Irregular reward-related responses in the nucleus accumbens (NAcc) have been reported
Irregular reward-related responses in the nucleus accumbens (NAcc) have been reported for major depressive disorder (MDD) patients. suicidal ideation Rabbit Polyclonal to MYLIP and anhedonia symptoms. The intermediate subjects had less severity in these symptoms. These results suggest that differing propensities in incentive responsiveness in the NAcc may impact the development of specific symptoms in MDD. Major depressive disorder (MDD) 16676-29-2 supplier is a heterogeneous disease associated with multiple symptoms and showing large variability across individuals. The Diagnostic and Statistical Manual of Mental Disorders (DSM) assigns the analysis of MDD to individuals with heterogeneous medical syndromes1. Multiple sign factors including stressed out feeling, anhedonia, psychomotor symptoms, and somatic symptoms, are characteristic of MDD2, maybe explaining why no single biomarker matches the clinically useful levels of specificity and level of sensitivity3. This heterogeneity needs to become accounted for in efforts to elucidate the neurobiological basis of MDD4,5. Abnormalities in incentive processing are considered a major component of MDD pathology6,7,8. Anhedonia is one of the two core symptoms, along with stressed out feeling, in MDD9. Irregular reward-related behaviors in various probabilistic learning and decision-making jobs10,11,12,13 as well as fMRI-measured mind activation in reward-processing areas such as the nucleus accumbens (NAcc), the striatum, and the medial prefrontal cortex have been reported in MDD14,15,16,17,18,19,20,21,22,23,24. Although abnormalities of incentive processing possess consistently been reported for MDD, the degree of dysfunction varies across studies8,25,26. Several studies showed reduced neural activity during the anticipation of prize16,18, while others showed reduced activity during receipt of rewards14,15,27 or in both anticipation and receipt of prize19,20,22. There is also another statement21 showed no difference at both anticipation and acceptance of incentive within the NAcc. This variability could be due to heterogeneity of MDD subjects. Indeed recent work28 reports two types of MDD subjects with higher and lower activity after incentive receipt compared to healthy control (HC) in the ventral tegmental area (VTA) and the ventral 16676-29-2 supplier striatum. The heterogeneity of MDD patients imposes limitations on the standard study approach, in which subjects are classified into case (MDD) and control groups based on their diagnoses and/or symptom measures and then a difference between the groups is examined. While some studies carefully selected the case subjects based on specific criteria (e.g. anhedonia), symptom-based selection does not necessarily ensure individual group homogeneity. As anhedonia is not a specific symptom in MDD, but can also be seen in schizophrenia, substance abuse disorders, Parkinsons disease, and over-eating patients9, identical symptoms are likely associated with different forms of neuropathology. For instance, distinct brain abnormalities have been reported in stressed out and schizophrenia patients with anhedonia27. Moreover, the control group may also be heterogeneous. Individual variability in activation of the NAcc has been reported for healthy subjects29,30,31. Deficits in reward-related brain responses similar to those reported in MDD have also been found in remitted MDD subjects32,33 and psychiatrically-healthy subjects with a parental history of depressive disorder34,35,36. A twins study37 indicated that more than 46% of incentive responsiveness could be explained by genetic factor, which suggest incentive responsiveness may reflect a genetically-influenced trait that is distributed across the populace. Heterogeneity in both MDD and HC groups and possible variability of associated neuropathology suggest that diagnosis- or symptom-based classification and comparison of group averages can limit elucidation of the neurobiological basis of MDD. Studies focusing on group common differences could have missed important information residing in individual variability, which might be able to explain heterogeneous symptoms in MDD. In this study, we focused on individual variability across subjects within a healthy and depressed group and its association with 16676-29-2 supplier depressive disorder symptoms. The importance of investigating individual variability within a diagnostic group has been raised in the Research Domain Criteria (RDoC) project of the National Institute of Mental 16676-29-2 supplier Health (NIMH) Strategic Plan5. RDoC suggested a dimensional approach, which examines the full range of variance from normal to abnormal among the fundamental functional components4,5. 16676-29-2 supplier In line with the RDoC dimensional approach, our study recognized heterogeneity of reward-related brain activation impartial of diagnosis and symptomatology. Specifically, we extracted subtypes of fMRI-measured NAcc activations to incentive and punishment using an unsupervised classification analysis for MDD and HC subjects together. The extracted subtypes were then used as a reference to extract symptom factors that correlated with the derived phenotypic subtypes. We coined.