| BackgroundTreatment-resistant depression is one of the most debilitating psychiatric disorders. Around30-40%major depressive disorder patients are subsequently diagnosed with this disorder for their recurrent depressive episodes, and unsatisfactory responses of meditation and psychological treatments. At the moment, the pathological mechanism underpinning this particular mood disorder is still unclear, which causes marked amount of resources from both medical and social welfare systems consumed in finding a proper treatment for this disorder. Treatment-resistant depression, as the most severe depressive form, often displays a negative emotion bias as its core syndrome of "emotion-laden" cognitive impairment as well as some "emotion-neutral" cognitive impairment (e.g., attention). Aside from those cognitive malfunctions, clinical studies also unveil the truth that most patients with treatment-resistant depression are cormorbid with the borderline personality disorder. Therefore, full understandings of the pathological mechanisms of treatment-resistant depression require the clarification of its comorbidity with borderline personality disorder as well as the disentangling of the dysfunctions of cerebral cognitive and emotional information processing. These efforts would eventually add our basic knowledge about how to improve the diagnostic accuracy and the treatment responsibility of treatment-resistant depression.Aims1. To study the "emotion-neutral" cerebral pre-attention cognitive function in treatment resistant depression.2. To study the "emotion-laden" cerebral cognitive function of processing facial expressions of emotion in treatment resistant depression.3. To investigate the functional contribution of borderline personality disorder into its comorbidity with treatment-resistant depression given the above mentioned two cerebral cognitive functions, and to distinguish the impartment patterns of the comorbidity condition from treatment-resistant depression itself.Methods1. The Mismatch Negativity (MMN) test was applied in32healthy controls and22patients with treatment-resistant depression,19with borderline personality disorder, and22with their comorbidity to record the MMN component of the Event-related Potentials (ERPs).2. The Oddball paradigm with four basic facial expressions of emotion (i.e., Neutral, Anger, Happiness, and Sadness) was applied in37healthy controls and25patients with treatment-resistant depression,15with borderline personality disorder, and22with their comorbidity to record the ERP components of N1, P2, N2, P3a, and P3b.3. The multiple-way ANOVA (MANOVA) was employed to test the variences of the amplitudes and latencies of N1and MMN among the four groups.4. The MANOVA was employed to test the variences of the amplitudes and latencies of the facial expressions of emotion evoked N1, P2, N2, P3a, and P3b among the four groups.5. We measured depressive tendencies in all participants with the Plutchik-van Praag Depression Inventory (PVP), and correlated the PVP sores with the age, duration of life-long depression, reaction times, and amplitudes and latencies of MMN and facial expressions of emotion evoked ERPs.Results1. The amplitude of MMN in treatment-resistant depression patients was significantly larger than those of all other groups. However, the amplitudes and latencies of MMN in patients of borderline personality disorder and their comorbidity condition did not differ significantly from those of the healthy controls.2. There was no group difference regarding either the amplitude or the latency of N1(N170), P2, N2, P3a or P3b to the four facial epressions of emotions.3. Reaction times to Anger, Happiness, and Sadness in treatment-resistant depression patients, and those to Anger and Happiness in the comorbidity patients were longer than those in the healthy controls. There was no significant difference of reaction times between borderline personality disorder patients and healthy controls.4. PVP sores positively correlated with the P2latency to Anger in the comorbidity patients. In addition, reaction times to the four facial expressions of emotion positively correlated with their depressive moods in all participants.Conclusions1. The cerebral pre-attention cognitive function might be deteriorated in the treatment-resistant depression patients, rather than in the patients with borderline personality disorder or their comorbidity.2. The cerebral cognitive function of processing facial expressions of emotion remained intact in patients with treatment-resistant depression, borderline personality disorder, and their comorbidity. 3. Treatment-resistant depression patients showed abnormal response patterns for Anger, Happiness, and Sadness, and the comorbidity patients for Anger and Happiness in later stage of "emotion-laden" cognitive information processing.4. The unaffected cerebral pre-attention and cognitive function of processing facial expressions of emotion in borderline personality disorder might contribute to the corresponding cerebral funtions in the comorbidity patients.To sum up, the present thesis is based on two published original articles from this PhD candidate (Firs author, Prog Neuro-Psychoph2010and2012), applying the high temporal resolution neurophysiologcial technology-ERPs to investigate the cerebral functions of pre-attention and processing of facial expressions of emotion in treatment-resistant depression. Focusing on the temoporal dimension, this study has shown the specific cerebral pre-attention dysfunction and the unaffected cerebral cognitive function of processing facial expressions of emotion in patients with treatment-resistant depression. Meanwhile, the present study also suggests that the comorbidity with borderline personality disorder might affect the patterns of these two cerebral cognitive functions in treatmet-resistant depression, which highlights the importance of referring to the comorbidity condition when studying severe psychiatric disorders such as the treatment-resistant depression. |
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