Brain imaging in pediatric obsessive-compulsive disorder

ObjectiveTo review progress in understanding pediatric obsessive-compulsive disorder (OCD). The focus is on the frontal-striatal-thalamic model of OCD, neurobiological and genetic studies of the disorder, and their influence on recent advances in treatment.MethodComputerized literature searches were conducted with the key words Bobsessive-compulsive disorder” in conjunction with “pediatric,” “genetics,” and “imaging.”ResultsNeuroimaging studies find evidence to support the frontal-striatal-thalamic model. Genetic and neurochemical studies also implicate glutamate in the pathological finding of OCD. This has led to the application of glutamate-modulating agents to treat OCD.ConclusionsStudies of pediatric OCD have led to a refined frontal-striatal-thalamic model of pathogenesis and are having an evidence-based impact on treatment. Despite this progress, fully explanatory models are still needed that would allow for accurate prognosis and the development of targeted and efficacious treatments.     

Brain structural abnormalities in young children with autism spectrum disorder

OBJECTIVE: To explore the specific gross neuroanatomic substrates of this brain developmental disorder, the authors examine brain morphometric features in a large sample of carefully diagnosed 3- to 4-year-old children with autism spectrum disorder (ASD) compared with age-matched control groups of typically developing (TD) children and developmentally delayed (DD) children. METHODS: Volumes of the cerebrum, cerebellum, amygdala, and hippocampus were measured from three-dimensional coronal MR images acquired from 45 children with ASD, 26 TD children, and 14 DD children. The volumes were analyzed with respect to age, sex, volume of the cerebrum, and clinical status. RESULTS: Children with ASD were found to have significantly increased cerebral volumes compared with TD and DD children. Cerebellar volume for the ASD group was increased in comparison with the TD group, but this increase was proportional to overall increases in cerebral volume. The DD group had smaller cerebellar volumes compared with both of the other groups. Measurements of amygdalae and hippocampi in this group of young children with ASD revealed enlargement bilaterally that was proportional to overall increases in total cerebral volume. There were similar findings of cerebral enlargement for both girls and boys with ASD. For subregion analyses, structural abnormalities were observed primarily in boys, although this may reflect low statistical power issues because of the small sample (seven girls with ASD) studied. Among the ASD group, structural findings were independent of nonverbal IQ. In a subgroup of children with ASD with strictly defined autism, amygdalar enlargement was in excess of increased cerebral volume. CONCLUSIONS: These structural findings suggest abnormal brain developmental processes early in the clinical course of autism. Research currently is underway to better elucidate mechanisms underlying these structural abnormalities and their longitudinal progression.     

强迫症患者脑结构异常的多模态研究

目的探讨强迫症患者脑灰质和白质结构改变是否在同一样本中反映了相同环路的异常。方法对54例强迫症患者(强迫症组)和54名健康对照(对照组)进行3D结构磁共振成像扫描和弥散张量成像扫描。基于SPM分析软件,采用基于体素的形态学分析方法分析强迫症组全脑灰质体积与对照组的差异;基于FSL软件,采用基于纤维束示踪的空间统计学探讨强迫症组各向异性分数(fractional anisotropy,FA)与对照组的差异。结果与对照组相比,强迫症组左侧额中回、左侧前扣带和旁扣带脑回、左侧中央前回及右侧颞下回灰质体积减小(P<0.05,Alphasim校正),胼胝体体部和胼胝体膝部FA值减小(P<0.05,FWE校正)。结论强迫症患者的灰质体积和白质完整性均存在异常,且异常区域多位于皮质-纹状体-丘脑-皮质环路相关脑区,强迫症的灰、白质结构异常可能同时出现。     

Brain MRI in obsessive-compulsive disorder

Magnetic resonance imaging (MRI) brain scans were performed on 12 patients with obsessive-compulsive disorder and 12 healthy controls. Measurements of the area of the head of the caudate nucleus, cingulate gyrus thickness, intracaudate/frontal horn ratio, and area of the corpus callosum did not differ between the two groups. These limited data do not support the presence of a consistent gross brain structural abnormality in obsessive-compulsive disorder. Further studies using other anatomic measurements and other brain structural imaging techniques are warranted.     

