Background: Outpatient physicians in private practice, as inpatient physicians, are on the frontline of the COVID19 pandemic. Mental-health consequences of the pandemic on hospital staff have been published, but the psychological distress among outpatient physicians in private practice due to COVID-19 has never been specifically assessed. Methods: A French national online cross-sectional survey assessed declared psychological distress among outpatient physicians in private practice linked to COVID-19, sociodemographic and work conditions, mental health (Copenhagen Burn-out Inventory, Hospital Anxiety and Depression Scale, and the Insomnia severity Index), consequences on alcohol, tobacco, and illegal substance misuse, and sick leave during the 2nd COVID-19 wave. Findings: Among the 1,992 physicians who answered the survey, 1,529 (76.8%) declared psychological distress linked to COVID-19. Outpatient physicians who declared psychological distress linked to COVID-19 had higher rates of insomnia (OR = 1.4; CI95 [1.1-1.7], p = 0.003), burnout (OR = 2.7; CI95 [2.1; 3.2], p < 0.001), anxiety and depressive symptoms (OR = 2.4; CI95 [1.9-3.0], p < 0.001 and OR = 1.7; CI95 [1.3-2.3], p < 0.001) as compared to physicians who did not. They also had higher psychotropic drug use in the last twelve months, or increased alcohol or tobacco consumption due to work-related stress and were more frequently general practitioners. Interpretation: The feeling of being in psychological distress due to COVID-19 is highly frequent among outpatient physicians in private practice and is associated with mental health impairment. There is a need to assess specific interventions dedicated to outpatient physicians working in private practice.

Background Lithium (Li) is the gold standard treatment for bipolar disorder (BD). However, its mechanisms of action remain unknown but include neurotrophic effects. We here investigated the influence of Li on cortical and local grey matter (GM) volumes in a large international sample of patients with BD and healthy controls (HC). Methods We analyzed high-resolution T1-weighted structural magnetic resonance imaging scans of 271 patients with BD type I (120 undergoing Li) and 316 HC. Cortical and local GM volumes were compared using voxel-wise approaches with voxel-based morphometry and SIENAX using FSL. We used multiple linear regression models to test the influence of Li on cortical and local GM volumes, taking into account potential confounding factors such as a history of alcohol misuse. Results Patients taking Li had greater cortical GM volume than patients without. Patients undergoing Li had greater regional GM volumes in the right middle frontal gyrus, the right anterior cingulate gyrus, and the left fusiform gyrus in comparison with patients not taking Li. Conclusions Our results in a large multicentric sample support the hypothesis that Li could exert neurotrophic and neuroprotective effects limiting pathological GM atrophy in key brain regions associated with BD.

Panic disorder in the elderly is an understudied disorder, despite being associated with substantial functional impairment, a diminished quality of life and an increased suicide risk in this population. This disorder is likely to be underdiagnosed and sometimes inadequately treated due to the absence of national and international guidelines for this vulnerable population. Few therapeutic trials have specifically focused on the efficacy and tolerability of pharmacological and psychotherapy treatments for panic disorder in the elderly and current approaches to detect and manage this disorder are mainly based on expert opinions or extrapolation from data available on younger adults. This report aims to provide a summary of current knowledge on pharmacological and psychotherapeutic treatments for panic disorder in the elderly and to propose a medical treatment algorithm, which should be viewed as a tool that may contribute to the choice of treatment, especially for treatment-resistant older patients with panic disorder. The main results here are the emphasis on antidepressant treatment, such as selective serotonin reuptake inhibitor (SSRI), restricted benzodiazepine usage, awareness of drug interactions and the importance of psychotherapy such as cognitive behavioural therapy (CBT).

