No abnormality in the gene for the G protein stimulatory alpha subunit in patients with bipolar disorder.

BACKGROUND: The available evidence for an involvement of the heterotrimeric guanine-nucleotide-binding proteins (G proteins) in bipolar disorder relies primarily on the effects of lithium salts on G protein function and on alterations in the concentration or function of G proteins (most notably Gs-alpha) in peripheral leukocytes and in postmortem tissues of patients with bipolar disorder. METHODS: The hypothesis that a mutation in Gs-alpha gene confers an increased susceptibility to bipolar disorder was tested by the following strategies: (1) mutational screening of the Gs-alpha subunit gene coding sequences and promoter sequences by denaturing gradient gel electrophoresis in unrelated individuals with bipolar disorder and (2) association and linkage analyses with a common silent exonic polymorphism, using genetic allelic information from American families with at least 1 affected child. For association analysis, the transmission test for linkage disequilibrium was used; for linkage analysis, nonparametric methods were used. RESULTS: No structural or regulatory mutations in this gene were found in bipolar disorder; the results of association and genetic linkage were negative. CONCLUSION: Our results do not support the speculation that the Gs-alpha protein gene has a role in the genetic predisposition to bipolar disorder.

Effect of transcranial magnetic stimulation in posttraumatic stress disorder: a preliminary study.

BACKGROUND: Transcranial magnetic stimulation (TMS) has become, over the last few years, a promising avenue for new research in affective disorders. In this study we have evaluated the clinical effect of slow TMS on posttraumatic stress disorder (PTSD) symptoms. METHODS: Ten PTSD patients were given one session of slow TMS with 30 pulses of 1 m/sec each, 15 to each side of the motor cortex. RESULTS: Symptoms of PTSD were assessed by using three psychological assessment scales, at four different time points. In this first, pilot, open study, TMS was found to be effective in lowering the core symptoms of PTSD: avoidance (as measured by the Impact of Event Scale), anxiety, and somatization (as measured by the Symptom Check List-90). A general clinical improvement was found (as measured by the Clinical Global Impression scale); however, the effect was rather short and transient. CONCLUSIONS: The present study showed TMS to be a safe and tolerable intervention with possibly indications of therapeutic efficacy for PTSD patients.

Transcranial magnetic stimulation in mania: a controlled study.

OBJECTIVE: Left prefrontal transcranial magnetic stimulation has been reported to have ECT-like effects in depression; therefore, the authors planned a study of transcranial magnetic stimulation in mania. METHOD: Sixteen patients completed a 14-day double-blind, controlled trial of right versus left prefrontal transcranial magnetic stimulation at 20 Hz (2-second duration per train, 20 trains/day for 10 treatment days). Mania was evaluated with the Mania Scale, the Brief Psychiatric Rating Scale, and the Clinical Global Impression. RESULTS: Significantly more improvement was observed in patients treated with right than with left prefrontal transcranial magnetic stimulation. CONCLUSIONS: The therapeutic effect of transcranial magnetic stimulation in mania may show laterality opposite to its effect in depression.

Transcranial magnetic stimulation and antidepressive drugs share similar cellular effects in rat hippocampus.

Transcranial magnetic stimulation (TMS) has been proposed as a safe and efficient treatment of human clinical depression. Although its antidepressive mechanism of action remained unknown, our previous studies indicate that TMS has a long-lasting effect on neuronal excitability in the hippocampus. We now compare the effects of chronic TMS with those of the antidepressant drugs desipramine and mianserin. The three treatments did not affect basal conduction in the perforant path to the dentate gyrus, but markedly suppressed paired-pulse and frequency-dependent inhibition, resulting from a reduction in local circuit inhibition in the dentate gyrus. Concomitantly, these treatments enhanced the expression of long-term potentiation in the perforant path synapse in the dentate gyrus. Finally, chronic TMS as well as mianserin suppressed the serotonin-dependent, potentiating action of fenfluramine on population spike in the dentate gyrus. Thus, TMS, mianserin, and desipramine are likely to affect the same neuronal populations, which may be relevant to their antidepressant action.

Slow magnetic stimulation of prefrontal cortex in depression and schizophrenia.

1. The authors used transcranial magnetic stimulation (TMS) of pre-frontal cortex to study mood changes in 10 depressed patients and 10 schizophrenic patients. 2. A slow rate of stimuli was used, one per 30 seconds; maximal intensity of about 2 Tesla was given for 30 stimuli, 15 on each side of the brain. 3. No side effects were seen and at least three depressed patients and two schizophrenic patients appeared to improve, at least transiently. 4. These results suggest that rapid rate TMS may not be necessary to elicit mood effects.

