Posts Tagged Depression
[Abstract + References] Antidepressant effect of vagal nerve stimulation in epilepsy patients: a systematic review
Vagal nerve stimulation (VNS) is an effective palliative therapy in drug-resistant epileptic patients and is also approved as a therapy for treatment-resistant depression. Depression is a frequent comorbidity in epilepsy and it affects the quality of life of patients more than the seizure frequency itself. The aim of this systematic review is to analyze the available literature about the VNS effect on depressive symptoms in epileptic patients.
Material and methods
A comprehensive search of PubMed, Medline, Scopus, and Google Scholar was performed, and results were included up to January 2020. All studies concerning depressive symptom assessment in epileptic patients treated with VNS were included.
Nine studies were included because they fulfilled inclusion criteria. Six out of nine papers reported a positive effect of VNS on depressive symptoms. Eight out of nine studies did not find any correlation between seizure reduction and depressive symptom amelioration, as induced by VNS. Clinical scales for depression, drug regimens, and age of patients were broadly different among the examined studies.
Reviewed studies strongly suggest that VNS ameliorates depressive symptoms in drug-resistant epileptic patients and that the VNS effect on depression is uncorrelated to seizure response. However, more rigorous studies addressing this issue are encouraged.
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Epinephrine and norepinephrine belong to a group of compounds called catecholamines, and they act as both neurotransmitters and hormones. While these compounds have similar chemical structures, they produce different effects on the body.
Epinephrine is also known as adrenaline, while some people refer to norepinephrine as noradrenaline. Both of these substances play a role in the regulation of the sympathetic nervous system, which is the part of the autonomic nervous system that is responsible for the body’s “fight or flight” response.
In this article, we discuss the similarities and differences between epinephrine and norepinephrine, along with their functions. We also cover their medical uses and the health effects of having too much or too little of either compound in the body.
Epinephrine and norepinephrine are both hormones and neurotransmitters.
Hormones are chemical messengers that travel through the bloodstream. The endocrine glands and reproductive organs make and secrete a wide range of hormones to regulate the body’s organs, tissues, and cells.
Neurotransmitters are also a type of chemical messenger, but they only occur in nerve cells and travel across synapses, which are junctions where two nerve fibers meet. Nerves cells produce neurotransmitters in response to electrical impulses.
The adrenal medulla, the inner portion of the adrenal gland, regulates and secretes both epinephrine and norepinephrine in response to stress and other imbalances in the body, such as low blood pressure.
Epinephrine activates both alpha- and beta-adrenoreceptors in cells, whereas norepinephrine mainly stimulates alpha-adrenoreceptors.
We discuss the main functions of epinephrine and norepinephrine below:
When the brain perceives danger, the amygdala triggers the hypothalamus to activate the autonomic nervous system.
Signals from the autonomic nervous system stimulate the adrenal gland to start pumping epinephrine into the bloodstream. People often refer to this surge of epinephrine as an adrenaline rush or the fight or flight response.
Epinephrine affects the heart, lungs, muscles, and blood vessels. Its release into the bloodstream brings about several physiological changes, such as:
- increased heart rate and blood flow
- faster breathing
- raised blood sugar levels
- increased strength and physical performance
The adrenal medulla produces norepinephrine in response to low blood pressure and stress. Norepinephrine promotes vasoconstriction, which is a narrowing of the blood vessels, and this increases blood pressure.
Like epinephrine, norepinephrine also increases the heart rate and blood sugar levels.
Chronic stress, poor nutrition, some medications, and certain health conditions can affect the body’s ability to produce or respond to epinephrine and norepinephrine.
A rare condition called genetic dopamine beta-hydroxylase deficiency prevents the body from converting dopamine into norepinephrine.
According to a 2018 article, genetic dopamine beta-hydroxylase deficiency results from a mutation in the norepinephrine transporter gene g237c. The authors concluded that this condition might decrease sympathetic nerve activity and increase the risk of damage to the heart and blood vessels.
