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Efficacy of bilateral repetitive transcranial magnetic stimulation for negative symptoms of schizophrenia: results of a multicenter double-blind randomized controlled trial

Published online by Cambridge University Press:  30 October 2014

J. J. Dlabac-de Lange ,
L. Bais ,
F. D. van Es ,
B. G. J. Visser ,
E. Reinink ,
B. Bakker ,
E. R. van den Heuvel ,
A. Aleman  and
H. Knegtering
J. J. Dlabac-de Lange*
Affiliation:
University of Groningen, University Medical Center Groningen, Department of Psychiatry, Hanzeplein 1, Groningen, The Netherlands University of Groningen, University Medical Center Groningen, Rob Giel Research Centrum, Hanzeplein 1, Groningen, The Netherlands University of Groningen, University Medical Center Groningen, Department of Neuroscience and BCN Neuroimaging Center, Antonius Deusinglaan 2, Groningen, The Netherlands
L. Bais
Affiliation:
University of Groningen, University Medical Center Groningen, Department of Neuroscience and BCN Neuroimaging Center, Antonius Deusinglaan 2, Groningen, The Netherlands Lentis Research, Center for Mental Health, Hereweg 80, Groningen, The Netherlands
F. D. van Es
Affiliation:
University of Groningen, University Medical Center Groningen, Department of Psychiatry, Hanzeplein 1, Groningen, The Netherlands
B. G. J. Visser
Affiliation:
University of Groningen, University Medical Center Groningen, Department of Psychiatry, Hanzeplein 1, Groningen, The Netherlands
E. Reinink
Affiliation:
Lentis Research, Center for Mental Health, Hereweg 80, Groningen, The Netherlands
B. Bakker
Affiliation:
Lentis Research, Center for Mental Health, Hereweg 80, Groningen, The Netherlands
E. R. van den Heuvel
Affiliation:
University of Groningen, University Medical Center Groningen, Department of Epidemiology, Hanzeplein 1, Groningen, The Netherlands
A. Aleman
Affiliation:
University of Groningen, University Medical Center Groningen, Department of Neuroscience and BCN Neuroimaging Center, Antonius Deusinglaan 2, Groningen, The Netherlands
H. Knegtering
Affiliation:
University of Groningen, University Medical Center Groningen, Department of Psychiatry, Hanzeplein 1, Groningen, The Netherlands University of Groningen, University Medical Center Groningen, Rob Giel Research Centrum, Hanzeplein 1, Groningen, The Netherlands University of Groningen, University Medical Center Groningen, Department of Neuroscience and BCN Neuroimaging Center, Antonius Deusinglaan 2, Groningen, The Netherlands Lentis Research, Center for Mental Health, Hereweg 80, Groningen, The Netherlands
*
* Address for correspondence: J. J. Dlabac-de Lange, Department of Psychiatry, University of Groningen, University Medical Center Groningen, Postbox 30.001, 9700 RB Groningen, The Netherlands. (Email: j.j.l.a.s.n.dlabac@umcg.nl)
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Abstract

Background.

Few studies have investigated the efficacy of repetitive transcranial magnetic stimulation (rTMS) treatment for negative symptoms of schizophrenia, reporting inconsistent results. We aimed to investigate whether 10 Hz stimulation of the bilateral dorsolateral prefrontal cortex during 3 weeks enhances treatment effects.

Method.

A multicenter double-blind randomized controlled trial was performed in 32 patients with schizophrenia or schizo-affective disorder, and moderate to severe negative symptoms [Positive and Negative Syndrome Scale (PANSS) negative subscale ⩾15]. Patients were randomized to a 3-week course of active or sham rTMS. Primary outcome was severity of negative symptoms as measured with the Scale for the Assessment of Negative Symptoms (SANS) and the PANSS negative symptom score. Secondary outcome measures included cognition, insight, quality of life and mood. Subjects were followed up at 4 weeks and at 3 months. For analysis of the data a mixed-effects linear model was used.

