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ABSTRACT: Despite the evidence of an association between depression and increased inflammatory markers, still little is known in relation to the most severe cases of the disorder i.e., those who fail to respond to antidepressants. We have assessed the cytokine profile and cortisol levels in 21 healthy controls (HC) and 19 medicated patients with depression with treatment-resistance (TRD) moderately ill. As an initial exploratory analysis, we have also related cytokine profile to the patient's clinical treatment outcome after an inpatient admission. Cytokine profile was measured in the serum by the Cytokine Array I kit (Randox(®)). Plasma cortisol was carried out using a commercially available for the IMMULITE(®) system. When compared to healthy controls, depressed patients had higher levels of cortisol, IL-6, IL-10, but lower levels of IL-4 and VEGF. Our exploratory analysis showed subjects who did not go on to respond to the inpatient admission treatment package had lower levels of MCP-1, and a trend toward lower levels of VEGF. Taking together, these data suggest that lack of clinical therapeutic benefit of antidepressants is associated with overall activation of the inflammatory system.
Journal of affective disorders 11/2012; · 3.76 Impact Factor
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ABSTRACT: Identifying predictors of outcome among patients with treatment-resistant depression (TRD) is challenging. We hypothesised that discrepancy between self-rated and observer-rated scales may be a simple way of making such a prediction.
102 patients were admitted to a unit specialising in the treatment of resistant depression and underwent fortnightly assessment with clinician-rated (Hamilton Depression Rating Scale-21, HAM-D) and self-rated (Beck Depression Inventory, BDI) measures. All patients had significant depressive symptoms that were treatment resistant, 70% as part of a major depressive disorder and the remainder as part of a bipolar or other disorder. A discrepancy score between the HAM-D and BDI was calculated on admission and its association with patient clinico-demographic factors was determined. A subset of 67 patients remained as inpatients for 40 weeks or until clinical response and were entered into a responder analysis, in which response was defined as ≥50% reduction in admission HAM-D score. The association of the admission BDI-HAM-D discrepancy score with subsequent patient response, was determined.
The magnitude of BDI-HAM-D discrepancy was higher in those with co-morbid personality disorder, lower in those with psychosis and positively correlated with anxiety. High BDI-HAM-D discrepancy score predicted delayed treatment response (odds ratio 5.40, p = 0.005).
Within TRD, higher discrepancy predicts slower response to treatment independent of objective illness severity; this may be mediated by underlying personality traits and co-morbid anxiety.
Journal of psychiatric research 11/2010; 44(15):1082-7. · 3.72 Impact Factor
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Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 06/2009; · 6.99 Impact Factor
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ABSTRACT: To examine the value of combining cervical length and maternal characteristics in a prolonged-pregnancy clinic in the prediction of the probability of firstly, spontaneous onset of labor within the subsequent 10 days and secondly, the need for Cesarean section.
This was a prospective study of women with singleton pregnancies attending an ultrasound-based prolonged-pregnancy clinic at 40 + 4 to 41 + 6 weeks of gestation. The policy was to delay induction of labor by 7-10 days unless there was evidence of a specific medical or obstetric indication or the mother wanted earlier delivery. The measurement of cervical length was not given to the obstetrician, midwife or patient. Regression analysis was used to determine which of the following factors had a significant contribution in predicting induction of labor: maternal age, body mass index (BMI), ethnic origin, parity and cervical length. Regression analysis was also used to determine which of the factors amongst the maternal characteristics, onset of labor and cervical length provided significant prediction of Cesarean section.
We examined 2316 pregnancies but we excluded from further analysis 452 (19.5%) cases because iatrogenic delivery was carried out within the subsequent 6 days, including 427 cases of induction of labor (340 at the request of the mother and 87 for medical indications) and 25 cases of Cesarean section. In the remaining 1864 cases there was spontaneous onset of labor and delivery within 10 days in 1536 (82.4%) and induction of labor in 7-10 days in 328 (17.6%). The rate of Cesarean section was 15.2% (233 of 1536) in those with spontaneous onset of labor and 36.0% (118 of 328) in those whose labor was induced. Regression analysis demonstrated that in the prediction of induction of labor there were significant contributions from cervical length, BMI, parity and gestational age, and in the prediction of Cesarean section there were significant contributions from onset of labor, cervical length, BMI, parity and ethnicity.
Ultrasonographic measurement of cervical length at 41 weeks together with maternal factors can define the patient-specific probability of spontaneous onset of labor in the subsequent week and the risk of Cesarean section.
Ultrasound in Obstetrics and Gynecology 10/2008; 32(5):646-51. · 3.01 Impact Factor
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ABSTRACT: To evaluate the performance of screening for pre-eclampsia by uterine artery pulsatility index (PI) at 11 + 0 to 13 + 6 weeks' gestation and the change in uterine artery PI between 11 + 0 to 13 + 6 and 21 + 0 to 24 + 6 weeks.
In 3107 singleton pregnancies attending for routine care at 11 + 0 to 13 + 6 and 21 + 0 to 24 + 6 weeks' gestation we recorded maternal characteristics and medical and obstetric history, and measured uterine artery PI. The distributions of uterine artery PI were made Gaussian after logarithmic transformation and the log of the ratio of uterine artery PI at 21 + 0 to 24 + 6 weeks to that at 11 + 0 to 13 + 6 weeks was calculated. Multiple regression analysis was used to determine which of the maternal variables and Doppler findings were significant predictors of early and late pre-eclampsia. The performance of screening was described by receiver-operating characteristics curves.
