Depressive symptoms and the onset of menarche

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Depressive symptoms and the onset of menarche
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What is ALSPAC?

• Avon Longitudinal Study of Parents and Children
  
• AKA Children of the Nineties
• Cohort study of 14,000 children and their
  parents, based in south-west England
• Eligibility criteria Mothers had to be resident
  in Avon and have an expected date of delivery
  between April 1st 1991 and December 31st 1992
• Population based prospective cohort study

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Wheres Avon to?
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What data does ALSPAC have?

• Self completion questionnaires
• Mothers, Partners, Children, Teachers
• Hands on assessments
• 10 sample tested regularly since birth
• Yearly clinics for all since age 7
• Data from external sources
• SATS from LEA, Child Health database
• Biological samples
• DNA / cell lines

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Data for current models - outcome

• Depressive symptoms
• Short form of Mood and Feelings Questionnaire
• Angold, A., Costello, E. J., Messer, S. C.,
  Pickles, A., Winder, F., Silver, D. (1995).
  Development of a short questionnaire for use in
  epidemiological studies of depression in children
  and adolescents. International Journal of Methods
  in Psychiatric Research, 5, 237249.
• Costello, E. J., Angold, A. (1988). Scales to
  assess child and adolescent depression
  Checklists, screens and nets. Journal of the
  American Academy of Child and Adolescent
  Psychiatry, 27, 726737.
• Assessed in clinic self report
• 3 time points 10y7m, 12y10m, 13y10m

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Depressive symptoms Short MFQ

• I felt miserable or unhappy
  (True/Sometimes/Not at all)
• I didn't enjoy anything at all
• I felt so tired I just sat around and did nothing
• I was very restless
• I felt I was no good any more
• I cried a lot
• I found it hard to think properly or concentrate
• I hated myself
• I was a bad person
• I felt lonely
• I thought nobody really loved me
• I thought I could never been as good as other
  kids
• I did everything wrong

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Depressive symptoms Short MFQ

• I felt miserable or unhappy
  (True/Sometimes/Not at all)
• I didn't enjoy anything at all
• I felt so tired I just sat around and did nothing
• I was very restless
• I felt I was no good any more
• I cried a lot
• I found it hard to think properly or concentrate
• I hated myself
• I was a bad person
• I felt lonely
• I thought nobody really loved me
• I thought I could never been as good as other
  kids
• I did everything wrong

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Restless non-response more common
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Restless non-monotonic change
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Subscales odd / even

• Measured using short MFQ (13 items)
• I felt miserable or unhappy
• I didn't enjoy anything at all
• I felt so tired I just sat around and did nothing
• I was very restless
• I felt I was no good any more
• I cried a lot
• I found it hard to think properly or concentrate
• I hated myself
• I was a bad person
• I felt lonely
• I thought nobody really loved me
• I thought I could never been as good as other
  kids
• I did everything wrong

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Depression scales basic stats
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Depression scales basic stats
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Data for current models - exposure

• Age at onset of menarche
• Assessed repeatedly by questionnaire
• Respondent mother and/or daughter
• 3 groups
• Before 11½ (14.7)
• 11½ - 13½ (65.5)
• After 13½ (19.8)

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Study sample

• 2063 with complete data
• All are girls (obviously!)
• Intention is to repeat models with boys using
  alternative measures of pubertal onset

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1 Simple cross-sectional models
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1 Standardized results

• --------------------------------------------------
  --------------
• Coef. SE t Pgtt
  95 CI
• -------------------------------------------------
  --------------
• t1 (10y7m)
• Early menarche .042 .064 0.67 0.505
  -.082 .167
• Late menarche .027 .057 0.47 0.637
  -.084 .137
• --------------------------------------------------
  --------------
• --------------------------------------------------
  --------------
• t2 (12y10m)
• Early menarche .220 .063 3.48 0.001
  .096 .344
• Late menarche .005 .056 0.08 0.936
  -.106 .115
• --------------------------------------------------
  --------------
• --------------------------------------------------
  --------------
• t3 (13y10m)
• Early menarche .191 .063 3.02 0.003
  .067 .315
• Late menarche -.170 .056 -3.03 0.002
  -.281 -.060
• --------------------------------------------------
  --------------

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However

• Scales are skewed
• Data is longitudinal
• Heterogeneity in patterns of change
• Scale properties may not be invariant across time

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2 Measurement Invariance model
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2 Measurement Invariance model - on items
Optional
Item-1
Item-12
Item-1
Item-12
Item-1
Item-12



