SciCombinator

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Concept: Sertraline

145

Cognitive impairment (CI) and major depressive disorder (MDD) remain prevalent in treated HIV-1 disease; however, the pathogenesis remains elusive. A possible contributing mechanism is immune-mediated degradation of tryptophan (TRP) via the kynurenine (KYN) pathway, resulting in decreased production of serotonin and accumulation of TRP degradation products. We explored the association of these biochemical pathways and their relationship with CI and MDD in HIV-positive (HIV+) individuals.

Concepts: Serotonin, Selective serotonin reuptake inhibitor, Major depressive disorder, Dysthymia, Tryptophan, Sertraline, Fluoxetine, Serotonin transporter

144

The efficacy of antidepressant medication has been shown empirically to be overestimated due to publication bias, but this has only been inferred statistically with regard to psychological treatment for depression. We assessed directly the extent of study publication bias in trials examining the efficacy of psychological treatment for depression.

Concepts: Selective serotonin reuptake inhibitor, Bipolar disorder, Major depressive disorder, Sertraline

136

Cognitive behavioral therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs) are both effective treatments for some patients with obsessive-compulsive disorder (OCD), yet little is known about the neurochemical changes related to these treatment modalities. Here, we used positron emission tomography and the α-[11C]methyl-L-tryptophan tracer to examine the changes in brain regional serotonin synthesis capacity in OCD patients following treatment with CBT or SSRI treatment. Sixteen medication-free OCD patients were randomly assigned to 12 weeks of either CBT or sertraline treatment. Pre-to-post treatment changes in the α-[11C]methyl-L-tryptophan brain trapping constant, K* (ml/g/min), were assessed as a function of symptom response, and correlations with symptom improvement were examined. Responders/partial responders to treatment did not show significant changes in relative regional tracer uptake; rather, in responders/partial responders, 12 weeks of treatment led to serotonin synthesis capacity increases that were brain-wide. Irrespective of treatment modality, baseline serotonin synthesis capacity in the raphe nuclei correlated positively with clinical improvement. These observations suggest that, for some patients, successful remediation of OCD symptoms might be associated with greater serotonergic tone.

Concepts: Positron emission tomography, Serotonin, Fluvoxamine, Antidepressant, Selective serotonin reuptake inhibitor, Major depressive disorder, Sertraline, Obsessive–compulsive disorder

117

We developed computational models to predict the emergence of depression and Post-Traumatic Stress Disorder in Twitter users. Twitter data and details of depression history were collected from 204 individuals (105 depressed, 99 healthy). We extracted predictive features measuring affect, linguistic style, and context from participant tweets (N = 279,951) and built models using these features with supervised learning algorithms. Resulting models successfully discriminated between depressed and healthy content, and compared favorably to general practitioners' average success rates in diagnosing depression, albeit in a separate population. Results held even when the analysis was restricted to content posted before first depression diagnosis. State-space temporal analysis suggests that onset of depression may be detectable from Twitter data several months prior to diagnosis. Predictive results were replicated with a separate sample of individuals diagnosed with PTSD (Nusers = 174, Ntweets = 243,775). A state-space time series model revealed indicators of PTSD almost immediately post-trauma, often many months prior to clinical diagnosis. These methods suggest a data-driven, predictive approach for early screening and detection of mental illness.

Concepts: Diagnosis, Psychological trauma, Machine learning, Selective serotonin reuptake inhibitor, Cognitive behavioral therapy, Posttraumatic stress disorder, Sertraline, Supervised learning

87

Depression is a significant public health problem for which currently available medications, if effective, require weeks to months of treatment before patients respond. Previous studies have shown that the G protein responsible for increasing cAMP (Gαs) is increasingly localized to lipid rafts in depressed subjects and that chronic antidepressant treatment translocates Gαs from lipid rafts. Translocation of Gαs, which shows delayed onset after chronic antidepressant treatment of rats or of C6 glioma cells, tracks with the delayed onset of therapeutic action of antidepressants. Since antidepressants appear to specifically modify Gαs localized to lipid rafts, we sought to determine whether structurally diverse antidepressants, accumulate in lipid rafts. Sustained treatment of C6 glioma cells, which lack 5HT transporters, showed marked concentration of several antidepressants in raft fractions, as revealed by increased absorbance and by mass fingerprint. Closely related molecules without antidepressant activity, did not concentrate in raft fractions. Thus, at least two classes of antidepressants accumulate in lipid rafts and effect translocation of Gαs to the non-raft membrane fraction where it activates the cAMP-signaling cascade. Analysis of the structural determinants of raft localization may both help to explain the hysteresis of antidepressant action and lead to design and development of novel substrates for depression therapeutics.

