274PubMedCrossRef

29.

American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders (DSM-IV), text revision, 4th edn. American Psychiatric Association, Washington DC

30.

Kovacs M (1992) Children’s depression inventory. Multi-Health Systems, Toronto

31.

Cruvinel M, Boruchovitch E, Santos AAA (2008) Inventário de depressão infantil (CDI): análise dos parâmetros psicométricos. Revista do Departamento de Psicologia (UFF) 20(2):473–490

32.

Cruvinel M, Boruchovitch E (2008) Sintomas depressivos em crianças: estudos com duas versões do CDI/depressive symptoms in children: studies with two versions of CDI/Síntomas depresivos en niños: estudios con dos versiones del CDI. Psicol cienc prof 28(3):574–585CrossRef

33.

Spielberger CD (1973) Manual for the state-trait anxiety inventory for children. Consulting Psychologists Press, Palo Alto

34.

Assumpção F Jr, e Resch CR (2006) Escala de Avaliação da Ansiedade-Traço Infantil – Um estudo de sensibilidade e especificidade. Arq Bras de Psiquiatria, Neurologia e Medicina Legal 100(1):19–25

35.

Grevet EH, Bau CH, Salgado CA, Fischer AG, Kalil K, Victor MM, Garcia CR, Sousa NO, Rohde LA, Belmonte-de-Abreu P (2006) Lack of gender effects on subtype outcomes in adults with attention-deficit/hyperactivity disorder: support for the validity of subtypes. Eur Arch Psychiatry Clin Neurosci 256(5):311–319PubMedCrossRef

36.

Sousa NO, Grevet EH, Salgado CA, Silva KL, Victor MM, Karam RG, Vitola ES, Picon FA, Zeni GD, Rohde LA, Belmonte-de-Abreu P, Bau CH (2011) Smoking and ADHD: an evaluation of self medication and behavioral disinhibition models based on comorbidity and personality patterns. J Psychiatr Res 45(6):829–834PubMedCrossRef

37.

Gomes-Oliveira M, Gorenstein C, Lotufo Neto F, Andrade L, Wang Y (2011) Validation of the Brazilian Portuguese version of the beck depression inventory-II in a community sample/Validação da versão brasileira em português do Inventário de Depressão de Beck-II numa amostra da comunidade. Revista Brasileira de Psiquiatria 34(4):389–394CrossRef

38.

Spielberger CD, Gorsuch RL, Lushene RE (1970) Manual for the state-trait anxiety inventory. Consulting Psychologists Press, Palo Alto

39.

Gorenstein C, Andrade L (1996) Validation of a Portuguese version of the beck depression inventory and the state-trait anxiety inventory in Brazilian subjects. Braz J Med Biol Res 29(4):453–457PubMed

40.

Serra-Pinheiro MA, Mattos P, Angélica Regalla M (2008) Inattention, hyperactivity, and oppositional—defiant symptoms in Brazilian adolescents: gender prevalence and agreement between teachers and parents in a non-English speaking population. J Atten Disord 12(2):135–140PubMedCrossRef

41.

Von Korff M, Koepsell T, Curry S, Diehr P (1992) Multi-level analysis in epidemiologic research on health behaviors and outcomes. Am J Epidemiol 135(10):1077–1082

42.

Lambert D (1992) Zero-inflated Poisson regression, with an application to defects in manufacturing. Technometrics 34(1):1–14CrossRef

43.

Neelson B, O’Malley A, Normand ST (2010) A Bayesian model for repeated measures zero-inflated count data with application to outpatient psychiatric service use. Stat Modell 10(4):421–439CrossRef

44.

Box GEP, Cox DR (1964) An analysis of transformations. J R Stat Soc Ser B (Methodological) 26(2):211–252

45.

Qiu Z, Song PX, Tan M (2002) Bayesian hierarchical models for multi-level repeated ordinal data using WinBUGS. J Biopharm Stat 12(2):121–135PubMedCrossRef

46.

