Is serotonin an upper or a downer? The evolution of the serotonergic system and its role in depression and the antidepressant response.

Andrews, Paul W.; Bharwani, Aadil; Lee, Kyuwon R.; Fox, Molly; Thomson, J. Anderson

doi:10.1016/j.neubiorev.2015.01.018

Cited by 281Treatment of Major DepressionNeurotransmitter Receptor Influence on BehaviorTryptophan and brain disorders

Is serotonin an upper or a downer? The evolution of the serotonergic system and its role in depression and the antidepressant response.

Andrews, Paul W., Bharwani, Aadil, Lee, Kyuwon R., Fox, Molly, Thomson, J. Anderson·2015·Neuroscience & Biobehavioral Reviews

DOI 10.1016/j.neubiorev.2015.01.018

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Abstract

The role of serotonin in depression and antidepressant treatment remains unresolved despite decades of research. In this paper, we make three major claims. First, serotonin transmission is elevated in multiple depressive phenotypes, including melancholia, a subtype associated with sustained cognition. The primary challenge to this first claim is that the direct pharmacological effect of most symptom-reducing medications, such as the selective serotonin reuptake inhibitors (SSRIs), is to increase synaptic serotonin. The second claim, which is crucial to resolving this paradox, is that the serotonergic system evolved to regulate energy. By increasing extracellular serotonin, SSRIs disrupt energy homeostasis and often worsen symptoms during acute treatment. Our third claim is that symptom reduction is not achieved by the direct pharmacological properties of SSRIs, but by the brain's compensatory responses that attempt to restore energy homeostasis. These responses take several weeks to develop, which explains why SSRIs have a therapeutic delay. We demonstrate the utility of our claims by examining what happens in animal models of melancholia and during acute and chronic SSRI treatment.