强迫症患者抑制功能受损的脑影像学特征

目的分析强迫症患者是否存在抑制功能受损,及其抑制功能受损的脑影像学特征。方法16例首次发病未用药的强迫症患者(强迫症组)和18名健康对照者(对照组)完成测查抑制功能的Go-Nogo任务,同步采集被试者任务态脑影像数据。采用方差分析比较强迫症组和对照组在Go条件和Nogo条件下平均反应时和反应正确率的组间差异,以及在成功反应抑制与错误监测过程中脑激活特征的组间差异。结果在Nogo条件下,强迫症组的正确率显著低于对照组(0.85±0.08比0.93±0.51;t=-3.06,P<0.05);在错误监测过程中,2组大脑激活模式存在差异,强迫症组双侧颞下回(左侧:t=3.11;右侧:t=2.71)、右侧额中回(t=2.52)、右侧海马旁回(t=2.53)、左侧后扣带回(t=3.03)大脑活动增强(均P<0.05);双侧壳核(左侧:t=-3.03;右侧:t=-3.12)、右侧额下回(t=-3.29)、右侧额上回(t=-3.12)、右侧中央前回(t=-2.91)大脑活动显著降低(均P<0.05)。结论强迫症患者存在抑制功能受损,在错误监测过程中相关脑区的功能活动存在异常。     

Brain functional connectivity during induced sadness in patients with obsessive-compulsive disorder

Background

Obsessive–compulsive disorder (OCD) is associated with a range of emotional abnormalities linked to its defining symptoms, comorbid illnesses and cognitive deficits. The aim of this preliminary study was to examine functional changes in the brain that are associated with experimentally induced sad mood in patients with OCD compared with healthy controls in a frontolimbic circuit relevant to both OCD and mood regulation.

Methods

Participants underwent a validated sad mood induction procedure during functional magnetic resonance imaging. Analyses focused on mapping changes in the functional connectivity of the subgenual anterior cingulate cortex (ACC) within and between the 2 groups in response to successfully induced sadness.

Results

We enrolled 11 patients with OCD and 10 age-, sex- and IQ-matched controls in our study. Unlike controls, patients with OCD did not demonstrate predicted increases in functional connectivity between the subgenual ACC and other frontal regions during mood induction. Instead, patients demonstrated heightened connectivity between the subgenual ACC and ventral caudate/nucleus accumbens region and the hypothalamus.

Limitations

Our study included a small, partially medicated patient cohort that precluded our ability to investigate sex or drug effects, evaluate behavioural differences between the groups and perform a whole-brain analysis.

Conclusion

The ventral striatum and ventral frontal cortex were distinctly and differentially modulated in their connectivity with the subgenual ACC during the experience of sad mood in patients with OCD. These results suggest that, in patients with OCD, induced sadness appears to have provoked a primary subcortical component of the hypothesized “OCD circuit,” which may offer insights into why OCD symptoms tend to develop and worsen during disturbed emotional states.     

未服药强迫症患者双侧杏仁核静息态功能连接的初步观察

目的探讨静息状态下未服药强迫症患者双侧杏仁核功能连接的模式。方法纳入符合ICD-10中强迫症诊断标准的40例未服药强迫症患者(强迫症组),38名在性别、年龄和受教育程度与之相匹配的健康对照者(对照组)。采用Y-BOCS、HAMD17、HAMA评估强迫思维、强迫行为以及抑郁、焦虑症状。所有被试者进行全脑静息态fMRI,以左右杏仁核为种子点,采用基于体素的全脑功能连接方法分析强迫症患者静息状态下双侧杏仁核的功能连接模式;采用皮尔逊相关分析方法探讨强迫症患者异常功能连接与临床症状之间的关系。结果与对照组相比,强迫症组左侧杏仁核与右背侧前脑岛(0.16±0.13与0.27±0.13,t=-2.75,P<0.05,高斯随机场理论校正)、左侧杏仁核与左腹侧前扣带回(0.09±0.12与0.19±0.13,t=-3.40,P<0.05,高斯随机场理论校正)功能连接降低;强迫症组左侧杏仁核与右背侧前脑岛之间功能连接Z值与HAMA总分呈正相关(r=0.377,P=0.016,未校正)。结论静息状态下未服药强迫症患者情绪调节网络功能连接降低;左侧杏仁核与右背侧前脑岛之间降低的功能连接可能与强迫症患者的焦虑症状相关。     

