- Email: [email protected]
Left Dorsolateral Prefrontal Cortex Anodal tDCS Effects on Negative Symptoms in Schizophrenia
Letters to the Editor / Brain Stimulation 8 (2015) 974e991
Cognitive functions maintained stable (20 at baseline and 24 at the final outcome) as assessed by MOCA, with improvement on memory tasks. MDD symptoms substantially improved during the 10day treatment course and remained stable after three months follow-up, and the patient reported significant global clinical gains (see the Fig. 1). The patient was followed on a monthly basis and no risk issues were observed, such as gestational diabetes or hypertension. Caesarean section was performed opted by the gynecology and obstetrics team due to be considered high-risk pregnancy because of the MDD treatment. No complications during child-birth occurred. The neonate was a healthy full-term, 8 pounds newborn, with APGAR 10/10 and no malformations. The TNS protocol is based on a “bottom up” mechanism [7]. The electric stimuli follows the peripheral nerves pathway through central structures [7] such as the amygdala and the hippocampus, toward higher cortical area such as the dorsolateral prefrontal cortex, previously demonstrated to be involved in MDD with symptoms amelioration when stimulated with other neuromodulation techniques [8]. Data on the use of cranial nerve stimulation for MDD during pregnancy is scant. In fact, TNS was not evaluated before. Only one case of vagus nerve stimulation (VNS) for the treatment of MDD in pregnancy was performed with no safety issues [9]. Safety evaluation on the use of VNS in an animal model (pilot study of the teratogenicity) was performed with 10 rabbits with no safety issues reported [10]. We present the first report using TNS in a pregnant patient with successful amelioration of MDD symptoms and no considerable side effects to the newborn. TNS is a focused electrical stimulation technique without likely electric stimulation propagation to the fetus. Our findings are based on a case study, thus having limited generalizability. Nonetheless, these encouraging results should be seen as hypothesis-driven for further controlled, randomized trials exploring the safety and impact of TNS in the treatment of MDD in pregnancy. The present work was performed at the Interdisciplinary Center for Clinical Neuromodulation, Santa Casa School of Medical Sciences, São Paulo, Brazil. Declaration of interest: All authors confirm that this manuscript has not been published elsewhere and is not under consideration by another journal. All authors have approved the manuscript and agree with its submission to Brain Stimulation. We here declare no conflict of interest related to the present manuscript.
Alisson Paulino Trevizol* Isa Albuquerque Sato Bianca Bonadia Bianca Maria Liquidato Mirna Duarte Barros Quirino Cordeiro Pedro Shiozawa Interdisciplinary Center for Clinical Neuromodulation Santa Casa School of Medical Sciences São Paulo, Brazil
* Corresponding
author. Departamento de Psiquiatria, Faculdade de Ciências Médicas da Santa Casa de São Paulo; Rua Major Maragliano, 241 Vila Mariana; 04600-010 São Paulo, SP, Brazil. Tel.: þ55 113466 2200. E-mail address: [email protected] (A.P. Trevizol) Received 6 July 2015
http://dx.doi.org/10.1016/j.brs.2015.07.034
989
References [1] Shenoy S, Bose A, Chhabra H, et al. Transcranial direct current stimulation (tDCS) for auditory verbal hallucinations in schizophrenia during pregnancy: a case report. Brain Stimul 2015;8(1):163e4. [2] Grote NK, Bridge JA, Gavin AR, Melville JL, Iyengar S, Katon WJ. A metaanalysis of depression during pregnancy and the risk of preterm birth, low birth weight, and intrauterine growth restriction. Arch Gen Psychiatry 2010; 67(10):1012e24. [3] Huang H, Coleman S, Bridge JA, Yonkers K, Katon W. A meta-analysis of the relationship between antidepressant use in pregnancy and the risk of preterm birth and low birth weight. Gen Hosp Psychiatry 2014;36(1):13e8. [4] Walton GD, Ross LE, Stewart DE, Grigoriadis S, Dennis CL, Vigod S. Decisional conflict among women considering antidepressant medication use in pregnancy. Arch Womens Ment Health 2014;17(6):493e501. [5] Shiozawa P, Duailibi MS, da Silva ME, Cordeiro Q. Trigeminal nerve stimulation (TNS) protocol for treating major depression: an open-label proof-ofconcept trial. Epilepsy Behav 2014;39:6e9. [6] Shiozawa P, da Silva ME, Netto GT, Taiar I, Cordeiro Q. Effect of a 10-day trigeminal nerve stimulation (TNS) protocol for treating major depressive disorder: a phase II, sham-controlled, randomized clinical trial. Epilepsy Behav 2015;44c:23e6. [7] Shiozawa P, Silva ME, Carvalho TC, Cordeiro Q, Brunoni AR, Fregni F. Transcutaneous vagus and trigeminal nerve stimulation for neuropsychiatric disorders: a systematic review. Arq Neuropsiquiatr 2014;72(7):542e7. [8] Shiozawa P, Fregni F, Benseñor IM, et al. Transcranial direct current stimulation for major depression: an updated systematic review and meta-analysis. Int J Neuropsychopharmacol 2014;17(9):1443e52. [9] Husain MM, Stegman D, Trevino K. Pregnancy and delivery while receiving vagus nerve stimulation for the treatment of major depression: a case report. Ann Gen Psychiatry 2005;4:16. [10] Danielsson I, Lister L. A pilot study of the teratogenicity of vagus nerve stimulation in a rabbit model. Brain Stimul 2009;2(1):41e9.
