Sleep disturbance mediates the link between childhood trauma and clinical outcome in severe mental disorders.

BACKGROUND: The experience of childhood trauma is linked to more severe symptoms and poorer functioning in severe mental disorders; however, the mechanisms behind this are poorly understood. We investigate the relationship between childhood trauma and sleep disturbances in severe mental disorders including the role of sleep disturbances in mediating the relationship between childhood trauma and the severity of clinical symptoms and poorer functioning. METHODS: In total, 766 participants with schizophrenia-spectrum (n = 418) or bipolar disorders (n = 348) were assessed with the Childhood Trauma Questionnaire. Sleep disturbances were assessed through the sleep items in the self-reported Inventory of Depressive Symptoms. Clinical symptoms and functioning were assessed with The Positive and Negative Syndrome Scale and the Global Assessment of Functioning Scale. Mediation analyses using ordinary least squares regression were conducted to test if sleep disturbances mediated the relationship between childhood trauma and the severity of clinical symptoms and poorer functioning. RESULTS: Symptoms of insomnia, but not hypersomnia or delayed sleep phase, were significantly more frequent in participants with childhood trauma experiences compared to those without. Physical abuse, emotional abuse, and emotional neglect were significantly associated with insomnia symptoms. Insomnia symptoms partly mediate the relationship between childhood trauma and the severity of positive and depressive/anxiety symptoms, in addition to poorer functioning. CONCLUSION: We found frequent co-occurrence of childhood trauma history and current insomnia in severe mental disorders. Insomnia partly mediated the relationship between childhood trauma and the severity of clinical symptoms and functional impairment.

Affective Immunology: The Crosstalk Between Microglia and Astrocytes Plays Key Role?

Emerging evidence demonstrates the critical role of the immune response in the mechanisms relating to mood disorders, such as major depression (MDD) and bipolar disorder (BD). This has cast a spotlight on a specialized branch committed to the research of dynamics of the fine interaction between emotion (or affection) and immune response, which has been termed as "affective immunology." Inflammatory cytokines and gut microbiota are actively involved in affective immunology. Furthermore, abnormalities of the astrocytes and microglia have been observed in mood disorders from both postmortem and molecular imaging studies; however, the underlying mechanisms remain elusive. Notably, the crosstalk between astrocyte and microglia acts as a mutual and pivotal intermediary factor modulating the immune response posed by inflammatory cytokines and gut microbiota. In this study, we propose the "altered astrocyte-microglia crosstalk (AAMC)" hypothesis which suggests that the astrocyte-microglia crosstalk regulates emotional alteration through mediating immune response, and thus, contributing to the development of mood disorders.

Integration of Clozapine-associated Harm Obsessions into Cognitive Behavioral Conceptualization and Treatment Planning for Thought Broadcasting: A Case Study.

BACKGROUND AND OBJECTIVES: As many as 30% of individuals with a schizophrenia spectrum disorder experience obsessive-compulsive symptoms (OCS). Clozapine has demonstrated superior efficacy for the treatment of medication-resistant schizophrenia but it is also associated with an increased risk for OCS. Because pharmacologic management of clozapine-related OCS can be particularly challenging, cognitive behavioral therapy (CBT) should be considered. Nevertheless, there are few detailed accounts of CBT for OCS and schizophrenia. METHODS: The authors describe the interdisciplinary outpatient care of a client who had a 25-year history of schizoaffective disorder, bipolar type, and OCS. The case formulation was used to guide interventions to target core schemas of being dangerous and defective. The case study describes the cognitive behavioral formulation, treatment targets, treatment course, and functional and symptom response. RESULTS: The client received 21 sessions of a formulation-based CBT for psychosis protocol, which included a 6-session course of exposure with response prevention, consisting of imaginal and in vivo exposure to multiple salient harm stimuli. Reduced ratings of distress and a 50% reduction in OCS suggest that habituation and inhibitory learning occurred. The treatment of OCS resulted in the complete resolution of thought broadcasting. Subsequently, the client was more successful in his efforts to adhere to an action schedule. LIMITATIONS: The use of both the treatment approach described in this clinical case report and contemporaneous medication management preclude comment on the mechanism(s) of the therapeutic change observed in this case. CONCLUSIONS: This report presents a means of conceptualizing the interplay between thought broadcasting and harm obsessions and discusses considerations in identifying and treating individuals with similar comorbid conditions, particularly in the context of clozapine treatment for medication-resistant psychosis.

