Schizophrenia—An Overview

JAMA Psychiatry, Journal Year: 2019, Volume and Issue: 77(2), P. 201 - 201

Published: Oct. 30, 2019

Importance

Schizophrenia is a common, severe mental illness that most clinicians will encounter regularly during their practice. This report provides an overview of the clinical characteristics, epidemiology, genetics, neuroscience, and psychopharmacology schizophrenia to provide basis understand disorder its treatment. educational review integrated with case highlight how recent research findings can inform understanding.

Observations

The first theme considered role early-life environmental genetic risk factors in altering neurodevelopmental trajectories predispose individual leading development prodromal symptoms. second cortical excitatory-inhibitory imbalance cognitive negative symptoms disorder. third considers psychosocial stressors, psychological factors, subcortical dopamine dysfunction onset positive final mechanisms underlying treatment for common adverse effects

Conclusions Relevance

has complex presentation multifactorial cause. Nevertheless, advances neuroscience have identified roles key circuits, particularly involving frontal, temporal, mesostriatal brain regions, positive, negative, Current pharmacological treatments operate using same mechanism, blockade D₂receptor, which contribute effects. However, circuit discussed herein identify novel potential targets may be particular benefit symptom domains not well served by existing medications.

Language: Английский

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Schizophrenia, Dopamine and the Striatum: From Biology to Symptoms

Trends in Neurosciences, Journal Year: 2019, Volume and Issue: 42(3), P. 205 - 220

Published: Jan. 6, 2019

The mesolimbic hypothesis has been a central dogma of schizophrenia for decades, positing that aberrant functioning midbrain dopamine projections to limbic regions causes psychotic symptoms. Recently, however, advances in neuroimaging techniques have led the unanticipated finding dopaminergic dysfunction is greatest within nigrostriatal pathways, implicating dorsal striatum pathophysiology and calling into question theory. At same time our knowledge striatal anatomy function progressed, suggesting new mechanisms via which may contribute symptoms schizophrenia. This Review draws together these developments, explore what they mean understanding pathophysiology, clinical manifestations, treatment disorder.

Language: Английский

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Striatal circuits for reward learning and decision-making

Nature reviews. Neuroscience, Journal Year: 2019, Volume and Issue: 20(8), P. 482 - 494

Published: June 6, 2019

Language: Английский

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Dopamine and glutamate in schizophrenia: biology, symptoms and treatment

World Psychiatry, Journal Year: 2020, Volume and Issue: 19(1), P. 15 - 33

Published: Jan. 10, 2020

Glutamate and dopamine systems play distinct roles in terms of neuronal signalling, yet both have been proposed to contribute significantly the pathophysiology schizophrenia. In this paper we assess research that has implicated aetiology disorder. We examine evidence from post‐mortem, preclinical, pharmacological vivo neuroimaging studies. Pharmacological preclinical studies implicate systems, imaging system consistently identified elevated striatal synthesis release capacity Imaging glutamate other aspects on produced less consistent findings, potentially due methodological limitations heterogeneity Converging indicates genetic environmental risk factors for schizophrenia underlie disruption glutamatergic dopaminergic function. However, while influences may directly dysfunction, few variants system, indicating aberrant signalling is likely be predominantly factors. discuss neural circuits through which two interact, how their cause psychotic symptoms. also mechanisms existing treatments operate, recent highlighted opportunities development novel therapies. Finally, consider outstanding questions field, including what remains unknown regarding nature function schizophrenia, needs achieved make progress developing new treatments.

Language: Английский

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Dopamine and Cognitive Control in Prefrontal Cortex

Trends in Cognitive Sciences, Journal Year: 2019, Volume and Issue: 23(3), P. 213 - 234

Published: Jan. 31, 2019

Language: Английский

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The connectome of the adult Drosophila mushroom body provides insights into function

eLife, Journal Year: 2020, Volume and Issue: 9

Published: Dec. 14, 2020

Making inferences about the computations performed by neuronal circuits from synapse-level connectivity maps is an emerging opportunity in neuroscience. The mushroom body (MB) well positioned for developing and testing such approach due to its conserved architecture, recently completed dense connectome, extensive prior experimental studies of roles learning, memory, activity regulation. Here, we identify new components MB circuit Drosophila, including visual input output neurons (MBONs) with direct connections descending neurons. We find unexpected structure sensory inputs, transfer information different modalities MBONs, modulation that dopaminergic (DANs). provide insights into circuitry used integrate outputs, between central complex inputs DANs, feedback MBONs. Our results a foundation further theoretical work.

Language: Английский

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Dopamine and Addiction

Annual Review of Psychology, Journal Year: 2020, Volume and Issue: 71(1), P. 79 - 106

Published: Jan. 4, 2020

Addiction is commonly identified with habitual nonmedical self-administration of drugs. It usually defined by characteristics intoxication or withdrawal symptoms. Such addictions can also be in terms the brain mechanisms they activate; most addictive drugs cause elevations extracellular levels neurotransmitter dopamine. Animals unable to synthesize use dopamine lack conditioned reflexes discussed Pavlov appetitive behavior Craig; have only unconditioned consummatory reflexes. Burst discharges (phasic firing) dopamine-containing neurons are necessary establish long-term memories associating predictive stimuli rewards and punishers. Independent (tonic pacemaker determine motivation respond such cues. As a result intake drugs, receptors expressed decreased, thereby reducing interest activities not already stamped rewards.

Language: Английский

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A Unified Framework for Dopamine Signals across Timescales

Cell, Journal Year: 2020, Volume and Issue: 183(6), P. 1600 - 1616.e25

Published: Nov. 27, 2020

Language: Английский

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What, If, and When to Move: Basal Ganglia Circuits and Self-Paced Action Initiation

Annual Review of Neuroscience, Journal Year: 2019, Volume and Issue: 42(1), P. 459 - 483

Published: April 24, 2019

Deciding what to do and when move is vital our survival. Clinical fundamental studies have identified basal ganglia circuits as critical for this process. The main input nucleus of the ganglia, striatum, receives inputs from frontal, sensory, motor cortices interconnected thalamic areas that provide information about potential goals, context, actions directly or indirectly modulates outputs. striatum also dopaminergic can signal reward prediction errors behavioral transitions movement initiation. Here we review models how direct indirect pathways modulate outputs facilitate initiation, discuss role cortical in determining if it. Complex but exciting scenarios emerge shed new light on self-paced

Language: Английский

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Dopamine: The Neuromodulator of Long-Term Synaptic Plasticity, Reward and Movement Control

Cells, Journal Year: 2021, Volume and Issue: 10(4), P. 735 - 735

Published: March 26, 2021

Dopamine (DA) is a key neurotransmitter involved in multiple physiological functions including motor control, modulation of affective and emotional states, reward mechanisms, reinforcement behavior, selected higher cognitive functions. Dysfunction dopaminergic transmission recognized as core alteration several devastating neurological psychiatric disorders, Parkinson’s disease (PD), schizophrenia, bipolar disorder, attention deficit hyperactivity disorder (ADHD) addiction. Here we will discuss the current insights on role DA control learning mechanisms its involvement synaptic dynamics through different pathways. In particular, consider neuromodulator two forms plasticity, known long-term potentiation (LTP) depression (LTD) cortical subcortical areas. Finally, delineate how effect dendritic spines places this molecule at interface between systems. Specifically, be focusing PD, vascular dementia, schizophrenia.

Language: Английский

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