EMDR治疗:适应性信息加工、临床应用及研究介绍

恭祝中国EMDR学组的成立,同时对所有致力于帮助那些遭遇痛苦的人们减轻伤痛的同仁们致以敬意。谢谢给我这个机会,让我能够对EMDR（眼动脱敏再加工）的最新进展及其理论基础作些阐述。过去二十年来,很多事情都发生了变化,也需要作些澄清。

EMDR、适应性信息加工与个案概念化(上)

EMDR是一个整合性的、以咨客为中心的心理治疗方法,它着重于大脑的信息加工系统、烦扰经历的记忆,这些病理学基础不是由器质性的损伤导致的。EMDR强调对临床情境有作用的经历,和那些需要带领咨客达到更健康的心理状态的经历。EMDR作为以经验为主的支持治疗,本文综述其历史、发展和研究,在阐述适应性信息加工模型之后,用一个延续的个案实例来说明了EMDR的个案概念化和8个阶段的治疗。这个方法用于加工那些建立病理学基础的和触发当前功能失调的早期记忆,并为将来恰当的行为提供模板,包括克服技能和(或)发展性的不足所需的知识与行为。整合的EMDR与家庭系统观点的好处是可以提供最综合的治疗效果。

EMDR用于边缘型人格障碍的治疗

边缘型人格障碍(BPD)患者通常有显著的功能行使能力损害。其特征是冲动、情绪不稳、人际困难和身份认同问题,常常导致自杀行为和自杀姿态。虽然传统上认为BPD是一种慢性持久的障碍,但近期的研究却提示它可能会随着时间流逝而有所缓解,而且心理治疗可以促进缓解。BPD的病因与童年期虐待和不恰当的依恋关系有关。由于童年期虐待和创伤的重要意义,被公认有效的创伤治疗方法——眼动脱敏与再加工(EMDR)可能作为BPD的合理备选治疗方案之一。本文中的个案所获得的良好疗效阐明了EMDR在BPD治疗中的运用,提示有理由进行深入的对照研究。

Platelets and Alzheimer's disease:Potential of APP as a biomarker

Platelets are the first peripheral source of amyloid precursor protein(APP). They possess the proteolytic machinery to produce Aβ and fragments similar to those produced in neurons, and thus offer an ex-vivo model to study APP processing and changes associated with Alzheimer's disease(AD). Platelet process APP mostly through the α-secretase pathway to release soluble APP(s APP). They produce small amounts of Aβ, predominantly Aβ40 over Aβ42. s APP and Aβ are stored inα-granules and are released upon platelet activation by thrombin and collagen, and agents inducing platelet degranulation. A small proportion of full-length APP is present at the platelet surface and this increases by 3-fold upon platelet activation. Immunoblotting of platelet lysates detects APP as isoforms of 130 kD a and106-110 kD a. The ratio of these of APP isoforms is significantly lower in patients with AD and mild cognitive impairment(MCI) than in healthy controls. This ratio follows a decrease that parallels cognitive decline andcan predict conversion from MCI to AD. Alterations in the levels of α-secretase ADAM10 and in the enzymatic activities of α- and β-secretase observed in platelets of patients with AD are consistent with increased processing through the amyloidogenic pathway. β-APP cleaving enzyme activity is increased by 24% in platelet membranes of patients with MCI and by 17% in those with AD. Reports of changes in platelet APP expression with MCI and AD have been promising so far and merit further investigation as the search for blood biomarkers in AD, in particular at the prodromal stage, remains a priority and a challenge.

PrP^C-related signal transduction is influenced by copper, membrane integrity and the alpha cleavage site

