Open Journal of Genetics, 2013, 3, 14-26 OJGen
http://dx.doi.org/10.4236/ojgen.2013.32A3003 Published Online August 2013 (http://www.scirp.org/journal/ojgen/)
Anxiety and pre-symptomatic testing for
neurodegenerative disorders
Lêdo Susana1,2,3*, Leite Ângela1,4,5, Jorge Sequeiros1,2
1Centre for Predictive and Preventive Genetics (CGPP), IBMC—Institute for Molecular and Cell Biology, Porto, Portugal
2ICBAS, Universidade do Porto, Porto, Portugal
3ISCS-Norte (CESPU), Porto, Portugal
4ISCET—Instituto Superior de Ciências Empresariais e do Turismo, Porto, Portugal
5ULP—Universidade Lusófona do Porto, Porto, Portugal
Received 17 May 2013; revised 2 June 2013; accepted 10 July 2013
Copyright © 2013 Lêdo Susana et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
In this retrospective study we have investigated the
anxiety as an impact of pre-symptomatic testing (PST)
for 3 autosomal dominant late-onset diseases: Hunt-
ington disease (HD), Machado-Joseph disease (MJD)
and familial amyloidotic po lyneuropathy (FAP) V 3 0M
TTR. The study included 686 subjects: 586 (85.4%)
were the offspring at risk for FAP, 92 (13.4%) for HD
and 8 (1.2%) to MJD. Of these, 352 received the car-
rier result and 305 the non-carrier result. As indica-
tor of anxiety distress was taken the Self-Rating An-
xiety Scale of Zung (SAS), applied in the pre-test and
the three post-test moments: three weeks, 6 months
and one year after notification of test results. Values
decreased significantly along the four evaluation mo-
ments, regardless the studied disease or test result.
For female population, SAS means cores revealed
results of clinical anxiety at pre-test, only decreasing
to non clinical scores a year after PST disclosure.
Keywords: Anxiety; Subscales; SAS; Psychological
Impact; FAP; HD; MJD
1. INTRODUCTION
There are numerous diagnostic or pre-symptomatic tests
(PST) for hereditary diseases [1-3] Machado-Joseph dis-
ease (MJD) or amyloidotic polyneuropathy (FAP) TTR
V30M, all late onset autosomal dominant diseases, the
PST can predict if, in future more or less distant, the per-
son will develop the symptoms of the disease [2,4].
It’s in this field of monogenic autosomal dominant late
onset diseases, that the Center for Predictive and Preven-
tive Genetics (CGPP) at Institute for Molecular and Cell
Biology (IBMC), Oporto University, provides a multid-
isciplinary approach for HD, PAF and MJD PST.
A Predictive protocol for neurodegenerative diseases
implemented in CGPP is a national reference model for
genetic counseling and psychosocial support for people
at risk of suffering such progressive and debilitating dis-
eases without effective treatment and cure until the pre-
sent days [2].
The Studied Diseases
HD, MJD and FAP are three examples of monogenic au-
tosomal dominant of late onset, clinically considered as
neurodegenerative diseases, incurable and highly debili-
tating and that may take a broad spectrum of symptoma-
tic manifestations.
Huntington’s disease [5,6] is the most studied, largely
due to the discovery by Guselli and colleagues, of its ge-
netic marker since 1983 [7]. Thus, the predictive test for
Huntington’s disease began to be held in Canada in 1986
and US [1,8], with over the 90’s progress and the new
laboratory techniques for mutation detection [5,6].
MJD and FAP are very specific Portuguese diseases,
that also have a severe neurodegenerative pathway, and
for which there is still no effective treatment or cure. In
1993, the MJD gene was finally located on chromosome
14 by a group of researchers led by Shoji Tsuji, later con-
firmed in the Portuguese households by Sequeiros and
colleagues [9]. The genetic mutation present in FAP leads
to the production of an amyloid protein, immunologi-
cally related to transthyretin (TTR) that is abnormally de-
graded, precipitated and stored in tissues as amyloid sub-
stance [10], deposited in the tissues of various organs
leading these patients for a progressive limitation [11,12].
*Corresponding author.

L. Susana et al. / Open Journal of Genetics 3 (2013) 14-26 15
Pre-symptomatic diagnosis is available since 1984 [11].
Several psychosocial studies have been done with fami-
lies and their descendants at risk for neurodegenerative
diseases diagnosed in CGPP [13-15].
Lêdo [13] studied FAP carriers after a year of knowl-
edge of their genetic status, and concluded there had
been no presence of emotional distress and feelings of
hopelessness.
Other studies with subjects at risk for FAP, HD and
MJD pointed to the existence of psychological well-be-
ing and better health perception than the control subjects
[14]. Also in this field, there have been published psy-
chosocial genetic studies related to the experience of
more than 10 years in the counseling of individuals at
risk [16], as well as studies about the importance of con-
tact time with the disease or affected father figure in the
psychological impact of PST [15].
Despite the different approaches that have been made,
there are still issues to be elucidated regarding the impact
of the application of PST to diseases with common start-
ing symptoms at the early adulthood and a degenerative
path, but with different treatment options and clinical
outcomes (e.g. the psychiatric disorders, unique to Hunt-
ington’s disease, and for MJD frequent signs of cerebel-
lar ataxia, progressive external ophthalmoplegia and py-
ramidal signs [9,17,18].
On the other hand, it continues to be relevant studies
related to psychological impact of test results, mainly the
anxiety indexes because this is one of the most expressed
feelings at the first evaluation. In this sense, we estab-
lished as objectives of this research: 1) the anxiety in-
dexes observed before and after completion of the PST,
and 2) the differences on anxiety indexes related to types
of disease, carrier or non carrier status, and some demo-
graphic variables.
2. MATERIAL AND METHODS
It was designed a retrospective study of clinical files of
subjects who underwent pre-symptomatic testing for ge-
netic autosomal dominant diseases with late onset (MJD,
HD and FAP), in CGPP, between 2000 and 2010. These
files contained psychological evaluations data conducted
along the four moments of the general psychological
evaluation protocol: 1) 1st moment, pre-test, prior to the
genetic test; 2) 2nd moment of evaluation, three weeks af-
ter receiving the test result and knowing genetic status; 3)
3rd moment, six months after disclosure; 4) 4th moment,
one year after disclosure.