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Serotonin and decision making processes
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Fluoxetine Combined with a Serotonin-1A Receptor Antagonist Reversed Reward Deficits Observed during Nicotine and Amphetamine Withdrawal in Rats
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A Single Dose of the Selective Serotonin Reuptake Inhibitor Citalopram Exacerbates Anxiety in Humans: A Fear-Potentiated Startle Study
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Environmental Factors Preceding the Onset of Severe Depressions
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Learned helplessness at fifty: Insights from neuroscience.
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Rethinking IL-6 and CRP: Why they are more than inflammatory biomarkers, and why it matters
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Serotonin and brain function: a tale of two receptors
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A Unified Model of Depression: Integrating Clinical, Cognitive, Biological, and Evolutionary Perspectives
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Beyond a neurotransmitter: The role of serotonin in inflammation and immunity
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Serotonin in Animal Cognition and Behavior
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Opposite effects of dopamine and serotonin on resting-state networks: review and implications for psychiatric disorders
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From Serotonin to Neuroplasticity: Evolvement of Theories for Major Depressive Disorder
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The neurobiology of addiction
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The Anatomy of Inference: Generative Models and Brain Structure
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A Cybernetic Theory of Psychopathology
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Critical Neurotransmitters in the Neuroimmune Network
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Tryptophan Metabolism in Central Nervous System Diseases: Pathophysiology and Potential Therapeutic Strategies
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“For MDD patients, two feasible treatment options include the use of KYNA competitive inhibitors, Aging and Disease • 8 such as AV-101, and inhibiting transport of L-KYN to the brain.”
BackgroundInfluential
The role of the microbiome in the neurobiology of social behaviour
Sarkar, A., Harty, S., Johnson, K. V. ‐., Moeller, A. H., Carmody, R. N., Lehto, S. M., Erdman, S. E., Dunbar, R. I. M., & Burnet, P. W. J. (2020) · Biological Reviews · doi:10.1111/brv.12603 · Cited by 135 · see citing works
Molecular biomarkers of depression
Gururajan, A., Clarke, G. A., Dinan, T. G., & Cryan, J. F. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.02.011 · Cited by 134 · see citing works
Optimal vitamin D spurs serotonin: 1,25-dihydroxyvitamin D represses serotonin reuptake transport (SERT) and degradation (MAO-A) gene expression in cultured rat serotonergic neuronal cell lines
Sabir, M. S., Haussler, M. R., Mallick, S., Kaneko, I., Lucas, D. A., Haussler, C. A., Whitfield, G. K., & Jurutka, P. W. (2018) · Genes & Nutrition · doi:10.1186/s12263-018-0605-7 · Cited by 128 · see citing works
Neuroinflammation as an etiological trigger for depression comorbid with inflammatory bowel disease
Craig, C. F., Filippone, R. T., Stavely, R., Bornstein, J. C., Apostolopoulos, V., & Nurgali, K. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02354-1 · Cited by 124 · see citing works
Depression subtyping based on evolutionary psychiatry: Proximate mechanisms and ultimate functions
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Depression: Biological markers and treatment
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RETRACTED: Neuroprotective Effects of Ginsenoside-Rg1 Against Depression-Like Behaviors via Suppressing Glial Activation, Synaptic Deficits, and Neuronal Apoptosis in Rats
Fan, C., Song, Q., Wang, P., Li, Y., Yang, M., & Yu, S. Y. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02889 · Cited by 109 · see citing works
Retracted
Hypernatural Monitoring: A Social Rehearsal Account of Smartphone Addiction
Veissière, S. P. L., & Stendel, M. (2018) · Frontiers in Psychology · doi:10.3389/fpsyg.2018.00141 · Cited by 105 · see citing works
