Better understanding of c-reactive protein and leukocytes in psychiatric inpatients with affective disorders:A biopsychosocial approach

BACKGROUND Affective disorders(AD)have been linked to inflammatory processes,although the underlying mechanisms of this relationship are still not fully elucidated.It is hypothesized that demographic,somatic,lifestyle,and personality variables predict inflammatory parameters in AD.AIM To identify biopsychosocial factors contributing to inflammation in AD measured with two parameters,C-reactive protein(CRP)and leukocytes.METHODS This observational study investigated 186 hospital inpatients diagnosed with AD using demographic parameters,serum inflammatory markers,somatic variables,psychological questionnaires,and lifestyle parameters.Hierarchical regression analyses were used to predict inflammatory markers from demographic,somatic,lifestyle,and personality variables.RESULTS Analyses showed that 33.8%of the variance of CRP was explained by body mass index and other somatic medication(e.g.anti-diabetics),age and education,and age of affective disorder diagnosis.For leukocytes,20.1%of the variance was explained by smoking,diet,metabolic syndrome(MetS),and anti-inflammatory medication(e.g.non-steroidal anti-inflammatory drugs).Other psychiatric or behavioural variables did not reach significance.CONCLUSION Metabolic components seem important,with mounting evidence for a metabolic affective disorder subtype.Lifestyle modifications and psychoeducation should be employed to prevent or treat MetS in AD.

Preferences for participation in shared decision making of psychiatric outpatients with affective disorders

Objective: To assess preferences for participation in shared decision making in a representative sample of psychiatric outpatients with affective disorders and to understand how clinical and socio-demographic variables influence patients’ preferences for participation. Method: A cross-sectional survey of 172 consecutive psychiatric outpatients with affective disorders attending at Community Mental Health Care setting was carried out. Patients expressed preferences on each of 3 aspects of decision making (seeking information, discussing options, making the final decision). The “CGI Severity and Improvement Scales” and the “Beck Depression Inventory” scale were used for severity assessment. Additionally the “Drug Attitude Inventory”, the “Beliefs about Medicine Questionnaire” and the “Leeds Attitude toward Concordance Scale” were applied to all participants. Effects of variables considered on preferences were assessed using proportional odds regression models. Results: We registered a high response rate of 85%. Nearly all patients (91%) preferred to leave final decisions to their treating psychiatrists and 87% preferred to rely on psychiatrists for medical knowledge rather than seeking their own information. In contrast, 81% of patients preferred to be offered options and to be asked their opinion by their doctors. Gender, age, educational level, number of psychotropics used and belief about psychiatric medication overuse were significant predictors in decision making dimensions considered. Conclusion: Shared decision making approach of patients with affective disorder must take into consideration a more doctor-directed approach preferred by the patients in which the desire to be offered options is not automatically linked with the willingness of taking decisions or getting more knowledge.

White matter abnormalities:Insights into the pathophysiology of major affective disorders

The presence of white matter hyperintensities(WMHs) has been commonly associated with poor outcome in subjects with major affective disorders. Unfortunately, WMHs may be frequently confounded by the use of psychoactive medications and duration of illness. Al-though findings from the current literature are quite conflicting, we proposed that subjects with WMHs may be at higher suicidal risk when compared to other sub-groups without. Based on the Fazekas modified scale, the severity of WMHs may serve as a trait marker of disease. Interestingly, the presence of WMHs may rep-resent a neurobiological marker between the underlying vulnerability and clinical presentation of major affective disorders.

Psychological impact of the COVID-19 pandemic on individuals with serious mental disorders: A systematic review of the literature

BACKGROUND The coronavirus disease 2019(COVID-19)pandemic is having a great impact on individuals from all over the world,particularly on individuals with mental disorders.Several studies found more pronounced psychiatric symptoms,notably symptoms of depression and anxiety.AIM To assess the situation of patients with serious mental illness(SMI:Affective disorders and schizophrenia)regarding their mental health outcome during the pandemic.METHODS A systematic search using the databases PubMed and MEDLINE was conducted,employing the key words“COVID-19”,“SARS-CoV-2”,“psychiatric/mental disorder/illness”,“affective/mood disorder”,“bipolar disorder”,“(major)depression”,“schizoaffective disorder”,and“schizophrenia”.Studies that had been published up until January 9,2021 were included.Information of studies in languages other than English and German was mostly taken from their English abstracts.RESULTS The literature search concluded in the finding of 36 studies containing relevant clinical data.A general impairment of the mental health of individuals with SMI could be detected,particularly in individuals with affective disorders,as compared to those with schizophrenia.Compared to healthy controls,symptoms of anxiety,depression,and stress were more pronounced in individuals with SMI.Relevant factors found that impacted their mental health were age,resilience,and socioeconomic environment,especially the shortage of mental health services,lack of social support,and inadequate information about COVID-19.CONCLUSION In light of these results,mental health services should be reinforced,notably the use of telemental health services.Furthermore,supplying individuals with SMI with adequate information about the COVID-19 pandemic and increasing their resilience is important.When researching the impact of the COVID-19 pandemic on individuals with SMI,standardization as well as follow-up studies are needed to enable better comparability and understanding.

