Yuval Bloch

Positive effects of repetitive transcranial magnetic stimulation on attention in ADHD Subjects: A randomized controlled pilot study

Abstract Objectives. Repetitive transcranial stimulation (rTMS) affects dopaminergic secretion in the prefrontal cortex. Attention deficit hyperactivity disorder (ADHD) had been suggested to involve dopaminergic prefrontal abnormalities. Methods. In this crossover double-blind randomized, sham-controlled pilot study, patients diagnosed as having adult ADHD received either a single session of high-frequency rTMS directed to the right prefrontal cortex (real rTMS) or a single session of sham rTMS. Results. A total of 13 patients (seven males, six females) who fulfilled the criteria for adult ADHD, according to DSM-IV criteria gave informed consent and were enrolled. There was a specific beneficial effect on attention 10 minutes after a real rTMS course. The post-real rTMS attention score improved significantly (M=3.56, SD=0.39) compared to the pre-real rTMS attention score (M=3.31, SD=0.5) [t(12)=2.235, P < 0.05]. TMS had no effect on measures of mood and anxiety. The sham rTMS had no effect whatsoever. Conclusions. Our findings should encourage future research on the possibility of amelioration of attention difficulties in patients suffering from ADHD by using high frequency rTMS directed to the right dorsolateral prefrontal cortex. (NIH registry NCT00825708)

H-coil repetitive transcranial magnetic stimulation for treatment resistant major depressive disorder: An 18-week continuation safety and feasibility study

Abstract Objective. Evidence has shown that repetitive transcranial magnetic stimulation (rTMS) can be effective as an acute treatment for major depressive disorder (MDD). However, few studies have examined the safety and feasibility of rTMS as a long-term\continuation treatment. Deep-TMS is a novel tool enabling deeper stimulation than standard coils. The current study examined the safety and feasibility of repetitive deep-TMS continuation treatment for MDD over the course of 18 weeks, following 4 weeks of acute treatment. Method. A total of 29 MDD patients were enrolled in the study. rTMS sessions (20 Hz) were given for a total of 22 weeks, divided into: 4 weeks of acute daily treatments, followed by 18 weeks of continuation treatments. Clinical evaluations were performed weekly throughout the study. Results. A significant decrease from baseline in Hamilton Depression Rating Scale (HDRS) score was found at the end of the acute phase, and maintained throughout the study (P < 0.0001). The Kaplan–Meier estimated probability of response was 46.15% (SE = 9.78%) at the end of the acute phase, and 81.12% (SE = 9.32%) at the end of the study (22 weeks). probability of remission at the end of the acute phase was 26.92% (SE = 8.70%) and 71.45% (SE = 10.99%) at the end of the study. Response in the acute phase was indicative of response in the continuation phases. The procedure was generally well tolerated and no adverse events were reported. Conclusion. The results suggest that H-coil deep-TMS administered continuation treatment can help maintain an antidepressant effect for 18 weeks, following 4 weeks of acute treatment.

Repetitive transcranial magnetic stimulation in the treatment of depression in adolescents: an open-label study.

Objective: This open-label pilot study examined repetitive transcranial magnetic stimulation as a possible treatment of adolescent resistant depression. Method: Nine adolescents (aged 16-18 years) with severe resistant depression (determined by SCID) were recruited, and their depression, suicidality, and cognitive functions were evaluated before, during, and after a course of twenty 10-Hz, 2-second trains (intertrain intervals of 58 seconds) given over 20 min/d over 14 working days. Results: Lower levels of depression with progression in therapy were recorded by both the Beck Depression Inventory and Child Depression Rating Scale measures (F1.7,14.01 = 4.52, P < 0.05; F4,32 = 6.645, P < 0.01, respectively). Three patients reached the primary outcome measure of less than 30% reduction in their Child Depression Rating Scale. The effect on suicidality was not significant. Side effects were considered mild. Conclusions: Repetitive transcranial magnetic stimulation might be a possible therapy for adolescent depression. Our preliminary findings warrant double-blind, controlled studies.

rTMS for adolescents: Safety and efficacy considerations

In light of both the FDAs clearance of repetitive transcranial magnetic stimulation (rTMS) for adult major depressive disorder and concerns about safety and efficacy of existing antidepressant therapies for adolescent depression, there is increasing interest in rTMS as a novel treatment for adolescent depression. We reviewed English-language studies using rTMS in persons under the age of 18, yielding 6 published reports. Because rTMS is typically delivered at or above 1 Hz for psychiatric indications, our search was confined to these frequencies. Also included are studies involving rTMS above 1 Hz for non-psychiatric indications. Articles were retrieved from the MEDLINE database. There were 19 reported subjects under age 18 who have been administered rTMS at a frequency above 1 Hz: 10 for major depression, 5 for spastic cerebral palsy and 4 for epilepsia partialis continua. We found that most subjects responded favorably to rTMS and no adverse events have been reported. However data are insufficient for drawing firm conclusions about safety and efficacy. Further studies of rTMS as a treatment for adolescent depression are warranted.

Effect of L-tryptophan on Memory in patients with schizophrenia

It has been well established that patients with schizophrenia have impaired cognitive abilities on neuropsychological tasks related to memory. Previous studies also suggest a central role for serotonin in memory. This double-blind crossover study aimed to explore the effect of l-tryptophan, a serotonin precursor, on a variety of memory tasks in schizophrenic patients. Antipsychotic-treated schizophrenic patients in remission (N = 21) were randomly treated with l-tryptophan or placebo and then evaluated at three consecutive points on clinical measures (including Positive and Negative Syndrome Scale for Schizophrenia, Clinical Global Impression, and Extrapyramidal Symptoms Rating Scale) and by neuropsychological tests (including Digit-Span, Paired Association, Rey-Osterich Complex Figure Test, Digit Symbol, Number Facility Test, and the Rivermead Behavioral Memory Tests. Compared with placebo, l-tryptophan had a beneficial effect on memory functions but not on the patients’ psychotic state or on the side effects of medications. These preliminary results suggest the possibility of using serotonin precursor to enhance memory function in schizophrenia.