The copper-binding, membrane-anchored, cellular prion protein （PrP~） has two constitutive cleavage sites producing distinct N- and C-terminal fragments （N1/C1 and N2/C2）. Using RK13 cells expressing either human PrPc, mouse PrPc or mouse PrP^C carrying the 3F4 epitope, this study explored the influence of the PrP^C primary sequence on endoproteolytic cleavage and one putative PrPc function, MAP kinase signal transduction, in response to exogenous copper with or without a perturbed membrane environment. PrPc primary sequence, especially that around the N1/C1 cleavage site, appeared to influence basal levels of proteolysis at this location and extracellular signal-regulat- ed kinase 1/2 （ERK1/2） phosphorylation, with increased processing demonstrating an inverse relationship with basal ERK1/2 activation. Human PrP^C showed increased N1/C1 cleavage in response to copper alone, accompanied by specific p38 and JNK/SAPK phosphorylation. Combined exposure to copper plus the cholesterol-sequestering antibiotic filipin resulted in a mouse PrP^C-specific substantial increase in signal protein phosphorylation, accompanied by an increase in N1/C1 cleavage. Mouse PrPc harboring the human N1/C1 cleavage site assumed more human-like profiles basally and in response to copper and altered membrane environments. Our results demonstrate that the PrPc pri- mary sequence around the N1/C1 cleavage site influences endoproteolytic processing at this location, which appears linked to MAP kinase signal transduction both basally and in response to copper. Further, the primary sequence appears to confer a mutual dependence of N1/C1 cleavage and membrane integrity on the fidelity of PrP^C-related signal transduction in response to exogenous stimuli.

Understanding the pathophysiology of postpartum psychosis: Challenges and new approaches

Postpartum psychosis is a severe psychiatric condition which affects 1-2 of every 1000 mothers shortly after childbirth. Whilst there is convincing evidence that the condition is precipitated by a complex combination of biological and environmental factors, as yet the pathophysiological mechanisms remain extremely poorly defined. Here, I critically review approaches that have been, or are being, employed to identify and characterise such mechanisms; I also review a recent animal model approach, and describe a novel biological risk model that it suggests. Clarification of biological risk mechanisms underlying disorder risk should permit the identification of relevant predictive biomarkers which will ensure that "at risk" subjects receive prompt clinical intervention if required.

Deriving striatal projection neurons from human pluripotent stem cells with Activin A

The striatum is the main input structure of the basal ganglia and is involved in voluntary motor control,habit learning and reward processing.Medium spiny neurons（MSNs）comprise80%and 95%of striatal neurons in primates and rodents,respectively.

High mobility group box protein 1 and white matter injury following traumatic brain injury: perspectives on mechanisms and therapeutic strategies

Traumatic brain injury(TBI)is a major cause of morbidity and mortality worldwide.Despite significant medical advances over recent decades,many survivors of TBI develop long term neuro-cognitive deficits.Previously,only moderate and severe injuries were thought to account for the devastating consequences of TBI.However,there is increasing evidence that even milder injuries may result in problematic lifelong cognitive and affective disturbances.TBI is typically characterized by an an acute physical injury followed by a protracted innate neuro-inflammatory response.These reponses,mediated via neuronal,astrocyte and microglial cells,amongst others,and may result in widespread neuronal death and a micro-environment that is not conducive to brain repair(Manivannan et al.,2021).Whilst the primary physical injury often evades intervention from a medical perspective,the subsequent neuro-inflammatory response offers a potential therapeutic target.Nonetheless,effective pharmacological strategies continue to elude clinicians and scientists due to the complex underlying pathogenesis and difficulties of modelling such a heterogeneous disease.However,the majority of research to date has focused on investigating the effects of post-traumatic neuro-inflammation on grey matter injury rather than the consequences upon white matter(WM),which contributes greatly to cognitive dysfunction across many neurological diseases(Filly and Kelly,2018).Herein,we will briefly discuss:(i)high mobility group box protein 1(HMGB1)as a potential therapeutic target;(ii)the relevance of WM injury in TBI and current understanding of WM repair following injury;and(iii)perspectives on how HMGB1 may play a role.

Pluripotent stem cell derived inhibitory interneurons–principles and applications in health and disease

Inhibitory interneurons are gamma-aminobutyric acid-ergic (GABAergic) nerve cells that act to maintain the appropriate excitation-inhibition balance, and synchronise the output of principle cells to generate rhythmic patterns of firing (Kessaris et al., 2014). This critical role, along with their brain-wide distribution, has led to the implication of interneurons in many neuropathologies, including schizophrenia, autism, dystonia and epilepsies (Marín, 2012).

