Severe Mood Disorders Research Articles

Motives, Offending Behavior, and Gender Differences in Murder Perpetrators With or Without Psychosis.

Little is known whether differences exist in motivation and reactive/instrumental offense behaviors between murder offenders with and without psychotic disorder. To contribute to better prevention strategies, the aim of this study was to investigate offense characteristics in murder offenders with a psychotic, nonpsychotic or no psychiatric diagnosis, and whether these factors differ according to sex. This data study examined the population of murder offenders between 1997 and 2005 (N = 435) in Victoria, Australia. Apparent motive for murder was allocated to one of six classifications. Assignations of reactive versus instrumental offense categories, co-offending, victim-offender relationship were determined by review of case material. Mental health service usage and prevalence of mental illnesses were identified through data with the statewide register of contacts with the public mental health system. Of the 435 offenders, 43 (9.9%) had been diagnosed with a psychotic illness. Gender differences between and within offenders with and without a psychotic disorder were analyzed. Murder offenders with a psychotic disorder were 3.19 (95% confidence interval [CI] = [1.27, 8.03]) times more likely to be motivated by revenge than nonpsychotic offenders and those with no diagnosis (odds ratio [OR] = 2.46, 95% CI = [1.10, 5.53]). The diagnostic groups did not differ on premeditation of their offenses or prior convictions. Perpetrators with psychotic illness were significantly more likely to kill family members and others known to them. It appears that for the psychotic disorder group, the perception of having been wronged in some way is a potential risk marker for planning and committing a serious offense. Care should be taken to improve adherence and access to care to avoid possible future serious violence especially in female patients with a high burden of mental illness like schizophrenia or severe mood disorders.

T127. OFFSPRING OF ANTENATALLY DEPRESSED MOTHERS AND PARENTS WITH SEVERE MENTAL DISORDER – A LONG FOLLOW-UP IN THE NORTHERN FINLAND 1966 BIRTH COHORT

BackgroundDepression during pregnancy is common, but long-term outcomes in the offspring of antenatally depressed mothers are unknown. Among severe mental disorders at least schizophrenia is considered to be a neurodevelopmental disorder acting already in utero with high genetic vulnerability. The aim was to study whether offspring of antenatally depressed mothers have an elevated risk for severe mood disorders till middle adulthood, taking account parental severe mental disorder.MethodsThe general population-based Northern Finland 1966 Birth Cohort includes 12,058 children, whose mothers were asked at mid-gestation if they felt depressed. The offspring were followed for over 40 years, and hospitalised severe mental disorders were detected using the Finnish Hospital Discharge Register. It was also used for identifying severe mental disorders in the parents till 1984, when the offspring were of age.ResultsOf the mothers, 14% self-reported depression during pregnancy. Of the parents, 10% had suffered from a hospitalised severe mental disorder.Adult offspring of antenatally depressed mothers had modestly increased risk for mood disorders both non-psychotic (crude OR 1.6; 95%CI 1.1–2.2) and psychotic (2.0; 1.0–4.1) but not for schizophrenia nor substance use disorder, when compared with the children of mothers without antenatal depression.Maternal depression during pregnancy combined with parental severe mental disorder increased the risks for severe mental disorders in the offspring widely. The risks for both non-psychotic (crude OR 3.8; 95%CI 2.1–6.6) and psychotic mood disorder (5.4; 1.6–18.1) and also for schizophrenia (4.3; 2.3–8.2) and substance use disorder (2.8; 1.7–4.7) were higher in the offspring with both maternal antenatal depression and parental severe mental disorder than in those without maternal depression and with severe mental disorder in the parent (for non-psychotic 1.5; 1.0–2.4 and psychotic mood disorder 4.2; 1.9–9.2, for schizophrenia 1.3; 0.8–2.4 and for substance disorder 1.5; 1.1–2.2) or in those with a depressed mother but without parental severe mental disorder (for non-psychotic 1.3; 0.9–1.9, and for psychotic mood disorder 2.1; 0.9–5.0, for schizophrenia 0.9; 0.5–1.6 and substance disorder 1.4; 1.1–2.0). The reference group was birth cohort members without maternal antenatal depression and without paren¬tal hospital-treated mental disorder. The risks remained statistically significant even after adjustment for maternal smoking during pregnancy, perinatal complications, father’s social class and family type at birth. In the offspring of antenatally depressed mother and a father with severe mental disorder the risk was elevated only for schizophrenia (7.5; 2.2–26.2).DiscussionMaternal depression during pregnancy increased the risk for mood disorders in the offspring slightly but not for schizophrenia nor substance use disorder when compared with the children of mothers without antenatal depression. Maternal antenatal depression combined with parental severe mental disorder increased the risks for all of these severe mental disorders in the adult offspring.The risk was highest for schizophrenia in the offspring of antenatally depressed mother and a father with severe mental disorder.To our knowledge, this is the first study of mood disorders, schizophrenia and substance use disorder in the offspring of antenatally depressed mothers with long follow-up till middle age where familial vulnerability for severe mental disorders was taken into account in a general population-based sample.

