The co-morbidity between smoking and mood disorders is striking. Preclinical and clinical studies of nicotinic effects on mood, anxiety, aggression, and related behaviors, such as irritability and ...agitation, suggest that smokers may use the nicotine in tobacco products as an attempt to self-medicate symptoms of affective disorders. The role of nicotinic acetylcholine receptors (nAChRs) in circuits regulating mood and anxiety is beginning to be elucidated in animal models, but the mechanisms underlying the effects of nicotine on aggression-related behavioral states (ARBS) are still not understood. Clinical trials of nicotine or nicotinic medications for neurological and psychiatric disorders have often found effects of nicotinic medications on ARBS, but few trials have studied these outcomes systematically. Similarly, the increase in ARBS resulting from smoking cessation can be resolved by nicotinic agents, but the effects of nicotinic medications on these types of mental states and behaviors in non-smokers are less well understood. Here we review the literature on the role of nAChRs in regulating mood and anxiety, and subsequently on the closely related construct of ARBS. We suggest avenues for future study to identify how nAChRs and nicotinic agents may play a role in these clinically important areas.
This article is part of the Special Issue entitled ‘The Nicotinic Acetylcholine Receptor: From Molecular Biology to Cognition’.
•There is high co-morbidity between smoking and mood disorders.•Clinical trials have shown effects of nicotine on aggression-related behaviors.•Few trials of nicotine study aggression-related outcomes systematically.•Further studies nicotine and nAChR effects on aggression are necessary.
In order to reinforce more disciplined approaches to correlational research, our editorial board commits to considering negative studies that are rigorous in their design as superior to positive ...studies that came to significance by testing too many relationships. 2. Most often, this problem will occur when a hypothesis was developed after the fact to ‘fit’ a significant finding, or when the initial hypothesis was changed for the same purpose: “Given the interest of the authors in the impacts of paternal education level, we sought to test the hypothesis that paternal education was correlated with excess screen time in a sample of youth” A more honest presentation could be: “We tested the hypothesis that socio-economic status would be correlated with increased screen time in a sample of youth, but this finding proved to not be significant in our sample. A significant number of manuscripts justify the topic under investigation by a vague statement of needing to ‘better understand the factors’ that drive or influence an outcome, and then conclude that ‘further research is required’, or that more resources be dedicated to addressing which ever risk factor or mediator was identified. A contrasting and superior approach would be: “The lack of understanding on whether screen time impacts cognitive function a) directly, or, b) by limiting other important activities, is a critical limitation in our ability to issue guidance to patients and families.
IMPORTANCE: Posttraumatic stress disorder (PTSD) is a common psychiatric illness, increasingly in the public spotlight in the United States due its prevalence in the soldiers returning from combat in ...Iraq and Afghanistan. This educational review presents a contemporary approach for how to incorporate a modern neuroscience perspective into an integrative case formulation. The article is organized around key neuroscience “themes” most relevant for PTSD. Within each theme, the article highlights how seemingly diverse biological, psychological, and social perspectives all intersect with our current understanding of neuroscience. OBSERVATIONS: Any contemporary neuroscience formulation of PTSD should include an understanding of fear conditioning, dysregulated circuits, memory reconsolidation, epigenetics, and genetic factors. Fear conditioning and other elements of basic learning theory offer a framework for understanding how traumatic events can lead to a range of behaviors associated with PTSD. A circuit dysregulation framework focuses more broadly on aberrant network connectivity, including between the prefrontal cortex and limbic structures. In the process of memory reconsolidation, it is now clear that every time a memory is reactivated it becomes momentarily labile—with implications for the genesis, maintenance, and treatment of PTSD. Epigenetic changes secondary to various experiences, especially early in life, can have long-term effects, including on the regulation of the hypothalamic-pituitary-adrenal axis, thereby affecting an individual’s ability to regulate the stress response. Genetic factors are surprisingly relevant: PTSD has been shown to be highly heritable despite being definitionally linked to specific experiences. The relevance of each of these themes to current clinical practice and its potential to transform future care are discussed. CONCLUSIONS AND RELEVANCE: Together, these perspectives contribute to an integrative, neuroscience-informed approach to case formulation and treatment planning. This may help to bridge the gap between the traditionally distinct viewpoints of clinicians and researchers.
