Compulsivity in opioid dependence

This study was part funded by an unrestricted educational grant provided by Schering-Plough and a grant by an Anonymous Trust. Study support was also provided by the Scottish Mental Health Research Network. AB has received educational grants from Schering Plough and he has received research project funding from Schering-Plough, Merck Serono, and Indivior.Objective: This study aimed to investigate the relationship between compulsivity versus impulsivity and structural MRI abnormalities in opioid dependence. Method: We recruited 146 participants: i) patients with a history of opioid dependence due to chronic heroin use (n=24), ii) heroin users stabilised on methadone maintenance treatment (n=48), iii) abstinent participants with ahistory of opioid dependence due to heroin use (n=24) and iv) healthy controls(n=50). Compulsivity was measured using Intra/Extra-Dimensional (IED) Task and impulsivity was measured using the Cambridge Gambling Task (CGT).Structural Magnetic Resonance Imaging (MRI) data were also obtained. Results: As hypothesised, compulsivity was negatively associated with impulsivity (p<0.02). Testing for the neural substrates of compulsivity versus impulsivity, we found a higher compulsivity/impulsivity ratio associated with significantly decreased white matter adjacent to the nucleus accumbens, bed nucleus of stria terminalis and rostral cingulate in the abstinent group,compared to the other opioid dependent groups. In addition, self-reported duration of opioid exposure correlated negatively with bilateral globus pallidus grey matter reductions. Conclusion: Our findings are consistent with Volkow & Koob’s addiction models and underline the important role of compulsivity versus impulsivity inopioid dependence. Our results have implications for the treatment of opioid dependence supporting the assertion of different behavioural and biological phenotypes in the opioid dependence and abstinence syndromes.PostprintPeer reviewe

Chronic heroin use disorder and the brain:current evidence and future implications

The incidence of chronic heroin use disorder, including overdose deaths, has reached epidemic proportions. Here we summarise and evaluate our knowledge of the relationship between chronic heroin use disorder and the brain through a narrative review. A broad range of areas was considered including causal mechanisms, cognitive and neurological consequences of chronic heroin use and novel neuroscience-based clinical interventions. Chronic heroin use is associated with limited or very limited evidence of impairments in memory, cognitive impulsivity, non-planning impulsivity, compulsivity and decision-making. Additionally, there is some evidence for certain neurological disorders being caused by chronic heroin use, including toxic leukoencephalopathy and neurodegeneration. However, there is insufficient evidence on whether these impairments and disorders recover after abstinence. Whilst there is a high prevalence of comorbid psychiatric disorders, there is no clear evidence that chronic heroin use per se causes depression, bipolar disorder, PTSD and/or psychosis. Despite the growing burden on society from heroin use, knowledge of the long-term effects of chronic heroin use disorder on the brain remains limited. Nevertheless, there is evidence for progress in neuroscience-based interventions being made in two areas: assessment (cognitive assessment and neuroimaging) and interventions (cognitive training/remediation and neuromodulation). Longitudinal studies are needed to unravel addiction and neurotoxic mechanisms and clarify the role of pre-existing psychiatric symptoms and cognitive impairments.PostprintPeer reviewe

Multifaceted impairments in impulsivity and brain structural abnormalities in opioid dependence and abstinence

This study was part funded by an unrestricted educational grant provided by Schering-Plough, a grant by an anonymous trust and the Scottish Mental Health Research Network.Background: Chronic opioid exposure, as a treatment for a variety of disorders or as drug of misuse, is common worldwide, but behavioural and brain abnormalities remain under-investigated. Only a small percentage of patients who receive methadone maintenance treatment (MMT) for previous heroin misuse eventually achieve abstinence and studies on such patients are rare. Method: The Cambridge Neuropsychological Test Automated Battery and T1 weighted magnetic resonance imaging (MRI) were used to study a cohort of 122 male individuals: a clinically stable opioid-dependent patient group receiving MMT (n = 48), an abstinent previously MMT maintained group (ABS) (n = 24) and healthy controls (n = 50). Results: Stable MMT participants deliberated longer and placed higher bets earlier in the Cambridge Gambling Task (CGT) and showed impaired strategic planning compared with healthy controls. In contrast, ABS participants showed impairment in choosing the least likely outcome, delay aversion and risk adjustment on the CGT, and exhibited non-planning impulsivity compared with controls. MMT patients had widespread grey matter reductions in the orbitomedial prefrontal cortex, caudate, putamen and globus pallidus. In contrast, ABS participants showed midbrain–thalamic grey matter reductions. A higher methadone dose at the time of scanning was associated with a smaller globus pallidus in the MMT group. Conclusions: Our findings support an interpretation of heightened impulsivity in patients receiving MMT. Widespread structural brain abnormalities in the MMT group and reduced brain structural abnormality with abstinence suggest benefit of cessation of methadone intake. We suggest that a longitudinal study is required to determine whether abstinence improves abnormalities, or patients who achieve abstinence have reduced abnormalities before methadone cessation.Publisher PDFPeer reviewe