Results.

A significant improvement of the SANS in the active group compared with sham up to 3 months follow-up (p = 0.03) was found. The PANSS negative symptom scores did not show a significant change (p = 0.19). Of the cognitive tests, only one showed a significant improvement after rTMS as compared with sham. Finally, a significant change of insight was found with better scores in the treatment group.

Conclusions.

Bilateral 10 Hz prefrontal rTMS reduced negative symptoms, as measured with the SANS. More studies are needed to investigate optimal parameters for rTMS, the cognitive effects and the neural basis.

Keywords

Cognitiondorsolateral prefrontal cortexinsightnegative symptomsrandomized controlled trialsschizophreniatranscranial magnetic stimulation
Type
Original Articles
Information
Psychological Medicine , Volume 45 , Issue 6 , April 2015 , pp. 1263 - 1275
Copyright
Copyright © Cambridge University Press 2014 

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References

Aghababian, V, Auquier, P, Baumstarck-Barrau, K, Lancon, C (2011). Relationship between insight and self-reported quality of life among schizophrenic patients. L'Encephale 37, 162–171.CrossRefGoogle Scholar
Andreasen, NC (1982). Negative symptoms in schizophrenia. Definition and reliability. Archives of General Psychiatry 39, 784–788.Google Scholar
Anonymous (1944). Army Individual Test Battery: Manual of Directions and Scoring. War Department, Adjutant General's Office: Washington, DC.Google Scholar
Anonymous (1998). Development of the World Health Organization WHOQOL-BREF quality of life assessment. The WHOQOL Group. Psychological Medicine 28, 551–558.CrossRefGoogle Scholar
Barr, MS, Farzan, F, Tran, LC, Fitzgerald, PB, Daskalakis, ZJ (2012). A randomized controlled trial of sequentially bilateral prefrontal cortex repetitive transcranial magnetic stimulation in the treatment of negative symptoms in schizophrenia. Brain Stimulation 5, 337–346.CrossRefGoogle ScholarPubMed
Beam, W, Borckardt, JJ, Reeves, ST, George, MS (2009). An efficient and accurate new method for locating the F3 position for prefrontal TMS applications. Brain Stimulation 2, 50–54.Google Scholar
Ben-Shachar, D, Gazawi, H, Riboyad-Levin, J, Klein, E (1999). Chronic repetitive transcranial magnetic stimulation alters β-adrenergic and 5-HT2 receptor characteristics in rat brain. Brain Research 816, 78–83.CrossRefGoogle ScholarPubMed
Berlim, MT, van den Eynde, F, Tovar-Perdomo, S, Daskalakis, ZJ (2013). Response, remission and drop-out rates following high-frequency repetitive transcranial magnetic stimulation (rTMS) for treating major depression: a systematic review and meta-analysis of randomized, double-blind and sham-controlled trials. Psychological Medicine 44, 225–239.CrossRefGoogle ScholarPubMed
Berman, RM, Prudic, J, Brakemeier, EL, Olfson, M, Sackeim, HA (2008). Subjective evaluation of the therapeutic and cognitive effects of electroconvulsive therapy. Brain Stimulation 1, 16–26.Google Scholar
Birchwood, M, Smith, J, Drury, V, Healy, J, Macmillan, F, Slade, M (1994). A self-report Insight Scale for psychosis: reliability, validity and sensitivity to change. Acta Psychiatrica Scandinavica 89, 62–67.CrossRefGoogle ScholarPubMed