F_t1
F_t2
F_t3
Menarche onset
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2 Measurement Invariance model
Decent fit for fully invariant model

• CFI
  0.952
• TLI
  0.975
• Number of Free Parameters
  57
• RMSEA (Root Mean Square Error Of Approximation)
  0.043
• WRMR (Weighted Root Mean Square Residual)
  1.892

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2 Measurement Invariance results

• Meas Inv model
• Estimate (SE), P-Value
  Estimate (SE), P-Value
• F_t1 ON
• EARLYMEN 0.044 (0.071), p 0.534 0.042
  (0.064), p 0.505
• LATEMEN 0.025 (0.064), p 0.700 0.027
  (0.057), p 0.637
• F_t2 ON
• EARLYMEN 0.239 (0.073), p 0.001 0.220
  (0.063), p 0.001
• LATEMEN 0.004 (0.065), p 0.956 0.005
  (0.056), p 0.936
• F_t3 ON
• EARLYMEN 0.206 (0.073), p 0.005 0.191
  (0.063), p 0.003
• LATEMEN -0.198 (0.065), p 0.002 -0.170
  (0.056), p 0.002

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c.f. with equivalent simple C/S results

• Meas Inv model
  Simple C/S
• Estimate (SE), P-Value
  Estimate (SE), P-Value
• t1/F_t1 ON
• EARLYMEN 0.044 (0.071), p 0.534 0.042
  (0.064), p 0.505
• LATEMEN 0.025 (0.064), p 0.700 0.027
  (0.057), p 0.637
• t2/F_t2 ON
• EARLYMEN 0.239 (0.073), p 0.001 0.220
  (0.063), p 0.001
• LATEMEN 0.004 (0.065), p 0.956 0.005
  (0.056), p 0.936
• t3/F_t3 ON
• EARLYMEN 0.206 (0.073), p 0.005 0.191
  (0.063), p 0.003
• LATEMEN -0.198 (0.065), p 0.002 -0.170
  (0.056), p 0.002

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1 C/S 2 Meas Invariant
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Considerable variability between subjects
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3 2nd Order Growth Model
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3 2nd Order Growth Model piecewise
Optional
t1_odd
t1_even
t2_odd
t2_even
t3_odd
t3_even
F_t1
F_t2
F_t3
F_i
F_s1
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3 2nd Order Growth Model piecewise
t1_odd
t1_even
t2_odd
t2_even
t3_odd
t3_even
F_t1
F_t2
F_t3
Zero residual variance
F_i
F_s1
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3 Growth model fit

• CFI
  0.972
• TLI
  0.970
• Number of Free Parameters
  13
• Akaike (AIC)
  46763.214
• Bayesian (BIC)
  46836.429
• Sample-Size Adjusted BIC
  46795.126
• RMSEA (Root Mean Square Error Of Approximation)
• Estimate
  0.077
• 90 Percent C.I.
  0.068 0.088
• Probability RMSEA lt .05
  0.000
• SRMR (Standardized Root Mean Square Residual)
• Value 0.037

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3 Growth model parameters

• 
  Two-Tailed
• Estimate S.E.
  Est./S.E. P-Value
• Means
• INTCPT 2.370 0.045
  52.119 0.000
• SLOPE1 0.112 0.021
  5.435 0.000
• SLOPE2 0.686 0.050
  13.660 0.000
• Variances
• INTCPT 3.382 0.144
  23.462 0.000
• SLOPE1 0.653 0.029
  22.313 0.000
• SLOPE2 4.053 0.170
  23.864 0.000
• INTCPT WITH
• SLOPE1 0.985 0.052
  19.072 0.000
• SLOPE2 -0.946 0.105
  -9.003 0.000
• SLOPE1 WITH
• SLOPE2 -0.324 0.049
  -6.678 0.000

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3 Growth model - add menarche

• INTCPT ON
• EARLYMEN 0.061 (0.071), p 0.386
• LATEMEN 0.037 (0.063), p 0.559
• INTCPT ON
• EARLYMEN 0.237 (0.068), p 0.001
• LATEMEN -0.003 (0.061), p 0.959
• INTCPT ON
• EARLYMEN 0.210 (0.066), p 0.002
• LATEMEN -0.185 (0.059), p 0.002
• SLOPE1 ON
• EARLYMEN 0.189 (0.073), p 0.010
• LATEMEN -0.033 (0.065), p 0.606
• SLOPE2 ON
• EARLYMEN 0.029 (0.071), p 0.683
• LATEMEN -0.214 (0.063), p 0.001