Chronic tobacco smoking and neuropsychological impairments:A systematic review and meta-analysis

The link between neuropsychological impairments and chronic tobacco smoking is not clear and in the current literature there is a lack of robust analyses investigating this association. A systematic review of the literature was conducted in order to identify relevant longitudinal and cross-sectional studies conducted from 1946 to 2017. A meta-analysis was performed from 24 studies testing the performance of chronic tobacco smokers compared with non-smokers on neuropsychological tests related to eight different neuropsychological domains. The results revealed a cross-sectional association between neuropsychological impairments and chronic tobacco smoking in cognitive impulsivity, non-planning impulsivity, attention, intelligence, short term memory, long term memory, and cognitive flexibility, with the largest effect size being related to cognitive impulsivity (SDM = 0.881, p <0.005), and the smallest effect size being related to intelligence (SDM = 0.164, p < 0.05) according to Cohen’s benchmark criteria. No association was found between chronic smoking and motor impulsivity (SDM = 0.105, p = 0.248). Future research is needed to investigate further this association by focusing on better methodologies and alternative methods for nicotine administration.PostprintPeer reviewe

A causal role for the anterior mid-cingulate cortex in negative affect and cognitive control

Converging evidence has linked the anterior mid-cingulate cortex to negative affect, pain and cognitive control. Shackman and colleagues proposed this region uses information about punishment to control aversively motivated actions. Studies on the effects of lesions allow causal inferences about brain function; however, naturally occurring lesions in the anterior mid-cingulate cortex are rare. In two studies we therefore recruited 94 volunteers, comprising 15 patients with treatment-resistant depression who had received bilateral Anterior Cingulotomy, which consists of lesions made within the anterior mid-cingulate cortex, 20 patients with treatment-resistant depression who had not received surgery and 59 healthy controls. Using the Ekman 60 Faces paradigm and two Stroop paradigms, we tested the hypothesis that patients who received Anterior Cingulotomy were impaired in recognising negative facial affect expressions but not positive or neutral facial expressions, and impaired in Stroop cognitive control, with larger lesions being associated with more impairment. Consistent with hypotheses, we found that larger volume lesions predicted more impairment in recognising fear, disgust and anger, and no impairment in recognising facial expressions of surprise or happiness. However we found no impairment in recognising expressions of sadness. Also consistent with hypotheses, we found that larger volume lesions predicted impaired Stroop cognitive control. Notably, this relationship was only present when anterior mid-cingulate cortex lesion volume was defined as the overlap between cingulotomy lesion volume and Shackman and colleague’s meta-analysis derived binary masks for negative affect and cognitive control. Given substantial evidence from healthy subjects that the anterior mid-cingulate cortex is part of a network associated with the experience of negative affect and pain, engaging cognitive control processes for optimising behaviour in the presence of such stimuli, our findings support the assertion that this region has a causal role in these processes. Whilst the clinical justification for cingulotomy is empirical and not theoretical, it is plausible that lesions within a brain region associated with the subjective experience of negative affect and pain may be therapeutic for patients with otherwise intractable mood, anxiety and pain syndromes.PostprintPeer reviewe

Statistical Mechanics of Semiflexible Bundles of Wormlike Polymer Chains

We demonstrate that a semiflexible bundle of wormlike chains exhibits a state-dependent bending stiffness that alters fundamentally its scaling behavior with respect to the standard wormlike chain. We explore the equilibrium conformational and mechanical behavior of wormlike bundles in isolation, in crosslinked networks, and in solution.Comment: 4 pages, 3 figures, final version as publishe

Structure and mechanics of supporting cells in the guinea pig organ of Corti.

