Antipsychotic Polypharmacy in Time Course: Evidence for a Cross-titration Trap.

Purpose/background: Antipsychotic polypharmacy (APP) is controversial yet applied in 20% of patients with psychotic disorders. We investigated indications for initiating and continuing APP, including the contribution of unfinished cross-titrations.

Methods/procedures: This 2-month study was part of a prospective study to reduce inappropriate APP in inpatients.

The pharmacokinetics and pharmacodynamics of ibogaine in opioid use disorder patients.

Objective: Ibogaine is a hallucinogenic drug that may be used to treat opioid use disorder (OUD). The relationships between pharmacokinetics (PKs) of ibogaine and its metabolites and their clinical effects on side effects and opioid withdrawal severity are unknown. We aimed to study these relationships in patients with OUD undergoing detoxification supported by ibogaine.

Amygdala response predicts clinical symptom reduction in patients with borderline personality disorder: A pilot fMRI study.

Borderline personality disorder (BPD) is a prevalent, devastating, and heterogeneous psychiatric disorder. Treatment success is highly variable within this patient group. A cognitive neuroscientific approach to BPD might contribute to precision psychiatry by identifying neurocognitive factors that predict who will benefit from a specific treatment.

Safety of ibogaine administration in detoxification of opioid-dependent individuals: a descriptive open-label observational study.

Background And Aims: Ibogaine is an indole alkaloid used in rituals of the African Bwiti tribe. It is also used in non-medical settings to treat addiction. However, ibogaine has been linked to several deaths, mainly due to cardiac events called torsades des pointes preceded by QTc prolongation as well as other safety concerns.

The relationship between childhood adversity and adult personality revealed by network analysis.

Background: Childhood adversity is known to influence personality development. Studies suggest that distinct types of childhood adversities have differential effects on personality dimensions. However, different types of adversity often co-occur, and personality dimensions are strongly interconnected.

Five factor model personality traits relate to adult attention-deficit/hyperactivity disorder but not to their distinct neurocognitive profiles.

Deficits in multiple neuropsychological domains and specific personality profiles have been observed in attention-deficit/hyperactivity disorder (ADHD). In this study we investigated whether personality traits are related to neurocognitive profiles in adults with ADHD. Neuropsychological performance and Five Factor Model (FFM) personality traits were measured in adults with ADHD (n = 133) and healthy controls (n = 132).

Acute effects of cocaine and cannabis on response inhibition in humans: an ERP investigation.

Substance abuse has often been associated with alterations in response inhibition in humans. Not much research has examined how the acute effects of drugs modify the neurophysiological correlates of response inhibition, or how these effects interact with individual variation in trait levels of impulsivity and novelty seeking. This study investigated the effects of cocaine and cannabis on behavioural and event-related potential (ERP) correlates of response inhibition in 38 healthy drug using volunteers.

Effects of tetrahydrocannabinol on balance and gait in patients with dementia: A randomised controlled crossover trial.

Oral tetrahydrocannabinol (THC) is currently studied for its possible efficacy on dementia-related neuropsychiatric symptoms (NPS), but might lead to increased risk of falling. This was a randomised, double-blind, crossover study to evaluate the effects of THC on mobility in dementia patients. Eighteen community-dwelling patients ( M=77 years) received 1.

Opposite effects of cannabis and cocaine on performance monitoring.

Drug use is often associated with risky and unsafe behavior. However, the acute effects of cocaine and cannabis on performance monitoring processes have not been systematically investigated. The aim of the current study was to investigate how administration of these drugs alters performance monitoring processes, as reflected in the error-related negativity (ERN), the error positivity (Pe) and post-error slowing.

Testosterone Modulates Altered Prefrontal Control of Emotional Actions in Psychopathic Offenders(1,2,3).

Psychopathic individuals are notorious for their controlled goal-directed aggressive behavior. Yet, during social challenges, they often show uncontrolled emotional behavior. Healthy individuals can control their social emotional behavior through anterior prefrontal cortex (aPFC) downregulation of neural activity in the amygdala, with testosterone modulating aPFC-amygdala coupling.

Acute effects of cocaine and cannabis on reversal learning as a function of COMT and DRD2 genotype.

Rationale: Long-term cannabis and cocaine use has been associated with impairments in reversal learning. However, how acute cannabis and cocaine administration affect reversal learning in humans is not known.

Objective: In this study, we aimed to establish the acute effects of administration of cannabis and cocaine on valence-dependent reversal learning as a function of DRD2 Taq1A (rs1800497) and COMT Val108/158Met (rs4680) genotype.

Tryptophan depletion in chronic fatigue syndrome, a pilot cross-over study.

Background: Chronic fatigue syndrome (CFS) is still an enigmatic disorder. CFS can be regarded as a complex disorder with tremendous impact on lives of CFS-patients. Full recovery without treatment is rare.

Substance use disorders in forensic psychiatric patients.

There is a lack of detailed information on the role of substance use disorders (SUD) as a substantial factor in offences and treatment in forensic psychiatric patients. The aim of this study was to get a better understanding of these specifics. Clinical records of 193 male patients admitted to a Dutch forensic psychiatric hospital were scrutinized on anamnestic, diagnostic and risk assessment data.

Dopaminergic drug effects during reversal learning depend on anatomical connections between the orbitofrontal cortex and the amygdala.

