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Effects of Soy Lecithin Phosphatidic Acid and Phosphatidylserine Complex (PAS) on the Endocrine and Psychological Responses to Mental Stress

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Phosphatidylserine, derived from cow brains, has been shown previously to dampen the ACTH and cortisol response to physical stress. Further research investigated the influence of soy lecithin phosphatidylserine supplementation on mood and heart rate when faced with an acute stressor. In this study, we investigated the effects of soy lecithin phosphatidic acid and phosphatidylserine complex (PAS) supplementation on pituitary adrenal reactivity (ACTH, cortisol) and on the psychological response (Spielberger State Anxiety Inventory stress subscale) to a mental and emotional stressor. Four groups of 20 subjects were treated for three weeks with daily dosages of either 400 mg PAS, 600 mg PAS, 800 mg PAS, or placebo before exposure to the Trier Social Stress Test (TSST). Treatment with 400 mg PAS resulted in a pronounced blunting of both serum ACTH and cortisol, and salivary cortisol responses to the TSST, but did not affect heart rate. The effect was not seen with larger doses of PAS. With regard to the psychological response, 400 mg PAS seemed to exert a specific positive effect on emotional responses to the TSST. While the placebo group showed the expected increase in distress after the test, the group treated with 400 mg PAS showed decreased distress. These data provide initial evidence for a selective stress dampening effect of PAS on the pituitary-adrenal axis, suggesting the potential of PAS in the treatment of stress related disorders.
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Effects of Soy Lecithin Phosphatidic Acid
and Phosphatidylserine Complex (PAS) on the Endocrine
and Psychological Responses to Mental Stress
Neuropattern, Trier, Germany;
Department for Psychobiology, University of Trier, Germany;
Lipogen Ltd., Haifa, Israel
(Received 7 February 2004; Revised 17 May 2004; In final form 28 May 2004)
Phosphatidylserine, derived from cow brains, has been shown previously to dampen the ACTH and
cortisol response to physical stress. Further research investigated the influence of soy lecithin
phosphatidylserine supplementation on mood and heart rate when faced with an acute stressor. In this
study, we investigated the effects of soy lecithin phosphatidic acid and phosphatidylserine complex
(PAS) supplementation on pituitary adrenal reactivity (ACTH, cortisol) and on the psychological
response (Spielberger State Anxiety Inventory stress subscale) to a mental and emotional stressor. Four
groups of 20 subjects were treated for three weeks with daily dosages of either 400 mg PAS, 600 mg
PAS, 800 mg PAS, or placebo before exposure to the Trier Social Stress Test (TSST). Treatment with
400 mg PAS resulted in a pronounced blunting of both serum ACTH and cortisol, and salivary cortisol
responses to the TSST, but did not affect heart rate. The effect was not seen with larger doses of PAS.
With regard to the psychological response, 400 mg PAS seemed to exert a specific positive effect on
emotional responses to the TSST. While the placebo group showed the expected increase in distress
after the test, the group treated with 400 mg PAS showed decreased distress. These data provide initial
evidence for a selective stress dampening effect of PAS on the pituitary– adrenal axis, suggesting the
potential of PAS in the treatment of stress related disorders.
Keywords: ACTH; Cortisol; Phosphatidic acid; Phosphatidylserine; STAI; Stress
In this study we investigated a possible stress dampening
effect of soy lecithin phosphatidic acid and phosphatidyl-
serine complex (PAS) on endocrine, autonomic and
psychological measures evoked by the trier social stress
test (TSST).
Phospholipids have the very important biological
function of constituting the basis of all biological cell
membranes. Phosphatidylserine was first derived from
cow brains (Bovine Cortex Phosphatidylserine—BCPS).
Different studies showed that single intravenous treatment
(50 and 75 mg, respectively) as well as repeated oral intake
(800 mg per day for 10 days) of BCPS reduced ACTH- and
cortisol responses to physical stress (Monteleone et al.,
1990, 1992). Since 1992, soy lecithin phosphatidylserine,
the first 100% solvent free phosphatidylserine, has become
available, and this has excellent bioavailability by the oral
route (Shinitzky, 1999). In a first clinical trial, 72 subjects
aged 60–80 years, were randomly assigned to placebo and
therapy groups and treated for three months with 300 mg
phosphatidylserine and phosphatidic acid daily. The
results indicated a strong and significant positive effect
of treatment on memory and mood (Gindin et al., 1993,
1995). Benton et al. (2001) demonstrated a positive effect
of a one month treatment with 300 mg/day phosphatidyl-
serine on perceived stress during a stressful mental
arithmetic task. These data suggest a possible beneficial
effect on hypothalamus pituitary adrenal axis (HPA)
responsivity under psychological stress. Based on these
data, we were interested to explore effects of phosphati-
dylserine and phosphatic acid (PAS) on subjects under
mental stress conditions. As seen under physical stress, we
expected to see a blunted ACTH and cortisol response in
both men and women, associated with an attenuated heart
rate and psychological stress response. We further
expected a dose dependent effect of PAS, increasing
from 400 to 800 mg. To study PAS effects, we used
ISSN 1025-3890 print/ISSN 1607-8888 online q2004 Taylor & Francis Ltd
DOI: 10.1080/10253890410001728379
*Corresponding author. Address: Department for Psychobiology, University of Trier–FB I, Johanniterufer 15, D - 54290 Trier, Germany.
Tel.: þ49-651-2013464. Fax: þ49-651-2012934. E-mail:
Stress, June 2004 Vol. 7 (2), pp. 119–126
the TSST, a stress protocol that has been developed in
this laboratory.
A recent meta-analysis of Dickerson and Kemeny (2004)
compared 208 laboratory studies of acute psychological
stressors. The analysis showed that the TSST (Kirschbaum
et al., 1993) is the best standardised and most efficient
psychological stress protocol for studies on HPA-reactivity
in humans. Concerning psychological parameters, the TSST
leads to a moderate increase in fear. The biological response
comprises an increase in circulating ACTH, cortisol,
prolactin, growth hormone, norepinephrine and epinephrine
concentrations, and increased heart rate and blood pressure
(e.g. Kirschbaum et al., 1993). Thus, we decided to use the
TSST protocol to assess stress dampening effects of PAS.
The study examined the effects of three dosages of PAS
versus placebo.
This was a double-blind, single centre study. The study
duration was 4 weeks. Eighty panelists were invited to the
laboratory for pre-tests and for the experiment. They were
assigned to one of the four treatment groups (20 subjects
per group; 10 males and 10 females): per day, the first
group used placebo, the second group received
400 mg/day PAS, the third group 600 mg/day PAS and
the fourth group 800 mg/day PAS. Soy lecithin PAS
complex capsules as well as placebo capsules were
provided by Lipogen Ltd., Haifa, Israel.
PAS is a complex of phospholipids of which every
“100 mg” PAS capsule consists of 100 mg phosphadityl-
serine (PS) and 125 mg phosphatic-acid (PA), plus 270 mg
of other inert phospholipids (PC, PI, PE, Lyso Phospho-
lipids) and 5 mg silicon dioxide (anti-caking material). PAS
is patent protected (US 6,410,522 published in June 25,
2002). The placebo was maize starch and the capsules
looked identical to the PAS capsules.
Eighty subjects (adults age 20– 45) were recruited for the
study. All of the women were using oral contraceptives.
Groups were matched for sex and socioeconomic status.
