Neuromodulatory treatments for psychiatric disease: A comprehensive survey of the clinical trial landscape

BackgroundNumerous neuromodulatory therapies are currently under investigation or in clinical use for the treatment of psychiatric conditions.Objective/hypothesisWe sought to catalogue past and present human research studies on psychiatric neuromodulation and identify relevant trends in this field.MethodsClinicalTrials.gov (https://www.clinicaltrials.gov/) and the International Clinical Trials Registry Platform (https://www.who.int/ictrp/en/) were queried in March 2020 for trials assessing the outcome of neuromodulation for psychiatric disorders. Relevant trials were categorized by variables such as neuromodulation modality, country, brain target, publication status, design, and funding source.ResultsFrom 72,086 initial search results, 1252 unique trials were identified. The number of trials registered annually has consistently increased. Half of all trials were active and a quarter have translated to publications. The largest proportion of trials involved depression (45%), schizophrenia (18%), and substance use disorders (14%). Trials spanned 37 countries; China, the second largest contributor (13%) after the United States (28%), has increased its output substantially in recent years. Over 75% of trials involved non-convulsive non-invasive modalities (e.g., transcranial magnetic stimulation), while convulsive (e.g., electroconvulsive therapy) and invasive modalities (e.g., deep brain stimulation) were less represented. 72% of trials featured approved or cleared interventions. Characteristic inter-modality differences were observed with respect to enrollment size, trial design/phase, and funding. Dorsolateral prefrontal cortex accounted for over half of focal neuromodulation trial targets. The proportion of trials examining biological correlates of neuromodulation has increased.Conclusion(s)These results provide a comprehensive overview of the state of psychiatric neuromodulation research, revealing the growing scope and internationalism of this field.     

Metacognitive beliefs in obsessive-compulsive patients: A comparison with healthy and schizophrenia participants

Introduction. Distorted metacognitive beliefs are increasingly considered in theoretical models of obsessive-compulsive disorder (OCD). However, so far no consensus has emerged regarding the specific metacognitive profile of OCD.

Methods. Participants with OCD (n=55), schizophrenia (n=39), and nonclinical controls (n=49) were assessed with the Metacognitions Questionnaire (MCQ-30).

Results. Except for positive beliefs about worry, both patient samples exceeded nonclinical controls on all MCQ subscales. The MCQ “need to control thoughts” and “negative beliefs about uncontrollability and danger” subscales showed strong correlations with obsessions, and scores in the former scale were elevated in hallucinators. In contrast to several prior studies, “cognitive confidence” was related neither to core OCD nor to schizophrenia symptomatology.

Conclusions. Notwithstanding large pathogenetic differences between OCD and schizophrenia, findings suggest that obsessions and hallucinations may share a common metacognitive pathway. Need to control thoughts and dysfunctional beliefs about the malleability of worries may represent critical prerequisites for the two phenomena to emerge.     

The effect of red light on backward masking in individuals with psychometrically defined schizotypy

Introduction. Previous research has suggested that individuals with schizophrenia and their relatives show a change in backward masking performance with a red background that is in the opposite qualitative direction as that found in nonpsychiatric controls. The present study examines this effect in individuals with psychometrically defined schizotypy to explore the potential of this effect to be a useful new qualitative endophenotype for schizophrenia-spectrum traits.

Methods. The Abbreviated Youth Psychosis At-Risk Questionnaire was used to screen a large number of undergraduates for schizotypy symptoms. A sample of 23 participants scoring high on this measure were compared to a sample of 26 controls on a location backward masking task that was presented on both red and green backgrounds.

Results. Consistent with findings in patients with schizophrenia, the participants reporting a high number of schizotypy features showed a decrease in performance to the red (compared to green) background and the controls showed a nonsignificant increase in performance—although this finding was limited to the stimulus–onset asynchrony (SOA) value that approximated the SOA with the largest effect size in the previous schizophrenia study (69 ms).

Conclusions. Although limited to one SOA, results extend earlier findings approximating this SOA to include a psychometrically defined schizotypy sample.     

Factor structure of the BPRS in deaf people with schizophrenia: Correlates to language and thought

Introduction. There has been a relative lack of research on deaf people with schizophrenia, and no data exist regarding symptom structure in this population. Thus, we determined the factor structure of the 24-item Brief Psychiatric Rating Scale (BPRS) in deaf (n=34) and hearing (n=31) people with schizophrenia and compared it to a standard four-factor solution.

Method. An obliquely rotated factor analysis produced a solution for the BPRS that resembled others in the literature. Symptom clusters were additionally compared to cognitive and social-cognitive abilities.

Results. Activity and disorganised symptoms were the most consistent correlates of visual- and thought and language-related skills for deaf and hearing subjects respectively. Affective symptoms and facial affect processing were positively correlated among deaf but not hearing subjects.

Conclusions. The data suggest that current symptom models of schizophrenia are valid in both hearing and deaf patients. However, relations between symptoms, cognition, and outcome from the general (hearing) literature cannot be generalised to deaf patients. Findings are broadly consistent with pathophysiologic models of schizophrenia suggesting a fundamental cortical processing algorithm operating across several domains of neural activity including vision, and thought and language. Support is provided for recent advances in social-cognitive interventions for people with schizophrenia.     

精神分裂症发病机制及治疗靶点的研究现状

精神分裂症是一种严重的精神疾病,但确切的机制至今尚未研究透彻。近来,研究者们发现D1、D2受体的过度活化、多巴胺和环腺苷酸调节的磷蛋白的调节机制、受体磷酸化磷酸酶β/ζ的编码基因PTPRZ1(蛋白酪氨酸磷酸酶,受体类型,Z多肽1)与精神分裂症密切相关;γ氨基丁酸α受亚单位α5受体进行变构调节,能逆转多巴胺功能异常亢进,进而缓解精神分裂症的阳性症状。