Psychiatric Therapeutics Research Articles

Ketamine infusions for treatment-resistant bipolar depression: Commentary.

Ketamine infusions for treatment-resistant bipolar depression: Commentary.

Mental Health Care Education and Training in Pharmacy Programs in Arabic-Speaking Countries

ObjectiveThis study aimed to assess how entry-level pharmacy programs in Arab countries prepare graduates to provide mental health care, specifically examining the didactic curricula and experiential training in psychiatry in bachelor and PharmD programs. MethodsAn electronic survey was sent to all entry-level pharmacy programs in the 22 Arab countries asking to report on the 2021-2022 academic year. The survey assessed teaching and learning (eg, psychiatric diseases taught and extent of the coverage; contact hours dedicated to psychiatric therapeutics, pharmacology, and medicinal chemistry), experiential training in psychiatry and its challenges, and graduates’ preparedness to provide mental health. A descriptive analysis of the data was undertaken, and data were reported for bachelor and PharmD programs separately. ResultsOverall, 35 pharmacy programs completed the survey. All PharmD programs and 80% of bachelor programs covered psychiatric therapeutics, and most contact hours were dedicated to pharmacology, followed by psychiatric therapeutics and medicinal chemistry. Over half of the faculty considered that depression and anxiety disorders were covered sufficiently, and 56.2% of programs did not offer experiential training in psychiatry. Common challenges in psychiatry experiential training included a lack of sites and qualified preceptors. Overall, 26.4% of faculty positively rated graduates’ preparedness to provide mental health care. Graduates who completed experiential training in psychiatry and PharmD graduates were rated higher. ConclusionPharmaceutical education in Arab countries could be improved by enhancing the teaching and assessment of mental health topics and expanding psychiatry experiential training. Such changes would improve entry-level pharmacists’ competencies in mental health care provision.

Unsupervised Machine Learning to Identify Depressive Subtypes.

ObjectivesThis study evaluated an unsupervised machine learning method, latent Dirichlet allocation (LDA), as a method for identifying subtypes of depression within symptom data.MethodsData from 18,314 depressed patients were used to create LDA models. The outcomes included future emergency presentations, crisis events, and behavioral problems. One model was chosen for further analysis based upon its potential as a clinically meaningful construct. The associations between patient groups created with the final LDA model and outcomes were tested. These steps were repeated with a commonly-used latent variable model to provide additional context to the LDA results.ResultsFive subtypes were identified using the final LDA model. Prior to the outcome analysis, the subtypes were labeled based upon the symptom distributions they produced: psychotic, severe, mild, agitated, and anergic-apathetic. The patient groups largely aligned with the outcome data. For example, the psychotic and severe subgroups were more likely to have emergency presentations (odds ratio [OR] = 1.29; 95% confidence interval [CI], 1.17–1.43 and OR = 1.16; 95% CI, 1.05–1.29, respectively), whereas these outcomes were less likely in the mild subgroup (OR = 0.86; 95% CI, 0.78–0.94). We found that the LDA subtypes were characterized by clusters of unique symptoms. This contrasted with the latent variable model subtypes, which were largely stratified by severity.ConclusionsThis study suggests that LDA can surface clinically meaningful, qualitative subtypes. Future work could be incorporated into studies concerning the biological bases of depression, thereby contributing to the development of new psychiatric therapeutics.

How is mental health care provided through community pharmacies? A quest for improvement

Background:Mental disease burden is increasing globally, and a substantial shortage of mental health professionals remains. Community pharmacists can improve population mental health outcomes to bridge the mental health care gap. However, there is a paucity of data on community pharmacists’ provision of mental health care.Objective:To assess community pharmacist-delivered care to people with mental illness in the United Arab Emirates (UAE), focusing on dispensing and counseling practices, pharmacists’ confidence and comfort in providing care, and attitudes and beliefs towards mental illness.Methods:This was a mixed-methods study with an exploratory, sequential design. Semi-structured interviews explored community pharmacists’ practices, challenges and strategies to improve care. Data were analyzed thematically, and the results guided questionnaire development. The questionnaire was also informed by the Framework of Core Mental Health Competencies for All Pharmacy Professionals and other relevant literature and administered to community pharmacists in four out of seven emirates. Logistic regression was used to identify the predictors of pharmacist practices.Results:In the interviews, community pharmacists described adopting a precautionary attitude and perceived their role as a dispensing one. They reported challenges such as emotional discomfort and lack of training but highlighted the need for a different approach to patients with mental illness. In total, 252 pharmacists completed the questionnaire, and 74% reported performing at least five counseling practices. Logistic regression showed that pharmacists who performed a higher number of practices (≥5) were younger, received continuing education on mental health care in the last two years, and had higher confidence levels.Conclusion:UAE community pharmacists performed basic dispensing practices and reported discomfort during encounters with patients with mental illness. Training on patient-centered communication skills and psychiatric therapeutics is needed to improve pharmacist-delivered services, alongside increased collaboration with other providers and services.

