Negative symptoms of schizophrenia: Clinical characteristics, pathophysiological substrates, experimental models and prospects for improved treatment

https://doi.org/10.1016/j.euroneuro.2014.03.008Get rights and content
Under a Creative Commons license
open access

Abstract

Schizophrenia is a complex and multifactorial disorder generally diagnosed in young adults at the time of the first psychotic episode of delusions and hallucinations. These positive symptoms can be controlled in most patients by currently-available antipsychotics. Conversely, they are poorly effective against concomitant neurocognitive dysfunction, deficits in social cognition and negative symptoms (NS), which strongly contribute to poor functional outcome. The precise notion of NS has evolved over the past century, with recent studies – underpinned by novel rating methods – suggesting two major sub-domains: “decreased emotional expression”, incorporating blunted affect and poverty of speech, and “avolition”, which embraces amotivation, asociality and “anhedonia” (inability to anticipate pleasure). Recent studies implicate a dysfunction of frontocortico-temporal networks in the aetiology of NS, together with a disruption of cortico-striatal circuits, though other structures are also involved, like the insular and parietal cortices, amygdala and thalamus. At the cellular level, a disruption of GABAergic–glutamatergic balance, dopaminergic signalling and, possibly, oxytocinergic and cannibinoidergic transmission may be involved. Several agents are currently under clinical investigation for the potentially improved control of NS, including oxytocin itself, N-Methyl-d-Aspartate receptor modulators and minocycline. Further, magnetic-electrical “stimulation” strategies to recruit cortical circuits and “cognitive–behavioural–psychosocial” therapies likewise hold promise. To acquire novel insights into the causes and treatment of NS, experimental study is crucial, and opportunities are emerging for improved genetic, pharmacological and developmental modelling, together with more refined readouts related to deficits in reward, sociality and “expression”. The present article comprises an integrative overview of the above issues as a platform for this Special Issue of European Neuropsychopharmacology in which five clinical and five preclinical articles treat individual themes in greater detail. This Volume provides, then, a framework for progress in the understanding – and ultimately control – of the debilitating NS of schizophrenia.

Abbreviations

BTBR
Black and Tan Brachyury
CB
Cannibinoid
CBT
Cognitive-Behavioural Therapy
CRT
Cognitive Remediation Therapy
DA
dopamine
DLPFC
Dorsolateral Prefrontal Cortex
DSM
Diagnostic and Statistical Manual
EEG
electroencephalography
ERP
Event Related Potential
fMRI
functional Magnetic Resonance Imaging
LSD
Lysergic-diethylamide
MHC
Major Histocompatability Complex
MRI
Magnetic Resonance Imaging
NIMH
National Institute of Mental Health
NMDA
N-Methyl-d-Aspartate
OFC
orbitofrontal cortex
PAM
positive Allosteric Modulator
PANSS
Positive and Negative Symptom Scale
PCP
Phencyclidine
NS
negative symptoms
PET
Positron Emission Tomography
PFC
prefrontal cortex
rTMS
repetitive Transcranial Magnetic Stimulation
SPECT
Single Photon Emission Computerised Tomography
USV
Ultrasonic Vocalisation
VHL
ventral hippocampus lesion

Keywords

Prefrontal cortex
Striatum
Motivation
Social cognition
Social interaction
Oxytocin

Cited by (0)