Low levels of epinephrine and norepinephrine can result in physical and mental symptoms, such as:
- changes in blood pressure
- changes in heart rate
- low blood sugar, or hypoglycemia
- migraine headaches
- problems sleeping
In addition, norepinephrine plays a role in focus and promotes periods of sustained attention. Low levels of norepinephrine may contribute to the development of attention deficit hyperactivity disorder (ADHD).
The following medications can increase levels of norepinephrine:
- amphetamines, such as methylphenidate (Ritalin) and dextroamphetamine (Adderall)
- serotonin-norepinephrine reuptake inhibitors (SNRIs), such as venlafaxine (Effexor) and duloxetine (Cymbalta)
Certain medical conditions, such as tumors, chronic stress, and obesity, can affect the adrenal glands and cause excess production of epinephrine and norepinephrine.
Symptoms of high levels of epinephrine or norepinephrine can include:
- excessive sweating
- rapid or irregular heartbeat
- high blood pressure
- jitteriness or shakiness
- intense headaches
- pale or cold skin
A 2018 research paper states that having high levels of norepinephrine can increase a person’s risk of cardiovascular and kidney damage.
An epinephrine overdose can occur in people who use epinephrine injections to treat certain medical conditions. An overdose of injected epinephrine can lead to dangerously high blood pressure, stroke, or even death.
Synthetic forms of epinephrine and norepinephrine have several medical uses, which we discuss below:
Doctors prescribe epinephrine to treat severe medical conditions that affect the heart and airways, such as anaphylaxis.
Anaphylaxis is a severe allergic reaction that can interfere with a person’s ability to breathe, and it requires emergency medical treatment. Epinephrine counters anaphylactic shock by narrowing the blood vessels, relaxing the muscles, and opening up the airways.
It is common for people at risk of anaphylaxis to carry an epinephrine autoinjector with them at all times.
Doctors also use epinephrine to treat severe asthma attacks, cardiac arrest, and serious infections.
Norepinephrine can help raise systolic blood pressure in people who have had a heart attack.
Doctors also use norepinephrine to treat:
- septic shock
- neurogenic shock
- pericardial tamponade
- critical hypotension
Epinephrine and norepinephrine are similar chemicals that act as both neurotransmitters and hormones in the body. Both substances play an important role in the body’s fight or flight response, and their release into the bloodstream causes increased blood pressure, heart rate, and blood sugar levels.
Epinephrine acts on the alpha- and beta-adrenoreceptors in the muscles, lungs, heart, and blood vessels. Norepinephrine is a metabolite of dopamine that primarily acts on the alpha-adrenoreceptors in the blood vessels.
Reviewed by Emily Henderson, B.Sc.May 15 2020
Epilepsy is a central nervous system disorder characterized by recurrent seizures resulting from excessive excitation or inadequate inhibition of neurons.
Ultrasound stimulation has recently emerged as a noninvasive method for modulating brain activity; however, its range and effectiveness for different neurological disorders, such as Parkinson’s Disease, Epilepsy and Depression, have not been fully elucidated.
Researchers from the Shenzhen Institutes of Advanced Technology (SIAT) of the Chinese Academy of Sciences developed a noninvasive ultrasound neuromodulation technique, which could potentially modulate neuronal excitability without any harm in the brain.
Low-intensity pulsed ultrasound and ultrasound neuromodulation system were prepared for non-human primate model of epilepsy and human epileptic tissues experiments, respectively.
The results showed that ultrasound stimulation could exert an inhibitory influence on epileptiform discharges and improve behavioral seizures in a non-human primate epileptic model.
Ultrasound stimulation inhibited epileptiform activities with an efficiency exceeding 65% in biopsy specimens from epileptic patients in vitro.
The mechanism underlying the inhibition of neuronal excitability could be due to adjusting the balance of excitatory-inhibitory (E/I) synaptic inputs by the increased activity of local inhibitory neurons. In addition, the variation of temperature among these brain slices was less than 0.64°C during the experimental procedure.
The study demonstrated for the first time that low-intensity pulsed ultrasound improved electrophysiological activities and behavioral outcomes in a non-human primate model of epilepsy and suppressed epileptiform activities of neurons from human epileptic slices.
