Journal of Psychopharmacology最新文献

Subanesthetic doses of ketamine produce complex neuropsychiatric effects, which include rapid psychotomimetic symptoms and antidepressant effects that can last several weeks. Despite over 60 years of research, the mechanism(s) of action underlying ketamine's effects in the brain remains largely mysterious. Neurophysiological field potential recordings provide a direct window into brain activity, with different frequency bands reflecting functionally distinct neural networks. Two decades ago, we reported on the existence of high-frequency oscillations (HFO, >100 Hz) in freely moving rodents that were markedly enhanced by subanesthetic doses of ketamine. Since then, a large body of evidence has shown that HFO after ketamine (and other N-methyl-d-aspartate receptor (NMDAR) antagonists) are largely wake-related and prominent across diverse olfactory and frontostriatal brain regions. This rhythm, which is remarkably coherent across distinct regions, is modulated by slower oscillations with respiration-locked olfactory bulb activity a major driving force behind it. Similar activity has been reported in vivo in a variety of mammals with preclinical validity. This review is the first synthesis of studies reporting on the NMDAR antagonist-enhanced HFO rhythm. We identify current gaps and provide suggestions for future research, including the urgent need for more human studies.

Background: Given the limited understanding of the pathogenesis underlying depression and the specific targets of antidepressant medications, treatment of depression predominantly relies on empirical methodologies. Previous magnetic resonance imaging studies utilizing connectome gradient methods have revealed disruptions of the principal gradient in major depressive disorder (MDD) patients. However, the semiological meaning of the brain gradient and the effect of antidepressants are unknown.

Methods: We recruited MDD patients and healthy controls to investigate baseline alterations in the principal connectome gradient. Changes in gradient scores were further analyzed within the responder group post-treatment, and repeated measures ANOVA was used to assess the gradient score changes across time (within-subject) and antidepressant types (between-subject).

Results: Compared to controls, MDD patients exhibited gradient score alterations in default and visual networks. After antidepressant treatment, the gradient scores for the left ventromedial prefrontal cortex (VMPFC) increased in patients who responded to therapy. The gradient scores for left VMPFC had an interaction effect between time and antidepressant types and correlated negatively with the core factor scores of HRSD₁₇ at baseline.

Conclusion: These results highlight the single-target antidepressants' effects on gradient scores for left VMPFC and provide evidence for future treatment targets and neurobiological underpinnings of antidepressant therapy.

Background: Behavioral and psychological symptoms of dementia (BPSD) affect patients' and caregivers' well-being. Cannabinoids may offer a promising therapeutic option for managing BPSD.

Aims: This systematic review aims to explore the strengths of using this class of substances in the context of dementia care.

Methods: We conducted a comprehensive search across Embase Ovid, PubMed, Cochrane Library, APA PsycInfo, and Web of Science, identifying 1839 studies, with 14 selected for full review. Quality was assessed using the Newcastle-Ottawa and the modified Jadad Scales.

Results/outcomes: Ten studies (278 participants) were finally included. They showed cannabinoids helped reduce agitation and nocturnal disturbances.

Conclusions/interpretation: In conclusion, cannabinoids show promise in managing BPSD in dementia, with good tolerability and safety. Further studies could solidify these findings.

Human facial emotion recognition (FER) is an evolutionarily preserved process that influences affiliative behaviours, approach/avoidance and fight-or-flight responses in the face of detecting threat cues, thus enhancing adaptation and survival in social groups. Here, we provide a narrative literature review on how human FER is modulated by neurotransmitters and pharmacological agents, classifying the documented effects by central neurotransmitter systems. Synthesising the findings from studies involving functional neuroimaging and FER tasks, we highlight several emerging themes; for example, noradrenaline promotes an overall positive bias in FER, while serotonin, dopamine and gamma-aminobutyric acid modulate emotions relating to self-preservation. Finally, other neurotransmitters including the cholinergic and glutamatergic systems are responsible for rather non-specific pro-cognitive effects in FER. With the ongoing accumulation of evidence further characterising the individual contributions of each neurotransmitter system, we argue that a sensible next step would be the integration of experimental neuropharmacology with computational models to infer further insights into the temporal dynamics of different neurotransmitter systems modulating FER.

Background: Lithium, a mainstay treatment for bipolar disorders, has shown promise in treating cognitive impairments. However, concerns about cognition-related side effects persist.

Aims: We aimed to synthesise the evidence on how lithium affects cognition by comparing cognitive performance before and after starting lithium treatment.

Methods: A systematic search was conducted to identify studies examining lithium's effects on cognition. The review considered studies with adult human participants that reported quantitative cognitive outcomes using within-subject comparisons between lithium-absent and lithium-present conditions.

Results: Thirty-two articles describing 30 studies were included (727 participants, approximately 54% female, mean age ± 50 years old). The studies exhibited significant heterogeneity within cognitive domains, including global cognition (15 studies), memory (19 studies), processing and psychomotor speed (8 studies), attention (9 studies), verbal fluency (4 studies) and executive function (6 studies). The included studies comprised 16 randomised controlled trials (RCTs) and 14 non-RCTs, with study populations ranging from individuals with affective disorders (13 studies) to neurocognitive disorders (11 studies) and healthy individuals (6 studies). Some studies reported cognitive enhancements, particularly in individuals with affective disorders, while others documented declines or mixed results.