2.1. Subjects
The initial sample (Table 1) is constituted by 686 sub-
jects at base line: 586 (85.4%) attended the service to ac-
complish the pre-symptomatic test for FAP, 92 (13.4%)
for HD and 8 (1.2%) for MJD. Subjects underwent the
evaluation protocol voluntarily when they were informed
they were 50% at-risk for these diseases and were in-
formed about the purpose of the research, simultaneously
with PST protocol procedure and signed a written con-
sent for the use of their data with the finality of scientific
research. 58.6% of the complete sample were women. It
was found that 51.3% of the subjects were single, 44.7%
were married. Of the total initial subjects, 29 did not ap-
pear to know their test result, 352 (51.6%) received the
result of carriers and 305 (44.7%) received the result of
non-carriers. Along the four moment of the general pro-
tocol, subjects were given up. This is why we witnessed
a sharp decline in the subject number at the post-test one
year later.
Men and women have proven to be equivalent in their
distribution regarding the age (X2 = 636.939; df = 625; p
Table 1. Sample characteristics along the four moments of the general psychological evaluation protocol.
Pre-test a (N = 686) Post-test b (N = 290) Post-test c (N = 143) Post-test d (N = 54)
FAP HD MJD FAP HD MJD FAP HD MJD FAP HD MJD
N 586 92 8 248 38 4 114 25 4 40 13 1
Gender F 340
M 246
F 54
M 38
F 8
M 0
F 146
M 102
F 20
M 18
F 4
M 0
F 64
M 50
F 14
M 11
F 4
M 0
F 25
M 15
F 7
M 6
F 1
M 0
Mean Age 35.09 43.69 38.75 34.83 46.45 48.00 34.68 45.24 48.00 31.85 45.46 37.00
Marital
Status
S 320
M 239
D 10
W 8
S 27
M 59
D 0
W 0
S 2
M 6
D 0
W 0
S 134
M 104
D 3
W 3
S 13
M 23
D 1
W 1
S 1
M 3
D 0
W 0
S 59
M 52
D 0
W 1
S 9
M 14
D 1
W 1
S 1
M 3
D 0
W 0
S 22
M 17
D 0
W 0
S 2
M 11
D 0
W 0
S 0
M 1
D 0
W 0
Test Result NC 311
C 254
DK 17
NC 39
C 45
DK 8
NC 2
C 6
DK 0
NC 124
C 117
DK 5
NC 16
C 21
DK 1
NC 0
C 4
DK 0
NC 47
C 62
DK 3
NC 5
C 19
DK 1
NC 0
C 4
DK 0
NC 10
C 29
DK 0
NC 2
C 9
DK 2
NC 0
C 1
DK 0
Gender (Female; Male); Marital Status (Single; Married; Divorced; Widow); Test Result (Non Carrier; Carrier; Don’t know).

L. Susana et al. / Open Journal of Genetics 3 (2013) 14-26 16
= 0.362), marital status (X2 = 5.733; df = 2; p = 0.057),
and test result (X2 = 2.446; df = 2; p = 0.294).
2.2. Procedure
The PST protocol queries for neurodegenerative diseases
in CGPP have been published elsewhere [2].
In the context of the protocol, each subject answered
the anxiety scale evaluation along four stages: 1) pre-test:
the first psychological evaluation, it was done the survey
and evaluation of the motivations that led the person to
pre-symptomatic test, exploring his/her own decision
making processes and detection of emotional states that
might jeopardize a good adjustment to the predictive test
result (hereafter designated 1st moment); 2) post-test:
three weeks after receiving the test result post-test (here-
after designated 2nd moment); 3) six months after disclo-
sure (hereafter designated 3rd moment); 4) one year after
reporting the genetic test result (hereafter designated 4th
moment).
The socio-demographic variables (gender, age and ma-
rital status) and medical history were collected at the first
psychological evaluation.
The anxiety variable was collected by the application
of the Portuguese version [19] of the Self-Rating Anxiety
Scale of Zung (SAS) [20]. This scale is composed of 20
items rated on a Likert scale of four grades (1 “rarely or
never” to 4 “most or all of the time”) and measure the
anxiety clinical symptoms.
Anxiety is evaluated from the description of its most
common symptoms and signals through four anxiety
components (subscales): cognitive (items 1 - 3, 4 and 5)
which can reach a maximum of 20 points, motor (items 6,
7, 8 and 9) which can reach a maximum of 16, vegetative
(items 10 - 16, 17 and 18) that can reach a maximum of
36 and central nervous system—CNS—(items 19 and 20)
with a maximum value of 8 points. The score ranges be-
tween 20 and 80 and the cut point is 40 [19].
2.3. Data Analysis
The statistical analysis was performed with the software
PASW Statistics 19.0 [21]. We carry out procedures re-
lated to descriptive statistics (frequencies, mean, stan-
dard deviation, minimum, maximum), bi-variate statis-
tics (mean, ANOVA, correlation bi-varied); prediction of
numerical results (multiple linear regression, stepwise)
predicting for the identification of groups (factor analysis
and discriminant analysis).
3. RESULTS
3.1. Descriptive Analysis for the Four
Evaluation Moments
We analyzed the mean and standard deviation of the re-
sults obtained from the application of SAS in the four
moments considered, for the total sample and for female
and male subsamples.
Reading Table 2, it can be seen that, along the four
moments, women had always higher averages than men.
For both genders, 1st moment revealed higher mean val-
ues (male: M = 39.6, SD = 8.07; female: M = 43.7, SP =
8.87), however, in women, there is a slight increase in
average from the second to the third moment of data col-
lection.
3.2. Descriptive Statistics of the 20 SAS Items
for the Four Stages of Evaluation
We proceeded to the descriptive analysis for the 20 items
of the scale (mean, standard deviation and percentage of
symptomatic responses, i.e., those scored with 2, 3 or 4
points) for the total sample and male and female sub-
samples, for four moment’s evaluation. We can see that,
at first assessment (Table 3), i.e., before genetic testing
(1st moment), women, in general, have significantly higher
averages in some of the items that described anxiety
symptoms, for example, restlessness and fear, headaches,
neck and back pain and stomachache, or more night-
mares.
