Memory-directed acupuncture as a neuromodulatory treatment for PTSD: Theory, clinical model and case studies.

Posttraumatic stress disorder (PTSD) poses an ongoing challenge to society, to health systems, and to the trauma victims themselves. Today PTSD is often considered an incurable chronic problem that lacks effective treatment. While PTSD is closely related to memory, it also affects many physiological systems. PTSD is usually treated with medications and psychotherapy with moderate success, leaving a substantial proportion of patients with enduring distress and disability. Therefore, a search for better treatment options is vital. In this paper, we propose a model in which a conversation-based technique is integrated with bodily manipulation through acupuncture. This approach first emerged in clinical experience showing intriguing results from treating PTSD patients using acupuncture as a main strategy. Its theoretical foundations derive from the clinic and rely on contemporary neuroscience's understanding of memory consolidation and reconsolidation processes. Research shows that acupuncture can have potentially positive effects at three levels: (a) achieving a balance between sympathetic and parasympathetic neural activity; (b) reducing activation in the limbic system, hence inducing a calming effect; (c) reshaping the functional connectivity map within important and relevant cortical regions that encompass the default-mode network. We suggest that coupling traumatic memory retrieval leading to reconsolidation, combined with acupuncture, offers considerable potential for positive clinical improvement in patients with PTSD. This may explain the positive results of the described case studies and can pave the path for future advances in research and treatment in this field.

Exploring the effectiveness of a patient-tailored integrative oncology program on emotional distress during chemotherapy for localized cancer.

STUDY OBJECTIVE: There is a need to explore how patient-tailored integrative oncology (IO) programs reduce emotional distress. This study set out to bridge the IO research gap between non-specific, quality of life-related and specific emotional-related concerns in chemotherapy-treated patients. METHODS: This pragmatic, prospective and preference-controlled study examined patients attending an integrative-physician consultation and weekly IO treatments during adjuvant/neo-adjuvant chemotherapy for localized cancer. Patients choosing to attend ≥4 IO sessions (highly adherent to integrative care, AIC) were compared to low AIC patients using the ESAS (Edmonton Symptom Assessment Scale) anxiety, depression and sleep; and the EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire) emotional functioning scale, at baseline, 6 and 12 weeks. Emotional distress was assessed by ESAS anxiety and depression, considered as the primary study outcomes. RESULTS: Of 439 participants, 260 (59%) were high-AIC and 179 low-AIC, both with similar baseline demographic and cancer-related characteristics. At 6 weeks, high-AIC patients reported greater improvement on ESAS sleep (p = 0.044); within-group improvement on ESAS anxiety and; and EORTC emotional functioning. Compared with low-AIC, high-AIC patients showed greater improvement on ESAS depression (p = 0.022) and sleep (p = 0.015) in those with high baseline ESAS anxiety scores (≥7); and ESAS anxiety (p = 0.049) for patients moderately anxious (4-6) at baseline. CONCLUSIONS: High-AIC was associated with significantly reduced anxiety, depression and sleep severity at 6 weeks, especially those with high-to-moderate baseline anxiety levels. These findings reduce the research gap, suggesting specific emotional-related effects of IO.

Psychiatrists' attitude towards the use of clozapine in the treatment of refractory schizophrenia: A nationwide survey.

OBJECTIVES: Clozapine is the most effective treatment for refractory schizophrenia, yet it remains underused in clinical practice. The current study examined the awareness, familiarity and attitude of a nationwide sample of Israeli psychiatrists regarding the use of clozapine. METHODS: Data were collected using questionnaires, completed by 295 psychiatrists. Participants were asked to score questions regarding clozapine procedures; familiarity with guidelines, drug properties, prescription and attitude towards specialized clozapine resources. RESULTS: About half (53.3%) of the psychiatrists reported initiating treatment with clozapine according to the guidelines, whereas 33% reported that they administered clozapine only after three or more unsuccessful antipsychotic treatments. Surprisingly, availability of specialized resources for clozapine treatment (such as clozapine clinics) was associated with delayed initiation of clozapine treatment, and a lower rate of clozapine administration. Barriers to clozapine use included concerns about patient adherence, side effects and partial compliance with the required blood monitoring. CONCLUSIONS: Delaying or avoiding clozapine treatment to potentially eligible patients, despite familiarity with the drug efficacy and treatment guidelines, is a major mental health concern. However, executive allocation of resources to support the use of clozapine may be ineffective in promoting clozapine use.

