The Effectiveness of a Knowledge Translation Cognitive-Educational Intervention for Family Members of Persons Coping with Severe Mental Illness.

Keshet, a course for family members of persons' coping with mental illness, was developed to enhance positive family cognitive communication skills. Improving communication with the use of mediation techniques, primarily used by therapists, creates a learning environment viewed as a strategy of Knowledge Translation. To examine the effectiveness of Keshet in improving attitudes, problem solving, communication skills and attenuation of burden a quasi-experimental research design was applied with study and control condition. The same group of participants (N = 38) completed questionnaires at different stages: 3 months prior to course, initiation and completion. Following participation, significant changes were observed in attitudes regarding knowledge of how to cope and interact with family member. A correlation was found between improved knowledge and decline in burden. Implementing interventions which provide caregivers with professional "know-how" leads to lessened burden, thus contributing to maintaining well-being of family caregiver population.

Bruxism and oral parafunctional hyperactivity in social phobia outpatients.

Anxiety and selective serotonin reuptake inhibitors (SSRIs) are considered aggravating factors for bruxism. We examined the influence of anxiety, depression and SSRI on bruxism in social phobia (SP). Twenty-three drug naïve, 17 SSRI-treated SP patients and 33 healthy controls underwent a psychiatric assessment and completed Leibowitz Social Anxiety Scale and Beck Depression Inventory. Oral parafunctional activity (PF) was evaluated by TM-dental examination and by a questionnaire. Drug- naïve and SSRI-treated SP patients did not differ on demographic and clinical measures. Awake bruxism, 'JAW PLAY' and at least one PF were more prevalent in SP than in controls. Severity of SP predicted the presence of PF. SP, but not depression, was associated with higher risk of oral PF and awake bruxism. Chronic SSRI treatment of SP did not affect sleep and awake bruxism. Dental and anxiety screening may improve the prognosis psychiatric and dental patients. Effective treatment of SP may mitigate bruxism.

Validity of proposed DSM-5 diagnostic criteria for nicotine use disorder: results from 734 Israeli lifetime smokers.

BACKGROUND: The fifth edition of the diagnostic and statistical manual of mental disorders (DSM-5) proposes aligning nicotine use disorder (NUD) criteria with those for other substances, by including the current DSM fourth edition (DSM-IV) nicotine dependence (ND) criteria, three abuse criteria (neglect roles, hazardous use, interpersonal problems) and craving. Although NUD criteria indicate one latent trait, evidence is lacking on: (1) validity of each criterion ; (2) validity of the criteria as a set ; (3) comparative validity between DSM-5 NUD and DSM-IV ND criterion sets ; and (4) NUD prevalence. METHOD: Nicotine criteria (DSM-IV ND, abuse and craving) and external validators (e.g., smoking soon after awakening, number of cigarettes per day) were assessed with a structured interview in 734 lifetime smokers from an Israeli household sample. Regression analysis evaluated the association between validators and each criterion. Receiver operating characteristic analysis assessed the association of the validators with the DSM-5 NUD set (number of criteria endorsed) and tested whether DSM-5 or DSM-IV provided the most discriminating criterion set. Changes in prevalence were examined. RESULTS: Each DSM-5 NUD criterion was significantly associated with the validators, with strength of associations similar across the criteria. As a set, DSM-5 criteria were significantly associated with the validators, were significantly more discriminating than DSM-IV ND criteria, and led to increased prevalence of binary NUD (two or more criteria) over ND. CONCLUSIONS: All findings address previous concerns about the DSM-IV nicotine diagnosis and its criteria and support the proposed changes for DSM-5 NUD, which should result in improved diagnosis of nicotine disorders.

Compression anastomoses in colorectal surgery: a review.