At post-test, three weeks after the communication of
the PST result (2nd moment), it was found, with statis-
tically significant results, that women continued to show
a greater tendency to feel more nervous and anxious than
men and have higher sleep disturbance (Table 4).
Regarding Table 5, six months after knowing test re-
sult (3rd moment), women fell more scared for no reason
and have hands dry and warm more often than men; fur-
thermore, men fell that things will be all right more than
women.
Reading Table 6, at 4th moment, there are no statisti-
cally significant differences between female and male
subsamples.
3.3. Comparison of the Total Means along
the Four Evaluation Moments
We found that the for the total anxiety average decreased
over the four moments. In almost all moments compared,
except between the 1st and the 3rd moments, and the 2nd
and 3rd moments, the mean values obtained from the ap-
plication of SAS decreased significantly with a p value
less than 0.05 (see Table 7).
3.4. Comparison of the SAS Subscales Means
along the Four Evaluation Moments
We observed a decrease in all SAS subscales over the
four moments of our evaluation as we can see from the
reading Tables 8-11.
In Table 8, we found statistically significant differ-
ences between 1st and 2nd moments, 1st and 3rd moments,

L. Susana et al. / Open Journal of Genetics 3 (2013) 14-26 17
and 2nd and 3rd moments regarding motor anxiety sub-
scale.
In Table 9, we found statistically significant differ-
ences between 1st and 2nd moments, and 1st and 4th mo-
ments regarding cognitive anxiety subscale.
In Table 10, we found statistically significant differ-
ences between 1st and 2nd moments, 1st and 4th moments,
and 3rd and 4th moments regarding vegetative anxiety
subscale.
In Table 11, we found statistically significant differ-
ences between 1st and 3rd moments, and 1st and 4th mo-
ments regarding CNS anxiety subscale.
Tab le 2. Total SAS results (mean, standard deviation) for the four moments evaluated (1st, 2nd, 3rd, 4th), for the total sample and fe-
male and male subsamples.
Total Sample Female Male
M SD M SD M SD
SAS 41.9 8.75 43.7 8.87 39.6 8.07
1st moment (n = 653; α = 0.80) (n = 378; α = 0.79) (n = 275; α = 0.78)
SAS 40.2 8.21 41.4 8.45 38.6 7.61
2nd moment (n = 232; α = 0.82) (n = 135; α = 0.82) (n = 97; α = 0.79)
SAS 41.0 9.87 43.0 10.10 38.4 9.05
3rd moment (n = 85; α = 0.83) (n = 48; α = 0.82) (n = 37; α = 0.85)
SAS 36.7 8.10 37.2 7.40 35.8 9.02
4th moment (n = 62; α = 0.83) (n = 35; α = 0.79) (n = 27; α = 0.87)
Ta b l e 3 . Results of the items of the SAS 1st moment (mean, standard deviation, and percentage of symptomatic responses) for the
total sample and female and male subsamples.
Total Sample Female Male
Item
M SD % M SD % M SD %
1—I feel more nervous and anxious than usual.** 1.86 0.82 62.6 1.960.80 70.4 1.72 0.8351.4
2—I feel afraid for no reason.* 1.39 0.65 31.1 1.440.66 35.9 1.32 0.6324.4
3—I get upset easily or feel panicky. 1.220.5317.71.240.55 19.0 1.20 0.5015.2
4—I feel like I'm falling apart and going to pieces. 1.400.6631.31.430.66 34.8 1.35 0.65 26.4
5—I feel that everything is all right and nothing bad will happen.** 2.58 0.95 85.6 2.670.93 88.0 2.46 0.9782.0
6—My arms and legs shake and tremble.* 1.42 0.62 35.9 1.470.62 40.4 1.35 0.6129.7
7—I am bothered by headaches neck and back pain.** 1.70 0.77 54.1 1.80 0.79 60.6 1.56 0.71 45.2
8—I feel weak and get tired easily.* 1.44 0.67 34.6 1.490.72 37.1 1.36 0.5931.1
9—I feel calm and can sit still easily.** 2.41 1.04 76.7 2.511.02 81.2 2.26 1.0470.6
10—I can feel my heart beating fast. 1.420.62357 1.450.63 38.2 1.37 0.6032.2
11—I am bothered by dizzy spells. 1.250.5221.11.270.53 23.9 1.21 0.5217.2
12—I have fainting spells or feel like it. 1.080.327.2 1.100.36 8.9 1.06 0.265.0
13—I can breathe in and out easily.** 1.70 1.02 38.5 1.791.05 42.7 1.57 0.9531.8
14—I get feelings of numbness and tingling in my fingers & toes. 1.360.6429.31.390.67 30.6 1.33 0.5827.5
15—I am bothered by stomach aches or indigestion.** 1.43 0.70 33.6 1.500.75 38.7 1.33 0.6126.8
16—I have to empty my bladder often. 1.75 0.78 56.6 1.780.81 57.9 1.70 0.7554.6
17—My hands are usually dry and warm. 2.81 1.09 83.4 2.871.08 85.1 2.74 1.1081.1
18—My face gets hot and blushes.** 1.95 0.86 66.8 2.080.91 71.5 1.77 0.7660.2
19—I fall asleep easily and get a good night’s rest.** 1.98 1.0555.5 2.07 1.07 58.9 1.85 1.00 50.7
20—I have nightmares.** 1.39 0.66 31.6 1.460.70 36.4 1.30 0.5824.9
Note: *Differences between men and women to p < 0.05; **Differences between men and women to p < 0.01.

L. Susana et al. / Open Journal of Genetics 3 (2013) 14-26 18
Tab l e 4 . Results of the items of the SAS 2nd moment (mean, standard deviation, and percentage of symptomatic responses) for the
total sample and female and male subsamples.