Prevalence of Mental Disorders and Addictions among Homeless People in the Greater Paris Area, France.

The Samenta study was conducted in 2009 in the Greater Paris area to estimate the prevalence of psychiatric disorders in homeless people. A cross-sectional survey was performed with a three-stage random sample of homeless people (n = 859), including users of day services, emergency shelters, hot meal distribution, long-term rehabilitation centres, and social hotels. Information was collected by a lay interviewer, using the Mini International Neuropsychiatric Interview, and completed by a psychologist through an open clinical interview. In the end, a psychiatrist assessed the psychiatric diagnosis according to the International Statistical Classification of Diseases and Related Health Problems (ICD, 10th revision). One third of homeless people in the Paris area had at least one severe psychiatric disorder (SPD): psychotic disorders (13%), anxiety disorders (12%), or severe mood disorders (7%). One in five was alcohol-dependent and 18% were drug users. Homeless women had significantly higher prevalence of anxiety disorders and depression compared to men, who were more likely to suffer from psychotic disorders. Homeless people of French origin were at higher risk of SPD, as well as people who experienced various adverse life events before the age of 18 (running away, sexual violence, parental disputes, and/or addictions) and those who experienced homelessness for the first time before the age of 26. The prevalence rates of the main psychiatric disorders within the homeless population of our study are consistent with those reported in other Western cities. Our results advocate for an improvement in the detection, housing, and care of psychiatric homeless people.

EHMT1 mosaicism in apparently unaffected parents is associated with autism spectrum disorder and neurocognitive dysfunction

BackgroundGenetic mosaicism is only detected occasionally when there are no obvious health or developmental issues. Most cases concern healthy parents in whom mosaicism is identified upon targeted testing of a genetic defect that was initially detected in their children. A germline genetic defect affecting the euchromatin histone methyltransferase 1 (EHMT1) gene causes Kleefstra syndrome, which is associated with the typical triad of distinct facial appearance, (childhood) hypotonia, and intellectual disability. A high degree of psychopathology is associated with this syndrome. A few parents with a mosaic EHMT1 mutation have been detected upon testing after a child was diagnosed with a germline EHMT1 defect. At first glance, carriers of a mosaic EHMT1 mutation appeared to function normally. However, recent studies have shown that de novo, postzygotic mutations in important developmental genes significantly contribute to autism spectrum disorder (ASD). Therefore, we hypothesized that EHMT1 mosaicism could cause neuropsychiatric defects. To investigate this, we performed a detailed investigation of cognitive neuropsychiatric parameters in parents identified with EHMT1 mosaicism.MethodsThree adults (two males, one female) with a genetically confirmed diagnosis of EHMT1 mosaicism were examined by means of a battery of tests and observational instruments covering both neurocognitive and psychiatric features. The battery included the following instruments: the Autism Diagnostic Observation Schedule (ADOS), the mini Psychiatric Assessment Schedules for Adults with Developmental Disabilities (mini PAS-ADD), the Vineland Adaptive Behavior Scales (VABS), and the Cambridge Neuropsychological Test Automated Battery (CANTAB). These measures were compared with our previously reported data from Kleefstra syndrome patients with confirmed (germline) EHMT1 defects.ResultsAll three subjects achieved maximum total scores on the VABS, indicative of adequate (adaptive) functioning. In all, scores above cutoff were found on the ADOS for ASD and on the mini PAS-ADD for major depressive disorder (lifetime). Finally, results on the CANTAB showed impaired cognitive flexibility in all subjects.ConclusionIndividuals with EHMT1 mosaicism seem to have increased vulnerability for developing severe psychopathology, especially ASD and mood disorders. Although at first glance they appear to be well-adapted in their daily functioning, they may experience significant psychiatric symptoms and show reduced cognitive flexibility in comparison to the general population.