A Pilot Study of Possible Easy-to-Use Electrophysiological Index for Early Detection of Antidepressive Treatment Non-Response.

INTRODUCTION: The evaluation of response to pharmacological treatment in MDD requires 4-8 weeks. Therefore, the ability to predict response, and especially lack of response to treatment, as early as possible after treatment onset or change, is of prime significance. Many studies have demonstrated significant results regarding the ability to use EEG and ERP markers, including attention-associated markers such as P300, for early prediction of response to treatment. But these markers are derived from long EEG/ERP samples, often from multiple channels, which render them impractical for frequent sampling. METHODS AND RESULTS: We developed a new electrophysiological attention-associated marker from a single channel (two electrodes), using 1-min samples with auditory oddball stimuli. This work presents an initial evaluation of the ability to use this marker's dynamics between repetitive measures for early (<2 weeks) differentiation between responders and non-responders to antidepressive treatment, in 26 patients with various levels of depression and heterogeneous treatment interventions. The slope of change in the marker between early consecutive samples was negative in the non-responders, but not in the responders. This differentiation was stronger for patients suffering from severe depression (p < 0.001). CONCLUSION: This pilot study supports the feasibility of the EEG marker for early recognition of treatment-resistant depression. If verified in large-scale prospective studies, it can contribute to research and clinical work.

[THE SCHIZOPHRENIC PATIENT IN THE DEPARTMENT OF MEDICINE IN THE 21ST CENTURY: IS THERE ANYTHING NEW UNDER THE SUN?]

INTRODUCTION: A retrospective analysis of information from the computerized data of the Emek Medical Center (EMC) and Clalit Community Healthcare Services (CCHS) was conducted. Two hundred and seventy-five SPs and four hundred and twenty eight NPPs were enrolled in the study. AIMS: Patients returning to the emergency room, and re-hospitalizations in the internal medicine wards. BACKGROUND: Schizophrenic patients (SPs) are at risk for organic co-morbidities and tend to be excessively hospitalized in medical departments. It is important to understand the pattern of SP re-admissions to emergency rooms and medical departments in order to avoid re-hospitalizations. OBJECTIVES: To compare re-admissions to medical emergency rooms and medical departments between SP and non-psychiatric patients (NPPs) and to assess the changes that took place during the years 2001-2011. RESULTS: The likelihood that SPs would be referred to the ER during the first 6 months after discharge was 1.51 (95% CI 1.10-2.07), higher than in NPPs. The likelihood of being re-hospitalized in medical departments during the first 6 months after discharge was higher in SPs but did not reach statistical significance (26.18% among SPs vs.20.09% among NPPs (P = 0.059). The time from the index hospitalization to re-hospitalization during the first year was shorter in the SPs when compared with NPPs (P=0.0032). CONCLUSIONS: Medical patients with schizophrenia tend to be referred to the medical emergency room and to be re-hospitalized after their index hospitalization. The integration of medical and psychiatric systems may improve their medical care and reduce their re-admission rates.

[THE CLINICAL AND DEMOGRAPHIC CHARACTERISTICS OF PATIENTS WHO FREQUENT THE PSYCHIATRIC EMERGENCY ROOM IN A GENERAL HOSPITAL].

INTRODUCTION: The recent policy implemented in Israel of reducing psychiatric admissions and the concomitant shifting of treatment to outpatient clinics, together with briefer stays in hospital and a growing number of repeat emergency room (ER) visits have created a "revolving door" phenomenon, whereby a small number of frequent attenders are responsible for a disproportionate fraction of ER visits. OBJECTIVES: To characterize psychiatric ER frequent attenders and understand their special needs by analyzing the "revolving door" phenomenon and defining the at-risk group. METHODS: Psychiatric attenders at the Ha'Emek Medical Center in Afula during a single year were divided retrospectively into three groups according to the number of their visits to the ER. One group had a single ER visit, an intermediate group had two to three ER visits, and a third group had four or more ER visits (frequent attenders). The groups were weighted by the respective number of attenders and analyzed using the optimal allocation technique. RESULTS AND CONCLUSIONS: The findings showed that people prone to frequently repeat visits to a psychiatric emergency room are familiar with the psychiatric system, unemployed, with an unstable income (or recipients of an allowance from the National Insurance), single or divorced, of Sephardic origin, have been hospitalized in the past, and are urban, native-born with social and family problems. From a clinical perspective the findings also showed thatthis subgroup comes to the ER without a referral, suffers from depression and psychotic states, personality disorders or mental retardation, has past suicide attempts, and the patients are under medication treatment. DISCUSSION AND SUMMARY: Frequent attenders make up a particularly difficult group of patients with major psychiatric disorders. The ER is not a fit setting for the treatment of such patients. The construction of a proper therapist-patient relationship is cardinal to attaining a meaningful remission. Prompt recognition of frequent attenders and their respective visiting pattern is required, allowing for a structured therapeutic approach which will include patient and family guidance and an algorithmic handling of emergency situations.