Brain magnetic resonance imaging of structural abnormalities in bipolar disorder

BACKGROUND: The neuropathogenesis of bipolar disorder remains poorly described. Previous work suggests that patients with bipolar disorder may have abnormalities in neural pathways that are hypothesized to modulate human mood states. We examined differences in brain structural volumes associated with these pathways between patients with bipolar disorder hospitalized with mania and healthy community volunteers. METHODS: Twenty-four patients with bipolar disorder and mania were recruited from hospital admission records. Twenty-two healthy volunteers were recruited from the community who were similar to the patients in age, sex, race, height, handedness, and education. All subjects were scanned using a 3-dimensional radio-frequency-spoiled Fourier acquired steady state acquisition sequence on a 1.5-T magnetic resonance imaging scanner. Scans were analyzed using commercial software. Prefrontal, thalamic, hippocampal, amygdala, pallidal, and striatal volumetric measurements were compared between the 2 groups. RESULTS: Patients with bipolar disorder demonstrated a significant (A = 0.64; F6,37 = 3.4; P = .009) overall difference in structural volumes in these regions compared with controls. In particular, the amygdala was enlarged in the patients. Brain structural volumes were not significantly associated with duration of illness, prior medication exposure, number of previous hospital admissions, or duration of substance abuse. Separating patients into first-episode (n = 12) and multiple-episode (n = 12) subgroups revealed no significant differences in any structure (P>.10). CONCLUSION: Patients with bipolar disorder exhibit structural abnormalities in neural pathways thought to modulate human mood.     

Neurochemical analyses in pediatric obsessive-compulsive disorder in patients treated with cognitive-behavioral therapy

OBJECTIVE: To investigate neurochemical changes in the caudate nucleus of pediatric obsessive-compulsive disorder (OCD) patients before and after cognitive-behavioral therapy (CBT), and to examine corresponding changes in symptom severity. METHOD: Single-voxel proton magnetic resonance spectroscopic (1H-MRS) examination of the left caudate was conducted in 21 treatment-na?ve children, aged 6 to 16 years, before and after 12 weeks of CBT. Subjects were measured at baseline and posttreatment by the Yale-Brown Obsessive Compulsive Scale for Children, Hamilton Depression Rating Scale, and Hamilton Anxiety Rating Scale. RESULTS: No significant changes in caudate neurochemistry were observed in OCD patients before and after CBT despite unambiguous improvement in OCD symptoms, depression, and anxiety. CONCLUSIONS: Findings suggest that reduction in caudate Glx may be specific to SSRI treatment and not due to a more generalized treatment response or spontaneous improvement of symptoms. Differential sets of pathophysiologic and treatment response markers may moderate/mediate the effects of particular treatments on outcome.     

Sleep-related problems in pediatric obsessive-compulsive disorder

Although attention has been given to presence of sleep related problems (SRPs) in children with psychiatric conditions, little has been reported on SRPs in youth with obsessive-compulsive disorder (OCD). Sixty-six children and adolescents with OCD were administered the Children's Yale Brown Obsessive-Compulsive Scale and completed the Children's Depression Inventory and Multidimensional Anxiety Scale. Their parents completed the Child Behavior Checklist and Children's Obsessive-Compulsive Impact Scale. A subset of youth (n=41) completed a trial of cognitive-behavioral therapy. Frequency of eight specific SRPs was examined in relation to age, gender, OCD symptom severity, child-rated symptoms of depression and anxiety, parent-proxy ratings of internalizing and externalizing problems, and functional impairment. Ninety-two percent of youth experienced at least one SRP, with 27.3% reporting five or more SRPs. Total SRPs were positively associated with OCD symptom severity, child-rated anxiety, and parent-proxy ratings of internalizing problems. Total and several specific SRPs were reduced following cognitive-behavioral treatment. These results suggest that SRPs are relatively common in youth with OCD, are associated with symptom severity, and warrant attention during assessment and treatment.     

