Background:Evolutionary psychiatry is a growing field that emphasizes the value of evolutionary explanations for traits that make individuals vulnerable to mental disorders. Some articles that apply evolutionary theory in psychiatry make errors, such as viewing a disease as an adaptation. We assessed article quality and error quantity in the most cited articles on evolutionary psychiatry and examined the relationship of these measures to citation number. Methods:PubMed, Web of Science, and Google Scholar were searched in 2023 and again in 2025 using specific terms related to "evolution" and "psychiatry", to find the most highly cited articles in the field. Based on the work of Nesse, we developed a measure for assessing overall article quality and error quantity in evolutionary psychiatry articles. We applied the measure to the 20 most highly cited articles, and calculated the correlations of article quality and error quantity with number of citations. Results:Twenty highly cited articles, with a mean citation count of 413.30 and publication year from 1964 to 2011, were rated. While the most highly cited articles had good quality on average, they also made important errors. There was no significant correlation of article quality or error quantity with citation count. Conclusion:Highly cited articles in evolutionary psychiatry demonstrated strengths but also weaknesses. The lack of a relationship of article quality and error quantity to citation rates suggests that other factors influence such citations. Future research should focus on achieving consensus on how best to assess the quality of evolutionary psychiatry articles and what errors should be avoided.

Background: Benzodiazepines and antidepressants are effective agents for the treatment of generalized anxiety disorder (GAD), with the HAM-A frequently used as a primary outcome measure. The GAD literature is inconsistent regarding which medications are more effective for somatic versus psychic symptoms of GAD, and treatment guidelines do not advocate for prescribing based on subtype. This meta-analysis aimed to determine whether benzodiazepines and antidepressants have a differential impact on the somatic versus psychic subscales of the HAM-A in GAD. Methods: An electronic search was undertaken for randomized controlled trials of either benzodiazepines or antidepressants for GAD that reported treatment response using the HAM-A subscales. Data were extracted by independent reviewers. A random effects assessment of weighted mean difference with 95% confidence intervals and subgroup difference was applied. All analysis was done on SPSS 26. An assessment of bias, and of quality of evidence was performed. Results: 24 randomized controlled trials met the inclusion criteria: 18 antidepressant trials, 5 benzodiazepine trials and 1 of both. 14 studies were assessed as having between some and high risk of bias, while 10 were assessed as having low risk of bias. Benzodiazepines (WMD of 1.81 [CI 1.03, 2.58]) were significantly more effective than antidepressants (WMD of 0.83 [CI 0.64, 1.02]) for reducing somatic symptoms of GAD (Chi2 = 5.81, p = 0.02), and were also more effective (WMD of 2.46 [CI 1.83, 3.09]) in reducing psychic symptoms than antidepressants (WMD of 1.83 [CI 1.55, 2.10]), although this comparison did not reach statistical significance (Chi2 = 3.31, p = 0.07). Conclusion: The finding that benzodiazepines were significantly more effective than antidepressants for somatic symptoms needs to be weighed up against potential benefits of antidepressants over benzodiazepines. It may be useful for future treatment guidelines for GAD to explicitly consider symptom subtype.

Abstract While exposure to traumatic events is highly prevalent, only a small proportion of those exposed to such stressors develop psychiatric illnesses. This raises a number of questions for social psychiatry. What are the mechanisms underlying risk and resilience after trauma? And what can be done to further decrease risk and increase resilience? This chapter reviews the epidemiology, neurobiology, and social determinants of post-traumatic stress disorder (PTSD) and resilience, in order to address these questions and to provide an integrative approach. An integrative approach to trauma and PTSD requires the recognition of a broad range of biological and societal risk and resilience factors that are relevant to trauma exposure, and that are important after such trauma, as well as the need for a range of interventions to target these factors. Such an approach aims to avoid both biological and sociological reductionism, instead emphasizing the need for a public health approach that reduces vulnerability to trauma and to PTSD, and to increase resilience.