Thiamine deficiency in self-induced refeeding syndrome, an undetected and potentially lethal condition.

Rapid restoration of nutrients and electrolytes after prolonged starvation could result in a life threatening condition characterized by sensory and neurological dysfunction and severe metabolic imbalance that has been designated as refeeding syndrome. Its diagnosis is frequently missed resulting in severe complications and even death. We describe a 25-years-old female patient with mental disorders and severe malnutrition who developed severe clinical manifestations and biochemical abnormalities characteristic of the refeeding syndrome, after restarting oral feeding on her own. Schizophrenia was later diagnosed. Increased awareness of this condition and its complications is necessary to prevent its detrimental complications.

The Effects of Acupuncture Treatment on Sleep Quality and on Emotional Measures among Individuals Living with Schizophrenia: A Pilot Study.

Purpose. To examine the effects of acupuncture on sleep quality and on emotional measures among patients with schizophrenia. Methods. Twenty patients with schizophrenia participated in the study. The study comprised a seven-day running-in no-treatment period, followed by an eight-week experimental period. During the experimental period, participants were treated with acupuncture twice a week. During the first week (no-treatment period) and the last week of the experimental period, participants filled out a broad spectrum of questionnaires and their sleep was continuously monitored by wrist actigraph. Results. A paired-sample t-test was conducted comparing objective and subjective sleep parameters manifested by participants before and after sequential acupuncture treatment. A significant effect of acupuncture treatment was observed for seven objective sleep variables: sleep onset latency, sleep percentage, mean activity level, wake time after sleep onset, mean number of wake episodes, mean wake episode and longest wake episode. However, no significant effects of acupuncture treatment were found for subjective sleep measures. Likewise, the results indicate that acupuncture treatment improved psychopathology levels and emotional measures, that is, depression level and anxiety level. Conclusions. Overall, the findings of this pilot study suggest that acupuncture has beneficial effects as a treatment for insomnia and psychopathology symptoms among patients with schizophrenia.

The effects of music relaxation on sleep quality and emotional measures in people living with schizophrenia.

The aim of the present study was to examine the effects of music relaxation on insomnia and emotional measures in people living with schizophrenia. Twenty-four people living with schizophrenia participated in the study. The study involved a 7-day running-in no-treatment period, followed by a 7-day experimental period. Treatment consisted of music relaxation played at bedtime. During each of these periods, participants' sleep was continuously monitored with a wrist actigraph, and participants completed a wide spectrum of questionnaires. Results showed an improvement in sleep latency and sleep efficiency after the music relaxation was played. Likewise, music relaxation was shown to improve participants' total psychopathology score (PANSS) as well as their level of depression. Moreover, a significant correlation was found between reduction in level of situational anxiety and improvement in sleep efficiency. The findings suggest the beneficial effect of music relaxation as a treatment both for insomnia and for emotional measures in people living with schizophrenia.

Preliminary effects of bupropion and the promoter region (HTTLPR) serotonin transporter (SLC6A4) polymorphism on smoking behavior in schizophrenia.

