Table 1. DTI studies of healthy relatives of SZ and related disorders.

Authors	Sample	Mean age (years) ±SD	Field strength	Analysis method	Abnormalities in relatives compared to healthy controls	Additional modalities	Comments/limitations
DeLisi et al., 2006	15 Relatives 25 HC 15 SZ	19.3 ± 4.6 23.7 ± 3.7 34.3 ± 10.7	1.5 T	VBA	ADC didn't differ in the region of the body of the CC	Gray matter Volumetric quantification	Several of the patients and relatives were biologic relatives Relatives were still in the peak age of risk for SZ (defined as ages 12-30) Only psychotic disorders excluded for relatives and HC Family history of psychotic disorders excluded for HC None of the relatives or HC were on antipsychotic or antidepressant medications
Hoptman et al., 2008	22 Relatives 37 HC 23 DSM-IV SZ+ SZAF	20.1±4.1 23.1±4.0 36.8±11.0	1.5 T	VBA	Reduced FA in: Left inferior frontal gyrus WM Bilateral left posterior cingulate WM Bilateral angular gyral WM Increased FA in: Left subgenual anterior cingulate Bilateral pontine tegmental WM Right middle/ superior frontal gyri	---	Most of the patients and relatives were biologic relatives Relatives were still in the peak age of risk for SZ (defined as ages 12-30) Fourteen relatives satisfied criteria for the prodrome, of those without the prodrome seven satisfied criteria for schizotypal personality disorder or had some schizotypal traits and five had a history (but not current) of major depression Relatives have never experienced acute psychotic symptoms Psychotic disorders and family history of psychotic disorders excluded for HC None of the HC were currently taking medication for any psychiatric condition There was a significant difference in sex distribution across groups In this study some of the participants were recruited from the study De Lisiet al., 2006, but the sample size was enlarged.
Munoz Maniega et al., 2008	22 Relatives 51 HC 31 DSM-IV SZ	30±3 35±11 37±10	1.5 T	VBA ROI	VBA showed that FA didn't differ significantly Automatic ROI analysis showed that FA was reduced in the ALIC	---	Relatives had at least two or more first or second degree relatives with SZ None of the relatives and patients were related Not specified whether relatives or HC have another psychiatric illness, other than SZ or are taking medicine.
Hao et al., 2009	34 Siblings 32 HC 34 DSM-IV SZ	25.8±7.1 26.6±6.0 25.4±5.9	1.5 T	VBA	Reduced FA in: Left hippocampus Left PFC	---	All of the patients and relatives were biologic relatives All of the psychiatric disorders excluded for relatives and HC First degree relatives of HC didn't have a history of any psychiatric disorder
Camchong et al., 2009	22 Relatives 30 HC 18 healthy MZ twin pairs	48.5 ±8.2 43.8 ±11.4	3 T	ROI VBA TBSS	ROI analysis and TBSS showed decreased FA in right genu of CC VBA showed no differences	Correlation of FA values between healthy MZ twin pairs	Current alcohol or drug abuse, drug dependence, major depressive episode, current or previous use of anti-psychotic medications, a personal history of psychosis or BD, or an Axis II Cluster A personality disorder was excluded for all subjects HC were excluded if they have a family history of psychosis or BD
Clark et al., 2011	20 Relatives 32 HC 31 DSM-IV SZ	41.1 ±13.0 34.8 ±14.0 32.7 ±9.3	1.5 T	ROI	Decreased FA in: The bilateral IFOF The left ILF The left tSLF Age was not significantly different among these groups, but post-hoc analysis (age as a covariate) showed only decreased FA in the left ILF remained significant There were no significant differences in ADC values	Genetic liability effects Correlation with BPRS scores	None of the relatives were biologic relatives of the patients No individual with a schizophrenia spectrum disorder or a psychotic disorder was included in relatives or HC Six control and eight patient relatives met diagnostic criteria for additional Axis I or II diagnoses (mood disorders, anxiety disorder, attention-deficit/hyperactivity disorder, conduct disorders, antisocial personality disorder) HC or relatives were not taking psychiatric medicine HC were excluded if they had any evidence of drug abuse or alcoholism within six months
Phillips et al., 2011	49 Relatives (P+S) 21 HC 54 HCR (P+S) 26 DSM-IV SZ	P: 54.4 ± 8.3 S: 30.1 ± 11.5 25.9 ± 6.7 P: 55.7 ± 8.5 S: 26.9 ± 9.8 29.5 ± 7.4	1.5 T	VBA	Decreased FA in: bilateral temporal lobe bilateral occipital lobe Results didn't withstand permutation correction	Genetic liability effects	All of the psychiatric disorders were excluded for HC and HCR subjects Recent or past history of significant and habitual drug abuse or alcoholism were excluded for all subjects Age was similar between HC and patient siblings, HC and patient parents, and between patients and their siblings
