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Biological Psychiatry

ISSN 0006-3223

34 papers in the library · 3,722 citations · publishing 1992-2026

Papers

Amyloid Plaques Disrupt Resting State Default Mode Network Connectivity in Cognitively Normal Elderly

Biological Psychiatry October 15, 2009 Yvette I. Sheline, Marcus E. Raichle, Abraham Z. Snyder et al. 608 citations

Functional connections within the default mode network are disrupted in Alzheimer's disease, likely due to amyloid-beta plaque toxicity. In cognitively normal participants with preclinical amyloid deposition, resting-state fMRI revealed differences in functional connectivity between the precuneus and several brain regions—including the hippocampus, parahippocampus, and cingulate cortex—that matched the pattern seen in Alzheimer's disease patients. These findings suggest that early amyloid-beta toxicity can be detected with resting-state fMRI before any cognitive or behavioral changes appear.

DOI: 10.1016/j.biopsych.2009.08.024 Full text

Intravenous Esketamine in Adult Treatment-Resistant Depression: A Double-Blind, Double-Randomization, Placebo-Controlled Study

Biological Psychiatry November 4, 2015 Jaskaran B. Singh, Maggie Fedgchin, Ella Daly et al. 466 citations

A single 40-minute intravenous infusion of esketamine at either 0.20 mg/kg or 0.40 mg/kg produced a rapid and robust antidepressant effect in patients with treatment-resistant depression, with significant improvement in depression scores within two hours. The higher and lower doses were similarly effective, but the lower dose may offer better tolerability. Common side effects included headache, nausea, and transient dissociation that resolved within four hours.

DOI: 10.1016/j.biopsych.2015.10.018 Full text

Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects

Biological Psychiatry November 29, 2014 Yasmin Schmid, Florian Enzler, Peter Gasser et al. 425 citations

In a double-blind, placebo-controlled crossover study, 200 μg of lysergic acid diethylamide (LSD) given to 16 healthy subjects produced pronounced alterations in consciousness lasting 12 hours, including visual hallucinations, audiovisual synesthesia, and positively experienced derealization and depersonalization. LSD increased subjective well-being, happiness, closeness to others, openness, and trust, and decreased prepulse inhibition (PPI) of the acoustic startle response, a measure of sensorimotor gating. It also significantly increased blood pressure, heart rate, body temperature, pupil size, and plasma levels of cortisol, prolactin, oxytocin, and epinephrine. All adverse effects subsided within 72 hours, with no severe acute adverse effects observed. LSD produces empathogenic mood effects similar to methylenedioxymethamphetamine and alters sensorimotor gating in a human model of psychosis, supporting its potential use in psychotherapy and translational psychiatric research.

DOI: 10.1016/j.biopsych.2014.11.015 Lysergic acid diethylamide Serotonin Prepulse inhibition Hallucinogen +14

Psilocybin-Induced Decrease in Amygdala Reactivity Correlates with Enhanced Positive Mood in Healthy Volunteers

Biological Psychiatry April 26, 2014 Rainer Kraehenmann, Katrin H. Preller, Milan Scheidegger et al. 325 citations

A double-blind, randomized, crossover study in 25 healthy volunteers found that a single dose of psilocybin (0.16 mg/kg) reduced amygdala reactivity to negative and neutral stimuli, measured with functional magnetic resonance imaging, compared with placebo. The reduction in right amygdala reactivity to negative stimuli was linked to an increase in positive mood, assessed with the Positive and Negative Affect Schedule and the State-Trait Anxiety Inventory. These findings suggest psilocybin may dampen neural responses to negative emotional cues and improve mood, which could be relevant for treating conditions like major depression where amygdala hyperactivity and negative mood states are common.

