Thus, acupuncture treatment may have positive effects on the symptoms of anxiety. Acupuncture may also be of benefit in anxiety-related insomnia. A Canadian study reported that acupuncture significantly improved sleep quality in patients with anxiety and insomnia At the end of acupuncture treatment, urine 6-sulfatoxymelatonin a metabolite of melatonin levels were normalized and several polysomnographic measures, as well as self-reported fatigue, sleepiness, anxiety, and level of depression, were significantly improved. Combined with the evidence of treatment efficacy in depression-related insomnia, acupuncture may have broader utility in neuropsychiatric disorders with impaired quality of sleep.
Interestingly, acupuncture treatment may also reduce anxiety levels in medical conditions other than neuropsychiatry. An early study reported that auricular acupuncture reduced state anxiety in patients waiting for surgery by a significantly greater extent than either body or sham acupuncture Another study has reported that both body and auricular acupuncture effectively reduce preoperative anxiety; self-rated anxiety scores were significantly reduced from baseline in both groups Possible underlying mechanisms remain unclear.
One plausible explanation is that acupuncture regulates the autonomic nervous system. For instance, acupuncture appears to modulate heart rate variability, a non-invasive indicator of changes in autonomic state. In patients with mild depression or anxiety, verum acupuncture but not sham acupuncture was associated with significant reductions from baseline in mean resting heart rate at 5 and 15 min after needle application, with a trend toward an increase in high frequency HF; 0. These results suggest that verum acupuncture modulates autonomic activity in response to alterations of internal and external environments, and thus reduces overall anxiety in patients with depression or anxiety.
However, it should be recognized that the interpretation of results from clinical trials investigating acupuncture interventions in depression and anxiety disorders is complicated by different interventions, different comparators used against acupuncture interventions, and the small sample sizes in many trials These shortcomings prevent any accurate assessment of acupuncture for these conditions or a true comparison of the relative effectiveness of different treatment regimens.
Moreover, the data are difficult to interpret from those studies where needling at specific and non-specific points have yielded similar outcomes The evidence consulted for depression and anxiety is summarized in Table 1. Table 1. Overview of characteristics of included studies evaluating acupuncture for depression and anxiety. Compared with depression and anxiety, relatively few studies have addressed the efficacy of acupuncture in schizophrenia.
A meta-analysis of 13 RCTs including patients, all from China, provides positive evidence for the effectiveness of acupuncture with or without EA or moxibustion in treating the symptoms of schizophrenia Some of the RCTs reported that acupuncture plus drug therapy significantly improved auditory hallucinations, positive symptoms and response rates compared with antipsychotics alone or in combination with sham EA.
In a recent systematic review of data from 26 studies 1, participants reporting limited evidence for the use of adjunctive acupuncture therapy in the treatment of positive, negative and cognitive symptoms, the authors point out the importance of differences between quantitative and qualitative changes The limited evidence for treatment efficacy may be partly due to the fact that positive symptoms still exist, but patients are suffering less. Other evidence suggests that individualized acupuncture is beneficial for patients with schizophrenia as an adjunctive treatment with routine care After completing individualized acupuncture sessions, patients reported improvements in symptoms of schizophrenia, side effects of medication, energy, motivation, sleep, addictions and other associated physical problems.
A case study has reported that positive and negative symptoms can be improved for up to 3 months after add-on acupuncture treatment A more recent case study describes how add-on acupuncture treatment improved general psychopathology and negative symptoms but not positive symptoms Thus, individualized add-on acupuncture treatment may help to alleviate symptoms of schizophrenia. Interestingly, the review by van den Noort et al.
Several of the studies in that review reported improvements in subjective and objective sleep measurements. Acupuncture treatment appears to have similar effects to but is safer than zopiclone, a prescription medication for sleep disorder. Thus, acupuncture treatment may improve sleep dysregulation in schizophrenia.
As with the clinical evidence for acupuncture in depression and anxiety disorders, the clinical evidence is limited for the effectiveness of acupuncture as a treatment for schizophrenia. The meta-analysis performed by Lee and colleagues found that all of the included studies were limited by low methodological quality, the low overall number, and the small sample sizes Moreover, as all of the studies were conducted in China, international trials are needed to investigate whether the effects can be replicated in other ethnicities.