BACKGROUND: Lithium (Li) is a first-line treatment for bipolar disorder (BD). To study its cerebral distribution and association with plasma concentrations, we used Li-7 magnetic resonance imaging at 7T in euthymic patients with BD treated with Li carbonate for at least 2 years. METHODS: Three-dimensional Li-7 magnetic resonance imaging scans (N = 21) were acquired with an ultra-short echo-time sequence using a non-Cartesian k-space sampling scheme. Lithium concentrations ([Li]) were estimated using a phantom replacement approach accounting for differential T-1 and T-2 relaxation effects. In addition to the determination of mean regional [Li] from 7 broad anatomical areas, voxel-and parcellation-based group analyses were conducted for the first time for Li-7 magnetic resonance imaging. RESULTS: Using unprecedented spatial sensitivity and specificity, we were able to confirm the heterogeneity of the brain Li distribution and its interindividual variability, as well as the strong correlation between plasma and average brain [Li] ([Li](B) approximate to 0.40 x [Li](P), R = .74). Remarkably, our statistical analysis led to the identification of a well-defined and significant cluster corresponding closely to the left hippocampus for which high Li content was displayed consistently across our cohort. CONCLUSIONS: This observation could be of interest considering 1) the major role of the hippocampus in emotion processing and regulation, 2) the consistent atrophy of the hippocampus in untreated patients with BD, and 3) the normalization effect of Li on gray matter volumes. This study paves the way for the elucidation of the relationship between Li cerebral distribution and its therapeutic response, notably in newly diagnosed patients with BD.

OBJECTIVE:The cerebellum is involved in cognitive processing and emotion control. Cerebellar alterations could explain symptoms of schizophrenia spectrum disorder (SZ) and bipolar disorder (BD). In addition, literature suggests that lithium might influence cerebellar anatomy. Our aim was to study cerebellar anatomy in SZ and BD, and investigate the effect of lithium.METHODS:Participants from 7 centers worldwide underwent a 3T MRI. We included 182 patients with SZ, 144 patients with BD, and 322 controls. We automatically segmented the cerebellum using the CERES pipeline. All outputs were visually inspected.RESULTS:Patients with SZ showed a smaller global cerebellar gray matter volume compared to controls, with most of the changes located to the cognitive part of the cerebellum (Crus II and lobule VIIb). This decrease was present in the subgroup of patients with recent-onset SZ. We did not find any alterations in the cerebellum in patients with BD. However, patients medicated with lithium had a larger size of the anterior cerebellum, compared to patients not treated with lithium.CONCLUSION:Our multicenter study supports a distinct pattern of cerebellar alterations in SZ and BD.

Fronto-limbic white matter (WM) abnormalities are assumed to lie at the heart of the pathophysiology of bipolar disorder (BD); however, diffusion tensor imaging (DTI) studies have reported heterogeneous results and it is not clear how the clinical heterogeneity is related to the observed differences. This study aimed to identify WM abnormalities that differentiate patients with BD from healthy controls (HC) in the largest DTI dataset of patients with BD to date, collected via the ENIGMA network. We gathered individual tensor-derived regional metrics from 26 cohorts leading to a sample size of N = 3033 (1482 BD and 1551 HC). Mean fractional anisotropy (FA) from 43 regions of interest (ROI) and average whole-brain FA were entered into univariate mega- and meta-analyses to differentiate patients with BD from HC. Mega-analysis revealed significantly lower FA in patients with BD compared with HC in 29 regions, with the highest effect sizes observed within the corpus callosum ( R 2 = 0.041, P corr < 0.001) and cingulum (right: R 2 = 0.041, left: R 2 = 0.040, P corr < 0.001). Lithium medication, later onset and short disease duration were related to higher FA along multiple ROIs. Results of the meta-analysis showed similar effects. We demonstrated widespread WM abnormalities in BD and highlighted that altered WM connectivity within the corpus callosum and the cingulum are strongly associated with BD. These brain abnormalities could represent a biomarker for use in the diagnosis of BD. Interactive three-dimensional visualization of the results is available at www.enigma-viewer.org.

Objectives: Despite evidence of low representativeness of clinical trial results for depression in adults, the generalizability of clinical trial results for late-life depression is unknown. This study sought to quantify the representativeness of pharmacologic and psychotherapy clinical trial results for late-life unipolar depression. Method: Data were derived from the 2004-2005 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a nationally representative sample of 34,653 adults from the United States population. To assess the generalizability of clinical trial results for late-life depression, we applied a standard set of eligibility criteria representative of pharmacologic and psychotherapy clinical trials to all individuals aged 65 years and older in NESARC with a DSM-IV diagnosis of MDE and no lifetime history of mania/hypomania (n = 273) and in a subsample of individuals seeking help for depression (n = 78). Results: More than four of ten respondents and about two of ten respondents would have been excluded by at least one exclusion criterion in a typical pharmacologic and psychotherapy efficacy trial, respectively. Similar results (i.e.41.1% and 25.9%, respectively) were found in the subsample of individuals seeking help for depression. Excess percentage of exclusion in typical pharmacologic studies was accounted for by the criterion "significant medical condition". We also found that populations typically included in pharmacologic and psychotherapy clinical trials for late-life unipolar depression may substantially differ. Conclusion: Psychotherapy trial results may be representative of most patients with late-life unipolar depression in routine clinical practice. By contrast, pharmacologic clinical trials may not be readily generalizable to community samples.