The Role of the Dorsal-Lateral Prefrontal Cortex in Reward Sensitivity During Approach-Avoidance Conflict.

Approach-Avoidance conflict (AAC) arises from decisions with embedded positive and negative outcomes, such that approaching leads to reward and punishment and avoiding to neither. Despite its importance, the field lacks a mechanistic understanding of which regions are driving avoidance behavior during conflict. In the current task, we utilized transcranial magnetic stimulation (TMS) and drift-diffusion modeling to investigate the role of one of the most prominent regions relevant to AAC-the dorsolateral prefrontal cortex (dlPFC). The first experiment uses in-task disruption to examine the right dlPFC's (r-dlPFC) causal role in avoidance behavior. The second uses single TMS pulses to probe the excitability of the r-dlPFC, and downstream cortical activations, during avoidance behavior. Disrupting r-dlPFC during conflict decision-making reduced reward sensitivity. Further, r-dlPFC was engaged with a network of regions within the lateral and medial prefrontal, cingulate, and temporal cortices that associate with behavior during conflict. Together, these studies use TMS to demonstrate a role for the dlPFC in reward sensitivity during conflict and elucidate the r-dlPFC's network of cortical regions associated with avoidance behavior. By identifying r-dlPFC's mechanistic role in AAC behavior, contextualized within its conflict-specific downstream neural connectivity, we advance dlPFC as a potential neural target for psychiatric therapeutics.

Psychedelic drugs as new tools in psychiatric therapeutics.

Psychedelic drugs as new tools in psychiatric therapeutics.

Lithium therapy in literature and art

Introduction. In 1949, Australian psychiatrist John Cade described a therapeutic action of lithium carbonate in mania. This date is regarded as an introduction of lithium into contemporary psychiatric therapeutics and the beginning of modern psychopharmacology. In the early 1960s, a prophylactic activity of lithium was observed, preventing recurrences of affective episodes in mood disorders. Lithium has become a prototype of the mood-stabilising drugs and remains a drug of the first choice for the prophylaxis of recurrences in bipolar mood disorder. Literature review. Both the introduction of lithium into psychiatric therapy and its therapeutic action has been reflected in literature and art. This article presents the connections of lithium therapy with literature and art. They pertain to such characters as John Cade, Salvador Luria, Patty Duke, Kay Jamison, Jerzy Broszkiewicz, Ota Pavel, Robert Lowell, Jaime Lowe, Nicole Lyons, Kurt Cobain, Sting, and the band Evanescence. Conclusions. Special attention was given to the book Unquiet mind, written in 1996 by Kay Jamison, professor of psychology. In the book, her personal bipolar disorder and lithium treatment were described from the viewpoint of the eminent professional. Polish translation of the book titled Niespokojny umysł already has two editions: in 2000 and 2018.

The biosynthetic origin of psychoactive kavalactones in kava.

Kava (Piper methysticum) is an ethnomedicinal shrub native to the Polynesian islands with well-established anxiolytic and analgesic properties. Its main psychoactive principles, kavalactones, form a unique class of polyketides that interact with the human central nervous system through mechanisms distinct from those of conventional psychiatric drugs. However, an unknown biosynthetic machinery and difficulty in chemical synthesis hinder the therapeutic use of kavalactones. In addition, kava also produces flavokavains, which are chalconoids with anticancer properties structurally related to kavalactones. Here, we report de novo elucidation of the key enzymes of the kavalactone and flavokavain biosynthetic network. We present the structural basis for the evolutionary development of a pair of paralogous styrylpyrone synthases that establish the kavalactone scaffold and the catalytic mechanism of a regio- and stereo-specific kavalactone reductase that produces a subset of chiral kavalactones. We further demonstrate the feasibility of engineering styrylpyrone production in heterologous hosts, thus opening a way to develop kavalactone-based non-addictive psychiatric therapeutics through synthetic biology.

L’evidence-based medicine, un projet épistémologique et éthique en porte-à-faux avec la psychiatrie ?