“Andrews and colleagues see this as further evidence that a significant part of mental life is dedicated to rehearsing social scenarios (Andrews and Thomson, 2009; Andrews et al., 2012, 2015).”
Background
High-cholesterol diet promotes depression- and anxiety-like behaviors in mice by impact gut microbe and neuroinflammation
Zou, L., Tian, Y., Wang, Y., Chen, D., Lu, X., Zeng, Z., Chen, Z., Lin, C., & Liang, Y. (2023) · Journal of Affective Disorders · doi:10.1016/j.jad.2023.01.122 · Cited by 107 · see citing works
Biomarkers of post-covid depression
Lorkiewicz, P., & Waszkiewicz, N. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10184142 · Cited by 102 · see citing works
The Mortality and Myocardial Effects of Antidepressants Are Moderated by Preexisting Cardiovascular Disease: A Meta-Analysis
Maslej, M. M., Bolker, B. M., Russell, M. J., Eaton, K., Durisko, Z., Hollon, S. D., Swanson, G. M., Thomson Jr., J. A., Mulsant, B. H., & Andrews, P. W. (2017) · Psychotherapy and Psychosomatics · doi:10.1159/000477940 · Cited by 98 · see citing works
Strategies to reduce use of antidepressants
Kendrick, T. (2020) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.14475 · Cited by 92 · see citing works
Serotonin and depression
Healy, D. (2015) · BMJ · doi:10.1136/bmj.h1771 · Cited by 96 · see citing works
Impact of the widespread pharmaceutical pollutant fluoxetine on behaviour and sperm traits in a freshwater fish
Martin, J. M., Bertram, M. G., Saaristo, M., Ecker, T. E., Hannington, S. L., Tanner, J. L., Michelangeli, M., O’Bryan, M. K., & Wong, B. B. M. (2018) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2018.09.294 · Cited by 91 · see citing works
Barriers and facilitators to discontinuing antidepressant use: A systematic review and thematic synthesis
Maund, E., Dewar-Haggart, R., Williams, S., Bowers, H., Geraghty, A. W. A., Leydon, G., May, C., Dawson, S., & Kendrick, T. (2019) · Journal of Affective Disorders · doi:10.1016/j.jad.2018.10.107 · Cited by 90 · see citing works
The microbiome as a novel paradigm in studying stress and mental health.
Liu, R. T. (2017) · American Psychologist · doi:10.1037/amp0000058 · Cited by 89 · see citing works
Mechanisms of Neurotoxicity Associated with Exposure to the Herbicide Atrazine
Stradtman, S. C., & Freeman, J. L. (2021) · Toxics · doi:10.3390/toxics9090207 · Cited by 89 · see citing works
Serotonin 2A receptors are a stress response system: implications for post-traumatic stress disorder
Murnane, K. S. (2019) · Behavioural Pharmacology · doi:10.1097/fbp.0000000000000459 · Cited by 85 · see citing works
Gut microbiota dysbiosis in depressed women: The association of symptom severity and microbiota function
Chen, Y.-H., Xue, F., Yu, S.-F., Li, X.-S., Liu, L., Jia, Y., Yan, W., Tan, Q.-R., Wang, H., & Peng, Z. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2020.12.143 · Cited by 80 · see citing works
Is depression the missing link between inflammatory mediators and cancer?
Polityńska, B., Pokorska, O., Wojtukiewicz, A. M., Sawicka, M., Mysliwiec, M., Honn, K. V., Tucker, S. C., & Wojtukiewicz, M. Z. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2022.108293 · Cited by 80 · see citing works
Cross-sectional networks of depressive symptoms before and after antidepressant medication treatment
Bos, F. M., Fried, E. I., Hollon, S. D., Bringmann, L. F., Dimidjian, S., DeRubeis, R. J., & Bockting, C. (2018) · Social Psychiatry and Psychiatric Epidemiology · doi:10.1007/s00127-018-1506-1 · Cited by 80 · see citing works
Brain serotonergic activation in growth-stunted farmed salmon: adaption versus pathology
Vindas, M. A., Johansen, I. B., Folkedal, O., Höglund, E., Gorissen, M., Flik, G., Kristiansen, T., & Øyvind Øverli, A. (2016) · Royal Society Open Science · doi:10.1098/rsos.160030 · Cited by 77 · see citing works
Abnormal Functional Relationship of Sensorimotor Network With Neurotransmitter-Related Nuclei via Subcortical-Cortical Loops in Manic and Depressive Phases of Bipolar Disorder
Martino, M., Magioncalda, P., Conio, B., Capobianco, L., Russo, D., Adavastro, G., Tumati, S., Tan, Z., Lee, H., Lane, T. J., et al. (2019) · Schizophrenia Bulletin · doi:10.1093/schbul/sbz035 · Cited by 72 · see citing works
The Serotonin Transporter and Early Life Stress: Translational Perspectives