Lithium is used as a first line treatment in bipolar disorder. The neuroprotective effects of lithium in this indication tend to be well known and are mediated by its action on two enzymes: glycogen synthase kinase-3 and inositol monophosphatase-1. Preclinical and clinical studies seek to evaluate the neuroprotective effect of lithium in neurodegenerative disorders. The aims of this literature review is to gather clinical studies that investigated the efficacy of lithium in neurodegenerative diseases, using a systematic method based on PubMed data. Results were found concerning Alzheimer's disease and related dementias, Huntington's disease, amyotrophic lateral sclerosis and spino-cerebellar ataxia. Lithium exposure showed a potential neuroprotective effect in studies on psychiatric populations with a lower prevalence of Alzheimer's disease in exposed patients. In patients with mild cognitive impairment, lithium would be associated with clinical improvement and a lower level of cerebrospinal phosphorylated tau protein. Lithium would allow at least a partial improvement in symptoms, including suicidal thoughts, in Huntington's disease. Despite several positive case reports and short studies, further controlled researches have failed to substantiate any positive effects of lithium exposure in amyotrophic lateral sclerosis. In spinocerebellar ataxia, introduction of lithium may be of benefits in terms of improvement of cerebellar symptoms. Large randomized controlled trials are required to asses the effect of early exposure lithium in these indications, based on reliable biological markers of disease.

OBJECTIVES:Brain sulcation is an indirect marker of neurodevelopmental processes. Studies of the cortical sulcation in bipolar disorder have yielded mixed results, probably due to high variability in clinical phenotype. We investigated whole-brain cortical sulcation in a large sample of selected patients with high neurodevelopmental load.METHODS:A total of 263 patients with bipolar disorder I and 320 controls were included in a multicentric magnetic resonance imaging (MRI) study. All subjects underwent high-resolution T1-weighted brain MRI. Images were processed with an automatized pipeline to extract the global sulcal index (g-SI) and the local sulcal indices (l-SIs) from 12 a priori determined brain regions covering the whole brain. We compared l-SI and g-SI between patients with and without early-onset bipolar disorder and between patients with and without a positive history of psychosis, adjusting for age, gender and handedness.RESULTS:Patients with early-onset bipolar disorder had a higher l-SI in the right prefrontal dorsolateral region. Patients with psychotic bipolar disorder had a decreased l-SI in the left superior parietal cortex. No group differences in g-SI or l-SI were found between healthy subjects and the whole patient cohort. We could replicate the early-onset finding in an independent cohort.CONCLUSIONS:Our work suggests that bipolar disorder is not associated with generalized abnormalities of sulcation, but rather with localized changes of cortical folding restricted to patients with a heavy neurodevelopmental loading. These findings support the hypothesis that bipolar disorder is heterogeneous but may be disentangled using MRI, and suggest the need for investigations into neurodevelopmental deviations in the disorder.

Objectives. - Ghrelin is an orexigenic digestive hormone that plays a role in sleep and memory. Our work aims is to synthesize the effects of ghrelin on appetite, sleep and memory, and also to evidence its role in depressive disorders. Methods. - A systematic search was carried out on PubMed with no time boundaries. The following MeSH terms were used: ghrelin AND (appetite regulation OR obesity), (sleep wake disorders OR sleep) (memory OR cognition disorders) (depression OR depressive disorder OR mood disorder). Results. - Ghrelin triggers appetite and alters meal patterns by making them longer and richer. This can lead to pathologies, obesity and insulin-resistance. Ghrelin seems to have a favourable effect on sleep in human beings. It tends to make sleep more efficacious and better quality. Finally, it seems to have an effect on synaptic plasticity in the zones involved in memory and it has been shown to improve memory capacity in rodents. Regarding depression, the administration of ghrelin leads to an anti-depressive effect in animals and in humans. Conversely, post anti-depressant ghrelin titrations have generally shown a decrease in ghrelin levels. Resistant patients seem to retain high levels. Finally, the seriousness of depression could be related to ghrelin levels. Conclusion. - Ghrelin plays a probable part in depression, especially for particular endophenotypes. A better understanding of ghrelin in depression could potentially help to optimize future therapeutic treatments. (C) 2017 L'Encephale, Paris.

