Self-Regulatory Neuronal Mechanisms and Long-Term Challenges in Schizophrenia Treatment (original) (raw)
Related papers
Developing treatments for impaired cognition in schizophrenia
Trends in Cognitive Sciences, 2012
Schizophrenia is one of the most debilitating of all common brain disorders, exacting a heavy toll on the afflicted and having a tremendous public health impact. Clinical outcome is more strongly predicted by cognitive deficits than psychotic symptoms, with no established treatment for these deficits. In this review, we discuss the status of treatment development for impaired cognition in schizophrenia. These treatments include a range of pharmacological targets within diverse neurotransmitter systems. New technologies, including transcranial magnetic stimulation and transcranial direct current stimulation, and psychological therapies, such as computer-based cognitive training, may also benefit cognition in schizophrenia. Each of these approaches shows promise and their integration may optimize benefits for patients in the future.
Transcranial magnetic stimulation (TMS) is a very popular tool used within neuroscience. This and other associated techniques allow the in vivo investigation of cortical excitability, cortical connectivity and cortical plasticity. Schizophrenia is a brain disorder and various theories other than the dopamine hypothesis have been developed to describe its underlying neurobiology. Supported by animal and post mortem studies, findings from TMS studies indicate that schizophrenia is a disease of reduced cortical inhibition and impaired intra-and intercortical connectivity. Further studies using repetitive TMS and other plasticity-inducing techniques have shown that corti-cal plasticity is altered in schizophrenia patients, supporting the recently discussed plasticity deficiency theory of schizophrenia. This review gives an introduction to the most frequently applied techniques, describes findings in schizophrenia patients and discusses these findings with regard to the neurotransmitters and associated receptors involved. In summary, there is emerging evidence of an important pathophysiological interplay between reduced inhibition, impaired connectivity and reduced plasticity in schizophrenia patients. Gamma-aminobutyric-acid-receptors and glutamtergic N-Methyl-D-aspartic-acid-receptors are most likely to be involved in this complex interplay , which may reflect a disturbed signal-to-noise ratio in schizophrenia patients. This review will discuss this issue with regard to the available treatment options and will give implications for future research and therapeutic strategies regarding disinhibition and neuroplas-ticity in schizophrenia.
Enhancing Neuroplasticity to Augment Cognitive Remediation in Schizophrenia
Frontiers in Psychiatry, 2017
been disappointing, and currently, there is no drug approved for cognition enhancement in schizophrenia (5). Therefore, treatment studies in this population have started to shift to cognitive remediation (CR) strategies. Although CR in schizophrenia is effective at the group level (6, 7), there is substantial individual variability in treatment response, and many patients exhibit little benefit (8). Moreover, the training effects resulting from CR alone do not always generalize to improvements in real-life functioning (9). Thus, as the best validated treatment for the cognitive dysfunction in schizophrenia, CR only leads to a moderate effect-size improvement in cognition (0.45), with an even lower impact on daily functioning (0.36) (6, 9). It is, therefore, critical to consider ways of enhancing the impact of CR. Recently, "neuroplasticity-based" interventions have been developed to train perceptual processes in schizophrenia, while also engaging attentional and working memory operations (10). These interventions are explicitly designed to drive adaptive plastic changes throughout distributed prefrontal-temporoparietal systems (11). Many studies in schizophrenia patients have demonstrated that this neuroscience-informed approach to training generates meaningful restoration of prefrontal functions and higher-order cognition (12-14), with associated improvements in community functioning (15). Thus, neuroplasticity may be an important mechanism underlying effective intervention approaches. However, this CR method requires lengthy hours of repetitive, intensive practice to induce significant changes. Combining CR with strategies that promote neuroplasticity may not only lead to larger and longer-lasting improvements, but also require shorter training protocols. Although there have been efforts to combine CR with cognitive-enhancing medications that affect neuroplasticity, such as d-cycloserine (16) and modafinil (17), less attention has been devoted to non-pharmacological approaches that could potentially augment CR effects and maximize improvements in functional outcomes. In this brief review, we will discuss two recent non-pharmacological approaches that are thought to enhance neuroplasticity in schizophrenia: physical exercise and transcranial direct current stimulation (tDCS). It should be noted that there are many other neurostimulation techniques that have been discussed in the literature, such as transcranial magnetic stimulation (TMS), transcranial electrical stimulation (TES), magnetic seizure therapy, vagus nerve stimulation, and deep brain stimulation. However, only tDCS has been combined with CR. Review OF PHYSiCAL eXeRCiSe AnD tDCS STUDieS Physical exercise and Cognition The reviewers SI and ZN and handling editor declared their shared affiliation.
Reinforcement of Self-Regulated Brain Activity in Schizophrenia Patients Undergoing Rehabilitation
BioMed Research International, 2021
The experiment was aimed to compare the effects of different forms of rehabilitation applied in patients with schizophrenia. Verification of the obtained results was based on the analysis of the level of cognitive and social functioning of the subjects. For this purpose, the following clinical tools were used: Positive and Negative Syndrome Scale (PANSS), Beck Cognitive Insight Scale (BCIS), Color Trial Test (CTT-1, CTT-2), d2 psychological tests, Acceptance of Illness Scale (AIS), Self-efficacy Scale (GSES), Quantitative Electroencephalogram Biofeedback (QEEG-BF), auditory event-related potentials (ERPs), and serum levels of brain-derived neurotrophic factor (BDNF). The subjects were mentally stable male schizophrenia patients who had been in remission. They were divided into two groups which received different types of rehabilitation for three months. Group 1 patients followed a standard rehabilitation and Group 2 patients received GSR Biofeedback (galvanic skin response Biofeedba...