EMDR、适应性信息加工与个案概念化(中)

EMDR是一个整合性的、以咨客为中心的心理治疗方法,治疗那些不是由器质性的损伤为病理学基础的心理问题,它的治疗重点在于大脑的信息加工系统和困扰经历的记忆。EMDR处理导致临床困扰的经验,也处理能使咨客达到更健康的心理状态所需的那些经验。综览EMDR的历史、发展和研究,它是一个主要以经验为支持的治疗方法。本文在阐述适应性信息加工模型之后,用一个延续的个案实例,来说明EMDR的个案概念化和8个阶段的治疗。这个方法用于加工那些建立在病理学基础上的早期记忆、触发当前功能失调的早期记忆,并为将来恰当的行为提供模板,包括克服技能和(或)发展性的不足所需的知识与行为。整合的EMDR与家庭系统观点的好处是可以提供最综合的治疗效果。

EMDR、适应性信息加工与个案概念化(下)

EMDR是一个整合性的、以咨客为中心的心理治疗方法。该方法用于治疗那些不是由器质性损伤为病理学基础的心理问题,它的治疗重点是处理大脑的信息加工系统中的痛苦记忆。EMDR既能处理那些引起困扰的经历和体验,也能帮助咨客获得达到更健康的心理状态所需要的经历和体验。综览EMDR的历史、发展和研究,它是一个主要以经验为支持的治疗方法。本文在阐述适应性信息加工模型之后,用一个延续的个案实例,来说明EMDR的个案概念化和8个阶段的治疗。EMDR技术主要是加工那些有病理学基础的早期记忆和引发不良功能的当前情境,并为未来适应性的行为提供模板,包括克服技能不足和(或)发展性的不足所需的知识与行为。整合的EMDR与家庭系统观点的好处是可以提供最综合的治疗效果。

How random is the random forest ? Random forest algorithm on the service of structural imaging biomarkers for Alzheimer's disease: from Alzheimer's disease neuroimaging initiative(ADNI) database

Neuroinformatics is a fascinating research field that applies computational models and analytical tools to high dimensional experimental neuroscience data for a better understanding of how the brain functions or dysfunctions in brain diseases. Neuroinformaticians work in the intersection of neuroscience and informatics supporting the integration of various sub-disciplines（behavioural neuroscience, genetics, cognitive psychology, etc.） working on brain research. Neuroinformaticians are the pathway of information exchange between informaticians and clinicians for a better understanding of the outcome of computational models and the clinical interpretation of the analysis. Machine learning is one of the most significant computational developments in the last decade giving tools to neuroinformaticians and finally to radiologists and clinicians for an automatic and early diagnosis-prognosis of a brain disease. Random forest（RF） algorithm has been successfully applied to high-dimensional neuroimaging data for feature reduction and also has been applied to classify the clinical label of a subject using single or multi-modal neuroimaging datasets. Our aim was to review the studies where RF was applied to correctly predict the Alzheimer＇s disease（AD）, the conversion from mild cognitive impairment（MCI） and its robustness to overfitting, outliers and handling of non-linear data. Finally, we described our RF-based model that gave us the 1 ^（st） position in an international challenge for automated prediction of MCI from MRI data.

Cognitive, behavioural and psychiatric phenotypes associated with steroid sulfatase deficiency

The enzyme steroid sulfatase(STS)desulfates a variety of steroid compounds thereby altering their activity.STS is expressed in the skin,and its deficiency in this tissue has been linked to the dermatological condition X-linked ichthyosis.STS is also highly expressed in the developing and adult human brain,and in a variety of steroidogenic organs(including the placenta and gonads);therefore it has the potential to influence brain development and function directly and/or indirectly(through influencing the hormonal milieu).In this review,we first discuss evidence from human and animal model studies suggesting that STS deficiency might predispose to neurobehavioural abnormalities and certain psychiatric disorders.We subsequently discuss potential mechanisms that may underlie these vulnerabilities.The data described herein have potential implications for understanding the complete spectrum ofclinical phenotypes associated with X-linked ichthyosis,and may indicate novel pathogenic mechanisms underlying psychological dysfunction in developmental disorders such as attention deficit hyperactivity disorder and Turner syndrome.

