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Concept: Major depressive disorder


Psilocybin with psychological support is showing promise as a treatment model in psychiatry but its therapeutic mechanisms are poorly understood. Here, cerebral blood flow (CBF) and blood oxygen-level dependent (BOLD) resting-state functional connectivity (RSFC) were measured with functional magnetic resonance imaging (fMRI) before and after treatment with psilocybin (serotonin agonist) for treatment-resistant depression (TRD). Quality pre and post treatment fMRI data were collected from 16 of 19 patients. Decreased depressive symptoms were observed in all 19 patients at 1-week post-treatment and 47% met criteria for response at 5 weeks. Whole-brain analyses revealed post-treatment decreases in CBF in the temporal cortex, including the amygdala. Decreased amygdala CBF correlated with reduced depressive symptoms. Focusing on a priori selected circuitry for RSFC analyses, increased RSFC was observed within the default-mode network (DMN) post-treatment. Increased ventromedial prefrontal cortex-bilateral inferior lateral parietal cortex RSFC was predictive of treatment response at 5-weeks, as was decreased parahippocampal-prefrontal cortex RSFC. These data fill an important knowledge gap regarding the post-treatment brain effects of psilocybin, and are the first in depressed patients. The post-treatment brain changes are different to previously observed acute effects of psilocybin and other ‘psychedelics’ yet were related to clinical outcomes. A ‘reset’ therapeutic mechanism is proposed.

Concepts: Brain, Magnetic resonance imaging, Cerebral cortex, Cerebrum, Hippocampus, Serotonin, Schizophrenia, Major depressive disorder


The possible therapeutic impact of dietary changes on existing mental illness is largely unknown. Using a randomised controlled trial design, we aimed to investigate the efficacy of a dietary improvement program for the treatment of major depressive episodes.

Concepts: Randomized controlled trial, Schizophrenia, Major depressive disorder, Major depressive episode, Dysthymia, Depression, Suicide, Sickness behavior


To reanalyse SmithKline Beecham’s Study 329 (published by Keller and colleagues in 2001), the primary objective of which was to compare the efficacy and safety of paroxetine and imipramine with placebo in the treatment of adolescents with unipolar major depression. The reanalysis under the restoring invisible and abandoned trials (RIAT) initiative was done to see whether access to and reanalysis of a full dataset from a randomised controlled trial would have clinically relevant implications for evidence based medicine.

Concepts: The Canon of Medicine, Systematic review, Randomized controlled trial, Avicenna, Major depressive disorder, Paroxetine, GlaxoSmithKline, Beecham


Depressive disorders were a leading cause of burden in the Global Burden of Disease (GBD) 1990 and 2000 studies. Here, we analyze the burden of depressive disorders in GBD 2010 and present severity proportions, burden by country, region, age, sex, and year, as well as burden of depressive disorders as a risk factor for suicide and ischemic heart disease.

Concepts: Death, Risk, 1920, Heart disease, Ischemia, Major depressive disorder, Ischaemic heart disease, 1922


Individuals with a history of recurrent depression have a high risk of repeated depressive relapse or recurrence. Maintenance antidepressants for at least 2 years is the current recommended treatment, but many individuals are interested in alternatives to medication. Mindfulness-based cognitive therapy (MBCT) has been shown to reduce risk of relapse or recurrence compared with usual care, but has not yet been compared with maintenance antidepressant treatment in a definitive trial. We aimed to see whether MBCT with support to taper or discontinue antidepressant treatment (MBCT-TS) was superior to maintenance antidepressants for prevention of depressive relapse or recurrence over 24 months.

Concepts: Selective serotonin reuptake inhibitor, Bipolar disorder, Major depressive disorder, Bupropion, Sertraline, Mindfulness-based cognitive therapy


Intake of sweet food, beverages and added sugars has been linked with depressive symptoms in several populations. Aim of this study was to investigate systematically cross-sectional and prospective associations between sweet food/beverage intake, common mental disorder (CMD) and depression and to examine the role of reverse causation (influence of mood on intake) as potential explanation for the observed linkage. We analysed repeated measures (23,245 person-observations) from the Whitehall II study using random effects regression. Diet was assessed using food frequency questionnaires, mood using validated questionnaires. Cross-sectional analyses showed positive associations. In prospective analyses, men in the highest tertile of sugar intake from sweet food/beverages had a 23% increased odds of incident CMD after 5 years (95% CI: 1.02, 1.48) independent of health behaviours, socio-demographic and diet-related factors, adiposity and other diseases. The odds of recurrent depression were increased in the highest tertile for both sexes, but not statistically significant when diet-related factors were included in the model (OR 1.47; 95% CI: 0.98, 2.22). Neither CMD nor depression predicted intake changes. Our research confirms an adverse effect of sugar intake from sweet food/beverage on long-term psychological health and suggests that lower intake of sugar may be associated with better psychological health.

Concepts: Scientific method, Psychology, Epidemiology, Nutrition, Mental disorder, Major depressive disorder, Sugar, Whitehall Study


Access to Cognitive behavioural therapy (CBT) for depression is limited. One solution is CBT self-help books. Trial Objectives: To assess the impact of a guided self-help CBT book (GSH-CBT) on mood, compared to treatment as usual (TAU). Hypotheses:GSH-CBT will have improved mood and knowledge of the causes and treatment of depression compared to the control receiving TAUGuided self-help will be acceptable to patients and staff.