As seen from Fig. 1, the mean age did not differ among the
four groups (Fð3;75Þ¼0:11; p¼0:95). Further, the four
treatment groups did not differ with respect to stress load and
depression (Gindin et al., 1993, 1995) as measured with the
Patient Health Questionnaire (PHQ; Spitzer et al.,1999;
Loewe et al.,2002)(Fð33;174Þ¼0:80; p¼0:77) when
entering the study.
Inclusion Criteria
Good medical health was verified by a clinical
examination, the patient health questionnaire and a
hemogram. The hemogram included assessments of
glutamate pyruvate transaminase, gamma-glutamyl
transferase, creatinine, leukocytes, erythrocytes (haemo-
globin, haematocrit, mean corpuscular volume, mean
corpuscular haemoglobin, mean corpuscular haemoglobin
concentration), thrombocytes and leukocyte (lymphocyte,
basophil, eosinophil, monocyte and neutrophil counts).
Exclusion Criteria
The following exclusion criteria were applied: subjects
with a history of mental illness, subjects who used any
systemic medication considered to affect the endocrine or
behavioural measures, subjects who were pregnant or
nursing, subjects participating in any other clinical study,
subjects regarded by the investigator as not being able to
complete the study, subjects deemed to be physically
Subjects were recruited by e-mail and newspaper
advertising. Pre-screening and introduction to the study
were conducted by telephone and an appointment for the
medical pre-examination was made. The medical pre-
examination and the hemogram allowed exclusion of
medically unhealthy subjects. Altogether, 85 subjects
were pre-screened, 5 subjects were excluded according to
the exclusion criteria or for personal reasons. As the great
majority of the women were using oral contraceptives, we
decided to keep the groups homogenous by including oral
contraceptive use as a further inclusion criterion for
women. The study finally included healthy male and
female non-smoking subjects between the age 20 and 45.
Subjects were assigned to one of the four treatment
groups. Ten males and 10 females were randomly assigned
FIGURE 1 *One male subject withdrew during the study (available TSST data in this group only for 19 subjects).
J. HELLHAMMER et al.120
to each group, carefully matched for socioeconomic
status. Subjects were provided with extensive information
on the study and read and signed a written informed
consent form. Subjects received 100 Euro for their
participation in the study. The protocol was approved by
the Landesa
¨rztekammer Rheinland-Pfalz (ethical com-
mission of the state’s Chamber of Medicine).
Before entry into the study, subjects were pre-screened by
the investigator for the criteria indicated above in the
subject selection section. A medical history was also taken
from each subject.
One day before initiation of treatment, salivary cortisol
levels were assessed in all subjects (at 4 p.m.) in order to
establish a pre-treatment salivary cortisol baseline level, to
exclude hyper- or hypocortisolism and to familiarise the
subjects with the saliva sampling procedure.
Groups received their respective test product dosage
three weeks before the TSST exposure. Each test product
consisted of 21 daily containers with 8 identical capsules
each containing in sum, either 400, 600, 800 mg PAS
(as “100 mg” PAS per capsule), or placebo (i.e. 0– 4
placebo capsules per day for PAS-treated subjects, or
8 placebo capsules for the controls). Subjects were
instructed to take any three capsules at breakfast, any three
capsules at lunch and the last two capsules at dinner in the
evening, every day. For compliance inspection, each
subject was instructed to bring all the empty containers of
the treatment capsules on the last day of treatment
(the TSST exposure date) and to use daily a salivette
before bedtime. Subjects expected that product levels
would be assessed in these saliva samples. On the last day
of treatment (day 21) subjects took the three capsules in
the morning as usual. In the early afternoon they attended
the TSST. Immediately before the introduction to the
TSST (90 min before TSST exposure) the last three
capsules were taken in the presence of the investigator.
Trier Social Stress Test (TSST)
Every subject spent about 165 min in the laboratory for an
introduction to the TSST, a pre-experimental resting
period (90 min), the TSST itself (15 min) and a post-
experimental resting period (60 min). After a first
instruction the subject was led to experimental room #1,
which served as the rest and preparatory area.
To gain spontaneous subjective responses about side
effects of the test products, subjects were asked upon
arrival in the laboratory if they experienced any
psychological or physical changes during drug intake.
Forty-five minutes after arrival, subjects received an
indwelling catheter in a forearm vein for the collection of
blood samples. This first resting phase was necessary to
exclude potential activation of the hypothalamic–
pituitary adrenal axis (HPA), possibly confounding later
responsivity to the TSST. At the end of the resting
period the first saliva and blood samples were collected.
A detailed protocol of the TSST has been described
elsewhere by Kirschbaum et al. (1993). For a detailed
description of our study protocol on TSST-day, see Fig.2.
Before the TSST, each proband was introduced to the
testing room (#2) and instructed to stand behind a
microphone in front of a two-man committee. The subject
was informed that the whole session would be video- and
tape-recorded and that the committee was trained in
behavioural observation. The experimenter instructed the
subject to deliver a 5-min speech as if for a job application,
for which he/she had 3 min to prepare, and that a second task
would follow. After the free speech, the subject had to solve a
mental arithmetic task (counting backwards from 2083 to 0
in steps of 17) asquickly and correctly as possible for 5 min.
Before and after the TSST subjects filled out
two questionnaires, the “MDBF Mehrdimensionaler
Befindlichkeitsfragebogen” (Steyer et al., 1987) aiming
at assessing psychological well-being, and the German
version of the State scale of the Spielberger State/Trait
Anxiety Inventory (Spielberger et al., 1970) by Laux et al.
(1981). The MDBF consists of 24 items (each with a five-
level response scale) measuring three bipolar dimensions
FIGURE 2 Experimental procedure.
of acute psychological well-being: “good bad disposi-
tion” (e.g. content, unhappy), “alertness fatigue” (e.g.
tired, rested) and “calmnessagitation” (e.g. tense,
composed). A high MDBF-score indicates psychological
well-being, and low scores indicate low mood. After the
TSST procedure subjects stayed for another hour during
which six more blood and saliva samples were collected.
Post-experimental Resting
The subject returned to experimental room #1, where the
post-test assessments and debriefing took place. Saliva and
blood samples were collected directly after the stress test
and after a further 10 min and later at 15 min intervals. The
STAI and MDBF were once again administered
immediately after the stress test. At the end, the subject
was debriefed, by being informed about the nature of the
experiment and the behaviour of the experimenters.
ACTH, Cortisol and Heart Rate Measurements
As shown in Fig. 2, blood and saliva samples were
collected 2 min before, and 1, 10, 20, 30, 45 and 60 min
after the TSST. Salivary and serum cortisol levels were
assessed in all samples, while ACTH was only determined
at 22 and þ1 min, respectively. For ACTH, two blood
samples were collected in EDTA-Monovettes (Sarstedt,
¨mbrecht). After centrifugation for 10 min at 68C and
1000 g, plasma aliquots were stored at 2208C until
analysis. ACTH levels where determined via chemilumi-
niscent immunoassay (Nichols Institute Diagnostics, Bad
Nauheim, Germany). Monoclonal mouse-ACTH anti-
bodies for immobilisation, and biotinylated polyclonal
goat-ACTH with a chemiluminescent avidin-complex
were added to the sample. Luminescent detection of the
hormone-antibody sandwich was measured using a
commercial readout system (Auto-CliniLumat LB 952,
Berthold, Bad Wildbad, Germany). This assay has a lower
and upper detection threshold of 0.5 –1550 pg/ml respect-
ively, inter-assay variation ranged from 4.6 to 7.0% and
intra-assay variation was between 3.4 and 3.8%. Serum
cortisol was assessed by a commercial ELISA kit (IBL,
Hamburg). The intra- and interassay variabilities were
below 5 and 10%, respectively.