Pathological Gambling after Administration of Pramipexole

Parkinson’s disease is a common condition usually treated by dopaminergic agents and many behavioral abnormalities such as impulse control disorders (ICD) are connected with that usage. Pathological gambling, a form of ICD includes is a clinical condition that disrupts personal, family and occupational activity. Pramipexole a D2 AND D3 agonist may be associated with pathological gambling. We present a case of 74-year-old male patient who was diagnosed with Parkinson’s disease (PD). His doctor advised him to take pramipexole 0.18 mg/p.o./day. A month after the onset of treatment he manifested a behavior of pathological gambling. After the discontinuation of the drug all this behavior was interrupted.

Dysmorphic Concern Questionnaire: Greek Translation, Validation and Psychometric Properties

Aim of this study is to assess the reliability, validity and psychometric properties of the Greek language version of the Dysmorphic Concern Questionnaire (DCQ). Method: The Greek language version of the DCQ scale was presented to 88 healthy individuals (57 women and 31 men) and 32 subjects suffering from body dysmorphic disorder BDD (20 women and 12 men) matched for age and sex. All the BDD group subjects and 57 subjects from the healthy individual group were also assessed according to the following psychometric scales: Symptom Checklist-90-R (SCL-90) scale, Eysenck Personality Questionnaire (EPQ), State-Trait Anxiety Inventory (STAI 1 and STAI-2) and the Zung Self-Rating Depression scales. Results: Regarding the DCQ scale, the analysis revealed that one single factor was extracted that accounted for 71.4% of the total variance. Cronbach’s alpha was 0.933, indicating a high level of internal consistency. Comparison between groups, healthy individuals vs BDD patients, showed statistically significant differences in almost every item of the SCL-90 scale (p < 0.05). The Spearman correlations of DCQ score, the DCQ factor score and DCQ T factor with SCL-90, EPQ, as well as the ZUNG depressive scales present high correlation with most items of SCL-90 and ZUNG and STAI-2 (p < 0.005). Conclusion: The Greek version of the Dysmorphic Concern Questionnaire (DCQ) is a valid and reliable instrument, appropriate for both research and clinical settings where dysmorphic concern or body image is a variable which needs to be measured or screened for.

Impact of the biological definition of Alzheimer’s disease using amyloid, tau and neurodegeneration (ATN):what about the role of vascular changes,inflammation,Lewy body pathology?

Background:The NIA-AA research framework proposes a biological definition of Alzheimer’s disease,where asymptomatic persons with amyloid deposition would be considered as having this disease prior to symptoms.Discussion:Notwithstanding the fact that amyloid deposition in isolation is not associated with dementia,even the combined association of amyloid and tau pathology does not inevitably need to dementia over age 65.Other pathological factors may play a leading or an accelerating role in age-associated cognitive decline,including vascular small vessel disease,neuroinflammation and Lewy Body pathology.Conclusion:Research should aim at understanding the interaction between all these factors,rather than focusing on them individually.Hopefully this will lead to a personalized approach to the prevention of brain aging,based on individual biological,genetic and cognitive profiles.

Impaired Parahippocampal Gyrus-Orbitofrontal Cortex Circuit Associated with Visuospatial Memory Deficit as a Potential Biomarker and Interventional Approach for Alzheimer Disease

The parahippocampal gyrus-orbitofrontal cortex(PHG-OFC)circuit in humans is homologous to the postrhinal cortex(POR)-ventral lateral orbitofrontal cortex(vlOFC)circuit in rodents.Both are associated with visuospatial malfunctions in Alzheimer’s disease(AD).However,the underlying mechanisms remain to be elucidated.In this study,we explored the relationship between an impaired POR-vlOFC circuit and visuospatial memory deficits through retrograde tracing and in vivo local field potential recordings in 5XFAD mice,and investigated alterations of the PHG-OFC circuit by multi-domain magnetic resonance imaging(MRI)in patients on the AD spectrum.We demonstrated that an impaired glutamatergic POR-vlOFC circuit resulted in deficient visuospatial memory in 5XFAD mice.Moreover,MRI measurements of the PHG-OFC circuit had an accuracy of 77.33%for the classification of amnestic mild cognitive impairment converters versus non-converters.Thus,the PHG-OFC circuit explains the neuroanatomical basis of visuospatial memory deficits in AD,thereby providing a potential predictor for AD progression and a promising interventional approach for AD.