Cohen, E, Bernardo, M, Masana, J, Arrufat, FJ, Navarro, V, Valls-Solé, J, Boget, T, Barrantes, N, Catarineu, S, Font, M, Lomeña, FJ (1999). Repetitive transcranial magnetic stimulation in the treatment of chronic negative schizophrenia: a pilot study. Journal of Neurology, Neurosurgery, and Psychiatry 67, 129–130.CrossRefGoogle ScholarPubMed
Cordes, J, Thunker, J, Agelink, MW, Arends, M, Mobascher, A, Wobrock, T, Schneider-Axmann, T, Brinkmeyer, J, Mittrach, M, Regenbrecht, G, Wolwer, W, Winterer, G, Gaebel, W (2010). Effects of 10 Hz repetitive transcranial magnetic stimulation (rTMS) on clinical global impression in chronic schizophrenia. Psychiatry Research 177, 32–36.CrossRefGoogle ScholarPubMed
Dlabac-de Lange, JJ, Knegtering, R, Aleman, A (2010). Repetitive transcranial magnetic stimulation for negative symptoms of schizophrenia: review and meta-analysis. Journal of Clinical Psychiatry 71, 411–418.CrossRefGoogle ScholarPubMed
Ehlis, AC, Herrmann, MJ, Plichta, MM, Fallgatter, AJ (2007). Cortical activation during two verbal fluency tasks in schizophrenic patients and healthy controls as assessed by multi-channel near-infrared spectroscopy. Psychiatry Research 156, 1–13.Google Scholar
Eisenegger, C, Treyer, V, Fehr, E, Knoch, D (2008). Time-course of “off-line” prefrontal rTMS effects – a PET study. NeuroImage 42, 379–384.Google Scholar
Fenton, WS, McGlashan, TH (1991). Natural history of schizophrenia subtypes. II. Positive and negative symptoms and long-term course. Archives of General Psychiatry 48, 978–986.Google Scholar
Fenton, WS, McGlashan, TH (1994). Antecedents, symptom progression, and long-term outcome of the deficit syndrome in schizophrenia. American Journal of Psychiatry 151, 351–356.Google Scholar
Fitzgerald, PB, Herring, S, Hoy, K, McQueen, S, Segrave, R, Kulkarni, J, Daskalakis, ZJ (2008). A study of the effectiveness of bilateral transcranial magnetic stimulation in the treatment of the negative symptoms of schizophrenia. Brain Stimulation 1, 27–32.CrossRefGoogle ScholarPubMed
Gasquet, I, Haro, JM, Novick, D, Edgell, ET, Kennedy, L, Lepine, JP, SOHO Study Group (2005). Pharmacological treatment and other predictors of treatment outcomes in previously untreated patients with schizophrenia: results from the European Schizophrenia Outpatient Health Outcomes (SOHO) study. International Clinical Psychopharmacology 20, 199–205.Google Scholar
George, MS, Post, RM (2011). Daily left prefrontal repetitive transcranial magnetic stimulation for acute treatment of medication-resistant depression. American Journal of Psychiatry 168, 356–364.Google Scholar
Gershon, AA, Dannon, PN, Grunhaus, L (2003). Transcranial magnetic stimulation in the treatment of depression. American Journal of Psychiatry 160, 835–845.CrossRefGoogle ScholarPubMed
Giel, R, Nienhuis, FJ (1996). SCAN-2.1: Schedules for Clinical Assessment in Neuropsychiatry (in Dutch). WHO: Geneva/Groningen.Google Scholar
Glahn, DC, Ragland, JD, Abramoff, A, Barrett, J, Laird, AR, Bearden, CE, Velligan, DI (2005). Beyond hypofrontality: a quantitative meta-analysis of functional neuroimaging studies of working memory in schizophrenia. Human Brain Mapping 25, 60–69.Google Scholar
Gonul, AS, Kula, M, Esel, E, Tutus, A, Sofuoglu, S (2003). A Tc-99 m HMPAO SPECT study of regional cerebral blood flow in drug-free schizophrenic patients with deficit and non-deficit syndrome. Psychiatry Research 123, 199–205.Google Scholar