Total Sample Female Male
Item M SD % M SD % M SD %
1—I feel more nervous and anxious than usual.* 1.580.7345.41.660.7850.5 1.46 0.6538.1
2—I feel afraid for no reason. 1.320.5826.11.360.6229.4 1.25 0.5121.5
3—I get upset easily or feel panicky. 1.200.4517.91.210.4618.9 1.18 0.4316.6
4—I feel like I'm falling apart and going to pieces. 1.320.5926.21.340.63 27.2 1.29 0.54 24.8
5—I feel that everything is all right and nothing bad will happen.*2.46 0.93 83.1 2.56 0.90 86.5 2.31 0.95 78.5
6—My arms and legs shake and tremble. 1.330.5430.01.360.5532.6 1.30 0.5326.4
7—I am bothered by headaches neck and back pain. 1.640.7350.61.660.7451.8 1.60 0.7148.8
8—I feel weak and get tired easily. 1.43 0.70 33.0 1.46 0.76 33.0 1.39 0.61 33.0
9—I feel calm and can sit still easily. 2.39 1.00 75.9 2.48 0.96 80.0 2.26 1.04 69.3
10—I can feel my heart beating fast. 1.370.5732.31.400.5835.3 1.33 0.5728.1
11—I am bothered by dizzy spells. 1.270.5522.11.290.6221.8 1.23 0.4222.5
12—I have fainting spells or feel like it. 1.090.327.9 1.110.379.4 1.06 2.235.8
13—I can breathe in and out easily. 1.590.9633.61.580.9731.7 1.60 0.9436.4
14—I get feelings of numbness and tingling in my fingers & toes.1.280.5324.11.250.5221.2 1.32 0.5328.3
15—I am bothered by stomach aches or indigestion. 1.430.6535.41.440.6435.9 1.43 0.6634.7
16—I have to empty my bladder often. 1.710.7555.61.720.7755.3 1.70 0.7255.8
17—My hands are usually dry and warm. 2.82 1.09 83.6 2.84 1.05 85.2 2.80 1.15 80.1
18—My face gets hot and blushes. 1.84 0.79 64.01.890.87 63.3 1.77 0.67 65.0
19—I fall asleep easily and get a good night’s rest.* 1.971.0157.02.081.0262.3 1.82 0.9849.6
20—I have nightmares.* 1.340.6028.21.400.6731.2 1.26 0.4724.0
Note: *Differences between men and women to p < 0.05.
Ta b le 5 . Results of the items of the SAS 3rd moment (mean, standard deviation, and percentage of symptomatic responses) for the
total sample and female and male subsamples.
Total Sample Female Male
Item M SD % M SD % M SD %
1—I feel more nervous and anxious than usual. 1.770.7657.71.810.7561.3 1.71 0.7853.2
2—I feel afraid for no reason.* 1.290.5921.71.380.6627.5 1.17 0.4614.3
3—I get upset easily or feel panicky. 1.250.5419.41.260.5322.3 1.22 0.5615.5
4—I feel like I’m falling apart and going to pieces. 1.430.6335.11.490.64 40.8 1.34 0.61 27.6
5—I feel that everything is all right and nothing bad will happen.*2.37 0.92 82.1 2.54 0.92 88.2 2.14 0.89 74.2
6—My arms and legs shake and tremble. 1.360.5731.41.410.6134.2 1.29 0.5027.6
7—I am bothered by headaches neck and back pain. 1.690.7852.61.690.7952.0 1.69 0.7553.5
8—I feel weak and get tired easily. 1.40 0.63 32.1 1.43 0.62 36.9 1.34 0.64 25.8
9—I feel calm and can sit still easily. 2.11 0.9569.4 2.09 0.91 71.1 2.14 1.02 67.3
10—I can feel my heart beating fast. 1.370.5135.11.430.5540.8 1.28 0.4527.6
11—I am bothered by dizzy spells. 1.360.6427.51.360.6726.3 1.36 0.6129.3
12—I have fainting spells or feel like it. 1.130.479.7 1.200.5913.1 1.05 0.225.2
13—I can breathe in and out easily. 1.660.9539.61.710.9942.1 1.59 0.9036.3
14—I get feelings of numbness and tingling in my fingers & toes.1.370.6629.11.290.6321.1 1.48 0.6839.7
15—I am bothered by stomach aches or indigestion. 1.420.6435.11.460.6638.2 1.36 0.6131.0
16—I have to empty my bladder often. 1.810.8258.91.870.8163.1 1.74 0.8553.4
17—My hands are usually dry and warm.** 2.811.1281.93.051.0688.2 2.49 1.1473.7
18—My face gets hot and blushes. 1.75 0.80 56.71.790.85 57.9 1.71 0.73 55.2
19—I fall asleep easily and get a good night’s rest. 1.840.9950.01.910.9755.3 1.76 1.0143.1
20—I have nightmares. 1.370.6629.81.450.7035.4 1.28 0.5622.4
Note: *Differences between men and women to p < 0.05; **Differences between men and women to p < 0.01.

L. Susana et al. / Open Journal of Genetics 3 (2013) 14-26 19
Table 6. Results of the items of the SAS d (mean, standard deviation, and percentage of symptomatic responses) for the total sample
and subsamples female and male.
