Is Saffron as good as fluoxetine? Human psycho pharm. 2014.Nov

17.11.2014

Saffron is the dried  stigmas and styles of the saffron flower (Crocus sativus L.). It is  the most expensive spice in the world. Saffron has been used as an anticonvulsive, analgesic, aphrodisiac and antispasmodic in traditional medicine. Pharmacological studies have shown that it may have anticancer, anti-inflammatory, antioxidant and anti platelet effects. A recent meta-analysis, was confirmed to be effective for the treatment of depression (Hausenblas et al., 2013).

What are the underlying mechanisms that make saffron an antidepressant?

Lopresti &  Drummond explores the evidence for saffrons antidepressant action and describes possible mechanisms in this article.

Actions:

1. Constituents of saffron like   crocin, crocetin and safranal, are potent antioxidants. Depression is associated with lowered antioxidant enzymes and elevated oxidative stress. The antioxidant action is high  when  the above three constituents are delivered collectively.

2. Crocin and crocetin  in saffron is shown to have strong anti-inflammatory activity. Depression is associated with inflammatory disorders. Inflammatory markers like C-reactive protein , interleukin-6 , and tumour necrosis factor-α are repeatedly shown to be higher in depression. Cytokine therapy is known to increase depression. Some anti-inflammatory agents have antidepressant action. Some antidepressants have anti-inflammatory action.

3. Evidence of saffron’s action on serotenerigic system is lacking

4.  Saffron might have a role in lowering the HPA response to stress, there is limited preliminary evidence to support this.

5. Saffron have some neuroprotective effect .It can increase BDNF.

4 published RCTs suggest that in mild moderate depression saffron is as effective as fluoxetine or imipramine. The effect size in 2013 metaanlysis was 1.62. The dosage used was 30mg/day. Daily dose up to 1.5 gm is considered safe.  Authors caution  use in individuals with coagulation disorders.Long term efficacy is not been studies beyond 8 weeks.

It appears that it is a promising option in mild to moderate depression. Studies on severe depression and for longer periods are lacking. Trials has not been conducted outside Iran.  Larger clinical trials with long-term follow-ups are needed before firm conclusions can be made regarding saffron‘s efficacy and safety for treating depressive symptoms.

 Author  (AL)has declared that he has shares in a neutraceutical company.

Summary of the article:

Saffron (Crocus sativus) for depression: a systematic review of clinical studies and examination of underlying antidepressantmechanisms of action.

Lopresti AL, Drummond PD.Hum Psychopharmacol. 2014 Nov;29(6):517-27

Do proton pump inhibitors increase the risk of dementia? Eur Arch Psychiatry Clin Neurosci. 2014. (ahead of print)

14.11.2014

Global prevalence of dementia is increasing. Estimated cost of dementia worldwide in 2010 was US$604 billion. It is thus important to consider all factors (especially those preventable ones) that might be contributing to cause dementia. Proton pump inhibitors (PPIs: Omeprazole and other prazoles) are widely used medications, Many countries record many fold increase in PPI prescription over the last decade. Many  such prescriptions are considered inappropriate.  PPI can cause Vit B12 deficiency and this may contribute to cognitive decline. They can also affect the brain enzymes like b- and c-secretase which can lead to increased Amyloid beta levels.

Britta Haenisch et al looked at the correlation between PPI use and developing dementia in a German elderly population sample over 6 years.Information from 3,327 participants from  German dementia research database were analysed. These were patients 75 or older with no dementia at entry to the study. Potential confounders like  age, sex, education, polypharmacy, and the comorbidities depression, diabetes, ischemic heart disease and stroke, and the Apolipoprotein E4 (ApoE4) allele status were also studied. 3,076 subjects were included in this analysis.  713 patients received a PPI during the study period.

Results

Use of PPIs was associated with a significant increased risk of dementia [hazard ratio (HR) 1.38, 95 % confidence interval (CI) 1.04–1.83; p = 0.02). As expected presence of an ApoE4 allele (2.25), depression (HR 2.28), diabetes, and stroke showed a significant increase in risk of incident dementia.

Limitation: whether PPI was taken regularly is known in follow-up 3 and 4 only. Statistical association is shown- biological  mechanisms to be understood.

Conclusion: This is the first epidemiological investigation showing evidence that PPI use might have an impact on dementia risk. Among primary care patients aged 75 years and older the use of PPIs was associated with a significant increase in the risk of incident dementia.

Summary of the article:

Risk of dementia in elderly patients with the use of proton pump inhibitors.

Haenisch B, von Holt K, Wiese B, Prokein J, Lange C, Ernst A, Brettschneider C, König HH, Werle J, Weyerer S, Luppa M, Riedel-Heller SG, Fuchs A, Pentzek M, Weeg D, Bickel H, Broich K, Jessen F, Maier W, Scherer M. Eur Arch Psychiatry Clin Neurosci. 2014 Oct 24. [Epub)

Would Avatar therapies become main stream soon? School Bulletin.Nov.2014

12.11.2014

VR (Virtual Reality)  is the experience of a sense of presence in an interactive 3D world where virtual world changes according to the participant’s movements and actions. VR elicits psychological and physiological responses remarkably similar to those in the real world. Are we entering an era where VR  based interventions  would form one of the main means of delivering mental health interventions?