Introduction: Community engagement (CE) is an ethical imperative in research, but the knowledge base for what constitutes effective and ethically sound CE is limited. Ubuntu, as a component of responsive communitarianism where communal welfare is valued together with individual autonomy, is useful in furthering our understanding of effective CE and how it could best be achieved. Similarly, a relative solidarity model serves as a compromise between extreme individualism and extreme communalism and is more appropriate in a heterogenous African context. Approaching CE from an Ubuntu philosophical perspective in southern Africa is particularly important in genomic biobanking, given the implications for individuals, families, and communities. Discussion: CE is often implemented in a tokenistic manner as an ancillary component of research. Understanding consent information is challenging where genomic biobanking is concerned due to scientific complexity. We started a process of CE around genomic biobanking and conducted empirical research in an attempt to develop a model to promote effective and ethically sound CE, using relative solidarity to create a nuanced application of Ubuntu. The TRUCE model is an eight-step model that uses social mapping to identify potential communities, establishes the scope of CE, and requires that communities are approached early. Co-creation strategies for CE are encouraged and co-ownership of knowledge production is emphasized. Recruiting and engaging communities at each stage of research is necessary. Evaluation and adaptation of CE strategies are included. Discussion and dissemination of results after the research is completed are encouraged. Conclusions: There is a significant gap between the theory of CE and its authentic application to research in Africa. This Ubuntu-inspired model facilitates bridging that gap and is particularly suited to genomic biobanking. The CE model enhances and complements the consent process and should be integrated into research as a funding and regulatory requirement where applicable.

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.

Objective: The goal of this meta-analysis was to quantify the risk of dry mouth associated with commonly prescribed antidepressant agents and examine the potential implications of medication class, dose, and pharmacodynamics and dose on risk of treatment-induced dry mouth. Data sources and study selection: A PubMed search was conducted to identify double-blind, randomized, placebo-controlled trials examining the efficacy and tolerability of second generation antidepressant medications for adults with depressive disorders, anxiety disorders, and OCD. Data extraction: A random-effects meta-analysis was used to quantify the pooled risk ratio of treatment-emergent dry mouth with second generation antidepressants compared to placebo. Stratified subgroup analysis and meta-regression was utilized to further examine the effects antidepressant agent, class, dosage, indication, and receptor affinity profile on the measured risk of dry mouth. Results: 99 trials involving 20,868 adults. SNRIs (Relative Risk (RR) = 2.24, 95% Confidence Interval (CI): 1.95-2.58, z = 11.2, p < 0.001) were associated with a significantly greater risk of dry mouth (test for subgroup differences chi(2) = 7.6, df = 1; p = 0.006) compared to placebo than SSRIs (RR = 1.65, 95% CI: 1.39-1.95, z = 5.8, p < 0.001). There was a significant difference found in the risk of dry mouth between diagnostic indications within the SNRI class (test for subgroup differences chi(2) = 9.63, df = 1; p = 0.002). Anxiety diagnoses (RR = 2.78, 95% CI: 2.29-3.38, z = 10.32, p < 0.001) were associated with a greater risk of dry mouth compared to depression (RR = 1.80, 95% CI: 1.48-2.18, z = 5.85, p < 0.001). Decreased affinity for Alpha-1 (PE = 0.18, 95% CI: 0.07-0.28, z = 3.26, p = 0.001) and Alpha-2 (PE = 0.49, 95% CI: 0.22-0.75, z = 3.64, p < 0.001) receptors and SERT (PE = 0.07, 95% CI: 0.01-0.14, z = 2.10, p < 0.05) was significantly associated with increased risk of dry mouth. Conclusions: The current meta-analysis suggests that SSRIs, SNRIs, and atypical antidepressants are all associated with varying degrees of increased risk of dry mouth. SNRIs were associated with a significantly greater risk of dry mouth compared to SSRIs.

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.

