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Prenatal exposure to maternal infection may be associated with the development of neurodevelopmental disorders as well as increased susceptibility to the development of schizophrenia. Prenatal administration of polyriboinosinic-polyribocytidilic-acid, mimicking RNA virus exposure, has been shown to induce schizophrenia-like behavioral, neurochemical and neuorophysiological abnormalities in rodent offspring. In the present study PIC prenatal administration at gestation day 15 was associated with alterations in the acoustic-startle-response/prepulse-inhibition [ASR/PPI] and the HPA-axis stress response in rat offspring on day 90. We show that pretreatment with dehydroepiandrosterone (DHEA) reverses PIC-related ASR/PPI disruption in female rats and normalizes HPA-axis stress response in a united group of male and female rats. Further research in both animal and human studies is recommended in order to confirm these preliminary findings and their application to the understanding and management of schizophrenia and related conditions., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Monoamines and dehydroepiandrosterone (DHEA) levels were measured in a genetic animal model for childhood depression in four subcortical structures: nucleus accumbens (Nac), ventral tegmental area (VTA), amygdala and hypothalamus. The "depressive-like" strain was the Flinders Sensitive Line (FSL), compared to their controls, Sprague-Dawley (SD) rats. Prepubertal FSL rats showed abnormal levels of only a few monoamines and their metabolites in these brain regions. This is in contrast to former studies, in which adult FSL rats exhibited significantly higher levels of all the monoamines and their metabolites measured. These different abnormal monoamine patterns between the "depressed" prepubertal rats and their adults, may help to explain why depressed children and adolescents fail to respond to antidepressant treatment as well as adults do. On the other hand, FSL prepubertal rats exhibited the same pattern of abnormal DHEA basal levels as was found in adults in previous experiments. The results from the current study may imply that treatment with DHEA could be a promising novel therapeutic option for depressed children and adolescents that fail to respond to common (monoaminergic) antidepressant treatments.

Objective: In previous studies we have demonstrated high serum molar ratios of cortisol to dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) [together abbreviated DHEA(S)], and the value of both cortisol/DHEA(S) molar ratios for prediction of responsivity to antipsychotic treatment in schizophrenia patients. The present study aimed to examine the contribution of anxiety, and severity of symptoms to the prediction of serum cortisol, DHEA(S) levels and two molar ratios across three examinations., Method: Serum concentrations of cortisol and DHEA(S)were examined in 43 schizophrenia inpatients and in 20 age matched healthy controls at baseline, and after 2 and 4 weeks. The Positive and Negative Symptom Scale and the State-Trait Anxiety Inventory scores were used as independent variables for multiple regression analysis., Results: Despite clinical improvement during the study period cortisol/DHEA(S) molar ratios were found persistently elevated as compared to healthy controls. Multiple regression analysis revealed that across three examinations cortisol/DHEA(S) molar ratios negatively associated with trait-anxiety (partial R(2)=7-14%) rather than with negative symptoms (partial R(2)=3-6%). Age and age of onset account for 12.7% for variability of cortisol/DHEAS ratio. Serum cortisol concentrations are predicted by trait and state-anxiety, activation symptoms and daily doses of antipsychotics. A small portion of variability in serum DHEA levels (R(2)=9%) is associated with symptom severity, while DHEAS levels were predicted by age at examination and age of onset., Conclusion: Elevated serum cortisol/DHEA(S) molar ratios were attributed to trait-anxiety and age rather than to clinical symptoms. The findings may indicate persistent dysfunction of the hypothalamic-pituitary-adrenal axis that is independent of the patients' clinical state.

We aimed to verify whether DHEA, a neuoroactive neurosteroid, has a protective role in preventing the occurrence or enhancement of the severity of depression and anxiety in mice. Four groups were tested: controls, mice possessing significantly high frontal cortex DHEA levels, achieved by repeated DHEA injections (1.6 mg/Kg, i.p.), mice that have significantly low frontal cortex DHEA levels, consequent to castration and mice possessing significantly low frontal cortex DHEA levels, treated with DHEA to reverse its level to normal, achieved by castration and repeated DHEA injections (0.4 mg/Kg, i.p.). The Forced Swim Test to determine depressive-like and the Elevated Plus Maze (EPM) to evaluate anxiety-like behaviors, were used. We found that DHEA had an anti-depressive-like effect, as shown by a decreased immobility time in mice possessing a high level of frontal cortex DHEA and increased immobility time in mice that have a low frontal cortex DHEA level. DHEA also demonstrated an anti-anxiety-like effect, as shown by the open-arm time in EPM, which correlated with DHEA level. Mice with significantly low DHEA levels when restored to normal, did not differ from controls. In conclusion, high levels of DHEA have an anti-anxiety-like and an anti-depressive-like effect in mice and those with low levels of frontal cortex DHEA are more vulnerable to depression and/or anxiety.