Goyal, N, Nizamie, SH, Desarkar, P (2007). Efficacy of adjuvant high frequency repetitive transcranial magnetic stimulation on negative and positive symptoms of schizophrenia: preliminary results of a double-blind sham-controlled study. Journal of Neuropsychiatry and Clinical Neurosciences 19, 464–467.Google Scholar
Grant, DA, Berg, EA (1948). A behavioral analysis of degree of reinforcement and ease of shifting to new responses in a Weigl-type card-sorting problem. Journal of Experimental Psychology 38, 404–411.Google Scholar
Hajak, G, Marienhagen, J, Langguth, B, Werner, S, Binder, H, Eichhammer, P (2004). High-frequency repetitive transcranial magnetic stimulation in schizophrenia: a combined treatment and neuroimaging study. Psychological Medicine 34, 1157–1163.Google Scholar
Holi, MM, Eronen, M, Toivonen, K, Toivonen, P, Marttunen, M, Naukkarinen, H (2004). Left prefrontal repetitive transcranial magnetic stimulation in schizophrenia. Schizophrenia Bulletin 30, 429–434.Google Scholar
Ikezawa, K, Iwase, M, Ishii, R, Azechi, M, Canuet, L, Ohi, K, Yasuda, Y, Iike, N, Kurimoto, R, Takahashi, H, Nakahachi, T, Sekiyama, R, Yoshida, T, Kazui, H, Hashimoto, R, Takeda, M (2009). Impaired regional hemodynamic response in schizophrenia during multiple prefrontal activation tasks: a two-channel near-infrared spectroscopy study. Schizophrenia Research 108, 93–103.Google Scholar
Jandl, M, Bittner, R, Sack, A, Weber, B, Gunther, T, Pieschl, D, Kaschka, WP, Maurer, K (2005). Changes in negative symptoms and EEG in schizophrenic patients after repetitive transcranial magnetic stimulation (rTMS): an open-label pilot study. Journal of Neural Transmission 112, 955–967.Google Scholar
Jin, Y, Kemp, AS, Huang, Y, Thai, TM, Liu, Z, Xu, W, He, H, Potkin, SG (2012). Alpha EEG guided TMS in schizophrenia. Brain Stimulation 5, 560–568.Google Scholar
Jin, Y, Potkin, SG, Kemp, AS, Huerta, ST, Alva, G, Thai, TM, Carreon, D, Bunney, WE Jr (2006). Therapeutic effects of individualized alpha frequency transcranial magnetic stimulation (alphaTMS) on the negative symptoms of schizophrenia. Schizophrenia Bulletin 32, 556–561.Google Scholar
Kapur, S, Remington, G, Zipursky, RB, Wilson, AA, Houle, S (1995). The D2 dopamine receptor occupancy of risperidone and its relationship to extrapyramidal symptoms: a PET study. Life Sciences 57, 103–107.Google Scholar
Karow, A, Pajonk, FG (2006). Insight and quality of life in schizophrenia: recent findings and treatment implications. Current Opinion in Psychiatry 19, 637–641.Google Scholar
Kay, SR, Fiszbein, A, Opler, LA (1987). The Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Schizophrenia Bulletin 13, 261–276.Google Scholar
Kirkpatrick, B, Fenton, WS, Carpenter, WT Jr, Marder, SR (2006). The NIMH-MATRICS consensus statement on negative symptoms. Schizophrenia Bulletin 32, 214–219.Google Scholar
Kirkpatrick, B, Strauss, GP, Nguyen, L, Fischer, BA, Daniel, DG, Cienfuegos, A, Marder, SR (2011). The brief negative symptom scale: psychometric properties. Schizophrenia Bulletin 37, 300–305.Google Scholar
Klein, E, Kolsky, Y, Puyerovsky, M, Koren, D, Chistyakov, A, Feinsod, M (1999). Right prefrontal slow repetitive transcranial magnetic stimulation in schizophrenia: a double-blind sham-controlled pilot study. Biological Psychiatry 46, 1451–1454.CrossRefGoogle ScholarPubMed