Houwing, D. J., Buwalda, B., van der Zee, E. A., de Boer, S. F., & Olivier, J. D. A. (2017) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2017.00117 · Cited by 76 · see citing works
Oral administration of Lactococcus lactis WHH2078 alleviates depressive and anxiety symptoms in mice with induced chronic stress
Gao, K., Farzi, A., Ke, X., Yu, Y., Chen, C., Chen, S., Yu, T., Wang, H., & Li, Y. (2021) · Food & Function · doi:10.1039/d1fo03723d · Cited by 72 · see citing works
Effects of Creatine Monohydrate Augmentation on Brain Metabolic and Network Outcome Measures in Women With Major Depressive Disorder
Yoon, S., Kim, J. E., Hwang, J., Kim, T.-S., Kang, H. J., Namgung, E., Ban, S., Oh, S., Yang, J., Renshaw, P. F., et al. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.11.027 · Cited by 71 · see citing works
Manual or electroacupuncture as an add-on therapy to SSRIs for depression: A randomized controlled trial
Zhao, B., Li, Z., Wang, Y., Ma, X., Wang, X., Wang, X., Liu, J., Huang, Y., Zhang, J., Li, L., et al. (2019) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2019.04.005 · Cited by 71 · see citing works
Analysis and measurement of serotonin
Szeitz, A. J., & Bandiera, S. M. (2017) · Biomedical Chromatography · doi:10.1002/bmc.4135 · Cited by 69 · see citing works
Sustained Activation of Postsynaptic 5-HT2A Receptors Gates Plasticity at Prefrontal Cortex Synapses
Berthoux, C., Barre, A., Bockaert, J., Marin, P., & Bécamel, C. (2018) · Cerebral Cortex · doi:10.1093/cercor/bhy064 · Cited by 68 · see citing works
Serotonergic Plasticity in the Dorsal Raphe Nucleus Characterizes Susceptibility and Resilience to Anhedonia
Prakash, N., Stark, C. J., Keisler, M. N., Luo, L., Der‐Avakian, A., & Dulcis, D. (2019) · Journal of Neuroscience · doi:10.1523/jneurosci.1802-19.2019 · Cited by 70 · see citing works
Stress-Related Dysfunction of Adult Hippocampal Neurogenesis—An Attempt for Understanding Resilience?
Leschik, J., Lutz, B., & Gentile, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22147339 · Cited by 70 · see citing works
Primary functional brain connections associated with melancholic major depressive disorder and modulation by antidepressants
Ichikawa, N., Lisi, G., Yahata, N., Okada, G., Takamura, M., Hashimoto, R.-I., Yamada, T., Yamada, M., Suhara, T., Moriguchi, S., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-60527-z · Cited by 68 · see citing works
Iron and manganese-related CNS toxicity: mechanisms, diagnosis and treatment
Chen, P., Totten, M. S., Zhang, Z., Bucinca, H., Erikson, K. M., Santamarı́a, A., Bowman, A. B., & Aschner, M. (2019) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2019.1581608 · Cited by 66 · see citing works
Understanding the role of serotonin in psychiatric diseases
Marazziti, D. (2017) · F1000Research · doi:10.12688/f1000research.10094.1 · Cited by 62 · see citing works
Psychological mechanisms and functions of 5-HT and SSRIs in potential therapeutic change: Lessons from the serotonergic modulation of action selection, learning, affect, and social cognition
Roberts, C., Sahakian, B. J., & Robbins, T. W. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.09.001 · Cited by 61 · see citing works
Intrinsic brain activity of subcortical-cortical sensorimotor system and psychomotor alterations in schizophrenia and bipolar disorder: A preliminary study
Magioncalda, P., Martino, M., Conio, B., Lee, H., Ku, H., Chen, C.-J., Inglese, M., Amore, M., Lane, T. J., & Northoff, G. (2020) · Schizophrenia Research · doi:10.1016/j.schres.2020.01.009 · Cited by 60 · see citing works
Improving outcome for mental disorders by enhancing memory for treatment
Harvey, A. G., Lee, J., Smith, R. L., Gumport, N. B., Hollon, S. D., Rabe‐Hesketh, S., Hein, K., Dolsen, E. A., Haman, K., Kanady, J. C., et al. (2016) · Behaviour Research and Therapy · doi:10.1016/j.brat.2016.03.007 · Cited by 60 · see citing works
Multisensory cortical processing and dysfunction across the neuropsychiatric spectrum
Hornix, B., Havekes, R., & Kas, M. J. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.02.010 · Cited by 60 · see citing works
Linking unfolded protein response to inflammation and depression: potential pathologic and therapeutic implications
Timberlake, M. A., & Dwivedi, Y. (2018) · Molecular Psychiatry · doi:10.1038/s41380-018-0241-z · Cited by 57 · see citing works
Additive genetic risk from five serotonin system polymorphisms interacts with interpersonal stress to predict depression.
