A randomized, double blind, sham-controlled trial of repetitive transcranial magnetic stimulation (rTMS) in the treatment of negative symptoms in schizophrenia

Abstract

a b s t r a c tBackground: Research has implicated hypofrontality in the pathogenesis of Negative symptoms of schizophrenia.These symptoms are often resistant to treatment. Repetitive Transcranial Magnetic Stimulation (rTMS) has been shown to reverse this hypofrontality. Higher frequency rTMS has shown better promise, but so far there has been very little research in this area. Objective: We aimed to evaluate the efficacy of high-frequency (20 Hz) unilateral rTMS over the left Dorso-Lateral Pre-frontal Cortex (DLPFC) in the improvement of Negative symptoms in Schizophrenia. Methods:100 patients of schizophrenia with predominantly negative symptoms, were enrolled for this randomized, sham-controlled, double-blind trial.Each participant received 20 sessions of rTMS at 20 Hz frequency and 100% motor threshold, via either the active or the sham coil, over 4 weeks. A total of 2000 pulses were imparted in 10 trains per session. Negative symptoms were assessed with the SANS and PANSS. CDSS was used to rule out depressive symptoms. Assessments were carried out at baseline, postintervention, and 1-month, 2-months, 3-months and 4-months follow ups. Results: The improvement in the negative symptoms (Anhedonia, Alogia, Avolition, Attention impairment) in active group was statistically significant at 0.01 and 0.05 (p-value) as compared to sham group. Conclusions: These results suggest that high-frequency rTMS may lead to improvement in negative symptoms of schizophrenia. It may be worth considering its use as an adjunct to pharmacological treatment of negative symptoms.

Frontal–striatal connectivity and positive symptoms of schizophrenia: implications for the mechanistic basis of prefrontal rTMS

“…Neuromodulatory interventions such as repetitive transcranial magnetic stimulation (rTMS) are appropriate when antipsychotic treatment fails to control psychotic symptoms [40]. While rTMS applied to left dorsolateral prefrontal cortex (LDLPFC) reduces the burden of negative symptoms [22,39] in schizophrenia, a recent review has highlighted that, in some cases, high-frequency left prefrontal rTMS could worsen the severity of positive symptoms [20]. In this work, we explore the mechanistic basis of this phenomenon, and expound a circuit-based model to treat positive symptoms, which are currently not clinical targets for rTMS therapy.…”

“…More recent trials indicate that some positive symptoms such as excitement may indeed improve with HF-rTMS of LDLPFC [13]. Importantly, out of 11 controlled trials investigating the effect of prefrontal HF-rTMS, worsening of positive symptoms have been reported in only some (e.g., [22]), as highlighted by Kennedy et al [20] and Marzouk et al [27]. Similarly, the extensive literature on HF-rTMS to LDLPFC in depression does not indicate any increase in the risk of positive psychotic symptoms [36].…”

Activity flow underlying abnormalities in brain activations and cognition in schizophrenia

“…Existing attempts to use brain stimulation as a therapeutic intervention in SZ have largely focussed on stimulating DLPFC with mixed outcomes (Kumar et al, 2020;Lett et al, 2014). The evidence for PFC stimulation sites in SZ is supported by its abnormal activation during cognitive control (Callicott et al, 2003;Cannon et al, 2005), its disrupted connectivity profile (Fornito et al, 2011;Meyer-Lindenberg et al, 2001) and neurotransmitter regulation (Lewis and Moghaddam, 2006).…”

Genome-wide mutagenesis identifies factors involved inEnterococcus faecalisvaginal adherence and persistence

“…Mice were swabbed daily until no colonies appeared on agar selective for V583 or OG1RF, indicating bacterial clearance from the vaginal lumen. While V583 persisted longer in the mouse vaginal tract, the mean CFU recovered for both V583 and OG1RF remained constant for the first week and then declined as mice eventually cleared both strains by [11][12][13] days ( Fig. 2A, B).…”

“…Surface proteins such as the adhesin to collagen (Ace), enterococcal fibronectin binding protein A (EfbA), aggregation substance (AS), and the endocarditis-and biofilmassociated pilin (Ebp) have been previously shown to play important roles in infective endocarditis and UTIs (reviewed in 11). Secreted factors such as gelatinase (12), autolysin A (13), and serine protease (SprE) are biofilm-associated factors that are involved in the degradation of host substrates, including collagen, fibrin and certain complement components (14). Many of these virulence factors are regulated via quorum sensing, which may be responsible for the switch from a commensal to pathogenic state (15)(16)(17).…”