Episode forecasting in bipolar disorder: Is energy better than mood?

Bipolar disorder is a severe mood disorder characterized by alternating episodes of mania and depression. Several interventions have been developed to decrease high admission rates and high suicides rates associated with the illness, including psychoeducation and early episode detection, with mixed results. More recently, machine learning approaches have been used to aid clinical diagnosis or to detect a particular clinical state; however, contradictory results arise from confusion around which of the several automatically generated data are the most contributory and useful to detect a particular clinical state. Our aim for this study was to apply machine learning techniques and nonlinear analyses to a physiological time series dataset in order to find the best predictor for forecasting episodes in mood disorders. We employed three different techniques: entropy calculations and two different machine learning approaches (genetic programming and Markov Brains as classifiers) to determine whether mood, energy or sleep was the best predictor to forecast a mood episode in a physiological time series. Evening energy was the best predictor for both manic and depressive episodes in each of the three aforementioned techniques. This suggests that energy might be a better predictor than mood for forecasting mood episodes in bipolar disorder and that these particular machine learning approaches are valuable tools to be used clinically. Energy should be considered as an important factor for episode prediction. Machine learning approaches provide better tools to forecast episodes and to increase our understanding of the processes that underlie mood regulation.

Complementary and alternative medicine contacts by persons with mental disorders in 25 countries: results from the World Mental Health Surveys.

A substantial proportion of persons with mental disorders seek treatment from complementary and alternative medicine (CAM) professionals. However, data on how CAM contacts vary across countries, mental disorders and their severity, and health care settings is largely lacking. The aim was therefore to investigate the prevalence of contacts with CAM providers in a large cross-national sample of persons with 12-month mental disorders. In the World Mental Health Surveys, the Composite International Diagnostic Interview was administered to determine the presence of past 12 month mental disorders in 138 801 participants aged 18-100 derived from representative general population samples. Participants were recruited between 2001 and 2012. Rates of self-reported CAM contacts for each of the 28 surveys across 25 countries and 12 mental disorder groups were calculated for all persons with past 12-month mental disorders. Mental disorders were grouped into mood disorders, anxiety disorders or behavioural disorders, and further divided by severity levels. Satisfaction with conventional care was also compared with CAM contact satisfaction. An estimated 3.6% (standard error 0.2%) of persons with a past 12-month mental disorder reported a CAM contact, which was two times higher in high-income countries (4.6%; standard error 0.3%) than in low- and middle-income countries (2.3%; standard error 0.2%). CAM contacts were largely comparable for different disorder types, but particularly high in persons receiving conventional care (8.6-17.8%). CAM contacts increased with increasing mental disorder severity. Among persons receiving specialist mental health care, CAM contacts were reported by 14.0% for severe mood disorders, 16.2% for severe anxiety disorders and 22.5% for severe behavioural disorders. Satisfaction with care was comparable with respect to CAM contacts (78.3%) and conventional care (75.6%) in persons that received both. CAM contacts are common in persons with severe mental disorders, in high-income countries, and in persons receiving conventional care. Our findings support the notion of CAM as largely complementary but are in contrast to suggestions that this concerns person with only mild, transient complaints. There was no indication that persons were less satisfied by CAM visits than by receiving conventional care. We encourage health care professionals in conventional settings to openly discuss the care patients are receiving, whether conventional or not, and their reasons for doing so.

Brief Web-Based Interventions for Young Adult Smokers With Severe Mental Illnesses: A Randomized, Controlled Pilot Study.