Mannens M, Alders M (1999) Genomic imprinting: concept and clinical consequences. Ann Med 31(1):4–11PubMedCrossRef

47.

Posserud MB, Ullebø AK, Plessen KJ, Stormark KM, Gillberg C, Lundervold AJ (2013) Influence of assessment instrument on ADHD diagnosis. Eur Child Adolesc Psychiatry. doi:10.1007/s00787-013-0442-6 PubMed

48.

Jans T, Weyers P, Schneider M, Hohage A, Werner M, Pauli P, Warnke A (2009) The Kiddie-SADS allows a dimensional assessment of externalizing symptoms in ADHD children and adolescents. Atten Defic Hyperact Disord 1(2):215–222PubMedCrossRef

49.

Langberg JM, Epstein JN, Simon JO, Loren REA, Arnold LE, Hechtman L et al (2010) Parent agreement on ratings of children’s attention deficit/hyperactivity disorder and broad band externalizing behaviors. J Emot Behav Disord 18:41–50PubMedCentralPubMedCrossRef

50.

Solanto MV, Alvir J (2009) Reliability of DSM-IV symptom ratings of ADHD: implications for DSM-V. J Attent Disord 13:107–116CrossRef

51.

Rabiner DL, Murray DW, Rosen L, Hardy K, Skinner A, Underwood M (2010) Instability in teacher ratings of children’s inattentive symptoms: implications for the assessment of ADHD. J Dev Behav Pediatr 31(3):175–180PubMedCentralPubMedCrossRef

52.

Johnston C, Weiss M, Murray C, Miller N (2011) The effects of instructions on mothers’ ratings of child attention-deficit/hyperactivity disorder symptoms. J Abnorm Child Psychol 39(8):1099–1110PubMedCrossRef

53.

Mattos P, Louzã MR, Palmini AL, de Oliveira IR, Rocha FL (2013) A multicenter, open-label trial to evaluate the quality of life in adults with ADHD treated with long-acting methylphenidate (OROS MPH): concerta Quality of Life (CONQoL) study. J Atten Disord 17(5):444–448PubMedCrossRef

54.

Waschbusch DA, Sparkes SJ (2003) Rating scale assessment of attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD): Is there a normal distribution and does it Matter? J Psychoedu Asses 21:261–281CrossRef

55.

Hasson R, Fine JG (2012) Gender differences among children with ADHD on continuous performance tests: a meta-analytic review. J Atten Disord 16(3):190–198PubMedCrossRef

56.

Fedele DA, Lefler EK, Hartung CM, Canu WH (2012) Sex differences in the manifestation of ADHD in emerging adults. J Atten Disord 16(2):109–117PubMedCrossRef

57.

Pressman LJ, Loo SK, Carpenter EM, Asarnow JR, Lynn D, McCracken JT, McGough JJ, Lubke GH, Yang MH, Smalley SL (2006) Relationship of family environment and parental psychiatric diagnosis to impairment in ADHD. J Am Acad Child Adolesc Psychiatry 45(3):346–354PubMedCrossRef

58.

Johnston C, Mash EJ, Miller N, Ninowski JE (2012) Parenting in adults with attention-deficit/hyperactivity disorder (ADHD). Clin Psychol Rev 32(4):215–228PubMedCrossRef

59.

Agha SS, Zammit S, Thapar A, Langley K (2013) Are parental ADHD problems associated with a more severe clinical presentation and greater family adversity in children with ADHD? Eur Child Adolesc Psychiatry 22(6):369–377PubMedCentralPubMedCrossRef

60.

Harold GT, Leve LD, Barrett D, Elam K, Neiderhiser JM, Natsuaki MN, Shaw DS, Reiss D, Thapar A (2013) Biological and rearing mother influences on child ADHD symptoms: revisiting the developmental interface between nature and nurture. J Child Psychol Psychiatry 54(10):1038–1046PubMedCentralPubMedCrossRef

61.

Hager R, Cheverud JM, Wolf JB (2008) Maternal effects as the cause of parent-of-origin effects that mimic genomic imprinting. Genetics 178(3):1755–1762PubMedCentralPubMedCrossRef

62.