Total Sample Female Male
Item M SD % M SD % M SD %
1—I feel more nervous and anxious than usual. 1.540.7341.8 1.58 0.76 44.7 1.48 0.69 37.9
2—I feel afraid for no reason. 1.120.3710.51.110.3110.5 1.14 0.4410.3
3—I get upset easily or feel panicky. 1.120.3710.51.110.3110.5 1.14 0.4410.3
4—I feel like I'm falling apart and going to pieces. 1.270.5920.91.240.49 21.0 1.31 0.71 19.8
5—I feel that everything is all right and nothing bad will happen.2.250.0570.2 2.39 1.00 76.3 2.07 1.10 62.0
6—My arms and legs shake and tremble. 1.280.6022.41.290.5723.7 1.28 0.6520.6
7—I am bothered by headaches neck and back pain 1.660.6953.71.740.7257.9 1.55 0.6348.3
8—I feel weak and get tired easily. 1.450.6338.8 1.47 0.60 42.1 1.41 0.68 34.4
9—I feel calm and can sit still easily. 2.031.0359.7 2.05 1.04 60.5 2.00 1.03 58.6
10—I can feel my heart beating fast. 1.340.5928.41.450.6536.8 1.21 0.4917.2
11—I am bothered by dizzy spells. 1.160.4812.01.210.5315.8 1.10 0.416.8
12—I have fainting spells or feel like it. 1.010.121.5 1.030.162.6 1.00 0.000.0
13—I can breathe in and out easily. 1.360.7125.41.240.4921.0 1.52 0.9131.0
14—I get feelings of numbness and tingling in my fingers & toes.1.340.5929.91.420.6436.8 1.24 0.5120.6
15—I am bothered by stomach aches or indigestion. 1.390.6331.4 1.26 0.50 23.7 1.55 0.74 41.4
16—I have to empty my bladder often. 1.840.7564.2 1.87 0.74 65.8 1.79 0.77 62.0
17—My hands are usually dry and warm. 2.601.1179.2 2.82 1.11 81.6 2.31 1.07 75.9
18—My face gets hot and blushes. 1.940.8762.7 1.97 0.89 63.1 1.90 0.86 62.0
19—I fall asleep easily and get a good night’s rest. 1.520.7438.8 1.53 0.76 39.4 1.52 0.74 37.9
20—I have nightmares. 1.400.6831.41.420.6434.2 1.38 0.7327.5
Table 7. Comparison of the total obtained from the application of SAS in the first (1st), second (2nd), third (3rd) and fourth (4th)
evaluation moments.
Comparison (moments) Mean N t d.f. Sig. (2-tailed)
SAS 1st 41.70 219
1st Moment* 2nd Moment SAS 2nd 40.07 219 3.508 218 0.001*
SAS 1st 42.17 80
1st Moment* 3rd Moment SAS 3rd 40.94 80 1.297 79 0.198
SAS 1st 41.86 59
1st Moment* 4th Moment SAS 4th 36.65 59 4.614 58 0.000*
SAS 2nd 39.48 60
2nd Moment* 3rd Moment SAS 3rd 40.19 60 −0.807 59 0.423
SAS 2nd 39.81 45
2nd Moment* 4th Moment SAS 4th 37.14 45 2.342 44 0.024*
SAS 3rd 39.55 33
3rd Moment* 4th Moment SAS 4th 36.48 33 2.960 32 0.006*
3.5. Comparison of the Anxiety Rates Regarding
Socio-Demographic Variables over the Four
Moments Evaluated
We compared the SAS questionnaire total mean, as well
as the subscales means regarding socio-demographic va-
riables (age, gender, marital status, type of disease, ge-
netic test result) and we found some significant values.
Thus, with respect to gender variable it was found that
women had, over the several moments, significantly
higher values than men (p < 0.050) for total SAS ques-
tionnaire and for motor anxiety subscale (1st moment),
for cognitive anxiety subscale (1st, 2nd and 3rd moments),
for vegetative anxiety subscale (1st and 3rd moment), and
for CNS anxiety subscale (1st and 2nd moment) as we can
see consulting Table 12.
Respecting to the age variable, when compared the
mean of CNS anxiety (1st moment) we verify that sub-
jects between 61 - 70 and 41 - 50 have higher values;
when compared the motor anxiety subscale mean (2nd
and 3rd moment), we found that older subjects (age be-

L. Susana et al. / Open Journal of Genetics 3 (2013) 14-26 20
Tab le 8. Comparison of the total means for the SAS motor anxiety subscale in the first (1st), second (2nd), third (3rd) and fourth (4th)
evaluation moments.
Comparison (moments) Motor Anxiety Mean N t df Sig. (2-tailed)
MASAS 1st 7.02 279
1st Moment* 2nd Moment MASAS 2nd 6.76 279
2.139 278 0.033*
MASAS 1st 7.16 128
1st Moment* 3rd Moment MASAS 3rd 6.57 128 3.068 127 0.003*
MASAS 1st 6.92 66
1st Moment* 4th Moment MASAS 4th 6.45 66
1.878 65 0.065
MASAS 2nd 6.97 118
2nd Moment* 3rd Moment MASAS 3rd 6.61 118
2.096 117 0.038*
MASAS 2nd 6.78 50
2nd Moment* 4th Moment MASAS 4th 6.54 50 0.678 49 0.501
MASAS 3rd 6.38 45
3rd Moment* 4th Moment MASAS 4th 6.62 45
−0.788 44 0.435
Ta bl e 9 . Comparison of the total means for the SAS cognitive anxiety subscale in the first (1st), second (2nd), third (3rd) and fourth
(4th) evaluation moments.
Comparison (moments) Cognitive Anxiety Mean N t df Sig. (2-tailed)
CASAS 1st 8.52 283
1st Moment* 2nd Moment CASAS 2nd 7.85 283 4.468 282 0.000*
CASAS 1st 8.33 131
1st Moment* 3rd Moment CASAS 3rd 8.10 131 0.890 130 0.375
CASAS 1st 8.57 67
1st Moment* 4th Moment CASAS 4th 7.30 67
3.470 66 0.001*
CASAS 2nd 7.84 116
2nd Moment* 3rd Moment CASAS 3rd 8.05 116 −0.830 115 0.408
CASAS 2nd 7.96 50
2nd Moment* 4th Moment CASAS 4th 7.42 50
1.537 49 0.131
CASAS 3rd 7.93 45
3rd Moment* 4th Moment CASAS 4th 7.38 45
1.375 44 0.176
Table 10. Comparison of the total means for the SAS vegetative anxiety subscale in the first (1st), second (2nd), third (3rd) and fourth
(4th) evaluation moments.
Comparison (moments) Vegetative Anxiety Mean N t df Sig. (2-tailed)
VASAS 1st 14.70 274
1st Moment* 2nd Moment VASAS 2nd 14.39 274
2.012 273 0.045*
VASAS 1st 14.79 129
1st Moment* 3rd Moment VASAS 3rd 14.60 129
0.752 128 0.454
VASAS 1st 14.85 65
1st Moment* 4th Moment VASAS 4th 13.92 65 2.672 64 0.010*
VASAS 2nd 14.54 113
2nd Moment* 3rd Moment VASAS 3rd 14.71 113
−0.664 112 0.508
VASAS 2nd 14.24 50
2nd Moment* 4th Moment VASAS 4th 13.96 50
0.768 49 0.446
VASAS 3rd 14.32 44
3rd Moment* 4th Moment VASAS 4th 13.66 44
2.048 43 0.047*

L. Susana et al. / Open Journal of Genetics 3 (2013) 14-26 21
Tab le 1 1 . Comparison of the total means for the SAS CNS anxiety subscale in the first (1st), second (2nd), third (3rd) and fourth (4th)
evaluation moments.
