Alpha7 Nicotinic Receptors as Therapeutic Targets in Schizophrenia

Tregellas, Jason R.; Wylie, Korey P.

doi:10.1093/ntr/nty034

Cited by 68 publications

(55 citation statements)

References 88 publications

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“…Our findings provide additional evidence that a nicotinebased treatment has the potential to improve attentional performance in a subgroup of predisposed subjects that show atypical patterns of low attentional or executive behaviour and differences in local integration of functional brain network topology. This finding may also be of relevance for other disorders such as mild cognitive impairment where a pilot trial on long term nicotine treatment resulted in improved attention, memory and psychomotor speed (Newhouse et al, 2012) or the treatment of cognitive dysfunction in patients with schizophrenia (Tregellas and Wylie, 2019).…”

Section: Discussionmentioning

confidence: 74%

“…Previous clinical studies on the therapeutic use of nicotine and nicotinic agonists often failed to show a positive effect on cognition, attention and psychomotor functions in patients with neuropsychiatric disorders (Newhouse, 2019). Despite these failures in clinical studies, previous experimental results revealed significant nicotine effects on motor performance and attention (Heishman et al, 2010;Tregellas and Wylie, 2019). In addition, previous clinical studies documented an increased percentage of smokers in patients with a variety of psychiatric disorders, including attention-deficit hyperactivity disorder (ADHD) and schizophrenia (Pomerleau et al, 1995;Tregellas and Wylie, 2019).…”

Section: Introductionmentioning

confidence: 99%

“…Despite these failures in clinical studies, previous experimental results revealed significant nicotine effects on motor performance and attention (Heishman et al, 2010;Tregellas and Wylie, 2019). In addition, previous clinical studies documented an increased percentage of smokers in patients with a variety of psychiatric disorders, including attention-deficit hyperactivity disorder (ADHD) and schizophrenia (Pomerleau et al, 1995;Tregellas and Wylie, 2019). This was seen as further evidence for the effectiveness of nicotine to self-medicate attentional and emotional dysfunctions (Gehricke et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

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Healthy Subjects With Extreme Patterns of Performance Differ in Functional Network Topology and Benefits From Nicotine

Gießing

Ahrens

Thiel

2020

Front. Syst. Neurosci.

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Do subjects with atypical patterns in attentional and executive behaviour show different brain network topology and react differently towards nicotine administration? The efficacy of pro-cognitive drugs like nicotine considerably varies between subjects and previous theoretical and empirical evidence suggest stronger behavioural nicotine effects in subjects with low performance. One problem is, however, how to best define low performance, especially if several cognitive functions are assessed for subject characterisation. We here present a method that used a multivariate, robust outlier detection algorithm to identify subjects with suspicious patterns of performance in attentional and executive functioning. In contrast to univariate approaches, this method is sensitive towards extreme positions within the multidimensional space that do not have to be extreme values in the individual behavioural distributions. The method was applied to a dataset of healthy, non-smoking subjects (n = 34) who were behaviorally characterised by an attention and executive function test on which N = 12 volunteers were classified as outliers. All subjects then underwent a resting-state functional magnetic resonance imaging (fMRI) scan to characterise brain network topology and an experimental behavioural paradigm under placebo and nicotine (7 mg patch) that gauged aspects of attention and executive function. Our results indicate that subjects with an atypical multivariate pattern in attention and executive functioning showed significant differences in nodal brain network integration in visual association and pre-motor brain regions during resting state. These differences in brain network topology significantly predicted larger individual nicotine effects on attentional processing. In summary, the current approach successfully identified a subgroup of healthy volunteers with low behavioural performance who differ in brain network topology and attentional benefit from nicotine.

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Section: Discussionmentioning

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Healthy Subjects With Extreme Patterns of Performance Differ in Functional Network Topology and Benefits From Nicotine

Gießing

Ahrens

Thiel

2020

Front. Syst. Neurosci.

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“…Los mecanismos que causan la disfunción de la ganancia de control incluyen la disfunción de los sistemas de NMDA y del GABA. Otros neurotransmisores que también están implicados en la (36) esquizofrenia, igualmente modulan el procesamiento visual . Por ejemplo, la deficiencia de dopamina ha sido ligada al daño en la respuesta perceptiva y electrofisiológica a las señales de (37,38) contraste…”

Section: Ganancia De Control E Integración En La Esquizofreniaunclassified

Schizophrenia and visual perception disturbances

Torales

Meyer

Fariña

2020

Rev. virtual Soc. Parag. Med. Int

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“…Nevertheless, differences in prescription patterns in smokers vs. nonsmokers cannot be exclusively attributed to differences in blood levels. Other factors, e. g., alteration in nicotinergic neurotransmission, that may be implicated in TRS have to be taken into account [13].…”

Section: Introductionmentioning

confidence: 99%

Effects of Smoking Status on Remission and Metabolic and Cognitive Outcomes in Schizophrenia Patients Treated with Clozapine

et al. 2020

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Background Even though clozapine is the recommended last-resort antipsychotic, many patients fail to respond and show treatment-refractory psychotic symptoms. Smoking has been suggested as a possible risk factor for poor clozapine response, hampering remission and negatively impacting somatic outcomes. Methods Our aim was to test whether smoking status is associated with remission rates and other symptomatic and somatic outcomes. We therefore assessed remission rates according to The Remission in Schizophrenia Working Group (RSWG) criteria, and metabolic and cognitive outcomes among patients with schizophrenia-spectrum disorders treated with clozapine for at least 6 months. For analyses, we grouped our cohort into 3 groups according to clozapine treatment duration (6 months, 2 years, 5 years). Results One hundred five patients were included in our analyses and grouped according to their clozapine treatment duration. In the 6-months analyses, patients who smoked were significantly more likely to be younger of age (p=0.002) despite on average shorter duration of clozapine treatment (p=0.041) and significantly more likely to be treated with mood-stabilizing co-medication (p=0.030) compared to nonsmokers. Remission rates (p=0.490), as well as a set of metabolic and cognitive variables did not differ between the 2 groups. A related pattern could be observed for the 2- and 5-years analyses. Conclusions Smoking behavior among clozapine-treated schizophrenia patients might delineate a cohort with an earlier onset of the disease. Nevertheless, most findings comparing disease-specific and clinical outcomes among smokers and nonsmokers were negative. Further research is needed to identify strategies to overcome insufficient remission rates in this patient group.

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Alpha7 Nicotinic Receptors as Therapeutic Targets in Schizophrenia

Abstract: By examining alpha7 nicotinic receptor biology and recent efforts to target the receptor in clinical trials, it is hoped that investigators will be motivated to explore novel, promising directions focusing on the receptor as a strategy to treat cognitive symptoms in schizophrenia.

Cited by 68 publications

References 88 publications

Healthy Subjects With Extreme Patterns of Performance Differ in Functional Network Topology and Benefits From Nicotine

Healthy Subjects With Extreme Patterns of Performance Differ in Functional Network Topology and Benefits From Nicotine

Schizophrenia and visual perception disturbances

Effects of Smoking Status on Remission and Metabolic and Cognitive Outcomes in Schizophrenia Patients Treated with Clozapine

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