Left Dorsolateral Prefrontal Cortex Anodal tDCS Effects on Negative Symptoms in Schizophrenia Dear Editor, Despite optimal treatment with antipsychotics, most patients with schizophrenia persist with severe functional impairment and poor quality of life [1]. Negative symptoms are among the major determinants of such functional impairment and have no specific treatment [2]. In a recent study, Fervaha and collaborators showed that motivational deficits were present in more than 75% of a cohort of young patients (18e35 years). According to the authors, these deficits e which are at the core of negative symptoms e are manifested earlier in the disease’s course then generally assumed, and impose one of the main challenges of the field as a whole [3]. The effects of transcranial direct current stimulation (tDCS) in schizophrenia have been investigated (mostly case studies), with promising results in the amelioration of both positive and negative symptoms. However, only a few randomized controlled trials have been conducted with this clinical population [4]. For instance, Brunelin and colleagues [5] demonstrated the efficacy of a protocol consisting of two daily sessions (20 min each) of 2 mA tDCS for five consecutive days in reducing hallucinatory symptoms of 30 refractory patients. They also reported improvements in negative symptoms, which they suggested to be tied to a partial reversal of left dorsolateral prefrontal cortex (LDPFC) hypoactivity. More recently, an open label study also showed significant improvements in negative symptoms of 9 patients. This study used a protocol with a similar montage (both had the anodal over the LDPFC), current intensity and overall stimulation duration but involved one session per day for 10 consecutive days, [6].
990
Letters to the Editor / Brain Stimulation 8 (2015) 974e991
Table 1 Mean difference and analysis of variance of the clinical data between baseline and after stimulation protocol. Mean difference Calgary Active 0.143 Sham 0.250 GAF Active 4.286 Sham 2.500 P_Positive Active 0.429 Sham 0.375 P_Negative Active 5.000 Sham 0.125 P_General Active 6.857 Sham 0.000 P_Total Active 11.429 Sham 0.250
SD
Baseline
After
F
P
h2p
0.900 0.707
3.42 1
3.29 0.75
0.896
0.361
0.064
7.868 4.629
36.43 39.75
40.71 42.25
4.286
0.59
0.248
1.618 1.188
17.43 14.25
17.86 14.62
1.205
0.288
0.086
2.708 2.997
25.71 24.25
20.71 24.12
11.928
0.004
0.478
6.962 4.440
47.28 39.62
40.43 39.62
5.321
0.038
0.29
7.547 7.106
90.43 78.12
79 78.37
8.724
0.011
0.402
Here we report our findings from a randomized, double blind, controlled trial on negative symptoms of patients with schizophrenia, using anodal tDCS stimulation over LDPFC and cathodal at the right contralateral area. These patients were stimulated once a day for 10 days (no sessions during the weekends), with a direct current of 2.0 mA for 20 min. This trial took advantage of computational modeling to define the ideal position of the electrodes, so as to maximize current flow in the superior and middle frontal gyrus. Our decision was to place them at F3 (anode) and F4 (cathode), following the 10-10 system, as published elsewhere [7]. Recruitment took place in a day-hospital psychiatric center and all patients were diagnosed with schizophrenia, according to the DSM-5. Clinical outcomes were assessed by the Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale for Schizophrenia and Global Assessment of Functioning (GAF). Fifteen patients were randomized into two groups: 7 active and 8 sham, with 2 females in each group. The rater was blind to the groups. There was one dropout from the sham group after 4 sessions and, as imputation method, we used last observation carried forward (LOCF). Mean age was found to be 43.29 (9.72) for tDCS and 34.25 (11.21) for the sham group, with no significant difference between groups (t(13) ¼ 1.65, P < 0.122). At baseline, tDCS group had higher PANSS scores for positive (tDCS ¼ 17.43, sham ¼ 