Frontostriatal deficits in unipolar major depression
ABSTRACT Recent accounts of major depression have tended to focus on dysfunction of frontothalamic-striatal reentrant circuits as a possible source of the disorder. Evidence of frontostriatal involvement in unipolar major depression from lesion and neuropsychological studies, and functional and structural imaging studies is examined. The high incidence of depressive symptomatology following left frontal and basal ganglia lesions implicate these as possible sites of dysfunction. Neuropsychological evidence indicates similar deficits in patients with major depression, perhaps with dorsolateral prefrontal deficits most prominent. Structural imaging studies report frontal and basal ganglia (BG) abnormalities particularly in cases of late-age onset depression. Resting state functional imaging studies show deficits in dorsolateral, anterior cingulate (medial frontal), and BG structures. Activation imaging studies show less consistent evidence of dorsolateral deficit, while anterior cingulate deficit is more consistently demonstrated. Variability in findings across studies may reflect differences between subtypes of depression and differences in methodology. Possible involvement of the BG in the psychomotor retardation of depression is examined. It is concluded that, while there is evidence of frontostriatal deficit in major depression, the exact nature of such deficits is uncertain. Issues such as component vs. system dysfunction need to be addressed.
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ABSTRACT: The success of serotonin-selective reuptake inhibitors has lent support to the monoamine theory of major depressive disorder (MDD). This issue has been addressed in a number of molecular imaging studies by positron emission tomography or single-photon emission computed tomography of serotonin reuptake sites (5-HTT) in the brain of patients with MDD, with strikingly disparate conclusions. Our meta-analysis of the 18 such studies, totaling 364 MDD patients free from significant comorbidities or medication and 372 control subjects, revealed reductions in midbrain 5-HTT (Hedges' g=-0.49; 95% CI: (-0.84, -0.14)) and amygdala (Hedges' g=-0.50; 95% CI: (-0.78, -0.22)), which no individual study possessed sufficient power to detect. Only small effect sizes were found in other regions with high binding (thalamus: g=-0.24, striatum: g=-0.32, and brainstem g=-0.22), and no difference in the frontal or cingulate cortex. Age emerged as an important moderator of 5-HTT availability in MDD, with more severe reductions in striatal 5-HTT evident with greater age of the study populations (P<0.01). There was a strong relationship between severity of depression and 5-HTT reductions in the amygdala (P=0.01). Thus, molecular imaging findings indeed reveal widespread reductions of ∼10% in 5-HTT availability in MDD, which may predict altered spatial-temporal dynamics of serotonergic neurotransmission.Journal of Cerebral Blood Flow & Metabolism advance online publication, 7 May 2014; doi:10.1038/jcbfm.2014.82.Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 05/2014; · 5.46 Impact Factor
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ABSTRACT: To illuminate candidate neural working mech-anisms of Mindfulness-Based Cognitive Therapy (MBCT) in the treatment of recurrent depressive disorder, parallel to the potential interplays between modulations in electro-cortical dynamics and depressive symptom severity and self-compassionate experience. Linear and nonlinear α and γ EEG oscillatory dynamics were examined concomitant to an affective Go/NoGo paradigm, pre-to-post MBCT or natural wait-list, in 51 recurrent depressive patients. Spe-cific EEG variables investigated were; (1) induced event-related (de-) synchronisation (ERD/ERS), (2) evoked power, and (3) inter-/intra-hemispheric coherence. Sec-ondary clinical measures included depressive severity and experiences of self-compassion. MBCT significantly downregulated α and γ power, reflecting increased cortical excitability. Enhanced α-desynchronisation/ERD was observed for negative material opposed to attenuated α-ERD towards positively valenced stimuli, suggesting acti-vation of neural networks usually hypoactive in depression, related to positive emotion regulation. MBCT-related increase in left-intra-hemispheric α-coherence of the fron-to-parietal circuit aligned with these synchronisation dynamics. Ameliorated depressive severity and increased self-compassionate experience pre-to-post MBCT corre-lated with α-ERD change. The multi-dimensional neural mechanisms of MBCT pertain to task-specific linear and non-linear neural synchronisation and connectivity network dynamics. We propose MBCT-related modulations in dif-fering cortical oscillatory bands have discrete excitatory (enacting positive emotionality) and inhibitory (disengag-ing from negative material) effects, where mediation in the α and γ bands relates to the former. Keywords Major Depressive Disorder (MDD) · Mindfulness-Based Cognitive Therapy (MBCT) · ERD/ERS · Oscillatory EEG · α-Band coherence · γ-Band · EEG power IntroductionCognitive Neurodynamics 02/2015; 9(1):13-29. · 1.77 Impact Factor
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ABSTRACT: Neuropsychiatric symptoms (NPS) are very common in neurodegenerative diseases and are a major contributor to disability and caregiver burden. There is accumulating evidence that NPS may be a prodrome and/or a “risk factor” of neurodegenerative diseases. The medications used to treat these symptoms in younger patients are not very effective in patients with neurodegenerative disease and may have serious side effects. An understanding of the neurobiology of NPS is critical for the development of more effective intervention strategies. Targeting these symptoms may also have implications for prevention of cognitive or motor decline. Molecular brain imaging represents a bridge between basic and clinical observations and provides many opportunities for translation from animal models and human post-mortem studies to in vivo human studies. Molecular brain imaging studies in Alzheimer's disease (AD) and Parkinson's disease (PD) are reviewed with a primary focus on positron emission tomography studies of NPS. Future directions for the field of molecular imaging in AD and PD to understand the neurobiology of NPS will be discussed.Neuroscience & Biobehavioral Reviews 11/2014; 49. · 10.28 Impact Factor