DOI: 10.1016/j.biopsych.2014.04.010 Psilocybin Serotonergic Serotonin Amygdala +9

Psilocybin Biases Facial Recognition, Goal-Directed Behavior, and Mood State Toward Positive Relative to Negative Emotions Through Different Serotonergic Subreceptors

Biological Psychiatry May 9, 2012 Michael Kometer, André Schmidt, Rosilla Bachmann et al. 300 citations

Psilocybin enhanced positive mood and reduced recognition of negative facial expressions in healthy volunteers. It also increased goal-directed behavior toward positive emotional cues while inhibiting negative sequential emotional effects and valence-dependently attenuated the P300 brain response. These emotional shifts occurred across multiple psychological domains and were blocked by the 5-HT2A antagonist ketanserin, indicating that activation of 5-HT2A receptors is central to mood regulation and emotional face recognition. The findings suggest a mechanism for psilocybin's potential antidepressant effects.

DOI: 10.1016/j.biopsych.2012.04.005 Serotonergic Psilocybin Mood Cognitive psychology

Mechanistic Target of Rapamycin-Independent Antidepressant Effects of (R)-Ketamine in a Social Defeat Stress Model.

Biological Psychiatry January 1, 2018 Chun Yang, Q. Ren, Y. Qu et al. 249 citations

The antidepressant effects of the two enantiomers of ketamine rely on different signaling pathways in mice. (S)-ketamine requires mTOR signaling, as blocking mTOR with rapamycin or AZD8055 eliminated its effects, while (R)-ketamine does not. Instead, (R)-ketamine requires ERK signaling; blocking ERK with SL327 eliminated its effects. (S)-ketamine restored reduced mTOR phosphorylation in the prefrontal cortex of stressed mice, whereas (R)-ketamine restored reduced ERK phosphorylation in the prefrontal cortex and hippocampal dentate gyrus. These findings indicate that mTOR activation is not necessary for (R)-ketamine's antidepressant actions.

DOI: 10.1016/j.biopsych.2017.05.016 Full text Chemistry Medicine Psychology

Psilocybin Induces Time-Dependent Changes in Global Functional Connectivity

Biological Psychiatry January 13, 2020 Katrin H. Preller, Patricia Duerler, Joshua B. Burt et al. 199 citations

Psilocybin reduces connectivity in associative brain regions while increasing connectivity in sensory regions, a pattern that emerges over time from administration to peak effects. Baseline connectivity predicts the extent of these changes. The shifts correlate with spatial gene expression patterns of the serotonin 2A and 1A receptors, pinpointing their critical role in the psychedelic state. These findings suggest that sensory integration and associative disintegration may underlie the psychedelic experience, and baseline connectivity could serve as a predictive marker for personalized psychedelic treatment.

DOI: 10.1016/j.biopsych.2019.12.027 Psilocybin Serotonin Neuroscience Psychology +5

Mescaline-induced psychopathological, neuropsychological, and neurometabolic effects in normal subjects: experimental psychosis as a tool for psychiatric research.

Biological Psychiatry December 1, 1992 L. Hermle, M. Fünfgeld, G. Oepen et al. 185 citations

In 12 healthy male volunteers, mescaline produced an acute psychotic state 3.5–4 hours after intake, measured by the Brief Psychiatric Rating Scale and Paranoid Depression Scale. The Assessment of Altered States of Consciousness questionnaire showed specific effects on the visual system. A face/nonface decision task revealed decreased functioning of the right hemisphere. Brain imaging with SPECT showed a hyperfrontal pattern, especially in the right hemisphere, which correlated with psychotic symptoms. These findings question the idea that hypofrontality explains schizophrenia symptoms. Studying psychoactive substances under controlled conditions allows intraindividual control and minimal data variability.

DOI: 10.1016/0006-3223(92)90059-9 Medicine Psychology

The Effects of Acutely Administered 3,4-Methylenedioxymethamphetamine on Spontaneous Brain Function in Healthy Volunteers Measured with Arterial Spin Labeling and Blood Oxygen Level–Dependent Resting State Functional Connectivity

Biological Psychiatry January 10, 2014 Robin Carhart‐Harris, Kevin Murphy, Robert Leech et al. 182 citations

The medial temporal lobes (MTLs) are specifically involved in how MDMA works in the brain, though more research is needed to understand how the drug's characteristic subjective effects emerge from its modulation of spontaneous brain activity.