The main serious risks of anastomotic construction in the colon and rectum include dehiscence and stricture formation. There is a resurgence of interest in sutureless anastomoses formed by compression elements since the introduction of shape memory alloy (SMA) systems, which evoke minimal early inflammatory response whilst maintaining anastomotic integrity. Currently, the most commonly used SMA is the nickel-titanium (NiTi) alloy that is highly biocompatible, returning to its pre-deformed stable (austenite) shape under different mechanical and thermal loads for use in humans. Pre-clinical data for shape memory alloy systems in colorectal anastomoses are limited, but it appears to be safe in porcine and canine models with limited leakage and reduced stricture formation. There does not appear to be any difference in tissue biochemistry of inflammatory markers when compared with conventional stapled techniques, although the few studies available show a markedly reduced early inflammatory response at the anastomotic site with the NiTi device. The majority of the clinical data concerning compression anastomoses are derived from the biofragmentable anastomotic ring device. This device has fallen out of use because of reported leaks, instrumental failure and problems with device expulsion. A novel SMA device, the NiTi anastomotic ring, permits construction of a low rectal anastomosis construction during open or laparoscopic procedures. The preliminary data demonstrate a safety comparable to conventional staple technology. This device also provides the potential of benefit of reduced anastomotic inflammation, because the compression ring results in direct serosa-to-serosa (or alternatively serosa-to-muscularis propria) apposition without the persistence of residual foreign material. This type of construction could lead to a reduced incidence of early anastomotic leakage and/or the development of anastomotic stenosis. Randomized clinical trials employing a NiTi arm for elective, emergency and high-risk colorectal anastomoses are required to determine its indications and clinical profile as well as to assess whether such technology may selectively obviate the need for proximal diversion in low colorectal anastomoses.

Effects of country of origin and wave of immigration on prevalence of schizophrenia among first and second-generation immigrants: A 30-year retrospective study.

OBJECTIVES: To compare the rates of schizophrenia among 1st and 2nd generation immigrants from two distinct backgrounds and across sequential periods of immigration. METHODS: A 30-years retrospective cohort study (187,184 individuals) of 1st and 2nd generation East-African immigrants (EAIs) and former Soviet-Union immigrants (FSUIs) who migrated to Israel between 1980 and 2012. EAIs were further divided according to waves of immigration. Period prevalence was calculated between the years 2002-2012. Multivariate logistic regression models were used to examine the association between immigration-related factors and prevalence of schizophrenia (Native-Born Israelis serving as reference group). RESULTS: The prevalence of schizophrenia in 1st generation EAIs and FSUIs was 1.8% and 1.2%, respectively, compared to 1.0% among NBIs (p<0.001). The prevalence of schizophrenia among 2nd generation EAIs and FSUIs was 1.3% and 0.8%, respectively, compared to 0.6% among NBIs (p<0.001). Adjusted odds ratios for developing schizophrenia compared to NBIs were 1.6 (95%CI:1.4-1.8) and 2.1 (95%CI:1.6-2.7), among 1st and 2nd generation EAIs and 1.1 (95%CI:0.9-1.2) and 1.3 (95%CI:1.0-1.8) among 1st and 2nd generation FSUIs respectively. Among EAIs, we observed the highest rate of schizophrenia in the pioneer wave of immigrants with gradual decline across subsequent waves: 2.4%, 1.9% and 1.0% for the 1st, 2nd and 3rd waves of immigration, respectively (p<0.001). CONCLUSIONS: The increased risk for developing schizophrenia among 2nd generation immigrants and among pioneer groups of immigrants emphasizes the importance of persistent investment in acculturation. Further studies elucidating the impact of country of origin and ethnic density on the risk for developing schizophrenia are warranted.

Colon cancer screening in 2010: an up-date.

Colorectal cancer is among the most common cancers worldwide. The prognosis for limited disease is excellent; however, it becomes poor for more advanced disease. The majority of colorectal cancers arise from premalignant adenomatous polyps. This makes the detection of polyps and early carcinoma an attractive screening strategy. This article will review the current tests available for screening for colorectal cancer. These include stool based tests (guaiac-based fecal occult blood tests, immunochemical fecal tests, stool DNA panel), radiologic tests (double contrast barium enema and computed tomography colonography), and endoscopy (flexible sigmoidoscopy and colonoscopy). The current use of these tests in population-based screening programs and the most recent screening guidelines from the largest advisory groups in North America and Europe will be discussed.

Dehydroepiandrosterone and monoamines in the limbic system of a genetic animal model of childhood depression.

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.

A cross-fostering study in a genetic animal model of depression: maternal behavior and depression-like symptoms.