Comparison (moments) CNS Anxiety Mean N t df Sig. (2-tailed)
CNSSAS 1st 3.42 285
1st Moment* 2nd Moment CNSSAS 2nd 3.29 285
1.696 284 0.091
CNSSAS 1st 3.54 132
1st Moment* 3rd Moment CNSSAS 3rd 3.20 132
2.581 131 0.011*
CNSSAS 1st 3.36 67
1st Moment* 4th Moment CNSSAS 4th 2.93 67
2.580 66 0.012*
CNSSAS 2nd 3.37 118
2nd Moment* 3rd Moment CNSSAS 3rd 3.25 118 1.185 117 0.238
CNSSAS 2nd 3.04 50
2nd Moment* 4th Moment CNSSAS 4th 3.02 50
0.118 49 0.907
CNSSAS 3rd 2.93 45
3rd Moment* 4th Moment CNSSAS 4th 2.96 45 −0.133 44 0.895
Table 12. Comparison between SAS total and subscales mean values regarding variable gender over the several moments.
Total Scores SAS Mean N F Sig.
Female 43.47 378
1st moment (SAS 1st)
Male 39.62 275
32.247 0.000
Female 41.36 135
2nd moment (SAS 2nd)
Male 38.57 97
6.680 0.010
Female 42.97 48
3rd moment (SAS 3rd)
Male 38.41 37
4.651 0.034
SAS Subscales Scores Mean N F Sig
Female 7.26 390
Motor Anxiety 1st moment (MASAS 1st) Male 6.53 278 18.927 0.000
Female 8.75 390
Cognitive anxiety 1st moment (CASAS 1st) Male 8.01 278 14.430 0.000
Female 8.15 169
Cognitive anxiety 2nd moment (CASAS 2nd) Male 7.50 121
5.797 0.017
Female 8.50 76
Cognitive anxiety 3rd moment (CASAS 3rd) Male 7.60 57
4.555 0.035
Female 15.26 384
Vegetative anxiety 1stmoment (VASAS 1st) Male 14.09 279
26.853 0.000
Female 15.16 76
Vegetative anxiety 3rd moment (VASAS 3rd) Male 13.98 57
5.095 0.026
Female 3.53 392
CNS anxiety 1st moment (CNSSAS 1st) Male 3.15 280
12.899 0.000
Female 3.48 170
CNS anxiety 2nd moment (CNSSAS 2nd) Male 3.07 121
6.622 0.011
tween 61 and 80 years) are those with higher average
(Table 13).
Concerning marital status, it was found significant dif-
ferences, at 1st moment, for vegetative anxiety subscale (t
= 2.996; df = 4; p = 0.018): widow individuals had the
highest average and, at 3rd moment, six months after dis-
closure, married subjects had the highest averages in the
SAS total mean (Table 14).
Finally, it was found significant values when compar-
ing the total SAS and subscales SAS means with the
variable type of disease.
As shown by the observation of Ta ble 15, at 1st mo-
ment, only the CNS anxiety subscale presents significant
values, indicating that the subjects who performed the
HD PST as having the highest values.
At 2nd, 3rd and 4th moments, after disclosure, MJD sub-

L. Susana et al. / Open Journal of Genetics 3 (2013) 14-26 22
Table 13. Comparison between SAS total and subscales mean values regarding variable age over the several moments.
Moments Subscales Mean N F Sig.
1st moment CNS anxiety
CNSSAS 1st
17 - 30
31 - 40
41 - 50
51 - 60
61 - 70
71 - 80
3.38
3.16
3.60
3.51
3.94
3.43
262
229
73
55
33
7
2.880 0.014
2nd moment Motor Anxiety
MASAS 2nd
17 - 30
31 - 40
41 - 50
51 - 60
61 - 70
71 - 80
6.82
6.38
7.18
6.77
8.06
7.77
111
99
28
26
16
3
2.247 0.050
3rd moment Motor Anxiety
MASAS 3rd
17 - 30
31 - 40
41 - 50
51 - 60
61 - 70
71 - 80
6.35
6.00
6.87
7.50
8.29
8.00
48
45
15
14
7
1
2.433 0.039
Table 14. Comparison between the mean values of the SAS subscales regarding the variable marital status over the several moments.
Moments Subscales/Totals Mean N F Sig.
1st moment Vegetative anxiety
Single
Married
Divorced
Widow
14.52
14.94
13.92
17.10
336
294
12
10
2.996 0.018
3rd moment Total SAS
Single
Married
Divorced
Widow
38.48
44.24
0
0
46
38
0
0
4.230 0.018
Table 15. Comparison between the mean values of the SAS totals and subscales with the variable type of disease over the several
moments.
Moments Subscales/Totals Mean N F Sig.
1st moment CNS anxiety
FAP
MJD
HD
3.34
2.75
3.66
574
8
90
3.019 0.050
Total SAS
FAP
MJD
HD
39.80
51.25
41.17
195
4
33
2nd moment
Cognitive anxiety
FAP
MJD
HD
7.83
11.00
7.82
247
4
39
4.194
3.839
0.016
0.023
3rd moment Motor Anxiety
FAP
MJD
HD
6.28
8.50
7.48
104
4
25
5.154 0.007
4th moment CNS anxiety
FAP
MJD
HD
2.73
5.00
3.25
49
2
16
5.183 0.008
jects are those having significantly higher values in SAS
subscales and also in the SAS total score, three weeks
after disclosure, presenting total scores (>40 points) re-
vealing clinical anxiety.
3.6. Predictors of the Self-Rating Anxiety
Scale of Zung (SAS)
We intend to know the predictive value of some socio-
demographic and other variables that could take an expli-
cative character to the values found in the SAS scale
over the four evaluation moment sand for the three stud-
ied diseases.