Olanzapine treatment of clozapine-induced NMS.

No Abstract

Photoperiodicity and annual rhythms of wars and violent crimes.

The seasonal variations of individual violent crimes, i.e. sexual offenses and aggravated assaults, and non-violent offenses, i.e. burglary, in Israel, the USA, Denmark and New South Wales, Australia, representing four continents, were analyzed. Seasonal variations in the opening dates of wars were similarly analyzed. In northern hemisphere countries, although non-violent offenses are distributed equally throughout the year, individual violent crimes and collective acts of hostility are characterized by an annual rhythm of incidence, with a peak in the months of July-August and a nadir in December-February. Inverse rhythms were obtained in southern hemisphere countries. These rhythms were found to be correlated in a statistically significant manner with the duration of the daily photoperiod. The existence of similar patterns of annual variations in violent crimes and in the opening dates of wars indicate similarities between individual and collective aggressiveness with respect to the underlying mechanisms and probably also to the means of their prevention.

Possession by the 'Zar' among Ethiopian immigrants to Israel: psychopathology or culture-bound syndrome?

The article describes a cultural pattern related to altered states of consciousness, observed amongst new immigrants from Ethiopia to Israel. The belief in possession by Zar spirits is one of the most common possession phenomena in Africa and in other continents. Possession by Zar is expressed by a wide range of behaviors, such as involuntary movements, mutism and incomprehensible language. Such behavior can be misinterpreted as representing symptoms of neuralgic or psychiatric disorders. We demonstrate the Zar phenomenon by a description of a detailed case. The article discusses the cultural and anthropological aspects of the Zar and its clinical implications and suggests that the Zar phenomenon should be understood as a culture-bound syndrome.

Magnetic stimulation of the brain in animal depression models responsive to ECS.

Studies in humans show antidepressant potential for transcranial magnetic stimulation (TMS). We therefore studied TMS in animal models of depression and compared its effects with those of ECS. ECS in rats has several robust behavioral effects, including enhancement of apomorphine-induced stereotypy, reduction of immobility time in the Porsolt swim test, and increases in seizure threshold for subsequent stimulation. Seven or 10 days of daily TMS consistently enhanced apomorphine-induced stereotypy, whereas a single session of TMS did not. Two TMS treatments markedly reduced immobility in the Porsolt swim test, as does ECS. A single TMS treatment markedly reduces the percentage of rats seizing in response to a ECS-like electrical stimulus to the brain 10 s later, as does an ECS treatment itself but not a sub-convulsive electrical stimulus to the brain. Long-term administration of ECS as well as other antidepressant treatments downregulates beta-adrenergic receptors. We found that TMS significantly reduced the density of [3H]CGP-12177 (a radioligand with beta-adrenergic affinity) binding sites in cortical (p < 0.05) but not hippocampal membranes. The role of monoamines in the mechanism of action of antidepressant treatments was investigated in numerous studies. Region-specific changes in the brain steady-state levels, and turnover rates of monoamines were detected 10 s after administration of a single repetitive TMS (rTMS) session. In the striatum and hippocampus, dopamine levels were increased by 25 +/- 1.5% and 18 +/- 0.8%, respectively, but were reduced in frontal cortex and decreased in the striatum and hippocampus in the TMS-treated rats with no change to the midbrain. TMS caused an increase in serotonin and 5-HIAA levels in the hippocampus but not in other brain regions examined in this study. The ability of TMS to induce behavioral and biochemical alterations similar to those of ECS may further support the potential role of TMS as an antidepressant treatment and bring us closer to the understanding of the mechanism of action of TMS.

The 'Zar' possession syndrome among Ethiopian immigrants to Israel: cultural and clinical aspects.

This article describes a cultural pattern related to altered states of consciousness, observed amongst new immigrants from Ethiopia in Israel. The belief in possession by Zar spirits is one of the most common possession phenomena in Africa and in other continents. Possession by Zar is expressed by a wide range of behaviours, such as involuntary movements (often resembling epileptiform convulsions), mutism and incomprehensible language. Such behaviour can be misinterpreted as representing symptoms of neurologic or psychiatric disorders. Such misinterpretation has led to inappropriate psychiatric admissions and to misdiagnosis of such cases as major psychiatric disorders. The article illustrates the Zar phenomenon by three clinical vignettes and discusses its cultural and anthropological aspects, as well as its clinical implications within a Western society.

Effect on the emotions of healthy individuals of slow repetitive transcranial magnetic stimulation applied to the prefrontal cortex.

