Rethinking psychopharmacotherapy: The role of treatment context and brain plasticity in antidepressant and antipsychotic interventions (2015)

While I’m struggling a bit at the moment, I really want to avoid getting back on clozapine for many reasons. I’m optimistic that “helpful social and physical environmental stimulation” will augment my current regime nicely!

The following goes into “the basics” in good detail.

Rethinking psychopharmacotherapy: The role of treatment context and brain plasticity in antidepressant and antipsychotic interventions.

Emerging evidence indicates that treatment context profoundly affects psychopharmacological interventions. We review the evidence for the interaction between drug application and the context in which the drug is given both in human and animal research. We found evidence for this interaction in the placebo response in clinical trials, in our evolving knowledge of pharmacological and environmental effects on neural plasticity, and in animal studies analyzing environmental influences on psychotropic drug effects. Experimental placebo research has revealed neurobiological trajectories of mechanisms such as patients’ treatment expectations and prior treatment experiences. Animal research confirmed that “enriched environments” support positive drug effects, while unfavorable environments (low sensory stimulation, low rates of social contacts) can even reverse the intended treatment outcome. Finally we provide recommendations for context conditions under which psychotropic drugs should be applied. Drug action should be steered by positive expectations, physical activity, and helpful social and physical environmental stimulation. Future drug trials should focus on fully controlling and optimizing such drug x environment interactions to improve trial sensitivity and treatment outcome


Exercise Improves Clinical Symptoms, Quality of Life, Global Functioning, and Depression in Schizophrenia: A Systematic Review and Meta-analysis (2015)

Trying to find that “pure happiness, elation, a feeling of unity with one’s self and/or nature, endless peacefulness,” and “inner harmony.” that comes with a ‘runner’s high‘ [1] these days…

Exercise Improves Clinical Symptoms, Quality of Life, Global Functioning, and Depression in Schizophrenia: A Systematic Review and Meta-analysis

Background: Physical exercise may be valuable for patients with schizophrenia spectrum disorders as it may have beneficial effect on clinical symptoms, quality of life and cognition. Methods: A systematic search was performed using PubMed (Medline), Embase, PsychInfo, and Cochrane Database of Systematic Reviews. Controlled and uncontrolled studies investigating the effect of any type of physical exercise interventions in schizophrenia spectrum disorders were included. Outcome measures were clinical symptoms, quality of life, global functioning, depression or cognition. Meta-analyses were performed using Comprehensive Meta-Analysis software. A random effects model was used to compute overall weighted effect sizes in Hedges’ g. Results: Twenty-nine studies were included, examining 1109 patients. Exercise was superior to control conditions in improving total symptom severity (k = 14, n = 719: Hedges’ g = .39, P < .001), positive (k = 15, n = 715: Hedges’ g = .32, P < .01), negative (k = 18, n = 854: Hedges’ g = .49, P < .001), and general (k = 10, n = 475: Hedges’ g = .27, P < .05) symptoms, quality of life (k = 11, n = 770: Hedges’ g = .55, P < .001), global functioning (k = 5, n = 342: Hedges’ g = .32, P < .01), and depressive symptoms (k = 7, n = 337: Hedges’ g = .71, P < .001). Yoga, specifically, improved the cognitive subdomain long-term memory (k = 2, n = 184: Hedges’ g = .32, P < .05), while exercise in general or in any other form had no effect on cognition. Conclusion: Physical exercise is a robust add-on treatment for improving clinical symptoms, quality of life, global functioning, and depressive symptoms in patients with schizophrenia. The effect on cognition is not demonstrated, but may be present for yoga.

See also:

Physical Exercise Alleviates Health Defects, Symptoms, and Biomarkers in Schizophrenia Spectrum Disorder.

Voluntary wheel running ameliorates symptoms of MK-801-induced schizophrenia in mice.

Neuroprotective effects of physical activity on the brain: a closer look at trophic factor signaling.