Le discours psychiatrique contemporain dominant repose principalement sur un paradigme médico-technologique où la souffrance mentale est conceptualisée comme un « mécanisme défectueux » qui nécessite une « réparation » grâce à l’arsenal médical. Dans ce contexte, l’evidence-based medicine(EBM) a donc été largement adopté par la psychiatrie à la fin des années 90. L’EBM est une proposition qui vise à influencer et même légiférer la prise de décisions cliniques en mettant de l’avant l’idée d’une hiérarchie des évidences, où le savoir tiré d’essais contrôlés randomisés (ECR) et de méta-analyses a préséance sur les informations tirées d’autres sources. Ainsi, comme l’EBM favorise ces outils de création de savoir (ECRs et méta-analyses) il en découle que le savoir qui compte véritablement dans le paradigme EBM est celui qui est mesurable et spécifique ; deux conditions préalables nécessaires pour l’utilisation même de ces outils. En conséquence, l’EBM diminue la valeur et va même jusqu’à ignorer d’autres formes d’évidences, de savoir et de justifications pour la prise de décisions cliniques. Du point de vue éthique, le concept EBM soutient que la « bonne chose à faire » est d’appliquer le savoir produit par l’EBM dans le contexte clinique. Les autres formes de savoir pouvant être impliquées dans la prise de décisions cliniques, mais qui ne peuvent pas être étudiées via l’EBM, sont dévalorisées d’un point de vue éthique. La littérature révisée et explorée ici considère donc que l’EBM est mal adapté à la réalité de la pratique psychiatrique. L’EBM ne peut pas, par définition, prendre en compte les spécificités de la discipline, notamment pour ce qui est des diagnostics psychiatriques ; leur complexité rend les évidences produites par l’EBM d’une validité questionnable. Le concept ne peut pas non plus tenir compte des spécificités des thérapeutiques psychiatriques. Les facteurs thérapeutiques non spécifiques, ceux discrédités par l’EBM, sont cruciaux pour les soins de santé mentale. Également, les observations portant sur des aspects de l’esprit, sur des expériences subjectives, ne sont que bien incorrectement traduites en résultats statistiques, mesurables et spécifiques. Ces observations amènent le présent essai à considérer qu’il serait peut-être préférable pour la psychiatrie, de rejeter la « hiérarchie des évidences » de l’EBM, et de développer son propre « système des savoirs ». Celui-ci devrait prendre en compte la position épistémologique unique de la psychiatrie, où subjectivité, contextes, et valeurs pourraient occuper de façon légitime la place qui leur revient dans la prise de décisions cliniques en psychiatrie. Bien qu’une alternative à l’EBM en psychiatrie n’ait pas encore été établie, la littérature, et ce papier pointent vers l’idée d’un « système des savoirs » plus flexible que ce qu’offre l’EBM en termes épistémologiques, où les aspects éthiques reliés à la discipline, incluant l’éthique du savoir, l’éthique de « ce qui compte comme évidence », revêtent une importance cruciale.

Psychiatric Jim Crow: Desegregation at the Crownsville State Hospital, 1948-1970.

The Crownsville State Hospital, located in Maryland just outside of Annapolis, provides a thought-provoking example of the impact of desegregation in the space of the mental hospital. Using institutional reports, patient records, and oral histories, this article reconstructs the three phases of desegregation at Crownsville. First, as a result of its poor conditions, lack of qualified staff, and its egregious mistreatment of patients, African American community leaders and organizations such as the NAACP called for the desegregation of the care staff of Crownsville in the late 1940s. Second, the introduction of a skilled African American staff created unprecedented and morally complex issues about access to psychiatric therapeutics. Last, in 1963, Health Commissioner Dr. Isadore Tuerk officially desegregated patients in all Maryland state hospitals. Though desegregation brought much needed improvements to Crownsville, these gains were ultimately swamped by deinstitutionalization and the shift towards outpatient psychiatric care. By the 1970s, Crownsville had returned to the poor conditions that existed during segregation.

The daunting polygenicity of mental illness: making a new map.

An epochal opportunity to elucidate the pathogenic mechanisms of psychiatric disorders has emerged from advances in genomic technology, new computational tools and the growth of international consortia committed to data sharing. The resulting large-scale, unbiased genetic studies have begun to yield new biological insights and with them the hope that a half century of stasis in psychiatric therapeutics will come to an end. Yet a sobering picture is coming into view; it reveals daunting genetic and phenotypic complexity portending enormous challenges for neurobiology. Successful exploitation of results from genetics will require eschewal of long-successful reductionist approaches to investigation of gene function, a commitment to supplanting much research now conducted in model organisms with human biology, and development of new experimental systems and computational models to analyse polygenic causal influences. In short, psychiatric neuroscience must develop a new scientific map to guide investigation through a polygenic terra incognita.This article is part of a discussion meeting issue ‘Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists’.

