Tomas Hajek1, Michael W Weiner. 1. Department of Psychiatry, Dalhousie University, QEII HSC, A.J.Lane Bldg., Room 3093, 5909 Veteran's Memorial Lane, Halifax, NS. B3H 2E2, Canada. tomas.hajek@dal.ca.
Abstract
BACKGROUND: There is a growing body of pre-clinical evidence suggesting that lithium (Li) may protect neurons from a range of neurotoxic insults, hence the term neuroprotective effects. Does Li have similar effects also in human subjects? METHODS: We reviewed the neuroimaging literature investigating the association between Li treatment and brain structure. RESULTS: There is level I evidence for positive association between Li treatment and brain grey matter volume, which is one of the most replicated neuroimaging findings. It has been reported in the majority of cross sectional studies, all 8 prospective studies, including a randomized controlled trial as well as in 2 meta-analyses and one mega-analysis. The association between Li treatment and grey matter volume occurs regardless of mood state, diagnostic subtype, presence or absence of concomitant medications. It was documented in multiple brain regions, including hippocampus, amygdala, anterior cingulate, subgenual cingulate, inferior frontal gyrus, postcentral gyrus, habenula. CONCLUSION: Although some methodological and clinical issues complicate the interpretation of findings, there is robust and highly replicated level 1 evidence for positive association between Li treatment and grey matter volumes. These "neuroprotective" effects of Li have been shown even in healthy subjects and appear independent of prophylactic treatment response. Consequently, Li might help maintain brain health even in patients without bipolar disorders and could possibly demonstrate diseasemodifying properties in neurodegenerative disorders.
BACKGROUND: There is a growing body of pre-clinical evidence suggesting that lithium (Li) may protect neurons from a range of neurotoxic insults, hence the term neuroprotective effects. Does Li have similar effects also in human subjects? METHODS: We reviewed the neuroimaging literature investigating the association between Li treatment and brain structure. RESULTS: There is level I evidence for positive association between Li treatment and brain grey matter volume, which is one of the most replicated neuroimaging findings. It has been reported in the majority of cross sectional studies, all 8 prospective studies, including a randomized controlled trial as well as in 2 meta-analyses and one mega-analysis. The association between Li treatment and grey matter volume occurs regardless of mood state, diagnostic subtype, presence or absence of concomitant medications. It was documented in multiple brain regions, including hippocampus, amygdala, anterior cingulate, subgenual cingulate, inferior frontal gyrus, postcentral gyrus, habenula. CONCLUSION: Although some methodological and clinical issues complicate the interpretation of findings, there is robust and highly replicated level 1 evidence for positive association between Li treatment and grey matter volumes. These "neuroprotective" effects of Li have been shown even in healthy subjects and appear independent of prophylactic treatment response. Consequently, Li might help maintain brain health even in patients without bipolar disorders and could possibly demonstrate diseasemodifying properties in neurodegenerative disorders.
Authors: Tomas Hajek; Katja Franke; Marian Kolenic; Jana Capkova; Martin Matejka; Lukas Propper; Rudolf Uher; Pavla Stopkova; Tomas Novak; Tomas Paus; Miloslav Kopecek; Filip Spaniel; Martin Alda Journal: Schizophr Bull Date: 2019-01-01 Impact factor: 9.306
