When should meta-analysis avoid making hidden normality assumptions?

Meta-analysis is a widely used statistical technique. The simplicity of the calculations required when performing conventional meta-analyses belies the parametric nature of the assumptions that justify them. In particular, the normal distribution is extensively, and often implicitly, assumed. Here, we review how the normal distribution is used in meta-analysis. We discuss when the normal distribution is likely to be adequate and also when it should be avoided. We discuss alternative and more advanced methods that make less use of the normal distribution. We conclude that statistical methods that make fewer normality assumptions should be considered more often in practice. In general, statisticians and applied analysts should understand the assumptions made by their statistical analyses. They should also be able to defend these assumptions. Our hope is that this article will foster a greater appreciation of the extent to which assumptions involving the normal distribution are made in statistical methods for meta-analysis. We also hope that this article will stimulate further discussion and methodological work.

Olfactory aversive conditioning during sleep reduces cigarette-smoking behavior.

Recent findings suggest that novel associations can be learned during sleep. However, whether associative learning during sleep can alter later waking behavior and whether such behavioral changes last for minutes, hours, or days remain unknown. We tested the hypothesis that olfactory aversive conditioning during sleep will alter cigarette-smoking behavior during ensuing wakefulness. A total of 66 human subjects wishing to quit smoking participated in the study (23 females; mean age, 28.7 ± 5.2 years). Subjects completed a daily smoking diary detailing the number of cigarettes smoked during 7 d before and following a 1 d or night protocol of conditioning between cigarette odor and profoundly unpleasant odors. We observed significant reductions in the number of cigarettes smoked following olfactory aversive conditioning during stage 2 and rapid eye movement (REM) sleep but not following aversive conditioning during wakefulness (p < 0.05). Moreover, the reduction in smoking following aversive conditioning during stage 2 (34.4 ± 30.1%) was greater and longer lasting compared with the reduction following aversive conditioning during REM (11.9 ± 19.2%, p < 0.05). Finally, the reduction in smoking following aversive conditioning during sleep was significantly greater than in two separate control sleep experiments that tested aversive odors alone and the effects of cigarette odors and aversive odors without pairing. To conclude, a single night of olfactory aversive conditioning during sleep significantly reduced cigarette-smoking behavior in a sleep stage-dependent manner, and this effect persisted for several days.

Formation of aversive memories associated with conditioned drug withdrawal requires BDNF expression in the amygdala in acute morphine-dependent rats.

AIM: Brain-derived neurotrophic factor (BDNF) plays an important role in learning and memory in multiple brain areas. In the present study, we investigated the roles of BDNF in aversive memories associated with conditioned drug withdrawal in acute morphine-dependent rats. METHODS: Conditioned place aversion (CPA) was induced in male SD rats exposed to a single dose of morphine (10 mg/kg, sc) followed by naloxone (0.3 mg/kg, sc). In some rats, BDNF receptor antagonist K252a (8.5 ng per side) or BDNF scavenger TrkB-FC (0.65 µg per side) was bilaterally microinjected into amygdala before naloxone injection. BDNF mRNA and protein expression levels in amygdala were detected after the behavior testing. RESULTS: CPA behavior was induced in rats by the naloxone-precipitated morphine withdrawal, which was accompanied by significantly increased levels of BDNF mRNA and protein in the amygdala. Bilateral microinjection of TrkB-FC or K252a into the amygdala completely blocked CPA behavior in the rats. CONCLUSION: Formation of aversive memories associated with conditioned drug withdrawal in acute morphine-dependent rats requires BDNF expression in the amygdala.

Young and old Pavlovian fear memories can be modified with extinction training during reconsolidation in humans.