Thus, we performed the multiple linear regression
analysis using stepwise estimation method [22] for the
total scores of the SAS scale, as well as for cognitive,
motor, vegetative and CNS SAS subscales. We consid-

L. Susana et al. / Open Journal of Genetics 3 (2013) 14-26 23
ered the socio-demographic variables as independent va-
riables.
Analyzing Table 16, we can see that gender is the
variable that has a higher predictive value in the regres-
sion equation explaining 4% of the dependent variable
Total SAS variance, at 1st moment. The final equation is
made by the independent variables gender and test result
(R2 = 0.51, F = 17.849, df = 2, p = 0.000) explaining,
overall, 5.1% of the total SAS score variance, at 1st mo-
ment (Table 16).
It was also found that the independent variable gender
is the one with the most predictive power in the regres-
sion equation, explaining 2% of the dependent variable
Total SAS variance, at 2nd moment; the final equation is
made by the independent variables gender, type of dis-
ease and test result (R2 = 0.06, F = 4.644, df = 3, p =
0.004) explaining, overall, 6% of the total SAS score
variation, at 2nd moment (Table 17).
Analyzing Table 18, we can see that the independent
variable, marital status, shows the highest predictive
value in the regression equation, explaining 9% of the
dependent variable Total SAS variance, at 3rd moment;
the final equation is made by the independent variables
marital status, gender and test result (R2 = 0.21, F =
6.804, df = 3, p = 0.000) which explain, overall, 21% of
the total SAS score variation, at 3rd moment (Table 18).
Then, we conducted linear regression analyzes for all
SAS subscales and for all the evaluation moments con-
sidered. These analyze yielded the following significant
results:
For the cognitive anxiety subscale, it was found that
the independent variable gender was the only one that
had predictive value in the regression equation (R2 =
Table 16. Multiple linear regression analysis for variables pre-
dicting the Total SAS 1st moment.
MODEL VARIABLE B SE β
1 Gender −3.817 0.688 −0.216**
2 Gender −3.900 0.687 −0.220**
Test Result −1.327 0.612 −0.084*
R2 = 0.04 step 1; ΔR2 = 0.05 step 2; **p < 0.010, *p < 0.050.
Table 17. Multiple linear regression analysis for variables pre-
dicting the Total SAS 2nd moment.
MODEL VARIABLE B SE β
1 Gender −2.520 1.114 −0.151*
2 Gender
Type of Disease
−2.412
2.767
1.105
1.276
−0.144*
0.143*
3 Gender
Type of Disease
Test Result
−2.611
3.161
−2.012
1.103
1.283
1.020
−0.156*
0.164
−0.132
R2 = 0.02 step 1; ΔR2 = 0.04 step 2 ΔR3 = 0.06 step 3; **p < 0.010, *p <
0.050.
Table 18. Multiple linear regression analysis for variables pre-
dicting the Total SAS 3rd moment.
MODEL VARIABLE B SE β
1 Marital Status 5.577 2.021 0.293**
2 Marital Status
Gender
5.540
−4.514
1.976
2,064
0.291**
−0.227*
3 Marital Status
Gender
Test Result
6.237
−5.565
−5.589
1.927
2.034
2.153
0.324**
−0.280**
−0.268*
R2 = 0.09 step 1, ΔR2 = 0.14 step 2, ΔR3 = 0.21 step 3; **p < 0.010, *p <
0.050.
0.20, F = 13.032, df = 1, p = 0.000), explaining 2% of the
variance at 1st moment. The same can be said, for the
same dependent variable, at 2nd moment, the independent
variable gender continued to explained 2% of the vari-
ance (R2 = 0.20, F = 5.756, df = 1, p = 0.017). Concern-
ing yet this dependent variable, at 3rd moment, we ob-
served that the independent variable type of disease was
the only one that explained 4% of the variance (R2 = 0,43,
F = 5,722, df = 1, p = 0,018).
It was verified that the independent variable gender
was the only one that had predictive value in the regres-
sion equation (R2 = 0.27, F = 18.018, df = 1, p = 0.000),
by explaining 3% of the variance of the dependent vari-
able motor anxiety subscale, at 1st moment. At 3rd mo-
ment, we found that the two independent variables type
of disease and test results, together, explained 11% of the
dependent variable motor anxiety subscale variance (R2
= 0.11, F = 7.892, df = 2, p = 0.001).
For the dependent variable vegetative anxiety subscale,
at 1st moment, the independent variables gender, test
result, and marital status explained6% of its variance (R2
= 0.06, F = 12.670, df = 3, p = 0.000); at 3rd moment, the
independent variables age and gender, together, ex-
plained 8% of the variance of this same dependent vari-
able (R2 = 0.08, F = 5.610, df = 2, p = 0.005); finally, at
4th moment, the independent variable marital status was
the one that explained 9% of the variance.
At last, regarding the dependent variable CNS anxiety
subscale, at 1st moment, the dependent variables gender
and age, together, explained 3% (R2 = 0.03, F = 8.817, df
= 2, p = 0.000) of its variance; at 2nd moment, the inde-
pendent variable gender, explained 2% of its variance
(R2 = 0.02, F = 4.729, df = 1, p = 0.031); finally, at 4th
moment, the independent variable type of disease, ex-
plained 11% of its variance (R2 = 0.11, F = 8.191, df = 1,
p = 0.006).
4. DISCUSSION
We have found that the number of patients leaving the
protocol over one year was quite high and this can be the
principal limitation of this study; thus, this can bias the
conclusions we draw from the data obtained. We found

L. Susana et al. / Open Journal of Genetics 3 (2013) 14-26 24
that, proportionally, the number of carriers increases and
non carriers decreases over protocol, i.e., the carriers
remain in the protocol more than non carriers; therefore,
it is necessary to take into account this point as one of
the limitations of this study.
The descriptive analysis, such as a previous study of
measurement of scale to Portuguese population [19],
revealed that female had higher values of anxiety symp-
toms. The pre-test (1st moment) recorded higher values
for both genders, although for women values were in-
dicative of clinical anxiety (score ≥ 40) and men were on
the border between normal and pathological anxiety. For
both groups it can be stated that anxiety decreased over
four assessment moments.