Heterogeneity in psychiatric diagnostic classification.

The theory and practice of psychiatric diagnosis are central yet contentious. This paper examines the heterogeneous nature of categories within the DSM-5, how this heterogeneity is expressed across diagnostic criteria, and its consequences for clinicians, clients, and the diagnostic model. Selected chapters of the DSM-5 were thematically analysed: schizophrenia spectrum and other psychotic disorders; bipolar and related disorders; depressive disorders; anxiety disorders; and trauma- and stressor-related disorders. Themes identified heterogeneity in specific diagnostic criteria, including symptom comparators, duration of difficulties, indicators of severity, and perspective used to assess difficulties. Wider variations across diagnostic categories examined symptom overlap across categories, and the role of trauma. Pragmatic criteria and difficulties that recur across multiple diagnostic categories offer flexibility for the clinician, but undermine the model of discrete categories of disorder. This nevertheless has implications for the way cause is conceptualised, such as implying that trauma affects only a limited number of diagnoses despite increasing evidence to the contrary. Individual experiences and specific causal pathways within diagnostic categories may also be obscured. A pragmatic approach to psychiatric assessment, allowing for recognition of individual experience, may therefore be a more effective way of understanding distress than maintaining commitment to a disingenuous categorical system.

Primary healthcare utilisation among adults with mood and anxiety disorders: an analysis of the New Zealand Health Survey.

INTRODUCTION In New Zealand, as in other OECD countries, there is a high and growing prevalence of mental health problems, particularly anxiety and depression. These conditions are associated with a range of physical illnesses, and as a result this population have high and often complex needs for healthcare services, particularly through primary care. AIM To use data from the New Zealand Health Survey (NZHS) to examine the associations between internalising disorders (including anxiety, depression and bipolar disorder) and measures related to the utilisation of primary healthcare services. METHODS The study was based on responses from 13,719 adults who took part in the 2015-16 NZHS. Logistic regression analyses adjusted for sociodemographic variables were undertaken to examine the effect of having an internalising disorder on each measure related to primary healthcare utilisation. The strength of associations was indicated by odds ratios (ORs). RESULTS Adults with an internalising disorder were more likely to utilise primary health services (OR = 1.43-2.56, P < 0.001) compared to adults without an internalising disorder. However, they were more likely to have unmet needs due to cost or transport (OR = 2.45-3.38, P < 0.001), unfilled prescriptions due to cost (OR = 3.03, P < 0.001) and less likely to report positive experiences with general practitioners (OR = 0.67-0.79, P < 0.01). DISCUSSION Adults with internalising disorders require a higher level of support from primary healthcare, yet experience more barriers to accessing these services, and report less positive experiences with general practitioners. The NZHS may be a useful source of routinely collected data for understanding, monitoring and improving primary health service utilisation among people with internalising disorders.

Risk of psychiatric disorders in irritable bowel syndrome-A nationwide, population-based, cohort study.

AIMS: This cohort study aimed to investigate the association between irritable bowel syndrome (IBS) and the risk of developing psychiatric disorders. METHODS: Utilizing the National Health Insurance Research Database (NHIRD) of Taiwan, IBS patients were identified and compared with age, sex, and index year-matched controls (1:3). RESULTS: Of the IBS subjects, 3934 in 22 356 (17.60%, or 1533.68 per 100 000 person-years) developed psychiatric disorders when compared with 6127 in 67 068 (9.14%, or 802 per 100 000 person-years) in the non-IBS control group. Fine and Gray's survival analysis revealed that the study subjects were more likely to develop psychiatric disorders. The crude hazard ratio (HR) is 3.767 (95% CI: 3.614-3.925, P < .001), and the adjusted HR is 3.598 (95% CI: 3.452-3.752, P < .001) in the risk of developing psychiatric disorders after being adjusted for age, sex, comorbidities, geographical area of residence, urbanisation level of residence, and monthly insurance premiums. The cohort study revealed that IBS subjects were associated with an increased risk of anxiety, depression, bipolar, and sleep disorders. CONCLUSIONS: This cohort study, using NHIRD, shows evidence support that patients with IBS have a 3.6-fold risk of developing psychiatric disorders. Other large or national datasets should be done to explore to underlying mechanisms.