Table 2. Overview of characteristics of included studies evaluating acupuncture for schizophrenia.
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Another disorder that commonly exhibits neuropsychiatric symptoms is dementia. Neuropsychiatric symptoms are amongst the earliest signs and symptoms of neurocognitive disorders and incipient cognitive decline, and can be challenging to treat Evidence shows that acupuncture can increase a patient's verbal and motor skills and improve mood and cognitive function.
In an early Chinese trial, 38 patients with senile dementia were treated with acupuncture and acupoint-injection with aceglutamide After treatment, symptoms had improved in 16 patients. In a small pilot study, 1 month of acupuncture treatment improved cognitive function in 8 patients with mild-to-moderate AD Mini-Mental State Examination subscores assessing verbal orientation and motor coordination, as well as overall scores, were significantly improved from baseline.
In a US study that included 11 patients with dementia 10 with AD and 1 with vascular dementia , depression and anxiety scores improved significantly after acupuncture treatment These early pilot studies indicated that acupuncture treatment may be of benefit for neuropsychiatric symptoms in dementia, especially in AD. More recently, a larger clinical trial involving 87 patients with mild-to-moderate AD reported that acupuncture may significantly improve cognitive function When used as monotherapy, acupuncture treatment was associated with significantly greater decreases from baseline in Alzheimer's disease Assessment Scale-Cognitive ADAS-cog scores compared with donepezil.
The improvement in cognitive function was observed for up to 12 weeks after the end of acupuncture treatment. Moreover, no patients discontinued treatment because of adverse events in the acupuncture group, but four patients did so in the donepezil group.
In addition, a small-scale functional magnetic resonance imaging study explored the relationships between de qi sensations a special needling sensation evoked by acupuncture induced by different needling depths of acupuncture and their differential effects on the reorganizations of whole-brain networks in 12 patients with mild cognitive impairment The results show that as compared with superficial needling, acupuncture with deep needling induces stronger, wider-ranging de qi sensations and enhances nodal centrality, primarily in the abnormal regions of the brain implicated in mild cognitive impairment.
Hence, acupuncture treatment in mild-to-moderate AD appears to be not only beneficial but also safe, with the capacity to improve dysfunctional neural mechanisms involved in mild cognitive impairment. Table 3. Overview of characteristics of included studies evaluating acupuncture for Alzheimer's disease. In the past decade, increasing evidence implicates the important role of glutamate in the pathophysiology of many CNS disorders 42 , L-Glutamate, the most common excitatory neurotransmitter in the CNS, is involved in synaptic plasticity and cognition 42 , 44 , Glutamate receptors, synaptic receptors located primarily on the membranes of neuronal cells, are responsible for the glutamate-mediated postsynaptic excitation of neural cells and are important for neural communication, memory formation, learning, and regulation.
Neural glutamate signaling is accommodated by two receptor families: ionotropic glutamate receptors iGluRs; e. The iGluRs produce excitatory glutamate-evoked currents, whereas the mGluRs are G protein-coupled receptors that control cellular processes through the G protein signaling cascades. Its activation allows cations to flow through the cell membrane. The NMDA receptor is very important for controlling synaptic plasticity and memory function Recent studies indicate that the dysregulation of the NMDA receptor may play an important role in schizophrenia 49 , 50 and depression Modulation of AMPA receptor numbers explains much of the plasticity of excitatory transmission in the brain, whereby increasing or decreasing AMPA receptors alters synaptic strength, which may be linked to neuropsychiatric disorders such as schizophrenia and depression 52 , The release of glutamate in the synaptic cleft at a particular concentration is maintained by either glutamine synthetase or excitatory amino acid proteins, i.
A high density of EAATs near the synapse ensures quick removal or transportation of any unbound glutamate. When this process is impaired, it can allow large amounts of glutamate to spill out from the synapse, which may be a pathophysiological mechanism in CNS disorders 54 including schizophrenia, cognitive deficits, dementia and AD, and other disorders.
