Current and potential pharmacological and psychosocial interventions for anxiety symptoms and disorders in patients with schizophrenia: structured review

Howells, Fleur M.; Kingdon, David; Baldwin, David S.

doi:10.1002/hup.2628

Cited by 21 publications

(11 citation statements)

References 178 publications

(182 reference statements)

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“…In the 65 years since the first antipsychotic was discovered, inhibition of neurotransmission via the dopamine receptor has proven to be an important strategy for the treatment of schizophrenia ( Miyamoto et al, 2005 ; Stroup et al, 2006 ). However, these therapies are only effective in two-thirds of all patients, and their efficacy is limited by the lack of an effect on negative and cognitive symptoms ( Nielsen et al, 2015 ; Howells et al, 2017 ). Therefore, there is an urgent need to identify new molecular targets to address the various dimensions of schizophrenia symptoms.…”

Section: Discussionmentioning

confidence: 99%

“…Despite some benefits of antipsychotic drugs, they do not often effectively treat the cognitive and emotional symptoms that the majority of schizophrenia patients also have ( Nielsen et al, 2015 ; Howells et al, 2017 ; Ibi et al, 2017 ). Cognitive impairment in schizophrenia patients is selective and often includes dysfunction in attention, executive function, and working memory ( Rodriguez-Blanco et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

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Reelin Supplementation Into the Hippocampus Rescues Abnormal Behavior in a Mouse Model of Neurodevelopmental Disorders

Ibi

Nakasai

Koide

et al. 2020

Front. Cell. Neurosci.

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In the majority of schizophrenia patients, chronic atypical antipsychotic administration produces a significant reduction in or even complete remission of psychotic symptoms such as hallucinations and delusions. However, these drugs are not effective in improving cognitive and emotional deficits in patients with schizophrenia. Atypical antipsychotic drugs have a high affinity for the dopamine D 2 receptor, and a modest affinity for the serotonin 5-HT 2A receptor. The cognitive and emotional deficits in schizophrenia are thought to involve neural networks beyond the classical dopaminergic mesolimbic pathway, however, including serotonergic systems. For example, mutations in the RELN gene, which encodes Reelin, an extracellular matrix protein involved in neural development and synaptic plasticity, are associated with neurodevelopmental disorders such as schizophrenia and autism spectrum disorder. Furthermore, hippocampal Reelin levels are down-regulated in the brains of both schizophrenic patients and in rodent models of schizophrenia. In the present study, we investigated the effect of Reelin microinjection into the mouse hippocampus on behavioral phenotypes to evaluate the role of Reelin in neurodevelopmental disorders and to test a therapeutic approach that extends beyond classical monoamine targets. To model the cognitive and emotional deficits, as well as histological decreases in Reelin-positive cell numbers and hippocampal synaptoporin distribution, a synaptic vesicle protein, offspring that were prenatally exposed to maternal immune activation were used. Microinjections of recombinant Reelin protein into the hippocampus rescued impairments in object memory and anxiety-like behavior and recruited synaptoporin in the hippocampus in offspring exposed to antenatal inflammation. These results suggest that Reelin supplementation has the potential to treat cognitive and emotional impairments, as well as synaptic disturbances, in patients with neurodevelopmental disorders such as schizophrenia.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Reelin Supplementation Into the Hippocampus Rescues Abnormal Behavior in a Mouse Model of Neurodevelopmental Disorders

Ibi

Nakasai

Koide

et al. 2020

Front. Cell. Neurosci.

View full text Add to dashboard Cite

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“…Here, we detected a genetic correlation between anxiety disorders and SCZ for the first time. The prevalence of comorbid anxiety disorders in patients with SCZ ranges between 30% and 62% (Temmingh and Stein, 2015; Howells et al ., 2017). Common comorbid anxiety disorders in patients with SCZ include social phobia/SAD, GAD, PD, agoraphobia and specific phobia (Achim et al ., 2011).…”