Concepts: Psychology, Randomized controlled trial, Cognitive behavioral therapy, Major depressive disorder, Control, Book, Self-help, Books


We wanted to examine tolerability and efficacy of NSI-189, a benzylpiperizine-aminiopyridine neurogenic compound for treating major depressive disorder (MDD). This was a Phase 1B, double blind, randomized, placebo controlled, multiple-dose study with three cohorts. The first cohort received 40 mg q.d. (n=6) or placebo (n=2), the second cohort 40 mg b.i.d. (n=6) or placebo (n=2), and the third cohort 40 mg t.i.d. (n=6) or placebo (n=2). Twenty-four patients with MDD were recruited, with the diagnosis and severity confirmed through remote interviews. Eligible patients received NSI-189 or placebo for 28 days in an inpatient setting with assessments for safety, pharmacokinetics (PK) and efficacy. Outpatient follow-up visits were conducted until day 84 (±3). NSI-189 was relatively well tolerated at all doses, with no serious adverse effects. NSI-189 area under the curve increased in a dose-related and nearly proportional manner across the three cohorts, with a half-life of 17.4-20.5 h. The exploratory efficacy measurements, including Symptoms Of Depression Questionnaire (SDQ), Montgomery-Asberg Depression Scale (MADRS), Clinical Global Impressions-Improvement (CGI-I), and The Massachusetts General Hospital (MGH) Cognitive and Physical Functioning Questionnaire (CPFQ) showed a promising reduction in depressive and cognitive symptoms across all measures for NSI-189, with significant improvement in the SDQ and CPFQ, and a medium to large effect size for all measures. These improvements persisted during the follow-up phase. In summary, NSI-189 shows potential as a treatment for MDD in an early phase study. The main limitation of this preliminary study was the small sample size of each cohort.Molecular Psychiatry advance online publication, 8 December 2015; doi:10.1038/mp.2015.178.

Concepts: Sample size, Cognitive behavioral therapy, Bipolar disorder, Major depressive disorder, Seasonal affective disorder, Dysthymia, Depression, Types of psychological depression


The recent questioning of the antidepressant effect of selective serotonin reuptake inhibitors (SSRIs) is partly based on the observation that approximately half of company-sponsored trials have failed to reveal a significant difference between active drug and placebo. Most of these have applied the Hamilton depression rating scale to assess symptom severity, the sum score for its 17 items (HDRS-17-sum) serving as effect parameter. In this study, we examined whether the negative outcomes of many SSRI trials may be partly caused by the use of this frequently questioned measure of response. We undertook patient-level post-hoc analyses of 18 industry-sponsored placebo-controlled trials regarding paroxetine, citalopram, sertraline or fluoxetine, and including in total 6669 adults with major depression, the aim being to assess what the outcome would have been if the single item depressed mood (rated 0-4) had been used as a measure of efficacy. In total, 32 drug-placebo comparisons were reassessed. While 18 out of 32 comparisons (56%) failed to separate active drug from placebo at week 6 with respect to reduction in HDRS-17-sum, only 3 out of 32 comparisons (9%) were negative when depressed mood was used as an effect parameter (P<0.001). The observation that 29 out of 32 comparisons detected an antidepressant signal from the tested SSRI suggests the effect of these drugs to be more consistent across trials than previously assumed. Further, the frequent use of the HDRS-17-sum as an effect parameter may have distorted the current view on the usefulness of SSRIs and hampered the development of novel antidepressants.Molecular Psychiatry advance online publication, 28 April 2015; doi:10.1038/mp.2015.53.

Concepts: Serotonin, Antidepressant, Selective serotonin reuptake inhibitor, Major depressive disorder, Sertraline, Fluoxetine, Paroxetine, Venlafaxine


BACKGROUND: Cola is an extremely popular caffeinated soft drink. The media have recently cited a poll in which 16% of the respondents considered themselves to be addicted to cola soft drinks. We find the contrast between the apparent prevalence of cola addiction and the lack of scientific literature on the subject remarkable. To our knowledge, this is the first case of cola dependency described in the scientific literature. CASE PRESENTATION: The patient is a 40-year-old woman, who when feeling down used cola to give her an energy boost and feel better about herself. During the past seven years her symptoms increased, and she was prescribed antidepressant medication by her family doctor. Due to worsening of symptoms she was hospitalised and later referred to a specialised outpatient clinic for affective disorders. At entry to the clinic she suffered from constant tiredness, lack of energy, failing concentration, problems falling asleep as well as interrupted sleep. She drank about three litres of cola daily, and she had developed a metabolic syndrome.The patient fulfilled the ICD-10 criteria for dependency, and on the Yale Food Addiction Scale (YFAS) she scored 40 points. Her clinical mental status was at baseline assessed by the Major Depression Inventory (MDI) = 41, Hamilton Depression - 17 item Scale (HAMD-17) = 14, Young Mania Rating Scale (YMRS) = 2 and the Global Assessment of Functioning (GAF) Scale = 45.During cognitive therapy sessions she was guided to stop drinking cola and was able to moderate her use to an average daily consumption of 200 ml of cola Her concentration improved and she felt mentally and physically better. At discharge one year after entry her YFAS was zero. She was mentally stable (MDI =1, HAMD-17 = 0, YMRS = 0 and GAF = 85) and without antidepressant medication. She had lost 7.2 kg, her waistline was reduced by 13 cm and the metabolic syndrome disappeared. CONCLUSION: This case serves as an example of how the overconsumption of a caffeinated soft drink likely was causing or accentuating the patient’s symptoms of mental disorder. When diagnosing and treating depression, health professionals should pay attention to potential overuse of cola or other caffeinated beverages.

Concepts: Coffee, Addiction, Caffeine, Bipolar disorder, Major depressive disorder, Soft drink, Energy drink, Coca-Cola