Cognitive dysfunction in schizophrenia (SCZ) and Alzheimer's disease (AD) is a major driver of functional disability but is largely unresponsive to current therapeutics. Animal models of cognitive ...dysfunction relevant to both disorders suggest the α7 nicotinic acetylcholine receptor (nAChR) may be a promising drug development target, with multiple clinical trials subsequently testing this hypothesis in individuals with SCZ and AD. However, the translational value of rodent cognitive tasks for predicting the overall efficacy of this therapeutic target in clinical trials is unknown. To compare effect sizes between rodent and human studies, we searched PubMed and the Cochrane Library for all randomized, placebo-controlled trials of compounds with pharmacological activity at the α7 nAChR for treatment of cognitive dysfunction in SCZ and AD and identified 18 studies comprising 2670 subjects treated with eight different compounds acting as full or partial agonists. Cognitive outcomes were standardized, and random-effects meta-analyses revealed no statistically significant effects of α7 nAChR agonists on overall cognition or any of eight cognitive subdomains when all doses were included (Range of all cognitive outcomes: Cohen's d=−0.077 to 0.12, negative favoring drug). In contrast, analysis of 29 rodent studies testing the same α7 agonists revealed large effect sizes in multiple commonly used preclinical behavioral tests of cognition (Range: d=−1.18 to – 0.73). Our results suggest that targeting the α7 nAChR with agonists is not a robust treatment for cognitive dysfunction in SCZ or AD and necessitate a better understanding of the translational gap for therapeutics targeting the α7 nAChR.
•Novel drugs to improve cognition in schizophrenia and Alzheimer's disease are needed.•The α7 nicotinic receptor is a potential drug target to treat cognitive dysfunction.•Meta-analyses find large effect sizes of α7 agonists in rodent cognitive studies.•Meta-analyses find no or limited effects of α7 agonists on human subject cognition.•Significant translational barriers exist for α7 nicotinic receptor-targeting drugs.
Emotional Lability (EL) is a common symptom dimension in a variety of psychiatric disorders. However, as it is not typically a diagnosis in its own right, it lacks a consistently applied clinical ...definition and treatment approach. Therefore, in this review we performed a meta-analysis to determine the effect sizes for treatments of EL across diagnostic categories. We then conducted subgroup analyses to compare effect sizes for pharmacologic (MED) and behavioral (BEH) treatments, according to underlying diagnosis, and according to medication class. We found that pharmacologic and non-pharmacologic treatments are effective for EL, and that the effect sizes were similar - a finding with implications for clinical practice. Our findings also support future research which approaches EL as an important construct independent of underlying diagnosis.
•Pharmacologic (MED), behavioral (BEH), and interventional (INT) treatments are all effective for treating emotional lability.•Pharmacologic (MED) treatments have similar effect sizes to behavioral (BEH) interventions for emotional lability.•Serotonin reuptake inhibitors showed smaller effect sizes compared to other medications for emotional lability.•There were significant differences in effect sizes between diagnostic groups with ADHD > BPD and PMS.
ABSTRACT
Resilient prescribing is an approach to the use of psychotropics that considers the significance of the treatment beyond the direct effects of the medication. Within this strengths-based ...approach, those who are prescribed medications must retain a sense of self-efficacy, understand the importance of their own actions in their recovery, have reasonable expectations of what a medication can and cannot do, and avoid the adoption of a disempowering illness identity. These constitute the principles of resilient prescribing. In this manuscript, we explore these principles with consideration for how they may be applied in deployed settings where the ability of service members to recover from behavioral health concerns is mission critical. These principles offer a roadmap to prescribing that builds upon the service members’ own strengths and has the potential to amplify the positive impacts of mental health treatment.