Subjects obtained saliva samples using Salivette
sampling devices (Sarstedt, Nu
¨mbrecht, Germany). Saliva
samples were stored at 2208C until assay. After thawing,
saliva samples were centrifuged at 3000 rpm for 5 min,
which resulted in a clear supernatant of low viscosity.
Cortisol concentrations were determined employing a
commercial kit immunoassay with luminescence detec-
tion (IBL, Hamburg). This assay has a detection limit of
0.4134 nmol/l, an intra-assay variability of 4.5 7.7% and
an inter-assay variability of 6.2 11.5%; to reduce error,
all samples of one participant were analysed in one assay.
Heart rate was recorded by Polar Vantage NV heart rate
measurement devices. Data were transmitted by a Polar-
Electro interface to a personal computer and imported to
the Polar Precision Performance SW program (Version
4.00.020, Polar Electro Oy 2003).
Data were compared by analysis of variance (ANOVA).
Since all women were taking oral contraceptives, serum
cortisol concentrations were higher, while ACTH and
salivary cortisol concentrations were lower than in the
men. To adjust for such gender differences, we compared
net increases from baseline between treatment groups and
controls. In the case of serum and salivary cortisol
measurements, the data were analysed by ANOVA with
repeated measures comparing the increase for each time
point after the TSST to baseline. The data set was cleaned
for extreme values ranging more than 2 s.d. from the
mean. Since the study objective predicted dampening
effects of PAS on plasma ACTH and serum cortisol, and
salivary cortisol concentrations in response to the
psychosocial stressor (TSST), we compared differences
between treatment groups and the placebo group by one-
tailed tests of significance.
As shown in Figs. 3– 5, treatment with 400 mg of PAS daily
resulted in a significant blunting of the HPA response to
psychological stress. Evidently, PAS exerts a central
dampening effect on HPA axis stress responses, as can be
seen from a significantly blunted ACTH response (Effect of
group: Fð1;32Þ¼6:58; p¼0:008) to the TSST (Fig. 3).
Subjects treated with 400 mg PAS showed a strong
reduction in the increase in (total) serum cortisol
concentration (Main Effect Time Fð2:8;84:3Þ¼24:03;
p,0:001 and Main Effect Group Fð1;30Þ¼2:84; p¼
0:05; Fig. 4), which was even more pronounced for the
biologically active, free steroid fraction, as assessed in
saliva (Main Effect Time Fð2;65:1Þ¼4:21; p¼0:001
and Main Effect Group Fð1;33Þ¼5:24; p¼0:015).
Here, the 400 mg treatment group showed only about 20%
of the salivary cortisol response when compared to
placebo (Fig. 5). In both measures there was no significant
interaction for group by time (serum cortisol
Fð2:8;84:3Þ¼0:62;p¼0:38; saliva cortisol:
Fð2;65:1Þ¼0:574;p¼0:28), indicating that treatment
with 400 mg PAS dampens the serum and salivary cortisol
response to the TSST to all time points.
Comparing 600 mg PAS daily with placebo, no
treatment effects were found for the increase in ACTH
(Fð1;32Þ¼1:17;p¼0:29), or the increase in serum
cortisol (Fð1;32Þ¼0:20;p¼0:66), or the increase in
salivary cortisol concentration (Fð1;35Þ¼1:73;
p¼0:20). The same was found for subjects treated with
800 mg PAS daily. Comparisons with placebo treated
subjects showed no significant treatment effects for
the increase in ACTH (Fð1;32Þ¼1:2;p¼0:28),
J. HELLHAMMER et al.122
FIGURE 3 Effects of PAS on the ACTH response to the TSST. Baseline levels were 26.57 pg/ml (placebo), 21.3 pg/ml (400 mg), 21.29 pg/ml (600 mg)
and 25.28 pg/ml (800 mg), respectively.
FIGURE 4 Effects of PAS on the serum cortisol response to the TSST. Baseline levels were 122.45 ng/ml (placebo), 129.54 ng/ml (400 mg),
107.13 ng/ml (600 mg) and 121.54ng/ml (800 mg), respectively.
or the increase in serum cortisol (Fð1;34Þ¼0:14;
p¼0:71), or the increase in salivary cortisol
Also, no treatment effects were found for the heart rate
response to the TSST, as well as for effects on total anxiety
scores and mood under stress. Since no mood changes
were observed in the MDBF, and knowing that the 20
STAI items assess a spectrum of mood and stress, not
specific for the TSST, we expected that PAS may have
exerted only specific effects on stress measures of the
STAI. To test this hypothesis, we performed a factor
analysis of STAI responses to the TSST of an independent
sample of 113 subjects, matched for age and sex from the
data bank of this laboratory. A principal component
analysis (Promax rotation) was performed and three
factors were extracted, assessing nervousness (F1),
relaxation (F2) and distress (F3), respectively. The
Eigenvalues and percentages of explained variance of
the three factors were F1 ¼6:14=30:7%;F2 ¼1:51=7:6%
and F3 ¼1:42=7:1%). Commonalities ranged from 21 to
71. Reliabilities (Cronbach’s alpha) were for F1 ¼0:76;
F2 ¼0:77 and F3 ¼0:75;respectively.
Indeed, subjects treated with 400 mg PAS daily did not
show the expected increase on the distress subscale (F3), as
the control group did. Thus, 400 mg PAS resulted in a
significant reduction of the psychological stress response to
the TSST, when compared to placebo (Fig.6;two-tailed
t-test for the increase; tð34Þ¼2:026; p¼0:05), and there
was a similar tendency in the 800 mg group. When all three
treatment groups were analysed together and compared to
placebo, PAS significantly prevented the expected increase
in stress after the TSST (Mean increase value in the placebo
group with n¼20 : 1.05; mean increase value in the PAS
group with n¼53 : 20.755; two tailed t-test of the
increase: tð71Þ¼1:941; p¼0:056).
The data obtained from this study demonstrate the first
evidence of a pronounced dampening effect of 400 mg
PAS daily on the reactivity of the pituitary adrenal axis to
stress. For the other two treatment groups (600 and 800 mg
PAS daily) these effects became weaker with increasing
dosages, and did not reach a sufficient level of
significance. This study was not designed to study PAS
effects with respect to body weight and gender, and
sample sizes did not allow more detailed statistical post
hoc analyses. An explorative data analysis, however,
revealed that women in this study had significantly lower
body weight, so they received relatively more PAS per kg
than men. Indeed, it seemed that PAS effects were even
more pronounced in men when compared to women, as
well as in individuals with lower PAS/body weight ratios
(data not shown). The fact that the effects of PAS were not
seen with increasing dosage still needs to be clarified.
In the TSST, women routinely show blunted ACTH and
cortisol responses, when compared to men. Many studies
FIGURE 5 Effects of PAS on the salivary cortisol response to the TSST. Baseline levels were 11.58 nmol/l (placebo), 10.54 nmol/l (400 mg),
8.49 nmol/l (600 mg) and 12.38 nmol/l (800 mg), respectively.
J. HELLHAMMER et al.124
have been undertaken to understand the gender differences
of the stress response. However, sex differences have not
been explained by effects of sex steroids—they even
persist in postmenopausal women (see, for review,
Kudielka et al. (2004)). Consequently, the magnitude of
the PAS effect was expected to be smaller in women, but
still in proportion to the changes in men. As mentioned
above, we did not expect gender effects on PAS action.
Thus, group size and statistical error did not allow the
necessary analyses. However, with the evidence available
to date, we cannot exclude that PAS exerts stronger
actions in men.