Background: Aggression and irritability in children occur across a range of diagnoses, and are associated with both economic cost and negative psychosocial outcomes. Antipsychotics are frequently prescribed in these cases. Methods: A random effects meta-analysis of 14 random controlled trials was conducted. Overall effect sizes for antipsychotics for irritability and aggression were extracted. Subgroup analyses were conducted according to diagnostic indication, specific medication and degree of sedation. Meta-regression examined effects of antipsychotic dose. Results: Overall, antipsychotics were effective in reducing aggression and irritability (SMD = 0.74, 95% confidence interval [CI] 0.57-0.92, z = 8.4, p < 0.0001). In stratified subgroup analysis, individual antipsychotic agents did not differ in efficacy (X-2 = 1.1, df = 3, p = 0.78). However, aripiprazole and risperidone demonstrated significant benefit over placebo. Antipsychotic efficacy did not differ significantly based on diagnostic indication (X-2 = 4.2, df = 4, p = 0.39). Meta-regression showed no overall dose effect. Conclusions: Clinical data supports the efficacy of risperidone and aripiprazole for aggression and irritability across diagnoses, with insufficient data available for other agents. Available data does not support a difference in efficacy based on underlying diagnosis, choice of agent, or its degree of sedation.

ABSTRACT Background: Aggression and irritability in children occur across a range of diagnoses, and are associated with both economic cost and negative psychosocial outcomes. Antipsychotics are frequently prescribed in these cases. Methods: A random effects meta-analysis of 14 random controlled trials was conducted. Overall effect sizes for antipsychotics for irritability and aggression were extracted. Subgroup analyses were conducted according to diagnostic indication, specific medication and degree of sedation. Meta-regression examined effects of antipsychotic dose. Results: Overall, antipsychotics were effective in reducing aggression and irritability (SMD = 0.74, 95% confidence interval [CI] 0.57–0.92, z = 8.4, p < 0.0001). In stratified subgroup analysis, individual antipsychotic agents did not differ in efficacy (χ2 = 1.1, df = 3, p = 0.78). However, aripiprazole and risperidone demonstrated significant benefit over placebo. Antipsychotic efficacy did not differ significantly based on diagnostic indication (χ2 = 4.2, df = 4, p = 0.39). Meta-regression showed no overall dose effect. Conclusions: Clinical data supports the efficacy of risperidone and aripiprazole for aggression and irritability across diagnoses, with insufficient data available for other agents. Available data does not support a difference in efficacy based on underlying diagnosis, choice of agent, or its degree of sedation.

Ketamine has been demonstrated to be an effective, rapidly acting treatment for adults with major depressive disorder (MDD) in multiple randomized, controlled trials.1 More than half of adults with MDD who are given a single ketamine infusion experience a greater than 50% reduction in depressive symptoms within 1 day.1 Although the benefits of ketamine typically dissipate within 3 to 14 days, recent research has suggested that an acute three-times-weekly treatment followed by a continuation phase may prolong antidepressant effects.

Background: There is a poor correlation between total concentrations of proton-accepting compounds (most basic drugs) in unstimulated oral fluid and in plasma. The aim of this study was to compare clozapine, norclozapine, and amisulpride concentrations in plasma and in oral fluid collected using commercially available collection devices [Thermo Fisher Scientific Oral-Eze and Greiner Bio-One (GBO)]. Methods: Oral-Eze and GBO samples and plasma were collected in that order from patients prescribed clozapine. Analyte concentrations were measured by liquid chromatography–tandem mass spectrometry. Results: There were 112 participants [96 men, aged (median, range) 47 (21–65) years and 16 women, aged 44 (21–65) years]: 74 participants provided 2 sets of samples and 7 provided 3 sets (overall 2 GBO samples not collected). Twenty-three patients were co-prescribed amisulpride, of whom 17 provided 2 sets of samples and 1 provided 3 sets. The median (range) oral fluid within the GBO samples was 52 (13%–86%). Nonadherence to clozapine was identified in all 3 samples in one instance. After correction for oral fluid content, analyte concentrations in the GBO and Oral-Eze samples were poorly correlated with plasma clozapine and norclozapine (R2 = 0.57–0.63) and plasma amisulpride (R2 = 0.65–0.72). Analyte concentrations in the 2 sets of oral fluid samples were likewise poorly correlated (R2 = 0.68–0.84). Mean (SD) plasma clozapine and norclozapine were 0.60 (0.46) and 0.25 (0.21) mg/L, respectively. Mean clozapine and norclozapine concentrations in the 2 sets of oral fluid samples were similar to those in plasma (0.9–1.8 times higher), that is, approximately 2- to 3-fold higher than those in unstimulated oral fluid. The mean (±SD) amisulpride concentrations (microgram per liter) in plasma (446 ± 297) and in the Oral-Eze samples (501 ± 461) were comparable and much higher than those in the GBO samples (233 ± 318). Conclusions: Oral fluid collected using either the GBO system or the Oral-Eze system cannot be used for quantitative clozapine and/or amisulpride therapeutic drug monitoring.