14.25; t(13) ¼ 3.094, P < 0.009) and general (tDCS ¼ 47.28, sham ¼ 39.62; t(13) ¼ 2.379, P < 0.033) scales, but not for the negative scale (tDCS ¼ 25.71, sham ¼ 24.25; t(13) ¼ 0.516, P < 0.615) and total score (tDCS ¼ 90.43, sham ¼ 78.12; t(13) ¼ 2.024, P < 0.064), neither for Calgary (tDCS ¼ 3.43, sham ¼ 1; t(13) ¼ 1.646, P < 0.124) and GAF (tDCS ¼ 36.43, sham ¼ 39.75; t(13) ¼ -0.435, P < 0.670). After stimulation, patients who received active stimulation showed reduced PANSS negative, general and total scores, with significant time and group interactions, as seen in Table 1. The percentages of changes in the negative, general and total scores due to the interaction between time and group were 45.4%, 29% and 42.3%, respectively. No effects were observed for depression scores, functional outcomes or for positive symptoms. In addition, no significant differences were found for the sham group in any variable. Changes in negative and general PANSS scale were strongly correlated (r(13) ¼ 0.593, P ¼ 0.020), as well as negative and PANSS total score (r(13) ¼ 0.809, P < 0.001). The general scale was also correlated with the PANSS total score (r(13) ¼ 0.872, P < 0.001). No other
correlations were found (the full correlation table can be seen in: https://drive.google.com/file/d/0ByRmzoh7IRqBSV9ZaTh6OFNx REU/view?usp¼sharing). Our findings suggest that increases in the excitability at the left dorsolateral prefrontal cortex may contribute to the transient diminishing of negative symptoms, possibly due to regulatory effects on brain circuits related to motivation. It is worth noting that changes in negative symptoms were not found to be associated with changes in positive symptoms, depressed mood or global functioning in the current study. These results endorse the use of tDCS for amelioration of negative symptoms in schizophrenia, whereas caution should be applied until the same controlled experimental conditions are replicated with a larger cohort.
July Silveira Gomes* Clinical Neuroscience Interdisciplinary Laboratory Federal University of Sao Paulo Medical School Department of Psychiatry Sao Paulo, Brazil Pedro Shiozawa Clinical Neuromodulation Laboratory Department of Psychiatry Santa Casa School of Medicine São Paulo, Brazil Álvaro Machado Dias Daniella Valverde Ducos Clinical Neuroscience Interdisciplinary Laboratory Federal University of Sao Paulo Medical School Department of Psychiatry Sao Paulo, Brazil Henrique Akiba Clinical Neuroscience Interdisciplinary Laboratory Federal University of Sao Paulo Medical School Department of Psychiatry Sao Paulo, Brazil Institute of Psychology University of Sao Paulo São Paulo, Brazil Alisson Paulino Trevizol Clinical Neuromodulation Laboratory Department of Psychiatry Santa Casa School of Medicine São Paulo, Brazil Marom Bikson Mohamed Aboseria City College of New York NY, USA Ary Gadelha Aciolly Luiz Tavares de Lacerda Clinical Neuroscience Interdisciplinary Laboratory Federal University of Sao Paulo Medical School Department of Psychiatry Sao Paulo, Brazil Quirino Cordeiro Clinical Neuromodulation Laboratory Department of Psychiatry Santa Casa School of Medicine São Paulo, Brazil
Letters to the Editor / Brain Stimulation 8 (2015) 974e991 * Corresponding author. Federal University of Sao Paulo Medical School, Department of Psychiatry. Pedro de Toledo St, 669, Third Floor, Sao Paulo 04039-032, SP, Brazil. Tel.: þ55 11 5576 4845. E-mail address: july.fl[email protected] (J.S. Gomes)
Received 13 June 2015
http://dx.doi.org/10.1016/j.brs.2015.07.033
References [1] Zugman A, Gadelha A, Assunção I, et al. Reduced dorso-lateral prefrontal cortex in treatment resistant schizophrenia. Schizophr Res 2013;148(1):81e6. http:// dx.doi.org/10.1016/j.schres.2013.05.002. [2] Carbon M, Correll CU. Thinking and acting beyond the positive: the role of the cognitive and negative symptoms in schizophrenia. CNS Spectr 2014;19:35e53, http://dx.doi.org/10.1017/S1092852914000601.