Transmission of NOTCH4 and GRIK2 in a population of Han Chinese with schizophrenia and affective disorder

BACKGROUND： Increasing evidence suggests overlapped genetic susceptibility across traditional classification systems that divided psychotic disorders into schizophrenia or affective disorder. OBJECTIVE： This study aimed to explore whether schizophrenia and affective disorder share genetic susceptibility in NOTCH4 and GRIK2 loci in a population of Han Chinese. DESIGN： Repetitive measurements. SETTING： The experiment was carried out at Shanghai Mental Health Center and Hongkou Mental Health Center of Shanghai between January 2001 and June 2004. PARTICIPANTS： Sixty-five mixed pedigrees （suffering from various diseases, in combination with schizophrenia and affective disorder）, composed of 45 completed trios and 20 single-parent families, were selected from Shanghai Mental Health Center and Hongkou Mental Health Center of Shanghai between January 2001 and June 2004. Probands received clinical diagnosis according to ICD-10; an independent clinician used identical criteria to review all diagnoses. All subjects were Han Chinese in origin and provided informed consent. There were 65 probands and 110 parents among the subjects. The probands comprised 30 males and 35 females： 33 with schizophrenia, 32 with affective disorder, mean age of （30.9 ± 9.8） years, mean age of onset （24.3 ± 8.8） years, mean duration （6.6 ± 7.0） years, and mean age of parents （58.8 ±10.9） years. METHODS： DNA samples from probands and their biological parents were extracted from peripheral blood according to standard methods. Four polymorphisms, -1725T/G and -25T/C in NOTCH4, rs6922753T/C and rs2227283G/A in GRIK2, were amplified and genotyped with PCR-RFLP techniques. MAIN OUTCOME MEASURES： Association between NOTCH4, GRIK2 polymorphism, and schizophrenia was analyzed by transmission disequilibrium test （TDT）. RESULTS： Sixty-five probands and 110 parents were included in the result analysis, with no dropouts. The results showed that the -25T/C polymorphism of NOTCH4 associated significantly with affective disorder and -1725G/-25T haplotype with schizophrenia. SNP rs6922753 of GRIK2 did not associate with the two diseases; SNP rs2227283 and haplotypes, TG and CA, were significantly associated with both diseases. CONCLUSION： Schizophrenia and affective disorder might share genetic susceptibility among mixed pedigrees of the Han Chinese population. NOTCH4 and GRIK2 might be two of the most common susceptibility genes for these psychoses.

False dogmas in mood disorders research:Towards a nomothetic network approach

The current understanding of major depressive disorder(MDD)and bipolar disorder(BD)is plagued by a cacophony of controversies as evidenced by competing schools to understand MDD/BD.The DSM/ICD taxonomies have cemented their status as the gold standard for diagnosing MDD/BD.The aim of this review is to discuss the false dogmas that reign in current MDD/BD research with respect to the new,data-driven,machine learning method to model psychiatric illness,namely nomothetic network psychiatry(NNP).This review discusses many false dogmas including:MDD/BD are mind-brain disorders that are best conceptualized using a bio-psycho-social model or mind-brain interactions;mood disorders due to medical disease are attributable to psychosocial stress or chemical imbalances;DSM/ICD are the gold standards to make the MDD/BD diagnosis;severity of illness should be measured using rating scales;clinical remission should be defined using threshold values on rating scale scores;existing diagnostic BD boundaries are too restrictive;and mood disorder spectra are the rule.In contrast,our NNP models show that MDD/BD are not mind-brain or psycho-social but systemic medical disorders;the DSM/ICD taxonomies are counterproductive;a shared core,namely the reoccurrence of illness(ROI),underpins the intertwined recurrence of depressive and manic episodes and suicidal behaviors;mood disorders should be ROI-defined;ROI mediates the effects of nitro-oxidative stress pathways and early lifetime trauma on the phenome of mood disorders;severity of illness and treatment response should be delineated using the NNP-derived causome,pathway,ROI and integrated phenome scores;and MDD and BD are the same illness.