Research Domain Criteria as Psychiatric Nosology.

Diagnostic classification systems in psychiatry have continued to rely on clinical phenomenology, despite limitations inherent in that approach. In view of these limitations and recent progress in neuroscience, the National Institute of Mental Health (NIMH) has initiated the Research Domain Criteria (RDoC) project to develop a more neuroscientifically based system of characterizing and classifying psychiatric disorders. The RDoC initiative aims to transform psychiatry into an integrative science of psychopathology in which mental illnesses will be defined as involving putative dysfunctions in neural nodes and networks. However, conceptual, methodological, neuroethical, and social issues inherent in and/or derived from the use of RDoC need to be addressed before any attempt is made to implement their use in clinical psychiatry. This article describes current progress in RDoC; defines key technical, neuroethical, and social issues generated by RDoC adoption and use; and posits key questions that must be addressed and resolved if RDoC are to be employed for psychiatric diagnoses and therapeutics. Specifically, we posit that objectivization of complex mental phenomena may raise ethical questions about autonomy, the value of subjective experience, what constitutes normality, what constitutes a disorder, and what represents a treatment, enablement, and/or enhancement. Ethical issues may also arise from the (mis)use of biomarkers and phenotypes in predicting and treating mental disorders, and what such definitions, predictions, and interventions portend for concepts and views of sickness, criminality, professional competency, and social functioning. Given these issues, we offer that a preparatory neuroethical framework is required to define and guide the ways in which RDoC-oriented research can-and arguably should-be utilized in clinical psychiatry, and perhaps more broadly, in the social sphere.

The "Biopsychosocial Model": 40 years of application in Psychiatry.

In 1977, the American pathologist and psychiatrist George Engel (1913-1999) published in the Journal Science his paper "TheIn 1977, the American pathologist and psychiatrist George Engel (1913-1999) published in the Journal Science his paper "Theneed for a new medical model: A challenge for biomedicine", introducing the term Biopsychosocial Model. This model basedon the results of Engel's studies in ulcerative colitis, depression and psychogenic pain, constituted a challenge for biomedicineand the biomedical model. The basic principles of the model included the biological, psychological and social dimensions of the person's life and theperception that the person suffers as a whole and not as isolated organs. The doctor should use a holistic approach regardingillness and should consider his/her relation with the patient socially equal. The personality and the emotional reserves of thepatient, as well as the particular environmental conditions in which the person lives in should be taken into account. There is no doubt that the biopsychosocial model has established a more empathetic and compassionate approach in medical practice. Already since 1936, the general adaptation syndrome had been proposed by the Austrian-Canadian endocrinologist HansSeley (1907-1982), who emphasized that psychological stressful factors may have injurious consequences on health, while theresponse systems to stress may be dysregulated not only by genetic factors, but also from experiences and stressful life events,as well as by harmful behaviors such as smoking, alcohol consumption and lack of physical exercise. Psychosocial factors may co-determine the patient's vulnerability and the illness's severity and course. The biopsychosocialmodel consider the interactions with genetic susceptibility, personality, stressful events and, generally, with the patient's socialcontext. Environmental factors increase the probability of the clinical expression of a mental disorder, play a role in the time ofonset of an illness's manifestation, and they can also protect a vulnerable person from the disease. Stressful experiences modify immunological response and influence treatment compliance. Non adherence to pharmacotherapy,as well as to the psychosocial interventions, may cause defective recovery of psychosocial functioning, recurrence ofthe disorder, as well as insufficient use of health resources and a higher health care cost. The psychoeducation of patients andtheir relatives by the application of the biopsychosocial model plays an important role in psychiatric therapeutics, and it mayalso be used via Internet in the frame of telepsychiatry. Results from neuroimaging studies have shown that the different kinds of human experiences, traumatic or therapeutic, havemeasurable influences on the brain function. Psychotherapy may modify the neuronal connections of the brain in the frame ofits plasticity, as was found by the discovery of synaptogenesis in response to learning and can, thus, be considered not only as astrictly psychological but also as a biopsychosocial form of treatment. Among the disadvantages of the biopsychosocial model have been reported the lack of a concise theoretical frameworkregarding its function and content, that it is complicated, difficulties in its coordination and assignment of responsibilities, aswell as problems with the education on it being multifaceted. The biopsychosocial model has been criticized that it does notconstitute a scientific or philosophical model, it does not provide an answer to the crucial question of how the biological, psychologicaland social variables interact in the disease's expression, that it does not provide guidance on the exact time of itsapplication and, finally, that it allows for a wide range of interventions without providing specific guidelines of a concrete therapeutic scheme. The person-centered diagnosis is based on the biopsychosocial model, connects science with humanism and uses all thepossible ways so that the clinicians, the patients and their families collaborate for a more effective management of the disease.This approach has been established by the World Psychiatric Association (WPA, 2007) as the program "Psychiatry for the Person". Psychiatry in everyday practice presents particularities versus other medical disciplines due to the complexity and polymorphismPsychiatry in everyday practice presents particularities versus other medical disciplines due to the complexity and polymorphismof the expression of mental disorders, their close relation to psychosocial factors, the lack of explicit pathognomonicelements and the stigmatization of mental illness. For these reasons, the biopsychosocial model is particularly applicable inpsychiatric disorders, but it should not be over looked also in somatic illnesses. The biopsychosocial model, despite the criticism it was subjected to, continues to offer valuable clinical, educational andresearch services, as well as to provide an important contribution to the formation of health policies, not only for psychiatry, butfor the whole of medicine as well.

