Table 2 Neural correlates of depressive symptoms in 19 studies with functional MRI.
Source | No. of SSDs | Diagnostic Tool | Male, No./Total No. (%) | Age, mean (SD), y | QA score† | Main depressive symptoms measure(s) | Main neuroimaging measure(s) | Main finding |
|---|---|---|---|---|---|---|---|---|
rs-fMRI | ||||||||
Li et al., 202357 | 88 SCZ | DSM-IV | 38/88 (43.2) | 28.8 (8.3) | 6 | PANSS- depression factor score | Whole-brain amplitude of low-frequency fluctuations (ALFF) | The degree of ALFF increase in the dorsolateral region of the superior frontal gyrus after treatment with second-generation antipsychotics was significantly and positively related to the magnitude of the decrease in depression factor score. |
Doucet et al., 202056 | 76 SCZ | DSM-5 | 57/76 (75.0) | 26.9 (7.0) | 7 | BPRS-depression and anxiety subscale | Network-based functional connectivity | Strong mode of covariation linking functional network connectivity to clinical response; and particularly to improvement in positive and anxious/depressive symptoms. Higher internal cohesiveness of the default mode network was the single most important positive predictor. Key negative predictors involved the functional cohesiveness of central executive subnetworks anchored in the frontoparietal cortices and subcortical regions (including the thalamus and striatum) and the inter-network integration between the default mode and sensorimotor networks. |
Lee et al., 2019a 55 | 79 SCZ Good 25 Mod 31 Poor 23 | DSM-IV | Good 15/25 (60.0) Mod 16/31 (51.6) Poor 12/23 (52.2) | Good 41.0 (7.1) Mod 37.8 (7.5) Poor 37.3 (7.0) | 6 | BPRS- affect subscale | Functional connectivity of the default mode network | Default mode network connectivity in the right ventromedial prefrontal cortex negatively correlated with affect subscale scores in SCZ. |
Xu et al., 201934 | 84 SCZ & SAD | DSM-IV | 59/84 (70.2) | 34.9 (11.0) | 3 | PANSS- depression factor score | Seed-based functional connectivity of substantia nigra/ventral tegmental area | No correlation was found between depressive symptoms and substantia nigra/ventral tegmental area-seeded resting state functional connectivity. |
Lee et al., 201854 | 85 SCZ | DSM-5 | 64/85 (75.3) | 27.2 (7.3) | 7 | BPRS-depression and anxiety subscale | Network-based functional connectivity | The best stepwise multiple regression model explained 12% of the variance in depressive symptom severity in patients with recent-onset schizophrenia. The neuroimaging variables that made a statistically significant contribution to the model were the within-network connectivity of the salience network and the connectivity between salience-language networks and somatomotor-auditory networks. For any unit increase in any of these connectivity measures, the model predicted lower scores in BPRS anxiety/depression symptoms. |
Ohta et al., 201840 | 21 SCZ | DSM-IV | 11/21 (52.4) | 42.3 (10.2) | 5 | CDSS | Functional connectivity of the salience network | Structural equation model revealed significant and moderate-to-strong negative associations between the right pallidum functional connectivity and CDSS total scores, and between CDSS total scores and quality of life scale scores. |
Son et al.,201753 | 41 SCZ | DSM-IV | 20/41 (48.8) | 37.5 (8.6) | 7 | PANSS- depression factor score | Functional connectivity of the frontoparietal network | Mean connectivity of the left frontoparietal network was negatively correlated with the score of PANSS depressive factor in SCZ. |
Su et al., 201541 | 49 SCZ | DSM-IV | 22/49 (44.9) | 38.4 (13.4) | 5 | PANSS- depression and anxiety subscale | Whole-brain Small-world network metrics (global and network efficiency) | Depression and anxiety symptoms were observed to be correlated with the global efficiency of mid-distance subnetworks (edge 40–80 mm). Among patients with SCZ, integrated global network efficiency values were significantly correlated with depression and anxiety symptoms. |
Orliac et al., 201352 | 26 SCZ | DSM-IV | 20/26 (76.9) | 35.6 (8.9) | 6 | PANSS-general subscale (G6 item) | Intra-network connectivity strength of the salience network and default mode | Functional connectivity of the left striatum cluster showed a trend toward a negative correlation with PANSS-General Psychopathology subscale score. The same analysis with PANSS-General Psychopathology items revealed that the negative correlation was found only significant with the G6 item “depression”. |
task-fMRI | ||||||||