Dopamine in the striatum is known to be important for reversal learning. However, the striatum does not act in isolation and reversal learning is also well-accepted to depend on the orbitofrontal cortex (OFC) and the amygdala. Here we assessed whether dopaminergic drug effects on human striatal BOLD signaling during reversal learning is associated with anatomical connectivity in an orbitofrontal-limbic-striatal network, as measured with diffusion tensor imaging (DTI).

Characterizing the cognitive effects of cocaine: a comprehensive review.

Understanding the cognitive sequela of repeated cocaine use is a growing area of research and is crucial to the development of cognitive models of addiction. We systematically reviewed all available placebo-controlled and case-controlled studies on the acute and long-term effects of cocaine on cognitive functioning. In order to compare the magnitude of cognitive effects across cognitive domains we conducted several meta-analyses on a subset of data from long-term effect studies.

Reversal deficits in individuals with psychopathy in explicit but not implicit learning conditions.

Background: Psychopathy is a severe personality disorder that has been linked to impaired behavioural adaptation during reinforcement learning. Recent electrophysiological studies have suggested that psychopathy is related to impairments in intentionally using information relevant for adapting behaviour, whereas these impairments remain absent for behaviour relying on automatic use of information. We sought to investigate whether previously found impairments in response reversal in individuals with psychopathy also follow this dichotomy.

Anatomical connection strength predicts dopaminergic drug effects on fronto-striatal function.

Rationale: The neurotransmitter dopamine plays a key role in cognitive functions that are associated with fronto-striatal circuitry and has been implicated in many neuropsychiatric disorders. However, there is a large variability in the direction and extent of dopaminergic drug effects across individuals.

Objectives: We investigated whether individual differences in dopaminergic drug effects on human fronto-striatal functioning are associated with individual differences in white matter tracts.

Establishing the dopamine dependency of human striatal signals during reward and punishment reversal learning.

Drugs that alter dopamine transmission have opposite effects on reward and punishment learning. These opposite effects have been suggested to depend on dopamine in the striatum. Here, we establish for the first time the neurochemical specificity of such drug effects, during reward and punishment learning in humans, by adopting a coadministration design.

Differentiating psychopathy from general antisociality using the P3 as a psychophysiological correlate of attentional allocation.

Recent studies have shown that while psychopathy and non-psychopathic antisociality overlap, they differ in the extent to which cognitive impairments are present. Specifically, psychopathy has been related to abnormal allocation of attention, a function that is traditionally believed to be indexed by event-related potentials (ERPs) of the P3-family. Previous research examining psychophysiological correlates of attention in psychopathic individuals has mainly focused on the parietally distributed P3b component to rare targets.

Psychopaths lack the automatic avoidance of social threat: relation to instrumental aggression.

Psychopathy (PP) is associated with marked abnormalities in social emotional behaviour, such as high instrumental aggression (IA). A crucial but largely ignored question is whether automatic social approach-avoidance tendencies may underlie this condition. We tested whether offenders with PP show lack of automatic avoidance tendencies, usually activated when (healthy) individuals are confronted with social threat stimuli (angry faces).

Neural basis of recollection in first-episode major depression.

Background: Patients with major depressive disorder (MDD) display impairments in recollection, which have been explained by both hippocampal and prefrontal dysfunction. Here, we used an event-related fMRI design, to dissociate hippocampal and prefrontal contributions to the neural processes involved in recollection success and recollection attempt early in the course of MDD.

Methods: To disentangle state- and trait-effects of depression, we included 20 medication-naive patients with a first depressive episode, 20 medication-free patients recovered from a first episode, and 20 matched, healthy controls in an event-related fMRI study using a source recollection paradigm.

Acute effects of delta-9-tetrahydrocannabinol on performance monitoring in healthy volunteers.

Rationale: The error-related negativity (ERN) is a negative event-related potential that occurs immediately after an erroneous response and is thought to reflect human performance monitoring. Delta-9-Tetrahydrocannabinol (THC) administration in healthy volunteers has been linked to impaired performance monitoring in behavioral studies, but to date no studies have examined the effects of cannabinoids on the ERN.

Methods: EEG data from 10 healthy volunteers was recorded during execution of a speeded choice-reaction-time task (Flankers task) after administration of THC or placebo vapor in a double-blind randomized crossover design.

Short-term duloxetine administration affects neural correlates of mood-congruent memory.

It is unknown how antidepressants reverse mood-congruent memory bias, a cognitive core factor causing and maintaining depression. Using a double-blind, placebo-controlled, cross-over design, we investigated the effect of a short-term treatment (14 days) with the dual reuptake inhibitor duloxetine on neural correlates of mood-congruent and mood-incongruent memory formation and retrieval in healthy volunteers who underwent a sad mood induction procedure. Duloxetine did not affect acute mood state or memory performance, but interacted with brain processes mediating mood-congruent memory.

Human cognitive flexibility depends on dopamine D2 receptor signaling.

Rationale: Accumulating evidence indicates that the cognitive effects of dopamine depend on the subtype of dopamine receptor that is activated. In particular, recent work with animals as well as current theorizing has suggested that cognitive flexibility depends on dopamine D2 receptor signaling. However, there is no evidence for similar mechanisms in humans.

Two-week administration of the combined serotonin-noradrenaline reuptake inhibitor duloxetine augments functioning of mesolimbic incentive processing circuits.

Background: Anhedonia and lack of motivation are core symptoms of major depressive disorder (MDD). Neuroimaging studies in MDD patients have shown reductions in reward-related activity in terminal regions of the mesolimbic dopamine (DA) system, such as the ventral striatum. Monoamines have been implicated in both mesolimbic incentive processing and the mechanism of action of antidepressant drugs.