About 50% of young adults with schizophrenia, bipolar disorder, and other severe mental illnesses smoke tobacco, but few studies have evaluated interventions for this group. We conducted a randomized pilot study among 58 young adult smokers with severe mental illnesses comparing a brief interactive web-based motivational tool, Let's Talk About Smoking, to computerized standard education from the National Cancer Institute. An additional 23 subjects received minimal tobacco assessment at baseline and no intervention, providing a comparison condition for naturalistic cessation behavior. All participants (total n = 81) were assessed for smoking and breath carbon monoxide at baseline and 14 weeks and had access to standard cessation treatments. The 81 participants were stable outpatients ages 18-30 (mean 24.8 years): 43.2% were diagnosed with schizophrenia-spectrum disorders, the remainder with severe mood and anxiety disorders. They smoked 14.6 ± 10.2 cigarettes per day. All participants completed their assigned intervention; 83.4% of Let's Talk About Smoking users and 71.4% of standard education users rated their intervention "good" or "very good." At 14 weeks, less than 15% of participants in all conditions had used additional cessation treatment. Let's Talk About Smoking users were more likely to have biologically verified abstinence at 14 weeks than standard education users (14.8% vs. 0%; X2 = 3.7, p = .05). None of the participants in the naturalistic comparison condition were abstinent at 14 weeks. Interactive, web-based motivational interventions are feasible and promising for smoking cessation among young smokers with severe mental illnesses. Such interventions warrant further study among this group of smokers. Young adult smokers with severe mental illnesses are a vulnerable population that, without intervention, goes on to experience disparate morbidity and mortality. Brief, easily disseminable interventions are needed to facilitate cessation in this group. This pilot research indicates that brief, technology-delivered, motivational interventions that are tailored for this group may be able to activate a significant number to quit without additional cessation intervention.

Predictors of response to occipital nerve stimulation in refractory chronic headache.

Background Occipital nerve stimulation is a promising treatment for refractory chronic headache disorders, but is invasive and costly. Identifying predictors of response would be useful in selecting patients. We present the results of an open-label prospective cohort study of 100 patients (35 chronic migraine, 33 chronic cluster headache, 20 short-lasting unilateral neuralgiform headache attacks and 12 hemicrania continua) undergoing occipital nerve stimulation, using a multivariate binary regression analysis to identify predictors of response. Results Response rate of the cohort was 48%. Multivariate analysis showed short lasting unilateral neuralgiform headache attacks (OR 6.71; 95% CI 1.49-30.05; p = 0.013) and prior response to greater occipital nerve block (OR 4.22; 95% CI 1.35-13.21; p = 0.013) were associated with increased likelihood of response. Presence of occipital pain (OR 0.27; 95% CI 0.09-0.76; p = 0.014) and the presence of severe anxiety and/or depression (as measured on hospital anxiety and depression score) at time of implantation (OR 0.32; 95% CI 0.11-0.91; p = 0.032) were associated with reduced likelihood of response. Conclusion Possible clinical predictors of response to occipital nerve stimulation for refractory chronic headaches have been identified. Our data shows that those with short-lasting unilateral neuralgiform headache attacks respond better than those with chronic migraine, and that a prior response to greater occipital nerve block is associated with positive outcomes. This study suggests that the presence of occipital pain and severe mood disorder at time of implant are both associated with poor outcomes to occipital nerve stimulation.

Patterns of cannabis use and clinical correlates among individuals with Major Depressive Disorder and Bipolar Disorder

BackgroundMajor Depressive Disorder (MDD) and Bipolar Disorder (BPD) are the most severe mood disorders globally. Previous reports indicate high co-occurrence of cannabis use and cannabis use disorders (CUDs) associated with both disorders, yet studies comparing patterns of cannabis use between individuals with MDD and BPD are scarce. MethodsData were drawn from Wave 1 (2001–2002) of the National Epidemiologic survey on Alcohol and Related Conditions (NESARC). Cannabis users who qualified for a diagnosis of past-year MDD (N=217) were compared to those with BPD (N=168) in frequency and daily dose of cannabis use, rates of comorbid psychiatric disorders including specific criteria of CUDs, treatment utilization and suicidality. ResultsAmong past-year cannabis users, individuals with BPD reported using cannabis more frequently and smoking more joints per day compared to those with MDD. They were also more likely to suffer from comorbid personality disorders and qualify for specific CUD-criteria, including use in physically hazardous situations and unsuccessful efforts to control substance use. ConclusionsOur results indicate that individuals with BPD may present more intensive patterns of cannabis use compared to those with MDD. This may have potential effects on the course of BPD and should be further explored in longitudinal studies.

