Manic-depressive Psychosis as the Initial Symptom in Adult Siblings with Late-onset Combined Methylmalonic Aciduria and Homocystinemia, Cobalamin C Type

Methylmalonic aciduria （MMA） is an autosomal recessive disorder of cobalamin （cbl） metabolism. Cobalamin C （cblC） disease is the most common type of MMA and is characteristically concurrent with homocystinemia （HCY） due to impaired synthesis of two active forms of cbl, namely adenosylcobalamin （AdoCbl） and methylcobalamin （MeCbl）. The estimated worldwide incidence of MMA ranges between 1：48,000 and 1：250,000. Mutations of the MMA and HCY type C protein （MMACtfC） gene are responsible for cblC disease and were first identified by Lerner-Ellis et aL in 2006.By the year 2016, more than 82 different MMACHC gene mutations have been reported （http：// www.hgmd.cf.ac.uk/ac/index.php）. Among these mutations, c.609G〉A （p.W203X） was reported to be the most frequent cblC mutation in Chinese patients.

“Well-Track”: Fitbit Based Physical Activity and Sleep Hygiene Intervention for Early Intervention in Psychosis (EIP) and At-Risk Mental State (ARMS) Service Patients

Background: Compared to the general population, people who are at a high risk of or experience severe mental illness (SMI) such as psychosis, are more likely to have low levels of physical activity, high levels of sedentary behaviour, and sleep problems. Intervention: The Well-Track intervention comprises a wearable activity and sleep tracker (Fitbit);one session with mental health service staff providing physical activity and sleep hygiene advice;a brief motivational interview;completing a goal setting workbook;and one or two further engagement, feedback and discussion sessions. Participants: Twenty-four participants using an early intervention in psychosis (EIP) or at-risk mental state (ARMS) service completed an eight-week, three session intervention (14 males and 10 females), with an age range of 18 - 61, and average age of 27.75 years. Methods: An open-label patient cohort design with no control group. Pre-intervention, 4-week and 8-week intervention assessments using participant self-report measures: Patient Health Questionnaire (PHQ-9) (depression), Warwick–Edinburgh Mental Wellbeing Scale (WEMWBS), and Sleep Conditioning Index (SCI);and clinician measurement of body weight. Results: Mean scores showed a significant improvement in PHQ-9 from 9.29 (SD 5.89) to 5.58 (SD 3.68) at 4 weeks and to 5.83 (SD 4.40) at 8 weeks, with large effect sizes. For those who met a diagnosis of depression at baseline, at 4 week follow-up seven participants (26%) experienced remission and nine (33%) reliable improvement, and at 8 week follow-up four (21%) experienced remission and seven (37%) reliable improvement. WEMWBS scores significantly improved, from 44.04 (SD 9.44) to 48.54 (SD 8.71) at 4 weeks and to 48.67 (SD 8.76) at 8 weeks, with large effect sizes. Body weight did not change significantly, remaining unchanged at 4 weeks and reduced from a mean of 82.8 kg (baseline) to 80.15 kg at 8 weeks, a reduction of 2.65 kg. Conclusion: Well-Track was integrated into an EIP and ARMS service and was found to be beneficial in terms of wellbeing, depression, sleep, and preventing weight gain (either as a two or three engagement point intervention). Well-Track could be delivered through EIP and ARMS services to promote healthy lifestyle behaviours.

Experience and Impact of the “Well-Track” Physical Activity and Sleep Tracker Based Healthy Lifestyle Intervention for Patients in an Early Intervention in Psychosis (EIP) Service

