Background: The few previous studies on resting-state electroencephalography (EEG) microstates in depressive patients suggest altered temporal characteristics of microstates compared to those of healthy subjects. We tested whether resting-state microstate temporal characteristics could capture large-scale brain network dynamic activity relevant to depressive symptomatology. Methods: To evaluate a possible relationship between the resting-state large-scale brain network dynamics and depressive symptoms, we performed EEG microstate analysis in 19 patients with moderate to severe depression in bipolar affective disorder, depressive episode, and recurrent depressive disorder and in 19 healthy controls. Results: Microstate analysis revealed six classes of microstates (A–F) in global clustering across all subjects. There were no between-group differences in the temporal characteristics of microstates. In the patient group, higher depressive symptomatology on the Montgomery–Åsberg Depression Rating Scale correlated with higher occurrence of microstate A (Spearman’s rank correlation, r = 0.70, p < 0.01). Conclusion: Our results suggest that the observed interindividual differences in resting-state EEG microstate parameters could reflect altered large-scale brain network dynamics relevant to depressive symptomatology during depressive episodes. Replication in larger cohort is needed to assess the utility of the microstate analysis approach in an objective depression assessment at the individual level.
The cortico-striatal-pallidal-thalamic and limbic circuits are suggested to play a crucial role in the pathophysiology of depression. Stimulation of deep brain targets might improve symptoms in treatment-resistant depression. However, a better understanding of connectivity properties of deep brain structures potentially implicated in deep brain stimulation (DBS) treatment is needed. Using high-density EEG, we explored the directed functional connectivity at rest in 25 healthy subjects and 26 patients with moderate to severe depression within the bipolar affective disorder, depressive episode, and recurrent depressive disorder. We computed the Partial Directed Coherence on the source EEG signals focusing on the amygdala, anterior cingulate, putamen, pallidum, caudate, and thalamus. The global efficiency for the whole brain and the local efficiency, clustering coefficient, outflow, and strength for the selected structures were calculated. In the right amygdala, all the network metrics were significantly higher (p < 0.001) in patients than in controls. The global efficiency was significantly higher (p < 0.05) in patients than in controls, showed no correlation with status of depression, but decreased with increasing medication intake ( $${{\bf{R}}}^{{\bf{2}}}{\boldsymbol{=}}{\bf{0.59}}\,{\bf{and}}\,{\bf{p}}{\boldsymbol{=}}{\bf{1.52}}{\bf{e}}{\boldsymbol{ \mbox{-} }}{\bf{05}}$$ ). The amygdala seems to play an important role in neurobiology of depression. Practical treatment studies would be necessary to assess the amygdala as a potential future DBS target for treating depression.
Background: Neuroimaging studies provided evidence for disrupted resting-state functional brain network activity in bipolar disorder (BD). Electroencephalographic (EEG) studies found altered temporal characteristics of functional EEG microstates during depressive episode within different affective disorders. Here we investigated whether euthymic patients with BD show deviant resting-state large-scale brain network dynamics as reflected by altered temporal characteristics of EEG microstates. Methods: We used high-density EEG to explore between-group differences in duration, coverage, and occurrence of the resting-state functional EEG microstates in 17 euthymic adults with BD in on-medication state and 17 age- and gender-matched healthy controls. Two types of anxiety, state and trait, were assessed separately with scores ranging from 20 to 80. Results: Microstate analysis revealed five microstates (A–E) in global clustering across all subjects. In patients compared to controls, we found increased occurrence and coverage of microstate A that did not significantly correlate with anxiety scores. Conclusion: Our results provide neurophysiological evidence for altered large-scale brain network dynamics in BD patients and suggest the increased presence of A microstate to be an electrophysiological trait characteristic of BD.
Objective: The cytochrome P450 2D6 (CYP2D6) is an enzyme involved in the oxidative biotransformation of various widely used drugs, including paroxetine, a substrate and strong inhibitor of the enzyme. The aim is to report on a case of protracted intoxication with paroxetine after a single overdose in a genotype-predicted intermediate CYP2D6 metabolizer.Observation: A 49-year-old man was receiving chronic treatment for more than 6 years with paroxetine 60 mg/day for an indication of agoraphobia. The patient ingested fifty 20 mg tablets of paroxetine in a suicide attempt. The toxic plasma level, accompanied by delirium, persisted for approximately 1 month after the overdose. According to the genotype profile, the patient was evaluated as an intermediate metabolizer with reduced CYP2D6 enzyme activity.Conclusion: As a consequence of the suicide attempt with overdose and the chronic paroxetine treatment that preceded it, phenoconversion to a poor metabolizer with very low CYP2D6 enzyme activity is suggested as contributing to an extremely long intoxication accompanied by delirium. Prolonged monitoring over a standard 24 h of both physical symptoms and drug plasma levels, together with a genetic profile assessment and phenoconversion consideration, is recommended after a single overdose in patients chronically treated with paroxetine.