Table 1.

Characteristics of included studies.

Author (Year)	Country of Origin/Study Design	Participants	Healthy Controls	Interventions	Outcomes	Method of Measuring Adherence *	Notes
Addolorato et al. (2001) [65]	Italy Single centre BA comparison	35 newly diagnosed classical CD patients	59 HC recruited from hospital staff members	GFD for 1 y	Changes in depression score BA a GFD (M-SDS) Changes in no. patients positive for depression BA a GFD (M-SDS score > 49)	1—validated 2—family member interview 3—AGA, EmA 4—biopsy at 6–8 mo
Aziz et al. (2016) [63]	UK Single centre BA comparison	41 IBS-D patients; 20 HLA-DQ2/8+ and 21 HLA-DQ2/8−	NC	GFD for 6 wk; FU at 18 mo for those who continued on GFD	Changes in HADS before and after a GFD Difference between HLA-DQ2/8+/− groups	1—validated (“Patients scoring 0 or 1 do not follow a strict GFD. Patients scoring 2 follow a GFD but with errors necessitating correction. Finally, patients scoring three or four follow a strict GFD.”)	Educational grant from Dr. Schär (a gluten-free food manufacturer) to undertake investigator-conceived and -led research on gluten sensitivity
Bella et al. (2015) [59]	Italy Single centre BA comparison (FU study from Pennisi et al. (2014))	13 CD patients	NC	GFD for 16 mo	Changes in depression score BA a GFD (HDRS) Changes in no. patients positive for depression (dysthymia) BA a GFD (SCID-I)	1—validated 3—EmA, tTG
Collin et al. (2008) [64]	Finland Single centre BA comparison	20 biopsy-proven CD patients	HCs not recruited from same community (female students/male workers)	GFD for 1 y	Changes in depression score BA a GFD (sub-score of CCEI/Middlesex Hospital Questionnaire)	3—EmA 4—Vh/CrD
Di Sabatino et al. (2015) [56]	Italy Multicentre DB, PC, CO RCT	59 patients suspected of having NCGS (CD and WA excluded)	NA	2 arms; GFD (1 wk baseline period) followed by 1 wk: (a) 4.375 g/day gluten (b) rice starch placebo with 1 wk wash-out periods inbetween	Difference in mean daily depression scores (unvalidated questionnaire) between gluten and placebo groups	1—validated 6—unused capsules counted
Kurppa et al. (2010) [60]	Finland Single centre Cohort	73 EmA-positive adults; 27 mild enteropathy (Marsh I-II), 46 CD (Marsh III)	110 HCs (age and gender matched)	GFD for 1 y	Changes in depression score BA a GFD (sub-score of PGWB)	3—EmA, tTG 4—Vh/CrD
Kurppa et al. (2014) [53]	Finland Multicentre DB, CO RCT	40 asymptomatic EmA-positive adults (CD excluded)	NA	2 arms; participants randomised to a GFD or gluten-containing diet for 1 y then cross-over	Difference in mean depression score between gluten and GFD groups at 1 y (sub-score of PGWB)	2—NI on who conducted 3—EmA, tTG 4—Vh/CrD	Deviations from protocol: No-one in GFD group willing to restart gluten-containing diet so only data from 1 y FU used
Nachman et al. (2009) [58]	Argentina Single centre BA comparison/time-interrupted study	84 newly diagnosed biopsy-proven CD patients; 62 classical, 14 atypical and 8 asymptomatic	70 HCs recruited from hospital staff members (age and gender matched)	GFD for 1 y	At baseline, 3, 6, 9 and 12 mo: Changes in depression score BA a GFD (BDI) Changes in no. patients positive for depression BA a GFD (BDI score ≥ 18) Subgroup analysis: Compliant vs. noncompliant	Opinion of physician in charge, based on: 1—self-rated questionnaire 2—“meticulous enquiry by an experienced dietician” 3—tTG, DGP, EmA, AGA 4—Vh/CrD 5—4 day (self-reported)
Nachman et al. (2010) [57]	Argentina Single centre BA comparison/FU from Nachman et al. (2009)	53 CD patients; 37 classical and 16 atypical/asymptomatic	70 HCs recruited from hospital staff members (age and gender matched) (same as Nachman et al. (2009))	GFD for 4 y	At baseline, 1 y and 4 y: Changes in depression score BA a GFD (BDI) Changes in no. patients positive for depression BA a GFD (BDI score ≥ 18) Subgroup analysis: Compliant vs. noncompliant	Opinion of physician in charge, based on: 1—self-rated questionnaire 2—“meticulous enquiry by an experienced dietician” 3—tTG, DGP, EmA, AGA 4—Vh/CrD 5—4 day (self-reported)
Peters et al. (2014) [42]	Australia Single centre DB, PC, CO RCT	20 IBS patients (CD excluded by biospy); recruited from a preceding study in which subjects with self-reported NCGS were challenged with diets containing varying amounts of gluten (Biesiekierski et al., 2013)	NA	3 arms; low-FODMAPs + GFD (3 day baseline period) followed by 3 day: (a) gluten (16 g/day) (b) whey (16 g/day) (protein control) (c) placebo with 3–14 day washout period in between	Difference in depression scores following each dietary challenge (sub-score of STPI)	1—validated 5—3 day (self-reported) 6—unused/additional food counted	Peter R. Gibson has published two books on a diet for IBS. This study was supported by George Weston Foods as part of a partnership in an Australian Research Council Linkage Project and the National Health and Medical Research Council (NHMRC) of Australia.
Simsek et al. (2015) [11]	Turkey Single centre BA comparison	24 newly diagnosed biopsy-proven paediatric CD patients; age limit 9–16 y	25 HCs recruited from same centre; EmA-negative	GFD for 6–20 mo	Changes in depression score BA a GFD (CDI) Subgroup analysis: Compliant vs. noncompliant	3—EmA, tTG
Ukkola et al. (2011) [61]	Finland Nationwide BA comparison	698 newly diagnosed (within 1 y) biopsy-proven CD patients; 490 classical, 62 atypical and 146 screen-detected	110 HCs (age and gender matched)	GFD for 1 y	Changes in depression score BA a GFD (subscore of PGWB)	1—unvalidated FU question (“strict diet” or “dietary lapses”)
Vilppula et al. (2011) [62]	Finland Nationwide BA comparison	32 screen-detected biopsy-proven CD patients; age > 50 y	110 HCs recruited from neighbourhoods of CD patients (age and gender matched)	GFD for 1–2 y	Changes in depression score BA a GFD (subscore of PGWB)	2—with dietician 3—tTG, EmA 4—Vh/CrD (“Diet considered strict when there were no signs of dietary transgressions upon the interview. Occasional GFD defined as a gluten intake occurring less often than once in the month.”)