Learned irrelevance is disrupted in first-episode but not chronic schizophrenia patients

Learned irrelevance (LIrr) is a pre-exposure effect in which uncorrelated presentations of a conditioned stimulus (CS) and an unconditioned stimulus (US) retard subsequent CS-US association. LIrr is closely related to the phenomenon of latent inhibition (LI). LI refers to the retarding effects of inconsequential stimulus pre-exposure on subsequent conditioning to that stimulus, and is considered to reflect the organisms capacity to ignore irrelevant stimuli. LI is disrupted in schizophrenia patients, due to faster learning of the association between the preexposed CS and the US. A new within-subject target-recognition LIrr procedure was applied. The target was either cued by a priming signal or appeared at random, and priming signals were novel or preexposed cues. Schizophrenia patients were compared to age- and sex-matched control subjects. Normal subjects (n = 24) have shown robust LIrr, namely, faster cue-target associations of novel compared to preexposed cues. Schizophrenia patients at the early stages of their first episode (n = 7) showed LIrr disruption, namely, cue-target associations to preexposed cues were as fast as for novel cues. Chronic patients during an acute phase (n = 18) did not show LIrr as they failed to learn the cue-target association. In addition to the LIrr paradigm the same subjects were tested in a covert-orientation task. No differences were observed between the groups on this task. The possible advantages of the new LIrr paradigm are discussed.

Long-term follow-up of adolescents with resistant depression treated with repetitive transcranial magnetic stimulation.

Objective There is a paucity of information about repetitive transcranial magnetic stimulation (rTMS) as a treatment for adolescent depression, and there are no data about its long-term effectiveness and safety in this age group. The aim of this study was to evaluate symptoms of depression and cognitive functioning in young people who had been treated 3 years previously with rTMS for resistant depression. Methods Eight of 9 subjects who had participated in an open-label rTMS study were reassessed using the Child and Adolescent Depression Rating Scale—Revised and the Beck Depression Inventory II. Six of the subjects were also cognitively reassessed using the Cambridge Neuropsychological Test Automated Battery. The follow-up assessments were compared with the earlier pretreatment, inter-treatment and posttreatment assessments. Results At 3-year follow-up, there was no evidence of deterioration in symptoms of depression or cognitive functioning compared to the last assessment after rTMS. Conclusion Preliminary evidence suggests that rTMS treatment of resistant depression in adolescents is not associated with long-term cognitive deterioration and that posttherapy clinical improvement can be maintained. It seems that some subjects may derive long-term benefit from the rTMS course.

The effect of age on frontal lobe related cognitive functions of unmedicated depressed patients

BACKGROUND Aging is associated with a decline in frontal lobe related cognitive functioning of healthy subjects (i.e., executive functioning and higher-order cognition). Unipolar depression is associated with dysfunctions in similar cognitive domains--deficits that impact the functioning and quality of life of these patients. The effect of age on frontal lobe related cognitive functions of depressed patients, however, has not been adequately studied. The current study therefore assessed a wide age range of depressed patients and compared their frontal lobe related cognitive functions to that of matched healthy controls. Recruitment of unmedicated patients minimized the confounding effect of psychiatric medications. METHOD Depressed patients and healthy controls were divided into three age groups (<25, 25-45, and 46-65 years of age) and matched in gender, age and education level (N total=170). Cognition was assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB). RESULTS The depressed patients had deficits in cognitive planning/organization, working memory, and sustained attention compared to the healthy controls. Aging was associated with a decrease in frontal lobe related functioning. Except for working memory, no significant interactions were found between the age groups and the study group (depressed/healthy). CONCLUSIONS Depressed patients are impaired in most domains of frontal lobe related cognitive functions. These deficits are already evident at an early age and persist in older age cohorts (despite an overall age related decline). These findings may help clarify the profile and course of cognitive deficits among depressed patients while providing tentative support for a developmental model of cognitive impairment in depression.

Stimulants improve theory of mind in children with attention deficit/hyperactivity disorder

Impairments in ‘theory of mind’ (ToM) were linked to social cognition and reciprocal relationships deficits in children with attention deficit/hyperactivity disorder (ADHD). Twenty-four children with ADHD (13 with inattentive type and 11 with combined type, mean age 10.2 years) completed the Interpersonal Reactivity Index (IRI), a self-reported empathy questionnaire. All children performed the ‘faux pas’ task and a computerized ToM task in two different sessions either with or without administration of methylphenidate (MPH). Administration of MPH was associated with an improvement in cognitive and affective ToM. Children with ADHD-combined type had significantly lower scores in total IRI and the fantasy scale compared to children with ADHD-inattentive type. We conclude that deficits in empathy and ToM may play an important role in the impairments in social cognition and peer relationship in children with ADHD, especially children a hyperactive component. Stimulants may improve ToM and empathic functions. Future studies including larger samples and additional cognitive tasks are warranted in order to generalize these results and to identify possible underlying mechanisms for improvement in ToM following the administration of MPH.

Does the Internet offer social opportunities for individuals with schizophrenia? A cross-sectional pilot study

Web-browsing habits of 143 individuals with psychotic disorders were compared to individuals with non-psychotic disorders (n=118) and healthy volunteers (n=100). The psychotic group created social interactions via Internet use similarly to the control groups. Individuals with schizophrenia benefit from Internet use, as it bypasses some of their social difficulties.