TABLE 1.
Characteristics and quality assessments of eligible meta-analyses evaluating the associations between unsaturated fatty acids and mental disorders1
| Study, year (ref) | Population | Mental disorders | Outcomes | Outcome assessments | No. of studies (participants, n) | Study design | Intervention/comparison | Effect metrics | AMSTAR 2 rating2 |
|---|---|---|---|---|---|---|---|---|---|
| Unsaturated fatty acids supplementation | |||||||||
| Xu et al., 2022 (64) | Adults | Schizophrenia | Symptoms | Positive and Negative Syndrome Scale | 6 (317) | Randomized controlled studies | EPA/DHA/EPA+DHA vs. placebo | MD | ●●○○Low |
| Appleton et al., 2021 (56) | Adults | Depression | Depressive symptoms, adverse events, quality of life | Beck Depression Inventory, Montgomery Asberg Depression Rating Scale, Hamilton Depression Rating Scale, and others | 34 (1924) | Randomized controlled studies | n–3 fatty acids supplementation vs. placebo | SMD, OR | ●●●●High |
| de Andrade Wobido et al., 2021 (57) | Children | Autism spectrum disorder | Symptoms | Aberrant Behavior Checklist, Social Responsiveness Scale | 13 (372) | Clinical trial, community trial | n–3 and n–6 fatty acids supplementation vs. placebo | SMD | ●●●●High |
| Goh et al., 2021 (58) | Adults | Schizophrenia | Symptoms | Positive and Negative Syndrome Scale and General Psychopathology Scale | 14 (950) | Randomized controlled studies | n–3 fatty acids supplementation vs. placebo or non-supplementation | SMD | ●●●●High |
| Händel et al., 2021 (59) | Children | Attention-deficit/hyperactivity disorder | Symptoms, behavioral difficulties, quality of life | Multiple psychopathology scales assessed the parent-reported core symptoms, teacher-reported core symptoms, parent-reported behavioral difficulties, teacher-reported behavioral difficulties, quality of life (including diarrhea, gastrointestinal discomfort, and nausea) | 31 (1775) | Randomized controlled studies | n–3 and n–6 fatty acids supplementation vs. placebo and/or regular diet | SMD | ●●●●High |
| Suradom et al., 2021 (60) | Pregnant and postpartum women | Depression | Prevention and treatment of depression severity | Edinburgh Postnatal Depression Scale, Postpartum Depression Screening Scale,Center for Epidemiological Studies–Depression Scale | 11 (3181) | Randomized controlled studies | n–3 and n–6 fatty acids supplementation vs. placebo | SMD | ●●○○Low |
| Xu et al., 2021 (61) | Elderly | Mild cognitive impairment | Symptoms | Mini-Mental State Examination | 3 (96) | Randomized controlled studies | Unsaturated fatty acids vs. antioxidant or non-supplementation | MD | ●○○○Critically low |
| Araya-Quintanilla et al., 2020 (52) | The elderly | Alzheimer disease | Symptoms | Narcissistic Personality Inventor, Mini-Mental State Examination, Alzheimer's Disease Assessment Scale–Cognitive section | 6 (758) | Randomized controlled studies | n–3 fatty acids supplementation vs. placebo | SMD | ●○○○Critically low |
| Luo et al., 2020 (53) | Adults | Depression | Depressive symptoms | Hamilton Depression Rating Scale or others | 10 (910) | Randomized controlled studies | n–3 and n–6 fatty acids supplementation (≥2000 mg/d and <2000 mg/d) vs. placebo | SMD | ●○○○Critically low |
| Mocking et al., 2020 (54) | Pregnant and postpartum women | Perinatal and postpartum depression | Depressive symptoms | Edinburgh Postnatal Depression Scale; Hamilton Depression Rating Scale; Montgomery-Asberg Depression Rating Scale, or others | 18 (4052) | Randomized controlled studies | n–3 and n–6 fatty acids supplementation vs. placebo or regular diet | SMD | ●●●●High |