The mechanisms by which PAS affects HPA reactivity
are still unknown. Interestingly, the heart rate response to
stress was not dampened, questioning whether PAS has an
effect at the hypothalamic level. It is important to note that
PAS dampens but does not eliminate stress reactivity.
Furthermore, basal cortisol levels remained unaffected.
Thus, PAS does not seem to interfere with the integrity of
the pituitary adrenal axis.
Uncontrollability, unpredictability and uncertainty,
resulting in strain and worry, combined with ego-
involvement, are considered the key psychological
elements of both distress and HPA axis activation. From
this viewpoint, 400 mg PAS daily seems to exert a rather
specific effect on this biobehavioral response to the TSST,
as shown for a distress subscale, derived from the
Spielberger State Anxiety Inventory. While the placebo
group showed the expected increase in distress, the
400 mg treatment group even showed a slight decrease in
distress, suggesting a quicker habituation to a new
stressor, which may then result in a dampened HPA
The protocol of this study did not allow discrimination
between effects of chronic and acute PAS treatment. Thus,
we do not know yet if a bolus treatment alone can exert a
similar stress dampening effect as the chronic treatment.
There is currently strong evidence that an enhanced
reactivity of the pituitary adrenal axis is related to several
mental and physical diseases, such as depression, some
types of abdominal obesity and the metabolic syndrome
(Chrousos, 2000; Pasquali et al., 2000). The striking effect
of 400 mg PAS daily in dampening the stress response may
be promising with respect to possible clinical application
in stress related disorders. This view is supported by the
fact that no side effects were observed in this study.
This study was initiated and financed by Lipogen Ltd.,
Haifa, Israel.
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J. HELLHAMMER et al.126
... There is a growing awareness about the advantages of nutritional medicine in psychiatry [1], prompting an increased focus on the interrelationships between stress, mood, and nutrition. Several studies have shown the influence of nutrients and specific foods on an individual's physiological, neural, and psychological stress response [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]. For example, high-fat feeding increases circulating corticosterone in rodent models [17,18], and high-fat meals were shown to exacerbate detrimental autonomic nervous systems and cardiovascular responses to stress [8]. ...
... Salivary cortisol concentrations were logarithm-transformed. To examine effects of the intervention on log salivary cortisol, we first applied a mixed model procedure (SAS MIXED procedure), which included fixed effects of diet group (DGA vs. TAD, intervention week (baseline (week 1) and week 9), saliva sample (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14), all 2-and 3-factor interactions of the fixed effects, along with random effects of subject, subject by week, and subject by saliva sample to account for repeated measurements across the intervention week and the 14 saliva samples. Significant interactions between group and intervention week, and group, intervention week, and saliva sample were considered indicative of intervention effect. ...
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It is largely unknown whether and how whole food diets influence psychological stress and stress system responsiveness. To better understand the effects of whole diets on stress system responsiveness, we examined randomized control trial effects of a whole food diet based on the Dietary Guidelines for Americans (DGA) on cortisol responsiveness. A randomized, double-blind, controlled 8-week intervention was conducted in overweight and obese women to examine differentiated effects between two diet intervention groups: one based on the 2010 DGA and the other one based on a typical American diet (TAD). During a test week that occurred at baseline and again after 8 weeks of the intervention, we assessed salivary cortisol collected at 14 selected times across the day, including upon awakening, at bedtime, and during a test visit, and administered a standardized social stress task (Trier Social Stress Test, TSST). There were no statistical differences between the diet groups in salivary cortisol at baseline or after 8 weeks. However, when considering differences in dietary carbohydrate, but not fat or protein, from the pre-intervention (habitual) to the intervention period, there was a significant (P = 0.0001) interaction between diet group, intervention week, saliva sample, and level of intervention-based change in carbohydrate consumption. This interaction was reflected primarily by an 8-week reduction in salivary cortisol during a period just prior to (log Δ −0.35 ± 0.12 nmol/L) and 30 (log Δ −0.49 ± 0.12 nmol/L), 60 (log Δ −0.50 ± 0.13 nmol/L), 90 (log Δ −0.51 ± 0.13 nmol/L), and 120 (log Δ −0.4476 ± 0.1231 nmol/L) min after the TSST in the DGA group having the highest increase (90th percentile) in carbohydrate consumption. In support of this finding, we also found significant (P < 0.05) and inverse linear associations between dietary carbohydrate and log salivary cortisol, with the strongest negative association (β: −0.004 ± 0.0015, P = 0.009) occurring at 30 min post-TSST, but only in the DGA group and at week 9 of the intervention. Together, increasing dietary carbohydrate as part of a DGA-based diet may reduce circulating cortisol and dampen psychological stress-related cortisol responsiveness.
... Moreover, PA influences membrane curvature [22,25] and acts as a signaling lipid [11,34]. In combination with PS, PA has shown to lower cortisol levels and enhance wellbeing under acute social stress [17]. PS, a phospholipid component is found in mammalian cell membranes. ...
... PS, a phospholipid component is found in mammalian cell membranes. Previous studies indicated that acute and long-term administration of PS dampens cortisol responses to acute exercise and mental stress [17,26,36]. In addition, PS has shown to improve memory, learning, mood and stress management [4,17e20,38]. ...
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Background & aims Many women experience emotional and physical symptoms around the time of ovulation and more so before menstruation interfering with their daily normal life also known as premenstrual syndrome (PMS). Recent observational data suggest that supplementation with Lipogen's phosphatidylserine (PS) and phosphatidic acid (PA) complex (PAS) alleviates these PMS symptoms. The aim of this study was to confirm these observations on the effects of PAS on PMS symptom severity within a controlled clinical trial setting. Methods Forty women aged 18–45 years with a diagnosis of PMS were assigned to either take PAS (containing 400 mg PS & 400 mg PA per day) or a matching placebo. The study comprised 5 on-site visits including 1 baseline menstrual cycle followed by 3 treatment cycles. Treatment intake was controlled for by using an electronic device, the Medication Event Monitoring System (MEMS®). Primary outcome of the study was the PMS symptoms severity as assessed by using the Daily Record of Severity of Problems (DRSP). Further, SIPS questionnaire (a German version of the Premenstrual Symptoms Screening Tool (PSST)), salivary hormone levels (cortisol awakening response (CAR) and evening cortisol levels) as well as serum levels (cortisol, estradiol, progesterone and corticosteroid binding globulin (CBG)) were assessed. Results PMS symptoms as assessed by the DRSP Total score showed a significantly better improvement (p = 0.001) over a 3 cycles PAS intake as compared to placebo. In addition, PAS treated women reported a greater improvement in physical (p = 0.002) and depressive symptoms (p = 0.068). They also reported a lower reduction of productivity (p = 0.052) and a stronger decrease in interference with relationships with others (p = 0.099) compared to the placebo group. No other DRSP scale or item showed significant results. Likewise, the reduction in the number of subjects fulfilling PMS or premenstrual dysphoric disorder (PMDD) criteria as classified by the SIPS did not differ between the PAS and the placebo group. For the biomarkers, the salivary cortisol percentage increase of the CAR was significantly less pronounced in the follicular phase of cycle 4 than in the follicular phase of cycle 1 for subjects taking PAS when compared to subjects taking placebo (p = 0.018). Furthermore, the change of serum cortisol levels between visit 1 and visit 5 differed significantly between groups (p = 0.043). While serum cortisol levels of PAS treated females slightly decreased between visit 1 and visit 5, cortisol levels of females treated with placebo increased. For all other biomarkers, no treatment effects were observed over the 4 cycles study period. Overall, this study confirms that a daily intake of PAS, containing 400 mg PS and 400 mg PA, can be considered as safe. Conclusions Results substantiate the efficacy of PAS in reducing symptoms of PMS. In view of the recent inclusion of severe PMS symptoms (PMDD) in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), the positive results of this clinical study merits consideration of developing the PAS complex as a botanical drug for treatment of PMDD. Clinical trial registration The study is registered at Deutsches Register Klinischer Studien with the registration number DRKS00009005.