Background: Physical activity and sleep are interconnected with mental health, physical health, wellbeing, quality of life, cognition, and functioning. Compared to the general population, people who experience psychosis are more likely to have low levels of physical activity, high levels of sedentary behaviour, and sleep problems. Intervention: The Well-Track intervention addresses these issues through: provision of a wearable activity and sleep tracker (Fitbit);physical activity and sleep hygiene advice;a brief motivational interview;a goal-setting workbook;and three engagement, feedback and discussion sessions with early intervention in psychosis (EIP) staff. Participants: Thirty participants using an EIP service took part in an eight-week intervention. Thirteen participants (6 males;7 females) with an age range of 18 to 61 years old (M = 28 years) took part in an interview. Methods: A qualitative approach was used to conduct in-depth semi-structured interviews. Thematic and content analyses were employed to analyse the data. Results: Participants set goals, made lifestyle changes to their daily routine and integrated a Fitbit and its functions into their lives that resulted in more physical activity and enabled more effective sleep. This resulted in improved self-management, positive feelings and thoughts, motivation, confidence, social engagement, mood, health, and wellbeing. Participants made progress towards goals they had set. Conclusion: Well-Track has been successfully integrated into an EIP service and it could be delivered through all EIP and other healthcare services where there is a need to promote healthy lifestyle behaviours.

Steroid-induced psychosis related to pituitary adenoma status post trans-sphenoid excision and a history of psychiatric illness:A case

BACKGROUND Steroid-induced psychosis is a common adverse effect of steroid exposure.Reported cases were mostly related to rheumatologic disease.Despite its high incidence,there is only one case reported related to perioperative steroid replacement for pituitary adenoma surgery.This manuscript presents the second case of such and compared the two with the latest literature review of steroidinduced psychosis.CASE SUMMARY This is a case of an adult male with a chief complaint of auditory hallucinations and was referred by Neurosurgery to Psychiatry Out-patient department.He was diagnosed with pituitary adenoma who underwent trans-sphenoid excision of the mass from which steroid exposure led to steroid-induced psychosis.Also,patient had a history of psychiatric illness of severe depressive episode.At the out-patient department,patient was started on antipsychotic,Risperidone,which led to eventual improvement of his symptoms.CONCLUSION The two cases of pituitary adenoma surgery with steroid-induced psychosis had almost similar clinical profile with the latest literature review of steroid-induced psychosis.However,the present case highlights the association of psychiatric illness in predisposing an individual in developing it.Also,this manuscript emphasizes that early recognition of steroid-induced psychosis leads to better prognosis.Multispecialty treatment is vital in the holistic management of the patient with timely referral and close coordination.

Inter-relationships between isotretinoin treatment and psychiatric disorders: Depression, bipolar disorder, anxiety, psychosis and suicide risks

Isotretinoin(Accutane) is a treatment for severe acne that is resistant to other forms of treatment, including antibiotics and topical treatments. The prescription of this drug has been controversial ever since its initial marketing in 1982. It is the only non-psychotropic drug in the Food and Drug Administration top 10 drugs found to be associated with depression. Recently, Bremner et al published an extensive review(until 2010) of the evidence for the association of retinoic acid(RA) with depression and suicide. Some patients who are admitted in psychiatric hospitals report a history of present or past treatment with isotretinoin. Then, the imputability of the molecule in the occurrence of disorders represents necessarily an important question for both professionals and their patients. This paper aims to specify the links between the drug and specific psychiatric disorders. A review of the literature related to isotretinoin, RA, vitamin A, depression, suicide, anxiety, bipolar disorder, psychosis, schizophrenia was performed. Many studies demonstrated an increased risk of depression, attempted suicide and suicide following isotretinoin treatment. However, isotretinoin may have an antidepressant impact, according to some dermatological papers. They consider treating acne with this efficient treatment could improve selfimage and make the patient feel better. Several studies showed that patients with bipolar disorder had an increased risk for a clinical exacerbation of symptoms undergoing treatment with isotretinoin. A few studies also seem to suggest a possible link between isotretinoin and psychosis. Nonetheless, studies point out a link between retinoid dysregulation and schizophrenia through modulation of dopamine receptors. From this review, we propose guidelines for isotretinoin prescription to healthcare professionals.

Evidence for using pimavanserin for the treatment of Parkinson’s disease psychosis

The aim of this editorial is to evaluate the evidence for using pimavanserin for the treatment of Parkinson's disease psychosis(PDP)from randomized controlled trials(RCTs).We only identified two published trials that evaluated the use of pimavanserin among individuals with PDP.Both studies found that pimavanserin improved psychotic symptoms among individuals with PDP when compared to placebo.Pimavanserin was fairly well tolerated in both studies and did not appear to cause significant sedation or worsen motor symptoms among individuals with PDP.However,given the limited data,additional confirmatory studies are required before pimavanserin can be considered as a first line agent for the treatment of psychotic symptoms among individuals with PD.