In the current study, we investigated how individual variants in the serotonin promoter gene, previously associated with smoking cessation and linked to anxiety-related personality traits, were associated with individual differences in responsiveness to bupropion and cognitive behavioral therapy (CBT) in a clinical population. We hypothesize that subjects with the long allele may be less responsive to treatment. Altogether 61 schizophrenic patients (46 M, 15 F) on stable neuroleptic medication were initially enrolled in a smoking reduction program (prospective, double-blind, placebo-controlled) including cognitive behavioral therapy plus placebo or CBT plus bupropion. Additionally, subjects were genotyped for a polymorphism in the serotonin transporter (SLC6A4). Thirty-two subjects (23 M, 9 F) completed a 14-week course of treatment. While both groups of subjects demonstrated significant reductions in smoking behavior due to CBT, subjects receiving bupropion did not show significant differences in smoking behavior when compared to placebo. In addition, analysis by SPSS repeated measures multivariate showed a significant sex by SLC6A4 genotype interaction on the number of cigarettes smoked. Only male subjects with at least one short promoter region allele (short/short and short/long combined) showed a reduction in cigarette consumption as a result of treatment. This study provides preliminary evidence of how polymorphisms in the serotonin transporter can be informative in predicting individual responses to smoking reduction therapy.

Mitochondrial DNA HV lineage increases the susceptibility to schizophrenia among Israeli Arabs.

Haplotypes and haplogroups are linked sets of common DNA variants, acting as susceptibility or protective factors to complex disorders. Growing evidence suggests that dysfunction of mitochondrial bioenergetics contributes to the schizophrenia phenotype. We studied mitochondrial DNA haplogroups in schizophrenia patients. Since mitochondria are inherited from the mothers, we used healthy fathers as an ideal case-control group. Analysis of the distribution of mitochondrial haplogroups in schizophrenia patients compared to their healthy fathers (202 pairs) resulted in an over-representation of the mtDNA lineage cluster, HV, in the patients (p=0.01), with increased relative risk (odds ratio) of 1.8. Since mitochondrial DNA is small relative to nuclear DNA, a total mitochondrial genome analysis was possible in a hypothesis-free manner. However, mitochondrial DNA haplogroups are highly variable in human population and it will be necessary to replicate our results in other human ethnic groups.

No evidence for association between NOTCH4 and schizophrenia in a large family-based and case-control association analysis.

OBJECTIVES: An analysis of 80 British parent-offspring trios by Wei and Hemmings in 2000 revealed thre1e out of five markers within the NOTCH4 locus to be strongly associated with schizophrenia. In our present study, we have examined NOTCH4 markers in large samples of German and Palestinian-Arab origin. METHODS: Our study population comprised a German case-control sample (n=512 schizophrenia patients and n=232 controls) and two independent parent-offspring trio samples of German (n=159 trios) and Palestinian-Arab (n=208 trios) descent. We examined a total of ten single nucleotide polymorphisms within the NOTCH4 locus and the adjacent loci, spanning a region of approximately 100 kb. RESULTS: Neither single marker nor haplotype analyses showed association with schizophrenia. In addition, analyses of the German case-control and trio samples revealed no significant association between NOTCH4 polymorphisms and early-onset schizophrenia. CONCLUSIONS: Our results suggest that NOTCH4 is unlikely to play a major role in the genetic predisposition to schizophrenia in the German or the Palestinian-Arab population.

The effect of postpartum depression on women's consultations with physicians.

BACKGROUND: Postpartum depression is a well-known phenomenon that occurs in about 10% of births and affects the quality of life of the mother as well as the family. As in other cases of depression, under-diagnosis of PPD may keep patients from getting proper care and increase their physical and emotional distress. OBJECTIVES: To identify patients with PPD and to describe their consultation patterns with primary care physicians for themselves and their babies. METHODS: Using a telephone survey and the Edinburgh Postnatal Depression Scale questionnaire we identified PPD in a sample of women who gave birth in HaEmek Medical Center. We also assessed the extent to which the women consulted with family physicians, gynecologists and/or pediatricians. RESULTS: The survey included 574 women, of whom 9.9% were diagnosed with PPD. There was a higher rate of PPD among Arab compared to Jewish women, among women with a prior history of depression, among women whose pregnancy was unplanned, among those who described the course of pregnancy as "difficult," and among women who described their general health as "not good." Women with PPD consulted more with family physicians and pediatricians. The reasons for the consultations are physical and emotional. There were cases of somatization manifested directly by the mother or indirectly through the baby. CONCLUSIONS: Women with PPD have higher consultation rates than those without. By asking a few simple questions it is possible to identify a significant proportion of women with PPD.

Association of the serotonin transporter gene with smoking behavior.