... Indeed, several in vitro studies showed that chronic exposure to CORT exerts toxic effects on neurons (Gao et al., 2015;Pusceddu et al., 2016;Zhao et al., 2018). In this regard, previous studies have suggested that phospholipid-enriched diets may possess therapeutic effects against stress-related conditions (Hellhammer et al., 2004;Boyle et al., 2019;Schverer et al., 2020). Therefore, evidence demonstrating that phospholipids prevent the neurotoxic effects of glucocorticoids in vitro might provide novel insights into the mechanism underpinning anti-stress effects in vivo. ...
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Nutrition is a crucial component for maintenance of brain function and mental health. Accumulating evidence suggests that certain molecular compounds derived from diet can exert neuroprotective effects against chronic stress, and moreover improve important neuronal processes vulnerable to the stress response, such as plasticity and neurogenesis. Phospholipids are naturally occurring amphipathic molecules with promising potential to promote brain health. However, it is unclear whether phospholipids are able to modulate neuronal function directly under a stress-related context. In this study, we investigate the neuroprotective effects of phosphatidylcholine (PC), lysophosphatidylcholine (LPC), phosphatidylserine (PS), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylglycerol (PG), phosphatidic acid (PA), sphingomyelin (SM) and cardiolipin (CL) against corticosterone (CORT)-induced cytotoxicity in primary cultured rat cortical neurons. In addition, we examine their capacity to modulate proliferation and differentiation of hippocampal neural progenitor cells (NPCs). We show that PS, PG and PE can reverse CORT-induced cytotoxicity and neuronal depletion in cortical cells. On the other hand, phospholipid exposure was unable to prevent the decrease of Bdnf expression produced by CORT. Interestingly, PS was able to increase hippocampal NPCs neurosphere size, and PE elicited a significant increase in astrocytic differentiation in hippocampal NPCs. Together, these results indicate that specific phospholipids protect cortical cells against CORT-induced cytotoxicity and improve proliferation and astrocytic differentiation in hippocampal NPCs, suggesting potential implications on neurodevelopmental and neuroprotective pathways relevant for stress-related disorders.
... Nutritional medicine in psychiatry is an emerging field [1], and research-driven information on stress, mood, and nutrition interrelationships is increasing. There are studies showing that nutrients and specific foods can influence an individual's physiological, neural, and psychological response to stress [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]. For example, high-fat meals were shown to exacerbate detrimental autonomic nervous system and cardiovascular responses to stress [8], while increases in polyunsaturated fats reduced these stress-induced cardiovascular responses [3]; omega-3 fatty acid consumption normalized abnormally low cortisol responses to an acute stress test [6]; consuming milk-based phospholipids were also shown to improve memory in men reporting high levels of chronic stress [14]; and consuming egg powder was demonstrated to normalize the neuroendocrine response to stress and reduce adaptation to acute stress by normalizing the endocrine and the negative emotional response to stress [15]. ...
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Very little is known about how whole food diets, such as those based on the Dietary Guidelines for Americans (DGA), influence psychological stress and physiological stress load. To better understand the effects of whole food diets on stress, we examined in a randomized control trial the effects of a DGA-based diet on markers of psychological and physiological stress. A randomized, double-blind, controlled 8-week intervention was conducted in overweight and obese women randomly assigned to one of two diet groups: a diet based on the 2010 DGA or a diet based on a Typical American Diet (TAD). The Perceived Stress Scale and allostatic load were used to assess stress load. Eight-week change in perceived stress did not significantly (p = 0.45) differ between the DGA (+0.53 ± 0.99) and TAD (−0.57 ± 0.99) groups. Likewise, 8-week change in allostatic load did not significantly (p = 0.79) differ between the two diet intervention groups (DGA: +0.001 ± 0.26 vs. TAD: +0.105 ± 0.28). However, we did find strong inverse associations between 8-week change in stress and intervention-based improvements in diet quality (lower sodium and higher vegetable consumption). When statistically accounting for these inverse associations, we found that perceived stress and allostatic load were higher (p < 0.04) in the DGA group. These findings suggest that improvements in dietary vegetable and sodium intake mediated effects of the diet intervention on psychological and physiological stress load. That is, adopting and adhering to a diet of higher quality (DGA) for 8 weeks may have been generally more stressful in the absence of improvements in vegetable or sodium consumption. This study provides further evidence for the mental health benefits of maximizing vegetable and minimizing sodium consumption.
... Trends towards elevated anticipatory cortisol responses following PL intake have been reported 448 previously [11,17]. However, this contradicts previous evidence of the potential of PLs to attenuate 449 cortisol responses to acute stress [8, 10,6,7,9]. It is worth noting that a heightened pre-stress ...
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Objectives: The aim of this study was to examine the stress-buffering potential of phospholipid (PL) intake on cognitive performance and neuroendocrine and psychological responses under conditions of psychosocial stress in a high-stress vulnerable (perfectionist) sample. Methods: Fifty-four high-perfectionist men consumed a 6-wk daily intake of a bovine milk-derived PL (2.7 g/d) or placebo drink in a randomized, double-blind, placebo-controlled, parallel groups design. Working memory, executive control function, and acute physiological/subjective responses to an acute psychosocial stressor were examined before and after the 6-wk PL or placebo intake. Results: PL intake improved post-stress reaction time performance on an attention-switching task (P = 0.01). No significant attenuation of the salivary cortisol stress response was shown. PL intake significantly increased mid-stress induction energetic arousal (P = 0.03). A non-significant reduction in anticipatory subjective stress was reported after PL intake (P = 0.06). Systolic and diastolic blood pressures (P <0.04 and P = 0.01, respectively) were significantly augmented in the PL condition. Conclusions: Dietary intake of bovine milk PLs conferred cognitive performance benefit under conditions of psychosocial stress but failed to moderate cortisol response. Moderation of subjective response to stress exposure may have underpinned this performance protection.
... However, yolk lecithin has a perfectly balanced and unique composition and contains specific acids which are not found in products of plant origin. It is considered to be an essential substance in the production of new generation pharmaceuticals, including unique drugs against Alzheimer's disease and medicines enhancing memory processes in schizophrenic and autistic children (Hellhammer et al., 2004). It is also a basic component of special medicinal emulsions providing protection against peroxidation caused by local ischaemia and reperfusion during various transplantations (Lange, 2006;Rossi, 2007;Wojasinski, Duszynska, & Ciach, 2015). ...
Background Chicken eggs are considered to be nature's perfect food. The egg white is an excellent natural source of high quality protein, which is rich in essential amino acids. The yolk is a source of antioxidants, aromatic amino acids, carotenoids, vitamins, phospholipids and proteins, which not only provide nutritional value but also act pro-health and might prevent eg. from heart diseases. In turn eggshell supplies well absorbed by the human body minerals, of which the most important is calcium. Scope and approach In this review the new trends in chicken egg research are showed. The egg components which are the most important for human health are described. This study shows also the methods of isolating the most important health-promoting ingredients from chicken eggs. Key Findings and Conclusion: Eggs are not only a highly nutritious food, but also a rich source of diverse bioactive components also including nutraceuticals. Therefore, the current research trends focus on the new look at the egg as a material acting as health-promoting functions. Currently carried out research also concern the development of new technologies for the production of bioactive ingredients of chicken eggs.These new trends introduce a new era in egg science and technology and the future of eggs and egg ingredients remains bright.