A Neurophysiological and Neuropsychological Consideration of Mindful Movement: Clinical and Research Implications. (2015)

A Neurophysiological and Neuropsychological Consideration of Mindful Movement: Clinical and Research Implications.
In this article, we present ideas related to three key aspects of mindfulness training: the regulation of attention via noradrenaline, the importance of working memory and its various components (particularly the central executive and episodic buffer), and the relationship of both of these to mind-wandering. These same aspects of mindfulness training are also involved in the preparation and execution of movement and implicated in the pathophysiology of psychosis. We argue that by moving in a mindful way, there may be an additive effect of training as the two elements of the practice (mindfulness and movement) independently, and perhaps synergistically, engage common underlying systems (the default mode network). We discuss how working with mindful movement may be one route to mindfulness training for individuals who would struggle to sit still to complete the more commonly taught mindfulness practices. Drawing on our clinical experience working with individuals with severe and enduring mental health conditions, we show the real world application of these ideas and how they can be used to help those who are suffering and for whom current treatments are still far from adequate.

Main mindfulness instructions:

  • Awareness of sensations
  • Awareness of the present moment (PM)
  • Awareness of attention
  • Awareness of mind-wandering
  • Awareness of intention (on purpose)
  • Awareness of non-judgment

See the “Guidance for delivery of mindful movement for psychotic patients.

The Magic of Movement; the Potential of Exercise to Improve Cognition (2015)

The Magic of Movement; the Potential of Exercise to Improve Cognition

Effective treatment for cognitive dysfunction is the Holy Grail in research for most brain diseases. With the exception of stimulants for attention deficit hyperactivity disorder (ADHD), there is little evidence for any pharmacological intervention to restore cognitive dysfunction once a brain disease is diagnosed. Although future success of new drugs should not be ruled out yet, the many negative results so far suggest that drug interventions may be better to prevent cognitive dysfunction in brain diseases than to treat them once present.

In sharp contrast to the disappointing findings of pharmacological interventions, are the promising results of studies assessing the potential of physical exercise to improve cognition.

  • Malchow et al included 3 groups: patients with schizophrenia who were offered endurance training for 3 months, augmented in the last 6 weeks with cognitive remediation, a similar group of patients who were provided table soccer for 3 months, again augmented with cognitive remediation in the last 6 weeks and a healthy control group, given the same interventions as the first patient group. They showed superior effects of endurance training over table soccer on symptom severity, depression, and some (but not all) cognitive tasks.
  • Svatkova et al assessed the effect of biking for 6 months on the integrity of white matter connections in patients and controls, as compared with life as usual. In both groups, exercise improved fiber integrity, especially in the motor circuit, while the patients in the control group showed deterioration of fiber integrity over the 6 months of the study.
  • Kimhy et al demonstrated a 15% improvement in cognition as assessed with the Matrix Consensus Cognitive Battery in the exercise group as compared with 2% decline in the control group. They further showed that increases in the serum levels of BDNF could explain only a small percentage of the improvement in cognition.

“Since the beneficial effects of exercise are observed in many different brain disorders, the neurobiological mechanisms underlying these effects are expected to involve general aspects of brain function that are affected in all diseases. This indeed seems to be the case. Firstly, increased cardiac output improves cerebral circulation and optimizes oxygen extraction and glucose uptake of neurons and glia cells. Secondly, neurogenesis is improved, most pronounced in the hippocampal dentate gyrus, which may be secondary to increased neurotrophic factors such as brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor. Further, moderate exercise reduces the inflammatory status of the brain, by increasing levels of the anti-inflammatory cytokine interleukin-10, among others, although stringent exercise can have a negative impact on the immune system. Recently, the route to explain the association between cognition and exercise was further elucidated. Expression of peroxisome proliferator-activated receptor-gamma coactivator-1α1 is increased when skeletal muscles become active. This substance enhances the conversion of the tryptophan metabolite kynurenine to kynurenic acid, thereby lowering kynurenine levels in the blood. Through this mechanism, muscle activity restores the immune balance in the brain.”