Background Pioglitazone, a selective agonist of the nuclear transcription factor peroxisome proliferator-activated receptor-gamma (PPAR-γ), prescribed for the treatment of type 2 diabetes, could have antidepressant properties. However, its potential to induce remission of major depressive episodes, the optimal clinical target for an antidepressant drug, is a matter of concern. Indeed, only one out of four double-blind randomized controlled trials show higher remission rates with pioglitazone than with control treatments. Hence, the main aim of this study was to perform a meta-analysis of the efficacy of pioglitazone for the treatment of MDE, focusing on remission rates. Methods Four double-blind randomized controlled trials, comprising 161 patients with an MDE, were included in this meta-analysis. Pioglitazone was studied either alone (one study) or as add-on therapy to conventional treatments (antidepressant drugs or lithium salts). It was compared either to placebo (three studies) or to metformin (one study). Remission was defined by a Hamilton Depression Rating Scale score <8 after treatment. Results Pioglitazone could induce higher remission rates than control treatments (27% versus 10%, I2=17.3%, fixed-effect model: odds ratio [OR] =3.3, 95% confidence interval [95% CI; 1.4; 7.8], P=0.008). The OR was even higher in the subgroup of patients with major depressive disorder (n=80; 23% versus 8%, I2=0.0%; fixed-effect model: OR =5.9, 95% CI [1.6; 22.4], P=0.009) and in the subgroup of patients without metabolic comorbidities (n=84; 33% versus 10%, I2=0.0%; fixed-effect model: OR =5.1, 95% CI [1.5; 17.9], P=0.01). As compared to control treatments, results suggest six patients would need to be treated with pioglitazone in order to achieve the possibility of one more remission. Conclusion Pioglitazone, either alone or as add-on therapy to conventional treatments, could induce remission of MDE, suggesting that drugs with PPAR-γ agonist properties may be true and clinically relevant antidepressants, even in patients without metabolic comorbidities.

We performed RNA sequencing (RNA-Seq) at ten successive developmental stages in embryos of the common house spider Parasteatoda tepidariorum. Two independent datasets from two pairs of parents represent the normalized coverage of mapped RNA-Seq reads along scaffolds of the P. tepidariorum genome assembly. Transcript abundance was calculated against existing AUGUSTUS gene models. The datasets have been deposited in the Gene Expression Omnibus (GEO) Database at the National Center for Biotechnology Information (NCBI) under the accession number GSE112712.

After suicidal attempt, the rate of specialized out treatment engagement (SOTE) does not exceed 30-50%. We designed a multisite prospective naturalistic study, in order to investigate predictive factors of SOTE after emergency department discharge among 107 suicidal attempters without current psychiatric ambulatory care. Both bivariate and multivariate analyses highlighted that booking an appointment with a mental health professional before discharge was significantly associated with higher SOTE rate. Psychiatric caregivers of emergency departments should be informed that this approach is a simple, fast way to improve SOTE among this population.

Introduction: Selective agonists of the nuclear transcription factor peroxisome proliferator-activated receptor-gamma (PPAR-γ) are used for the treatment of type 2 diabetes. We reviewed their efficacy and safety for the treatment of major depression and the association of their potential antidepressant effects with changes in biomarkers of metabolism and inflammation. Methods: From 8 studies, 4 open-label trials, and 4 randomized controlled trials (RCT) (3 vs. placebo and 1 vs. metformin), 448 patients with major depression were included, of which 209 patients received PPAR-γ agonists (pioglitazone or rosiglitazone) for 6-12 weeks, either alone or in add-on therapy to conventional treatments. Results: PPAR-γ agonists have antidepressant effects in the 4 open-label studies and in 3 out of 4 RCT. No major adverse event was reported. Improvement in depression scores was associated with improvement in 3 biomarkers of insulin resistance (homeostatic model assessment [HOMA-IR], oral glucose tolerance test, and fasting plasma glucose) and 1 biomarker of inflammation (interleukin-6) among 21 biomarkers studied. Conclusion: PPAR-γ agonists may have antidepressant properties, which need to be assessed in further studies of major depressive episodes.

