Differential outcomes for frontal versus posterior demyelination in childhood cerebral adrenoleukodystrophy.

In the most common variant of childhood cerebral adrenoleukodystrophy (cALD), demyelinating brain lesions are distributed predominately in parieto-occipital white matter. Less frequently, lesions first develop in frontal white matter. This matched cohort study examined whether outcomes after standard treatment with hematopoietic cell transplantation (HCT) differ in patients with early stage frontal lesions as compared to parieto-occipital lesions. Retrospective chart review identified seven pediatric patients with frontal cALD lesions and MRI severity score < 10 who underwent a single HCT at our center between 1990 and 2019. Concurrent MRI, neurocognitive and psychiatric outcomes at last comprehensive follow-up (mean 1.2 years; range 0.5-2.1 years) were compared with a group of seven boys with the parieto-occipital variant matched on pre-HCT MRI severity score. Both groups showed similar rates of transplant complications and radiographic disease advancement. Neurocognitive outcomes were broadly similar, with more frequent working memory deficits among individuals with frontal lesions. Psychiatric problems (hyperactivity, aggression, and atypical behavior) were considerably more common and severe among patients with frontal lesions. Aligned with the critical role of the frontal lobes in emotional and behavioral regulation, functional disruption of self-regulation skills is widely observed among patients with frontal lesions. Comprehensive care for cALD should address needs for psychiatric care and management.

DTI for brain targeting: Diffusion weighted imaging fiber tractography-Assisted deep brain stimulation.

Fiber tractography assisted Deep Brain Stimulation (DBS) has been performed by different groups for more than 10 years to now. Groups around the world have adapted initial approaches to currently embrace the fiber tractography technology mainly for treating tremor (DBS and lesions), psychiatric indications (OCD and major depression) and pain (DBS). Despite the advantages of directly visualizing the target structure, the technology is demanding and is vulnerable to inaccuracies especially since it is performed on individual level. In this contribution, we will focus on tremor and psychiatric indications, and will show future applications of sophisticated tractography applications for subthalamic nucleus (STN) DBS surgery and stimulation steering as an example.

Psychiatric neuroimaging research in Brazil: historical overview, current challenges, and future opportunities

The last four decades have witnessed tremendous growth in research studies applying neuroimaging methods to evaluate pathophysiological and treatment aspects of psychiatric disorders around the world. This article provides a brief history of psychiatric neuroimaging research in Brazil, including quantitative information about the growth of this field in the country over the past 20 years. Also described are the various methodologies used, the wealth of scientific questions investigated, and the strength of international collaborations established. Finally, examples of the many methodological advances that have emerged in the field of in vivo neuroimaging are provided, with discussion of the challenges faced by psychiatric research groups in Brazil, a country of limited resources, to continue incorporating such innovations to generate novel scientific data of local and global relevance.

Incisionless MR-guided focused ultrasound: technical considerations and current therapeutic approaches in psychiatric disorders.

INTRODUCTION: MR-guided focused ultrasound operating at higher intensities have been reported to effectively and precisely ablate deeper brain structures like the basal ganglia or the thalamic nuclei for the treatment of refractory movement disorders, neuropathic pain and most recently neuropsychiatric disorders, while low-intensity focused ultrasound represents an approach promoting mechanical blood-brain-barrier opening and neuromodulation. This narrative review summarizes the technical development and the therapeutic potential of incisionless MRgFUS in order to treat neuropsychiatric disorders. AREAS COVERED: A narrative review of clinical trials assessing the safety and efficacy of MRgFUS. A literature review was performed using the following search terms: MR-guided focused ultrasound, psychiatric disorders, noninvasive and invasive brain modulation/stimulation techniques. EXPERT OPINION: MRgFUS ablation is under clinical investigation (unblinded study design) for obsessive-compulsive disorders (OCDs) [capsulotomy; ALIC] and depression/anxiety disorders [capsulotomy] and has demonstrated an improvement in OCD and depression, although of preliminary character. Low-intensity ultrasound applications have been explored in Alzheimer´s disease (phase 1 study) and healthy subjects. Currently, limited evidence hinders comparison and selection between MRgFUS and noninvasive/invasive brain modulation therapies. However, comparative, sham-controlled trials are needed to reexamine the preliminary findings for the treatment of psychiatric disorders.

Red Blood Cell Indices in Relation to Post-stroke Psychiatric Disorders: A Longitudinal Study in a Follow-up Stroke Clinic.