Humphreys K, Mehta N, Lee S (2012) Association of parental ADHD and depression with externalizing and internalizing dimensions of child psychopathology. J Attent Disord 16(4):267–275CrossRef

63.

Minde K, Eakin L, Hechtman L, Ochs E, Bouffard R, Greenfield B, Looper K (2003) The psychosocial functioning of children and spouses of adults with ADHD. J Child Psychol Psychiatry 44(4):637–646PubMedCrossRef

64.

Hane AA, Cheah C, Rubin KH, Fox NA (2008) The role of maternal behavior in the relation between shyness and social withdrawal in early childhood and social withdrawal in middle childhood. Soc Dev 17(4):795–811CrossRef

65.

Wood J, Mcleod BD, Sigman M, Hwang WC, Chu BC (2003) Parenting and childhood anxiety: theory, empirical findings, and future directions. J Child Psychol Psychiatry 44(1):134–151PubMedCrossRef

66.

Lewis G, Collishaw S, Thapar A, Harold GT (2013) Parent–child hostility and child and adolescent depression symptoms: the direction of effects, role of genetic factors and gender. Eur Child Adolesc Psychiatry. doi:10.1007/s00787-013-0460-4 PubMedCentral

67.

Sellers R, Collishaw S, Rice F, Thapar AK, Potter R, Mars B, Harold GT, Smith DJ, Owen MJ, Craddock N, Thapar A (2013) Risk of psychopathology in adolescent offspring of mothers with psychopathology and recurrent depression. Br J Psychiatry 202:108–114PubMedCrossRef

68.

Psychogiou L, Parry E (2014) Why do depressed individuals have difficulties in their parenting role? Psychol Med 44:1345–1347PubMedCrossRef

69.

Gau SS, Chang JP (2013) Maternal parenting styles and mother-child relationship among adolescents with and without persistent attention-deficit/hyperactivity disorder. Res Dev Disabil 34(5):1581–1594PubMedCrossRef

70.

Chronis AM, Lahey BB, Pelham WE, Williams SH, Baumann BL, Kipp H, Jones HA, Rathouz PJ (2007) Maternal depression and early positive parenting predict future conduct problems in young children with attention- deficit/hyperactivity disorder. Dev Psychol 43(1):70–82PubMedCrossRef

71.

Van Batenburg-Eddes T, Brion MJ, Henrichs J, Jaddoe VW, Hofman A, Verhulst FC, Lawlor DA, Davey Smith G, Tiemeier H (2013) Parental depressive and anxiety symptoms during pregnancy and attention problems in children: a cross-cohort consistency study. J Child Psychol Psychiatry 54(5):591–600PubMedCentralPubMedCrossRef

72.

Loeber R, Hipwell A, Battista D, Sembower M, Stouthamer-Loeber M (2009) Intergenerational transmission of multiple problem behaviors: prospective relationships between mothers and daughters. J Abnorm Child Psychol 37(8):1035–1048PubMedCentralPubMedCrossRef

73.

Lappenschaar M, Hommersom A, Lucas PJ, Lagro J, Visscher S (2013) Multilevel Bayesian networks for the analysis of hierarchical health care data. Artif Intell Med 57(3):171–183PubMedCrossRef

Title: Multilevel analysis of ADHD, anxiety and depression symptoms aggregation in families
Authors: Daniel Segenreich
Marina Silva Paez
Maria Angélica Regalla
Dídia Fortes
Stephen V. Faraone
Joseph Sergeant
Paulo Mattos
Publication date: 01-05-2015
Publisher: Springer Berlin Heidelberg
Published in: European Child & Adolescent Psychiatry / Issue 5/2015
Print ISSN: 1018-8827
Electronic ISSN: 1435-165X
DOI: https://doi.org/10.1007/s00787-014-0604-1

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Multilevel analysis of ADHD, anxiety and depression symptoms aggregation in families

Abstract

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Abstract

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