Vrshek‐Schallhorn, S., Stroud, C. B., Mineka, S., Zinbarg, R. E., Adam, E. K., Redei, E. E., Hammen, C. L., & Craske, M. G. (2015) · Journal of Abnormal Psychology · doi:10.1037/abn0000098 · Cited by 57 · see citing works
Neuroinflammation and neuroprogression in depression: Effects of alternative drug treatments
Richardson, B., MacPherson, A., & Bambico, F. R. (2022) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2022.100554 · Cited by 56 · see citing works
Kynurenine pathway metabolism and the neurobiology of treatment-resistant depression: Comparison of multiple ketamine infusions and electroconvulsive therapy
Allen, A. P., Naughton, M., Dowling, J. L., Walsh, A. E. L., O'Shea, R., Shorten, G., Scott, L. V., McLoughlin, D. M., Cryan, J. F., Clarke, G. A., et al. (2018) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2018.02.011 · Cited by 55 · see citing works
The Behavioral Biology of Teams: Multidisciplinary Contributions to Social Dynamics in Isolated, Confined, and Extreme Environments
Landon, L. B., Douglas, G. L., Downs, M. E., Greene, M. R., Whitmire, A. M., Zwart, S. R., & Roma, P. G. (2019) · Frontiers in Psychology · doi:10.3389/fpsyg.2019.02571 · Cited by 51 · see citing works
Early life stress and the programming of eating behavior and anxiety: Sex-specific relationships with serotonergic activity and hypothalamic neuropeptides
de Lima, R. M. S., Bento, L. V. D. S., Lugon, M. D. M. V., Baraúna, V. G., Bittencourt, A. S., Dalmaz, C., & Bittencourt, A. P. S. D. V. (2019) · Behavioural Brain Research · doi:10.1016/j.bbr.2019.112399 · Cited by 50 · see citing works
Seasonal changes in NRF2 antioxidant pathway regulates winter depression-like behavior
Nakayama, T., Okimura, K., Shen, J., Guh, Y.-J., Tamai, K., Shimada, A., Minou, S., Okushi, Y., Shimmura, T., Furukawa, Y., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2000278117 · Cited by 49 · see citing works
Temperament and character influence on depression treatment outcome
Balestri, M., Porcelli, S., Souery, D., Kasper, S. F., Dikeos, D. G., Ferentinos, P. P., Papadimitriou, G. N., Rujescu, D., Martinotti, G., Nicola, M. D., et al. (2019) · Journal of Affective Disorders · doi:10.1016/j.jad.2019.04.031 · Cited by 49 · see citing works
Serotonin acts through YAP to promote cell proliferation: mechanism and implication in colorectal cancer progression
Yu, H., Qu, T., Yang, J., & Dai, Q. (2023) · Cell Communication and Signaling · doi:10.1186/s12964-023-01096-2 · Cited by 46 · see citing works
Central serotonin attenuates LPS-induced systemic inflammation
Mota, C. M. D., Rodrigues-Santos, C., Fernández, R. A. R., Carolino, R. O. G., Antunes‐Rodrigues, J., Anselmo-Franci, J. A., & Branco, L. G. S. (2017) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2017.07.010 · Cited by 44 · see citing works
Early Developmental Stress Affects Subsequent Gene Expression Response to an Acute Stress in Atlantic Salmon: An Approach for Creating Robust Fish for Aquaculture?
Robinson, N. A., Johnsen, H., Moghadam, H. K., Andersen, Ø., & Tveiten, H. (2019) · G3 Genes Genomes Genetics · doi:10.1534/g3.119.400152 · Cited by 44 · see citing works
Antidepressants in Alzheimer’s Disease: A Focus on the Role of Mirtazapine
Correia, A. S., & Vale, N. (2021) · Pharmaceuticals · doi:10.3390/ph14090930 · Cited by 42 · see citing works
Not only serotonergic system, but also dopaminergic system involved in albiflorin against chronic unpredictable mild stress-induced depression-like behavior in rats
Song, J., Hou, X., Hu, X., Lu, C., Liu, C., Wang, J., Liu, W., Teng, L., & Wang, D. (2015) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2015.10.001 · Cited by 40 · see citing works
EthoCRED : a framework to guide reporting and evaluation of the relevance and reliability of behavioural ecotoxicity studies
Bertram, M. G., Ågerstrand, M., Thoré, E. S. J., Allen, J., Balshine, S., Brand, J. A., Brooks, B. W., Dang, Z., Duquesne, S., Ford, A. T., et al. (2024) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/brv.13154 · Cited by 39 · see citing works
Effects of a variable light intensity lighting program on the welfare and performance of commercial broiler chickens
Kang, S. W., Christensen, K. D., Kidd, M. T., Orlowski, S., & Clark, J. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1059055 · Cited by 38 · see citing works