BACKGROUND: Depression and anxiety after stroke are common conditions that are likely to be neglected. Abnormal red blood cell (RBC) indices may be associated with neuropsychiatric disorders. However, the association of RBC indices with post-stroke depression (PSD) and poststroke anxiety (PSA) has not been sufficiently investigated. METHODS: We aimed to investigate the trajectory of post-stroke depression and anxiety in our follow- up stroke clinic at 1, 3, and 6 months, and the association of RBC indices with these. One hundred and sixty-two patients with a new diagnosis of ischemic stroke were followed up at 1, 3, and 6 months, and underwent Patient Health Questionnaire-9 (PHQ-9) and the general anxiety disorder 7-item (GAD-7) questionnaire for evaluation of depression and anxiety, respectively. First, we used Kaplan-Meier analysis to investigate the accumulated incidences of post-stroke depression and post-stroke anxiety. Next, to explore the association of RBC indices with psychiatric disorders after an ischemic stroke attack, we adjusted for demographic and vascular risk factors using multivariate Cox regression analysis. RESULTS: Of the 162 patients with new-onset of ischemic stroke, we found the accumulated incidence rates of PSD (1.2%, 17.9%, and 35.8%) and PSA (1.2%, 13.6%, and 15.4%) at 1, 3, and 6 months, respectively. The incident PSD and PSA increased 3 months after a stroke attack. Multivariate Cox regression analysis indicated independent positive associations between PSD risk and higher mean corpuscular volume (MCV) (OR=1.42, 95% CI=1.16-1.76), older age (OR=2.63, 95% CI=1.16-5.93), and a negative relationship between male sex (OR=0.95, 95% CI=0.91-0.99) and PSA. CONCLUSION: The risks of PSD and PSA increased substantially 3 months beyond stroke onset. Of the RBC indices, higher MCV, showed an independent positive association with PSD.

Neurodevelopmental and Psychiatric Symptoms in Patients with a Cyst Compressing the Cerebellum: an Ongoing Enigma.

A patient diagnosed with developmental delay, intellectual disability, and autistic and obsessive-compulsive symptoms was found to have a posterior fossa arachnoid cyst (PFAC) compressing the cerebellum. The patient was referred to our Ataxia Unit for consideration of surgical drainage of the cyst to improve his clinical constellation. This scenario led to an in-depth analysis including a literature review, functional resting-state MRI analysis of our patient compared to a group of controls, and genetic testing. While it is reasonable to consider that there may be a causal relationship between PFAC and neurodevelopmental or psychiatric symptoms in some patients, there is also a nontrivial prevalence of PFAC in the asymptomatic population and a significant possibility that many PFAC are incidental findings in the context of primary cognitive or psychiatric symptoms. Our functional MRI analysis is the first to examine brain function, and to report cerebellar dysfunction, in a patient presenting with cognitive/psychiatric symptoms found to have a structural abnormality compressing the cerebellum. These neuroimaging findings are inherently limited due to their correlational nature but provide unprecedented evidence suggesting that cerebellar compression may be associated with cerebellar dysfunction. Exome gene sequencing revealed additional etiological possibilities, highlighting the complexity of this field of cerebellar clinical and scientific practice. Our findings and discussion may guide future investigations addressing an important knowledge gap-namely, is there a link between cerebellar compression (including arachnoid cysts and possibly other forms of cerebellar compression such as Chiari malformation), cerebellar dysfunction (including fMRI abnormalities reported here), and neuropsychiatric symptoms?

A Survey of Molecular Imaging of Opioid Receptors.

The discovery of endogenous peptide ligands for morphine binding sites occurred in parallel with the identification of three subclasses of opioid receptor (OR), traditionally designated as µ, δ, and κ, along with the more recently defined opioid-receptor-like (ORL1) receptor. Early efforts in opioid receptor radiochemistry focused on the structure of the prototype agonist ligand, morphine, although N-[methyl-11C]morphine, -codeine and -heroin did not show significant binding in vivo. [11C]Diprenorphine ([11C]DPN), an orvinol type, non-selective OR antagonist ligand, was among the first successful PET tracers for molecular brain imaging, but has been largely supplanted in research studies by the µ-preferring agonist [11C]carfentanil ([11C]Caf). These two tracers have the property of being displaceable by endogenous opioid peptides in living brain, thus potentially serving in a competition-binding model. Indeed, many clinical PET studies with [11C]DPN or [11C]Caf affirm the release of endogenous opioids in response to painful stimuli. Numerous other PET studies implicate µ-OR signaling in aspects of human personality and vulnerability to drug dependence, but there have been very few clinical PET studies of µORs in neurological disorders. Tracers based on naltrindole, a non-peptide antagonist of the δ-preferring endogenous opioid enkephalin, have been used in PET studies of δORs, and [11C]GR103545 is validated for studies of κORs. Structures such as [11C]NOP-1A show selective binding at ORL-1 receptors in living brain. However, there is scant documentation of δ-, κ-, or ORL1 receptors in healthy human brain or in neurological and psychiatric disorders; here, clinical PET research must catch up with recent progress in radiopharmaceutical chemistry.