991
[3] Fervaha G, Foussias G, Agid O, Remington G. Motivational deficits in early schizophrenia: prevalent, persistent, and key determinants of functional outcome. Schizophr Res; 2015. http://dx.doi.org/10.1016/j.schres.2015.04. 040. [4] Brunoni AR, Shiozawa P, Truong D, et al. Understanding tDCS effects in schizophrenia: a systematic review of clinical data and an integrated computation modeling analysis. Expert Rev Med Devices 2014;11(4):383e94. http://dx.doi. org/10.1586/17434440.2014.911082. [5] Brunelin J, Mondino M, Gassab L, et al. Examining transcranial direct-current stimulation (tDCS) as a treatment for hallucinations in schizophrenia. Am J Psychiatry 2012;169(7):719e24. http://dx.doi.org/10.1176/appi.ajp.2012. 11071091. [6] Kurimori M, Shiozawa P, Bikson M, Aboseria M, Cordeiro Q. Targeting negative symptoms in schizophrenia: results from a proof-of-concept trial assessing prefrontal anodic tDCS protocol. Schizophr Res, http://dx.doi.org/10.1016/j.schres. 2015.05.029; 2015. [7] Seibt O, Brunoni AR, Huang Y, Bikson M. The pursuit of DLPFC: nonneuronavigated methods to target the left dorsolateral pre-frontal cortex with symmetric bicephalic transcranial direct current stimulation (tDCS). Brain Stimul 2015;8(3):590e602. http://dx.doi.org/10.1016/j.brs. 2015.01.401.
Cognitive functions maintained stable (20 at baseline and 24 at the final outcome) as assessed by MOCA, with improvement on memory tasks. MDD symptoms substantially improved during the 10day treatment course and remained stable after three months follow-up, and the patient reported significant global clinical gains (see the Fig. 1). The patient was followed on a monthly basis and no risk issues were observed, such as gestational diabetes or hypertension. Caesarean section was performed opted by the gynecology and obstetrics team due to be considered high-risk pregnancy because of the MDD treatment. No complications during child-birth occurred. The neonate was a healthy full-term, 8 pounds newborn, with APGAR 10/10 and no malformations. The TNS protocol is based on a “bottom up” mechanism [7]. The electric stimuli follows the peripheral nerves pathway through central structures [7] such as the amygdala and the hippocampus, toward higher cortical area such as the dorsolateral prefrontal cortex, previously demonstrated to be involved in MDD with symptoms amelioration when stimulated with other neuromodulation techniques [8]. Data on the use of cranial nerve stimulation for MDD during pregnancy is scant. In fact, TNS was not evaluated before. Only one case of vagus nerve stimulation (VNS) for the treatment of MDD in pregnancy was performed with no safety issues [9]. Safety evaluation on the use of VNS in an animal model (pilot study of the teratogenicity) was performed with 10 rabbits with no safety issues reported [10]. We present the first report using TNS in a pregnant patient with successful amelioration of MDD symptoms and no considerable side effects to the newborn. TNS is a focused electrical stimulation technique without likely electric stimulation propagation to the fetus. Our findings are based on a case study, thus having limited generalizability. Nonetheless, these encouraging results should be seen as hypothesis-driven for further controlled, randomized trials exploring the safety and impact of TNS in the treatment of MDD in pregnancy. The present work was performed at the Interdisciplinary Center for Clinical Neuromodulation, Santa Casa School of Medical Sciences, São Paulo, Brazil. Declaration of interest: All authors confirm that this manuscript has not been published elsewhere and is not under consideration by another journal. All authors have approved the manuscript and agree with its submission to Brain Stimulation. We here declare no conflict of interest related to the present manuscript.
