Study characteristics of included articles
| ID | Author, year | NOS | Participants (patients/controls) | Age, years (SD or range) | Education (years) | Diagnostic category | Onset (bulbar/spinal) | Duration (months) | Disease severity | Depression/anxiety |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | David, 1986 | 6 | 14/9 | 53.7 (8.0) | – | – | 7/7 | 17.8 | – | – |
| 2 | Gallassi, 1989 | 6 | 18/36 | 55.7 (10.9) | 7.4 | – | – | 17.2 | – | – |
| 3 | Ludolph, 1992 | 6 | 17/17 | 58.5 (11.6) | – | – | 13/8 | – | – | 7.6 (5.7)f |
| 4 | Kew, 1993 | 7 | 16/16 | 59.1 (37–71) | – | Prob/def | 8/8 | 21.4 | – | – |
| 5 | Abrahams, 1997 | 6 | 52/28 | 57.2 (11.8) | 13.3 | Poss/prob | 24/28 | 22.3 | 31.8 (4.8)b | 9.8 (4.4)e |
| 6 | Rakowicz, 1998 | 7 | 15/24 | 68.3 (11.2) | 9.9 | Prob/def | 12/3 | 12.9 | – | – |
| 7 | Vieregge, 1999 | 6 | 8/8 | 54.2 (9.6) | 9.6 | Prob/def | 7/1 | 26.0 | 29.0 (12.0)a | 60.4 (5.3)j |
| 8 | McCullagh, 1999 | 7 | 18/10 | 62.3 (8.3) | 12.1 | Def | – | – | – | 6.3 (3.5)e |
| 9 | Abrahams, 2000 | 6 | 22/25 | 58.4 (10.6) | 14.1 | Poss | – | 25.9 | 32.2 (4.4)b | 6.8 (3.3)e |
| 10 | Hanagasi, 2002 | 5 | 20/13 | 55.8 (10.2) | 8.7 | Prob/def | 0/20 | 18.3 | 33.0 (2.5)a | 3.3 (2.3)g |
| 11 | Evdokimidis, 2002 | 6 | 51/28 | 58.8 (10.2) | 9.4 | – | 11/40 | 25.5 | 69.2 (25.0)c | – |
| 12 | Abrahams, 2004 | 6 | 28/18 | 53.0 (11.0) | 12.7 | Prob/def | – | 21.0 | – | 6.4 (3.5)e |
| 13 | Kilani, 2004 | 7 | 19/19 | 57.3 (11.1) | 12 | Prob/def | 2/17 | 24.0 | – | – |
| 14 | Papps, 2005 | 6 | 19/20 | 55.7 (11.7) | – | Prob/def | – | – | – | 8.5 (4.1)e |
| 15 | Ringholz, 2005 | 7 | 226/129 | – | 13.8 | Prob/def | – | 16.5 | 68.4 (20.5)c | 7.8 (6.0)h |
| 16 | Lulé, 2005 | 5 | 12/18 | 59.0 (9.0) | 12.6 | Prob/def | 0/12 | 40.0 | 75.5 (12.6)d | 8.9 (4.1)f |
| 17 | Rottig, 2006 | 7 | 15/15 | 58.8 (14.4) | – | – | 0/15 | 30.3 | – | – |
| 18 | Gibbons, 2007 | 6 | 16/16 | 60.8 (8) | 13 | – | 3/13 | 24.0 | – | – |
| 19 | Mezzapesa, 2007 | 5 | 16/9 | 62.0 (10.0) | 8.7 | Prob/def | – | 38.1 | 27.4 (8.6)a | – |
| 20 | Lulé, 2007 | 5 | 13/15 | 57.5 (10.5) | – | Prob/def | 0/14 | 23.0 | 36.8 (8)a | 12.7 (5.1)f |
| 21 | Raggi, 2008 | 5 | 10/10 | 64.7 (8.07) | 8.2 | Def | – | 42.9 | 28.4 (4.0)b | 1.1 (1.3)g |
| 22 | Lakerveld, 2008 | 7 | 11/11 | 52.3 (10.4) | 15 | – | – | 80.0 | 11.9 (8.2a | 21 (5.1)i |
| 23 | Ogawa, 2009 | 5 | 19/19 | 67.7 (7.4) | 10.3 | Def | 11/8 | 8.1 | – | 10.7 (6.5)f |
| 24 | Meier, 2010 | 8 | 18/18 | 64.5 (11.5) | 13.2 | Prob/def | – | 34.6 | 35.8 (5.2)a | 7.8 (3.6)e |
| 25 | Tsuji-Akimoto, 2010 | 6 | 18/16 | 65.4 (11.5) | 10.8 | Poss/prob/def | – | 19.4 | 34.7 (7.5)a | – |
| 26 | Volpato, 2010 | 5 | 24/17 | 54.8 (13.4) | 10.4 | Prob/def | 3/21 | 37.4 | 34.3 (6.9)a | 11.8 (3.8)f |