Successful treatment of psychosis induced by interferon alpha and ribavirin with paliperidone:first case reported

Several clinical studies have shown a large number of mental symptoms by immunomodulatory treatment with interferon (IFN). The most frequently described symptoms are depression, suicidal behaviour, manic symptoms, anxiety, psychosis and delirium, associated with other non-specific symptoms such as fatigue, irritability, psychomotor retardation, decreased libido, insomnia, difficulty in concentration and attention. Having a history of mental disorder contraindicates the use of IFN-alpha. These adverse effects that affect the mental state appear usually at the beginning of the treatment (most after 3 weeks of treatment). The incidence of psychotic episodes is low and the episodes usually remit when treatment is interrupted;only some cases require antipsychotic treatment. We present the case of a patient affected with hepatitis C who began to present self-referential delirious symptoms after receiving the treatment with IFN and who was successfully treated with paliperidone. This patient could be classified within the group of high-risk psychiatric patients given the family history of schizophrenia and his personal history of illegal drug consumption. The pharmacological actions of paliperidone are similar to other high potency atypical antipsychotics.丁he receptorbinding profile of paliperidone most closely resembles that of risperidone and ziprasidone. Paliperidone differs from risperidone and most other antipsychotics by its relatively low extent of enzymatic hepatic metabolism. To the best of our knowledge, this is the first case described that was successfully treated with paliperidone.

Artificial intelligence-assisted psychosis risk screening in adolescents:Practices and challenges

Artificial intelligence-based technologies are gradually being applied to psychiatric research and practice.This paper reviews the primary literature concerning artificial intelligence-assisted psychosis risk screening in adolescents.In terms of the practice of psychosis risk screening,the application of two artificial intelligence-assisted screening methods,chatbot and large-scale social media data analysis,is summarized in detail.Regarding the challenges of psychiatric risk screening,ethical issues constitute the first challenge of psychiatric risk screening through artificial intelligence,which must comply with the four biomedical ethical principles of respect for autonomy,nonmaleficence,beneficence and impartiality such that the development of artificial intelligence can meet the moral and ethical requirements of human beings.By reviewing the pertinent literature concerning current artificial intelligence-assisted adolescent psychosis risk screens,we propose that assuming they meet ethical requirements,there are three directions worth considering in the future development of artificial intelligenceassisted psychosis risk screening in adolescents as follows:nonperceptual realtime artificial intelligence-assisted screening,further reducing the cost of artificial intelligence-assisted screening,and improving the ease of use of artificial intelligence-assisted screening techniques and tools.

Why psychosis is frequently associated with Parkinson's disease?

Psychosis is a common non-motor symptom of Parkinson’s disease whose pathogenesis remains poorly understood. Parkinson’s disease in conjunction with psychosis has been shown to induce injury to extracorticospinal tracts as wel as within some cortical areas. In this study, Parkinson’s disease patients with psychosis who did not receive antipsychotic treatment and those without psychosis underwent diffusion tensor imaging. Results revealed that in Parkinson’s disease patients with psychosis, damage to the left frontal lobe, bilateral occipital lobe, left cingulated gyrus, and left hippocampal white-matter fibers were greater than damage to the substantia nigra or the globus pal idus. Damage to white-matter fibers in the right frontal lobe and right cingulate gyrus were also more severe than in the globus pal idus, but not the substantia nigra. Damage to frontal lobe and cingulate gyrus white-matter fibers was more apparent than that to occipital or hippocampal fiber damage. Compared with Parkinson’s disease patients without psychosis, those with psychosis had significantly lower fractional anisotropy ratios of left frontal lobe, bilateral occipital lobe, left cingu-lated gyrus, and left hippocampus to ipsilateral substantia nigra or globus pal idus, indicating more severe damage to white-matter fibers. These results suggest that psychosis associated with Par-kinson’s disease is probably associated with an imbalance in the ratio of white-matter fibers be-tween brain regions associated with psychiatric symptoms （frontal lobe, occipital lobe, cingulate gyrus, and hippocampus） and those associated with the motor symptoms of Parkinson’s disease （the substantia nigra and globus pal idus）. The relatively greater damage to white-matter fibers in psychiatric symptom-related brain regions than in extracorticospinal tracts might explain why psy-chosis often occurs in Parkinson’s disease patients.