Authors: Sean R McWhinney; Christoph Abé; Martin Alda; Francesco Benedetti; Erlend Bøen; Caterina Del Mar Bonnin; Tiana Borgers; Katharina Brosch; Erick J Canales-Rodríguez; Dara M Cannon; Udo Dannlowski; Ana M Diaz-Zuluaga; Lorielle Dietze; Torbjørn Elvsåshagen; Lisa T Eyler; Janice M Fullerton; Jose M Goikolea; Janik Goltermann; Dominik Grotegerd; Bartholomeus C M Haarman; Tim Hahn; Fleur M Howells; Martin Ingvar; Tilo T J Kircher; Axel Krug; Rayus T Kuplicki; Mikael Landén; Hannah Lemke; Benny Liberg; Carlos Lopez-Jaramillo; Ulrik F Malt; Fiona M Martyn; Elena Mazza; Colm McDonald; Genevieve McPhilemy; Sandra Meier; Susanne Meinert; Tina Meller; Elisa M T Melloni; Philip B Mitchell; Leila Nabulsi; Igor Nenadic; Nils Opel; Roel A Ophoff; Bronwyn J Overs; Julia-Katharina Pfarr; Julian A Pineda-Zapata; Edith Pomarol-Clotet; Joaquim Raduà; Jonathan Repple; Maike Richter; Kai G Ringwald; Gloria Roberts; Alex Ross; Raymond Salvador; Jonathan Savitz; Simon Schmitt; Peter R Schofield; Kang Sim; Dan J Stein; Frederike Stein; Henk S Temmingh; Katharina Thiel; Sophia I Thomopoulos; Neeltje E M van Haren; Holly Van Gestel; Cristian Vargas; Eduard Vieta; Annabel Vreeker; Lena Waltemate; Lakshmi N Yatham; Christopher R K Ching; Ole A Andreassen; Paul M Thompson; Tomas Hajek Journal: Bipolar Disord Date: 2021-12-16 Impact factor: 5.345
Authors: Eric H Decloedt; Carla Freeman; Fleur Howells; Martine Casson-Crook; Maia Lesosky; Eleni Koutsilieri; Simon Lovestone; Gary Maartens; John A Joska Journal: Medicine (Baltimore) Date: 2016-11 Impact factor: 1.889
Authors: Abraham Nunes; Hugo G Schnack; Christopher R K Ching; Ingrid Agartz; Theophilus N Akudjedu; Martin Alda; Dag Alnæs; Silvia Alonso-Lana; Jochen Bauer; Bernhard T Baune; Erlend Bøen; Caterina Del Mar Bonnin; Geraldo F Busatto; Erick J Canales-Rodríguez; Dara M Cannon; Xavier Caseras; Tiffany M Chaim-Avancini; Udo Dannlowski; Ana M Díaz-Zuluaga; Bruno Dietsche; Nhat Trung Doan; Edouard Duchesnay; Torbjørn Elvsåshagen; Daniel Emden; Lisa T Eyler; Mar Fatjó-Vilas; Pauline Favre; Sonya F Foley; Janice M Fullerton; David C Glahn; Jose M Goikolea; Dominik Grotegerd; Tim Hahn; Chantal Henry; Derrek P Hibar; Josselin Houenou; Fleur M Howells; Neda Jahanshad; Tobias Kaufmann; Joanne Kenney; Tilo T J Kircher; Axel Krug; Trine V Lagerberg; Rhoshel K Lenroot; Carlos López-Jaramillo; Rodrigo Machado-Vieira; Ulrik F Malt; Colm McDonald; Philip B Mitchell; Benson Mwangi; Leila Nabulsi; Nils Opel; Bronwyn J Overs; Julian A Pineda-Zapata; Edith Pomarol-Clotet; Ronny Redlich; Gloria Roberts; Pedro G Rosa; Raymond Salvador; Theodore D Satterthwaite; Jair C Soares; Dan J Stein; Henk S Temmingh; Thomas Trappenberg; Anne Uhlmann; Neeltje E M van Haren; Eduard Vieta; Lars T Westlye; Daniel H Wolf; Dilara Yüksel; Marcus V Zanetti; Ole A Andreassen; Paul M Thompson; Tomas Hajek Journal: Mol Psychiatry Date: 2018-08-31 Impact factor: 15.992
Authors: Sean R McWhinney; Christoph Abé; Martin Alda; Francesco Benedetti; Erlend Bøen; Caterina Del Mar Bonnin; Tiana Borgers; Katharina Brosch; Erick J Canales-Rodríguez; Dara M Cannon; Udo Dannlowski; Ana M Díaz-Zuluaga; Torbjørn Elvsåshagen; Lisa T Eyler; Janice M Fullerton; Jose M Goikolea; Janik Goltermann; Dominik Grotegerd; Bartholomeus C M Haarman; Tim Hahn; Fleur M Howells; Martin Ingvar; Tilo T J Kircher; Axel Krug; Rayus T Kuplicki; Mikael Landén; Hannah Lemke; Benny Liberg; Carlos Lopez-Jaramillo; Ulrik F Malt; Fiona M Martyn; Elena Mazza; Colm McDonald; Genevieve McPhilemy; Sandra Meier; Susanne Meinert; Tina Meller; Elisa M T Melloni; Philip B Mitchell; Leila Nabulsi; Igor Nenadic; Nils Opel; Roel A Ophoff; Bronwyn J Overs; Julia-Katharina Pfarr; Julian A Pineda-Zapata; Edith Pomarol-Clotet; Joaquim Raduà; Jonathan Repple; Maike Richter; Kai G Ringwald; Gloria Roberts; Raymond Salvador; Jonathan Savitz; Simon Schmitt; Peter R Schofield; Kang Sim; Dan J Stein; Frederike Stein; Henk S Temmingh; Katharina Thiel; Neeltje E M van Haren; Holly Van Gestel; Cristian Vargas; Eduard Vieta; Annabel Vreeker; Lena Waltemate; Lakshmi N Yatham; Christopher R K Ching; Ole Andreassen; Paul M Thompson; Tomas Hajek Journal: Mol Psychiatry Date: 2021-04-16 Impact factor: 15.992