Neuropsychological correlates of P300 abnormalities in patients with schizophrenia and obsessive-compulsive disorder

The cognitive significance of P300 abnormalities in schizophrenia and obsessive-compulsive disorder (OCD) was investigated. P300 was measured by an auditory oddball paradigm, in which a series of standard tones (1000 Hz) and target tones (1500 Hz) were presented. The subject's task was to count the number of the presented target tones. Cognitive functions were evaluated by neuropsychological tests, which were chosen to be sensitive to frontal and temporal dysfunction. Twenty-two schizophrenic patients, 19 OCD patients and 21 healthy controls participated. Event-related potentials measured at 15 electrode sites, which consisted of five levels on the left-right dimension and three levels on the anterior-posterior dimension, were included in the statistical analysis. P300 amplitudes on all 15 electrode sites were significantly smaller in schizophrenic and OCD patients than in the controls. Schizophrenic patients performed poorly on almost all neuropsychological tests, while OCD patients showed impaired performance on the Rey-Osterrieth Complex Figure Test and on a controlled oral word association test. In schizophrenic patients, P300 amplitude was associated with performance on verbal memory and learning by the Luria-Nebraska Neuropsychological Battery, while for OCD patients, P300 amplitude was related to the Trail Making Test, Part B response time. These results indicate that schizophrenic patients have generalized cognitive impairments, which are substrated by a wide range of cortical dysfunctions. The major cognitive deficits observed in OCD patients were impairments of controlled attention and self-guided, flexible behavior, which are mediated by the fronto-striatal system. The neurophysiological mechanisms underlying P300 abnormalities observed in schizophrenic and OCD patients are discussed.     

基于形变的形态学测量对首次发病未服药抑郁症患者大脑灰质异常的研究

目的:探讨首次发病未服药抑郁症患者（major depressive disorder）大脑灰质结构改变以及抑郁症早期诊断的影像学指标。方法:对38例抑郁症患者（抑郁症组）和65名年龄、性别相匹配的健康对照（对照组）进行3D T 1加权结构像磁共振成像扫描,采用基于形变的形态学测量（deformation-...     

Clinical features associated with treatment-resistant pediatric obsessive-compulsive disorder

OBJECTIVE: The objective of the study was to identify clinical and sociodemographic characteristics that may differentiate youth with obsessive-compulsive disorder (OCD) who are resistant to treatment vs those who have a favorable response. METHOD: Participants included 60 outpatients, aged 7-17 years, who were determined to have previously received an adequate trial of a first-line treatment (ie, serotonin reuptake inhibitors, cognitive behavioral therapy). Patients who were treatment-resistant were compared with responders on a number of factors, including severity and nature of OCD symptoms, levels of internalizing and externalizing symptoms, family accommodation of OCD symptoms, and functional impairment. RESULTS: The treatment-resistant group endorsed significantly more obsessions and compulsions, greater levels of internalizing symptoms, higher parental stress related to accommodation, and greater functional impairment than treatment responders. However, relative to treatment-resistant patients, treatment responders reported higher levels of depressive symptoms, perhaps indicating that they were more distressed by their OCD symptoms, as well as greater insight into their symptoms. CONCLUSIONS: This study indicates that youth with more severe symptoms of OCD, higher related parental stress, and greater functional impairment tend to be more resistant to first-line treatments, and that perhaps they may require more intensive or family-based interventions. Treatment responders report more depressive symptoms and insight into their OCD, which may suggest a greater readiness for treatment. Further research likely would help to identify which types of treatment would be most beneficial for individual youth.     