Ketamine has rapid-acting antidepressant effects. Frequently, ketamine administration also causes acute psychoactive effects – in trials, these effects are commonly measured using the Clinician ...Administered Dissociative State Scale (CADSS). However, the CADSS was not designed for this specific purpose, having been validated in other clinical contexts, and anecdotally does not appear to fully capture ketamine's acute psychoactive effects.
Data were obtained from 110 individuals with mood disorders (predominantly major depressive disorder) who underwent intravenous ketamine infusion. An exploratory factor analysis (EFA) was performed on the CADSS, along with assessment of internal consistency. Qualitative methods were used to conduct in-depth interviews with a subset of these participants to identify key features of the acute ketamine experience, including aspects that may not be captured by the CADSS.
The mean total score of the CADSS was low at 7.7 (SD 9.2). Analysis of internal consistency showed a Cronbach's alpha of 0.74. Five CADSS items had low correlations with the total score. EFA lead to a one-factor solution containing 16 items. Five of the six highest loading items involved perceptual disturbances, either of time or sensation. Qualitative analyses of 10 patient narratives revealed two phenomena not captured on the CADSS: disinhibition and a sense of peace.
This study was by limited by the absence of other ratings of the participants’ experience.
Findings suggest that the CADSS partially captures the acute effects of ketamine administration. Further research may seek to validate a revised version of the CADSS that more accurately measures these effects.
•Measuring the acute effects of ketamine is important for both clinical treatment and research efforts.•Currently used instruments do not appear to capture this experience adequately.•Ketamine's acute effects include experiences of altered perception, depersonalization, peace, and disinhibition.•There is a need to develop instruments which measure broader aspects of the acute ketamine experience.
The relationship between autism spectrum disorders (ASD) and psychotic disorders (PD) is a focus of continued interest. There are substantial conceptual and clinical difficulties associated with ...diagnosing comorbid PD in individuals who have ASD. In this case series, we report on five cases where adolescents with previously diagnosed ASD were also diagnosed as psychotic. In each case, we found that these patients’ ‘psychotic’ symptoms could be better understood as a part of their underlying ASD diagnosis, with significant implications for treatment, prognosis, and access to services. This misdiagnosis likely represents a combination of adult psychiatrists being relatively inexperienced with this population, and the system of care requiring providers to apply diagnostic labels to justify inpatient hospitalization.
Aggressive behavior complicates the presentation of many psychiatric illnesses, and is associated with significant morbidity. Antipsychotic medications are used to treat this symptom dimension across ...multiple diagnoses. In this meta-analysis we sought to identify the effect size of antipsychotic medications for the treatment of reactive-impulsive aggression in adults, and identify differences across underlying diagnosis and specific agent. A search was conducted of four databases, MEDLINE, PsychINFO, Embase and the Cochrane Library to end date of August 10, 2016. The search terms included “aggression”, “irritable mood”, “anger”, “hostility” and “antipsychotic agents” or “dopamine antagonists”. 505 results were found, of which 47 were reviewed in detail and 21 ultimately included in the analysis. Antipsychotics were broadly effective for the treatment of aggression, but with effect sizes similar to those for non-pharmacologic interventions (standard mean difference=0.29, 95% confidence interval 0.22–0.36, z=8.5, p<0.001). There was no evidence for differences according to choice of agent (χ2=2.7, df=6, p=0.85), or conclusive evidence as to the importance of the underlying diagnosis (χ2=3.2, df=3, p=0.36). A small but significant dose effect was identified (β=0.0002, 95% CI 0.0001–0.0004, p=0.038). Although antipsychotics appear to be effective for treatment of aggression, their small effect sizes in the context of their significant side-effects should be taken into account when making clinical decisions about their use.
•Antipsychotics are frequently prescribed for aggression.•They appear to have a modest effect for this symptom dimension.•Available clinical evidence does not support a difference in effect size between different antipsychotic medications.
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