Concepts: Medicine, Cell membrane, Lipid raft, Serotonin, Selective serotonin reuptake inhibitor, Bipolar disorder, Sertraline, Fluoxetine

86

Floatation-REST (Reduced Environmental Stimulation Therapy) reduces sensory input to the nervous system through the act of floating supine in a pool of water saturated with Epsom salt. The float experience is calibrated so that sensory signals from visual, auditory, olfactory, gustatory, thermal, tactile, vestibular, gravitational and proprioceptive channels are minimized, as is most movement and speech. This open-label study aimed to examine whether Floatation-REST would attenuate symptoms of anxiety, stress, and depression in a clinical sample. Fifty participants were recruited across a spectrum of anxiety and stress-related disorders (posttraumatic stress, generalized anxiety, panic, agoraphobia, and social anxiety), most (n = 46) with comorbid unipolar depression. Measures of self-reported affect were collected immediately before and after a 1-hour float session, with the primary outcome measure being the pre- to post-float change score on the Spielberger State Anxiety Inventory. Irrespective of diagnosis, Floatation-REST substantially reduced state anxiety (estimated Cohen’s d > 2). Moreover, participants reported significant reductions in stress, muscle tension, pain, depression and negative affect, accompanied by a significant improvement in mood characterized by increases in serenity, relaxation, happiness and overall well-being (p < .0001 for all variables). In reference to a group of 30 non-anxious participants, the effects were found to be more robust in the anxious sample and approaching non-anxious levels during the post-float period. Further analysis revealed that the most severely anxious participants reported the largest effects. Overall, the procedure was well-tolerated, with no major safety concerns stemming from this single session. The findings from this initial study need to be replicated in larger controlled trials, but suggest that Floatation-REST may be a promising technique for transiently reducing the suffering in those with anxiety and depression.

Concepts: Anxiety, Sensory system, Sense, Selective serotonin reuptake inhibitor, Cognitive behavioral therapy, Anxiety disorder, Sertraline, Panic attack

67

Ketamine is reported to have rapid antidepressant effects; however, there is limited understanding of the time-course of ketamine effects beyond a single infusion. A previous report including 10 participants with treatment-resistant major depression (TRD) found that six ketamine infusions resulted in a sustained antidepressant effect. In the current report, we examined the pattern and durability of antidepressant effects of repeated ketamine infusions in a larger sample, inclusive of the original.

Concepts: Selective serotonin reuptake inhibitor, Bipolar disorder, Sertraline

59

Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a genome-wide association meta-analysis based in 135,458 cases and 344,901 controls and identified 44 independent and significant loci. The genetic findings were associated with clinical features of major depression and implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved in gene splicing were enriched for smaller association signal. We found important relationships of genetic risk for major depression with educational attainment, body mass, and schizophrenia: lower educational attainment and higher body mass were putatively causal, whereas major depression and schizophrenia reflected a partly shared biological etiology. All humans carry lesser or greater numbers of genetic risk factors for major depression. These findings help refine the basis of major depression and imply that a continuous measure of risk underlies the clinical phenotype.

Concepts: Selective serotonin reuptake inhibitor, Cognitive behavioral therapy, Schizophrenia, Bipolar disorder, Major depressive disorder, Mood disorder, Sertraline, Suicide

56

Amygdala circuitry and early life stress (ELS) are both strongly and independently implicated in the neurobiology of depression. Importantly, animal models have revealed that the contribution of ELS to the development and maintenance of depression is likely a consequence of structural and physiological changes in amygdala circuitry in response to stress hormones. Despite these mechanistic foundations, amygdala engagement and ELS have not been investigated as biobehavioral targets for predicting functional remission in translational human studies of depression. Addressing this question, we integrated human neuroimaging and measurement of ELS within a controlled trial of antidepressant outcomes. Here we demonstrate that the interaction between amygdala activation engaged by emotional stimuli and ELS predicts functional remission on antidepressants with a greater than 80% cross-validated accuracy. Our model suggests that in depressed people with high ELS, the likelihood of remission is highest with greater amygdala reactivity to socially rewarding stimuli, whereas for those with low-ELS exposure, remission is associated with lower amygdala reactivity to both rewarding and threat-related stimuli. This full model predicted functional remission over and above the contribution of demographics, symptom severity, ELS, and amygdala reactivity alone. These findings identify a human target for elucidating the mechanisms of antidepressant functional remission and offer a target for developing novel therapeutics. The results also offer a proof-of-concept for using neuroimaging as a target for guiding neuroscience-informed intervention decisions at the level of the individual person.

Concepts: Selective serotonin reuptake inhibitor, Bipolar disorder, Norepinephrine, Bupropion, Sertraline

52

The association between the use of antidepressants during gestation and the risk of autism spectrum disorder (ASD) in children is still controversial. The etiology of ASD remains unclear, although studies have implicated genetic predispositions, environmental risk factors, and maternal depression.

Concepts: Autism, Pervasive developmental disorder, Asperger syndrome, Autism spectrum, PDD-NOS, Selective serotonin reuptake inhibitor, Bupropion, Sertraline