U potrazi za optimalnom psihoaktivacijom – stimulansi kao pojačivači kognitivne funkcije

An increasing number of people, students in particular, seek substances that improve their cognitive functioning. The most popular group of pharmacological cognitive enhancers (PCEs) are stimulants. Available studies suggest a small beneficial effect of methylphenidate and amphetamine on memory, executive functions, and processing speed. However small, this effect can make the difference between success and failure. In recent years, research has focused on the additional beneficial effect on the emotional state, increased motivation, and placebo-induced cognitive enhancement. This paper briefly reviews the latest and most important research on the relationship between popular stimulants and cognitive enhancement. One cannot understand this relationship without understanding the Yerkes-Dodson law, which explains the relationship between the degree of arousal and performance. It suggests that the effect of stimulants is a dose-dependent continuum. This law has repeatedly been confirmed by studies in which an optimal level of psychoactivation for cognitive enhancement was obtained with low stimulant doses, whereas exceeding the effective dose resulted in cognitive deficits, psychomotor agitation, and addiction. A separate section has been devoted to modafinil, an increasingly popular stimulant that differs from the rest in neurochemical profile and behavioural effects.Sve više ljudi, napose studenata, traži tvari kojima će poboljšati svoju kognitivnu funkciju. Najpopularniji među farmakološkim pojačivačima kognitivne funkcije jesu stimulansi. Rezultati dostupnih istraživanja pokazuju blago, povoljno djelovanje metilfenidata i amfetamina na pamćenje, izvršne funkcije i brzinu obrade (procesiranja). Premda je poboljšanje blago, ono u studenata može značiti razliku između uspjeha i neuspjeha. Posljednjih se je godina istraživanje usmjerilo na dodatne povoljne učinke stimulansa na emocionalno stanje, povećanu motivaciju, pa i na kognitivna poboljšanja povezana s placebom. U ovom se radu daje kratki pregled najnovijih i najvažnijih istraživanja odnosa između popularnih stimulansa i poboljšanja kognitivne funkcije. Taj se odnos ne može razumjeti bez poznavanja Yerkes-Dodsonova zakona, koji objašnjava odnos između razine uzbuđenosti i izvedbe (performanse) te govori o tome da stimulansi djeluju u kontinuumu koji je ovisan o dozi. Zakon je opetovano potvrđivan istraživanjima u kojima je optimalna razina psihoaktivacije za poboljšanje kognitivne funkcije postignuta niskim dozama stimulansa, a previsoke razine dovodile su do pada kognitivnih deficita, psihomotorne agitacije i ovisnosti. Dio je teksta posvećen modafinilu, sve popularnijem stimulansu koji se svojim neurokemijskim svojstvima i djelovanjem na ponašanje razlikuje od ostalih

Association between selective serotonin reuptake inhibitors and violent crime – could underlying psychopathology be the cause?

International audienceFuelling the discussion regarding the safety of selective serotonin reuptake inhibitors (SSRIs), the present large Swedish nationwide cohort registry study (Lagerberg et al., 2020) tries to answer whether treatment with SSRIs is associated with increased risk of committing a violent crime. This is a substantial extension of a previous population-based study (Molero et al., 2015), which reported a positive association between SSRI use and violent crime only in individuals younger than 25. As the previous study was possibly underpowered to detect differences in other age groups, the present study has twice as long follow-up period, and almost three times higher number of events, with more than 32 thousand violent crimes committed by 20 thousand individuals

Use of cognitive enhancers among medical students in Lithuania

AIMS – The purpose of this study is to analyse the use of cognitive enhancers among medical students in Lithuania, determine the reasons for usage and evaluate the contributing factors such as socio-demographic characteristics, stress levels, sleep quality and knowing somebody who has used a neuro-enhancing drug

Ketamine and esketamine for crisis management in patients with depression: Why, whom, and how?

International audienceCurrently, only a limited number of interventions can rapidly relieve depressive symptomatology in patients with major depressive disorder or bipolar disorder experiencing extreme distress. Such crises, especially when suicide attempt or ideation is involved, are a major risk factor of suicide. Ketamine, a N-methyl-d-aspartate glutamate receptor antagonist, and its enantiomer esketamine rapidly reduce depressive symptoms in depressed patients with current suicidal ideation. Recently, esketamine has been approved for use in patients with depression at risk of suicide and for psychiatric emergency by major medical agencies in the United States and Europe, whereas ketamine is increasingly used off-label. However, there is currently limited guidance on why, when, and how to use these drugs in patients with depression to treat a crisis. In this review article, we provide a succinct overview of the cellular and molecular mechanisms of action of ketamine and esketamine, and of the functional brain changes following their administration. We also summarize the major clinical studies on ketamine and esketamine efficacy in patients experiencing a crisis (generally, suicidal ideation), and propose a profile of patients who can benefit most from such drugs, on the basis of neurobiological and clinical observations. Finally, we describe the administration mode, the efficacy and tolerability profiles, the side effect management, possible concomitant treatments and the issue of deprescribing

Clinical insight in anorexia nervosa: Associated and predictive factors

International audienceClinical and cognitive factors associated with clinical insight regarding both baseline level and its time-related changes, in outpatients treated for anorexia nervosa. The 193 participants were recruited at 13 French centers specializing in eating disorders (FFAB network) and assessed for insight (SAI-ED), body mass index (BMI), eating disorder severity, symptoms of depression and anxiety, emotional state, silhouette, and functionality; two cognitive tests were also administered. The 137 patients were then re-assessed 18 weeks later. Minimum and ideal subjective BMI and premorbid intelligence were associated with poor baseline insight. Contrary to nearly all other clinical factors, the level of insight revealed no improvement after four months of care. Only the higher value of the minimum lifetime BMI was significantly predictive of increased insight. More positive emotions (PANAS), less symptoms of depression and anxiety (HADS scores), and fewer syndromes (HADS above threshold) were the only factors that covaried with the changes in the level of insight. In conclusion, poor insight has little time variability, contrary to nearly all clinical and cognitive factors. As increased insight is mainly accompanied by improvements in the emotional domain, the latter could represent potential targets for patients with lack of awareness about their eating disorder