Identification and predictive analysis for participants at ultra-high risk of psychosis:A comparison of three psychometric diagnostic interviews

BACKGROUND An accurate identification of individuals at ultra-high risk(UHR)based on psychometric tools to prospectively identify psychosis as early as possible is required for indicated preventive intervention.The diagnostic comparability of several psychometric tools,including the comprehensive assessment of at risk mental state(CAARMS),the structured interview for psychosis-risk syndrome(SIPS)and the bonn scale for the assessment of basic symptoms(BSABS),is unknown.AIM To address the psychometric comparability of CAARMS,SIPS and BSABS for subjects who are close relatives of patients with schizophrenia.METHODS In total,189 participants aged 18-58 years who were lineal relative by blood and collateral relatives by blood up to the third degree of kinship of patients with schizophrenia were interviewed in the period of May 2017 to January 2019.Relatives of the participants diagnosed schizophrenia were excluded.All the participants were assessed for a UHR state by three psychometric tools(CAARMS,SIPS and BSABS).The psychometric diagnosis results included at risk of psychosis(UHR+),not at risk of psychosis(UHR-)and psychosis.Demographic and clinical characteristics were also measured.The inter-rater agreement was assessed for evaluation of the coherence of the three scales.Transition rates for UHR+subjects to psychosis within 2 years were also recorded.RESULTS The overall agreement percentages were 93.12%,92.06%and 93.65%of CAARMS and SIPS,SIPS and BSABS and CAARMS and BSABS,respectively.The overall agreement percentage of the relative functional impairment of the three groups(UHR+,not at risk of psychosis and psychosis)were 89.24%,86.36%and 88.12%,respectively.The inter-rater reliability of the CAARMS,SIPS and BSABS total score was 0.90,0.89 and 0.85.The inter-rater reliability was very good to excellent for all the subscales of these three instruments.For CAARMS,SIPS and BSABS,the kappa coefficient about UHR criteria agreement was 0.87,0.84 and 0.82,respectively(P<0.001).The transition rates of UHR+to psychosis within 2 years were 16.7%(CAARMS),10.0%(SIPS)and 17.7%(BSABS).CONCLUSION There is good diagnostic agreement between the CAARMS,SIPS and BSABS towards identification of UHR participants who are close relatives of patients with schizophrenia.

Pimavanserin for the treatment of psychosis in Alzheimer’s disease: A literature review

BACKGROUND Alzheimer’s disease(AD)is among the most prevalent forms of dementia in the world and neuropathological studies suggest similar high prevalence of mixed(AD+vascular)dementias.Approximately 25%-50%of individuals with AD develop psychosis sometime during their illness.The presence of psychosis in AD worsens outcomes.Currently there are no United States Food and Drug Administration(FDA)approved medications for the treatment of psychosis in AD.Pimavanserin,a novel atypical antipsychotic medication,was approved by the FDA for the treatment of hallucinations and delusions associated with Parkinson disease psychosis and is currently in clinical trials for the treatment of psychosis in AD.AIM To evaluate the existing literature regarding the use of pimavanserin for treating psychosis among individuals with AD.METHODS A literature review of clinical studies of pimavanserin treatment for psychosis in individuals with AD was performed using the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines.Trials were identified by systematically searching PubMed,MEDLINE,EMBASE,Cochrane Central Register of Controlled Trials,Web of Science,and Scopus through October 2019.The 5-point Jadad scoring system was used to assess the methodologic quality of the randomized placebo-controlled trials.RESULTS A total of 499 citations were retrieved and pooled in EndNote and de-duplicated to 258 citations.This set was uploaded to Covidence for screening.Two separate screeners(Srinivasan S and Tampi RR)evaluated the titles,abstracts,and full text of eligible articles.Of the identified 258 abstracts,98 articles underwent full text review and 2 publications from 1 randomized controlled trial(RCT)were included in the final analysis.The quality of evidence was assessed to be of good methodologic quality,scoring 4 out of 5 using the 5-point Jadad questionnaire with the Jadad Scoring calculation.This systematic review found only one RCT that evaluated the use of pimavanserin for the treatment of psychosis among individuals with AD.This phase 2 trial resulted in two publications,the second of which was a subgroup analysis from the original study.The evidence from these two publications showed that pimavanserin improves psychotic symptoms among individuals with AD when compared to placebo at week 6.CONCLUSION Pimavanserin may be a pharmacologic consideration for the treatment for psychosis in AD.Additional RCTs are needed to assess the evidence of effectiveness before pimavanserin is considered a standard treatment.