Knöchel et al., 2012b	16 Relatives 15 HC 16 DSM-IV SZ	41.9± 8.6 39.3 ± 11.0 37.6 ± 7.8	3 T	ROI	Decreased FA in: The whole CC The inferior genu The superior genu(p=0.051) The isthmus Increased ADC in: The Whole CC The isthmus (p=0.053)	Volumetric quantification Correlation between clinical characteristics and FA values and volume	The patients and the relatives weren't biologic relatives Any psychiatric disorder including Axis I and Axis II disorders according to DSM-IV were excluded for relatives and HC
Knöchel et al., 2012a	18 Relatives 22 HC 28 DSM-IV SZ	39.4 ± 10.8 41.9 ± 10.5 40.8 ± 12.0	3 T	VBA ROI TBSS	VBA showed that FA didn't differ significantly ROI analysis showed that FA was significantly reduced in: commissural fibers(including CC) Association fibers(IFOF, left SLF, left IC,UF) Cingulum bundles ROI analysis showed that FA was significantly increased in AF	Correlation between FA values and clinical characteristics	Any psychiatric disorder including Axis I and Axis II disorders according to DSM-IV were excluded for relatives and HC Family history of SZ excluded for HC
Boos et al., 2013	123 Siblings 109 HC 126 DSM-IV SZ+SZAF+S ZFM	26.7± 6.4 27.3± 8.2 26.6± 5.6	1.5 T	TBSS	FA was increased in the left and right AF	Age × illness interaction Correlation between FA values and clinical characteristics	Siblings who met DSM-IV criteria for (related diagnoses of) SZ or substance dependence were excluded from the study. Some of the siblings had bipolar disorder (n= 3), major depression (n=22) or other psychiatric disorders (n= 5). None of the HC met the criteria for any DSM-IV axis I disorder at the time of inclusion Groups differed significantly in sex distribution and WAIS IQ
Domen et al., 2013	93 Siblings 80 HC 85 DSM-IV SZ and related disorders	29.4± 8.8 30.8± 10.8 28.3± 7.0	3 T	VBA TBSS	Although mean FA values of siblings were generally lower than HC, these differences were not signifficant	Cannabis and other drug use AP medication History of affective disorder	Most of the patients and relatives were biologic relatives Some of the HC subjects were biologic relatives Relatives and HC didn't have a lifetime diagnosis of any non-affective psychotic disorder Family history of psychotic disorders were excluded for HC 18 relatives and 12 HC had a history of major depressive disorder Three siblings and three HC used antidepressants and one HC used benzodiazepines. None of the siblings or HC met the criteria for a current depressive episode
Goghari et al., 2014	24 Relatives 27 HC 25 SZ+SZAF	40.2± 15.0 40.7± 11.1 41.3± 10.8	3 T	VBA Along-tract analysis	VBA showed that FA didn't differ significantly Along-tract analysis showed increased FA in the right fimbria of the fornix	Relationship between DTI metrics and clinical characteristics	Some of the patients and relatives were biological relatives None of the participants had a current drug/alcohol dependence/abuse Relatives and HC didn't have a lifetime diagnosis of a psychotic disorder or bipolar disorder or history of antipsychotic medication use But some of the relatives and HC were receiving antidepressants, antianxiety or other psychiatric medications No relatives or HC met criteria for a Cluster A disorder
Prasad et al., 2014	21 Relatives 29 HC 39 SZ+SZAF	23.0± 4.1 27.1± 6.8 26.8± 8.5	3T	TBSS	FA was decreased in forceps minor RD was decreased in the left SLF and forceps minor**	Cognitive measures and diffusion metrics	Substance abuse in the previous month or dependence 6 months prior to enrolment were excluded for all groups Not specified whether relatives or HC have another psychiatric illness, other than SZ or are taking medicine.

^*presumed typo in the publication;

^**results shown here are taken from the tables in this manuscript;

HC, healthy controls; HCR, relatives of healthy controls; SZ, schizophrenia; SZAF, schizoaffective disorder; SZFM, schizophreniform disorder; BD, bipolar disorders; P, parents; S, siblings; MZ, monozygotic; DTI, Diffusion tensor imaging; ROI, region of interest; VBA, voxel based analysis; TBSS, tract-based spatial statistics; FA, fractional anisotropy; ADC, apparent diffusion coefficient; WM, white matter; CC, corpus callosun; PFC, prefrontal cortex; IC, internal capsule; ALIC, anterior limb of internal capsules; AF, arcuate fasciculus; UF, uncnate fasciculus; SLF, superior longitudinal fasciculus; tSLF, temporal superior longitudinal fasciculus; ILF, inferior longitudinal fasciculus; IFOF, inferior fronto-occipital fasciculus; DSM-IV, Diagnostic and Statistical Manual of Mental Disorders Fourth Edition; BPRS, Brief Psychiatric Rating Scale; AP, antipsychotic; WAIS, The Wechsler Adult Intelligence Scale; IQ, intelligence quotient.