Perhaps the best way to consider schizophrenia is as a progressive neurodevelopmental disorder, in which events at various stages in life, from the antenatal period to adolescence, have their effects on the brain. There is already substantial evidence for the notion that the abnormal brain connectivity in schizophrenia may be related to synaptic plasticity. Various forms of psychological intervention, including cognitive-behaviour therapy (CBT), can positively alter not just the symptoms of schizophrenia, but its long-term course. Though medications form an integral part of most treatment guidelines, there is a growing realisation that psychological therapies do "work", at least for certain specific symptoms. Firm recommendations are also made regarding five kinds of specific psychological intervention for schizophrenia per se: supported employment, skills training, CBT, token economy-based interventions and family-based interventions. In future guidelines, cognitive remediation may join these five approaches. Since schizophrenia is a disorder that affects several aspects of functioning, it is logical to expect that targeting more than one domain could lead to a better outcome. While it is too early to speak of "preventing schizophrenia" through psychological interventions that target neuroplasticity, it is too early to write off this possibility either. Perhaps we need to stop thinking of "schizophrenia" as a monolithic entity. Instead, we should study it in terms of its constituent syndromes and dimensions.
Approaches to neuromodulation for schizophrenia
Journal of neurology, neurosurgery, and psychiatry, 2017
Based on the success of deep brain stimulation (DBS) for treating movement disorders, there is growing interest in using DBS to treat schizophrenia (SZ). We review the unmet needs of patients with SZ and the scientific rationale behind the DBS targets proposed in the literature in order to guide future development of DBS to treat this vulnerable patient population. SZ remains a devastating disorder despite treatment. Relapse, untreated psychosis, intolerable side effects and the lack of effective treatment for negative and cognitive symptoms contribute to poor outcome. Novel therapeutic interventions are needed to treat SZ and DBS is emerging as a potential intervention. Convergent genetic, pharmacological and neuroimaging evidence implicating neuropathology associated with psychosis is consistent with SZ being a circuit disorder amenable to striatal modulation with DBS. Many of the DBS targets proposed in the literature may modulate striatal dysregulation. Additional targets are co...
Assessment of Cortical Plasticity in Schizophrenia by Transcranial Magnetic Stimulation
Neural Plasticity, 2021
Neural plasticity refers to the capability of the brain to modify its structure and/or function and organization in response to a changing environment. Evidence shows that disruption of neuronal plasticity and altered functional connectivity between distinct brain networks contribute significantly to the pathophysiological mechanisms of schizophrenia. Transcranial magnetic stimulation has emerged as a noninvasive brain stimulation tool that can be utilized to investigate cortical excitability with the aim of probing neural plasticity mechanisms. In particular, in pathological disorders, such as schizophrenia, cortical dysfunction, such as an aberrant excitatory-inhibitory balance in cortical networks, altered cortical connectivity, and impairment of critical period timing are very important to be studied using different TMS paradigms. Studying such neurophysiological characteristics and plastic changes would help in elucidating different aspects of the pathophysiological mechanisms ...
International Journal of Environmental Research and Public Health, 2020
The aim of this pilot study was to analyse the influence of Galvanic Skin Response (GSR) Biofeedback training in a group of 18 men with schizophrenia at the remission stage. The results were verified according to: Positive and Negative Syndrome Scale (PANSS), Acceptance of Illness Scale (AIS), Self-efficacy Scale (GSES), Beck Cognitive Insight Scale (BCIS) scales, Colour Trial Test (CTT-1, CTT-2), d2 psychological tests, Quantitative Electroencephalogram (QEEG) Biofeedback, auditory event-related potentials (ERPs), and serum levels of brain-derived neurotrophic factor (BDNF). The results were compared in the same patients after 3 months. Statistically significant changes were noted in results for the variables on the PANSS scale. For the BDNF variable, a statistically significant increase occurred, indicating that GSR Biofeedback training may influence serum levels of the neurotrophic factor. Statistically significant changes were noted in results for the variables on the BCIS, AIS,...
Transcranial direct current stimulation to enhance cognitive remediation in schizophrenia
Brain Stimulation
fMRI study of behavioral reading treatment [9] found increased right hemisphere recruitment after short-term treatment, with shifts to left hemisphere perilesional areas occurring only after an additional 8 weeks of reinforcing the learned material. Similarly, in a study using audio-visual reading training of single words for 9 people with PA, 6 weeks of training resulted in improved reading speed and reduction of the length effect, similar to the current study. Also similar were the MEG results, showing increased connection strength in the left hemisphere and reduced connection strengths in the right hemisphere [10]. Here, we found functional connectivity to perilesional ventral occipitotemporal cortex increased from left frontal areas and decreased from right occipitotemporal and parietal areas after only 5 days of treatment using tDCS.
Annual Review of Clinical Psychology, 2013
Several important paradigm shifts have occurred in the field of schizophrenia treatment, including an increased focus on early detection, the development of preemptive interventions, and the view of schizophrenia as a neurodevelopmental disease characterized by decreased efficiency and abnormal connectivity in cortical and subcortical neural networks. In this review, we briefly describe some of the neural impairments that contribute to the development of schizophrenia, with an emphasis on the impact of stress and trauma on cognitively vulnerable neural systems. We then present current data on two behavioral interventions that target these critical risk factors and that aim to preempt the onset of schizophrenia in vulnerable individuals or improve the clinical course in recent-onset schizophrenia: cognitive therapy and computerized cognitive training.