Establishment and evaluation of a mouse model of affective disorder combined with atherosclerosis

Objective:To establish a mouse model of affective disorder complicated with atherosclerosis(AS)by high fat feeding and chronic mild unpredictable stimulation(CUMS),and to provide an animal model for the later study of the prevention and treatment of affective disorder complicated with atherosclerosis by traditional Chinese medicine.Methods:10 C57BL/6J mice were used as blank group,and 20 ApoE-/-mice were randomly divided into AS group and AS+CUMS group.After one week of adaptive feeding,except for the blank group,the other two groups were fed with high fat diet.Meanwhile,the AS+CUMS group was given chronic unpredictable mild stress.The model was evaluated after 16 weeks of modeling.During the experiment,the body weight,food intake,excitability,hair color and other general morphology of mice in each group were observed and recorded.Behavioral indexes(Sucrose preference tests and Open Field test)were detected in each group.The levels of 5-hydroxytryptamine(5-HT)and hypothalamic-pituitary-adrenal(HPA)axis hormones,including adrenocorticotropin(ACTH)and corticosterone(CORT),were detected by ELISA.Serum lipid levels,including total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C)and high density lipoprotein cholesterol(HDL-C),were detected by ELISA.HE staining was used to observe the pathological condition of aorta.Results:Compared with blank group,the excitability and food intake of AS+CUMS group were significantly decreased.There were no significant differences in sugar water consumption and activity capacity of mice in AS group,while sugar water consumption and activity capacity of mice in AS+CUMS group were significantly decreased(P<0.01).The serum 5-HT levels in AS group and AS+CUMS group were decreased,and the levels of ACTH and CORT in AS+CUMS group were significantly decreased(P<0.01),and the levels of ACTH and CORT in AS+CUMS group were significantly increased(P<0.01).The serum TC,TG and LDL-C levels of mice in AS group and AS+CUMS group were significantly increased(P<0.01),while the HDL-C level of mice in both groups was significantly decreased(P<0.01).HE staining results showed that the area and degree of plaques in the active vascular lumen of AS group and AS+CUMS group were larger and heavier.Conclusion:High fat feeding combined with CUMS was successful in establishing a mouse model of emotional disorder combined with atherosclerosis.

Parkinson’s disease and affective disorder: The temporal relationship

In relationship between the affective disorders and Parkinson’s disease (PD) it was found that comorbidity was higher than expected in the majority of the studies. Patients with PD are at increased risk of developing depression and, conversely, recent studies have shown that patients with depressive disorders have increased risk of incident PD. However, the temporal associations between the disorders are not fully elucidated. From this review it could be learned that the temporal aspects strongly suggest that a neurobiological association exists between affective disorder and PD. This is illustrated with hitherto unpublished data. Some of these issues may be investigated in case register studies, e.g. by linkage of registers of somatic and psychiatric illness, and suggestions for future research are given. For GP’s, psychiatrists, geriatricians, and neurologists these new findings will lead to a better understanding and better treatment for patients with complicated comorbid conditions. Here timing is important!

Rapid GFAP and Iba1 expression changes in the female rat brain following spinal cord injury

Evidence suggests that rapid changes to supporting glia may predispose individuals with spinal cord injury(SCI) to such comorbidities. Here, we interrogated the expression of astrocyte-and microglial-specific markers glial fibrillary acidic protein(GFAP) and ionized calcium binding adaptor molecule 1(Iba1) in the rat brain in the first 24 hours following SCI. Female Sprague-Dawley rats underwent thoracic laminectomy;half of the rats received a mild contusion injury at the level of the T10 vertebral body(SCI group), the other half did not(Sham group). Twenty-four hours post-surgery the amygdala, periaqueductal grey, prefrontal cortex, hypothalamus, lateral thalamus, hippocampus(dorsal and ventral) in rats were collected. GFAP and Iba1 m RNA and protein levels were measured by real-time quantitative polymerase chain reaction and Western blot. In SCI rats, GFAP m RNA and protein expression increased in the amygdala and hypothalamus. In contrast, gene and protein expression decreased in the thalamus and dorsal hippocampus. Interestingly, Iba1 transcripts and proteins were significantly diminished only in the dorsal and ventral hippocampus, where gene expression diminished. These findings demonstrate that as early as 24 hours post-SCI there are region-specific disruptions of GFAP and Iba1 transcript and protein levels in higher brain regions. All procedures were approved by the University of Technology Sydney Institutional Animal Care and Ethics Committee(UTS ACEC13-0069).