Objective: The goals of this study were to determine whether alterations in serum dehydroepiandrosterone (DHEA), its sulfated conjugate (DHEAS), androstenedione, testosterone, and progesterone concentrations occur in schizophrenia patients compared with healthy controls over two months, and their associations with psychopathology, emotional distress, and antipsychotic treatment., Method: Serum hormones were repeatedly determined for 21 antipsychotic-treated male DSM-IV schizophrenia patients and 14 healthy controls. Observations were at four time points: upon entry into the study, and after 2, 4 and 8 weeks., Results: In schizophrenia patients compared with healthy controls serum concentration of DHEA and androstenedione found increased, but that of DHEAS decreased, while progesterone and testosterone showed normal levels. Schizophrenia patients were also characterized by elevated androstenedione/DHEAS molar ratios, and reduced DHEAS/DHEA and testosterone/androstenedione molar ratios compared with healthy controls. Concentrations and molar ratios of serum hormones did not significantly change during the study either among schizophrenia patients, or healthy controls. Among patients alterations in DHEA, DHEAS and androstenedione were associated with emotional distress, anxiety, dysphoric mood, positive and activation symptoms, serum prolactin levels, but were not related to age, antipsychotic agents, and extrapyramidal side effects., Conclusions: Alterations in DHEA metabolism in schizophrenia are attributed to the distress, anxiety, severity of symptoms, prolactin levels, and may represent a marker for impaired hormonal responses to stress. These findings should be considered when evaluating the discrepancies in DHEA studies in schizophrenia.

Dehydroepiandrosterone (DHEA) or their sulfate conjugate (DHEAS) (together abbreviated DHEA(S)) exert multiple effects in the central nervous system, and may be involved in the pathophysiological processes in schizophrenia. This prospective study aimed to investigate whether serum cortisol/DHEA(S) molar ratios are associated with response to antipsychotic treatment during the exacerbation of schizophrenia. Serum DHEA(S) and cortisol were determined at baseline, and 2 and 4 weeks later for 43 medicated schizophrenia inpatients with acute exacerbation. The patients were treated with stable doses of antipsychotic agents up to 2 weeks prior to entering the study and for the 4-week duration of the study after which they were classified as either responders or nonresponders to treatment. Findings suggest that responders had significantly higher serum cortisol levels and cortisol/DHEA(S) ratios compared with nonresponders. These differences remained significant at three time points controlling for gender, age, severity of symptoms and emotional distress, benzodiazepines, type or dosage of antipsychotic agents, and background variables. The logistic regression model shows advantages of both cortisol/DHEA(S) molar ratios vs serum cortisol and DHEA(S) concentrations for prediction of responsivity to antipsychotic treatment. No significant canonical correlations were observed between changes from baseline through end-of-study in hormonal values and severity of symptoms and emotional distress among responders and nonresponders. Thus, these data provide evidence that elevated serum cortisol and cortisol/DHEA(S) ratios may serve as markers of biological mechanisms that are involved in responsivity of schizophrenia patients to antipsychotic treatment.

Background: Several endocrine abnormalities are reported in obesity. Some are considered as causative factors, whereas others are considered to be secondary effects of obesity. In the current study, we explored the changes in cortisol, growth hormone (GH), DHEA, DHEA-S and GH releasing hormone (ghrelin) plasma levels in morbidly obese subjects who lost abundant weight following laparoscopic adjustable gastric banding (LAGB)., Methods: 12 morbidly obese adult patients (15 females), age 21-56 years with BMI 46.0+/-4.4 kg/cm(2), were studied. Blood samples were collected before, 6 and 14 months after LAGB. The levels of DHEA, DHEA-S, cortisol, GH, and ghrelin were determined by commercial kits. Statistical analysis was based on one-way repeated measures ANOVA, followed by Student-Newman-Keuls post-hoc test., Results: Mean BMI reduced significantly along the study course (P=.000). Cortisol plasma levels significantly decreased 6 months after surgery (from 541.4+/-242.4 nM to 382.4+/-142.1 nM, P=.004), but did not change further after 14 months (460.2+/-244.9 nM), despite further reduction in BMI (P=.050). GH constantly increased throughout the study from 0.076+/-0.149 ng/ml, to 0.410+/-0.509 ng/ml at 6 months (NS), to 1.224+/-1.738 ng/ml at 14 months after surgery (P=.001). DHEA, DHEA-S and ghrelin plasma levels remained stable throughout the study., Conclusions: GH levels showed a persistent increase during the 14 months following LAGB in association with the weight loss, while a transient decrease in cortisol levels occurred at the 6-months time-point. In contrast, ghrelin, DHEA and DHEA-S were not altered after surgery. The association between GH and cortisol secretion and surgical- and nonsurgical-induced weight reduction merits further investigation.

Dehydroepiandrosterone (DHEA) is a neurosteroid synthesized de novo in the brain, in addition to the periphery, modulating some membrane, ion-gated channel neurotransmitter receptors. P450-17alpha-hydroxylase activity converting pregnenolone to DHEA, has not yet been identified in the brain of rodents. Studies in brain-derived primary cultures and cell lines, suggest a possible alternative pathway for DHEA synthesis involving oxygenated hydroxyperoxides. We investigated DHEA synthesis in the brains of castrated male mice before and after treatment with N-acetylcysteine amide (AD4) (a newly developed brain penetrating antioxidant). We found a significant increase in brain DHEA level 24 h after castration, which was totally blocked by AD4. This blockade of castration-induced increased brain DHEA synthesis, supports the assumption that this synthesis may also be affected by free radicals. This is the first in vivo study indicating the possible existence of an in-brain oxidative stress-related pathway leading to brain DHEA production.