Prevalence of neuropsychiatric symptoms associated with malformations of cortical development.

PURPOSE: Malformations of cortical development (MCD) are structural abnormality of the cortex or brain parenchyma with diverse clinical manifestations. Little is known about the association of psychiatric and behavioral problems in MCD. We aimed to determine prevalence and risk factors of neuropsychiatric symptoms in a cohort of adult patients with MCD. METHODS: We conducted a retrospective medical records review of 86 adult patients followed at the epilepsy clinic of the Montreal Neurological Hospital. Information on diagnosis of medical and psychiatric disorders, family history, intellectual disability, and psychiatric symptoms was obtained from their medical records. RESULTS: The cohort (n = 86) had a mean age of 39 ±â€¯14.07 (range: 18-74) years. The three most common MCD subtypes were focal cortical dysplasia (47.7%), periventricular nodular heterotopia (29.1%), and polymicrogyria (16.3%). Overall, prevalence of formally diagnosed psychiatric disorders and psychiatric symptoms were respectively 15.1% and 31.4%. The most frequently described symptoms were anxiety-related (59.3%), followed by irritability (40.7%) and agitation (37.0%). Patients with family psychiatric history (OR: 8.168, 95% CI: 1.44-46.48) and intellectual disability (OR: 5.824, 95% CI: 1.30-26.10) were significantly more likely to have psychiatric symptoms than those without. The prevalence of psychiatric symptoms did not defer between major groups of MCD. CONCLUSIONS: Neuropsychiatric symptoms are commonly associated with MCD, but psychiatric disorders may be underrecognized given that only half of the patients with psychiatric symptoms were referred for a specialized consultation. The presence of intellectual disability and family psychiatric history may help identify and predict risk of psychiatric manifestations in MCD.

Pallidal deep brain stimulation combined with capsulotomy for Tourette's syndrome with psychiatric comorbidity.

OBJECTIVE: A current challenge is finding an effective and safe treatment for severely disabled patients with Tourette's syndrome (TS) and comorbid psychiatric disorders, in whom conventional treatments have failed. The authors aimed to evaluate the utility of globus pallidus internus deep brain stimulation (GPi-DBS) combined with bilateral anterior capsulotomy in treating these clinically challenging patients. METHODS: The authors conducted a retrospective review of the clinical history and outcomes of 10 severely disabled patients with treatment-refractory TS and a psychiatric comorbidity, who had undergone GPi-DBS combined with bilateral anterior capsulotomy in their hospital. At the time of surgery, patients presented mainly with obsessive-compulsive disorder and affective disorders. Clinical outcome assessments of tic and psychiatric symptoms, as well as of general adaptive functioning and quality of life, were performed at the time of surgery and at 6, 12, and between 24 and 96 months postsurgery. RESULTS: After surgery, all patients showed significant progressive improvements in tic and psychiatric symptoms, along with improvements in general adaptive functioning and quality of life. Tic alleviation reached 64% at 12 months and 77% at the last follow-up on the Yale Global Tic Severity Scale. At the final follow-up, patients had functionally recovered and displayed no or only mild tic and psychiatric symptoms. All patients tolerated treatment reasonably well, with no serious side effects. CONCLUSIONS: GPi-DBS combined with bilateral anterior capsulotomy seems to offer major clinical benefits to severely disabled patients with otherwise treatment-refractory TS and psychiatric comorbidities.

Improvement of Hypothalamic Hamartoma-Related Psychiatric Disorder After Stereotactic Laser Ablation: Case Report and Review of Literature.