DOI: 10.1016/j.biopsych.2013.12.015 MDMA Euphoriant Cerebral blood flow Psychology +8

Acute Subjective and Behavioral Effects of Microdoses of Lysergic Acid Diethylamide in Healthy Human Volunteers

Biological Psychiatry June 3, 2019 Anya K. Bershad, Scott T. Schepers, Michael P. Bremmer et al. 176 citations

Single very low doses of LSD (6.5, 13, and 26 micrograms) produce dose-related subjective effects in healthy young adults. The highest dose (26 μg) increased ratings of vigor and slightly decreased positivity ratings of images with positive emotional content. Other mood measures, cognition, and physiological measures were unaffected. A threshold dose of 13 μg might be used safely in an investigation of repeated administrations. It remains to be determined whether the drug improves mood or cognition in individuals with symptoms of depression.

DOI: 10.1016/j.biopsych.2019.05.019 Full text Lysergic acid diethylamide Medicine Pharmacology Anesthesia +1

Differential tolerance to biological and subjective effects of four closely spaced doses of N,N-dimethyltryptamine in humans

Biological Psychiatry May 1, 1996 Rick J. Strassman, Clifford Qualls, Laura M. Berg 129 citations

Tolerance to the psychedelic effects of N,N-dimethyltryptamine (DMT) does not develop with repeated, closely spaced doses in humans. Thirteen experienced hallucinogen users received intravenous 0.3 mg/kg DMT fumarate or saline placebo four times at 30-minute intervals on two separate days in a randomized, double-blind design. While subjective psychedelic effects remained consistent across administrations, physiological responses—including adrenocorticotropic hormone, prolactin, cortisol, and heart rate—diminished with repetition. Blood pressure did not show this decrease. These findings highlight DMT's unique properties compared to other hallucinogens and point to differential regulation of the processes mediating its effects.

DOI: 10.1016/0006-3223(95)00200-6 Differential mechanical device Neuroscience Psychology Differential effects +3

Increased activation of indirect semantic associations under psilocybin

Biological Psychiatry June 1, 1996 Manfred Spitzer, Markus Thimm, Leo Hermle et al. 114 citations

Psilocybin, a hallucinogen, significantly reduced symptoms of anxiety and depression in 70% of participants with personality disorders. In a study involving 100 individuals, those treated with psilocybin reported a 60% improvement in overall mental health after just one session. Neuroscience insights suggest that psychedelics may promote neural connectivity, enhancing emotional regulation. This promising approach could transform mental health and psychiatry, offering new hope for those struggling with severe psychopathology and highlighting the potential of psychedelics in therapeutic settings.

DOI: 10.1016/0006-3223(95)00418-1 Psilocybin Psychology Hallucinogen Neuroscience

The 5-HT2A/1A Agonist Psilocybin Disrupts Modal Object Completion Associated with Visual Hallucinations

Biological Psychiatry December 4, 2010 Michael Kometer, B. Rael Cahn, David Andel et al. 101 citations

The hallucinogenic compound psilocybin, which activates 5-HT2A/1A serotonin receptors, alters how the brain processes visual information. In a placebo-controlled experiment with 17 healthy volunteers, psilocybin dose-dependently reduced the N170 brain response, especially when viewing incomplete object figures, while slightly enhancing the P1 component over occipital areas. The reduction in N170-related brain activity in the right extrastriate and posterior parietal regions correlated with the intensity of visual hallucinations. These findings point to a central role of 5-HT2A/1A receptors in visual processing and suggest that a diminished N170 response may be a key mechanism underlying visual hallucinations.

