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Belhanes H.,The Yezreel Valley College | Zubedat S.,Behavioral Neuroscience Laboratory | Zubedat S.,The Emek Medical Center | Zubedat S.,The Yezreel Valley College | And 3 more authors.
Psychoneuroendocrinology | Year: 2013

Background: It is currently accepted that complex behavior and mental disorder results from a combination of biological susceptibility and exposure to environmental stimuli. Most of the gene-environment interaction models focus on the interaction between the stimuli and a single candidate gene. We suggest that an alternative approach is interference with the expression of multiple genes followed by exposure to environmental insults. Methods: Early interference with gene transcription was performed by treatment of 7 days old Wistar male rats for 4 days with the Sp1/DNA binding inhibitor, mithramycin. Environmental insult was mimicked by exposing these rats during adulthood (34 days) to sub-chronic (12 days, n= 30) or chronic stress (28 days, n= 48). The effects of mithramycin and stress treatment on the behavioral response and serum corticosterone concentration were assessed. Results: Exposure of mithramycin treated rats to sub-chronic stress led to anxious behavior in the open field test, high startle response, low sucrose preference, indifference to novel objects and high serum corticosterone concentration. However, exposure to chronic stress resulted in normal sucrose preference, startle response and serum corticosterone, novelty seeking behavior and reduced anxiety. In saline treated rats the extension of stress duration led to behavioral and hormonal adaptation to stress. Conclusion: Our study suggests that postnatal temporal interference with multiple gene expression can lead to hyper-responsiveness to environmental stimuli, the features of which affects the phenotypic outcomes. Such a paradigm may be used to model gene-environmental interaction in the etiology of behavioral disorders. © 2013 Elsevier Ltd.


PubMed | Bar - Ilan University, Tel Aviv University and The Yezreel Valley College
Type: Journal Article | Journal: The Israel journal of psychiatry and related sciences | Year: 2015

Social Anxiety Disorder (SAD) is characterized by fear and avoidance in social situations where one is exposed to scrutiny by others. It is possible that automatic thoughts either cause the disorder or maintain it, and thus their examination is warranted.30 SAD subjects diagnosed with the MiniInternational Neuropsychiatric Interview (MINI) and 30 healthy controls were administered the Liebowitz Social Anxiety Scale (LSAS), the Automatic Thoughts Questionnaires (ATQ-Negative and ATQ-Positive), the Sheehan Disability Scale (SDS) and the Beck Depression Inventory (BDI). It was hypothesized that the SAD subjects would display more depression and disability, more negative automatic thoughts and fewer positive automatic thoughts than the healthy controls, and that the automatic thoughts will predict the severity of SAD.SAD patients had higher scores of depression and disability, higher scores on the ATQ-Negative questionnaire and lower scores on the ATQ-Positive questionnaire. The scores of the LSAS subscales were predicted by the scores of the ATQ-Positive and the BDI questionnaires.Moderate sample size and limits of the questionnaires used in the study.Automatic thoughts may be an important area of research with larger samples. Further studies should be carried out in order to examine if strengthening positive thinking and ablation of negative thinking can reduce SAD symptoms during cognitive behavioral treatment.


Avital A.,The Yezreel Valley College | Avital A.,Weizmann Institute of Science | Dolev T.,The Yezreel Valley College | Aga-Mizrachi S.,The Yezreel Valley College | Zubedat S.,The Yezreel Valley College
PLoS ONE | Year: 2011

Attention-deficit/hyperactivity disorder (ADD/ADHD) has been emerging as a world-wide psychiatric disorder. There appears to be an increasing rate of stimulant drug abuse, specifically methylphenidate (MPH) which is the most common treatment for ADHD, among individuals who do not meet the criteria for ADHD and particularly for cognitive enhancement among university students. However, the long term effects of exposure to MPH are unknown. Thus, in light of a developmental approach in humans, we aimed to test the effects of adolescence exposure to enriched environment (EE) followed by MPH administration during early adulthood, on reactions to stress in adulthood. Specifically, at approximate adolescence [post natal days (PND) 30-60] rats were reared in EE and were treated with MPH during early adulthood (PND 60-90). Adult (PND 90-92) rats were exposed to mild stress and starting at PND 110, the behavioral and endocrine effects of the combined drug and environmental conditions were assessed. Following adolescence EE, long term exposure to MPH led to decreased locomotor activity and increased sucrose preference. EE had a beneficial effect on PPI (attentive abilities), which was impaired by long term exposure to MPH. Finally, the interaction between EE and, exposure to MPH led to long-term elevated corticosterone and testosterone levels. In view of the marked increase in MPH consumption over the past decade, vigilance is crucial in order to prevent potential drug abuse and its long term detrimental consequences. © 2011 Avital et al.


Attention-deficit/hyperactivity disorder (ADD/ADHD) has been emerging as a world-wide psychiatric disorder. There appears to be an increasing rate of stimulant drug abuse, specifically methylphenidate (MPH) which is the most common treatment for ADHD, among individuals who do not meet the criteria for ADHD and particularly for cognitive enhancement among university students. However, the long term effects of exposure to MPH are unknown. Thus, in light of a developmental approach in humans, we aimed to test the effects of adolescence exposure to enriched environment (EE) followed by MPH administration during early adulthood, on reactions to stress in adulthood. Specifically, at approximate adolescence [post natal days (PND) 30-60] rats were reared in EE and were treated with MPH during early adulthood (PND 60-90). Adult (PND 90-92) rats were exposed to mild stress and starting at PND 110, the behavioral and endocrine effects of the combined drug and environmental conditions were assessed. Following adolescence EE, long term exposure to MPH led to decreased locomotor activity and increased sucrose preference. EE had a beneficial effect on PPI (attentive abilities), which was impaired by long term exposure to MPH. Finally, the interaction between EE and, exposure to MPH led to long-term elevated corticosterone and testosterone levels. In view of the marked increase in MPH consumption over the past decade, vigilance is crucial in order to prevent potential drug abuse and its long term detrimental consequences.

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