Bradykinesia in patients with obsessive-compulsive disorder

ObjectiveTo investigate the frequency of bradykinesia in patients with obsessive-compulsive disorder (OCD) and to see whether patients with OCD who also have bradykinesia display distinctive neuropsychological and neuropsychiatric features.MethodsWe studied 23 antipsychotic-free patients with OCD and 13 healthy controls. Bradykinesia was assessed with section III of the Unified Parkinson Disease Rating Scale. The Wechsler Adult Intelligent Scales-Revised (WAIS-R) was used to assess the Full Scale IQ and to measure visuospatial, visuoconstructional ability and psychomotor speed/mental slowness.ResultsOf the 23 patients with OCD studied, 8 (34%) had mild symptoms of bradykinesia. No relationship was found between bradykinesia and the sociodemographic variables assessed but this motor symptom was significantly associated with the severity of compulsions. Patients with bradykinesia differed from those without: they had a higher frequency of repeating compulsions, and lower IQ scores, performance scores, and WAIS-R subtest scores for similarities and picture completion. No significant differences were found between patients without bradykinesia and healthy controls in any test.ConclusionsClinical assessment of motor symptoms in adult patients with OCD often discloses mild bradykinesia sometimes associated with repeating compulsions and poor WAIS-R performance scores.     

不接受/禁忌思维亚型强迫障碍患者的脑白质磁共振弥散张量成像研究

目的:运用磁共振扩散张量成像技术探讨未经治疗的不接受/禁忌思维亚型强迫障碍(OCD)患者脑白质的变化及与临床症状之间的相关性。方法:对26例不接受/禁忌思维亚型OCD患者和28名性别、年龄、受教育程度相匹配的健康对照者进行弥散张量成像(DTI)扫描,采用耶鲁-布朗强迫量表(Y-BOCS)、17项汉密尔顿抑郁量表(HAMD-17)、汉密尔顿焦虑量表(HAMA)等评估临床症状,采用基于纤维束空间统计分析(TBSS)等方法比较两组全脑DTI的各向异性分数(FA),得出有差异脑区,并分析患者组脑白质改变与临床症状严重程度之间的关系。结果:和正常对照组相比,患者组的大脑胼胝体、右侧上纵束、右侧下额-枕束、右侧丘脑后辐射(视辐射部)等部位的FA值显著降低;未发现任何脑区的FA值与临床行为学量表之间的相关性。结论:多个脑白质区的结构异常可能构成不接受/禁忌思维亚型OCD患者的病理生理基础,这些脑白质区的变化可能是此亚型OCD的特征标志。     

Error-related negativity abnormalities in generalized anxiety disorder and obsessive-compulsive disorder

Enhanced error-related negativity (ERN) has been associated with anxiety among both non-clinical and clinical populations. However, whether it is abnormal among adult patients with generalized anxiety disorder (GAD) is still unknown. The present study investigated it across GAD and obsessive-compulsive disorder (OCD). Event related brain potentials (ERPs) were recorded from a group of 27 GAD patients, 25 OCD patients and 27 healthy control participants during a modified Erikson Flankers task. ERP difference waveforms were obtained by subtracting ERP to correct response (CRN) from ERP to error response (ERN). The Ne component of ERPs at medial frontal electrodes were analyzed and reported. The Ne component of ERP difference waveform was enhanced only in OCD patients, but not in GAD patients, as compared to the healthy controls. An exploratory analysis also revealed higher Ne amplitude of error trial waveforms in both GAD and OCD patients than in healthy controls, and an insignificant group difference in Ne component of correct trial waveforms. The Ne amplitude of error trial waveforms also correlated with Hamilton Anxiety Rating Scale (HAMA) scores and with Hamilton Depression Rating Scale (HAMD) scores across the three subject groups. The main findings of the present study suggest that error processing is altered in OCD but not in GAD, and that ERN abnormalities in GAD are possibly associated with an overactive response checking process or excessive response monitoring.