It provided evidence for the potential clinical use of non-invasive low-intensity pulsed ultrasound stimulation for epilepsy treatment.
Journal reference: Lin, Z., et al. (2020) Non-invasive ultrasonic neuromodulation of neuronal excitability for treatment of epilepsy. Theranostics. doi.org/10.7150/thno.40520.
[ARTICLE] Adaptive conjunctive cognitive training (ACCT) in virtual reality for chronic stroke patients: a randomized controlled pilot trial – Full Text
Current evidence for the effectiveness of post-stroke cognitive rehabilitation is weak, possibly due to two reasons. First, patients typically express cognitive deficits in several domains. Therapies focusing on specific cognitive deficits might not address their interrelated neurological nature. Second, co-occurring psychological problems are often neglected or not diagnosed, although post-stroke depression is common and related to cognitive deficits. This pilot trial aims to test a rehabilitation program in virtual reality that trains various cognitive domains in conjunction, by adapting to the patient’s disability and while investigating the influence of comorbidities.
Thirty community-dwelling stroke patients at the chronic stage and suffering from cognitive impairment performed 30 min of daily training for 6 weeks. The experimental group followed, so called, adaptive conjunctive cognitive training (ACCT) using RGS, whereas the control group solved standard cognitive tasks at home for an equivalent amount of time. A comprehensive test battery covering executive function, spatial awareness, attention, and memory as well as independence, depression, and motor impairment was applied at baseline, at 6 weeks and 18-weeks follow-up.
At baseline, 75% of our sample had an impairment in more than one cognitive domain. The experimental group showed improvements in attention ( (2) = 9.57, p < .01), spatial awareness ( (2) = 11.23, p < .01) and generalized cognitive functioning ( (2) = 15.5, p < .001). No significant change was seen in the executive function and memory domain. For the control group, no significant change over time was found. Further, they worsened in their depression level after treatment (T = 45, r = .72, p < .01) but returned to baseline at follow-up. The experimental group displayed a lower level of depression than the control group after treatment (Ws = 81.5, z = − 2.76, r = − .60, p < .01) and (Ws = 92, z = − 2.03, r = − .44, p < .05).
ACCT positively influences attention and spatial awareness, as well as depressive mood in chronic stroke patients.
The trial was registered prospectively at ClinicalTrials.gov (NCT02816008) on June 21, 2016.
Cognitive impairments are common after stroke, with incident rates up to 78% . Patients with mild cognitive impairment are at risk for developing dementia . Cognitive deficits correlate with poor functional outcomes and increased risk of dependence , have negative effects on the patient’s quality of life , and alter the patient’s ability to socialize . However, the current clinical practice seems to lack methods that specifically address cognitive sequelae. According to a meta-analysis that aimed at proposing recommendations for new clinical standards, currently available treatments that are used as control conditions are conventional therapies like physical therapy or occupational therapy, pseudo treatments like mental or social stimulation without therapeutic intent, as well as psychosocial interventions like psychotherapy or emotional support for individuals or groups . Besides, it has been shown that cognitively impaired patients participate less in rehabilitation activities, which potentially contributes to the poorer functional outcome they display . Finding effective cognitive rehabilitation methods that can be incorporated in clinical practice is therefore crucial. Numerous methods to improve cognitive deficits, for instance, specifically attention , memory , executive function , or spatial abilities , have been proposed. However, the results show mixed efficacies. A meta-analysis on the impact of attentional treatments showed an effect on divided attention in the short-term, but found no evidence for persisting effects on other attentional domains, global attention, or functional outcomes . Similarly, a meta-review that investigated the effect of memory rehabilitation found that training might benefit subjective reports of memory in the short term, but shows no effect in the long term, on objective memory measures, mood, functional abilities or quality of life . Ultimately, a meta-analysis over 6 Cochrane reviews shows insufficient research evidence or evidence of insufficient quality to support any recommendation for cognitive stroke rehabilitation . Besides methodological issues, one limitation of existing methods could be that they focus on one deficit only, ignoring that patients typically express deficits in multiple cognitive domains [1, 2]. A study on a large sample of heterogeneous stroke patients which aimed at linking lesions to cognitive deficits found that a given lesion location leads