Sustained attention in psychosis:Neuroimaging findings

To provide a systematic review of scientific literatureon functional magnetic resonance imaging(fMRI) stud-ies on sustained attention in psychosis. We searchedPubMed to identify fMRI studies pertaining sustainedattention in both affective and non-affective psycho-sis. Only studies conducted on adult patients using asustained attention task during fMRI scanning wereincluded in the final review. The search was conductedon September 10 th, 2013. 15 fMRI studies met our in-clusion criteria: 12 studies were focused on Schizophre-nia and 3 on Bipolar Disorder Type Ⅰ(BDI). Only halfof the Schizophrenia studies and two of the BDI stud-ies reported behavioral abnormalities, but all of themevidenced significant functional differences in brain re-gions related to the sustained attention system. Alteredfunctioning of the insula was found in both Schizophre-nia and BDI, and therefore proposed as a candidate trait marker for psychosis in general. On the other hand, other brain regions were differently impaired in affective and non-affective psychosis: alterations of cingulate cortex and thalamus seemed to be more common in Schizophrenia and amygdala dysfunctions in BDI. Neural correlates of sustained attention seem to be of great interest in the study of psychosis, highlight-ing differences and similarities between Schizophrenia and BDI.

Autoimmune thyroiditis presenting as psychosis

桥本氏甲状腺炎系一种罕见的自身免疫性疾病,血液中含有大量的自体抗体,主要表现为神经系统症状。有文献报道桥本氏甲状腺炎会出现一些行为症状,而没有明显的神经症状。我们报告的病例较少见,与其他的桥本氏甲状腺炎的常见临床表现不同。

Effects of age and sex on clinical high-risk for psychosis in the community

BACKGROUND Recent reports of both heightened prevalence rates and limited clinical relevance of clinical high-risk(CHR)criteria and their relevant symptoms in children and adolescents indicate an important role of neurodevelopment in the early detection of psychoses.Furthermore,sex effects in CHR symptoms have been reported,though studies were inconclusive.As sex also impacts on neurodevelopment,we expected that sex might have an additional contribution to age in the prevalence and clinical relevance of CHR symptoms and criteria.AIM To investigate age and sex effects on CHR criteria and symptoms and their association with psychosocial impairment and mental disorder.METHODS In this cross-sectional cohort study,n=29168-to 40-year-olds,randomly drawn from the population register of the Swiss canton Bern,were assessed in semistructured interviews by phone or face-to-face for CHR symptoms and criteria using the Structured Interview for Psychosis-Risk Syndromes and the Schizophrenia Proneness Instrument in its child and youth,and adult version,respectively.Furthermore,social and occupational functioning and DSM-IV axis I disorders were assessed.Simple and interaction effects of age and sex on CHR symptoms and criteria,and interaction effects of age,sex,and CHR symptoms and criteria on presentation of functional impairment and of non-psychotic disorder were investigated using logistic regression analyses.RESULTS Altogether,542(18.6%)participants reported any CHR symptom;of these,261(9.0%)participants reported any one of the 11 criteria relevant cognitive and perceptual basic symptoms,and 381(13.1%)any one of the five attenuated or transient psychotic symptoms(attenuated psychotic symptoms/brief intermittent psychotic symptoms).Fewer participants met any one of the CHR criteria(n=82,2.8%)or any one of the three recently recommended CHR criteria(n=38,1.3%).Both age and sex were significantly(P<0.05)associated with CHR symptoms and criteria,mostly by younger age and female sex.Though slightly differing between symptom groups,age thresholds were detected around the turn from adolescence to adulthood;they were highest for cognitive basic symptoms and CHR criteria.With the exception of the infrequent speech disorganization attenuated psychotic symptom,the interaction of age with CHR symptoms and criteria predicted functional impairment;whereas,independent of each other,sex and CHR symptoms mostly predicted mental disorders.CONCLUSION Age and sex differentially impact on CHR symptoms and criteria;these differences may support better understanding of causal pathways.Thus,future CHR studies should consider effects of sex and age.