NOTE: Studies in alphabetical order. Abbreviations: RCT, randomised controlled trial; BA, before-after; DB, double-blind; PC, placebo controlled; CO, cross-over; CD, coeliac disease; WA, wheat allergy; GFD, gluten-free diet; HC, healthy control; NC, no control group; IBS(-D), irritable bowel syndrome (diarrhoea-predominant); NCGS, non-coeliac gluten sensitivity; y, year; mo, month; wk, week; FU, follow-up; M-SDS, modified Zung Self-reported Depression Scale; HADS, Hospital Anxiety and Depression Scale; HDRS, Hamilton Depression Rating Scale; SCID-I, Structured Clinical Interview for DSM-IV Axis I Disorders; CCEI, Crown-Crisp Experiential Index; PGWB, Psychological General Well-Being Index; BDI, Beck Depression Inventory; STPI, State-Trait Personality Inventory; CDI, Children’s Depression Inventory; AGA, Anti-gliadin antibodies; EmA, anti-endomysial antibodies; tTG, Anti-tissue transglutaminase antibodies; Vh/CrD, villous height:crypt depth ratio; DGP, Deamidated Gliadin Peptide; NI, no information; NA, not applicable. * 1, Self-rated questionnaire; 2, Interview; 3, Serology; 4, Histology; 5, Food diary/record; 6, Other.