Acute nicotine administration effects on fractional anisotropy of cerebral white matter and associated attention performance

Abstract

Introduction: Nicotinic acetylcholine receptors are present in the cerebral white matter (WM). We hypothesized that WM response to nicotine can be detected by diffusion tensor imaging (DTI); and that such responses may be associated with nicotine-led cognitive enhancement in sustained attention.Methods: A randomized, nicotine-placebo patch, crossover, double-blind clinical trial in two non-overlapping cohorts of smokers was used to test the hypothesis. The discovery cohort consisted of 39 subjects (N = 20/19 controls/schizophrenic patients, age = 36.8 ± 10.1 years) and the replication cohorts consisted of 38 healthy smokers (31.7 ± 10.5 years). WM integrity was measured by fractional anisotropy (FA) values for the whole brain and nine preselected WM tracts using tract-based-spatial-statistics.Results: Nicotine significantly enhanced FA values for the genu of corpus callosum compared with placebo (ΔFAgenu) (p = 0.01) in smokers with low recent smoking exposure as measured by low average cotinine level. This finding was replicated in the second cohort (p = 0.02). ΔFAgenu values explained 22% of variance in performance of a sustained attention task during the nicotine session (p = 0.006). However, this effect was limited to schizophrenia patients (r = 0.62 and 0.09; p = 0.003 and 0.7 for patients and controls, respectively).Conclusion: Acute pharmacological influence of nicotine patch on WM integrity appeared present, but was dependent on nicotine intake from recent smoking. Change in the WM integrity in the genu of corpus callosum was associated with a significant proportion of variability of nicotine-led changes in sustained attention/working memory of the smokers. Further studies will be necessary to understand biophysical underpinning of the nicotine-related changes in FA.

White matter development and tobacco smoking in young adults: A systematic review with recommendations for future research

“…As discussed above, recent data from adult studies suggest effects of acute nicotine (Kochunov et al, 2013) – and of time since last cigarette (Savjani et al, 2014) – on DTI indices. Thus, an important consideration for future studies will be how best to disentangle acute versus chronic effects of nicotine in adolescents and young adults.…”

“…In human adult populations, increases in genual corpus callosal FA have been reported following acute nicotine administration (Kochunov et al, 2013). Thus, increased FA among adolescent/young adult smokers may be a consequence of exposure to nicotine.…”

“…Increases in FA within the genu of the corpus callosum have also been reported following acute nicotine administration in human adults (Kochunov et al, 2013). While several recent studies indicate white-matter alterations among adolescent and young adult tobacco-users, the relationship between tobacco smoking and neural development during adolescence and young adulthood is not yet well understood.…”

Frontal fasciculi and psychotic symptoms in antipsychotic-naive patients with schizophrenia before and after 6 weeks of selective dopamine D2/3 receptor blockade

“…Although smoking (number of cigarettes/d) did not significantly correlate with FA in patients or controls, these factors may still have influenced our findings. 57,58 Twenty-six per cent of the patients dropped out during follow-up, and those who dropped out had more years of education than those who did not drop out. As correction for education did not alter our results, we consider it unlikely that baseline differences substantially influenced our results.…”

Myelin, myelin-related disorders, and psychosis

“…In both neuropathology and neuroimaging, it is uncertain whether white matter changes are an intrinsic component of schizophrenia or are the consequence of neuroleptic treatment, social deprivation, or other epiphenomena related to suffering from a chronic psychiatric disorder. A number of studies have suggested that the DTI abnormalities in schizophrenia are confounded by multiple factors, including the duration of illness and treatment with antipsychotic medications (Konopaske et al, 2006(Konopaske et al, , 2008, age (Kochunov et al, 2013a(Kochunov et al, , 2013bGiezendanner et al, 2013;Mandl et al, 2013), sex of the subjects (Savadjiev et al, 2014), and even heavy cigarette smoking (Cullen et al, 2012;Kochunov et al, 2013aKochunov et al, , 2013b.…”