Pre-eclampsia developed in 93 (3.0%) pregnancies, including 22 (0.7%) in which delivery was before 34 weeks (early pre-eclampsia) and 71 (2.3%) with delivery at 34 weeks or more (late pre-eclampsia). Seventy-three (2.3%) women developed gestational hypertension, 346 (11.1%) delivered small-for-gestational-age (SGA) babies with no hypertensive disorders and 2595 (83.5%) were unaffected by pre-eclampsia, gestational hypertension or SGA. Multiple regression analysis demonstrated that maternal variables, uterine artery PI at 11 + 0 to 13 + 6 weeks and the change in uterine artery PI between 11 + 0 to 13 + 6 and 21 + 0 to 24 + 6 weeks' gestation provided significant independent contributions to the prediction of pre-eclampsia. For a false positive rate of 5% the predicted detection rates of early and late pre-eclampsia were 90.9 and 31.0%, respectively. The same performance of screening was achieved by reserving second-trimester testing for only the 20% of women at the highest risk after first-trimester screening.
The decrease in uterine artery PI between 11 + 0 to 13 + 6 and 21 + 0 to 24 + 6 weeks is steeper in pregnancies with a normal outcome than in those developing pre-eclampsia. Effective screening for pre-eclampsia can be achieved by the Doppler measurement of uterine artery PI at 11 + 0 to 13 + 6 weeks and the change in PI between 11 + 0 to 13 + 6 and 21 + 0 to 24 + 6 weeks.
Ultrasound in Obstetrics and Gynecology 08/2008; 32(2):138-46. · 3.01 Impact Factor
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ABSTRACT: The effects of acute administration of an indirect dopamine-agonist, d-amphetamine, and a non-selective dopamine receptor antagonist, haloperidol, were investigated in normal male volunteers on habituation and prepulse inhibition (PPI) of the acoustic startle reflex in two experiments. In Experiment 1, 40 male non-smoker volunteers were tested for habituation and PPI (defined as percentage reduction of the pulse-alone amplitude; prepulses 9 dB above background) before and after double-blind administration of either 2 mg haloperidol or placebo. No influence of haloperidol was observed on either habituation or PPI of the startle reflex in this experiment. In Experiment 2, 60 male volunteers underwent startle testing before and after double-blind administration of a single oral dose of 5 mg haloperidol, 5 mg d-amphetamine or placebo. Habituation and PPI (prepulses 15 dB above background) for the placebo group did not differ significantly from that observed for the d-amphetamine or for the haloperidol group. However, in a subgroup of smoking subjects, both d-amphetamine and haloperidol reduced PPI as compared to that observed prior to drug administration. The implications of these findings in relation to animal pharmacological studies and observed sensorimotor gating deficits in schizophrenia are discussed.
Behavioural Pharmacology 12/1998; 9(7):567-76. · 2.72 Impact Factor
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ABSTRACT: Salivary cortisol profiles (hourly sampling over a 16-hour period) of 10 patients with chronic fatigue syndrome (CFS) but without concurrent depressive disorder were compared with those of 10 healthy volunteers matched for age, sex and menstrual cycle. The mean saliva cortisol concentration over the 16-hour period was slightly but significantly greater in the patients than the controls (p < 0.05). These findings are at variance with earlier reports that CFS is a hypocortisolaemic state and suggest that in CFS the symptom of fatigue is not caused by hypocortisolaemia.
Neuropsychobiology 01/1998; 37(1):1-4. · 2.67 Impact Factor
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ABSTRACT: This study was conducted to determine whether an increase in salivary free cortisol would be reliably elicited by a midday meal, thus providing a convenient physiological challenge to the hypothalamic-pituitary-adrenal (HPA) axis, and whether this cortisol release depended on the protein content of the meal.
In healthy men, free cortisol was measured in saliva samples taken before and after two identical protein-rich midday meals (39% energy as protein) and compared with a day on which no meal was eaten. Next, in healthy women in a nonclinical setting, salivary cortisol was measured before and after a protein-rich meal (32% energy as protein) on one day and a low-protein meal (5% energy as protein) on another day. Measures of mood, appetite, and psychological well-being were also taken.
An acute meal-dependent increase in salivary cortisol occurred, which was reliable over 2 test days. This increase in cortisol depended on the proportion of protein in the meal, increasing after the high-protein but not the low-protein meal. The extent of this increase in cortisol correlated significantly with poor psychological well-being in women. Some postmeal improvement of mood (positive affect) was associated with the high- but not the low-protein meal.
The cortisol response to meals may have implications for the effects of meal composition on mood, cognitive function, and food choice. The measurement of free cortisol in saliva provides a psychologically stress-free and reliable technique to assess the cortisol response to a standard protein-rich meal, ie, a physiological challenge to the HPA axis in men and women that could be investigated in naturalistic settings outside the laboratory.
Psychosomatic Medicine 61(2):214-24. · 3.97 Impact Factor