... In different studies, PS-containing preparations were found to selectively dampen stress levels in humans [34][35][36], improve learning and perception parameters in children with attention-deficit hyperactivity disorder [37,38], and improve the calculation speed of athletes [39]. Due to concerns regarding bovine spongiform encephalopathy, the use of PS (and PA) produced by enzymatic conversion of soybean lecithin [40,41] is considered a safer alternative. ...
Phosphatidic acid (PA) and phosphatidylserine (PS) and are natural constituents of healthy brain cell membranes, which have been recognized since the 1970s as essential to normal neuronal functioning. PA is a precursor in the formation of other phospholipids, including PS and phosphatidylethanolamine (PE). Also, it has an impact on membrane rigidity/flexibility, which is important in modulating exo- and endocytosis. PS is also an important precursor for PE synthesis. Since PS predominantly occurs in brain cells, but normal diets do not include the consumption of brains, PS is available to our brains mostly via natural “production” in our bodies. Here, we present a tabulated literature survey of clinical studies on PS and/or PA regarding brain function in elderly people. In addition we give a summary on two of our our already published pilot studies performed with a brain-health food supplement containing a proprietary blend of 100 mg PS and 80 mg PA produced from soy lecithin: A three-month double-blind, placebo-controlled study demonstrated the positive influence of three PS+PA capsules/ day, (300 mg PS+240 mg PA per day; n=40)) or placebo (n=32) on memory and mood in functioning, non-depressive elderly people with memory problems. In a two-month randomized, double-blind, placebo-controlled study, three PS+PA capsules/day (300 mg PS+240 mg PA per day; n=56) or placebo (n=40) improved daily functioning, mental health, emotional state, and self-reported general condition in patients with Alzheimer’s disease (AD). Altogether there is encouraging clinical data that PS+PA supplementation could be beneficial to AD patients and other elderly people with memory or cognition problems. Long-term studies are, however, still lacking.
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Scope: Increasing scientific evidence is validating the use of dietary strategies to support and improve brain health throughout the lifespan, with tailored nutritional interventions catering for specific life stages. Dietary phospholipid supplementations in early life and adulthood have been shown to alleviate some of the behavioural consequences associated with chronic stress. This study aims to explore the protective effects of a tailored phospholipid-enriched buttermilk on behavioural and endocrine responses induced by chronic psychosocial stress in adulthood, and to compare these effects according to the life stage at which the supplementation was started. Methods and Results: We developed a novel phospholipid-enriched dairy product and assessed social, anxiety- and depressive-like behaviours, as well as the stress response and cognitive performance following chronic psychosocial stress in C57 BL/6 J mice, with supplementation beginning in adulthood or early life. Milk phospholipid supplementation from birth protected adult mice against chronic stress-induced changes in endocrine response to a subsequent acute stressor and reduced innate anxiety-like behaviour in non-stressed animals. When starting in adulthood, the dietary intervention reversed the anxiety-like phenotype caused by chronic stress exposure. Conclusion: Dairy-derived phospholipids exert differential protective effects against chronic psychosocial stress depending on the targeted life stage and duration of the dietary supplementation. This article is protected by copyright. All rights reserved
Adaptogens are agents which protect against stress and stress-related disorders. They act in a nonspecific manner and rejuvenate the body systems in a holistic manner by complex and interactive mechanisms. The ability to cope with the stressful experience maintains the physiological homeostasis and the lack of such adaptive mechanisms results in pathophysiological states, which can involve cardiovascular organs, the immunological system, neuroendocrinal axis, gastrointestinal system, central nervous system, etc. Conventional antistress agents used for such conditions, while being effective, have a plethora of undesirable effects which limit their long-term use, and thus there is a constant search for more effective and safer agents. Nutraceuticals are food additives and/or nutritional supplements used for the prevention and treatment of many diseases as well as for maintenance of normal wellbeing. Some such nutraceuticals with adaptogenic potential are primarily obtained from herbal sources (medicinal plants), and, in recent years, have gained considerable attention because of their safety, efficacy, and cost-effectiveness. Experimental and clinical studies have validated their uses in a plethora of human diseases and scientific research has clarified their efficacy and safety issues. In addition, several dietary supplements which provide potential adaptogenic molecules after chemical transformation in the body are also being increasingly recommended for stress and stress-related conditions. With the evolving scenario, and increasing general awareness about health and disease, the use of such nutraceuticals may revolutionize the management of some of these excruciating and debilitating disease states. Such adaptogens, in view of their holistic effectiveness and well known safety, could not only help to counteract stress effects on the biological system but also increase nonspecific resistance to a variety of threatening/aversive conditions. The outcome could be attenuation of stress-related disorders and improvement of the quality of life.
ntroducción. Las prácticas clínicas constituyen una parte esencial de la formación de pregrado en los estudios de enfermería, suponen el primer contacto real con escenarios clínico-asistenciales. En este sentido, las numerosas situaciones a las que deben hacer frente, pueden tener repercusiones en su salud física y psicológica. Objetivos. Conocer la respuesta fisiológica y psicológica ante las prácticas clínicas en los estudiantes de grado de enfermería, analizar los posibles cambios en estas respuestas entre antes y después de haber realizado dichas prácticas, y su posible relación con el género. Metodología. Se evaluaron 108 estudiantes de grado de enfermería (39 grupo control y 69 grupo experimental) y se evaluaron variables fisiológicas y variables psicológicas. Estas variables se recogieron en el grupo experimental en un segundo momento tras la realización de las prácticas clínicas. Se utilizó el SPSS 19. Resultados. Encontramos alteraciones en algunas de las variables fisiológicas analizadas, (cortisol, tensión arterial y frecuencia cardíaca) estando más alteradas en el grupo expuesto a las prácticas clínicas que también tuvo un nivel de percepción de los factores estresores mayor. Respecto a la ansiedad estado-rasgo, los alumnos presentan niveles normales. En relación con las estrategias de afrontamiento, se observa que ambos grupos utilizan estrategias similares. Conclusiones. La realización de las prácticas clínicas parece ser una situación que puede alterar algunos aspectos fisiológicos y psicológicos, pero principalmente la percepción de factores estresores. Las estrategias de afrontamiento encontradas son de tipo activo como un factor protector, minimizando los efectos estresantes de la exposición a las prácticas clínicas.