Extinction training during reconsolidation has been shown to persistently diminish conditioned fear responses across species. We investigated in humans if older fear memories can benefit similarly. Using a Pavlovian fear conditioning paradigm we compared standard extinction and extinction after memory reactivation 1 d or 7 d following acquisition. Participants who underwent extinction during reconsolidation showed no evidence of fear recovery, whereas fear responses returned in participants who underwent standard extinction. We observed this effect in young and old fear memories. Extending the beneficial use of reconsolidation to older fear memories in humans is promising for therapeutic applications.

Nurses and subordination: a historical study of mental nurses' perceptions on administering aversion therapy for 'sexual deviations'.

This study aimed to examine the meanings that nurses attached to the 'treatments' administered to cure 'sexual deviation' (SD) in the UK, 1935-1974. In the UK, homosexuality was considered a classifiable mental illness that could be 'cured' until 1992. Nurses were involved in administering painful and distressing treatments. The study is based on oral history interviews with fifteen nurses who had administered treatments to cure individuals of their SD. The interviews were transcribed for historical interpretation. Some nurses believed that their role was to passively follow any orders they had been given. Other nurses limited their culpability concerning administering these treatments by adopting dehumanising and objectifying language and by focussing on administrative tasks, rather than the human beings in need of their care. Meanwhile, some nurses genuinely believed that they were acting beneficently by administering these distinctly unpleasant treatments. It is envisaged that this study might act to reiterate the need for nurses to ensure their interventions have a sound evidence base and that they constantly reflect on the moral and value base of their practice and the influence that science and societal norms can have on changing views of what is considered 'acceptable practice'.

Contextual fear cues inhibit eating in food-deprived male and female rats.

Previously we have shown that food-deprived male and female rats inhibit food consumption when presented with a discrete conditioned stimulus that signals danger. Here, in a series of three experiments, we examined whether contextual conditioned stimuli can exert the same effect. Experiment 1 paired a distinct context with footshocks, to examine food intake in food-deprived rats upon re-exposure to the context. Experiment 2 used a discrimination protocol with two alternating contexts; rats were given food in one, and received footshocks in the other. This protocol allowed us to monitor food consumption during training in a context never associated with footshocks, and to evaluate consumption at test in a context that had been previously paired with footshocks. Experiments 1 and 2 compared experimental groups to controls that never received footshocks. Experiment 3 used a within-subjects design to assess the specificity of the inhibition by the contextual cues, separate from any generalized effects due solely to the prior experience of footshocks. Our results demonstrate that similar to discrete cues, contextual cues previously associated with aversive events can inhibit feeding in food-deprived animals. These findings are important for our understanding of environmental contributions to the control of food intake.

[The history of reorientation therapy]. / A reorientációs terápia története.

Most scientists today agree that sexual orientation is most likely the result of a complex interaction of environmental, cognitive, and biological factors. In past decades in the United States there has been a big discourse as to the necessity and effectiveness of changing same-sex attraction. Researchers disagree on whether same-sex attraction can be changed. Position statements of the major mental health organizations state that there is not enough scientific evidence to support the reorientation therapy. In addition, there is some evidence to indicate that some individuals experienced harm or believed they had been harmed by these interventions. The aim of this article is to give a historic overview of the reorientation therapies, to review the efficacy of the therapies, motivations for seeking therapy, arguments for and against the therapy, and to overview the actual mainstream organizations' statements.

Treatments for alcohol-related disorders in China: a developing story.

AIMS: Alcohol-related disorders (ARDs) have become an increasing mental health and social challenge in China. Research from China may provide important clinical information for researchers and clinicians around the world. However, most of the Chinese research on ARDs has only been published in Chinese language journals. This article summarizes publications related to treatments for ARDs found in the Chinese literature. METHODS: A descriptive study based on literature identified from searches of the China National Knowledge Infrastructure (1979-2012), Pubmed databases and hand-picked references with emphasis on traditional Chinese medicine (TCM). RESULTS: More than 1500 Chinese language papers on treatment for ARDs were found and ~110 were selected. Many medications used in the Western countries (e.g. disulfiram and acamprosate) are not available in China, and no drugs have been officially approved for alcohol dependence. TCM approaches (including acupuncture, electroacupunture and herbals) have played a role in treatment for ARDs with some positive results. These unique methods are reviewed and the need for additional controlled studies is noted. CONCLUSION: Currently, very limited facilities, medications or programs are available for patients with ARDs in China, thus much improvement is needed in the field, including setting up intervention/treatment programs.