to cognitive impairments in several domains . This emphasizes that cognitive functions rely on a network of brain regions. A lesion in one of those regions might cause a disturbance to the network, which leads to a multitude of symptoms. This is further supported by studies that revealed that pathological changes in brain structures are related to the occurrence of various cognitive deficits and symptoms for instance, in Alzheimer’s disease  or spatial neglect . Moreover, the presence of multiple cognitive deficits seems to be a marker in patients that are at risk of developing Alzheimer’s disease later in life . To what extent rehabilitation could potentially drive structural or functional changes to alleviate the symptoms of stroke is still under debate [19, 20]. Nevertheless, rehabilitation methods have to aid the patient in obtaining enough functionality to independently perform instrumental activities of daily living, be it through restoration of function or compensation. With this in mind, focusing on training a single cognitive skill might not be efficient because many daily tasks or jobs require several cognitive abilities for their execution . For instance, most patients would like to be mobile and drive a car again after their stroke. Driving requires the individual to use selective attention to deal with the traffic, traffic signs and distractions, to be cognitively flexible to react to changing situations on the road, to visually scan the mirrors at the front, at the side, and in the back, to have a visual field that includes the sidewalks and to perform all of this while steering the car effectively in real-time . Consequently, rehabilitation methods that address one specific cognitive ability only do not address the requirements of performing the activities of daily living and might not stimulate and train the underlying brain processes adequately. If a stroke leads to impairments in various cognitive domains, then these domains should be treated together to benefit a patient’s performance in everyday life.[…]
The UT Southwestern researchers hope that this tool could eventually play a critical role in deciding which course of treatment would be best for patients with depression, as well as being part of a new generation of “biology-based, objective strategies” which make use of technologies such as AI to treat psychiatric disorders.
The US-wide trial was initiated in 2011 with the intention of better understanding mood disorders such as major depression and seasonal affective disorder (Sad). The trial has reaped many studies, the latest of which demonstrates that doctors could use computational tools to guide treatment choices for depression. The study was published in Nature Biotechnology.
“These studies have been a bigger success than anyone on our team could have imagined,” said Dr. Madhukar Trivedi, the UT Southwestern psychiatrist who oversaw the trial. “We provided abundant data to show we can move past the guessing game of choosing depression treatments and alter the mindset of how the disease should be diagnosed and treated.”
This 16-week trial involved more than 300 participants with depression, who either received a placebo or SSRI (selective serotonin reuptake inhibitor), the most common type of antidepressant. Despite the widespread prescription of SSRIs, they have been criticised for their side effects and for inefficacy in many patients.
Trivedi had previously established in another study that up to two-thirds of patients do not adequately respond to their first antidepressant, motivating him to find a way of identifying much earlier which treatment path is most likely to help the patient before they begin and potentially suffer further through ineffectual treatment.
Trivedi and his collaborators used an electroencephalogram (EEG) to measure electrical activity in the participants’ cortex before they began the treatment. This data was used to develop a machine learning algorithm to predict which patients would benefit from the medication within two months.
The researchers found that the AI accurately predicted outcomes, with patients less certain to respond to an antidepressant more likely to improve with other interventions, such as brain stimulation or therapeutic approaches. Their findings were replicated across three additional patient groups.
“It can be devastating for a patient when an antidepressant doesn’t work,” Trivedi said. “Our research is showing that they no longer have to endure the painful process of trial and error.”
Dr Amit Etkin, a Stanford University professor of psychiatry who also worked on the algorithm, added: “This study takes previous research, showing that we can predict who benefits from an antidepressant, and actually brings it to the point of practical utility.”
Next, they hope to develop an interface for the algorithm to be used alongside EEGs – and perhaps also with other means of measuring brain activity like functional magnetic resonance imaging (functional MRI, aka fMRI) or MEG – and have the system approved by the US Food and Drug Administration.