UNLABELLED: Recent studies indicate that both slow and fast repetitive transcranial magnetic stimulation (rTMS) have a mood-elevating effect in major depressive episodes. The effect of slow rTMS on the emotions of healthy individuals has not been examined. METHODS: We studied the effects of slow rTMS applied to the left and right prefrontal cortex (PFC) of 18 healthy individuals. Active and sham stimulation was applied to both sides of all individuals. Stimulation was with a 9-cm figure-of-eight coil at the following parameters: 110% of motor threshold, 1 Hz, single train of 500 stimuli. Depression, happiness, irritability, and anxiety were measured before and 5, 30, and 240 min after stimulation using visual analogue scales. A sleep questionnaire was completed the morning after each stimulation session. A new method of providing sham was used. RESULTS: Slow rTMS applied to the PFC did not produce significant changes in the emotions of healthy individuals; nor was sleep influenced. DISCUSSION: In conclusion, slow rTMS at these parameters applied to the PFC does not produce significant changes in the emotions of healthy individuals.

Ritual female genital surgery among Ethiopian Jews.

Ritual female genital surgery is usually associated with Muslim countries although it is normative also among Ethiopian Coptic Christians. Ethiopian Jewish women immigrants to Israel report that ritual female genital surgery was normative in their culture in Ethiopia, but expressed no desire to continue the custom in Israel. This contrasts with Israeli Bedouin Muslims, who were reported to regard ritual female genital surgery as an important part of their identity. Physical examination of 113 Ethiopian Jewish immigrant women in Israel found a variety of lesions in about a third of women, with 27% showing total or partial clitoral amputation. The heterogeneity of the physical findings contrasts with uniform verbal reports in interviews of having undergone a ritual of female genital surgery.

Long-term effects of transcranial magnetic stimulation on hippocampal reactivity to afferent stimulation.

Transcranial magnetic stimulation (TMS) has become a promising treatment of affective disorders in humans, yet the neuronal basis of its long-lasting effects in the brain is still unknown. We studied acute and lasting effects of TMS on reactivity of the rat hippocampus to stimulation of the perforant path. Application of TMS to the brain of the anesthetized rat caused a dose-dependent transient increase in population spike (PS) response of the dentate gyrus to perforant path stimulation. In addition, TMS caused a marked decrease in inhibition and an increase in paired-pulse potentiation of reactivity to stimulation of the perforant path. Also, TMS suppressed the ability of fenfluramine (FFA), a serotonin releaser, to potentiate PS response to perforant path stimulation. Chronic TMS did not affect single population spikes but caused an increase in paired-pulse potentiation, which was still evident 3 weeks after the last of seven daily TMS treatments. After chronic TMS, FFA was ineffective in enhancing reactivity to perforant path stimulation, probably because it lost the ability to release serotonin. In addition, the beta adrenergic receptor agonist isoproterenol, which caused an increase in PS in the control rats, failed to do so in the TMS-treated rats. These results indicate that TMS produces a long-term reduction in efficacy of central modulatory systems.

Transcranial magnetic stimulation downregulates beta-adrenoreceptors in rat cortex.

Recently, a method for transcranial magnetic stimulation (TMS) of the brain has been developed. Thus, it is possible to explore neurochemical and behavioral effects of TMS in rats. Repeated TMS (9 days) reduced beta-adrenergic receptor binding in cortex, as does electroconvulsive shock (ECS) and other antidepressant treatments. Thus TMS appears to be a potential antidepressive treatment.

Transcranial magnetic stimulation induces alterations in brain monoamines.

Transcranial magnetic stimulation has been suggested as a possible therapeutic tool in depression. In behavioral models of depression, magnetic stimulation induced similar effects to those of electroconvulsive shock. This study demonstrates the effect of a single session of rapid TMS on tissue monoamines in rat brain. Alterations in monoamines were selective and specific in relation to brain areas and type of monoamine. The results imply on a biochemical basis to the suggested ECT-like treatment potential of TMS.

Transcranial magnetic stimulation in an amphetamine hyperactivity model of mania.

OBJECTIVES: Transcranial magnetic stimulation (TMS) of the brain has been reported to have therapeutic effects in mania, as well as depression. TMS has previously been reported to have effects similar to those of electroconvulsive shock in rat models of depression. METHODS: We, therefore, studied TMS in amphetamine-induced hyperactivity as a rat model of mania. RESULTS: While two and seven daily TMS sessions significantly reduced activity after amphetamine, twice-daily TMS for 7 days enhanced activity after amphetamine. CONCLUSIONS: The results suggest that TMS treatment to rats interacts with the effects of amphetamine; the specific effects may be dependent on the schedule of treatment.