Using an invertebrate model to investigate the mechanisms of short-term memory deficits induced by food deprivation.

Although prolonged food deprivation is known to cause memory deficits, the underlying mechanisms are only partially understood. In this study, we began to investigate the cellular substrates of food deprivation-induced memory impairments in the invertebrate Aplysia. Following a single trial of noxious stimuli, Aplysia concurrently express short-term sensitization (an elementary form of learning in which withdrawal reflexes are enhanced) and short-term feeding suppression for at least 15 min. Cellular correlates of sensitization and feeding suppression include increased excitability of the tail sensory neurons (TSNs) controlling the withdrawal reflexes, and decreased excitability of feeding decision-making neuron B51, respectively. Recently, 14 days of food deprivation (14DFD) was reported to break the co-expression of sensitization and feeding suppression in Aplysia without health deterioration. Specifically, under 14DFD, sensitization was completely prevented while feeding suppression was present albeit attenuated. This study explored the cellular mechanisms underlying the absent sensitization and reduced feeding suppression under 14DFD. A reduced preparation was used to evaluate the short-term cellular modifications induced by delivering an aversive training protocol in vitro. TSN excitability failed to increase following in vitro training under 14DFD, suggesting that the lack of sensitization may be a consequence of the fact that TSN excitability failed to increase. B51 excitability also failed to decrease following in vitro training, indicating that additional neurons may contribute to the conserved albeit reduced feeding suppression in 14DFD animals. This study lays the foundations for the future use of the Aplysia model system to investigate the mechanisms underlying the memory impairments induced by prolonged food deprivation.

Peripheral administration of PYY(3-36) produces conditioned taste aversion in mice.

Peptide YY (PYY) is a postprandially released gut hormone. Peripheral administration of one form of the peptide PYY3-36 produces a short-term reduction in food intake in rodents. Initial reports suggested that effects of PYY3-36 on food intake are mediated by increasing the anorexigenic drive from melanocortin neurons in the hypothalamic arcuate nucleus. However, more recent data have demonstrated that the anorexigenic activity of PYY3-36 is not dependent on melanocortin ligands or their receptors in the CNS. We demonstrate here that the anorexigenic actions of PYY3-36 are also not dependent on the vagus nerve, a common pathway of satiety signaling. Peripherally administered PYY3-36 activates neurons in the area postrema and nucleus tractus solitarius, brainstem areas known to mediate effects of certain aversive stimuli. Furthermore, peripheral administration of PYY3-36 causes conditioned taste aversion in mice. Thus, inhibition of food intake by PYY3-36 may result in part from induction of an aversive response.

Launch of IRCT report on conversion therapy.

On 23 April 2020, IRCT published its research on the global practice of conversion therapy. The report, entitled "It's Torture Not Therapy," compiles information on the "practices, practitioners and roles of states in conducting, supporting, promoting and acquiescing in conversion therapy" and is intended to supplement the Expert Statement of the Independent Forensic Expert Group on the same issue, also printed in this edition of Torture Journal.

Statement of the Independent Forensic Expert Group on Conversion Therapy.

