Noa Benaroya-Milshtein

Environmental enrichment in mice decreases anxiety, attenuates stress responses and enhances natural killer cell activity.

The importance of environment in the regulation of brain, behaviour and physiology has long been recognized in biological, social and medical sciences. Animals maintained under enriched conditions have clearly been shown to have better learning abilities than those maintained under standard conditions. However, the effects of environmental enrichment (EE) on immunity and emotionality have been less documented and remain questionable. Therefore, we investigated the effect of EE on natural killer (NK) cell activity, psychological stress responses and behavioural parameters. Male C3H mice were housed either in enriched or standard conditions for 6 weeks. Behaviour was then examined by the grip‐strength test, staircase and elevated plus maze, and corticosterone levels and NK cell activity were measured. Furthermore, animals exposed to the stress paradigm, achieved by electric shock with reminders, were tested for freezing time in each reminder. Corticosterone levels were also measured. The EE mice showed decreased anxiety‐like behaviour and higher activity compared to standard mice, as revealed by a greater percentage of time spent in the open arms of the elevated plus maze, and a higher rate of climbing the staircase. A shorter freezing time in the stress paradigm and no corticosterone level reactivity were measured in EE mice. In addition, NK cell activity in spleens of EE mice was higher than that demonstrated in those of standard mice. Thus, EE has a beneficial effect on anxiety‐like behaviour, stress response and NK cell activity. The effect on NK cell activity is promising, due to the role of NK cells in host resistance.

Environmental Enrichment Augments the Efficacy of Idiotype Vaccination for B-cell Lymphoma

Environmental enrichment is known to positively influence the organisms psychologic and physiologic well-being. However, the effects of environmental enrichment on immune responses and cancer prognosis have not been clearly established and its impact on cancer therapy is unknown. Here, we report that environmental enrichment mediated a statistically significant improvement of the outcome of immunotherapy in an experimental model of B-cell lymphoma. When mice were immunized with an idiotype-vaccine, those maintained under enriched environmental conditions produced statistically significant higher levels of anti-idiotype antibodies and revealed more attenuated tumor growth than those housed in standard environments. Most strikingly, enriched tumor-bearing mice had statistically significant prolonged survival, with 44% of them disease-free compared with 0% in the standard rearing tumor-bearing mice. The possible mechanisms for the enhancement of immunotherapy by environmental enrichment are cognitive, physical activity, and psychologic. The demonstration of synergistic effect of cancer therapy and environmental enrichment on tumor rejection has important implication for cancer treatment.

Subjective versus objective measures of tic severity in Tourette syndrome – The influence of environment

The objective of this study was to examine the influence of environmental challenges on tic expression by subjective and objective measures. The study group consisted of 41 children aged 6-18 years (M=10.15, SD=2.73) with a primary diagnosis of Tourette syndrome. Subjective measures included the Functional Assessment Interview developed for this study and three standard validated instruments. The objective measure was a video-recording of the patients in five daily-life situations: watching television, doing homework, being alone, receiving attention when ticcing, and talking to a stranger. In addition, the effect of premonitory urges on assessment of tic expression was evaluated. The associations between the subjective and objective measures of tic expression were moderate to low. A significantly higher number of tics were observed in the television situation, and a significantly lower number in the alone situation, compared to the other situations. Higher levels of premonitory urge were associated with greater awareness of objectively measured tic expression. In conclusion, tic expression is significantly influenced by the environment. Subjective measures of tic expression may be misleading. These results have implications for refining the clinical assessment of tics, improving research methodology, and developing new therapeutic strategies.

Antipsychotic monotherapy and adjuvant psychotropic therapies in schizophrenia patients: effect on time to readmission.