Levels of oxidative stress parameters and the protective effects of melatonin in psychosis model rat testis

Aim： To evaluate the effects of melatonin on antioxidant enzyme levels and histopathologic changes in dizocilpine （MK-801）-induced psychosis model rat testis. Methods： A total of 24 adult male Wistar-Albino rats were divided into three groups with 8 in each. Group I was used as control. Rats in Group II were injected with MK-801 （0.5 mg/kg body weight i.p. for 5 days）. In addition to MK-801, melatonin （50 mg/kg body weight i.p. once a day for 5 days） was injected into the rats in Group Ⅲ. The testes were harvested bilaterally for biochemical and histopathological examinations. Antioxidant enzyme activities, malondialdehyde, protein carbonyl and nitric oxide （NO） levels in testicular tissues were analyzed using spectrophotometric analysis methods. Histopathological examinations of the testes were also performed. Results： MK-801 induced testicular damage, which resulted in significant oxidative stress （OS） by increasing the levels of antioxidant enzymes. The malondialdehyde, protein carbonyl and NO levels were increased in testicular tissues of rats. Treatment with melatonin led to significant decrease in oxidative injury. Administration of melatonin also reduced the detrimental histopathologic effects caused by MK-801. Conclusion： The results of the present study showed that MK-801 cause OS in testicular tissues of rats and treatment with melatonin can reduce the harmful effects＇of MK-801. （Asian JAndro12008 Mar; 10： 259-265）

Early psychological interventions for psychosis

The manuscript correspond to an editorial in order to assess the most important and effective interventions for people with psychosis in the early stages.

COMPARATIVE OBSERVATION ON TREATMENT OF PSYCHOSIS WITH ELECTRODE AND ELECTRO-ACUPUNCTURE CONTROLLED BY PROCESSORS

Nineteen patients suffering from common rnental diseases were treated by computer-ized electrode and electro-acupuncture. lt was revealed that 66. 7% of 9 cases treated by electrodewere rnarkedly effective without significant difference to the effective rate of 1O cases treated throughelectro-acupuncture (P】0. 05). The score of self anxiety scale in the patients treated by electrodewas markedly reduced, while the score of sleep state scale was markedly decreased in those patientstreated by electro-acupuncture. There was no side-effect in the surface electrode therapy l the patientswere without fear, and accepted it with m0re pleasure.

Eating disorders and psychosis: Seven hypotheses

Psychotic disorders and eating disorders sometimes occur in the same person, and sometimes, but not always, at the same time. This can cause diagnostic confusion and uncertainty about treatment. This paper examines seven ways in which symptoms of both conditions can co-exist. The literature on this topic consists to a large extent of case reports, so that firm conclusions cannot be drawn from their examination. There is no consistent sequence in the co-occurrence of the two conditions-eating disorders sometimes precede, and sometimes follow the onset of psychosis. The advent of the psychosis, and sometimes the treatment of the psychosis can cure the eating disorder, but it can sometimes aggravate it. Psychosis is not necessarily a mark of severity in the course of an eating disorder, and food refusal can occur independent of severity in psychotic illness, but it can be a cause of death. There is some genetic association and some overlap of physiologic, cognitive and brain structure deficits in the two types of disorder. The connection between the two, however, remains speculative. The area of comorbidity and overlapping symptoms in psychiatry requires more research. Clinical recommendations include attentionto the different individual ways in which these two disparate conditions often overlap.