Study and clinical characteristics
| Study | Country | Study type | Inflammatory markers | N | Standardised diagnostic assessment/crit era | Anxiety measure | Age (years, SD) | % Female | BMI | Current smoking | Medicated | Physical health comorbidities | Mental health comorbidities | ||||
| GAD | Control | GAD | Control | GAD | Control | GAD | Control | ||||||||||
| Bankier et al 38 | USA | Case–control | CRP | 15 | 30 | SCID, DSM-IV | NR | NR | 67.6 (12.7) | NR | 33% | NR | NR | GAD: NR Controls: 10% | NR | All participants had CVD. Excluded other conditions. | Excluded. |
| Copeland et al 39 | USA | Cohort, prospective | CRP | 146 | 5664 | Child and Adolescent Psychiatric Assessment <16, Young Adult Psychiatric Assessment >16, DSM-IV criteria | Total number of anxiety symptoms (range: 0–6) | 14.21, all subjects (odds or means ratio 1.12 (1.03–1.22) with GAD dx) | 48.7% (odds or means ratio 2.02 (1.04–3.92) with GAD dx) | 22.37 (5.62) (odds or means ratio 1.08 (1.05–1.11) with GAD dx) | Total sample: 13.5% (odds/means ratio with GAD: 2.86) | 30.2% ‘use medication’ (odds/means ratio with GAD: 2.00) | 34.7% had ‘recent health ailments’. | Total sample: 39.9% comorbid MDD. | |||
| De Berardis et al 42 | Canada | Cross-sectional | CRP | 70 | No control | SCID, DSM-IV | HAM-A (score >20 for inclusion) | 28.2 (5.3) | – | 51.40% | – | 22.1 (1.67) | – | NR | Excluded. | Excluded. | Total sample: 44.3% of participants had alexithymia. Excluded other comorbid mental illness. |
| Hoge et al 44 | USA | RCT | TNF-α, IL-6 | 70 | No control | SCID, DSM-IV | NR | 39.12 | – | 45.70% | – | NR | – | NR | Excluded. | Excluded. | GAD: 14.3% comorbid MDD. Excluded other comorbid mental illness. |
| Hou et al 47 | UK | Case–control | IL-4, IL-10, TNF-α, IFN-γ | 54 | 64 | MINI, DSM-IV, ICD-10 criteria | HADS, GAD-7 (score >10 for inclusion) | 35.06 (14.45) | 25.75 (8.87) | 34% | 50% | 24.84 (5.70) | 22.45 (3.27) | GAD: 22% Controls: 34% | GAD: 67% use ‘anxiolytic’ medication. Excluded other medication use. | Excluded. | Excluded. |
| Khandaker et al 33 | UK | Cohort, prospective | CRP | 26 | 3392 | DAWBA, DSM-IV criteria | DAWBA | 15.56 (0.24) | 15.53 (0.31) | 90% | 52.30% | 22.55 (3.52) | 21.40 (3.63) | NR | NR | NR | GAD: 30.77% comorbid MDD. Excluded other comorbid mental illness. |
| Korkeila et al 40 | Finland | Cross-sectional | CRP, TNF-α, IFN-γ | 116 | MINI | NR | NR | NR | 100% | 100% | All 25.3 (5.0) | NR | Excluded. | NR | NR | NR | |
| Nayek and Ghosh34 | India | Case–control | CRP | 50 | 50 | ICD-10 | NR | 37.96 (10.7) | 37.00 (12.08) | 54% | 23% | NR | NR | Excluded. | Excluded if using HRT or OCP. Other medications not reported. | Excluded. | NR |
| Ogłodek et al 48 | Poland | Case–control | SDF-1, CCL-5, MCP-1 | 120 | 40 | DSM-V | NR | 41.4 (3.5) | 40.8 (3.1) | 50% | NR | NR | NR | NR | Excluded. | Excluded. | All participants had comorbid personality disorder. Excluded other comorbid mental illness. |
| Tang et al 35 | China | Case–control | CRP, IL-1α, IL-2, IL-5, IL-6, IL-8, IL-12p70, IFN-γ, GM-CSF | 48 | 48 | MINI, DSM-IV | GAD-7, SAI, TAI | 40.75 (12.21) | 39.56 (10.06) | 58.33% | 64.17% | 22.56 (2.73) | 22.69 (2.63) | GAD: 29% Controls: 23% | Excluded. | Excluded acute illness. Chronic comorbidities NR. | Excluded. |
| Tofani et al 46 | Italy | Case–control | IL-2, IL-10 | 14 | 10 | MINI, DSM-IV | GAD-7 | NR | NR | NR | NR | NR | NR | NR | Excluded. | NR | Excluded. |
| Vogelzangs et al 36 | Holland | Cohort | CRP, IL-6, TNF-α | 454 | 556 | CIDI, DSM criteria | BAI | Total sample: 41.8 (13.1) | 66.90% | 25.6 (5.1) | Total sample: 38.2% | NR | Total sample: 6.2% CVD, 4.9% diabetes, mean of 0.4 other chronic diseases. | Total sample: 58.4% comorbid MDD. Excluded other comorbid mental illness. | |||
| Yang et al 45 | China | Case–control | IL-1, IL-4, TNF-α | 28 | 41 | MINI, DSM-IV | HAM-A | 55.1 (6.9) | 55.9 (5.6) | 53.60% | 48.80% | 22.0 (4.4) | 22.5 (3.7) | GAD: 35.7% Control: 24.4% | Excluded. | Additional group with comorbid asthma. Excluded other comorbidities. | Excluded. |
| Zahm41 | USA | Cohort, prospective | CRP, IL-6, TNF-α | 93 | 728 | CDIS, DSM-IV | NR | 68 (9.6) | 17% | NR | NR | NR | NR | All patients had history of CVD. | GAD: 60.0% comorbid MDD, 86.2% had lifetime history MDD. | ||
–, not applicable; BAI, Beck Anxiety Inventory; CCL-5, chemokine C-C motif ligand 5; CDIS, Computerized Diagnostic Interview Schedule; CIDI, Composite Interview Diagnostic Instrument; CRP, C reactive protein; CVD, cardiovascular disease; DAWBA, Development and Well-Being Assessment; DSM, Diagnostic and Statistical Manual of Mental Disorders; dx, diagnosis; GAD, generalised anxiety disorder; GAD-7, Generalised Anxiety Disorder Assessment; GM-CSF, granulocyte-macrophage colony-stimulating factor; HADS, Hospital Anxiety and Depression Scale; HAM-A, Hamilton Anxiety Rating Scale; HRT, hormone replacement therapy; ICD, International Classification of Diseases; IFN-γ, interferon-γ; IL, interleukin; MCP-1, monocyte chemoattractant protein-1; MDD, major depressive disorder; MINI, Mini-International Neuropsychiatric Interview; NR, not reported; OCP, oral contraceptive pill; RCT, randomised controlled trial; SAI, State Anxiety Inventory; SCID, Structured Clinical Interview for DSM-IV; SDF-1, stromal derived factor-1; TAI, Test Anxiety Inventory; TNF-α, tumour necrosis factor-α.