Des données expérimentales et cliniques suggèrent que les thiazolidinediones (TZD), agonistes sélectifs du facteur de transcription nucléaire PPAR-gamma, exercent une action antidépressive. Nous avons réalisé une revue et une méta-analyse évaluant l’efficacité et la tolérance des TZD dans les épisodes dépressifs majeurs (EDM), en précisant les liens entre leurs effets antidépresseurs et leurs impacts métaboliques et inflammatoires. Sept études ont été sélectionnées dans Pubmed. Parmi les 230 patients avec EDM inclus, 150 ont reçu une TZD pendant 6 à 12 semaines. Dans les 4 études randomisées contre placebo, la pioglitazone a été comparée au placebo ou à la metformine. Dans les 3 essais ouverts, les patients ont reçu de la pioglitazone ou de la rosiglitazone. La sévérité de la dépression a été mesurée sur des échelles standardisées. L’emploi des TZD s’associe à une amélioration des symptômes de dépression. La méta-analyse des essais randomisés montre un taux de rémission nettement plus élevé avec la pioglitazone en comparaison du placebo (OR = 5,97 ; IC 95 % (1,90 ;18,80) ; z = 3,10 ; p = 0,002). Aucun effet secondaire n’a été enregistré sur cette courte période de suivi. Il existe une corrélation entre les changements des scores de dépression et ceux de biomarqueurs de l’insulinorésistance et de l’inflammation. Ce travail montre l’efficacité anti-dépressive et la bonne tolérance des TZD dans le traitement à court terme de l’EDM. Des études doivent se poursuivre afin de développer de nouveaux agonistes du PPAR-gamma pour traiter l’EDM.