OBJECTIVE:Adolescents with autism spectrum disorders (ASD) are increasingly attending college. This case report highlights the nature of the psychiatric difficulties these individuals may face and the potential role for college mental health practitioners.PARTICIPANTS:A case of a female student with ASD presenting with significant inattentive symptoms.METHODS:The authors describe the unique features of this patient's clinical presentation, discuss relevant diagnostic considerations, and make recommendations about how to best approach treatment.RESULTS:This student presented with symptoms of attention-deficit/hyperactivity disorder (ADHD), which were first relevant during her time at college, owing to increased demands on planning and other executive functions. She was eventually responsive to treatment with a stimulant, but had more side effects early on.CONCLUSIONS:As individuals with ASD attend college, their mental health needs will require treatment. However, such treatment draws on a comparatively limited evidence base, and providers need to be aware of potential challenges that may arise.

Background: The use of medical stimulants to sustain attention, augment memory and enhance intellectual capacity is increasing in society. The use of Methylphenidate for cognitive enhancement is a subject that has received much attention in the literature and academic circles in recent times globally. Medical doctors and medical students appear to be equally involved in the off-label use of Methylphenidate. This presents a potential harm to society and the individual as the long-term side effect profile of this medication is unknown.Discussion: The implication of the use of Methylphenidate by medical students and doctors has not been fully explored. This article considers the impact of this use on the traditional role of medicine, society, the patient and suggests a way forward. We discuss the salient philosophy surrounding the use of cognitive enhancement. We query whether there are cognitive benefits to the use of Methylphenidate in healthy students and doctors and whether these benefits would outweigh the risks in taking the medication. Could these benefits lead to tangible outcomes for society and could the off label-use of Methylphenidate potentially undermine the medical profession and the treatment of patients? If cognitive benefits are proven then doctors may be coerced explicitly or implicitly to use the drug which may undermine their autonomy. The increased appeal of cognitive enhancement challenges the traditional role of medicine in society, and calls into question the role of a virtuous life as a contributing factor for achievement. In countries with vast economic disparity such as South Africa an enhancement of personal utility that can be bought may lead to greater inequities.Summary: Under the status quo the distribution of methylphenidate is unjust. Regulatory governmental policy must seek to remedy this while minimising the potential for competitive advantage for the enhanced. Public debate on the use of cognitive enhancement is long overdue and must be stimulated. The use of Methylphenidate for cognitive enhancement is philosophically defendable if long-term research can prove that the risks are negligible and the outcomes tangible.

In the last decade, considerable evidence as accumulated to support the development of Transient Receptor Potential Vanilloid 1 (TRPV1) antagonists for the treatment of various chronic pain conditions. Whereas there is a widely accepted rationale for the development of TRPV1 antagonists for the treatment of various inflammatory pain conditions, their development for indications of chronic pain, where conditions of tactical, mechanical and spontaneous pain predominate, is less clear. Preclinical localization and expression studies provide a firm foundation for the use of molecules targeting TRPV1 for conditions of bone pain, osteoarthritis and neuropathic pain. Selective TRPV1 antagonists weakly attenuate tactile and mechanical hypersensivity and are partially effective for behavioral and electrophysiological endpoints that incorporate aspects of spontaneous pain. While initial studies with TRPV1 antagonist in normal human subjects indicate a loss of warm thermal perception, clinical studies assessing allelic variants suggests that TRPV1 may mediate other sensory modalities under certain conditions. The focus of this review is to summarize the current perspectives of TRPV1 for the treatment of conditions beyond those with a primary thermal sensitivity.