Evidence suggests that EAAT2 activation is a promising therapeutic approach in many neuropsychiatric disease models Glycine fluxes are regulated by two specific glycine transporters: GlyT1 and GlyT2. Whereas, GlyT2 is expressed in the spinal cord, brainstem and cerebellum, GlyT1 is expressed in these regions as well as in the forebrain areas such as the cortex, hippocampus, septum, and thalamus GlyT2 is expressed by glycinergic nerve endings in rat spinal cord, while GlyT1 appears to be preferentially expressed by glial cells.
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Preclinical investigations suggest that GlyT2 is predominantly responsible for glycine uptake at glycinergic synapses, and that GlyT1 is involved in monitoring glycine concentration surrounding NMDA receptor-expressing synapses. It is possible to modulate the function of the NMDA receptor by varying the availability of the glycine co-agonist.
This has potential in the treatment of schizophrenia: the NMDA hypofunction hypothesis of schizophrenia postulates that increasing glutamatergic transmission via the NMDA receptors and inhibiting GlyT1 on glial cells enhances NMDA receptor neurotransmission by slowing the process of removal of glycine from the synapse and thus elevates synaptic glycine levels 55 , However, no direct evidence supports a primary dysfunction of a specific monoamine system in patients with MDDs.
Moreover, not only do many patients fail to respond to monoamine antidepressants, but residual symptoms, relapses and recurrences are common even with adequate dosing of these medications 58 and it can take up to several days or weeks for core depressive symptoms to begin to lift after monoamine antidepressants have elevated synaptic monoamine levels 57 — MDD pathogenesis appears to involve something else beyond the monoamine system.
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Glutamatergic modulation shows potential in antidepressant treatment. A single subanesthetic intravenous dose of the NMDA receptor antagonist ketamine acts rapidly in treatment-resistant depression within hours of administration, with effects that are typically sustained for 7—14 days Moreover, the ketamine metabolite 2R,6R -hydroxynorketamine [ 2R,6R -HNK] appears to have the antidepressant effects of ketamine and lacks the psychiatric, psychotomimetic, cardiovascular, neurological, and other side effects associated with acute dosing of ketamine in patients with depression Thus, both NMDA and AMPA receptors may be involved in the pathophysiological changes of depression and potentially represent new targets for the development of rapid-acting antidepressants.
The glutamatergic system also plays a major role in the pathogenesis of anxiety 61 — Long-term administration of various antidepressant agents including selective serotonin reuptake inhibitors SSRIs , serotonin and norepinephrine reuptake inhibitors SNRIs , tricyclic antidepressants TCAs , and monoamine oxidase inhibitors MAOIs lowers glutamatergic activity in some regions, such as the hippocampus 61 , 64 , while the acute administration of NMDA receptor antagonists produces anti-anxiety and antidepressant effects in preclinical and clinical models 43 , Animal models of schizophrenia have implicated glutamate receptor dysregulation and other proteins relating to glutamate transmission, including EAAT2 The glutamate hypothesis of schizophrenia is supported by the finding that the NMDA receptor antagonist phencyclidine blocks glutamate-activated postsynaptic currents and induces schizophrenia-like symptoms, including psychosis and cognitive impairment Moreover, phencyclidine impairs prepulse inhibition PPI of the startle reflex, a simple form of information processing that is consistently reduced in schizophrenia.
In rats treated with ceftriaxone and acute phencyclidine, PPI was more impaired compared with rats given either treatment alone A broad-spectrum cephalosporin antibiotic, ceftriaxone stimulates EAAT2 expression and lessens neurotoxicity by inhibiting neuronal cell death associated with glutamate excitotoxicity Interestingly, expression of the presynaptic protein synaptophysin, which is involved in neurotransmitter release, is significantly increased in the same anatomical areas where EAAT2 levels are downregulated by clozapine This suggests that glutamate release may assist clozapine in potentiation of the excitatory synapse.
More support for glutamate receptor dysregulation in schizophrenia is seen with the selective GlyT1 inhibitor sarcosine N-methylglycine , which has shown promise in the treatment of cognitive impairment in patients with chronic schizophrenia 56 , It is well-known that AD is associated with reductions in glutamate transporter capacity and protein expression, as well as a selective loss of the vesicular glutamate transporter 73 — Although EAAT2b expression did not vary significantly according to disease severity, significantly upregulated levels of exon-skipping variant mRNA expression have been found, which reduces wild-type EAAT2 protein expression in primary astrocytes and inhibits glutamate transport The correlation of EAAT2 expression with increasing neurodegeneration, in combination with the ability of exon-skipping variants to reduce glutamate reuptake, suggests that increased glutamate levels may propagate excitotoxic processes implicated in AD pathogenesis.