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3 Growth model - add menarche

• INTCPT ON
• EARLYMEN 0.061 (0.071), p 0.386
• LATEMEN 0.037 (0.063), p 0.559
• INTCPT ON
• EARLYMEN 0.237 (0.068), p 0.001
• LATEMEN -0.003 (0.061), p 0.959
• INTCPT ON
• EARLYMEN 0.210 (0.066), p 0.002
• LATEMEN -0.185 (0.059), p 0.002
• SLOPE1 ON
• EARLYMEN 0.189 (0.073), p 0.010
• LATEMEN -0.033 (0.065), p 0.606
• SLOPE2 ON
• EARLYMEN 0.029 (0.071), p 0.683
• LATEMEN -0.214 (0.063), p 0.001

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Compare models so far
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Measurement Invariance model - alternative
Item-1
Item-12
Item-1
Item-12
Item-1
Item-12



F_t1
F_t2
F_t3
Menarche onset
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Compare models so far
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Compare models so far
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Effect of censoring on 1st order factors
Uncensored
Censored
t1
??
t2
??
t3
??
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4 Growth model with mixture
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4 Growth model with mixture

• overall
• lt. . .gt
• c1 on earlymen latemen
• c1
• slope1
• slope1
• slope2
• slope2
• intcpt
• intcpt
• intcpt on earlymen latemen
• slope1 slope2 on earlymen latemen
• intcpt with slope1 slope2
• slope1 with slope2

c2 slope1_at_0 slope1_at_0 slope2_at_0
slope2_at_0 intcpt intcpt intcpt on
earlymen latemen intcpt with slope1_at_0
slope2_at_0 slope1 with slope2_at_0
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4 Growth model with mixture

• overall
• lt. . .gt
• c1 on earlymen latemen
• c1
• slope1
• slope1
• slope2
• slope2
• intcpt
• intcpt
• intcpt on earlymen latemen
• slope1 slope2 on earlymen latemen
• intcpt with slope1 slope2
• slope1 with slope2

c2 slope1_at_0 slope1_at_0 slope2_at_0
slope2_at_0 intcpt intcpt intcpt on
earlymen latemen intcpt with slope1_at_0
slope2_at_0 slope1 with slope2_at_0
No change in symptoms
Change is permitted
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4 Two class results

• LATENT CLASSES BASED ON THE ESTIMATED MODEL
• c1 1074.91 52.1
• c2 988.09 47.9
• BASED ON MODAL CLASS
• c1 1033 50.1
• c2 1030 49.9

Average Latent Class Probabilities for Modal
Class (Row) by Latent Class (Column)
1 2 1 0.958 0.042 2 0.083
0.917 Entropy 0.774
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4 Two class results
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4 Two class results
C1 ON EARLYMEN 1.363 1.016, 1.828, p
0.039 LATEMEN 0.863 0.619, 1.112, p
0.254

• Class 1
• INTCPT ON
• EARLYMEN -0.002 (0.092), p0.980
• LATEMEN 0.130 (0.091), p0.154
• SLOPE1 ON
• EARLYMEN 0.159 (0.095), p0.094
• LATEMEN -0.061 (0.081), p0.448
• SLOPE2 ON
• EARLYMEN 0.003 (0.096), p0.972
• LATEMEN -0.213 (0.075), p0.004

Class 2 INTCPT ON EARLYMEN 0.136 (0.160),
p0.396 LATEMEN -0.105 (0.119), p0.377
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Has that really helped with the skewness?
Manifest measures within class
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Has that really helped with the skewness?
1st level factors within class
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What next?

• Semi-continuous models
• Zero-inflated models
• ideal for instance where a score of zero is
  substantively different to score of 1
• Split measures in binary (zero/non-zero) and cts
  (e.g. log of non-zero scores)
• Prevalence of non-zero is 60-70 so what does
  such an onset mean
• Limited scope for modelling of 3 binaries, i.e.
• i bin_fd_at_0 bin_ff_at_2.25 bin_fg_at_3.25

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Summary / conclusions

• We have 3 skewed measures of MFQ and wish to
  assess the extend to which early menarche leads
  to an earlier and/or greater onset in depressive
  symptoms
• The models considered thus far are in good
  agreement and have not altered the conclusions
  made on the initial figure
• Inclined to favour the invariance model based on
  items only model which appears to have
  successful dealt with skewness
• Thoughts gratefully received