Back to table of contents Previous article Next article LettersFull AccessDifferential Response to ECT of Psychotic and Affective Symptoms in Huntington's Disease: A Case ReportAnne-Cécile Petit, Ph.D., Franz Hozer, M.D., Katia Youssov, M.D., Pierre Lavaud, M.D., Patrick Hardy, M.D., Ph.D., Fayçal Mouaffak, M.D., Ph.D.Anne-Cécile Petit, Ph.D., Franz Hozer, M.D., Katia Youssov, M.D., Pierre Lavaud, M.D., Patrick Hardy, M.D., Ph.D., Fayçal Mouaffak, M.D., Ph.D.Published Online:27 Jan 2016https://doi.org/10.1176/appi.neuropsych.15040084AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Huntington's disease (HD) is a neurodegenerative disorder characterized by abnormal choreatic movements, subcortical dementia, and psychiatric symptoms. Psychiatric disorders encountered in HD include major depressive disorder, anxiety disorders, or isolated symptoms such as apathy or irritability in 33%−76% of patients. Psychotic disorders affect 3%−11% of patients.1 Although psychiatric symptomatology often precedes motor symptoms,2 there is a dearth of data regarding psychiatric care in HD.3The case reported here refers to a patient suffering from HD, major depressive disorder, and psychotic symptomatology. This patient displayed a very poor tolerance to clozapine treatment and differential results with electroconvulsivotherapy (ECT) with remission of major depressive disorder symptoms and a slight improvement in motor symptoms, but there was no effect on psychotic symptoms.Case ReportMr. E, a 60-year-old patient with HD, was brought to the emergency department for marked anxiety, depressed mood, major sleep disturbance, and marked weight loss. He planned to commit suicide by defenestration. He claimed to be under the surveillance of a spy network that used earpieces and hacked his electronic devices. Interestingly, the patient was partially convinced by his ideas. Motor symptoms consisted of choreatic movements of the head and extremities and moderate dysarthria. Initial neuropsychiatric assessment is shown in Table 1. The Mini-Mental State Examination z-score was calculated using norms provided by Crum et al.4 Results on CT scan showed a moderate degree of generalized cerebral atrophy.TABLE 1. Neuropsychiatric Assessment of HD at Admission, After 12 ECT Sessions, and After 1 Year of CareaScaleMaximal ScorePatient AssessmentAdmissionAfter 12 ECT SessionsAfter 1 YearPsychiatric assessment MADRS60477— BPRS-E1688838— CGI765—HD assessment (using the UHDRS) Motor symptoms124473757 Behavioral abnormalities885426— Functional assessment50413642 Independence scale100456055 Total functional capacity5234Cognitive assessment (using the MMSE) Raw score3024—— z scoreb0–2.35——aBPRS-E, expanded version of the Brief Psychiatric Rating Scale; CGI, Clinical Global Impression; HD, Huntington's disease; MADRS, Montgomery-Åsberg Depression Rating Scale; MMSE, Mini-Mental State Examination; UHDRS, Unified Huntington's Disease Rating Scale.bThe MMSE z-score was calculated using the norms provided by Crum et al.4 For this patient (aged 60 years and with an education level of 12 years), the mean MMSE score is 28±1.7.TABLE 1. Neuropsychiatric Assessment of HD at Admission, After 12 ECT Sessions, and After 1 Year of CareaEnlarge tableAt age 40 years, the patient developed major depressive disorder associated with persecutory delusional symptoms. The duration of the episode led to the diagnosis of late-onset schizoaffective disorder. During 20 years of care, the disease showed a particular refractoriness to all psychopharmacologic strategies implemented (antidepressants, neuroleptics, atypical antipsychotics, and mood stabilizers). No family history of psychosis or neurologic disorders has been reported.At age 59 years, the patient displayed abnormal writhing movements suggestive of HD, which prompted evaluation for this condition. Genetic testing found a CAG repeat size of 23 for the normal allele and 41 for the HD allele, thus confirming the diagnosis of HD.When the patient was admitted, clozapine was introduced and was titrated up to 350 mg per day in association with mirtazapine. At a dosage of clozapine of 350 mg daily, the patient experienced acute mental confusion, circadian rhythm reversal, restlessness, and a worsening of dysarthria and abnormal movements. All side effects disappeared after the clozapine was stopped (Naranjo score=8). An ECT course was implemented, with 18 ECT sessions. At the 12th session, Mr. E's symptoms were markedly improved, with complete disappearance of major depressive disorder symptoms and suicidal ideation. However, he was still having delusional ideas (Table 1).A continuation course and a maintenance course were decided: the frequency of sessions was progressively decreased to one session every 6 weeks. The patient was maintained with mirtazapine (30 mg per day). At 1 year later, no depressive relapse was observed but delusional symptoms remained unchanged (Table 1).DiscussionThis patient's presentation is remarkable for the long latency between symptom onset and identification of the underlying cause of the symptoms. The diagnosis of HD may explain, at least in part, the marked refractoriness of the patient's psychotic and depressive symptoms to pharmacologic treatments. Although psychiatric symptoms are known to be prodromal symptoms of HD,5 the very long latency between severe psychiatric symptoms and the onset of motor symptoms observed in this patient is uncommon. Nonetheless, the onset of symptoms suggestive of schizoaffective disorder at age 40 years should have prompted, in retrospect, evaluation for a neurologic cause of the patient's psychiatric symptoms. Perhaps most noteworthy is the differential response of the patient's psychotic and depressive symptoms to ECT.Other case reports describing major depressive disorder treatment in patients with HD showed positive results with mirtazapine and fluoxetine contrary to tricyclic antidepressants. Atypical antipsychotic drugs, such as risperidone and clozapine,6 showed good results for treating psychotic dimension. In this case, clozapine induced a worsening of motor symptoms with no efficacy on psychotic symptoms, which is contradictory to the data available in the literature.There are 14 reports of patients with HD with affective symptoms treated by ECT7 in the literature. ECT was effective and well tolerated in 13 of 14 cases. As for psychotic disorders, the five cases reported in the literature8 show positive results of ECT. The available studies often lack standardized assessment of psychopathologic improvement. Here, validated psychiatric scales (Montgomery-Åsberg Depression Rating Scale, Brief Psychiatric Rating Scale–Expanded, and Clinical Global Impressions Scale) were used to assess response to ECT. The Unified Huntington's Disease Rating Scale,9 which was developed as a clinical rating scale to