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Context The Primary Care Evaluation of Mental Disorders (PRIME-MD) was developed as a screening instrument but its administration time has limited its clinical usefulness.Objective To determine if the self-administered PRIME-MD Patient Health Questionnaire (PHQ) has validity and utility for diagnosing mental disorders in primary care comparable to the original clinician-administered PRIME-MD.Design Criterion standard study undertaken between May 1997 and November 1998.Setting Eight primary care clinics in the United States.Participants Of a total of 3000 adult patients (selected by site-specific methods to avoid sampling bias) assessed by 62 primary care physicians (21 general internal medicine, 41 family practice), 585 patients had an interview with a mental health professional within 48 hours of completing the PHQ.Main Outcome Measures Patient Health Questionnaire diagnoses compared with independent diagnoses made by mental health professionals; functional status measures; disability days; health care use; and treatment/referral decisions.Results A total of 825 (28%) of the 3000 individuals and 170 (29%) of the 585 had a PHQ diagnosis. There was good agreement between PHQ diagnoses and those of independent mental health professionals (for the diagnosis of any 1 or more PHQ disorder, κ = 0.65; overall accuracy, 85%; sensitivity, 75%; specificity, 90%), similar to the original PRIME-MD. Patients with PHQ diagnoses had more functional impairment, disability days, and health care use than did patients without PHQ diagnoses (for all group main effects, P<.001). The average time required of the physician to review the PHQ was far less than to administer the original PRIME-MD (<3 minutes for 85% vs 16% of the cases). Although 80% of the physicians reported that routine use of the PHQ would be useful, new management actions were initiated or planned for only 117 (32%) of the 363 patients with 1 or more PHQ diagnoses not previously recognized.Conclusion Our study suggests that the PHQ has diagnostic validity comparable to the original clinician-administered PRIME-MD, and is more efficient to use. Figures in this Article Mental disorders in primary care are common, disabling, costly, and treatable.1- 5 However, they are frequently unrecognized and therefore not treated.2- 6 Although there have been many screening instruments developed,7- 8 PRIME-MD (Primary Care Evaluation of Mental Disorders)5 was the first instrument designed for use in primary care that actually diagnoses specific disorders using diagnostic criteria from the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition9(DSM-III-R) and Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition10(DSM-IV). PRIME-MD is a 2-stage system in which the patient first completes a 26-item self-administered questionnaire that screens for 5 of the most common groups of disorders in primary care: depressive, anxiety, alcohol, somatoform, and eating disorders. In the original study,5 the average amount of time spent by the physician to administer the clinician evaluation guide to patients who scored positively on the patient questionnaire was 8.4 minutes. However, this is still a considerable amount of time in the primary care setting, where most visits are 15 minutes or less.11 Therefore, although PRIME-MD has been widely used in clinical research,12- 28 its use in clinical settings has apparently been limited. This article describes the development, validation, and utility of a fully self-administered version of the original PRIME-MD, called the PRIME-MD Patient Health Questionnaire (henceforth referred to as the PHQ). DESCRIPTION OF PRIME-MD PHQ ABSTRACT | DESCRIPTION OF PRIME-MD PHQ | STUDY PURPOSE | METHODS | RESULTS | COMMENT | REFERENCES The 2 components of the original PRIME-MD, the patient questionnaire and the clinician evaluation guide, were combined into a single, 3-page questionnaire that can be entirely self-administered by the patient (it can also be read to the patient, if necessary). The clinician scans the completed questionnaire, verifies positive responses, and applies diagnostic algorithms that are abbreviated at the bottom of each page. In this study, the data from the questionnaire were entered into a computer program that applied the diagnostic algorithms (written in SPSS 8.0 for Windows [SPSS Inc, Chicago, Ill]). The computer program does not include the diagnosis of somatoform disorder, because this diagnosis requires a clinical judgment regarding the adequacy of a biological explanation for physical symptoms that the patient has noted. A fourth page has been added to the PHQ that includes questions about menstruation, pregnancy and childbirth, and recent psychosocial stressors. This report covers only data from the diagnostic portion (first 3 pages) of the PHQ. Users of the PHQ have the choice of using the entire 4-page instrument, just the 3-page diagnostic portion, a 2-page version (Brief PHQ) that covers mood and panic disorders and the nondiagnostic information described above, or only the first page of the 2-page version (covering only mood and panic disorders) (Figure 1). Figure 1. First Page of Primary Care Evaluation of Mental Disorders Brief Patient Health QuestionnaireGrahic Jump Location+View Large | Save Figure | Download Slide (.ppt) | View in Article ContextCopyright held by Pfizer Inc, but may be photocopied ad libitum. For office coding, see the end of the article. The original PRIME-MD assessed 18 current mental disorders. By grouping several specific mood, anxiety, and somatoform categories into larger rubrics, the PHQ greatly simplifies the differential diagnosis by assessing only 8 disorders. Like the original PRIME-MD, these disorders are divided into threshold disorders (corresponding to specific DSM-IV diagnoses, such as major depressive disorder, panic disorder, other anxiety disorder, and bulimia nervosa) and subthreshold disorders (in which the criteria for disorders encompass fewer symptoms than are required for any specific DSM-IV diagnoses: other depressive disorder, probable alcohol abuse or dependence, and somatoform and binge eating disorders). One important modification was made in the response categories for depressive and somatoform symptoms that, in the original PRIME-MD, were dichotomous (yes/no). In the PHQ, response categories are expanded. Patients indicate for each of the 9 depressive symptoms whether, during the previous 2 weeks, the symptom has bothered them "not at all," "several days," "more than half the days," or "nearly every day." This change allows the PHQ to be not only a diagnostic instrument but also to yield a measure of depression severity that can be of aid in initial treatment decisions as well as in monitoring outcomes over time. Patients indicate for each of the 13 physical symptoms whether, during the previous month, they have been "not bothered," "bothered a little," or "bothered a lot" by the symptom. Because physical symptoms are so common in primary care, the original PRIME-MD dichotomous-response categories often led patients to endorse physical symptoms that were not clinically significant. An item was added to the end of the diagnostic portion of the PHQ asking the patient if he or she had checked off any problems on the questionnaire: "How difficult have these problems made it for you to do your work, take care of things at home, or get along with other people?" As with the original PRIME-MD, before making a final diagnosis, the clinician is expected to rule out physical causes of depression, anxiety and physical symptoms, and, in the case of depression, normal bereavement and history of a manic episode. STUDY PURPOSE ABSTRACT | DESCRIPTION OF PRIME-MD PHQ | STUDY PURPOSE | METHODS | RESULTS | COMMENT | REFERENCES Our major purpose was to test the validity and utility of the PHQ in a multisite sample of family practice and general internal medicine patients by answering the following questions: Are diagnoses made by the PHQ as accurate as diagnoses made by the original PRIME-MD, using independent diagnoses made by mental health professionals (MHPs) as the criterion standard?Are the frequencies of mental disorders found by the PHQ comparable to those obtained in other primary care studies?Is the construct validity of the PHQ comparable to the original PRIME-MD in terms of functional impairment and health care use?Is the PHQ as effective as the original PRIME-MD in increasing the recognition of mental disorders in primary care patients?How valuable do primary care physicians find the diagnostic information in the PHQ?How comfortable are patients in answering the questions on the PHQ, and how often do they believe that their answers will be helpful to their physicians in understanding and treating their problems?
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The effect of chronic administration of phosphatidylserine derived from brain cortex on the neuroendocrine responses to physical stress has been examined in a placebo-controlled study in 9 healthy men. Phosphatidylserine 800 mg/d for 10 days significantly blunted the ACTH and cortisol responses to physical exercise (P = 0.003 and P = 0.03, respectively), without affecting the rise in plasma GH and PRL. Physical exercise significantly increased the plasma lactate concentration both after placebo and phosphatidylserine. The results suggest that chronic oral administration of phosphatidylserine may counteract stress-induced activation of the hypothalamo-pituitary-adrenal axis in man.