| Zhang et al., 2020 (55) | The elderly | Mild cognition decline | Cognition | Mini-Mental State Examination | 7 (434) | Randomized controlled studies | n–3 and n–6 fatty acids supplementation vs. placebo | WMD | ●○○○Critically low |
| Devoe et al., 2019 (48) | Youth (age between 13 and 33) | Psychosis | Symptoms | Scale for the Assessment of Positive Symptoms, Brief Psychiatric Rating Scale, the Positive and Negative Syndrome Scale, the Scale of Prodromal Symptoms, and the Comprehensive Assessment of At-Risk Mental States | 3 (347) | Randomized controlled studies | n–3 fatty acids supplementation vs. placebo | SMD | ●●○○Low |
| Morsy et al., 2019 (49) | Adults | Huntington's disease | Total motor score; total motor score-4 | Unified Huntington disease rating scale (UHDRS) or other evaluations | 4 (782) | Randomized controlled studies | Ethyl-EPA vs. placebo | MD | ●●●○Medium |
| Zhang et al., 2019 (51) | Children | Depression | Depressive symptoms | The Children's Depression Rating Scale (CDRS), revised CDRS, Beck Depression Inventory, and Children's Depression Inventory | 4 (153) | Randomized controlled studies | n–3 fatty acids supplementation vs. placebo | SMD | ●○○○Critically low |
| Su et al., 2018 (47) | Adults | Anxiety | Symptoms | Clinician-administered post-traumatic stress disorder scale, Child Behavior Checklist anxiety subscale, children's Yale-Brown obsessive-compulsive scale, depression, anxiety, and stress scales, generalized anxiety disorder questionnaire, Hospital Anxiety and Depression Scale anxiety subscale, Hamilton anxiety rating scale, impact of event scale–revised, and Yale-Brown obsessive-compulsive scale | 19 (1203) | Clinical trials | n–3 fatty acids supplementation vs. placebo or education | Hedges' g | ●●●●High |
| Rosenblat et al., 2016 (45) | Adults | Bipolar depression | Symptoms | Bipolar Depression Rating Scale, Clinical Global Impressions Scale, Clinical Global Impressions Scale–Improvement–Bipolar, Clinical Global Impressions Scale–Improvement–Depression, Clinical Global Impressions Scale–Improvement–Mania, Clinical Global Impressions Scale–Severity–Bipolar, Clinical Global Impressions Scale–Severity–Depression, Clinical Global Impressions Scale–Severity–Mania, Hamilton Depression Rating Scale, Inventory of Depressive Symptomatology–Clinical Rating Scale, Montgomery–Asberg Depression Rating Scale, Quality of Life Enjoyment and Satisfaction Scale, Social and Occupational Functioning Assessment Scale, and Young Mania Rating Scale | 4 (140) | Randomized controlled studies | n–3 fatty acids supplementation vs. placebo | SMD | ●●○○Low |
| Tan et al., 2016 (46) | Children | Specific learning disorders | Adverse effects (gastrointestinal disturbances) | — | 2 (116) | Randomized controlled studies, quasi-RCTs | PUFA vs. placebo | RR | ●●●●High |
| Cooper et al., 2015 (42) | Children | Attention-deficit/hyperactivity disorder | Symptoms and brain functions | Wechsler Intelligence Scale for Children, test of variables of attention, digit span backwards (recalling a string of numbers backwards), immediate or delayed word recall, Wide Range Achievement Test, or others | 24 (8658) | Randomized controlled studies | n–3 fatty acids supplementation vs. placebo | SMD | ●○○○Critically low |
| Yang et al., 2015 (43) | Women | Depression | Depressive symptoms | Comprehensive evaluation (including Montgomery–Asberg Depression Rating Scale, Hamilton Depression Rating Scale, Clinical Global Impression, Beck Depression Inventory, or Geriatric Depression Scale) | 8 (267) | Randomized controlled studies | DHA and EPA vs. placebo | SMD | ●●●●High |