Implications from translational cross-validation of clinical assessment tools for diagnosis and treatment in psychiatry

Traditional therapeutic methods in psychiatry,such as psychopharmacology and psychotherapy help many people suffering from mental disorders,but in the long-term prove to be effective in a relatively small proportion of those affected.Therapeutically,resistant forms of mental disorders such as schizophrenia,major depressive disorder,and bipolar disorder lead to persistent distress and dysfunction in personal,social,and professional aspects.In an effort to address these problems,the translational approach in neuroscience has initiated the inclusion of novel or modified unconventional diagnostic and therapeutic techniques with promising results.For instance,neuroimaging data sets from multiple modalities provide insight into the nature of pathophysiological mechanisms such as disruptions of connectivity,integration,and segregation of neural networks,focusing on the treatment of mental disorders through instrumental biomedical methods such as electro-convulsive therapy(ECT),transcranial magnetic stimulation(TMS),transcranial direct current stimulation(tDCS)and deep brain stimulation(DBS).These methodologies have yielded promising results that have yet to be understood and improved to enhance the prognosis of the severe and persistent psychotic and affective disorders.The current review is focused on the translational approach in the management of schizophrenia and mood disorders,as well as the adaptation of new transdisciplinary diagnostic tools such as neuroimaging with concurrently administered psychopathological questionnaires and integration of the results into the therapeutic framework using various advanced instrumental biomedical tools such as ECT,TMS,tDCS and DBS.

Reduced paraoxonase 1 activities may explain the comorbidities between temporal lobe epilepsy and depression,anxiety and psychosis

BACKGROUND Temporal lobe epilepsy(TLE)is the most common focal epilepsy subtype in adults and is frequently accompanied by depression,anxiety and psychosis.Aberrations in total paraoxonase 1(PON1)status may occur in TLE and these psychiatric conditions.AIM To examine PON1 status,namely Q192R PON1 genotypes and PON1 enzymatic activities,in TLE.METHODS We recruited 40 normal controls and 104 TLE patients,27 without comorbidities and 77 with comorbidities including mood disorders(n=25),anxiety disorders(n=27)and psychosis(n=25).RESULTS Four-(chloromethyl)phenyl acetate hydrolysis(CMPAase)and arylesterase activities were significantly lower in TLE and mesial temporal sclerosis(MTS)with and without psychiatric comorbidities than those in normal controls.The areas under the receiver operating characteristic curve of CMPAase were 0.893(0.037)for TLE and 0.895(±0.037)for MTS.Partial least squares path analysis showed that there were specific indirect effects of PON1 genotype on TLE severity(P<0.0001)and psychopathology(P<0.0001),which were both mediated by lowered CMPAase activity,while arylesterase activity was not significant.The severity of TLE was significantly associated with psychopathology scores.Furthermore,PON1 CMPAase activity was inversely associated with Mini Mental State Examination score.CONCLUSION The severity of TLE and comorbidities are to a large extent explained by reduced PON1 enzyme activities and by effects of the Q192R genotype,which are mediated by reduced CMPAase activity.Total PON1 status plays a key role in the pathophysiology of TLE,MTS and psychiatric comorbidities by increasing the risk of oxidative toxicity.PON1 enzyme activities are new drug targets in TLE to treat seizure frequency and psychiatric comorbidities.