Postmarket Safety Events Among Novel Therapeutics Approved by the US Food and Drug Administration Between 2001 and 2010

Postmarket safety events of novel pharmaceuticals and biologics occur when new safety risks are identified after initial regulatory approval of these therapeutics. These safety events can change how novel therapeutics are used in clinical practice and inform patient and clinician decision making. To characterize the frequency of postmarket safety events among novel therapeutics approved by the US Food and Drug Administration (FDA), and to examine whether any novel therapeutic characteristics known at the time of FDA approval were associated with increased risk. Cohort study of all novel therapeutics approved by the FDA between January 1, 2001, and December 31, 2010, followed up through February 28, 2017. Novel therapeutic characteristics known at the time of FDA approval, including drug class, therapeutic area, priority review, accelerated approval, orphan status, near-regulatory deadline approval, and regulatory review time. A composite of (1) withdrawals due to safety concerns, (2) FDA issuance of incremental boxed warnings added in the postmarket period, and (3) FDA issuance of safety communications. From 2001 through 2010, the FDA approved 222 novel therapeutics (183 pharmaceuticals and 39 biologics). There were 123 new postmarket safety events (3 withdrawals, 61 boxed warnings, and 59 safety communications) during a median follow-up period of 11.7 years (interquartile range [IQR], 8.7-13.8 years), affecting 71 (32.0%) of the novel therapeutics. The median time from approval to first postmarket safety event was 4.2 years (IQR, 2.5-6.0 years), and the proportion of novel therapeutics affected by a postmarket safety event at 10 years was 30.8% (95% CI, 25.1%-37.5%). In multivariable analysis, postmarket safety events were statistically significantly more frequent among biologics (incidence rate ratio [IRR] = 1.93; 95% CI, 1.06-3.52; P = .03), therapeutics indicated for the treatment of psychiatric disease (IRR = 3.78; 95% CI, 1.77-8.06; P < .001), those receiving accelerated approval (IRR = 2.20; 95% CI, 1.15-4.21; P = .02), and those with near-regulatory deadline approval (IRR = 1.90; 95% CI, 1.19-3.05; P = .008); events were statistically significantly less frequent among those with regulatory review times less than 200 days (IRR = 0.46; 95% CI, 0.24-0.87; P = .02). Among 222 novel therapeutics approved by the FDA from 2001 through 2010, 32% were affected by a postmarket safety event. Biologics, psychiatric therapeutics, and accelerated and near-regulatory deadline approval were statistically significantly associated with higher rates of events, highlighting the need for continuous monitoring of the safety of novel therapeutics throughout their life cycle.

EHealth adventures in psychiatric therapeutics

Digital media are abundant and dominant in professional communications and health and social care practices.[1][1],[2][2]–[4][3] Therapeutic pioneers can now travel into digital landscapes to encounter virtual reality-based therapies, and positive voices and information that promote healthy living

Reconstructing the eclectic psychiatry of Thomas Ferguson Rodger.