Section: Discussionmentioning

confidence: 99%

Shared genetic etiology between anxiety disorders and psychiatric and related intermediate phenotypes

et al. 2019

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BackgroundPsychiatric disorders and related intermediate phenotypes are highly heritable and have a complex, overlapping polygenic architecture. A large-scale genome-wide association study (GWAS) of anxiety disorders identified genetic variants that are significant on a genome-wide. The current study investigated the genetic etiological overlaps between anxiety disorders and frequently cooccurring psychiatric disorders and intermediate phenotypes.MethodsUsing case–control and factor score models, we investigated the genetic correlations of anxiety disorders with eight psychiatric disorders and intermediate phenotypes [the volumes of seven subcortical brain regions, childhood cognition, general cognitive ability and personality traits (subjective well-being, loneliness, neuroticism and extraversion)] from large-scale GWASs (n = 7556–298 420) by linkage disequilibrium score regression.ResultsAmong psychiatric disorders, the risk of anxiety disorders was positively genetically correlated with the risks of major depressive disorder (MDD) (rg ± standard error = 0.83 ± 0.16, p = 1.97 × 10−7), schizophrenia (SCZ) (0.28 ± 0.09, p = 1.10 × 10−3) and attention-deficit/hyperactivity disorder (ADHD) (0.34 ± 0.13, p = 8.40 × 10−3). Among intermediate phenotypes, significant genetic correlations existed between the risk of anxiety disorders and neuroticism (0.81 ± 0.17, p = 1.30 × 10−6), subjective well-being (−0.73 ± 0.18, p = 4.89 × 10−5), general cognitive ability (−0.23 ± 0.08, p = 4.70 × 10−3) and putamen volume (−0.50 ± 0.18, p = 5.00 × 10−3). No other significant genetic correlations between anxiety disorders and psychiatric or intermediate phenotypes were observed (p > 0.05). The case–control model yielded stronger genetic effect sizes than the factor score model.ConclusionsOur findings suggest that common genetic variants underlying the risk of anxiety disorders contribute to elevated risks of MDD, SCZ, ADHD and neuroticism and reduced quality of life, putamen volume and cognitive performance. We suggest that the comorbidity of anxiety disorders is partly explained by common genetic variants.

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“…Moreover, negative symptoms and cognitive deficits are common in patients with chronic schizophrenia. Psychosocial therapy may be effective for the positive and negative symptoms or cognitive symptoms of early schizophrenia, but its therapeutic efficacy may be reduced when the course of schizophrenia is prolonged (11). Therefore, it is necessary to find other treatment options, such as other non-pharmaco-therapies, to better treat schizophrenia and meet the unmet needs of patients (12,13).…”

Section: Introductionmentioning

confidence: 99%

Effects of High-Frequency rTMS on Negative Symptoms and Cognitive Function in Hospitalized Patients With Chronic Schizophrenia: A Double-Blind, Sham-Controlled Pilot Trial

et al. 2021

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This study aimed to evaluate the efficacy of high-frequency repetitive transcranial magnetic stimulation (rTMS) over left dorsolateral pre-frontal cortex (DLPFC) in ameliorating negative symptoms and cognitive impairments in patients with chronic schizophrenia. Fifty-two patients with chronic schizophrenia were randomly assigned to two groups: active rTMS group and sham rTMS group, with existing antipsychotic drugs combined 20 sessions of 10 Hz active/sham rTMS over DLPFC (20 min/session, 5 times/week). The PANSS, RBANS, and SCWT were used to evaluate the clinical symptoms and cognitive functions of the patients. Our results indicated significant improvements in clinical symptoms (PANSS total and subscale scores) and cognitive functions (RBANS total and subscale scores, card 1 and card 3 of the SCWT test) (All p <0.05) after 4-week intervention both in active and sham rTMS group. Moreover, the active rTMS group showed more effective on ameliorating negative symptoms (p = 0.002), immediate memory (p = 0.016) and delayed memory (p = 0.047) compared to the sham group. Interestingly, PANSS negative symptom scores was negatively correlated with RBANS language scores in the real stimulation group (p = 0.046). The study found that the high frequency rTMS stimulation over left DLPFC as a supplement to antipsychotics may have potential benefits in improving clinical symptoms and cognitive functions in patients with chronic schizophrenia.

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Current and potential pharmacological and psychosocial interventions for anxiety symptoms and disorders in patients with schizophrenia: structured review

Abstract: The presence of coexisting anxiety symptoms and co-morbid anxiety disorders should be ascertained when assessing patients with schizophrenia or other psychoses as a range of pharmacological and psychosocial treatments are available.

Cited by 21 publications

References 178 publications

Reelin Supplementation Into the Hippocampus Rescues Abnormal Behavior in a Mouse Model of Neurodevelopmental Disorders

Reelin Supplementation Into the Hippocampus Rescues Abnormal Behavior in a Mouse Model of Neurodevelopmental Disorders

Shared genetic etiology between anxiety disorders and psychiatric and related intermediate phenotypes

Effects of High-Frequency rTMS on Negative Symptoms and Cognitive Function in Hospitalized Patients With Chronic Schizophrenia: A Double-Blind, Sham-Controlled Pilot Trial

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