Moreover, iGluRs may also contribute to the excitotoxic processes implicated in AD pathogenesis. It is well-established that the NMDA receptor plays an important role in excitotoxicity Hyperactivity of the NMDA receptor may result in a flooding of cations e. Notably, in preclinical models of AD, AMPA-mediated transmission, and altered synapse morphology correlated with cognitive decline An initial loss of dendritic spines and synapses is accompanied by a concomitant increase in presynaptic release probability, as the neuronal circuit attempts to compensate for synaptic dysfunction and loss This evidence suggests that increased synaptic glutamate levels induced by a reduction in reuptake may trigger iGluR hyperactivity and lead to the excitotoxic processes relating to the cognitive symptoms of AD.
To date, very little neuroscience research has explored the effects of acupuncture on the role of glutamate in neuropsychiatric disorders. While studies of acupuncture analgesia indicate that acupuncture stimulation may modulate levels of expression of glutamate expression and its receptor, as well as EAAT expression 79 , 80 , no existing studies have reported on acupuncture-induced modulation of the glycine transporter or other upstream regulatory mechanisms e.
Research has reported that both high- and low-frequency EA significantly decreases upregulated levels of NMDA receptor 1 and 2A and AMPA receptor 1 expression in the spinal cord in an inflammatory pain animal model These findings are corroborated by other research reporting that EA 10 Hz inhibited phosphorylation of NMDA receptor 1 in spinal cord and alleviated pain in a rat model of inflammatory pain At the supraspinal level, alternating high- and low-frequency EA decreased levels of NMDA receptor 1 and c-fos expression in the rostral ventromedial medulla in an animal model of visceral pain Acupuncture also modulates EAAT2 expression.
A recent study examined the effect of acupuncture on depressive behaviors and EAAT2 in rats subjected to chronic unpredictable mild stress Both acupuncture therapy and drug treatment with the glutamate reuptake enhancer riluzole significantly increased sucrose consumption in the sucrose preference test paradigm.
This increase in sucrose consumption was associated with an elevated food intake and shortened latency in the novelty-suppressed feeding test paradigm. The amelioration of depressive behavioral actions was consistent with increasing numbers of EAAT2-positive cells and protein expression in the hippocampus and prefrontal cortex. Moreover, the antidepressant effect was observed later with acupuncture than with riluzole, indicating that repeated acupuncture stimulation may be needed to accumulate EAAT2 expression.
Thus, acupuncture-mediated modulation of EAAT2 expression may ameliorate depression. In summary, evidence indicates that acupuncture treatment may be of benefit in several neuropsychiatric disorders, including depression, anxiety, schizophrenia, and AD. The pathophysiology of these disorders may be associated with glutamate dysregulation, marked by a high rate of glutamate release and elevated expression of glutamate receptors and glutamate transporters in the CNS.ipdwew0030atl2.public.registeredsite.com/95699-spy-cell.php
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In case an outcome is measured at multiple time points, data from the time point where efficacy is highest will be included. Example: Experimental groups, control group s and number of animals per group. Example: Dose, timing of administration, frequency of administration, route of administration, vehicle. Example: 1st author, year of publication, language, journal. An introduction as well as a practical guide to meta-analysis of pre-clinical studies are available. For subgroup analysis a minimum of 8 studies per subgroup is required.
- Acupuncture for Smoking Cessation, Addiction and Insomnia | Psychology Today New Zealand.
- About Acupuncture - Center for Integrative Medicine.
- term paper on consumer behavior!
- Schizophrenia – Sunrise Neuro – Acupuncture Integrative Clinic.
- Suicide in schizophrenia: a retrospective case-control study of 51 suicides.?
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Example: number of metastases: standardized mean difference; incidence of metastasis: risk ratio. The random-effects model is the typical model of choice for pre-clinical meta-analyses.