Conversion therapy is a set of practices that aim to change or alter an individual's sexual orientation or gender identity. It is premised on a belief that an individual's sexual orientation or gender identity can be changed and that doing so is a desirable outcome for the individual, family, or community. Other terms used to describe this practice include sexual orientation change effort (SOCE), reparative therapy, reintegrative therapy, reorientation therapy, ex-gay therapy, and gay cure. Conversion therapy is practiced in every region of the world. We have identified sources confirming or indicating that conversion therapy is performed in over 60 countries. In those countries where it is performed, a wide and variable range of practices are believed to create change in an individual's sexual orientation or gender identity. Some examples of these include: talk therapy or psychotherapy (e.g., exploring life events to identify the cause); group therapy; medication (including anti-psychotics, anti- depressants, anti-anxiety, and psychoactive drugs, and hormone injections); Eye Movement Desensitization and Reprocessing (where an individual focuses on a traumatic memory while simultaneously experiencing bilateral stimulation); electroshock or electroconvulsive therapy (ECT) (where electrodes are attached to the head and electric current is passed between them to induce seizure); aversive treatments (including electric shock to the hands and/or genitals or nausea-inducing medication administered with presentation of homoerotic stimuli); exorcism or ritual cleansing (e.g., beating the individual with a broomstick while reading holy verses or burning the individual's head, back, and palms); force-feeding or food deprivation; forced nudity; behavioural conditioning (e.g., being forced to dress or walk in a particular way); isolation (sometimes for long periods of time, which may include solitary confinement or being kept from interacting with the outside world); verbal abuse; humiliation; hypnosis; hospital confinement; beatings; and "corrective" rape. Conversion therapy appears to be performed widely by health professionals, including medical doctors, psychiatrists, psychologists, sexologists, and therapists. It is also conducted by spiritual leaders, religious practitioners, traditional healers, and community or family members. Conversion therapy is undertaken both in contexts under state control, e.g., hospitals, schools, and juvenile detention facilities, as well as in private settings like homes, religious institutions, or youth camps and retreats. In some countries, conversion therapy is imposed by the order or instructions of public officials, judges, or the police. The practice is undertaken with both adults and minors who may be lesbian, gay, bisexual, trans, or gender diverse. Parents are also known to send their children back to their country of origin to receive it. The practice supports the belief that non-heterosexual orientations are deviations from the norm, reflecting a disease, disorder, or sin. The practitioner conveys the message that heterosexuality is the normal and healthy sexual orientation and gender identity. The purpose of this medico-legal statement is to provide legal experts, adjudicators, health care professionals, and policy makers, among others, with an understanding of: 1) the lack of medical and scientific validity of conversion therapy; 2) the likely physical and psychological consequences of undergoing conversion therapy; and 3) whether, based on these effects, conversion therapy constitutes cruel, inhuman, or degrading treatment or torture when individuals are subjected to it forcibly2 or without their consent. This medico-legal statement also addresses the responsibility of states in regulating this practice, the ethical implications of offering or performing it, and the role that health professionals and medical and mental health organisations should play with regards to this practice. Definitions of conversion therapy vary. Some include any attempt to change, suppress, or divert an individual's sexual orientation, gender identity, or gender expression. This medico-legal statement only addresses those practices that practitioners believe can effect a genuine change in an individual's sexual orientation or gender identity. Acts of physical and psychological violence or discrimination that aim solely to inflict pain and suffering or punish individuals due to their sexual orientation or gender identity, are not addressed, but are wholly condemned. This medico-legal statement follows along the lines of our previous publications on Anal Examinations in Cases of Alleged Homosexuality1 and on Forced Virginity Testing.2 In those statements, we opposed attempts to minimise the severity of physical and psychological pain and suffering caused by these examinations by qualifying them as medical in nature. There is no medical justification for inflicting on individuals torture or other cruel, inhuman, or degrading treatment or punishment. In addition, these statements reaffirmed that health professionals should take no role in attempting to control sexuality and knowingly or unknowingly supporting state-sponsored policing and punishing of individuals based on their sexual orientation or gender identity.

Verbal aversive control in clinical interaction.