Connections between maternal behavior and childhood depression were examined by using a "genetic animal model"; Flinder Sensitive Line--(FSL) rats, and cross-fostering the offspring with the control strain, Sprague Dawley (SD) rats. The control procedure was "in-fostering", where the foster dam and her pups were from the same strain. Contribution of pups' characteristics/genotype to maternal behavior was examined. After weaning, we measured male offspring's body weight, immobility in the swim test, and basal corticosterone (CORT) and adrenocorticotropin (ACTH) levels at the prepubertal age of 35 days. While maternal behavior (of "depressive-like" dams and their controls) was not altered significantly by the pups' strain, the adoption procedure per se appeared to have more adverse effects on "depressive-like" symptoms of the SD prepubertal rats than on the FSL pups. Nevertheless, the combination between abnormal maternal behavior and genetic predisposition affected the hormonal stress responses of the offspring in a more severe manner than genetic predisposition or abnormal maternal behavior per se.

The interaction between neurocognitive functioning, subthreshold psychotic symptoms and pharmacotherapy in 22q11.2 deletion syndrome: A longitudinal comparative study.

BACKGROUND: The 22q11.2 deletion syndrome (22q11DS) is the most common genetic syndrome associated with schizophrenia. The goal of this study was to evaluate longitudinally the interaction between neurocognitive functioning, the presence of subthreshold psychotic symptoms (SPS) and conversion to psychosis in individuals with 22q11DS. In addition, we attempted to identify the specific neurocognitive domains that predict the longitudinal evolution of positive and negative SPS, as well as the effect of psychiatric medications on 22q11DS psychiatric and cognitive developmental trajectories. METHODS: Forty-four participants with 22q11DS, 19 with Williams syndrome (WS) and 30 typically developing (TD) controls, age range 12-35years, were assessed at two time points (15.2±2.1months apart). Evaluation included the Structured Interview for Prodromal Symptoms (SIPS), structured psychiatric evaluation and the Penn Computerized Neurocognitive Battery (CNB). RESULTS: 22q11DS individuals with SPS had a yearly conversion rate to psychotic disorders of 8.8%, compared to none in both WS and TD controls. Baseline levels of negative SPS were associated with global neurocognitive performance (GNP), executive function and social cognition deficits, in individuals with 22q11DS, but not in WS. Deficits in GNP predicted negative SPS in 22q11DS and the emergence or persistence of negative SPS. 22q11DS individuals treated with psychiatric medications showed significant improvement in GNP score between baseline and follow-up assessments, an improvement that was not seen in untreated 22q11DS. CONCLUSIONS: Our results highlight the time-dependent interplay among positive and negative SPS symptoms, neurocognition and pharmacotherapy in the prediction of the evolution of psychosis in 22q11DS.

Dehydroepiandrosterone in the nucleus accumbens is associated with early onset of depressive-behavior: a study in an animal model of childhood depression.

Although the monoamine theory of depression is well studied, regarding childhood depression it is poorly supported. Antidepressant treatments affecting the monoaminergic system fail to ameliorate childhood depression in the same manner that they affect adult depression. The present study used the Flinders sensitive line (FSL) rat, a well-investigated genetic animal model of depression and Sprague-Dawley (SD) rats as controls. We co-measured monoamines and dehydroepiandrosterone (DHEA) levels in the nucleus accumbens on postnatal day 1, in prepubertal rats (35 days), and adult rats (4 months) in order to examine developmental characteristics in the monoamine systems. The results suggest that there are different ontogenetic patterns of monoaminergic activity in FSL and SD rats. While monoamine levels were different only in adulthood, FSL rats exhibited lower DHEA levels already in prepubertal childhood. These differences may be relevant to the poor response to antidepressant drugs observed in depressed children and suggest DHEA as a new marker for childhood depression.

Stress hormones and emotion-regulation in two genetic animal models of depression.