The World Health Organization defines depression as a primary contributor to the global burden of disease and predicts it will become the second leading cause of death by 2020. The need to develop effective therapies has never been so pressing. Current antidepressant drugs have several limitations. This 2010 book looks at the future of mood-disorder research, covering the identification of new therapeutic targets, establishing new preclinical models, new medicinal chemistry opportunities, and fostering greater understanding of genetic influences. These strategies are likely to help build a better picture of the disease process, and lead to new opportunities for patient stratification and treatment. The ultimate goal for this strand of research is to develop more personalized and effective treatments for this chronic and debilitating condition. This is essential reading for all those involved in psychopharmacologic drug development, and mental health clinicians seeking a preview of discoveries soon to influence their practice.

Preface Chad E. Beyer 1. Current depression landscape: a state of the field today Laurence Mignon and Stephen M. Stahl 2. Novel therapeutic targets for treating affective disorders Eliyahu Dremencov and Thomas Cremers 3. Developing novel animal models of depression Lotte de Groote, Malgorzata Filip and Andrew C. McCreary 4. Translational research in mood disorders: using imaging technologies in biomarker research Jul Lea Shamy, Adam M. Brickman, Chris D. Griesemer, Anna Parachikova and Mark Day 5. Defining depression endophenotypes Lisa H. Berghorst and Diego A. Pizzagalli 6. Genetic and genomic studies of major depressive disorder Roy H. Perlis 7. Medicinal chemistry challenges in the design of next generation antidepressants David P. Rotella 8. Application of pharmacogenomics and personalized medicine for the care of depression Keh-Ming Lin, Chun-Yu Chen and Yu-Jui Yvonne Wan Index.

The responsiveness of central noradrenergic systems to stressors and cocaine poses norepinephrine as a potential common mechanism through which drug re-exposure and stressful stimuli promote relapse. This study investigated the role of noradrenergic systems in the reinstatement of extinguished cocaine-induced conditioned place preference by cocaine and stress in male C57BL/6 mice. Cocaine- (15 mg/kg, i.p.) induced conditioned place preference was extinguished by repeated exposure to the apparatus in the absence of drug and reestablished by a cocaine challenge (15 mg/kg), exposure to a stressor (6-min forced swim (FS); 20–25°C water), or administration of the α-2 adrenergic receptor (AR) antagonists yohimbine (2 mg/kg, i.p.) or BRL44408 (5, 10 mg/kg, i.p.). To investigate the role of ARs, mice were administered the nonselective β-AR antagonist, propranolol (5, 10 mg/kg, i.p.), the α-1 AR antagonist, prazosin (1, 2 mg/kg, i.p.), or the α-2 AR agonist, clonidine (0.03, 0.3 mg/kg, i.p.) before reinstatement testing. Clonidine, prazosin, and propranolol failed to block cocaine-induced reinstatement. The low (0.03 mg/kg) but not high (0.3 mg/kg) clonidine dose fully blocked FS-induced reinstatement but not reinstatement by yohimbine. Propranolol, but not prazosin, blocked reinstatement by both yohimbine and FS, suggesting the involvement of β-ARs. The β-2 AR antagonist ICI-118551 (1 mg/kg, i.p.), but not the β-1 AR antagonist betaxolol (10 mg/kg, i.p.), also blocked FS-induced reinstatement. These findings suggest that stress-induced reinstatement requires noradrenergic signaling through β-2 ARs and that cocaine-induced reinstatement does not require AR activation, even though stimulation of central noradrenergic neurotransmission is sufficient to reinstate.