Cortical activation for adolescent-onset minor depression and major depressive disorder: an fNIRS study

Depression is characterized by depressed mood, lack of interest and low energy, with additional clinical symptoms including poor concentration, feelings of guilt or worthlessness, appetite changes, sleep disturbances, psychomotor retardation or agitation, suicide attempt or thoughts, et al. There are several different subtypes of depression based on specific clinical symptoms (melancholic depression, psychotic depression), onset (seasonal affective disorder, postpartum, early versus late in life), course (single, recurrent, chronic), and severity. According to Diagnostic and Statistical Manual of Mental Disorders (DSM-5), depression have severity specifiers as mild, moderate and severe, also other specifiers such as with anxious distress, mixed feature, et al. When looking at patients suffering from depressive symptoms, some of them meet the criteria of full-blown Major Depressive Disorder (MDD), however, others do not meet the diagnostic criteria (such as clinical symptoms, severity, or illness duration), who are often regarded as having minor (or subsyndromal/subthreshold) depression. Minor depression was defined as ‘having two or more depressive symptoms for at least two weeks, accompanied by social dysfunction’ by Judd, et al. [1].

With regard to the treatment of antidepressants, patient-level meta-analysis showed minimal or non-benefit for patients suffering from minor depression and substantial benefit for patients having MDD [2].

The prevalence of minor depression ranges from 2.5 to 16% in community and primary care settings, and the prevalence is particularly higher in elderly patients [3, 4]. Individuals with minor depression are at higher risk of developing MDD and are more likely to have depressive episodes [5], as 12% of individuals with minor depression developed into MDD after a 3-year follow-up [6]. Risk factors for developing MDD from minor depression include poor social support, recurring short episodes of depressive symptoms, anxiety disorders, substance use disorders, suicidal thoughts across the lifetime, a chronic physical problem, and diminished social functioning, et al. Though minor depression occurs at a higher prevalence and causes a greater burden to personal, family and society, less is known about the diagnosis of minor depression.

Previous studies about neural correlates of minor depression focused on late-life patients. Fewer studies paid attention to adolescents. However, adolescents with depression are increasing, with a large number of adolescents suffering from minor depression [7]. Ghazi et al. used DTI (Diffusion Tensor Imaging) to explore the mechanism of young adults with subthreshold depressive symptoms and observed significantly reduced microstructural changes (using fractional anisotropy value, FA) in the depression symptoms group compared to the control group [8]. Polyakova et al. did not observe the difference in cortical thickness between the minor depression group and healthy subjects [9], which is also not observed in late-life minor depression and health controls [9].

fMRI was used by previous studies to investigate biomarkers of MDD and minor depression. However, most studies explored the difference between MDD and HC, and pervasively differentiated brain areas were observed between the MDD and HC groups, such as DLPFC, precuneus, amygdala, et al. [10,11,12]. The underlying neural mechanism for depressive symptoms was reported, however still lacking, for example, the changes in the left hippocampus and left caudate nucleus nodal centrality was correlated with the severity of depression severity (HAMD scores) [12]; some studies focused on minor depression and HC [13, 14], as left middle frontal gyrus(MFG), right precuneus, superior frontal gyrus(SFG), and hippocampus were reported; a significant positive correlation between Beck Depression Inventory- II (BDI-II, a 21 items self scale for assessing the severity of depression, higher score indicating severe depressive symptoms) scores and resting-state brain functional connectivity from MFG to hippocampus was reported. Fewer studies investigated the difference of MDD and minor depression. These studies suggest that MDD and minor depression lead to changes in a wide range of brain regions. The high spatial resolution of fMRI provided advantage for research, but the price limited its use. Functional near-infrared spectroscopy (fNIRS) has higher temporal resolution, lower cost, is harmless, and provides unlimited application scenes, which has been widely used for understanding mental disorders, including schizophrenia, bipolar disorder, depressive disorder, and other mental illness [15, 16]. fNIRS is used to measure the changes of oxygenated hemoglobin and deoxygenated hemoglobin at the cortical level (frontal and temporal areas) [17,18,19,20,21].

Previous reports compared the neuro mechanism of depression and healthy controls using fNIRS, for example, Dong et al. [22] observed reduced prefrontal activation (bilateral VLPFC and OFC) in the MDD group. Kim et al. [23] compared the change of oxy-Hb in young adults (18–34 years old) with MDD and suicidality. They found prefrontal oxygenation (right VLPFC) was lowest in MDD group with suicidality, compared with MDD group and healthy controls. Wang et al. [24] divided 41 college students into higher and lower depressive tendencies groups based on their BDI scores. Higher depression groups showed higher deactivation of oxyhemoglobin (HbO) in the superior external frontal cortex (BA46), inferior frontal gyrus (BA45), premotor cortex (BA6), and primary motor cortex (BA4). Liu et al. reported that significantly lower cortical activation was demonstrated in the prefrontal cortex (PFC) in adolescents with depression [25].

The current study hypothesizes that frontal and temporal cortex activation is lower in the minor depression group compared with the HC group, and higher compared with the MDD group. The present study also aimed to examine the neurological mechanisms of clinical symptoms (depressive and anxious symptoms) using fNIRS in MDD and minor depression groups separately.

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