BACKGROUND: Hypothalamic hamartomas (HHs) are nonneoplastic congenital malformations associated with refractory epilepsy and behavioral disorders. Improvement in behavioral functioning following resection of HHs has been reported. Stereotactic laser ablation (SLA), a minimally invasive technique, has been used for the treatment of HH-related epilepsy. We report the case of child with an HH, gelastic seizures, and severe psychiatric dysfunction who was successfully treated via SLA therapy. CASE DESCRIPTION: The patient was an 11-year-old female with a history of central hypothyroidism, precocious puberty, and localization-related epilepsy thought to be secondary to an HH. She had a significant psychiatric history including attention deficit hyperactivity disorder, depressed mood, impulsivity, threatening behavior, and suicidal ideation requiring management with dexmethylphenidate, bupropion, and aripiprazole. Seizure onset occurred at age 7, and her semiology included nighttime hypermotor seizures and uncontrollable laughing spells thought to be gelastic seizures. Her hypermotor seizures were successfully managed with oxcabazepine monotherapy, but she continued to have several weekly laughing spells and self-harming behavior. Her HH was successfully treated via SLA. Postoperatively, she remained neurologically intact and was discharged the next day. At her 6-month follow-up, she had a markedly improved affect and general mood. At 3 years postprocedure, she remains seizure free and has been weaned off her antiepileptic and antipsychotic medications. CONCLUSIONS: Severe behavioral dysfunction in the setting of an HH may constitute an indication for surgical intervention. The outcome of this case suggests there may be a role for SLA in the management of HH-related psychiatric dysfunction, even in patients with good seizure control.

Psychiatric Symptoms in Refractory Epilepsy During the First Year After Surgery.

Psychiatric morbidity in drug-resistant epilepsy is frequent. Surgery is the best therapeutic alternative for treating seizures, but the current evidence concerning the effects of surgery on psychiatric disorders (PDs) is inconclusive. We aim to clarify surgery's role in long-term PDs. Using a prospective controlled study, we analyzed the psychopathologic outcomes of patients with drug-resistant epilepsy, comparing those who underwent surgery to those who did not due to not being suitable. Surgical candidates were paired (n = 84) with the immediately following nonsurgical candidates (n = 68). Both groups continued their usual medical treatment. We studied psychiatric changes for each group and analyzed de novo and remission cases. The assessments were made during the presurgical evaluation, and at 6 months (6-M) and 12 months (12-M) after surgery. Finally, we determined associated factors for postsurgical PDs. At 12 months, using the Hospital Anxiety and Depression Scale (HADS), anxiety improved in both groups (p = 0.000), while depression improved only in the surgical group (p = 0.016). Moreover, all symptom dimensions on the Symptom Checklist-90-R (SCL-90), as well as severity, distress, and total symptoms, decreased only in the surgical group. These ameliorations reached not only statistical significance but also clinical significance for depression (HADS) (p = 0.014) and the interictal dysphoric disorder (p = 0.013). The main predictors for PDs after surgery were as follows: the presurgical and 6-month psychiatric symptoms, the absence of surgery, seizure outcomes, and some antiepileptic and psychiatric drugs. This study provides evidence that surgery for epilepsy could have a role in improving some symptoms of psychiatric disorders 12-M after the surgery.

Visual symptom provocation in skin picking disorder: an fMRI study.

Skin-picking disorder (SPD) is a common mental disorder characterized by recurrent and excessive picking of dermatological irregularities. Different disorder models have been developed to explain this behavior, but empirical evidence is still scarce. One model (the disgust-related disease avoidance model) suggests that SPD might be understood as pathological grooming elicited by skin imperfections that singal possible infection. Twenty-five women with SPD and 19 matched controls viewed and rated images depicting skin irregularities and smooth skin during functional magnetic resonance imaging. The participants did not engage in picking behavior. Relative to controls, SPD patients reported more disgust and urge to pick when looking at skin irregularities. This was accompanied by greater activation in the insula and amygdala, and stronger insula-putamen coupling. Disgust feelings elicited by viewing skin irregularities were positively correlated with activation of the insula and the putamen, in the clinical group. On personality questionnaires, the SPD patients reported elevated self-loathing and problems in regulating their disgust feelings. The current study provides first evidence for altered disgust processing in SPD patients.

Relevance of neuroimaging for neurocognitive and behavioral outcome after pediatric traumatic brain injury.

