Table 1.
Overview of studies reporting data-driven analysis for tinnitus subphenotyping.
| Studies | Variables for Subgrouping | N | Method for Subgrouping (Method for Selection of Number of Groups) | Validation | Group Descriptions |
|---|---|---|---|---|---|
| Erlandsson, Rubinstein [50] | Mood characteristics | 42 | Cluster analysis with k-means—distance measure not specified (prespecified three groups) | Comparison of subgroups against variables not used for subgrouping (hearing ability, age, anxiety, various tinnitus characteristics) |
3 groups: 1. Low mood, higher tinnitus impact, anxiety, and hearing asymmetry. 2. Moderate mood. 3. High mood. |
| Newman, Wharton [87] | Personality and somatic symptoms (self-focused attention, somatic attention) | 51 | Cluster analysis minimizing squared distances from cluster means (selection among 4 groupings based on clinical interpretation) | Comparison of subgroups against variables not used for subgrouping (tinnitus impact, depressive symptomatology, tinnitus psychoacoustic characteristics) |
2 groups: 1. Lower score on both self-attention and somatic attention measures. 2. More internally directed, higher score on the attention measures. On average more depressed, with greater emotional distress due to tinnitus, and with greater perceived tinnitus handicap. |
| Andersson and McKenna [86] | Depressive symptoms, hearing ability (PTA), tinnitus loudness, external sound effect on tinnitus (MML) | 30 | Hierarchical cluster analysis with Ward’s method and Euclidean distances (not specified) | Comparison of subgroups against variables not used for subgrouping (age, tinnitus duration and severity) |
3 groups: 1. Low depression, average loudness, slightly above average MML and PTA. 2. High value only in depression, the youngest. 3. High values in all variables, the oldest. |
| Rizzardo, Savastano [88] | Personality and other mental health characteristics including symptoms of anxiety and depression | 84 | Hierarchical cluster analysis with complete linkage—distance measure not specified (not specified) | Comparison of subgroups against variables not used for subgrouping (demographics, clinical characteristics) |
3 groups: 1. Higher scores for depression, anxiety, neuroticism, and hypochondriasis, more often somatic symptoms and psychotropic drug use, less ENT stays, higher tinnitus distress, and lesser degree of denial. 2. Normal psychological tests apart from marked denial. 3. One patient. |
| Tyler, Coelho [90] | Age, hearing function, symptoms of anxiety, depression, and stress, somatic symptoms, tinnitus duration, perceptual characteristics, modulating factors, and severity (not all variables specified) | 153 | 2-step cluster analysis (SPSS) (tested solutions with 4–6 clusters; chose 4 because it resulted in about equal group sizes) | None |
4 groups: 1. Loud, persistent and distressing tinnitus, highest anxiety and depression scores, with loudness hyperacusis. 2. Varying tinnitus pitch and loudness, worse in noise. 3. Copers, tinnitus not influenced by touch. 4. Copers, tinnitus worse in quiet and better in noise. |
| Schecklmann, Lehner [89] | Three analyses using different variables: A. Tinnitus severity, duration, and localisation B. Grey matter volume (MRI) C. Brain glucose metabolism (PET) |
44 | Hierarchical cluster analysis with Ward’s method and Euclidean distances (forced to 2 groups in order to have sample sizes with sufficient statistical power) | Comparison of subgroups against variables not used for subgrouping (age, sex, hearing function, and tinnitus duration, localisation and severity) |
2 groups from each of the three analyses: A. Unilateral versus mainly bilateral tinnitus. B. Higher versus lower grey matter volume in medial superior prefrontal, cingulate, temporal, insular, orbital frontal, temporal, pre- and post-central and thalamic areas. C. Higher versus lower glucose metabolism in middle and superior temporal, precuneus, and superior parietal areas. |
| van den Berge, Free [91] | Two analyses using different variables: A. The variables with the highest loading on each of 8 components from a principal components analysis on 30 variables (depression or anxiety symptoms, hearing ability, tinnitus onset-related and perceptual characteristics, modulating factors, and impact) B. 11 selected variables: Sex, hearing function, tinnitus perceptual characteristics, modulating factors, and severity |
A. 976, B. 761 | 2-step cluster analysis (SPSS) (probably silhouette measure for selection of number of groups) | Silhouette measure |
A. 4 groups 1. Tinnitus not easily influenced, higher hearing asymmetry, lower depression score. 2. Gradual onset of tinnitus, easily negatively influenced by loud sounds and sleep deprivation. 3. Tinnitus less loud with loud sounds, no effect from sleep deprivation or nap. 4. Acute onset tinnitus, tinnitus easily negatively influenced by loud sounds or sleep deprivation. B. 3 groups 1. Tinnitus not easily influenced, preference for noisy environments, tinnitus mostly unilateral, low tinnitus severity scores, lower depression scores, sounds not often uncomfortably loud. 2. Mainly males, tinnitus worse by stress, loud sounds and movement of head and neck, preference for noisy environments, sometimes sounds are uncomfortably loud, most with no or slight HL, bilateral tinnitus with variable loudness. 3. Tinnitus worse by loud sounds and stress, prefer silent environment, often find sounds uncomfortably loud, tinnitus often bilateral, most with no, slight, or asymmetric HL, variable loudness. |
| Langguth, Landgrebe [27] | Hearing function at 7 frequencies (0.125, 0.250, 0.5, 1, 2, 4, and 8 kHz) for each ear (categorically coded as normal, mild/moderate loss, severe/profound loss, or no data) | 2838 | Latent class analysis (tested 2–12 groups and used BIC to determine optimal solution) | Comparison of subgroups against variables not used for subgrouping (demographics, tinnitus severity, depressive symptomatology, and various tinnitus characteristics) |
8 groups: 1. Lacking audiometry: phenotypic characteristics similar to average. 2. Bilateral high frequency HL: more males, more often tonal tinnitus. 3. Near normal hearing: the youngest, youngest age at onset, lowest tinnitus severity, more often tonal tinnitus. 4. Bilateral medium-high frequency (2 kHz and above) HL: more males, gradual tinnitus onset. 5. Severe pantonal HL: the oldest, more females, older age at onset, highest tinnitus severity, highest depression scores, gradual tinnitus onset. 6. Left-sided pantonal medium HL: more females, older age at onset, more often abrupt tinnitus onset, left-sided tinnitus. 7. Right-sided pantonal severe HL: more often abrupt tinnitus onset and right-sided tinnitus, less often pulsatile tinnitus. 8. Left-sided pantonal severe HL: more often left sided and constant tinnitus. |
BIC: Bayesian Information Criterion; ENT: Ear, Nose, Throat; HF: High frequency; HL: Hearing Loss; MML: Minimal Masking Level; MRI: Magnetic Resonance Imaging; PET: Positron Emission Tomography; PTA: Pure Tone Average; SPSS: Statistical Package for the Social Sciences.