Children of depressed parents often exhibit emotion-regulation deficits, characterized by either excessive withdrawal or approach strategies toward the mother. The current study examined behavioral and physiological emotion-regulation in preweanling pups (postnatal day 17-19) belonging to two different genetic animal models of depression, Wistar-Kyoto (WKY) and Flinders Sensitive-Line (FSL) rats. The study also examined the effects of stress on the two animal models, hypothesizing an interactive effect of hereditary vulnerability and exposure to stress. Chronic-stress was simulated by providing limited bedding to the dam and litter for a week, in the early postnatal period. Acute-stress was generated by exposure to an adult male rat, an ethologically valid stressor. Emotion-regulation of the pups was examined using a Y-maze preference test and radioimmunoassay of Hypothalamic-Pituitary-Adrenal (HPA) axis hormones (corticosterone & adreno-corticotropin/ACTH). WKY and FSL pups exhibited reduced approach-behavior toward the dam, an emotion-regulation profile reminiscent of avoidant attachment evident in many children of depressed parents. In contrast, the two animal models did not show similar HPA axis activity. FSL pups exhibited markedly lower ACTH levels compared to controls, while WKY pups did not differ from controls. With regard to the stress manipulations, the limited-bedding condition had no effect, while the acute-stressor induced overall effects on all groups, with more pronounced reactivity evident in the WKY and FSL pups. Taken together, the experiments indicate a similar behavioral profile of the two strains at the preweanling period, while suggesting HPA dysfunction in only one of the strains.

Aggressive behavior and HPA axis hormones after social isolation in adult rats of two different genetic animal models for depression.

In the current study we explored behavioral and endocrinological effects of exposure to social isolation during adulthood in two different genetic animal models of depression, the Flinders Sensitive Line (FSL), and their controls, Sprague-Dawley (SD) rats and the Wistar-Kyoto (WKY) strain and their controls, Wistar rats. Behavioral patterns of the different strains in coping with an intruder were studied in the "aggression" or resident-intruder test. We also measured basal plasma levels of the hypothalamic-pituitary-adrenal (HPA) axis hormones corticosterone and ACTH and their levels after chronic stress (isolation). Significant alterations in the levels of HPA hormones after social isolation were noted in the "depressed-like" strains. There were no significant behavioral differences between FSL and SD rats in the "aggression" test. In contrast, WKY rats exhibited less frequent aggressive-like and social behavior compared to Wistar controls. The results suggest that the FSL and WKY strains, both genetic animal models of depression, exhibit separate patterns of HPA axis modulation and aggressive-like behavior after social isolation. These different patterns may reflect two different types of depression. An "avoidant" or socially inhibited type of depressive-like behavior is seen most clearly in the WKY strain.

Homocysteine levels in adolescent schizophrenia patients.

Homocysteine is a sulfur containing amino acid that has been widely investigated for its putative role in cardiovascular and neuropsychiatric disorders. It has been suggested that homocysteine has implications especially in young, male schizophrenia patients. In this prospective case-control study, we compared plasma homocysteine levels in a group of adolescent schizophrenia inpatients (aged 14-21 years; n=23) to normal healthy controls (n=51). Mean plasma homocysteine levels were significantly higher in the patient group than in the control group (15.40+/-2.00 and 9.78+/-0.33 micromol/L, respectively, p<0.032). The difference was almost entirely attributable to the male schizophrenia subgroup (18.18+/-5.65 in male patients vs. 10.31+/-5.33 micromol/L in female patients). The group x sex interaction was statistically significant (p=0.0035). These data indicate that a subgroup of male adolescent schizophrenia patients has high homocysteine blood levels. The role of homocysteine in the pathophysiology of adolescent-onset schizophrenia merits further investigation.

Elevated C-reactive protein levels in schizophrenia inpatients is associated with aggressive behavior.