Athanassiou et al., 2021b 51 | 62 SCZ SB– 42 SB + 20 | DSM-5 | SB– 36/42 (85.7) SB + 18/20 (90.0) | SB– N/A SB + N/A | 6 | PANSS- depression and anxiety subscale | Whole-brain functional activity | No significant correlation was observed between brain activations of the left median cingulate gyrus, left middle frontal gyrus, and left precuneus during an emotional processing task and affective symptoms. |
Kvarta et al., 202142 | 18 SAD & SSDs not specified | DSM-IV | 10/18 (55.6) | 40.8 (13.7) | 5 | MTSD | Whole-brain functional activity | Anticipatory stress by ankle-shock task-induced ventral anterior cingulate cortex cluster activation significantly and inversely correlated with trait depression scores in SSD. |
Kirschner et al.,201643 | 27 SCZ | DSM-IV | 18/27 (66.7) | 31.9 (7.1) | 5 | CDSS | Functional activity of the ventral striatum | When looking at potential confounding variables, a significant positive bivariate correlation between CDSS total score and left ventral striatum activation during reward anticipation while performing a Monetary Incentive Delay Task was found in individuals with SCZ. |
Kumari et al., 2016c 44 | 63 SCZ & SAD Min Dep 25 Mild Dep 17 Sev Dep 21 | DSM-IV | Min Dep 20/25 (80.0) Mild Dep 12/17 (70.6) Sev Dep 14/21 (66.7) | Min Dep 39.4 (9.8) Mild Dep 34.8 (8.2) Sev Dep 39.6 (10.6) | 5 | BDI-II | Whole-brain functional activity | BDI-II scores correlated significantly positively with activity during fearful expressions (fearful > no face) in the left thalamus extending to the para post-pre-central gyrus, putamen-globus pallidus, supramarginal gyrus, insula, and inferior-middle frontal gyrus. BDI-II scores also correlated significantly positively with activity for fearful expressions when compared with neutral (fearful > neutral) expressions in the right superior frontal gyrus extending to the middle/medial frontal, left precentral, and left anterior cingulate gyri. There was significantly higher activity across the thalamic and superior frontal gyrus clusters in the moderate-to-severe depression subgroup, relative to no/minimal, and mild depression. |
Lindner et al., 201650 | 36 SCZ | DSM-IV | 23/36 (63.9) | 30.6 (8.0) | 7 | BDI | Whole-brain functional activity | In a multiple regression analysis predicting the mean activation of right and left amygdala clusters in response to threat-related facial expression by the Scale for assessment of negative symptoms (SANS) global flat affect score, BDI, State-Trait-Anxiety-Inventory trait score, duration of illness, verbal intelligence, age and gender, SANS global flat affect score was the only significant predictor. |
Stephan-Otto et al., 201645 | 20 SCZ | DSM-IV | 12/20 (60.0) | 39.9 (11.5) | 5 | CDSS | Functional activity of vision-related brain regions | Activation in the right middle occipital gyrus during object perception was positively associated with CDSS and HAMRS. CDSS total score was found to be associated with increased activation in the bilateral calcarine gyrus, right precuneus, and left supramarginal gyrus during object perception, controlling for the effects of HAMRS. |
Arrondo et al., 201546 | 22 SCZ | DSM-IV | 19/22 (86.4) | 32.7 (7.6) | 5 | BDI | Whole-brain functional activity | A negative correlation between the severity of depression (BDI score) and ventral striatum activity during reward anticipation was found in the SCZ group. |
Lee et al., 2015d 47 | 28 SCZ SH– 14 SH + 14 | DSM-IV | SH– 11/14 (78.6) SH + 12/14 (85.7) | SH– 38.9 (7.3) SH + 43.6 (11.3) | 4 | CDSS | Whole-brain functional activity | In the self-harm patient group, activity in the left posterior cingulate cortex was negatively correlated with CDSS scores. This association was not found to be significant in the non-self-harm patient group. |
Simon et al.,201048 | 15 SCZ & SAD | DSM-IV | 10/15 (66.7) | 26.3 (5.4) | 5 | CDSS | Functional activity of medial orbitofrontal cortex and ventral striatum | A significant negative correlation was found between ventral striatum activation in patients with schizophrenia during the receipt of a reward while performing a monetary incentive delay task and CDSS. |
sMRI & rs-fMRI | ||||||||
Liang et al., 2023e 49 | 312 SCZ & SAD SCZ 178 SAD 134 | DSM-IV | SCZ 124/178 (69.7) SAD 58 /134 (37.7) | SCZ 34.5 (12.0) SAD 36.3 (12.3) | 5 | MADRS | Whole-brain fractional amplitude of low-frequency fluctuations (fALFF) | In SCZ, MADRS scores were positively associated with fALFF in the thalamus and hippocampus. In SAD, MADRS scores were positively associated with fALFF in the lingual and frontal gyrus. |