An Uncontrolled Pilot Study of an Integrated Family-Based Partial Hospitalization Program for Youth With Mood Disorders

ABSTRACTThere are many outpatient interventions for treating youth with mood disorders and their families. Despite the severity of impairment related to mood disorders, there is little research on the effectiveness of intensive outpatient or partial hospitalization programs that implement evidence-based treatment components for youth with mood disorders. A preliminary review of an innovative program, the Child and Adolescent Integrated Mood Program (CAIMP), that incorporates evidenced-based intervention within the service model of a partial hospitalization program for youth ages 9–18 is provided. Structured clinical interviews, broad-based assessment measures, and clinician-reported functioning scales were implemented to gather preliminary data. A brief description is included regarding the clinical setting, CAIMP treatment components, and pilot data. Favorable treatment outcomes post-CAIMP, including a reduction in inpatient hospitalization, are explored. Posttreatment clinical improvement was noted, and inpatient psychiatric hospital admissions decreased after completing CAIMP. Pilot data are favorable for CAIMP when providing treatment for youth with severe mood disorders and their caregivers. This intervention shows promise for being an important addition to the treatment options for youth with severe mood disorders and their families and is worthy of further evaluation. Providers have this clinical takeaway: Preliminary data suggest providing a partial hospitalization program specifically designed for mood disorders that engages both caregivers and youth with severe mood disorders has clinical benefit.

34 A lesion map of secondary bipolar disorder

Objective Bipolar Disorder (BPD) is a severe mood disorder, affecting 1.5%–4.4% of the population, and manifesting as an episodic, recurrent disturbance of mood, sleep, and behaviour. Secondary BPD (SBPD) develops following a brain insult, and is traditionally associated with right frontal lobe lesions. Yet, evidence supporting this association is mostly anecdotal. Here, we use two methodologies to study the neuroanatomy of SBPD: a systematic review of SBPD cases published in the literature, and reconstitution of brain lesions from a cohort of patients with SBPD in a single 3D template brain. Method Systematic search of pubmed and WebOfScience for SBPD. For the lesion-map, data were collected from 16 consecutive patients (6 women, 10 men, mean age 60,75±14,27 years) with SBPD developing after an MRI-documented right-sided brain-lesion. For each scan we selected the sequence (T1, T2, or FLAIR) providing the best lesion discrimination. Lesions were manually segmented using MITK software.1 After segmentation, each scan was co-registered onto a template reference brain2 using 3DSlicer software.3 Co-registration applies a transformation vector along the three axes of the source image, such that its voxels match the reference brain voxels to the highest possible degree. The resulting transformation vector was then applied to the image of each segmented lesion, and all the co-registered lesions were overlapped on the template brain scan (Automated anatomical labelling atlas or John Hopkins University white matter tractography Atlas for gray- and white-matter analysis, respectively). Results 1476 articles were found in literature review, with 207 eligible cases, including 193 with focal brain lesions, mostly right-sided (84.5%) and more rarely left-sided (34.7%). Lesions were overrepresented in the frontal and temporal lobes bilaterally. In the 3D lesion-map, lesions were spread over the right hemisphere, with highest overlap in a medial area of the superior frontal gyrus (6 patients). Grey-matter quantitative mapping showed that the right superior frontal gyrus right anterior cingulate and supramarginal gyrus and right insula were lesioned in the highest number of patients (respectively 8, 7 and 6 patients). White-matter analysis highlighted the right superior longitudinal fasciculus and superior corona radiata (6 patients each), anterior corona radiata and body of corpus callosum (5 patients each). Conclusion Our systematic review confirmed that right-sided frontotemporal lesions predominate in SBPD. In our cohort lesions converged on areas of the right executive control and anterior salience networks. Both have been implicated in the neurophysiology of primary BPD.4,5

Lithium exposure during pregnancy: outcomes for women who attended a specialist antenatal clinic