We also obtained results quite acceptable for internal
consistency, since the αvalues were always, for all mo-
ments and groups considered, very close to 0.80, leading
us to conclude that this instrument is reliable for the
studied population.
By examining the 20 items scale, we find that women,
in the pre-test (1st moment), revealed a higher level of
restlessness, pessimism and fear, and a greater pain asso-
ciated with the presence of a higher generalized tension
(head, neck and back); these findings seem to corrobo-
rate the presence of the total scores inducing anxiety
symptoms, even before the completion of the TPS, as
said in previous paragraph. Higher values of anxiety
symptoms at the beginning of PST, in women, could
mean that pre-test (1st moment) itself may bea trigger of
anxiety disturbance, as well as other studies have men-
tioned, supporting the need for psychological support
since the beginning of the genetic counseling PST proc-
ess [23,24].
Three weeks after PST disclosure (2nd moment), women
continued to show a greater presence of items answered
with options-inducing presence of anxiety symptoms, in
particular, revealing more likely to present sleep disor-
ders.
These data, i.e., the reduction of anxiety score during
the protocol (mostly, from 1st moment to 2nd moment,
first post-test immediately after the PST communication),
also seem to indicate that the PST brings advantages in
reducing the uncertainty and self control effects for the
disease to which the at-risk individual decides to make
the test [15,16,25].
Considering the anxiety total scores and subscales
values regarding socio-demographic variables, some sig-
nificant results were found:
Thus, with respect to gender variable it was found that
women had, over the several moments, significantly
higher values than men for total SAS questionnaire and
for motor anxiety subscale (1st moment), for cognitive
anxiety subscale (1st, 2nd and 3rd moments), for vegetative
anxiety subscale (1st and 3rd moment), and for CNS anxi-
ety subscale (1st and 2nd moment).
Respecting to the age variable, when compared the
mean of CNS anxiety (1st moment) we verify that sub-
jects between 61 - 70 and 41 - 50 have higher values;
when compared the motor anxiety subscale mean (2nd
and 3rd moment), we found that older subjects(age be-
tween 61 and 80 years) are those with higher average.
This can be explained, first, according to the SAS scale
normalization studies for the portuguese population,
there is a greater tendency for older individuals present
higher values of anxiety [26]; second, the age of these
subjects (between 40 and 51 years) is approaching the
age mean considered to the beginning of this late on-set
diseases first symptoms, that can lead to higher anxiety
values.
Considering marital status, we found a tendency for
widow subjects had the highest average in the vegetative
anxiety subscale at pre-test (1st moment); this result
seems to point to the hypothesis that people at risk and
more alone may have greater tendency for a higher level
of anxiety symptoms. Widowhood maybe relates to the
perceived lack of effective care, by becoming more dif-
ficult the existence of a future caregiver. The fact that, in
the divorced group, we did not observe the same trend,
canbe explained with the age factor, i.e., widows tend to
be older people. After 6months of PST disclosure (3rd
moment), the married subjects group had higher total
anxiety, compared with the single individuals (note that
this moment assessed only subjects with these two mari-
tal status); therefore, it may be the existence of a partner
or objectives of having a child, significant factors to in-
duce higher values of anxiety, since it was widely stud-
ied the importance of partners in the at-risk and/or ill
patients for HD [8,27].
Finally, when we compared the total scores and sub-
scales means regarding the type of disease variable, we
found significant values for the CNS anxiety subscale, in
the pre-test, for HD; this may indicate greater anxiety for
those at risk for this disease, given the severity of their
clinical condition. This may also be related to some HD
carriers psychopathological symptoms, that may already
be manifesting at the beginning of the PST protocol (1st
moment). This aspect concerning the disease severity
might explain why, at all post-test moments (2nd, 3rd and
4th moments), the HD subjects continued to reveal supe-
rior anxiety results, only being surpassed by the MJD
subjects (however, MJD group were not significant).
Subjects who performed the test for FAP showed lower
values, perhaps because they have hope on the drug
treatment in the near future or in the currently available
solution, the liver transplantation, in order to wage dis-
ease progression, both solutions nonexistent for HD or
MJD [3,28].
Regarding test result variable, there were no statisti-

L. Susana et al. / Open Journal of Genetics 3 (2013) 14-26 25
cally significant results, as previous studies were indi-
cated for HD: knowledge of carrier or non-carrier status
does not seem to bring a negative psychological impact
on individuals [7,8,28].
Several studies have indicated the importance of the
socio-demographic variables predictive character for po-
pulation that performs the PST [3,6-8,16,28] for the es-
tablishment of more effective interventions in those indi-
viduals identified as vulnerable. This study identified va-
riables such as gender, type of disease, marital status as
having some predictive value with respect to what can be
expected about future anxiety symptoms presented along
the several assessed moments. For this reason, the need
for a personalized and careful monitoring to each indi-
vidual who performs a PST protocol remains a substan-
tial ethical principle in conducting such genetic tests [2,
3].
5. CONCLUSIONS
We found a decrease in mean values over the four eva-
luations moments regarding total scores obtained by ap-
plying the Self-Ranting Anxiety Scale of Zung (SAS),
evidencing that subjects have higher values before pre-
symptomatic test (1st moment) than in the several post-
testing moments (2nd, 3rd and 4th moments), mainly a year
after knowing their genetic status. However, for the fe-
male population, the SAS means scores revealed a result
of clinical anxiety (>40 points) from the pre-test (1st mo-
ment), only decreasing to non clinical scores a year after
PST disclosure (4th moment).
The inherent characteristics of each disease here stud-
ied, as well as the knowledge of the genetic status—to be
or not to be a carrier—do not appear to significantly in-
fluence the presence of anxiety disorder. However, we
find a lower trend in subject’s average who took the PST
for FAP.
The variables gender, age and marital status, showed
an oscillating weight in the anxiety scores verifying that
female has higher values, as well as the older subjects or
those who are closer to the beginning of the first symp-
toms; widows also had the highest anxiety scores.
Although, from a clinical point of view, we have not
found values indicating anxiety disorder, we can con-
clude however that pre-symptomatic test for studying
diseases causes a considerable anxiety level, since the
averages were always very close to the cutoff point of
the SAS.
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