This study assessed the relationship between pharmacological regimens at hospital discharge and hospital readmission among schizophrenia patients. The records reviewed were all consecutive admissions (N=720) from a specific catchment area during the period 1991–2005. Two main groups were selected for analysis: the first group (N=537) included patients discharged with first-generation antipsychotics (FGA), and the second group (N=183) included patients with second-generation antipsychotics (SGA). Data on clinical and demographic characteristics at discharge, including a brief psychiatric rating scale and pharmacological treatment, were collected. The rate of readmission within 12 months was analyzed in relation to the specific pharmacological treatment at discharge. There was no significant difference in the risk of readmission in patients treated with SGA compared with FGA. Adjuvant psychotropic medications to either FGA or SGA did not attenuate the risk of readmission. The readmission rate in patients treated with clozapine (N=74) was significantly lower in comparison with depot FGA (N=293) medications (P=0.016). There was no advantage of SGA over FGA, with or without adjuvant psychotropic treatment, with regard to rehospitalization risk during the 12-month follow-up. Clozapine was found to reduce the risk for readmission in comparison with depot FGA.

Specific executive control impairments in Tourette syndrome: The role of response inhibition

BACKGROUND Tourette syndrome (TS) is a childhood-onset disorder characterized by motor and vocal tics. While cognitive features of common comorbid conditions such as attention deficit hyperactive disorder and obsessive compulsive disorder have been widely investigated, the cognitive profile of TS patients remains to be precisely defined. In this regard, the executive functions system (EF) is of especial interest. AIMS The aim of the study was to delineate the various components of executive processes in adult TS patients. METHODS A sample of 19 adults diagnosed with TS and 19 age-matched control subjects underwent computerized battery of executive tasks, as well as block design and memory tests. All patients received a thorough clinical assessment with an emphasis on illness severity. RESULTS There was a marked impairment in response inhibition ability regardless of comorbid conditions, In addition, there was decreased accuracy in set shifting, but not in response time. These results imply that impaired response inhibition in the EF system is the primary cognitive impairment in TS and that many of the previously reported impaired executive functions in TS are secondary to this impairment. CONCLUSIONS This finding of impaired response inhibition in TS may imply that rehabilitation of this inhibition component could prove to be an important therapeutic strategy in adults with TS.

Executive control development in Tourette syndrome and its role in tic reduction

Tourette syndrome (TS) is a childhood-onset disorder characterized by motor and vocal tics. Recent findings point to a possible role of executive functions system development in the tic reduction observed with age. The goal of the present work was to track the development of executive functions system measured by well-established cognitive tasks and its correlation with diminished tic severity over time in order to understand the role of executive functions in the remission process observed in most adults. The first study followed 25 young TS patients, measuring their executive functions and clinical condition at three time- points. In the second study we compared executive functions performance of 19 adult TS patients with 19 healthy controls and 12 remitted TS patients. The first study showed that tic reduction is related to the development of the executive functions components associated with response inhibition. The second study similarly showed impaired inhibition ability in TS patients but not in controls or the remitted TS patients. The remitted group performed at normal or even higher levels on certain measures. We conclude that inhibition, an important executive function, is impaired in subjects suffering from TS and that intact executive function development is related to remission processes.

Non-Motor Aspects of Tic Disorders—New Developments

The cardinal characteristics of tic-related disorders are stereotyped motor movements and vocalizations. However, they may be accompanied by non-motor features that appear sequentially during the course of the disorder and can sometimes be more disabling than the tics themselves. This review presents our perspectives on several non-motor aspects of Tourette syndrome based on the long experience of the Neuropsychiatric Tourette Clinic of a tertiary pediatric medical center. The effect of premonitory urges, sensory modulation disorder, tic-related cognitions, and environmental conditions on the expression and intensity of tics is elaborated, with suggestions for treatment approaches to each. We also describe the mediatory effect of parental attachment style on the link between maternal stress and ticcing intensity and the need to adjust psychotherapy interventions to account for the importance of this factor in emotion regulation. This review is intended to direct attention to the non-motor aspects of Tourette syndrome. An in-depth understanding of this complex and debilitating disorder will facilitate the formulation of innovative therapeutic protocols.

Stress conditioning in mice: alterations in immunity and tumor growth.