Alisson Paulino Trevizol* Isa Albuquerque Sato Bianca Bonadia Bianca Maria Liquidato Mirna Duarte Barros Quirino Cordeiro Pedro Shiozawa Interdisciplinary Center for Clinical Neuromodulation Santa Casa School of Medical Sciences São Paulo, Brazil
* Corresponding
author. Departamento de Psiquiatria, Faculdade de Ciências Médicas da Santa Casa de São Paulo; Rua Major Maragliano, 241 Vila Mariana; 04600-010 São Paulo, SP, Brazil. Tel.: þ55 113466 2200. E-mail address: [email protected] (A.P. Trevizol) Received 6 July 2015
http://dx.doi.org/10.1016/j.brs.2015.07.034
989
References [1] Shenoy S, Bose A, Chhabra H, et al. Transcranial direct current stimulation (tDCS) for auditory verbal hallucinations in schizophrenia during pregnancy: a case report. Brain Stimul 2015;8(1):163e4. [2] Grote NK, Bridge JA, Gavin AR, Melville JL, Iyengar S, Katon WJ. A metaanalysis of depression during pregnancy and the risk of preterm birth, low birth weight, and intrauterine growth restriction. Arch Gen Psychiatry 2010; 67(10):1012e24. [3] Huang H, Coleman S, Bridge JA, Yonkers K, Katon W. A meta-analysis of the relationship between antidepressant use in pregnancy and the risk of preterm birth and low birth weight. Gen Hosp Psychiatry 2014;36(1):13e8. [4] Walton GD, Ross LE, Stewart DE, Grigoriadis S, Dennis CL, Vigod S. Decisional conflict among women considering antidepressant medication use in pregnancy. Arch Womens Ment Health 2014;17(6):493e501. [5] Shiozawa P, Duailibi MS, da Silva ME, Cordeiro Q. Trigeminal nerve stimulation (TNS) protocol for treating major depression: an open-label proof-ofconcept trial. Epilepsy Behav 2014;39:6e9. [6] Shiozawa P, da Silva ME, Netto GT, Taiar I, Cordeiro Q. Effect of a 10-day trigeminal nerve stimulation (TNS) protocol for treating major depressive disorder: a phase II, sham-controlled, randomized clinical trial. Epilepsy Behav 2015;44c:23e6. [7] Shiozawa P, Silva ME, Carvalho TC, Cordeiro Q, Brunoni AR, Fregni F. Transcutaneous vagus and trigeminal nerve stimulation for neuropsychiatric disorders: a systematic review. Arq Neuropsiquiatr 2014;72(7):542e7. [8] Shiozawa P, Fregni F, Benseñor IM, et al. Transcranial direct current stimulation for major depression: an updated systematic review and meta-analysis. Int J Neuropsychopharmacol 2014;17(9):1443e52. [9] Husain MM, Stegman D, Trevino K. Pregnancy and delivery while receiving vagus nerve stimulation for the treatment of major depression: a case report. Ann Gen Psychiatry 2005;4:16. [10] Danielsson I, Lister L. A pilot study of the teratogenicity of vagus nerve stimulation in a rabbit model. Brain Stimul 2009;2(1):41e9.
Left Dorsolateral Prefrontal Cortex Anodal tDCS Effects on Negative Symptoms in Schizophrenia Dear Editor, Despite optimal treatment with antipsychotics, most patients with schizophrenia persist with severe functional impairment and poor quality of life [1]. Negative symptoms are among the major determinants of such functional impairment and have no specific treatment [2]. In a recent study, Fervaha and collaborators showed that motivational deficits were present in more than 75% of a cohort of young patients (18e35 years). According to the authors, these deficits e which are at the core of negative symptoms e are manifested earlier in the disease’s course then generally assumed, and impose one of the main challenges of the field as a whole [3]. The effects of transcranial direct current stimulation (tDCS) in schizophrenia have been investigated (mostly case studies), with promising results in the amelioration of both positive and negative symptoms. However, only a few randomized controlled trials have been conducted with this clinical population [4]. For instance, Brunelin and colleagues [5] demonstrated the efficacy of a protocol consisting of two daily sessions (20 min each) of 2 mA tDCS for five consecutive days in reducing hallucinatory symptoms of 30 refractory patients. They also reported improvements in negative symptoms, which they suggested to be tied to a partial reversal of left dorsolateral prefrontal cortex (LDPFC) hypoactivity. More recently, an open label study also showed significant improvements in negative symptoms of 9 patients. This study used a protocol with a similar montage (both had the anodal over the LDPFC), current intensity and overall stimulation duration but involved one session per day for 10 consecutive days, [6].