This study aims to (1) investigate the neuropathology of mild to severe pediatric TBI and (2) elucidate the predictive value of conventional and innovative neuroimaging for functional outcome. Children aged 8-14 years with trauma control (TC) injury (n = 27) were compared to children with mild TBI and risk factors for complicated TBI (mildRF+, n = 20) or moderate/severe TBI (n = 17) at 2.8 years post-injury. Neuroimaging measures included: acute computed tomography (CT), volumetric analysis on post-acute conventional T1-weighted magnetic resonance imaging (MRI) and post-acute diffusion tensor imaging (DTI, analyzed using tract-based spatial statistics and voxel-wise regression). Functional outcome was measured using Common Data Elements for neurocognitive and behavioral functioning. The results show that intracranial pathology on acute CT-scans was more prevalent after moderate/severe TBI (65%) than after mildRF+ TBI (35%; p = .035), while both groups had decreased white matter volume on conventional MRI (ps ≤ .029, ds ≥ -0.74). The moderate/severe TBI group further showed decreased fractional anisotropy (FA) in a widespread cluster affecting all white matter tracts, in which regional associations with neurocognitive functioning were observed (FSIQ, Digit Span and RAVLT Encoding) that consistently involved the corpus callosum. FA had superior predictive value for functional outcome (i.e. intelligence, attention and working memory, encoding in verbal memory and internalizing problems) relative to acute CT-scanning (i.e. internalizing problems) and conventional MRI (no predictive value). We conclude that children with mildRF+ TBI and moderate/severe TBI are at risk of persistent white matter abnormality. Furthermore, DTI has superior predictive value for neurocognitive out-come relative to conventional neuroimaging.

Early psychiatric morbidity in a Brazilian sample of acute ischemic stroke patients

OBJECTIVE: Stroke is a major public health problem worldwide, and its neuropsychiatric sequelae are frequent and disabling. Furthermore, there is evidence that these sequelae impair recovery. Brazil has the highest stroke rates in Latin America, but data on the frequency of neuropsychiatric disorders in these patients are scarce. This study aimed to identify mental disorders among in-hospital patients with acute ischemic stroke. METHODS: The Mini International Neuropsychiatric Interview-Plus (MINI-Plus) was applied to 60 patients during the first week of hospitalization. RESULTS: Psychiatric disorders were diagnosed in 55% of the patients. A wide range of neuropsychiatric disorders have been identified, mainly mood and anxiety disorders. Specifically, we identified major depression (26.7%), alcohol abuse or dependence (11.7%), specific phobia (8.3%), generalized anxiety disorder (6.7%), psychosis (5.0%), social phobia (3.3%), adjustment disorder (3.3%) and panic disorder (1.7%). CONCLUSION: Psychiatric comorbidity should be evaluated as part of the rehabilitation of stroke patients and should be carefully examined by physicians.

Disruption of behavior and brain metabolism in artificially reared rats.

Early adverse life stress has been associated to behavioral disorders that can manifest as inappropriate or aggressive responses to social challenges. In this study, we analyzed the effects of artificial rearing on the open field and burial behavioral tests and on GFAP, c-Fos immunoreactivity, and glucose metabolism measured in anxiety-related brain areas. Artificial rearing of male rats was performed by supplying artificial milk through a cheek cannula and tactile stimulation, mimicking the mother's licking to rat pups from the fourth postnatal day until weaning. Tactile stimulation was applied twice a day, at morning and at night, by means of a camel brush on the rat anogenital area. As compared to mother reared rats, greater aggressiveness, and boldness, stereotyped behavior (burial conduct) was observed in artificially reared rats which occurred in parallel to a reduction of GFAP immunoreactivity in somatosensory cortex, c-Fos immunoreactivity at the amygdala and primary somatosensory cortex, and lower metabolism in amygdala (as measured by 2-deoxi-2-[18 fluoro]-d-glucose uptake, assessed by microPET imaging). These results could suggest that tactile and/or chemical stimuli from the mother and littermates carry relevant information for the proper development of the central nervous system, particularly in brain areas involved with emotions and social relationships of the rat. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1413-1429, 2017.

Multimodal and simultaneous assessments of brain and spinal fluid abnormalities in chronic fatigue syndrome and the effects of psychiatric comorbidity.

The purpose of this study was to investigate whether CFS patients without comorbid psychiatric diagnoses differ from CFS patients with comorbid psychiatric diagnoses and healthy control subjects in neuropsychological performance, the proportion with elevated spinal fluid protein or white cell counts, cerebral blood flow (CBF), brain ventricular lactate and cortical glutathione (GSH). The results of the study did not show any differences in any of the outcome measures between CFS patients with and without psychiatric comorbidity, thus indicating that psychiatric status may not be an exacerbating factor in CFS. Importantly, significant differences were found between the pooled samples of CFS compared to controls. These included lower GSH and CBF and higher ventricular lactate and rates of spinal fluid abnormalities in CFS patients compared to healthy controls. Thirteen of 26 patients had abnormal values on two or more of these 4 brain-related variables. These findings, which replicate the results of several of our prior studies, support the presence of a number of neurobiological and spinal fluid abnormalities in CFS. These results will lead to further investigation into objective biomarkers of the disorder to advance the understanding of CFS.