Gamma band oscillations

McNally, James M.; McCarley, Robert W.

doi:10.1097/yco.0000000000000244

Cited by 119 publications

(72 citation statements)

References 90 publications

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“…Another strategy is to explore medicines that ameliorate dysfunctional GABAergic neurons. The latter strategy is based on the concept that the hypofunction of NMDA receptors located on GABAergic neurons leads to the attenuated activity of GABAergic neurons, and this, in turn, produces abnormal gamma oscillations and cognitive deficits in schizophrenia patients ( 113 ).…”

Section: A Direction Of Novel Therapeuticsmentioning

confidence: 99%

“…Furthermore, Nakamura et al ( 120 ) reported that the oral administration of T-817MA ameliorated behavioral, histological, and neurophysiological changes, such as deficits in prepulse inhibition, reduced levels of parvalbumin-immunoreactive neurons in the medial prefrontal cortex, hippocampus, and amygdala, and a deficit in the auditory phase-locked gamma oscillation in a mouse model of schizophrenia. The modulation of gamma band activity is noteworthy, because abnormal gamma band activity is thought to underlie the psychosis and cognitive deficits, and is considered a target for potential therapeutic interventions ( 113 ).…”

Section: A Direction Of Novel Therapeuticsmentioning

confidence: 99%

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Early Intervention and a Direction of Novel Therapeutics for the Improvement of Functional Outcomes in Schizophrenia: A Selective Review

Kurachi¹,

Takahashi

Sumiyoshi

et al. 2018

Front. Psychiatry

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BackgroundA recent review reported that the median proportion of patients recovering from schizophrenia was 13.5% and that this did not change over time. Various factors including the duration of untreated psychosis, cognitive impairment, negative symptoms, and morphological changes in the brain influence the functional outcome of schizophrenia. The authors herein reviewed morphological changes in the brain of schizophrenia patients, effects of early intervention, and a direction of developing novel therapeutics to achieve significant improvement of the functional outcome.MethodsA selective review of the literature including studies from our department was performed.ResultsLongitudinal structural neuroimaging studies on schizophrenia revealed that volume reductions in the peri-Sylvian regions (e.g., superior temporal gyrus and insula), which are related to positive psychotic symptoms, progress around the onset (critical stage) of schizophrenia, but become stable in the chronic stage. On the other hand, morphological changes in the fronto-thalamic regions and lateral ventricle, which are related to negative symptoms, neurocognitive dysfunction, and the functional outcome, progress during both the critical and chronic stages. These changes in the peri-Sylvian and fronto-thalamic regions may provide a pathophysiological basis for Crow’s two-syndrome classification. Accumulated evidence from early intervention trials suggests that the transition risk from an at-risk mental state (ARMS) to psychosis is approximately 30%. Differences in the cognitive performance, event-related potentials (e.g., mismatch negativity), and brain morphology have been reported between ARMS subjects who later developed psychosis and those who did not. Whether early intervention for ARMS significantly improves the long-term recovery rate of schizophrenia patients remains unknown. With respect to the development of novel therapeutics, animal models of schizophrenia based on the N-methyl-d-aspartate receptor hypofunction hypothesis successfully mimicked behavioral changes associated with cognitive impairments characteristic of the disease. Furthermore, these animal models elicited histological changes in the brain similar to those observed in schizophrenia patients, i.e., decreased numbers of parvalbumin-positive interneurons and dendritic spines of pyramidal neurons in the frontal cortex. Some antioxidant compounds were found to ameliorate these behavioral and histological abnormalities.ConclusionEarly intervention coupled with novel therapeutics may offer a promising approach for substantial improvement of the functional outcome of schizophrenia patients.

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Section: A Direction Of Novel Therapeuticsmentioning

confidence: 99%

Section: A Direction Of Novel Therapeuticsmentioning

confidence: 99%

Early Intervention and a Direction of Novel Therapeutics for the Improvement of Functional Outcomes in Schizophrenia: A Selective Review

Kurachi¹,

Takahashi

Sumiyoshi

et al. 2018

Front. Psychiatry

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“…However, these findings have not translated to better treatments for those with schizophrenia. The three primary symptom groups, positive, cognitive and negative (Box 1 ), have been associated with reports of abnormalities in virtually every neurotransmitter system 1 – 5 . The onset of psychotic symptoms, which is strongly associated with alterations in dopamine function, is a key feature underpinning a clinical diagnosis 6 , 7 .…”

Section: Introductionmentioning

confidence: 99%

Dopamine, psychosis and schizophrenia: the widening gap between basic and clinical neuroscience

et al. 2018

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The stagnation in drug development for schizophrenia highlights the need for better translation between basic and clinical research. Understanding the neurobiology of schizophrenia presents substantial challenges but a key feature continues to be the involvement of subcortical dopaminergic dysfunction in those with psychotic symptoms. Our contemporary knowledge regarding dopamine dysfunction has clarified where and when dopaminergic alterations may present in schizophrenia. For example, clinical studies have shown patients with schizophrenia show increased presynaptic dopamine function in the associative striatum, rather than the limbic striatum as previously presumed. Furthermore, subjects deemed at high risk of developing schizophrenia show similar presynaptic dopamine abnormalities in the associative striatum. Thus, our view of subcortical dopamine function in schizophrenia continues to evolve as we accommodate this newly acquired information. However, basic research in animal models has been slow to incorporate these clinical findings. For example, psychostimulant-induced locomotion, the commonly utilised phenotype for positive symptoms in rodents, is heavily associated with dopaminergic activation in the limbic striatum. This anatomical misalignment has brought into question how we assess positive symptoms in animal models and represents an opportunity for improved translation between basic and clinical research. The current review focuses on the role of subcortical dopamine dysfunction in psychosis and schizophrenia. We present and discuss alternative phenotypes that may provide a more translational approach to assess the neurobiology of positive symptoms in schizophrenia. Incorporation of recent clinical findings is essential if we are to develop meaningful translational animal models.

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“…In many subjects with schizophrenia, PFC PV neurons have 1) lower transcript and protein levels of PV and of a key GABA-synthesizing enzyme, GAD67 (Lewis et al, 2012; Mitchell et al, 2015), 2) compromised integrity of perineuronal nets (PNNs) which regulate structural and synaptic functions (Berretta et al, 2015; Enwright et al, 2016), and 3) lower density of excitatory inputs onto their somata (Chung et al, 2016a). These molecular and structural alterations are thought to impair GABA neurotransmission and to contribute to the lower power of PFC gamma oscillations seen in individuals with schizophrenia (McNally and McCarley, 2016). Indeed, in vivo studies indicate that measures of extracellular GABA, which more closely approximate synaptic GABA than do measures of total GABA levels, are lower in subjects with schizophrenia (Frankle et al, 2015).…”

mentioning

confidence: 99%