Introduction: Lithium treatment in pregnancy represents a significant dilemma for women and treating health professionals alike. The complexity of risk-benefit analysis is impacted by limited information.Methods: A cohort study of 33 women with severe mental illness, who were prescribed lithium at any time during the pregnancy, and gave birth between December 2007 and January 2015 at a specialist antenatal clinic in Western Australia. A descriptive comparison for women who continued lithium throughout pregnancy, and those who ceased on discovery of pregnancy was undertaken examining demographic, obstetric, neonatal and psychiatric variables.Results: Women who were prescribed lithium, irrespective of whether they continued or discontinued the medication represented a high risk group obstetrically, with high rates of smoking overall (33%) medical comorbidities (54%) and antenatal complications (88%). Preconception counseling occurred in 33% of the cohort but increased the likelihood of continuing lithium in pregnancy (p = .007). Compared to those who ceased lithium, women who remained on lithium through the pregnancy had increased rates of fetal ultrasound abnormalities such as abdominal circumference >90th % (p = .005). Psychiatric relapses through the antenatal and immediate postpartum period appeared to be due to a combination of factors.Discussion: Pregnant women with severe mood disorders treated with lithium are a vulnerable, high-risk obstetric population who would benefit from preconception counseling, regular antenatal care in a tertiary center, delivery with neonatal pediatric support and experienced psychiatric management.

Identification of rare nonsynonymous variants in SYNE1/CPG2 in bipolar affective disorder.

Bipolar affective disorder (BPD) is a severe mood disorder with a prevalence of ∼1.5% in the population. The pathogenesis of BPD is poorly understood; however, a strong heritable component has been identified. Previous genome-wide association studies have indicated a region on 6q25, coding for the SYNE1 gene, which increases disease susceptibility. SYNE1 encodes the synaptic nuclear envelope protein-1, nesprin-1. A brain-specific splice variant of SYNE1, CPG2 encoding candidate plasticity gene 2, has been identified. The intronic single-nucleotide polymorphism with the strongest genome-wide significant association in BPD, rs9371601, is present in both SYNE1 and CPG2. We screened 937 BPD samples for genetic variation in SYNE1 exons 14-33, which covers the CPG2 region, using high-resolution melt analysis. In addition, we screened two regions of increased transcriptional activity, one of them proposed to be the CPG2 promoter region. We identified six nonsynonymous and six synonymous variants. We genotyped three rare nonsynonymous variants, rs374866393, rs148346599 and rs200629713, in a total of 1099 BPD samples and 1056 controls. Burden analysis of these rare variants did not show a significant association with BPD. However, nine patients are compound heterozygotes for variants in SYNE1/CPG2, suggesting that rare coding variants may contribute significantly towards the complex genetic architecture underlying BPD. Imputation analysis in our own whole-genome sequencing sample of 99 BPD individuals identified an additional eight risk variants in the CPG2 region of SYNE1.

Animal Robot Assisted-therapy for Rehabilitation of Patient with Post-Stroke Depression

Recently, the utilization of therapeutic animal robots has expanded. This research aims to explore robotics application for mental healthcare in Malaysia through human-robot interaction (HRI). PARO, the robotic seal PARO was developed to give psychological effects on humans. Major Depressive Disorder (MDD) is a common but severe mood disorder. This study focuses on the interaction protocol between PARO and patients with MDD. Initially, twelve rehabilitation patients gave subjective evaluation on their first interaction with PARO. Next, therapeutic interaction environment was set-up with PARO in it to act as an augmentation strategy with other psychological interventions for post-stroke depression. Patient was exposed to PARO for 20 minutes. The results of behavioural analysis complemented with information from HRI survey question. The analysis also observed that the individual interactors engaged with the robot in diverse ways based on their needs Results show positive reaction toward the acceptance of an animal robot. Next, therapeutic interaction is set-up for PARO to contribute as an augmentation strategy with other psychological interventions for post-stroke depression. The outcome is to reduce the stress level among patients through facilitated therapy session with PARO

The Ethics of Clinical Trials Research in Severe Mood Disorders.