Opriş D et al 2012 ( meta analysis ) showed that VR exposure therapy is as effective as conventional therapies for anxiety disorders. VR is now being developed for assessment and intervention in psychosis. Wim Veling et al review this emerging field in this review.

VR experiments/studies  has shown that  paranoid ideas about avatars correlates with levels of anxiety, interpersonal sensitivity, perceptual abnormalities and paranoia in real life.  Individuals provide several types of ‘evidence’ supporting their paranoid beliefs.Patients more often use their own mood/affect and pre-existing beliefs about threat in daily interactions as evidence. It has also been shown that paranoia, social anxiety, and correlates of psychosis like cognitive biases were associated with paranoid thoughts about avatars, with correlation coefficients up to 0.7

It has also been used to study  cognitive functioning in schizophrenia ( e.g. maze task)  and  found that individuals with schizophrenia are less flexible in changing strategies for finding the best bus route, were slower and less successful in a shopping task and had poorer medication management skills in a virtual apartment. They also are less able to read others emotions, and tend to keep less eye contact etc. None of these will surprise clinicians working with such individuals.All these suggest the huge potential VR is offering to assess /study various domains and abilities in controlled  settings which otherwise would have been either impossible or hugely expensive.Only side effect of VR assessments so far noted was cyber sickness ( nausea).

Avatar Treatment examples

Positive symptoms:  Error feedback on reading others emotions in paranoid individuals has lead to decrease in paranoid beliefs. Avatar therapy for auditory hallucinations  where patients create an avatar of the entity they believe is talking to them. Then they have short dialogs with these  avatars. These interventions lead to reduce the impact of hallucinations in their life.

Negative symptoms:  Social skills training using VR helped patients to improve conversational skills and assertiveness and reduce negative symptoms

Cognitive intervention: Virtual shop was used for training schizophrenia patients being a salesperson, aiming at training of executive functions, problem solving, categorization, memory, and attention

VR treatments are conceivable for most dimensions of psychotic disorders. Possibilities of VR are only beginning to be explored. It definitely has great potential for increasing our understanding of psychosis and expanding the therapeutic toolbox.

Summary of the article

Brave new worlds-review and update on virtual reality assessment and treatment in psychosis.

Veling W, Moritz S, van der Gaag M. Schizophr Bull. 2014 Nov;40(6):1194-7

Is suicide a leading cause of death in children? Crisis.2014.

07 11 2014

Suicide is a leading cause of death among children under 15.  There is not much literature specifically focusing on under 15 suicide. Under 15 s differ from older young people in physical, sexual, cognitive and social development. Understanding suicide related factors in this age group is important in planning any intervention.

Rebecca Soole, Kairi Kõlves and  and Diego De Leo from Griffith University, Melbourne looked at psychosocial and psychiatric factors associated with child suicide using Queensland child death register. This is a comprehensive data base for the region.Suicdie occurring between ages 10- 14 were compared with that in 15-17 yrs ( adolescents) and against age matched control groups with external causes of death.

Findings:

Suicide accounted for almost one-third of external causes of death. ( 27% in children, 33% in adolescents). In both groups this was the second leading cause of death after transport related deaths.Boys died by suicide more often ( two-thirds)  in both groups . Indigenous status was more associated with suicide.Children living in remote areas were more likely to die by suicide. ( OR 3.46).

Nearly half children who died by suicide were known to child protection systems. Siblings of  victims were also more likely to be known to child protection systems.

Both children and adolescents used hanging more often, in children this was 91%, adolescents 80%.Mental and behavioural disorders  were detected in half of children. Half of these children had shown previous suicidal behaviour. One-third of children experienced various form of abuse.

Limitations: The data base have information on psychosocial and psychiatric variables only for suicides and not for other external causes. Prevalence of mental disorders can be underreported as the data come from police, coroner and family sources.

Conclusions

Factors related to child suicide are different from adolescents. family and  environment play an important role in child suicide. There were many opportunities for intervention.

Summary of the article:

Factors related to childhood suicides.

Soole R, Kõlves K, De Leo D.Crisis. 2014

Can Zolpidem increase the risk of Parkinson’s disease? J Psy Research.Nov.2014

06.11.2014

Zolpidem is the most widely prescribed ( and most costly)  hypnotic agent worldwide.It  act on the GABA  system. Previous reports suggest that it produce unexpected neuropsychiatric effects in patients with Parkinson’s disease. However, large population based studies were not available to conclude on this observation.Taiwanese researchers  lead by Yu-Wan Yang  did a population-based study using the National Health Insurance Research Database  in Taiwan to investigate the association between zolpidem and PD in patients with sleep disturbance.

Around 100,000 patients treated for sleep disturbance were included in this analysis. Nearly 60,000 received Zolpidem.They were compared against 42,000 who did not receive zolpidem for their sleep disturbance.