990
Letters to the Editor / Brain Stimulation 8 (2015) 974e991
Table 1 Mean difference and analysis of variance of the clinical data between baseline and after stimulation protocol. Mean difference Calgary Active 0.143 Sham 0.250 GAF Active 4.286 Sham 2.500 P_Positive Active 0.429 Sham 0.375 P_Negative Active 5.000 Sham 0.125 P_General Active 6.857 Sham 0.000 P_Total Active 11.429 Sham 0.250
SD
Baseline
After
F
P
h2p
0.900 0.707
3.42 1
3.29 0.75
0.896
0.361
0.064
7.868 4.629
36.43 39.75
40.71 42.25
4.286
0.59
0.248
1.618 1.188
17.43 14.25
17.86 14.62
1.205
0.288
0.086
2.708 2.997
25.71 24.25
20.71 24.12
11.928
0.004
0.478
6.962 4.440
47.28 39.62
40.43 39.62
5.321
0.038
0.29
7.547 7.106
90.43 78.12
79 78.37
8.724
0.011
0.402
Here we report our findings from a randomized, double blind, controlled trial on negative symptoms of patients with schizophrenia, using anodal tDCS stimulation over LDPFC and cathodal at the right contralateral area. These patients were stimulated once a day for 10 days (no sessions during the weekends), with a direct current of 2.0 mA for 20 min. This trial took advantage of computational modeling to define the ideal position of the electrodes, so as to maximize current flow in the superior and middle frontal gyrus. Our decision was to place them at F3 (anode) and F4 (cathode), following the 10-10 system, as published elsewhere [7]. Recruitment took place in a day-hospital psychiatric center and all patients were diagnosed with schizophrenia, according to the DSM-5. Clinical outcomes were assessed by the Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale for Schizophrenia and Global Assessment of Functioning (GAF). Fifteen patients were randomized into two groups: 7 active and 8 sham, with 2 females in each group. The rater was blind to the groups. There was one dropout from the sham group after 4 sessions and, as imputation method, we used last observation carried forward (LOCF). Mean age was found to be 43.29 (9.72) for tDCS and 34.25 (11.21) for the sham group, with no significant difference between groups (t(13) ¼ 1.65, P < 0.122). At baseline, tDCS group had higher PANSS scores for positive (tDCS ¼ 17.43, sham ¼ 14.25; t(13) ¼ 3.094, P < 0.009) and general (tDCS ¼ 47.28, sham ¼ 39.62; t(13) ¼ 2.379, P < 0.033) scales, but not for the negative scale (tDCS ¼ 25.71, sham ¼ 24.25; t(13) ¼ 0.516, P < 0.615) and total score (tDCS ¼ 90.43, sham ¼ 78.12; t(13) ¼ 2.024, P < 0.064), neither for Calgary (tDCS ¼ 3.43, sham ¼ 1; t(13) ¼ 1.646, P < 0.124) and GAF (tDCS ¼ 36.43, sham ¼ 39.75; t(13) ¼ -0.435, P < 0.670). After stimulation, patients who received active stimulation showed reduced PANSS negative, general and total scores, with significant time and group interactions, as seen in Table 1. The percentages of changes in the negative, general and total scores due to the interaction between time and group were 45.4%, 29% and 42.3%, respectively. No effects were observed for depression scores, functional outcomes or for positive symptoms. In addition, no significant differences were found for the sham group in any variable. Changes in negative and general PANSS scale were strongly correlated (r(13) ¼ 0.593, P ¼ 0.020), as well as negative and PANSS total score (r(13) ¼ 0.809, P < 0.001). The general scale was also correlated with the PANSS total score (r(13) ¼ 0.872, P < 0.001). No other
correlations were found (the full correlation table can be seen in: https://drive.google.com/file/d/0ByRmzoh7IRqBSV9ZaTh6OFNx REU/view?usp¼sharing). Our findings suggest that increases in the excitability at the left dorsolateral prefrontal cortex may contribute to the transient diminishing of negative symptoms, possibly due to regulatory effects on brain circuits related to motivation. It is worth noting that changes in negative symptoms were not found to be associated with changes in positive symptoms, depressed mood or global functioning in the current study. These results endorse the use of tDCS for amelioration of negative symptoms in schizophrenia, whereas caution should be applied until the same controlled experimental conditions are replicated with a larger cohort.
