Serotonin and Depression: A Disconnect between the Advertisements and the Scientific Literature

Lacasse, Jeffrey R.; Leo, Jonathan

doi:10.1371/journal.pmed.0020392

Cited by 317 publications

(202 citation statements)

References 26 publications

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“…19 Patients and supporters often questioned the construction of such boundaries, rejecting the notion of a medical cure and emphasising self-management. The majority of participants who were considering strategies for managing depression wanted to 'get out' of their depression.…”

Section: Summary Of Main Findingsmentioning

confidence: 99%

Qualitative study of depression management in primary care: GP and patient goals, and the value of listening

Johnston

Kumar²,

Kendall³

et al. 2007

Br J Gen Pract

107

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Section: Summary Of Main Findingsmentioning

confidence: 99%

Qualitative study of depression management in primary care: GP and patient goals, and the value of listening

Johnston

Kumar²,

Kendall³

et al. 2007

Br J Gen Pract

107

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“…The chemical hypothesis of depression emphasizes that the imbalance in the function of the serotonergic system is reinstated by SSRIs by elevating serotonin (5-HT) levels (Maes and Meltzer, 1995;Manji et al, 2001;Castrén, 2005), but alternative hypotheses have also been proposed (Lacasse and Leo, 2005;Nestler, 2008, 2010;Luscher et al, 2011). Nevertheless, it is generally recognized that early changes in emotional processing can be achieved by acute SSRI treatment while other symptoms of depression only respond to chronic medication (Lucki, 1998;Harmer et al, 2003;Cools et al, 2008;Harmer, 2008).…”

Section: Introductionmentioning

confidence: 99%

Fluoxetine (Prozac) and Serotonin Act on Excitatory Synaptic Transmission to Suppress Single Layer 2/3 Pyramidal Neuron-Triggered Cell Assemblies in the Human Prefrontal Cortex

et al. 2012

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Selective serotonin reuptake inhibitors are the most widely prescribed drugs targeting the CNS with acute and chronic effects in cognitive, emotional and behavioral processes. This suggests that microcircuits of the human cerebral cortex are powerfully modulated by selective serotonin reuptake inhibitors, however, direct measurements of serotonergic regulation on human synaptic interactions are missing. Using multiple whole-cell patch-clamp recordings from neurons in acute cortical slices derived from nonpathological human samples of the prefrontal cortex, we show that neuronal assemblies triggered by single action potentials of individual neurons in the human cortex are suppressed by therapeutic doses of fluoxetine (Prozac). This effect is boosted and can be mimicked by physiological concentrations of serotonin through 5HT-2A and 5HT-1A receptors. Monosynaptic excitatory connections from pyramidal cells to interneurons were suppressed by application of serotonin leaving the monosynaptic output of GABAergic cells unaffected. Changes in failure rate, in paired-pulse ratio, and in the coefficient of variation of the amplitude of EPSPs suggest a presynaptic action of serotonin. In conclusion, activation of neuronal assemblies, which were suggested as building blocks of high order cognitive processes, are effectively downregulated by the acute action of selective serotonin reuptake inhibitors or serotonin at the site of pyramidal output in human microcircuits.

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“…A direct role of a serotonergic deficiency in depression remains to be established (Lacasse and Leo, 2005), but central and peripheral markers of lowered 5-HT function have been observed in depressed patients, including low plasma tryptophan (Trp) levels, reduced platelet 5-HT uptake, decreased cerebrospinal fluid 5-hydroxyindoleacetic acid levels, and altered 5-HT receptor and 5-HT transporter binding, although not always consistently (see Schatzberg et al, 2002;Maes and Meltzer, 1995).…”

Section: Introductionmentioning

confidence: 99%

Effects of Acute Tryptophan Depletion on Mood and Facial Emotion Perception Related Brain Activation and Performance in Healthy Women with and without a Family History of Depression

Veen

Evers

Deutz

et al. 2006

Neuropsychopharmacol

108

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The present study examined the effects of acute tryptophan (Trp) depletion (ATD), a well-recognized method to lower central serotonin (5-HT) metabolism, on brain activation during a facial emotion perception task. Brain activation was measured using fMRI, and healthy female volunteers with a positive family history of unipolar depression (FH + ) were compared to healthy female volunteers without such a history (FHÀ). Participants viewed two morphed faces and were instructed to choose between the faces based either on the intensity of the emotional expression (direct task) or the gender of the face (incidental task). In the FH + group, depletion led to the expected lowering of mood, which partly determined the effect of depletion on performance and brain activation. A stronger mood lowering effect was associated with less accurate performance on faces expressing a negative emotion in the incidental task and a stronger right amygdala response to fearful faces in comparison to happy faces. These results were explained in terms of a mood-induced bias leading to a stronger impact of the expressed negative emotion which subsequently leads to more interference in the incidental task and a stronger amygdala response. It was concluded that the effects of ATD on mood, performance, and brain activation in a facial emotion perception task depend on family history of depression. Performance and brain activation partly depend on the effect of ATD on mood.

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Serotonin and Depression: A Disconnect between the Advertisements and the Scientific Literature

Abstract: Many ads for SSRI antidepressants claim that the drugs boost brain serotonin levels. Lacasse and Leo argue there is little scientific evidence to support this claim.

Cited by 317 publications

References 26 publications

Qualitative study of depression management in primary care: GP and patient goals, and the value of listening

Qualitative study of depression management in primary care: GP and patient goals, and the value of listening

Fluoxetine (Prozac) and Serotonin Act on Excitatory Synaptic Transmission to Suppress Single Layer 2/3 Pyramidal Neuron-Triggered Cell Assemblies in the Human Prefrontal Cortex

Effects of Acute Tryptophan Depletion on Mood and Facial Emotion Perception Related Brain Activation and Performance in Healthy Women with and without a Family History of Depression

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