« Rien ne fait moins mal qu’être mort »: La douleur psychologique dans les descriptions de cas d’euthanasie et de suicide assisté psychiatrique aux Pays-Bas

International audienceObjectives: Euthanasia and assisted suicide (EAS) of individuals with mental disorders is a growing practice in several countries, including the Netherlands. Here, we aimed to identify the most frequent dimensions of and associated factors to psychological pain, which has been associated with suicidality, in individuals undergoing psychiatric EAS. Methods: An exploratory retrospective content analysis of the English translation of 66 digital case records of individuals who died by EAS in the Netherlands between 2011 and 2014 was performed. Nine standard psychological pain dimensions (irreversibility, loss of control, emptiness, emotional flooding, freezing, social distancing, narcissistic wounds, confusion, and self-estrangement), illness, and sociodemographic variables were evaluated by 2 independent raters using a premade data abstraction form (Kohen κ > 0.8 in all cases). Results: The mean number of dimensions was 4.64 ± 1.20 (median = 5), out of 9. The most frequent dimensions were irreversibility, loss of control, emptiness, and emotional flooding, in decreasing order. Past treatment refusal and the mention of social connections in case descriptions were related to the higher number of psychological pain dimensions (4.89 ± 1.24 vs. 4.31 ± 1.07, P = 0.03 and 5.05 ± 1.17 vs. 4.43 ± 1.17, P = 0.03, respectively). Emotional flooding was the only dimension specifically associated with specific psychiatric conditions, namely posttraumatic phenomena and personality disorders. Conclusions: Numerous psychological pain dimensions were detected in case descriptions of individuals who underwent EAS before the procedure. Subjective nature of the study precludes definite conclusions but suggest that future studies should explore psychological pain and the role of interventions targeting it in patients requesting EAS

Improved functioning following computerized working memory training (COGMED®) in euthymic patients with bipolar disorder and cognitive complaints: An exploratory study

International audiencePatients with bipolar disorder (BD) frequently have cognitive deficits even when euthymic. These deficits are considered one of the main drivers of functional disability in BD. This study investigated whether computerized working memory training using the COGMED® program in patients with BD can improve global functioning, therapeutic compliance, and subjective quality of life. Methods: For this naturalistic prospective study, 40 patients with BD and cognitive complaints were recruited. Sociodemographic, clinical, neurocognitive and functional data were collected before starting the remediation intervention (baseline). At home, patients used the web-based working memory training program COGMED® that included a battery of interactive games (daily sessions, five days per week for five weeks), supported by weekly phone-based feedback. The clinical, neurocognitive and functional assessment was repeated four weeks after the intervention end and compared with the baseline data.Results: Thirty-two patients completed the study. Compared with baseline, general functioning was improved after the working memory training program, as indicated by a mean reduction of 6.78 (SD 4.65) points in the Functioning Assessment Short Test (p<0.001). This result remained significant after controlling for depressive symptomatology improvement. Similarly, the scores of neuropsychological tests for cognitive complaints, as well as verbal and visuospatial working memory components were significantly different before and after the intervention (p<0.05). Conversely, the subjective quality of life and therapeutic compliance did not change.Limitations: The naturalistic open-label, non-controlled design of this study precludes the conclusion regarding causality.Conclusions: In patients with BD, global functioning is improved by computerized working memory remediation

CYP2C19 polymorphisms are associated with severity of depression at initial evaluation and after the treatment independently of the prescribed medications: 4 weeks prospective study

International audienceBackground: The cytochrome P-450 2C19 (CYP2C19) enzyme is involved in the metabolism of numerous antidepressants. It also metabolises some endogenous substrates, which could also confer to vulnerability. We aimed to establish whether the severity of depression and treatment response are associated with the genetically predicted CYP2C19 phenotype.Methods: We assessed the CYP2C19 genotype-predicted metabolic phenotypes (normal, intermediate or ultrarapid, there were no poor metabolisers) in patients with moderate or severe depression. We used the self-rated Beck Depression Inventory-II (BDI-II) scale and the clinician-rated Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline, after 2 and 4 weeks of an empirical treatment trial. Patients and clinicians were blind to the genetic testing results.Results: Seventy-six patients participated in the present study. At baseline, impaired CYP2C19 metabolisers, compared to normal metabolisers, had higher BDI-II (P = 0.046; ηp2 = 0.08) but not MADRS score. Intermediate metabolisers more often had a diagnosis of severe depression than normal metabolisers (P = 0.003). After 4 weeks of empirical treatment, intermediate metabolisers had significantly higher MADRS and BDI-II scores than normal metabolisers (P = 0.006; ηp2 = 0.131 and P = 0.030; ηp2 = 0.091). These differences were independent of the use of CYP2C19-metabolised medications in the treatment trial, as well as the treatment discrepancy status.Conclusions: Intermediate CYP2C19 polymorphism-predicted activity was associated with more severe depression after an empirical treatment trial. The lack of association between the prescription of CYP2C19-metabolised drugs and treatment response calls for a further look into the role of endogenous substrates of CYP2C19