Coping with a changing environment: the effects of early life stress
Vindas, M. A., Madaro, A., Fraser, T. W. K., Höglund, E., Olsen, R. E., Øverli, Ø., & Kristiansen, T. (2016) · Royal Society Open Science · doi:10.1098/rsos.160382 · Cited by 38 · see citing works
Generation-specific and interactive effects of pesticide and antidepressant exposure in a fish model call for multi-stressor and multigenerational testing
Thoré, E. S. J., Hooreweghe, F. V., Philippe, C., Brendonck, L., & Pinceel, T. (2021) · Aquatic Toxicology · doi:10.1016/j.aquatox.2021.105743 · Cited by 38 · see citing works
Integrating the monoamine and cytokine hypotheses of depression: Is histamine the missing link?
Hersey, M., Hashemi, P., & Reagan, L. P. (2021) · European Journal of Neuroscience · doi:10.1111/ejn.15392 · Cited by 37 · see citing works
Perinatal reduction of functional serotonin transporters results in developmental delay
Kroeze, Y., Dirven, B. C. J., Janssen, S., Kröhnke, M., Barte, R. M., Middelman, A., van Bokhoven, H., Zhou, H., & Homberg, J. R. (2016) · Neuropharmacology · doi:10.1016/j.neuropharm.2016.05.012 · Cited by 35 · see citing works
Deuterium-Depleted Water as Adjuvant Therapeutic Agent for Treatment of Diet-Induced Obesity in Rats
Halenova, T., Zlatskiy, I. A., Syroeshkin, A. V., Maksimova, T. V., & Плетенева, Т. В. (2019) · Molecules · doi:10.3390/molecules25010023 · Cited by 35 · see citing works
Two models of inescapable stress increase tph2 mRNA expression in the anxiety-related dorsomedial part of the dorsal raphe nucleus
Donner, N. C., Kubala, K. H., Hassell, J. E., Lieb, M. W., Nguyen, K. T., Heinze, J. D., Drugan, R. C., Maier, S. F., & Lowry, C. A. (2018) · Neurobiology of Stress · doi:10.1016/j.ynstr.2018.01.003 · Cited by 35 · see citing works
Effect of chronic handling and social isolation on emotion and cognition in adolescent rats
Song, M. K., Lee, J. H., & Kim, Y. (2021) · Physiology & Behavior · doi:10.1016/j.physbeh.2021.113440 · Cited by 34 · see citing works
How psychosocial research can help the National Institute of Mental Health achieve its grand challenge to reduce the burden of mental illnesses and psychological disorders.
Teachman, B. A., McKay, D., Barch, D. M., Prinstein, M. J., Hollon, S. D., & Chambless, D. L. (2018) · American Psychologist · doi:10.1037/amp0000361 · Cited by 32 · see citing works
Recent Developments in the Treatment of Depression
Hollon, S. D., Cohen, Z. D., Singla, D. R., & Andrews, P. W. (2019) · Behavior Therapy · doi:10.1016/j.beth.2019.01.002 · Cited by 34 · see citing works
Decreased platelet 5-hydroxytryptamin (5-HT) levels: a response to antidepressants
Li, X., Fan, Y., Xiao, S., Peng, S., Dong, X., Zheng, X., Liu, C., Li, H., & Xiao, Z. (2015) · Journal of Affective Disorders · doi:10.1016/j.jad.2015.08.025 · Cited by 33 · see citing works
Exploring a post-traumatic stress disorder paradigm in Flinders sensitive line rats to model treatment-resistant depression I: bio-behavioural validation and response to imipramine
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Authors: Andrews, P. W., Bharwani, A., Lee, K. R., Fox, M., & Thomson, J. A.
Affiliations: McMaster University (CA)
University of California, Irvine (US)
University of Virginia (US)
Corresponding author: Andrews, Paul W.
ORCID: Andrews, Paul W.
Bharwani, Aadil
Lee, Kyuwon R.
Fox, Molly
Venue: Neuroscience & Biobehavioral Reviews
Publisher: Elsevier BV
Published: 2015-04
Volume: 51
Pages: 164-188
ISSN: 0149-7634 (ISSN-L)
DOI: 10.1016/j.neubiorev.2015.01.018
OpenAlex: W2163250198
Cited by: 281
References: 459
Citations by year: 2026: 12 · 2025: 13 · 2024: 25 · 2023: 21 · 2022: 20 · 2021: 34 · 2020: 31 · 2019: 36 · 2018: 37 · 2017: 24 · 2016: 17 · 2015: 10
FWCI: 3.69
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neuroscience & Biobehavioral Reviews (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords: serotonin, depression, antidepressant response, selective serotonin reuptake inhibitors, melancholia, energy homeostasis, treatment delay, animal models of depression
MeSH terms: Animals, Antidepressive Agents, Brain, Depressive Disorder, Humans, Serotonin, Selective Serotonin Reuptake Inhibitors

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Is serotonin an upper or a downer? The evolution of the serotonergic system and its role in depression and the antidepressant response.

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