This article provides an introduction to the approach of the Scottish psychiatrist Thomas Ferguson Rodger (1907-78), as reconstructed from his archive. Rodger's contribution has been largely neglected within the history of Scottish psychiatry. This paper amends this neglect through situating Rodger's eclecticism in relation to both the biopsychosocial approach of his mentors, Adolf Meyer and David Henderson, and psychiatry's de-institutionalization in the 1950s and 1960s. It is posited that Rodger's eclecticism was a considered response to the pressures of this transitional phase to balance physical, psychological and social approaches, and a critical acknowledgement of the instability of contemporary psychiatric therapeutics. More psychodynamic than his predecessors, the importance of social relations for Rodger led him to acknowledge psychiatry's limitations.

Adjunctive Therapy With Second-Generation Antipsychotics: The New Standard for Treatment-Resistant Depression?

Depressive episodes that do not respond to at least several adequate courses of standard antidepressants account for a substantial proportion of the socioeconomic and medical burden associated with this common illness. As such, treatment-resistant depression represents both an important public health problem and a great unmet need in psychiatric therapeutics. Among the several "add-on" strategies with established efficacy for treatment-resistant depression, the second-generation antipsychotics have become the most commonly used in psychiatric settings. This article briefly examines the benefits and limitations of adjunctive therapy with second-generation antipsychotics to determine whether these medications are now the standard of comparison for new therapies for treatment-resistant depression.

Do Psychiatric Medications Cause More Harm Than Good?

A head-to-head debate published in The BMJ was centered on the question "Does long-term use of psychiatric drugs cause more harm than good?" One of the debaters stated that virtually all psychotropic drug use could be stopped without deleterious effects, claiming that these drugs have minimal benefits, are immensely harmful, and cause more than 500,000 deaths each year. In the current article, this conclusion is disputed by the discussion of the history of psychiatric therapeutics, limitations of research investigations, inherent morbidity and mortality associated with mental disorders, and importance of direct care experience with psychiatric patients and their families.

ITI-007 demonstrates brain occupancy at serotonin 5-HT₂A and dopamine D₂ receptors and serotonin transporters using positron emission tomography in healthy volunteers.

Central modulation of serotonin and dopamine underlies efficacy for a variety of psychiatric therapeutics. ITI-007 is an investigational new drug in development for treatment of schizophrenia, mood disorders, and other neuropsychiatric disorders. The purpose of this study was to determine brain occupancy of ITI-007 at serotonin 5-HT2A receptors, dopamine D2 receptors, and serotonin transporters using positron emission tomography (PET) in 16 healthy volunteers. Carbon-11-MDL100907, carbon-11-raclopride, and carbon-11-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile) (carbon-11-DASB) were used as the radiotracers for imaging 5-HT2A receptors, D2 receptors, and serotonin transporters, respectively. Brain regions of interest were outlined using magnetic resonance tomography (MRT) with cerebellum as the reference region. Binding potentials were estimated by fitting a simplified reference tissue model to the measured tissue-time activity curves. Target occupancy was expressed as percent change in the binding potentials before and after ITI-007 administration. Oral ITI-007 (10-40 mg) was safe and well tolerated. ITI-007 rapidly entered the brain with long-lasting and dose-related occupancy. ITI-007 (10 mg) demonstrated high occupancy (>80 %) of cortical 5-HT2A receptors and low occupancy of striatal D2 receptors (~12 %). D2 receptor occupancy increased with dose and significantly correlated with plasma concentrations (r (2) = 0.68, p = 0.002). ITI-007 (40 mg) resulted in peak occupancy up to 39 % of striatal D2 receptors and 33 % of striatal serotonin transporters. The results provide evidence for a central mechanism of action via dopaminergic and serotonergic pathways for ITI-007 in living human brain and valuable information to aid dose selection for future clinical trials.

Rewarding and punishing properties of deep brain stimulation: The most promising entry points for constitutive studies of affective experiences in other animals...with profound psychiatric implications for human consciousness and psychiatric therapeutics.

Neither experimental psychology nor neuroscience has made much progress in understanding the constitution (the hard-problem) of consciousness, although affective issues are finally being intensively considered. Miskovic and colleagues provide a penetrating essay into the problem and the conceptual advances being made, without sufficient consideration of the critical role of animal brain research in such enterprises. I will argue that the task will be much easier when we integrate human and animal findings, especially because animal brain research—particularly with regard to the identification of rewarding and punishing brain systems (namely, the affective neuroscience strategy)—will be very useful in informing how primal affective states in humans are created from brain dynamics.