International study of the Complex Stress Reaction Syndrome:Implications for transdiagnostic clinical practice

BACKGROUND The debate regarding diagnostic classification systems in psychiatry(categorial vs dimensional systems)has essential implications for the diagnosis,prevention and treatment of stress reactions.We previously found a unique pattern of stress reaction in a study executed during the coronavirus disease 2019 pandemic using large representative samples in two countries,and termed it the Complex Stress Reaction Syndrome(CSRS).AIM To investigate CSRS,Type A(psychiatric symptoms,spanning anxiety,depression,stress symptoms,and posttraumatic stress disorder(PTSD)),with or without long-coronavirus disease(COVID)residuals(CSRS,Type B,neuropsychiatric symptoms spanning cognitive deficits and fatigue,excluding systemic symptoms).Our two-tailed hypothesis was that CSRS is a condition related to an unrecognized type of stress reaction in daily life in the general population(Type A)or that it is related to the severe acute respiratory syndrome coronavirus 2 infection and its long-COVID residuals(Type B).METHODS 977 individuals in four continents(North America,Europe,Australia and the Middle East)completed the online study questionnaire in six languages using the Qualtrics platform.The study was managed by six teams in six countries that promoted the study on social media.The questionnaire assessed anxiety,depression,stress symptoms and PTSD(CSRS,Type A),cognitive deficits and fatigue(CSRS,Type B).The data were analyzed using Proportion Analyses,Multivariate Analysis of Co-Variance(MANCOVA),linear regression analyses and validated clinical cutoff points.RESULTS The results of the Proportion Analyses showed that the prevalence of 4 symptoms spanning anxiety,depression,stress symptoms,and PTSD was significantly higher than the most prevalent combinations of fewer symptoms across 4 continents,age groups,and gender.This supports the transdiagnostic argument embedded in the CSRS(Type A).The same pattern of results was found in infected/recovered individuals.The prevalence of the 4 psychiatric symptoms combination was significantly greater than that of 5 and 6 symptoms,when adding cognitive deficits and fatigue,respectively.MANCOVA showed a significant three-way interaction(age×gender×continent).Further analyses showed that the sources of this three-way interaction were threefold relating to two sub-populations at-risk:(1)Individuals that self-identified as non-binary gender scored significantly higher on all 4 psychiatric symptoms of the CSRS,Type A at young age groups(<50 years old)in North America compared to(self-identified)women and men located in the 4 continents studied,and to other ages across the adult life span;and(2)This pattern of results(CSRS,Type A)was found also in women at young ages(<40 years old)in North America who scored higher compared to men and women in other continents and other ages.Linear regression analyses confirmed the MANCOVA results.CONCLUSION These results show a combined mental health risk factor related to stress reactivity,suggesting that the CSRS is sensitive to populations at risk and may be applied to future identification of other vulnerable sub-populations.It also supports the transdiagnostic approach for more accurate prevention and treatment.Time will tell if such transdiagnostic syndromes will be part of the discussions on the next revisions of the traditional classification systems or whether the crisis in psychiatry further evolves.

Genes in the serotonin pathway are associated with bipolar affective disorder in a Han Chinese population

Serotonin plays an important role in mood regulation, but the involvement of serotonin pathway genes in the development of bipolar I disorder. （BP-I）, a mood disorder, is not clear. We selected 21 single- nucleotide polymorphisms （SNPs） within the HTR2A gene, 8 within the SLC6A4 gene and 23 within the TPH2 gene for genotyping using the GoldenGate genotyping assay. A total of 375 patients with BP-I and 475 normal controls were recruited. Two out of 21 SNPs （rs1475196 and rs9567747） in the HTR2A gene and 1/23 SNPs （rs17110566） in the TPH2 gene were significantly associated with BP-I, both genotype-wise and allele-wise. Furthermore, a specific haplotype in the HTR2A gene showed a significant association with BP-I. Our results indicate that the HTR2A and TPH2 genes in the serotonin pathway play important roles in susceptibility to BP-I.

SDI/seasonal affective disorder,etc

SDI abbr. Strategic Defense Initiative,a system of computer-controlled defense using lasersand nuclear ballistic missiles in outer space to intercept and destroy enemy missilesbefore they reach their targets。战略防御计划(一种在外层空间使用激光器和核弹道导弹的计算机控制的防御系统,用以拦截并摧毁尚未到达目标的敌方导弹):

Exploring prefrontal cortex functions in healthy humans by transcranial electrical stimulation

The prefrontal cortex is involved in a multitude of cognitive, emotional, motivational, and social processes, so exploring its specific functions is crucial for understanding human experience and behavior. Functional imaging approaches have largely contributed to the enhancement of our understanding, but might have limitations in establishing causal relationships between physiology and the related psychological and behavioral processes. Non-invasive electrical stimulation with direct or alternating currents can help to enhance our understanding with regard to specific processes, and might provide future protocols able to improve them in case of malfunctions. We review the current state of the field, and provide an outlook for future developments.