Klemm, E, Danos, P, Grünwald, F, Kasper, S, Moller, HJ, Biersack, HJ (1996). Temporal lobe dysfunction and correlation of regional cerebral blood flow abnormalities with psychopathology in schizophrenia and major depression – a study with single photon emission computed tomography. Psychiatry Research 68, 1–10.Google Scholar
Ko, JH, Monchi, O, Ptito, A, Bloomfield, P, Houle, S, Strafella, AP (2008). Theta burst stimulation-induced inhibition of dorsolateral prefrontal cortex reveals hemispheric asymmetry in striatal dopamine release during a set-shifting task: a TMS-[11C]raclopride PET study. European Journal of Neuroscience 28, 2147–2155.Google Scholar
Kole, MH, Fuchs, E, Ziemann, U, Paulus, W, Ebert, U (1999). Changes in 5-HT1A and NMDA binding sites by a single rapid transcranial magnetic stimulation procedure in rats. Brain Research 826, 309–312.Google Scholar
Lahti, AC, Holcomb, HH, Medoff, DR, Weiler, MA, Tamminga, CA, Carpenter, WT Jr (2001). Abnormal patterns of regional cerebral blood flow in schizophrenia with primary negative symptoms during an effortful auditory recognition task. American Journal of Psychiatry 158, 1797–1808.Google Scholar
Lako, IM, Bruggeman, R, Knegtering, H, Wiersma, D, Schoevers, RA, Slooff, CJ, Taxis, K (2012). A systematic review of instruments to measure depressive symptoms in patients with schizophrenia. Journal of Affective Disorders 140, 38–47.Google Scholar
Lako, IM, van den Heuvel, ER, Knegtering, H, Bruggeman, R, Taxis, K (2013). Estimating dopamine D2 receptor occupancy for doses of 8 antipsychotics: a meta-analysis. Journal of Clinical Psychopharmacology 33, 675–681.Google Scholar
Lane, HY, Chang, YC, Liu, YC, Chiu, CC, Tsai, GE (2005). Sarcosine or d-serine add-on treatment for acute exacerbation of schizophrenia: a randomized, double-blind, placebo-controlled study. Archives of General Psychiatry 62, 1196–1204.Google Scholar
Leucht, S, Pitschel-Walz, G, Abraham, D, Kissling, W (1999). Efficacy and extrapyramidal side-effects of the new antipsychotics olanzapine, quetiapine, risperidone, and sertindole compared to conventional antipsychotics and placebo. A meta-analysis of randomized controlled trials. Schizophrenia Research 35, 51–68.Google Scholar
Liemburg, E, Castelein, S, Stewart, R, van der Gaag, M, Aleman, A, Knegtering, H, Genetic Risk and Outcome of Psychosis (GROUP) Investigators (2013). Two subdomains of negative symptoms in psychotic disorders: established and confirmed in two large cohorts. Journal of Psychiatric Research 47, 718–725.CrossRefGoogle ScholarPubMed
Lisanby, SH, Gutman, D, Luber, B, Schroeder, C, Sackeim, HA (2001). Sham TMS: intracerebral measurement of the induced electrical field and the induction of motor-evoked potentials. Biological Psychiatry 49, 460–463.CrossRefGoogle ScholarPubMed
Lisanby, SH, Maddox, JH, Prudic, J, Devanand, DP, Sackeim, HA (2000). The effects of electroconvulsive therapy on memory of autobiographical and public events. Archives of General Psychiatry 57, 581–590.Google Scholar
Loo, CK, McFarquhar, TF, Mitchell, PB (2008). A review of the safety of repetitive transcranial magnetic stimulation as a clinical treatment for depression. International Journal of Neuropsychopharmacology 11, 131–147.Google Scholar
Loo, CK, Mitchell, PB (2005). A review of the efficacy of transcranial magnetic stimulation (TMS) treatment for depression, and current and future strategies to optimize efficacy. Journal of Affective Disorders 88, 255–267.Google Scholar