BACKGROUND: Aversive control techniques involve aversive stimuli to generate behavioral change. The purpose of this work is to analyze the use of verbal aversive control by psychologists during the clinical interaction, combining respondent and operant explanations. METHOD: Observational methodology is used to analyze 26 session recordings of three different cases of anxiety disorder, relationship problem and low mood problem (27h 32') carried out by two psychologists of the Therapeutic Institute of Madrid. The variables considered were psychologists' aversive and non-aversive verbalizations and clients' antitherapeutic verbalizations. RESULTS: There is a strong relationship between clients' antitherapeutic verbalizations and psychologists' aversive verbalizations, both potential punishments (aversive verbalizations contingent on the client's response) and aversive pairings. Additionally, the possible psychologists' aversive verbalizations are accompanied by other verbalizations aimed to induce clients' non-problematic behaviors. CONCLUSIONS: This work opens a new way to an explanation of therapeutic change using learning processes (both respondent and operant conditioning) that take place through verbal interaction in clinical context.

Long-term effects of cognitive behavior therapy on brain activation in spider phobia.

This functional magnetic resonance imaging study investigated long-term effects of cognitive behavior therapy (CBT) in individuals suffering from spider phobia. Ten female patients who had shown positive immediate CBT effects were invited to take part in a 6-month follow-up investigation. Here, the patients, along with eight non-phobic females, were presented with the same pictures depicting spiders, generally disgust-inducing, generally fear-inducing and neutral content, which they had viewed 6 months earlier. Patients' self-report and overt behavior indicated a positive long-term clinical improvement. Related hemodynamic changes included an increase in medial orbitofrontal cortex (OFC) activity. As the medial OFC is involved in emotion-related learning, especially in the representation of positive stimulus-outcome associations, we conclude that the medial OFC effect constitutes the neuronal basis of the lasting positive CBT outcome. Activity to disorder-irrelevant pictures decreased across the sessions in the lateral OFC and in the insula, which most likely reflects general habituation.

Quantitative electroencephalographic (qEEG) correlates of craving during virtual reality therapy in alcohol-dependent patients.

Virtual reality (VR) is an evolving technology that is being applied to treat a wide range of medical and psychiatric diseases. A virtual reality therapy (VRT) with multisensory stimulation has been applied to patients with alcohol dependence (ADP). We hypothesized that the VRTP for alcohol dependence would reduce the craving for alcohol and increase alpha wave activity in frontal areas of individuals with ADP. Twenty ADP and eighteen ADP were exposed to a series of 10 VRTP sessions (VRTP-ADP) and cognitive behavioral therapy (nVRTP-ADP), respectively. Fifteen healthy controls were exposed to VRTP for comparing the changes of craving and EEG during all three phases of VRTP. The VRTP-ADP exhibited a greater decrease in craving after the 10th VRTP session, when compared to the nVRTP-ADP. Compared to the healthy control subjects, VRTP-ADP group showed higher magnitude of the change in craving throughout VRTP sessions. These results suggest that VRTP may be useful as an adjunct to treating alcohol dependence but may also serve as an evaluation tool to identify high-risk patients.

Calf aversion to hot-iron disbudding.

Dairy calves are routinely disbudded by cauterization with a hot iron. To mitigate the intra-operative and initial post-operative pain associated with this procedure some farmers provide calves general and local anesthetics, but it is unknown if the procedure remains aversive. We used a place-conditioning paradigm to assess aversion caused by hot-iron cautery with a local anesthetic compared to a sham procedure. A test area was divided into three equally sized pens: two 'treatment' pens with distinct visual cues were connected by a central 'neutral' pen. Each calf went through the disbudding procedure and a 6-h recovery period in one treatment pen and the control procedure in the other treatment pen. In three tests (48, 72 and 96 h after the second treatment), calves could freely roam among the pens until they chose to lie down, ending the session. Calves spent less time in either of the treatment pens compared to the central pen. When only comparing the two treatment pen, calves spent less time in the disbudding pen, especially during the first test. Calves were also less likely to lie down in the pen associated with the disbudding procedure. We conclude that even with the use of a local anesthetic, hot-iron disbudding is salient and aversive for calves, indicating the need to refine or avoid the procedure.