OBJECTIVE: In an ongoing molecular genetic study of temperament, participants were genotyped to examine the association of smoking with two polymorphisms of the serotonin transporter gene (SERT): the promoter region, 5-HTTLPR, and an intronic variable-number-of-tandem-repeats region (VNTR). METHOD: Full information was available for 330 families, and 244 "ever smokers" were identified (54 past smokers, 190 current smokers). The average number of cigarettes smoked per day was 13.12, and the mean Fagerstrom Tolerance Questionnaire score was 4.79. Associations of genotype, Tridimensional Personality Questionnaire scores, and smoking phenotype were tested by using a robust family design with a variance-components framework and by case-control analysis. RESULTS: There was a significant excess of the 5-HTTLPR long allele with the 12-repeat VNTR in current smokers, past smokers, and ever smokers, compared to participants who had never smoked. The results from the population design were confirmed in the family-based analysis. No association was observed between two quantitative measures of smoking and the polymorphisms. A weak association was observed between novelty seeking and the VNTR polymorphism and between reward and 5-HTTLPR. Smokers, regardless of gender, scored significantly higher on novelty seeking and did not differ on harm avoidance or reward. CONCLUSIONS: There was a highly significant association between SERT and the categorical definition of smoking, irrespective of dependence level, suggesting that this gene influences the initiation of smoking. Mediation analysis failed to substantiate the hypothesis that novelty seeking partially mediates the effect of SERT on smoking. SERT appears to independently contribute to novelty seeking and smoking.

[Weighing the efficacy and safety of herbal medicine: the case of Kava-Kava].

Kava-Kava is an indigenous plant in the Pacific islands and has been traditionally used for centuries for both ceremonial and social purposes. The efficacy of the plant for treatment of anxiety states was recently acknowledged in randomized controlled trials. Although these trials support the safety of Kava for short term usage, a major concern was raised in accordance with emerging reports that relate Kava use to major hepatic damage, including a few cases of fulminant hepatitis that required liver transplantation or ended in death. As a result, most medical authorities in the West restricted or banned Kava use. This review discusses evidence of efficacy and safety in the use of Kava for treating patients with anxiety, as well as its meaning in the therapeutic context and patient-doctor dialogue.

Pilot-controlled trial of D-cycloserine for the treatment of post-traumatic stress disorder.

Dysfunction of glutamatergic neurotransmission may be relevant to the pathogenesis of post-traumatic stress disorder (PTSD). Preclinical and clinical evidence suggests that PTSD symptoms could be alleviated following enhancement of neurotransmission mediated at the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors. Eleven patients with chronic PTSD participated in a double-blind, placebo-controlled, cross-over trial with 50 mg/d D-cycloserine which acts as a partial agonist at the glycine regulatory site on the NMDA receptor. D-cycloserine treatment resulted in significant improvements in numbing, avoidance, and anxiety symptoms; however, similar effects were also observed during placebo treatment. In addition, D-cycloserine treatment resulted in a significant (p=0.03), reduction in the perseverative error scores as measured by the Wisconsin Card Sorting Test. This pilot study is the first to assess the efficacy of a NMDA receptor modulator for PTSD treatment and its results warrant further, larger-scale investigation.

Increased mitochondrial complex I activity in platelets of schizophrenic patients.

It is believed that dopamine and alterations of energy metabolism in cortical and subcortical structures are involved in the pathophysiology of schizophrenia. Recently, we and others have shown that dopamine may affect energy metabolism by interacting with mitochondrial complex I activity in rats both in vivo and in vitro. In this study activity of complexes I and IV was assessed in mitochondria isolated from blood platelet of schizophrenic patients and compared to patients with affective disorders and healthy control subjects. Seventy-seven in-patients who met DSM-IV criteria for schizophrenia (in acute exacerbation), bipolar disorder depressed type (BP), or recurrent major depressive disorder (MDD) and 24 control subjects participated in the study. A highly significant increase (240%, p < 0.001) in complex I activity but not in complex IV, was detected in medicated and unmedicated schizophrenic patients compared to controls. No such change was observed in patients with affective disorders. The data demonstrate a specific and selective, alteration in platelet complex I activity in schizophrenic patients, which is not related to medication. If this abnormality in platelet mitochondria reflects brain alterations, it may further support the relevance of alterations in energy metabolism to the pathophysiology of schizophrenia. Finally in the lack of any clinically relevant biological marker for schizophrenia, complex I activity in platelets might become a useful peripheral marker for this disorder.