BACKGROUND: An association between inflammation and behavioral domains of mental disorders is of growing interest. Recent studies reported an association between aggression and inflammation. In this study, we investigated the association between aggressive behavior and inflammatory markers in schizophrenia inpatients. METHODS: Adult schizophrenia inpatients without affective symptoms (n=213) were retrospectively identified and categorized according to their C-reactive protein measurement at admission as either elevated (CRP>1 mg/dL; n=57) or normal (CRP<1 mg/dL; n=156). The following indicators of aggression were compared: PANSS excitement component (PANSS-EC), restraints and suicidal behavior during hospitalization. Univariate comparisons between elevated and normal CRP levels were performed and multivariate analysis was conducted to control for relevant covariates. RESULTS: CRP levels significantly correlated with other laboratory markers indicating increased inflammation including leukocyte count and neutrophil to lymphocyte ratio (r=0.387, P<0.0001 and r=0.356, P<0.0001) respectively. Inpatients with elevated C-reactive protein displayed increased aggressive behavior compared to patients with normal CRP levels (<1 mg/dL). This was manifested by higher rates of restraint during hospitalization (χ(2)=5.22, P=0.031) and increased PANSS-EC score (U=5410.5, P=0.012). Elevated CRP levels were not associated with suicidal behavior. Multivariate analysis revealed that higher PANSS-EC score was associated with elevated CRP after controlling for the covariates age, sex, BMI and smoking. CONCLUSION: This study identified a potential biological correlate (inflammation) of a specific behavioral endophenotype (aggression) in schizophrenia inpatients.

The CD44 ligand hyaluronic acid is elevated in the cerebrospinal fluid of suicide attempters and is associated with increased blood-brain barrier permeability.

BACKGROUND: The glycosaminoglycan hyaluronic acid (HA) is an important component of the extracellular matrix (ECM) in the brain. CD44 is a cell adhesion molecule that binds to HA in the ECM and is present on astrocytes, microglia and certain neurons. Cell adhesion molecules have been reported to be involved in anxiety and mood disorders. CD44 levels are decreased in the cerebrospinal fluid (CSF) of depressed individuals, and the CD44 gene has been identified in brain GWAS studies as a possible risk gene for suicidal behavior. METHOD: We measured the CSF levels of HA and the soluble CD44 (sCD44) in suicide attempters (n=94) and in healthy controls (n=45) using ELISA and electrochemiluminescence assays. We also investigated other proteins known to interact with CD44, such as osteopontin and the matrix metalloproteinases MMP1, MMP3 and MMP9. RESULTS: The suicide attempters had higher CSF levels of HA (p=.003) and MMP9 (p=.004). The CSF levels of HA correlated with BBB-permeability (rho=0.410, p<.001) and MMP9 correlated with sCD44 levels (rho=0.260, p=.005). LIMITATIONS: Other relevant biological contributors to suicidal behavior is not addressed in parallel to the specific role of CD44-HA signaling. The gender distribution of the patients from whom CSF was analyzed was uneven. CONCLUSIONS: Increased BBB-permeability and HA levels might be a results of increased neuroinflammation and can play a role in the pathobiology of suicidal behavior. The CD44 signaling pathway might be considered a novel target for intervention in mood disorders.

CD44 Deficiency Is Associated with Increased Susceptibility to Stress-Induced Anxiety-like Behavior in Mice.

CD44 is a cell surface adhesion molecule and its principal ligand is hyaluronic acid (HA), a key component of the brain's extracellular matrix. CD44 levels are decreased in the cerebrospinal fluid (CSF) of depressed individuals, and the CD44 gene has been identified in genome wide association study as a possible risk gene in suicidal behavior. In order to define the pathobiological mechanisms by which CD44 may affect behavior, we investigated the role of CD44 using male CD44 knockout (CD44KO) and wild-type mice that underwent chronic mild stress (CMS). Behavior was characterized using the sucrose preference and forced swim tests, open field, novel object recognition, social preference, and the elevated plus maze tests. Gene expression in hippocampus was evaluated using quantitative real-time PCR. Brain monoamines and their metabolites were assessed by high-performance liquid chromatography and serum HA and IL-1ß levels were measured using ELISA and electrochemiluminescence assays. CD44KO mice were more susceptible to stress-induced anxiety-like behavior and displayed increased anhedonia and despair than the wild-type controls. The behavioral phenotype of stressed CD44KO mice was associated with reduced cortical serotonergic and striatal dopaminergic turnover. The hippocampal expression of the receptor for HA-mediated motility (RHAMM) was reduced in the non- stressed CD44KO mice compared with WT mice, in a value similar to that observed in WT mice following exposure to stress. Taken together, our experiments suggest that CD44 plays a key role in stress response in mice.

An epidemiologic study of Gilles de la Tourette's syndrome in Israel.