assess four domains of clinical performance and capacity in HD: motor function, cognitive function, behavioral abnormalities, and functional capacity, was also used. To our knowledge, this case is the first to show a psychotic resistance to ECT in patients with HD. As for motor symptoms, these data provide clues for the safety of the procedure for nonpsychiatric features.HD motor symptoms are linked to a massive loss of striatal GABAergic medium spiny neurons. One current hypothesis consists of the involvement of excitotoxic neuronal death mediated by altered glutamatergic neurotransmission.10 Moreover, striatal medium spiny neurons expressing dopamine receptors are known to be mainly affected in the early stage of HD.11 Altered dopamine signaling may then play a key role in the pathogenesis of HD. In this case, the patient displayed psychotic and affective symptoms at the prodromal stage of HD. One may speculate that mesocorticolimbic dopaminergic projection may be implicated in these early symptoms. The hyperdopaminergic state in mesolimbic regions known to be involved in delusional disorders may lead to the loss of long-range GABAergic projections from the ventral tegmental area, making these structures unresponsive to antipsychotic treatment and ECT. However, such a mechanism cannot be extended to the regions involved in affective symptoms,12 in which a hypodopaminergic state—as well as a depletion in serotonin and norepinephrine—is observed. This may explain the differential response observed here, with potentially less severe GABAergic neuronal degeneration in the regions involved in affective symptoms, such as the long-range projections from the raphe nuclei. This leads to the hypothesis that the degenerative process may progress at various speeds according to the structures, or that slightly different degenerative processes are at work according to the affected structures. These hypotheses are, however, speculative because the imaging data from the patient show only a generalized cerebral atrophy. Large-scale neuroimaging studies are needed to identify the structural and functional neuroanatomic abnormalities in HD according to the various psychiatric symptoms observed.This case report is the first to describe a refractory psychotic symptomatology to clozapine and ECT in a patient with HD. The differences with other case reports may be explained by the possible existence of subtypes of HD. Moreover, this case underscores the importance of psychiatrists to take into account the possibility of a primary organic disorder in late-onset and atypical disorders.Hôpital Bicêtre, Assistance Publique Hôpitaux de Paris, Univ. Paris Sud XI, INSERM U1178, Département de Psychiatrie, Le-Kremlin Bicêtre, France (A-CP, FH, PL, PH, FM); and Centre de référence Maladie de Huntington, Hôpital Henri Mondor, Créteil, France (KY).Send correspondence to Dr. Petit; e-mail: [email protected]The authors report no financial relationships with commercial interests.References1 van Duijn E, Kingma EM, van der Mast RC: Psychopathology in verified Huntington's disease gene carriers. J Neuropsychiatry Clin Neurosci 2007; 19:441–448Link, Google Scholar2 Amann B, Sterr A, Thoma H, et al.: Psychopathological changes preceding motor symptoms in Huntington's disease: a report on four cases. World J Biol Psychiatry 2000;1:55–58.Crossref, Medline, Google Scholar3 Bonelli RM, Hofmann P: A systematic review of the treatment studies in Huntington's disease since 1990. Expert Opin Pharmacother 2007; 8:141–153Crossref, Medline, Google Scholar4 Crum RM, Anthony JC, Bassett SS, et al.: Population-based norms for the Mini-Mental State Examination by age and educational level. JAMA 1993; 269:2386–2391Crossref, Medline, Google Scholar5 Di Maio L, Squitieri F, Napolitano G, et al.: Onset symptoms in 510 patients with Huntington's disease. J Med Genet 1993; 30:289–292Crossref, Medline, Google Scholar6 Sajatovic M, Verbanac P, Ramirez LF, et al.: Clozapine treatment of psychiatric symptoms resistant to neuroleptic treatment in patients with Huntington's chorea. Neurology 1991; 41:156Crossref, Medline, Google Scholar7 Beale MD, Kellner CH, Gurecki P, et al.: ECT for the treatment of Huntington's disease: a case study. Convuls Ther 1997; 13:108–112Medline, Google Scholar8 Nakano T, Ono S, Yamaguchi J, et al.: Modified electroconvulsive therapy for the treatment of refractory schizophrenia-like psychosis associated with Huntington's disease. J Neurol 2013; 260:312–314Crossref, Medline, Google Scholar9 Huntington Study Group: Unified Huntington's Disease Rating Scale: reliability and consistency. Mov Disord 1996; 11:136–142Crossref, Medline, Google Scholar10 Estrada Sánchez AM, Mejía-Toiber J, Massieu L: Excitotoxic neuronal death and the pathogenesis of Huntington's disease. Arch Med Res 2008; 39:265–276Crossref, Medline, Google Scholar11 van Oostrom JC, Dekker M, Willemsen AT, et al.: Changes in striatal dopamine D2 receptor binding in pre-clinical Huntington's disease. Eur J Neurol 2009; 16:226–231Crossref, Medline, Google Scholar12 Koutsouleris N, Meisenzahl EM, Borgwardt S, et al.: Individualized differential diagnosis of schizophrenia and mood disorders using neuroanatomical biomarkers. Brain 2015; 138:2059–2073Crossref, Medline, Google Scholar FiguresReferencesCited byDetailsCited byNon-Invasive Neuromodulation Methods to Alleviate Symptoms of Huntington's Disease: A Systematic Review of the Literature2 March 2023 | Journal of Clinical Medicine, Vol. 12, No. 5Electroconvulsive therapy in Huntington's disease8 November 2021 | Progress in Neurology and Psychiatry, Vol. 25, No. 4Cerebellar Grey Matter Volume in Older Persons Is Associated with Worse Cognitive Functioning20 August 2020 | The Cerebellum, Vol. 20, No. 1Management of Agitation in Huntington's Disease: A Review of the LiteratureCureusTreating Depression and Suicidality in Huntington's DiseasePsychiatric Annals, Vol. 50, No. 2Worsening of movement disorder following treatment with electroconvulsive therapy in a patient with Huntington's disease10 August 2019 | BMJ Case Reports, Vol. 12, No. 8Huntington disease: A quarter century of progress since the gene discoveryJournal of the Neurological Sciences, Vol. 396Journal of Huntington's Disease, Vol. 8, No. 3EMC - Neurologia, Vol. 18, No. 2Case Reports in Psychiatry, Vol. 2018Frontiers in Neurology, Vol. 9Treatment of Agitation in Huntington's Disease With Electroconvulsive TherapyRohit Praful Shah, M.D., Vinod Alluri, M.D., Sarita Sharma, M.D.25 January 2017 | The Journal of Neuropsychiatry and Clinical Neurosciences, Vol. 29, No. 3Clozapine12 November 2016 | Reactions Weekly, Vol. 1627, No. 1 Volume 28Issue 1 Winter 2016Pages e3-e5 Metrics PDF download History Received 11 April 2015 Revised 7 June 2015 Accepted 20 June 2015 Published online 27 January 2016 Published in print 1 January 2016