July Silveira Gomes* Clinical Neuroscience Interdisciplinary Laboratory Federal University of Sao Paulo Medical School Department of Psychiatry Sao Paulo, Brazil Pedro Shiozawa Clinical Neuromodulation Laboratory Department of Psychiatry Santa Casa School of Medicine São Paulo, Brazil Álvaro Machado Dias Daniella Valverde Ducos Clinical Neuroscience Interdisciplinary Laboratory Federal University of Sao Paulo Medical School Department of Psychiatry Sao Paulo, Brazil Henrique Akiba Clinical Neuroscience Interdisciplinary Laboratory Federal University of Sao Paulo Medical School Department of Psychiatry Sao Paulo, Brazil Institute of Psychology University of Sao Paulo São Paulo, Brazil Alisson Paulino Trevizol Clinical Neuromodulation Laboratory Department of Psychiatry Santa Casa School of Medicine São Paulo, Brazil Marom Bikson Mohamed Aboseria City College of New York NY, USA Ary Gadelha Aciolly Luiz Tavares de Lacerda Clinical Neuroscience Interdisciplinary Laboratory Federal University of Sao Paulo Medical School Department of Psychiatry Sao Paulo, Brazil Quirino Cordeiro Clinical Neuromodulation Laboratory Department of Psychiatry Santa Casa School of Medicine São Paulo, Brazil
Letters to the Editor / Brain Stimulation 8 (2015) 974e991 * Corresponding author. Federal University of Sao Paulo Medical School, Department of Psychiatry. Pedro de Toledo St, 669, Third Floor, Sao Paulo 04039-032, SP, Brazil. Tel.: þ55 11 5576 4845. E-mail address: july.fl[email protected] (J.S. Gomes)
Received 13 June 2015
http://dx.doi.org/10.1016/j.brs.2015.07.033
References [1] Zugman A, Gadelha A, Assunção I, et al. Reduced dorso-lateral prefrontal cortex in treatment resistant schizophrenia. Schizophr Res 2013;148(1):81e6. http:// dx.doi.org/10.1016/j.schres.2013.05.002. [2] Carbon M, Correll CU. Thinking and acting beyond the positive: the role of the cognitive and negative symptoms in schizophrenia. CNS Spectr 2014;19:35e53, http://dx.doi.org/10.1017/S1092852914000601.
991
[3] Fervaha G, Foussias G, Agid O, Remington G. Motivational deficits in early schizophrenia: prevalent, persistent, and key determinants of functional outcome. Schizophr Res; 2015. http://dx.doi.org/10.1016/j.schres.2015.04. 040. [4] Brunoni AR, Shiozawa P, Truong D, et al. Understanding tDCS effects in schizophrenia: a systematic review of clinical data and an integrated computation modeling analysis. Expert Rev Med Devices 2014;11(4):383e94. http://dx.doi. org/10.1586/17434440.2014.911082. [5] Brunelin J, Mondino M, Gassab L, et al. Examining transcranial direct-current stimulation (tDCS) as a treatment for hallucinations in schizophrenia. Am J Psychiatry 2012;169(7):719e24. http://dx.doi.org/10.1176/appi.ajp.2012. 11071091. [6] Kurimori M, Shiozawa P, Bikson M, Aboseria M, Cordeiro Q. Targeting negative symptoms in schizophrenia: results from a proof-of-concept trial assessing prefrontal anodic tDCS protocol. Schizophr Res, http://dx.doi.org/10.1016/j.schres. 2015.05.029; 2015. [7] Seibt O, Brunoni AR, Huang Y, Bikson M. The pursuit of DLPFC: nonneuronavigated methods to target the left dorsolateral pre-frontal cortex with symmetric bicephalic transcranial direct current stimulation (tDCS). Brain Stimul 2015;8(3):590e602. http://dx.doi.org/10.1016/j.brs. 2015.01.401.