Mennemeier, M, Triggs, W, Chelette, K, Woods, A, Kimbrell, T, Dornhoffer, J (2009). Sham transcranial magnetic stimulation using electrical stimulation of the scalp. Brain Stimulation 2, 168–173.CrossRefGoogle ScholarPubMed
Milev, P, Ho, BC, Arndt, S, Andreasen, NC (2005). Predictive values of neurocognition and negative symptoms on functional outcome in schizophrenia: a longitudinal first-episode study with 7-year follow-up. American Journal of Psychiatry 162, 495–506.Google Scholar
Mogg, A, Purvis, R, Eranti, S, Contell, F, Taylor, JP, Nicholson, T, Brown, RG, McLoughlin, DM (2007). Repetitive transcranial magnetic stimulation for negative symptoms of schizophrenia: a randomized controlled pilot study. Schizophrenia Research 93, 221–228.CrossRefGoogle ScholarPubMed
Montgomery, SA, Asberg, M (1979). A new depression scale designed to be sensitive to change. British Journal of Psychiatry 134, 382–389.Google Scholar
Murphy, BP, Chung, YC, Park, TW, McGorry, PD (2006). Pharmacological treatment of primary negative symptoms in schizophrenia: a systematic review. Schizophrenia Research 88, 5–25.CrossRefGoogle ScholarPubMed
Novak, T, Horacek, J, Mohr, P, Kopecek, M, Skrdlantova, L, Klirova, M, Rodriguez, M, Spaniel, F, Dockery, C, Hoschl, C (2006). The double-blind sham-controlled study of high-frequency rTMS (20 Hz) for negative symptoms in schizophrenia: negative results. Neuro Endocrinology Letters 27, 209–213.Google Scholar
Potkin, SG, Alva, G, Fleming, K, Anand, R, Keator, D, Carreon, D, Doo, M, Jin, Y, Wu, JC, Fallon, JH (2002). A PET study of the pathophysiology of negative symptoms in schizophrenia. Positron emission tomography. American Journal of Psychiatry 159, 227–237.Google Scholar
Prikryl, R, Kasparek, T, Skotakova, S, Ustohal, L, Kucerova, H, Ceskova, E (2007). Treatment of negative symptoms of schizophrenia using repetitive transcranial magnetic stimulation in a double-blind, randomized controlled study. Schizophrenia Research 95, 151–157.Google Scholar
Prikryl, R, Ustohal, L, Prikrylova Kucerova, H, Kasparek, T, Venclikova, S, Vrzalova, M, Ceskova, E (2013). A detailed analysis of the effect of repetitive transcranial magnetic stimulation on negative symptoms of schizophrenia: a double-blind trial. Schizophrenia Research 149, 167–173.Google Scholar
Rabany, L, Weiser, M, Werbeloff, N, Levkovitz, Y (2011). Assessment of negative symptoms and depression in schizophrenia: revision of the SANS and how it relates to the PANSS and CDSS. Schizophrenia Research 126, 226–230.CrossRefGoogle Scholar
Rey, A (1958). L'examin clinique en psychologie (The examined clinical psychology). Presses universitaires de France: Paris.Google Scholar
Sabri, O, Erkwoh, R, Schreckenberger, M, Cremerius, U, Schulz, G, Dickmann, C, Kaiser, HJ, Steinmeyer, EM, Sass, H, Buell, U (1997). Regional cerebral blood flow and negative/positive symptoms in 24 drug-naive schizophrenics. Journal of Nuclear Medicine 38, 181–188.Google Scholar
Sachdev, P, Loo, C, Mitchell, P, Malhi, G (2005). Transcranial magnetic stimulation for the deficit syndrome of schizophrenia: a pilot investigation. Psychiatry and Clinical Neurosciences 59, 354–357.Google Scholar