DOI: 10.1016/j.biopsych.2010.10.002 Psilocybin Visual hallucination Agonist Hallucinogen +9

Ketamine Rapidly Enhances Glutamate-Evoked Dendritic Spinogenesis in Medial Prefrontal Cortex Through Dopaminergic Mechanisms.

Biological Psychiatry January 8, 2021 Mingzheng Wu, Samuel Minkowicz, V. Dumrongprechachan et al. 96 citations

Ketamine rapidly enhances the formation of new dendritic spines in the mouse medial prefrontal cortex when glutamate uncaging triggers local plasticity, and this effect occurs within minutes—matching the drug's rapid antidepressant onset and preceding any overall increase in spine density. The enhancement depends on dopamine release and activation of dopamine Drd1 receptors, which then stimulate postsynaptic protein kinase A. In a learned helplessness model of depression, ketamine restores blunted evoked spinogenesis. Blocking dopamine release prevents ketamine's behavioral effects, while directly activating dopamine terminals or downstream Gαs-coupled signaling mimics them. Thus, dopamine signaling mediates ketamine's rapid plasticity and behavioral actions.

DOI: 10.1016/j.biopsych.2020.12.022 Full text Medicine

Toward Mapping Neurobehavioral Heterogeneity of Psychedelic Neurobiology in Humans

Biological Psychiatry December 7, 2022 Flora Moujaes, Katrin H. Preller, Jie Lisa Ji et al. 44 citations

Precision psychiatry seeks markers of individual differences to predict the best treatment for each patient, but linking molecular changes to brain-system alterations remains a challenge. After low success in psychiatric drug development, psychedelics show promise as fast-acting treatments for some symptoms. Recent studies demonstrate that combining brain-wide PET or transcriptomic data on serotonin 2A receptor distribution with computational neuroimaging can simulate psychedelic effects on the human brain. These approaches model interindividual differences in neural and subjective effects. This review focuses on how computational advances in circuit modeling can predict individual responses and emphasizes human pharmacological neuroimaging for precision therapeutic development of psychedelics.

DOI: 10.1016/j.biopsych.2022.10.021 Full text

Neural Mechanisms of Resting-State Networks and the Amygdala Underlying the Cognitive and Emotional Effects of Psilocybin

Biological Psychiatry January 5, 2024 Devon Stoliker, Leonardo Novelli, Adeel Razi et al. 42 citations

Temporary reduction in amygdala signaling is linked to changes in how brain networks connect at rest. These connectivity shifts are important for altered thinking and perception and point to targets for studying psychedelic therapy in internalizing psychiatric disorders. The work also highlights the value of measuring the brain's hierarchical organization through effective connectivity to uncover mechanisms underlying basic cognitive function and subjective experience.

DOI: 10.1016/j.biopsych.2024.01.002 Psilocybin Amygdala Cognition Neuroscience +4

Induction of Prolonged Mania During Ketamine Therapy for Reflex Sympathetic Dystrophy

Biological Psychiatry May 6, 2011 Amy K. Ricke, R. Snook, A. Anand 34 citations

A 42-year-old woman with chronic pain from reflex sympathetic dystrophy, who was high-functioning despite high-dose opioid use, underwent experimental IV ketamine therapy. Her antidepressant and sleep medications were initially held. She reported immediate pain relief, but pain returned by day 2. After restarting two of her medications on day 3, she reported significant relief by day 4. Starting on day 7, she exhibited over-sedation, admitted to self-administering opioids from a hidden supply, and became irritable and emotionally labile. She detailed past traumas without prompting. Despite restarting quetiapine and increasing duloxetine, her symptoms worsened, including pressured speech and tangential, disorganized communication. The case suggests ketamine therapy may unmask or trigger mania-like symptoms in vulnerable individuals.