Mood disorders, including major depressive disorder (MDD) and bipolar disorder (BD), are highly prevalent, frequently disabling, and sometimes deadly. Additional research and more effective medications are desperately needed, but clinical trials research in mood disorders is fraught with ethical issues. Although many authors have discussed these issues, most do so from a theoretical viewpoint. This manuscript uses available empirical data to inform a discussion of the primary ethical issues raised in mood disorders research. These include issues of consent and decision-making capacity, including patients' motivations for participating in research. We also address drug withdrawals, placebo controls, and the overall safety of research. Finally, we examine the extant literature for studies discussing potential indirect benefits of clinical trials research to participants. Taken together, the evidence suggests that clinical trials research incorporating drug withdrawals and placebo controls can be conducted safely and ethically, even in patients with severe or treatment-resistant mood disorders. In fact, given the dearth of effective treatment options for this population, it is our opinion that a moral imperative exists to extend the offer of research participation to severely ill or treatment-resistant groups.

Clozapine reduces Toll-like receptor 4/NF-κB-mediated inflammatory responses through inhibition of calcium/calmodulin-dependent Akt activation in microglia

Clozapine is an atypical antipsychotic agent used in the treatment of schizophrenia and severe mood disorders. Accumulating evidence suggests that neuroinflammation is closely associated with the pathogenesis of various neurodegenerative diseases and psychiatric disorders. Clozapine exerts anti-inflammatory activity. However, the molecular mechanism underlying the anti-inflammatory activity of clozapine is poorly understood. In this study, we found that clozapine suppressed lipopolysaccharide (LPS)-induced phosphorylation of IκBα at Ser-32 and of p65/RelA at Ser-468, as well as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-dependent transcriptional activity in microglial cells. Clozapine downregulated LPS-induced Akt phosphorylation at Ser-473. Pharmacological Akt inhibitors ameliorated LPS-induced NF-κB activation. Removal of extracellular Ca2+ by EGTA or sequestration of intracellular Ca2+ by BAPTA-AM attenuated LPS-induced Akt phosphorylation. Treatment with calmodulin (CaM) antagonists and the CaM kinase inhibitor, KN-93, also prevented LPS-induced Akt and NF-κB activation, suggesting that Ca2+/CaM-dependent Akt activation is critical in LPS-induced NF-κB activation in microglia. These results suggest that clozapine exhibits anti-inflammatory activity through the inhibition of Ca2+/CaM/Akt-mediated NF-κB activation.

Age as a moderator of change following compensatory cognitive training in individuals with severe mental illnesses.

This study explored whether age moderated cognitive, symptom, and functional changes over a 12-week compensatory cognitive training (CCT) intervention for participants with severe mental illnesses. CCT focused on the cognitive domains of attention, learning, prospective memory, and executive functioning, often impaired in this population. Seventy-seven unemployed individuals (46 participants with severe mood disorders and 31 participants with schizophrenia/schizoaffective disorder; mean age = 44 years) received CCT for 12 weeks in the context of a supported employment program. Participants were administered cognitive, symptom severity, and functional measures at baseline and 3-, 6-, and 12-month follow-ups, as well as at 18 and 24 months for symptom/functional measures. Mixed effects models, controlling for diagnosis, examined whether age impacted the trajectories of change following CCT. Analyses showed several significant time by age interactions; younger participants improved more over time on category fluency, β = -.280, t(42.10) = -2.76, p = .008, and financial capacity (UCSD Performance-Based Skills Assessment), β = -.194, t(54.02) = -2.21, p = .031, whereas older participants showed greater reduction in positive symptom severity (Positive and Negative Syndrome Scale), β = -.109, t(78.35) = -2.34, p = .022, and less functional decline on the Independent Living Skills Survey, β = .118, t(109.77) = 2.05, p = .043. Age moderated the effects of CCT over time on measures of cognition, symptom severity, and functioning. Younger participants improved on objective measures of verbal processing speed and financial capacity, whereas older participants showed reduced positive symptom severity and less decline in self-reported daily functioning. These findings suggest that CCT may differentially benefit persons with severe mental illnesses depending on age. (PsycINFO Database Record

Role of glial cell line-derived neurotrophic factor in the pathogenesis and treatment of mood disorders.