OBJECTIVES: The goal of this study was to estimate the lifetime prevalence of Gilles de la Tourette's syndrome (GTS) in adolescents aged 16 to 17 years. DESIGN: Population-based epidemiologic study. SUBJECTS: Eighteen thousand three hundred sixty-four males and 9673 females aged 16 to 17 years screened for induction into the Israel Defense Force. RESULTS: Of the 28,037 individuals screened, 12 met diagnostic criteria for GTS. The point prevalence in this population was 4.3 +/- 1.2 (mean +/- SE) per 10,000. The 95% confidence interval for this estimate is 1.9 to 6.7 per 10,000. The point prevalence was 4.9 +/- 1.6 per 10,000 for males (95% confidence interval, 1.8 per 10,000) and 3.1 +/- 1.8 per 10,000 for females (95% confidence interval, 0 to 6.6 per 10,000). The rate of obsessive-compulsive disorder (OCD) was significantly elevated among the subjects with GTS (41.7%) compared with the population point prevalence of OCD (3.4) in those without GTS. In contrast, the rate of attention deficit hyperactivity disorder was only 8.3% compared with the population point prevalence of 3.9% in those individuals without GTS. CONCLUSIONS: The prevalence estimates from this population-based study are in agreement with previous results based on surveys of younger children. The sex ratio observed in this study is not as large as reported in previous studies and remains to be explored in other studies of adolescents and adults.

Circulatory neurosteroid levels in underweight female adolescent anorexia nervosa inpatients and following weight restoration.

Nineteen female adolescent inpatients diagnosed with anorexia nervosa, restricting type (AN-R) and 16 non-eating disordered (ED) controls were assessed for plasma dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulphate (DHEA-S), and cortisol levels, and for eating-related and non-eating-related psychopathology. AN-R patients were assessed at admission, 1 month and 4 months following hospitalization. The non-ED controls were assessed once. No baseline between-group differences were found in plasma cortisol, DHEA, and DHEA-S levels, whereas the patient group had a significantly lower Cortisol/DHEA-S ratio and elevated scores on most psychopathological parameters. A significant increase was found in the body mass index of the AN-R patients at 4 months post-hospitalization, accompanied by a decrease in plasma cortisol levels and a trend towards decreased Cortisol/DHEA and Cortisol/DHEA-S ratios, whereas no change occurred in psychopathology. The difference in Cortisol/DHEA-S ratio between AN-R patients and non-ED controls, and the different patterns of change in cortisol vs. DHEA(-S) levels following weight restoration, may in part account for the feeding difficulties in AN, particularly during refeeding.

Dehydroepiandrosterone Attenuates Cocaine-Seeking Behaviour Independently of Corticosterone Fluctuations.

The neurosteroid dehydroepiandrosterone (DHEA) is involved in the pathophysiology of several psychiatric disorders, including cocaine addiction. We have previously shown that DHEA attenuates cocaine-seeking behaviour, and also that DHEA decreases corticosterone (CORT) levels in plasma and the prefrontal cortex. Previous studies have found that rats demonstrate cocaine-seeking behaviour only when the level of CORT reaches a minimum threshold. In the present study, we investigated whether the attenuating effect of DHEA on cocaine seeking is a result of it reducing CORT levels rather than a result of any unique neurosteroid properties. Rats received either daily DHEA injections (2 mg/kg, i.p.) alone, daily DHEA (2 mg/kg, i.p.) with CORT infusion (to maintain stable basal levels of CORT; 15 mg/kg, s.c.) or vehicle (i.p.) as control, throughout self-administration training and extinction sessions. We found that both DHEA-treated and DHEA + CORT-treated groups showed a significantly lower number of active lever presses compared to controls throughout training and extinction sessions, as well as at cocaine-primed reinstatement. DHEA-treated rats showed lower CORT levels throughout the experimental phases compared to DHEA + CORT-treated and control rats. Additionally, we show that DHEA administered to cocaine-trained rats throughout extinction sessions, or immediately before reinstatement, attenuated cocaine seeking. These findings indicate that DHEA attenuates cocaine-seeking behaviour independently of fluctuations in CORT levels.