Conclusions: Definitive conclusions regarding lithium's isolated cognitive effects remain elusive, particularly considering the influence of factors such as affective state, population and methodological heterogeneity among studies. Further research is needed to conclusively determine the raw cognitive impacts of lithium therapy, requiring larger RCTs across distinct populations. Prioritising the resolution of main symptoms should remain the primary therapeutic goal of lithium treatment.

Background: Major depressive disorder (MDD) is a prevalent psychiatric illness, significantly contributing to disability and suicide rates. While dysfunctions in neurotransmission, notably monoaminergic transmission, are commonly attributed to MDD, involvement of the glutamatergic system in comorbid depressive disorders suggests its potential as a target for antidepressant therapy. Despite evidence of diminished glutamatergic neuron activity in the midbrain ventrolateral periaqueductal gray (vlPAG) in rodent models of depression-which projects to the ventral tegmental area (VTA), a region regulating depression-like behaviors-the precise neurocircuit mechanisms within the vlPAG remain unclear.

Methods: To investigate dysregulation of glutamatergic transmission in the vlPAG and its role in depression-like behavior, we combined behavioral testing, pharmacological manipulation, retrograde tracing, and electrophysiological recording in male C57BL/6 mice.

Results: Mice receiving intravlPAG infusion of the mGlu2/3 receptor antagonist LY341495 exhibited reversal of depression-like behaviors. Chronic restraint stress (CRS) elicited depression-like behavior, whereas intravlPAG administration of LY341495 reversed these behaviors. VTA-projecting vlPAG neurons exhibited reduced frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) and decreased neuronal excitability. Blocking mGlu2/3 receptors, which act as autoreceptors inhibiting glutamate release, in the vlPAG rescued these effects. Moreover, intravlPAG microinjection of the L-type voltage-dependent calcium channel (VDCC) blocker verapamil, tropomyosin-related kinase B (TrkB) receptor antagonist ANA-12, mammalian target of rapamycin complex 1 inhibitor rapamycin, and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist 6-cyano-7-nitroquinoxaline-2, 3-dione prevented LY341495-induced reversal of depression-like behaviors.

Conclusions: This provides the first direct evidence that blockade of mGlu2/3 receptors in the vlPAG ameliorates depression-like behavior, highlighting their role in regulating vlPAG-VTA neurocircuits implicated in MDD pathophysiology.

Background: Neuroimaging studies have linked the beneficial effects of subanaesthetic ketamine doses in psychiatric conditions characterized by chronic stress pathology (CSP) to altered functional connectivity (FC) within the pregenual anterior cingulate cortex (pgACC). Previous research indicates a potential role of glutamate concentration in FC changes; however, the precise relationship between glutamate release and increased FC remains unclear. Lamotrigine, a glutamate-release inhibitor, allows deeper exploration of this relationship. Additionally, CSP and treatment efficacy are closely associated with alterations in working memory (WM), necessitating the examination of FC during resting state and WM tasks.

Aims: This study aimed to investigate the acute and sustained effects of altered glutamate transmission induced by ketamine and lamotrigine on pgACC FC during rest and WM.

Methods: In this double-blind, placebo-controlled, randomized, single-dose, parallel-group study, resting-state and task-related functional Magnetic Resonance Imaging (fMRI) data were collected at baseline, during and 24 h after ketamine administration in 75 healthy participants. Participants were randomized to receive ketamine, ketamine with lamotrigine pretreatment or placebo. FC analyses utilized pgACC masks derived from the Julich Brain Atlas.

Results: Ketamine infusion significantly enhanced FC between the pgACC and dorsomedial prefrontal cortex during the WM task, and increased resting-state FC between the pgACC and left insula. These effects were absent following lamotrigine pretreatment.

Conclusions: The findings support the hypothesis that ketamine's favourable effects, reflected by enhanced FC within key neural networks, may be attributable to glutamate release.

Ketamine has emerged as a putative rapid-acting treatment option for psychiatric disorders, particularly treatment-resistant depression. Chronic recreational ketamine use is associated with ketamine-induced urological toxicity, raising concerns over the safety of repeated ketamine treatments. This systematic review aimed to synthesise urological findings from clinical trials and observational studies using ketamine for the treatment of psychiatric disorders. Electronic databases were searched up until 4th April 2024 for trials and observational studies using ketamine treatment for psychiatric disorders in adults, and which reported assessment of urinary, bladder or renal symptoms. Twenty-seven studies were included, mostly in depressive disorders (N = 24). Urological symptoms were reported in 0%-24.5% of patients receiving ketamine treatment; symptoms tended to be mild or moderate in severity. Where reported, continuous outcome measures (urinary parameters and symptom questionnaires) did not show significant changes from baseline to follow-up. Only 15% of studies were rated low risk of bias. Most studies did not assess long-term ketamine treatment, and many included undefined or passive monitoring of urological symptoms rather than systematic assessment. Based on the limited data available, ketamine treatment does not appear to be associated with elevated risk of urological symptoms; however, further long-term studies are required.