| Dietary unsaturated fatty acids intake | |||||||||
| Kosti et al., 2022 (63) | The elderly | Dementia,Alzheimer disease | Risk of dementia/Alzheimer disease | Cambridge Mental Disorders of the Elderly Examination, Clinical Dementia Rating Diagnostic and Statistical Manual of Mental Disorders-III-Revised, Geriatric Mental State Schedule, Mini-Mental State Examination Wechsler Memory Scale Revised | 9 (440,572) | Cohort | Highest intake of fish vs. reference group | RR | ●●●●High |
| Zhu et al., 2021 (62) | The elderly | Alzheimer disease | Risk of Alzheimer disease | NR | 14 (54,177) | Cohort | Highest intake of n–3 fatty acids vs. reference group | RR | ●●○○Low |
| Qu et al., 2019 (50) | Adults | Parkinson disease | Risk of Parkinson disease | NR | 9 (778,571) | Cohort, case-control | Highest intake of n–3 and n–6 fatty acids vs. reference group | RR | ●○○○Critically low |
| Grosso et al., 2016 (44) | Adults | Depression | Risk of depression | Center for Epidemiologic Studies–Depression, Composite International Diagnostic Interview Short Form, Depression, Anxiety and Stress Scales, Geriatric Depression Scale, Edinburgh Post-partum Depression Scale, and Munich-Composite International Diagnostic Interview | 16:15 (255,076) | Cohort, case-control | Highest intake of n–3 fatty acids and fish vs. reference group | RR | ●○○○Critically low |
| Zhang et al., 2016 (15) | The elderly | Alzheimer disease; cognitive decline; dementia; mild cognitive impairment; Parkinson disease | Risk of cognitive impairment | NR | 21 (181,580) | Cohort | Highest intake of n–3 fatty acids and fish vs. reference group | RR | ●●●●High |
| Tsai et al., 2014 (41) | Adults | Suicide | Suicide mortality | — | 3 (205,357) | Cohort | Highest intake of n–3 or n–6 fatty acids vs. reference group | RR | ●○○○Critically low |
| Circulating unsaturated fatty acids | |||||||||
| Mazahery et al., 2017 (11) | Children | Autism spectrum disorder | Circulating n–3, n–6 fatty acids and ratios between n–3/n–6 fatty acids | — | 15 (1193) | Case-control | Autism spectrum disorder vs. typically developing control | SMD | ●●●●High |
| McNamara et al., 2016 (12) | Youth | Bipolar disorder | Circulating n–3 and n–6 fatty acids | — | 6 (265) | Case-control | Bipolar disorder vs. typically developing control | SMD | ●○○○Critically low |
| Zhang et al., 2016 (15) | The elderly | Alzheimer disease; dementia; cognitive decline | Risk of cognitive impairment | — | 21 (181,580) | Cohort | A 1% increment of blood DHA concentrations | RR | ●●●●High |
| Hawkey et al., 2014 (13) | Children | Attention-deficit/hyperactivity disorder | Circulating n–3 fatty acids | — | 9 (586) | Case-control | Attention-deficit/hyperactivity disorder vs. typically developing control | Hedges' g | ●●●○Medium |
| van der Kemp et al., 2012 (14) | The elderly | Schizophrenia | Circulating n–3 and n–6 fatty acids | — | 14 (873) | Cohort, case-control | Schizophrenia vs. typically developing control | Cohen's d | ●○○○Critically low |
1
AMSTAR 2, A Measurement Tool to Assess Systematic Reviews; MD, mean difference; NR, not reported; RCT, randomized controlled trial; ref, reference; SMD, standardized mean difference; WMD, weighted mean difference.
2
AMSTAR 2 used 16 items to assess methodological quality of systematic reviews on the basis of the validity of review design, literature screening, data extraction, and individual study quality assessment. Details of the quality assessment for eligible reviews were provided in Supplemental Table 1.