The neuroendocrine and autonomic nervous systems are known regulators of brain–immune interaction. However, the functional significance of this interaction under stress is not fully understood. We investigated the effect of a stress paradigm by applying electric foot shock followed by three reminders, on behavior, immune parameters, and lymphoma tumor growth. Male C3H mice were divided into two groups: Group 1—exposed to electric foot shock followed by three reminders, and Group 2—untreated (controls). Sets of mice underwent the elevated plus maze, staircase, and hot plate tests. After foot shock, natural killer (NK) cell activity, and lymphocyte proliferation were measured. In addition, sets of mice were either vaccinated twice with B-cell lymphoma 38C-13 immunoglobulin for determination of anti-idiotype (Id) antibodies in sera, or inoculated with tumor cells and monitored for tumor development and survival time. Mice exposed to electric foot shock followed by the three reminders had higher NK cell activity, levels of anti-Id antibodies, and a higher proliferation rate of splenocytes in response to mitogens, than the control mice. The exposed mice also showed attenuated tumor growth. Thus, the stress paradigm inhibited tumor development and lead to some immune changes that were not accompanied by behavioral changes.

A study of sensory dysregulation in children with tic disorders

Disrupted somatosensory processing characterized by over- or under- responsiveness to environmental stimuli plays an important, yet often overlooked, role in typical development and is aberrant in various neurodevelopmental disorders. These dysfunctional somatosensory processes have been conceptualized as an entity termed somatosensory dysregulation (SMD). Since Tourette syndrome (TS) is a prototypical example of developmental psychopathological disorder, we hypothesised that SMD would be a feature found in children suffering from the disorder. Ninety-two subjects representing consecutive admissions to a tertiary paediatric Tourette syndrome clinic were admitted to the study. Comorbid conditions included ADHD, depression, anxiety disorder, and OCD. For purposes of the study, patients completed a battery of self-, caregiver-, and clinician-rated psychological instruments measuring TS core symptoms and comorbidities and quality of life. Sensory modulation was measured by self-report and by objective measures such as stimulation with Von Frey filaments. Almost 50% of the cohort had no SMD. Of the remainder, 14 (15%) had suspected SMD and 32 (34.8%) had SMD. SMD was significantly more common and severe when there were comorbidities. The presence of SMD was associated with more severe impairments in quality of life and less participation in daily activities. The SMD, as measured by subjective measures but not by objective, is probably more associated with central processing rather than peripheral perception.

Emotional Reactivity and Regulation Following Citalopram Therapy in Children and Adolescents with Anxiety Disorders

OBJECTIVE Emotional dysregulation is an important element in the pathophysiology of childhood anxiety disorders and can distinguish anxious subjects from controls. Treatment with selective serotonin inhibitors (SSRIs) has been found to lessen anxiety, but its effects on emotional reactivity and regulation are less documented. The aim of the study was to prospectively assess changes in emotional reactivity and regulation in response to citalopram in children and adolescents with anxiety disorders, with special focus on the mechanism of reappraisal. METHODS The sample included 70 children and adolescents (38 boys, 32 girls) 10-17 years of age, divided into three groups: Those with anxiety disorder treated with citalopram for 8 weeks (n = 35); untreated subjects with anxiety disorder on the waiting list for cognitive behavioral therapy (CBT) (n = 15); and subjects without anxiety disorder (controls) (n = 20). Emotional reactivity and regulation (i.e., reappraisal), were assessed at baseline and after 8 weeks (follow-up) with validated computer-based instruments, Reactivity and Regulation-Situations (REAR-S) and Reactivity and Regulation-Images (REAR-I). RESULTS Citalopram-treated subjects showed significantly greater improvement in reappraisal ability than CBT-waitlisted subjects. Improvement in the ability to reappraise threatening images correlated significantly with the decrease in anxiety. There was a decrease in negative emotional reactivity between assessments, which was positively correlated with clinical improvement. Higher intensity of baseline reactivity (on the REAR-S) predicted more severe symptoms at follow-up. CONCLUSIONS Citalopram therapy improves reappraisal ability in children and adolescents with anxiety. However, the improvement in other examined emotional reactivity indices occurred in both medicated and waitlisted groups. It is possible that these findings may have implications for understanding the pathophysiology of anxiety in children and adolescents.