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Arginine vasopressin modulates the release of adrenocorticotropic hormone, beta-endorphin, and prolactin from the anterior pituitary. Release is mediated by the V1b receptor through the mobilization of intracellular Ca2+ by phosphatidylinositol hydrolysis. In contrast to its well characterized peripheral actions, such as antidiuresis, contraction of vascular smooth muscle, and stimulation of hepatic glycogenolysis, the exact site and mechanism of vasopressin action in the pituitary remain unclear. This is largely due to a lack of information on the molecular identity and exact localization of the V1b receptor. This lack prompted us to try to isolate this receptor subtype. Here we report the molecular cloning and functional expression of a complementary DNA encoding the human V1b receptor. The deduced 424-amino acid sequence of the receptor has highest overall homology with the V1a, V2, and oxytocin receptors, with homologies of 45, 39, and 45%, respectively. The receptor expressed in COS-1 cells has a single binding site for arginine vasopressin with a Kd of 0.17 +/- 0.04 nM. It binds various agonists and antagonists of vasopressin with affinities distinct from those of V1a and V2 receptors but consistent with those anticipated for the V1b receptor on the basis of the pharmacological studies. Furthermore, arginine vasopressin evoked calcium-dependent chloride current in Xenopus oocytes transfected with the receptor, which was not affected by a V1a/V2 antagonist. In contrast, the current evoked in oocytes transfected with V1a receptor was abolished by the antagonist. Northern blot analysis revealed that the receptor expression is restricted to the pituitary. These data clearly indicate that the cloned cDNA encodes the V1b receptor.
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Recent studies have revealed that arginine vasopressin (AVP) has at least two types of receptors in the kidney: V1a receptor and V2 receptor. In this study, microlocalization of mRNA coding for V1a and V2 receptors was carried out in the rat kidney using a reverse transcription and polymerase chain reaction. Large signals for V1a receptor PCR product were detected in the glomerulus, initial cortical collecting duct, cortical collecting duct, outer medullary collecting duct, inner medullary collecting duct, and arcuate artery. Small but detectable signals were found in proximal convoluted and straight tubules, inner medullary thin limbs, and medullary thick ascending limbs. Large signals for V2 receptor mRNA were detected in the cortical collecting duct, outer medullary collecting duct, and inner medullary collecting duct. Small signals for V2 receptor were found in the inner medullary thick limbs, medullary thick ascending limbs, and initial cortical collecting duct. Next, we investigated V1a and V2 receptor mRNA regulation in the dehydrated state. During a 72-h water restriction state, the plasma AVP level increased and V2 receptor mRNA decreased in collecting ducts. In contrast, V1a receptor mRNA did not change significantly. Thus, the two AVP receptor subtypes are distributed differently along the nephron, and these mRNAs are regulated differently in the dehydrated state.
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This paper describes a protocol for induction of moderate psychological stress in a laboratory setting and evaluates its effects on physiological responses. The 'Trier Social Stress Test' (TSST) mainly consists of an anticipation period (10 min) and a test period (10 min) in which the subjects have to deliver a free speech and perform mental arithmetic in front of an audience. In six independent studies this protocol has been found to induce considerable changes in the concentration of ACTH, cortisol (serum and saliva), GH, prolactin as well as significant increases in heart rate. As for salivary cortisol levels, the TSST reliably led to 2- to 4-fold elevations above baseline with similar peak cortisol concentrations. Studies are summarized in which TSST-induced cortisol increases elucidated some of the multiple variables contributing to the interindividual variation in adrenocortical stress responses. The results suggest that gender, genetics and nicotine consumption can influence the individual's stress responsiveness to psychological stress while personality traits showed no correlation with cortisol responses to TSST stimulation. From these data we conclude that the TSST can serve as a tool for psychobiological research.
The gene of the mouse V3/V1b receptor was identified by homology cloning. One of the genomic clones contained the entire coding sequence. The cDNA presented high identity with rat (92%) and human (84%) sequences. Southern blot analysis indicated the existence of a single gene. Tissue distribution was studied by RT-PCR. The major site of expression was the pituitary. A faint signal was also present in hypothalamus, brain, adrenal, pancreas and colon. The mouse corticotroph cell line, AtT20, did not express the transcript. In order to confirm the identity of the sequence, the V3/V1b receptor cDNA was cloned and stably expressed in CHO-AA8 Tet-Off cells under the control of tetracycline. When transfected cells were treated with arginine vasopressin (AVP), inositol phosphate production increased in a dose-dependent manner, indicating that the V3/V1b receptor couples to phospholipase C. Moreover, AVP did not stimulate cAMP production. Binding studies with [3H]AVP indicated that the affinity of the mouse V3/V1b receptor (Kd=0.5 nM) is similar to that reported for rat and human receptors. The rank order of potency established in competition binding experiments with different analogues was representative of a V3/V1b profile, distinct from V1a and V2. However, significant differences were found between human and mouse receptors tested in parallel. Thus the pharmacology of V3/V1b receptors can not be transposed among different species.
Data from five independent studies were reanalyzed in order to investigate the impact of age and gender on HPA axis responses to an acute psychosocial laboratory stress task. The total sample consisted of 102 healthy subjects with 30 older adults (mean age: 67.3 y), 41 young adults (mean age: 23.5 y), and 31 children (mean age: 12.1 y). All participants were exposed to the Trier Social Stress Test (TSST). The stress protocol caused highly significant ACTH and total plasma cortisol responses in older and younger male and female adults (all p<0.0001) as well as salivary free cortisol responses in all six age and gender groups (all p<0.0001). Three-way ANOVAs for repeated measurement were applied to investigate the impact of age and gender on ACTH and cortisol responses. Results showed that the ACTH response to stress was higher in younger adults compared to older adults (main effect: p=0.009, interaction: p=0.06). Post hoc analyses revealed that there was no age effect in the subgroup of women (p=n.s.), while younger men had higher ACTH responses compared to older men (p=0.01). For total plasma cortisol, ANOVA results showed that the pattern of reactivity did not differ between age and gender groups (all interactional effects p=n.s.), although older females had hightened overall cortisol levels compared to the other groups, as proofed in post hoc analyses (all p<0.05). For free salivary cortisol, a significant main effect of gender (p=0.05) and an almost significant three-way-interaction (p=0.09) emerged. Post hoc analyses showed an elevated overall free salivary cortisol response in elderly men compared to elderly women (p=0.006), while no gender differences emerged in neither young adults nor children (both p=n.s.). In sum, the stressor induced significant HPA axis responses in all age and gender groups. The observed ACTH response patterns in young and elderly adults may suggest that a heightened hypothalamic drive in young men decreases with age, resulting in similar ACTH responses in elderly men and women. Alternative interpretations are also discussed. The data also supports the idea of a greater adrenal cortex sensitivity to ACTH signals in young females. Free salivary cortisol responses were elevated in elderly men compared to elderly women, an effect which cannot be explained by gender differences in perceived stress responses to the TSST. It can be speculated if corticosteroid binding globulin (CBG) and/or sex steroids are important modulators of these effects.
It is hoped that this review will give the reader a taste of some of the mechanisms used by the glucocorticoid receptor to repress gene function. These mechanisms include direct binding to DNA, antagonism of other transcription factor families and sequestration of necessary cofactors. Each of these mechanisms, and others, are discussed.
The activity of brain cortex-derived phosphatidylserine (BC-PS) on the neuroendocrine and neurovegetative responses to physical stress was tested in 8 healthy men who underwent three experiments with a bicycle ergometer. According to a double-blind design, before starting the exercise, each subject received intravenously, within 10 min, 50 or 75 mg of BC-PS or a volume-matched placebo diluted in 100 ml of saline. Blood samples were collected before and after the exercise for plasma epinephrine (E), norepinephrine (NE), dopamine (DA), adrenocorticotropin (ACTH), cortisol, growth hormone (GH), prolactin (PRL) and glucose determinations. Blood pressure and heart rate were also recorded. Physical stress induced a clear-cut increase in plasma E, NE, ACTH, cortisol, GH and PRL, whereas no significant change was observed in plasma DA and glucose. Pretreatment with both 50 and 75 mg BC-PS significantly blunted the ACTH and cortisol responses to physical stress.