Glial cell line-derived neurotrophic factor (GDNF) is widely recognized as a survival factor for dopaminergic neurons, but GDNF has also been shown to promote development, differentiation, and protection of other central nervous system neurons and was thought to play an important role in various neuropsychiatric disorders. Severe mood disorders, such as primarily major depressive disorder and bipolar affective disorder, attract particular attention. These psychopathologies are characterized by structural alterations accompanied by the dysregulation of neuroprotective and neurotrophic signaling mechanisms required for the maturation, growth, and survival of neurons and glia. The main objective of this review is to summarize the recent findings and evaluate the potential role of GDNF in the pathogenesis and treatment of mood disorders. Specifically, it describes (1) the implication of GDNF in the mechanism of depression and in the effect of antidepressant drugs and mood stabilizers and (2) the interrelation between GDNF and brain neurotransmitters, playing a key role in the pathogenesis of depression. This review provides converging lines of evidence that (1) brain GDNF contributes to the mechanism underlying depressive disorders and the effect of antidepressants and mood stabilizers and (2) there is a cross-talk between GDNF and neurotransmitters representing a feedback system: GDNF-neurotransmitters and neurotransmitters-GDNF.

Lester Adaptation of Cardio Metabolic Measurements: An Inpatient Interventional Framework for Women with Mental Illness

Aims of the study: To assess the prevalence of metabolic syndrome and implement a framework for screening and management of cardio metabolic risks in women on psychiatric in-patient wards. Background: An estimated 29-48% of psychiatric in-patients have metabolic syndrome. Severe mood disorders and psychotic illnesses are independent risk factors. 20-25% of the world’s adult population have metabolic syndrome and they are twice as likely to die from and three times as likely to have a heart attack or stroke compared with people without the syndrome. This study gives an overview of the application of Lester Tool on busy in-patient units and interventional approaches adapted by the team. Method: 46 admissions between April to July 2015 were included in Phase 1. Information on physical health medication and menopausal status was recorded in addition to metabolic syndrome parameters. Data on 47 admissions in Phase 2 between March to May 2016 was obtained. Advice on healthy lifestyle, diet, medication and smoking cessation was offered as routine. Results: Phase 1: Of the total 46 patients, 38 (82.60%) were on antipsychotics, 6 (13.04%) had metabolic syndrome and 14 (30.43%) did not and data was not available on 26 (56.52%). Most frequently missing criteria were waist circumference and triglyceride measurements. Phase 2: Of the total 45 patients, 14 (31.1%) had metabolic syndrome, 12 (26.6%) did not and data was unknown in 13 (28.8%). 2/3rd of admissions were compliant with investigations, as opposed to 1/3rd in Phase 1. 86.6% compliance was achieved in BMI checks. 20% were prescribed anti-hypertensive or anti-diabetic medication during admission and were referred to the dietician and diabetes clinic. Conclusion: Clinical identification and management of metabolic syndrome is essential and preventative measures by referral to specialist services or use of 3DFD model could be implemented. Lester Adaptation has been an effective tool for recording cardio metabolic risks; but in reality an effective interventional process could prove hard to achieve in mental health settings.

Clinical practice guidelines for Obsessive-Compulsive Disorder.

Obsessive-compulsive disorder (OCD) is a common psychiatric illness with lifetime prevalence of 1-3% [1]. It is the fourth-most common psychiatric illness and a leading cause of disability. OCD is associated with significant impairment in functioning, quality of life and disability. If untreated, OCD is a chronic illness with a waxing and waning of symptoms. A recent meta-analysis of long-term naturalistic prospective studies demonstrated that nearly a half of patients experience remission with much higher rates of remission in Indian patients compared to those in the west [2]. Early diagnosis and appropriate treatment may improve outcomes. Despite OCD being a common mental illness, most seek treatment after several years of suffering. Those who suffer from OCD tend to be secretive about their symptoms and suffer from shame and embarrassment. Less than a third of OCD sufferers receive appropriate pharmacotherapy and even less receive evidence-based psychotherapy. Symptoms The hallmarks of OCD are presence of obsessions and compulsions. Obsessions are repetitive, unwanted, intrusive thoughts, images or urges that are mostly ego-dystonic and cause severe distress or anxiety. Compulsions (or rituals) are repetitive behaviours or mental acts that are performed in response to an obsession to reduce anxiety/distress or prevent a dreaded consequence. Obsessions and compulsions are time consuming, distressing and are often resisted unsuccessfully. Clinical manifestations of OCD are remarkably similar across cultures and geographic locations. Common obsessions and compulsions and symptom dimensions identified through factor-analytical studies are shown in Table 1. Table 1 Common symptoms of OCD