Results

At the end of the follow up period (7 years), 522 (1.2%) in the zolpidem group and 287 (0.5%) in the control group developed Parkinson’s disease. Higher use of zolpidem was associated with higher incidence of Parkinson’s disease.

This is the first study to show a dose response relationship between zolpidem and risk of Parkinson’s disease. The large data base and the near complete follow up rate makes the conclusions more reliable.Previous observations of Zolpidem’s benefit in aphasia and its ability to improve brain perfusion etc need further assessment in light of these findings.

Conclusion: Zolpidem can increase the risk of Parkinson’s Disease. Clinicians need to weigh such risks before prescribing this medication.

Summary of the article:

Zolpidem and the risk of Parkinson’s disease: a nationwide population-based study.

Yang YW, Hsieh TF, Yu CH, Huang YS, Lee CC, Tsai TH. J Psychiatr Res. 2014 Nov;58:84-8

Is lower cholesterol linked to suicidal ideas? Acts Neuropsych.Oct 2014

03.11.2014

The relationship between low cholesterol levels and increased risk of suicide was revealed in 1980s. The 1990 metaanalyis ( Muldoon et al) showed that with 10% reduction in cholesterol, there were 28 fewer deaths due to ischaemic heart disease, but 29 more deaths due to suicide, violence and accidents. Low cholesterol has since been shown to predict future suicide during follow ups of individuals with depression. Cholesterol lowering interventions, in later studies , generally show a reduction in mortality from all causes.

A recent study (Baek et al 2014) found that among those with depression, recent suicide attempters had significantly lower triglyceride and higher HDL cholesterol levels. The literature generally supports the idea that lower lipid levels ( cholesterol, TG) are associated with increasing suicidal ideas, acts and suicide.

It is thought that low cholesterol lead to decreased activity of serotonergic system. Another interesting observation is the increase in 24 hydroxyesterol  ( oxidation product of cholesterol) in prefrontal cortex of  suicide victims suggesting higher turn over of cholesterol in brain and this leading to decrease in levels elsewhere raising the possibility that lowering of cholesterol is secondary to suicidal ideas/depressive cognition.

It has to be mentioned that many studies in Asian population did not find support for the association between low cholesterol and suicide.

Ainiyet et al from Poznan University of Medical Sciences ( Poland) studied lipid levels in unipolar and bipolar depression.They interviewed 223 patients to assess suicidal ideas, acts in the 3 months prior to admission. Lipid levels were measured to study the relationship.

Half of the depressed men and 39% of women reported suicidal ideas. Concentrations of total cholesterol, LDL cholesterol, triglycerides and total lipids were significantly lower in depressed patients with suicidal thoughts. Gender and diagnosis ( i.e. whether unipolar or bipolar) did not change this relationship.

Limitations: cross-sectional study.

Conclusion: Low cholesterol is linked to suicidal ideas in unipolar and bipolar depression. This study support the earlier findings.

Summary of the article:

Suicidal behaviour and lipid levels in unipolar and bipolar depression.

Ainiyet B, Rybakowski JK. Acta Neuropsychiatr. 2014 Oct;26(5):315-20.

How do physical exercise induce hippocampal neurogenesis and antidepressant effect? PNAS.2014.oct

28.10.2014

Physical exercise is effective in treating  depression. There is some evidence to suggest that exercise increase certain brain functioning ( hippocampal dependent learning, hippocampal neurogenesis). A hormone secreted by adipocytes- adiponectin- is shown to mimic the metabolic effects of exercise. Both adiponectin and exercise exhibit antidiabetic, antiinflammatory, antiatherogenic and cardio-protective properties.

Adiponectin levels are low in depression. It increase with antidepressant treatments. Do adiponection  mediate the hippocampal neurogenesis due to exercise?

Suk Yu Yau et al report the results of their  animal study to address this interesting and important question in this article.

They compared the effects of exercise using knock out models. ( i.e. one group had their adiponectin gene removed). Exercise was given using running wheels. Behavioural tests include forced swim test and tail suspension test.Immunoassays and Western blot analysis of brain tissue was carried out.

Results

1.Increased adiponection in CNS reduced depression like behaviours.

2. Adiponectin deficiency diminished the beneficial effects of exercise on depression like behaviours.

3. Adiponectin knock out diminished running induced hippocampal neurogenesis.

4. Adiponection stimulated hippocampal cell proliferation is mediated by adiponectin receptor 1

Limitations

Knock down receptors model has limitations.

Conclusion: 

Exercise increase Adiponectin and this possibly  mediate the antidepressant effect via increasing neurogenesis. Adiponectin is a downstream mediator of the peroxisome proliferation-activated receptor-γ (PPARγ).  PPARy agonists as well as other agents  that can increase adinoceptin   could be useful antidepressants.

Summary of the article:

Physical exercise-induced hippocampal neurogenesis and antidepressant effects are mediated by the adipocyte hormoneadiponectin.

Yau SY, Li A, Hoo RL, Ching YP, Christie BR, Lee TM, Xu A, So KF. Proc Natl Acad Sci U S A. 2014 Oct 20.