Background: Bipolar disorder heterogeneity is large, leading to difficulties in identifying neuropathophysiological and etiological mechanisms and hindering the formation of clinically homogeneous patient groups in clinical trials. Identifying markers of clinically more homogeneous groups would help disentangle BD heterogeneity. Neuroimaging may aid in identifying such groups by highlighting specific biomarkers of BD subtypes or clinical dimensions.Methods: We performed a systematic literature search of the neuroimaging literature assessing biomarkers of relevant BD phenotypes (type-I vs. II, presence vs. absence of psychotic features, suicidal behavior and impulsivity, rapid cycling, good vs. poor medication response, age at onset, cognitive performance and circadian abnormalities).Results: Consistent biomarkers were associated with suicidal behavior, i.e. frontal/anterior alterations (prefrontal and cingulate grey matter, prefrontal white matter) in patients with a history of suicide attempts; and with cognitive performance, i.e. involvement of frontal and temporal regions, superior and inferior longitudinal fasciculus, right thalamic radiation, and corpus callosum in executive dysfunctions. For the other dimensions and sub-types studied, no consistent biomarkers were identified.Limitations: Studies were heterogeneous both in methodology and outcome.Conclusions: Though theoretically promising, neuroimaging has not yet proven capable of disentangling subtypes and dimensions of bipolar disorder, due to high between-study heterogeneity. We issue recommendations for future studies. (C) 2016 Elsevier B.V. All rights reserved.

Depression is a severe and heterogeneous disorder resulting from interacting genetic, environmental, and epigenetic factors. Nutrient deficiency resulting from bariatric bypass surgery has been involved in the pathophysiological mechanisms of depression and treatment response.We report the case of a patient who developed, after a bariatric bypass surgery, a severe depressive episode, refractory to both pharmacological treatment and electroconvulsivotherapy (ECT). Folate deficiency was evidenced. A dramatic response to ECT was observed after folate supplementation.We focused on the involvement of folate in the pathophysiological mechanisms of depression and response to both pharmacological treatment and ECT. We emphasize on the need for close monitoring of patients experiencing psychiatric disorder (in particular, depressive unipolar disorder) after bariatric surgery.

Mouaffak, Fayçal MD, PhD; Hozer, Franz MD; Delomel, Olivia MD; Hardy, Patrick MD Author Information