| 27 | Palmieri, 2010 | 5 | 9/10 | 51.7 (11.5) | 8.9 | Prob/def | – | 24.0 | – | 10.4 (2.1)f |
| 28 | Raaphorst, 2011 | 6 | 30/24 | 61.2 (11.8) | 13.8 | Prob/def | 10/20 | 21.5 | 40.3 (4.6)a | 8.6 (5.8)e |
| 29 | Cavallo, 2011 | 6 | 15/21 | 61.0 (10.0) | 14.9 | Prob/def | 1/14 | 32.2 | 31.3 (7.3)a | 5.7 (3.2)e |
| 30.1 | Girardi, 2011, part 1 | 6 | 19/20 | 56.1 (8.3) | 13.1 | Prob/def | – | 33.2 | 29.4 (10.5)a | 9.7 (3.6)e |
| 30.2 | Girardi, 2011, part 2 | 6 | 14/20 | 57.4 (16) | 14.4 | Prob/def | – | 38.1 | 29.8 (10.6)a | – |
| 31 | Sarro, 2011 | 5 | 16/15 | 61.0 (10.0) | 9 | Prob/def | 1/13 | 29.0 | 33.0 (7.0)a | – |
| 32 | Christidi, 2012 | 5 | 22/22 | 59.1 (17.6) | 9 | – | 8/14 | 19.2 | 37.5 (7.1)a | – |
| 33 | Cuddy, 2012 | 7 | 19/19 | 63.3 (9.1) | – | Prob/def | – | – | 37.7 (6.4)a | 3.4 (2.9)e |
| 34 | Palmieri, 2012 | 6 | 24/27 | 61.6 (9.5) | 9.4 | Prob/def | 8/16 | 13.0 | 40.4 (5.1)a | 13.9 (8.5)f |
| 35 | Phukan, 2012 | 7 | 132/110 | 62.7 (9.5) | 12.2 | Poss/prob/def | – | – | – | 8.0 (4.9)e |
| 36 | Roberts-South, 2012 | 6 | 16/12 | 52.8 (9.2) | 14.9 | – | 5/11 | – | – | – |
| 37 | Zalonis, 2012 | 6 | 48/47 | 60.3 (11.2) | 9.7 | – | 18/30 | 21.0 | 27.7 (4.1)a | – |
| 38 | Christidi, 2013 | 5 | 26/26 | 61.4 (10.4) | 11.4 | – | 8/18 | 21.9 | 28.9 (4.1)a | – |
| 39 | Taylor, 2013 | 6 | 51/35 | 59.8 (9.1) | 13.8 | Prob/def | 13/38 | – | 33.2 (9.1)a | 8.3 (5.8)e |
| 40 | Fiori, 2013 | 5 | 23/23 | 56.6 (12.4) | 14.5 | Prob/def | 19/4 | 19.8 | 22.8 (10.9)a | – |
| 41 | Hu, 2013 | 5 | 27/43 | 57.7 (10.4) | 15.2 | Poss/prob/def | – | – | – | – |
| 42 | Savage, 2013 | 5 | 13/30 | 58.0 (8.4) | 14.1 | Prob/def | 2/11 | – | 37.3 (3.1)a | – |
| 43 | Staios, 2013 | 7 | 35/30 | 63.5 (9.7) | – | Prob/def | – | 32.1 | 36.4 (9.0)a | 9.5 (4.3)e |
| 44 | Mannerelli, 2014 | 7 | 33/32 | 63.3 (10.3) | 9.7 | Prob/def | 11/22 | 21.0 | 35.8 (8.8)a | – |
ID: study number; NOS: Newcastle—Ottawa quality assessment scale for case-control studies; N: number of participants; diagnostic category: according to the El Escorial criteria; poss: possible ALS; prob: probable ALS; def: definite ALS. Disease severity is measured with different disease severity scales, i.e. aALSFRS-R, bALSSS, cAppel scale and dNorris scale. The scores of the ALSFRS-R, ALSSS and Norris score range from 0 to 48, 40 and 100, respectively, which indicate no disability. The scores of the Appel score range between 30 and 164 and lower scores indicate less disability. Depression/anxiety is measured with eHADS, fBDI, gHamilton, hGDS, iALS depression Inventory and jthe Von Zerssen depression scale. For a list of the included articles, see online supplementary table S4.