The mechanical properties of the mammalian organ of Corti determine its sensitivity to sound frequency and intensity, and the structure of supporting cells changes progressively with frequency along the cochlea. From the apex (low frequency) to the base (high frequency) of the guinea pig cochlea inner pillar cells decrease in length incrementally from 75-55 µm whilst the number of axial microtubules increases from 1,300-2,100. The respective values for outer pillar cells are 120-65 µm and 1,500-3,000. This correlates with a progressive decrease in the length of the outer hair cells from >100 µm to 20 µm. Deiters'cell bodies vary from 60-50 µm long with relatively little change in microtubule number. Their phalangeal processes reflect the lengths of outer hair cells but their microtubule numbers do not change systematically. Correlations between cell length, microtubule number and cochlear location are poor below 1 kHz. Cell stiffness was estimated from direct mechanical measurements made previously from isolated inner and outer pillar cells. We estimate that between 200 Hz and 20 kHz axial stiffness, bending stiffness and buckling limits increase, respectively,~3, 6 and 4 fold for outer pillar cells, ~2, 3 and 2.5 fold for inner pillar cells and ~7, 20 and 24 fold for the phalangeal processes of Deiters'cells. There was little change in the Deiters'cell bodies for any parameter. Compensating for effective cell length the pillar cells are likely to be considerably stiffer than Deiters'cells with buckling limits 10-40 times greater. These data show a clear relationship between cell mechanics and frequency. However, measurements from single cells alone are insufficient and they must be combined with more accurate details of how the multicellular architecture influences the mechanical properties of the whole organ

Surgeon choice in the use of postdischarge antibiotics for prophylaxis following mastectomy with and without breast reconstruction

Multiple guidelines recommend discontinuation of prophylactic antibiotics \u3c24 hours after surgery. In a multicenter, retrospective cohort of 2,954 mastectomy patients ± immediate breast reconstruction, we found that utilization of prophylactic postdischarge antibiotics varied dramatically at the surgeon level among general surgeons and was virtually universal among plastic surgeons

Postdischarge antibiotic use for prophylaxis following spinal fusion

OBJECTIVE: Despite recommendations to discontinue prophylactic antibiotics after incision closure or \u3c24 hours after surgery, prophylactic antibiotics are continued after discharge by some clinicians. The objective of this study was to determine the prevalence and factors associated with postdischarge prophylactic antibiotic use after spinal fusion. DESIGN: Multicenter retrospective cohort study. PATIENTS: This study included patients aged ≥18 years undergoing spinal fusion or refusion between July 2011 and June 2015 at 3 sites. Patients with an infection during the surgical admission were excluded. METHODS: Prophylactic antibiotics were identified at discharge. Factors associated with postdischarge prophylactic antibiotic use were identified using hierarchical generalized linear models. RESULTS: In total, 8,652 spinal fusion admissions were included. Antibiotics were prescribed at discharge in 289 admissions (3.3%). The most commonly prescribed antibiotics were trimethoprim/sulfamethoxazole (22.1%), cephalexin (18.8%), and ciprofloxacin (17.1%). Adjusted for study site, significant factors associated with prophylactic discharge antibiotics included American Society of Anesthesiologists (ASA) class ≥3 (odds ratio [OR], 1.31; 95% CI, 1.00-1.70), lymphoma (OR, 2.57; 95% CI, 1.11-5.98), solid tumor (OR, 3.63; 95% CI, 1.62-8.14), morbid obesity (OR, 1.64; 95% CI, 1.09-2.47), paralysis (OR, 2.38; 95% CI, 1.30-4.37), hematoma/seroma (OR, 2.93; 95% CI, 1.17-7.33), thoracic surgery (OR, 1.39; 95% CI, 1.01-1.93), longer length of stay, and intraoperative antibiotics. CONCLUSIONS: Postdischarge prophylactic antibiotics were uncommon after spinal fusion. Patient and perioperative factors were associated with continuation of prophylactic antibiotics after hospital discharge