Novel Insights Into the Neurobiology of the Antidepressant Response From Ketamine Research: A Mini Review.

The serendipitous discovery of ketamine's antidepressant effects represents one of the major landmarks in neuropsychopharmacological research of the last 50 years. Ketamine provides an exciting challenge to traditional concepts of antidepressant drug therapy, producing rapid antidepressant effects seemingly without targeting monoaminergic pathways in the conventional way. In consequence, the advent of ketamine has spawned a plethora of neurobiological research into its putative mechanisms. Here, we provide a brief overview of current theories of antidepressant drug action including monoaminergic signaling, disinhibition of glutamatergic neurotransmission, neurotrophic and neuroplastic effects, and how these might relate to ketamine. Given that research into ketamine has not yet yielded new therapies beyond ketamine itself, current knowledge gaps and limitations of available studies are also discussed.

SIMON: A Digital Protocol to Monitor and Predict Suicidal Ideation.

Each year, more than 800,000 persons die by suicide, making it a leading cause of death worldwide. Recent innovations in information and communication technology may offer new opportunities in suicide prevention in individuals, hereby potentially reducing this number. In our project, we design digital indices based on both self-reports and passive mobile sensing and test their ability to predict suicidal ideation, a major predictor for suicide, and psychiatric hospital readmission in high-risk individuals: psychiatric patients after discharge who were admitted in the context of suicidal ideation or a suicidal attempt, or expressed suicidal ideations during their intake. Specifically, two smartphone applications -one for self-reports (SIMON-SELF) and one for passive mobile sensing (SIMON-SENSE)- are installed on participants' smartphones. SIMON-SELF uses a text-based chatbot, called Simon, to guide participants along the study protocol and to ask participants questions about suicidal ideation and relevant other psychological variables five times a day. These self-report data are collected for four consecutive weeks after study participants are discharged from the hospital. SIMON-SENSE collects behavioral variables -such as physical activity, location, and social connectedness- parallel to the first application. We aim to include 100 patients over 12 months to test whether (1) implementation of the digital protocol in such a high-risk population is feasible, and (2) if suicidal ideation and psychiatric hospital readmission can be predicted using a combination of psychological indices and passive sensor information. To this end, a predictive algorithm for suicidal ideation and psychiatric hospital readmission using various learning algorithms (e.g., random forest and support vector machines) and multilevel models will be constructed. Data collected on the basis of psychological theory and digital phenotyping may, in the future and based on our results, help reach vulnerable individuals early and provide links to just-in-time and cost-effective interventions or establish prompt mental health service contact. The current effort may thus lead to saving lives and significantly reduce economic impact by decreasing inpatient treatment and days lost to inability.

Validation of Visual and Auditory Digital Markers of Suicidality in Acutely Suicidal Psychiatric Inpatients: Proof-of-Concept Study.

BACKGROUND: Multiple symptoms of suicide risk have been assessed based on visual and auditory information, including flattened affect, reduced movement, and slowed speech. Objective quantification of such symptomatology from novel data sources can increase the sensitivity, scalability, and timeliness of suicide risk assessment. OBJECTIVE: We aimed to examine measurements extracted from video interviews using open-source deep learning algorithms to quantify facial, vocal, and movement behaviors in relation to suicide risk severity in recently admitted patients following a suicide attempt. METHODS: We utilized video to quantify facial, vocal, and movement markers associated with mood, emotion, and motor functioning from a structured clinical conversation in 20 patients admitted to a psychiatric hospital following a suicide risk attempt. Measures were calculated using open-source deep learning algorithms for processing facial expressivity, head movement, and vocal characteristics. Derived digital measures of flattened affect, reduced movement, and slowed speech were compared to suicide risk with the Beck Scale for Suicide Ideation controlling for age and sex, using multiple linear regression. RESULTS: Suicide severity was associated with multiple visual and auditory markers, including speech prevalence (ß=-0.68, P=.02, r2=0.40), overall expressivity (ß=-0.46, P=.10, r2=0.27), and head movement measured as head pitch variability (ß=-1.24, P=.006, r2=0.48) and head yaw variability (ß=-0.54, P=.06, r2=0.32). CONCLUSIONS: Digital measurements of facial affect, movement, and speech prevalence demonstrated strong effect sizes and linear associations with the severity of suicidal ideation.

Reduced neural differentiation between self-referential cognitive and emotional processes in women with borderline personality disorder.

Borderline personality disorder (BPD) is associated with disturbed emotion regulation. Psychotherapeutic interventions using mindfulness elements have shown effectiveness in reducing clinical symptoms, yet little is known about their underlying neurobiology. In this functional magnetic resonance imaging (fMRI) study, 19 female BPD patients and 19 healthy controls were compared during mindful introspection, cognitive self-reflection and a neutral condition. The activation pattern in the right dorsomedial prefrontal cortex (DMPFC) in BPD patients was different from that in healthy subject when directing attention onto their emotions and bodily feelings in contrast to cognitively thinking about themselves. Mindful introspection compared with the neutral condition was associated with higher activations in bilateral motor/pre-motor regions, left inferior frontal gyrus (IFG), and left posterior cingulate cortex (PCC), while cognitive self-reflection activated the right motor and somatosensory cortex, extending into the right supramarginal gyrus (SMG) and superior temporal gyrus (STG) in BPD patients compared with the controls. Results indicate that self-referential cognitive and emotional processes are not clearly differentiated in BPD patients at the neurobiological level. In particular, altered neural mechanism underlying self-referential thinking may be related to some aspects of the typical emotion dysregulation in BPD. Current data support the finding that mindful self-focused attention is effective in regulating amygdala activity in BPD as well as in healthy subjects.