Sanfilipo, M, Lafargue, T, Rusinek, H, Arena, L, Loneragan, C, Lautin, A, Rotrosen, J, Wolkin, A (2002). Cognitive performance in schizophrenia: relationship to regional brain volumes and psychiatric symptoms. Psychiatry Research 116, 1–23.Google Scholar
Schmand, B, Bakker, D, Saan, R, Louman, J (1991). The Dutch Reading Test for Adults: a measure of premorbid intelligence level. Tijdschrift voor gerontologie en geriatrie 22, 15–19.Google Scholar
Schneider, AL, Schneider, TL, Stark, H (2008). Repetitive transcranial magnetic stimulation (rTMS) as an augmentation treatment for the negative symptoms of schizophrenia: a 4-week randomized placebo controlled study. Brain Stimulation 1, 106–111.Google Scholar
Schutter, DJ, van Honk, J (2006). A standardized motor threshold estimation procedure for transcranial magnetic stimulation research. Journal of ECT 22, 176–178.Google Scholar
Selemon, LD, Mrzljak, J, Kleinman, JE, Herman, MM, Goldman-Rakic, PS (2003). Regional specificity in the neuropathologic substrates of schizophrenia: a morphometric analysis of Broca's area 44 and area 9. Archives of General Psychiatry 60, 69–77.CrossRefGoogle ScholarPubMed
Shad, MU, Tamminga, CA, Cullum, M, Haas, GL, Keshavan, MS (2006). Insight and frontal cortical function in schizophrenia: a review. Schizophrenia Research 86, 54–70.Google Scholar
Shi, C, Yu, X, Cheung, EF, Shum, DH, Chan, RC (2014). Revisiting the therapeutic effect of rTMS on negative symptoms in schizophrenia: a meta-analysis. Psychiatry Research 215, 505–513.CrossRefGoogle ScholarPubMed
Shioiri, T, Kato, T, Inubushi, T, Murashita, J, Takahashi, S (1994). Correlations of phosphomonoesters measured by phosphorus-31 magnetic resonance spectroscopy in the frontal lobes and negative symptoms in schizophrenia. Psychiatry Research 55, 223–235.Google Scholar
Sibon, I, Strafella, AP, Gravel, P, Ko, JH, Booij, L, Soucy, JP, Leyton, M, Diksic, M, Benkelfat, C (2007). Acute prefrontal cortex TMS in healthy volunteers: effects on brain 11C-alphaMtrp trapping. NeuroImage 34, 1658–1664.Google Scholar
Slotema, CW, Blom, JD, Hoek, HW, Sommer, IE (2010). Should we expand the toolbox of psychiatric treatment methods to include repetitive transcranial magnetic stimulation (rTMS)? A meta-analysis of the efficacy of rTMS in psychiatric disorders. Journal of Clinical Psychiatry 71, 873–884.Google Scholar
Strafella, AP, Paus, T, Barrett, J, Dagher, A (2001). Repetitive transcranial magnetic stimulation of the human prefrontal cortex induces dopamine release in the caudate nucleus. Journal of Neuroscience 21, RC157.Google Scholar
Strous, RD, Maayan, R, Lapidus, R, Stryjer, R, Lustig, M, Kotler, M, Weizman, A (2003). Dehydroepiandrosterone augmentation in the management of negative, depressive, and anxiety symptoms in schizophrenia. Archives of General Psychiatry 60, 133–141.Google Scholar
van den Burg, W, Saan, RJ, Deelman, BG (1985). 15-Woordentest. Provisional Manual (15 - Word Test Provisional Manual). University Hospital: Groningen.Google Scholar
Verhage, F (1983). Revised Scoring Method. University Hospital: Groningen.Google Scholar
Wechsler, D (1997). Wechsler Adult Intelligence Scale, 3rd edn. Psychological Corp.: San Antonio, TX.Google Scholar
Wolkin, A, Sanfilipo, M, Wolf, AP, Angrist, B, Brodie, JD, Rotrosen, J (1992). Negative symptoms and hypofrontality in chronic schizophrenia. Archives of General Psychiatry 49, 959–965.Google Scholar