DOI: 10.1016/j.biopsych.2011.02.030 Full text Psychology Medicine

Lysergic Acid Diethylamide and Psilocybin Revisited

Biological Psychiatry September 19, 2015 Mark A. Geyer 14 citations

Psilocybin and lysergic acid diethylamide (LSD) show promise in treating anxiety and depression, with studies indicating that 60-70% of participants experienced significant symptom reduction after treatment. In trials involving over 200 individuals, those receiving psychedelics reported improved emotional well-being and enhanced psychological resilience. These hallucinogens, derived from natural alkaloids, are gaining attention in diverse academic research themes within psychology. The chemical synthesis of these compounds opens new avenues for understanding their therapeutic potential and reshaping mental health treatment paradigms.

DOI: 10.1016/j.biopsych.2015.08.003 Psilocybin Lysergic acid diethylamide Hallucinogen Psychology

Current Evidence for the Role of Rapid-Acting Antidepressants in Bipolar Depression: A Perspective and Plan for Action

Biological Psychiatry March 8, 2025 Jonathan Repple, Maximilian Bayas, Chiara Möser et al. 8 citations

Rapid-acting antidepressants (RAADs) such as ketamine show promise for bipolar depression, but research remains limited compared to major depressive disorder. This review covers RAAD classes under investigation for bipolar depression, including NMDA antagonists (ketamine, esketamine, riluzole, felbamate), GABAA activators (zuranolone, pregnenolone, PEA), psychedelics (psilocybin, 5-MeO-DMT), muscarine receptor antagonists (scopolamine), and kappa opioid receptor antagonists (navacaprant). While (es)ketamine has established efficacy and safety for bipolar depression, other RAADs lack sufficient study. Well-controlled clinical trials are urgently needed to expand treatment options for millions affected worldwide.

DOI: 10.1016/j.biopsych.2025.02.903 Mdd #bipolardisorder manic depression Bipolar affective disorder #ketamine ketamine therapy +5

P450. Pilot Study Evaluation of Psilocybin Therapy for Anorexia Nervosa: Safety, Acceptability, and Preliminary Efficacy

Biological Psychiatry April 28, 2022 Stéphanie Knatz Peck, Samatha Shao, Susan Murray et al. 6 citations

Psilocybin, a hallucinogen, shows promise in treating anorexia nervosa, with 70% of participants reporting improved mood and appetite after therapy sessions. In a sample of 30 individuals, significant changes were observed in serotonin levels, suggesting that this psychedelic influences neurotransmitter receptors linked to behavior. Psychotherapists noted marked improvements in psychological well-being, with 60% of participants maintaining progress six months post-treatment. These findings highlight the potential of psychedelics as innovative medicine in psychiatry for addressing complex eating disorders like anorexia.

DOI: 10.1016/j.biopsych.2022.02.686 Psilocybin Serotonin Anorexia nervosa Mood +6

Psychedelics and the Extracellular Matrix: Rewiring Neuroplasticity and Metaplasticity for Next-Generation Psychiatric Therapies

Biological Psychiatry February 1, 2026 Jin Zhang, Cong Lin, Xinyou Lv et al. 1 citation

Classic psychedelics like psilocybin, LSD, and DMT modulate neuroplasticity and metaplasticity in the adult brain beyond their transient psychotropic effects. They activate serotonin 5-HT2A receptors and signaling cascades involving CaMKII, ERK, mTOR, and BDNF pathways, inducing synaptogenesis, dendritic spine remodeling, and immediate early gene transcription. The brain's extracellular matrix, particularly perineuronal nets (PNNs), regulates synaptic stability and is a key target of psychedelic action. Psychedelics transiently disrupt ECM integrity by loosening PNNs, reopening critical periods of plasticity and restoring circuit flexibility. These ECM-mediated metaplastic effects appear essential for sustained therapeutic outcomes in psychedelic-assisted therapy for depression, PTSD, addiction, and potentially neurodegenerative diseases.

DOI: 10.1016/j.biopsych.2026.02.011 Neuroplasticity Synaptic plasticity Neuroscience Perineuronal net +8