Trapped like a butterfly in a spider's web: Experiences of female spousal caregivers in the care of husbands with severe mental illness.

AIMS AND OBJECTIVES: To explore the experiences of female spousal caregivers in the care of husbands with severe mental illness. BACKGROUND: Family involvement in the care of patients with chronic illness is essential to provide a backbone of support for them. However, little is known about how female spousal caregivers are confronted with challenges while taking care of their husbands with severe mental illness. DESIGN: An exploratory qualitative study. METHODS: Fourteen female spousal caregivers of people with severe mental illness (defined here as schizophrenia, schizoaffective disorders and bipolar affective disorders) were recruited using purposive sampling and were interviewed using a semistructured in-depth interview method. Data were analysed by conventional content analysis until data saturation was achieved. RESULTS: Care of a husband with severe mental illness had a disruptive influence on the emotional relationships of the family and resulted in emotional detachment over time. Despite the caregivers' struggle to protect their families, the lack of supportive resources caused emotional exhaustion. Caregiving tasks interfering with their many other responsibilities, along with being a reference for family matters, led to loss of self. Consequently, they experienced psychological distress because of the transition to a caregiver role without any supportive resources. CONCLUSION: Constant caring, without supportive resources, forced them to do various roles and manage other issues within the family. Being unprepared for a caregiving role led to the psychological distress of female spousal caregivers. Therefore, adequate information, education and supportive resources must be provided for spouses to facilitate their transition to caregiving roles. RELEVANCE TO CLINICAL PRACTICE: It is necessary to pay close attention to the spousal caregivers' own mental health problems while they care for their mentally ill husbands. Mental health professionals should adopt a new approach to the prioritisation and planning of policies that support both family caregivers and patients.

Olfactory Functioning in First-Episode Psychosis.

Background: Though olfactory deficits are well-documented in schizophrenia, fewer studies have examined olfactory performance profiles across the psychosis spectrum. The current study examined odor identification, discrimination, and detection threshold performance in first-episode psychosis (FEP) patients diagnosed with schizophrenia, schizoaffective disorder, bipolar disorder with psychotic features, major depression with psychotic features, and other psychotic conditions. Method: FEP patients (n = 97) and healthy adults (n = 98) completed birhinal assessments of odor identification, discrimination, and detection threshold sensitivity for lyral and citralva. Participants also completed measures of anticipatory pleasure, anhedonia, and empathy. Differences in olfactory performances were assessed between FEP patients and controls and within FEP subgroups. Sex-stratified post hoc analyses were employed for a complete analysis of sex differences. Relationships between self-report measures and olfactory scores were also examined. Results: Individuals with psychosis had poorer scores across all olfactory measures when compared to the control group. Within the psychosis cohort, patients with schizophrenia-associated psychosis had poorer odor identification, discrimination, and citralva detection threshold scores relative to controls. In schizophrenia patients, greater olfactory disturbance was associated with increased negative symptomatology, greater self-reported anhedonia, and lower self-reported anticipatory pleasure. Patients with mood-associated psychosis performed comparable to controls though men and women in this cohort showed differential olfactory profiles. Conclusions: These findings indicate that olfactory deficits extend beyond measures of odor identification in FEP with greater deficits observed in schizophrenia-related subgroups of psychosis. Studies examining whether greater olfactory dysfunction confers greater risk for developing schizophrenia relative to other forms of psychosis are warranted.

Endocrinopathies and renal outcomes in lithium therapy: impact of lithium toxicity.

BACKGROUND: Lithium is the mainstay of treatment for bipolar disorder, mania and an augmentation therapy in patients with treatment resistant depression. It has a narrow therapeutic index, with recognized adverse multi-system and endocrine side effects. AIM: To assess the impact of lithium therapy, in particular lithium toxicity, on the development of endocrine and renal disorders in a cohort of patients in a single tertiary referral centre in Ireland. STUDY DESIGN: A retrospective analysis was performed of the prevalence of lithium toxicity and renal, thyroid and parathyroid dysfunction in our study population. METHODS: We collected laboratory data from the Clinical Chemistry department of the Adelaide and Meath Hospital incorporating the National Children's Hospital (AMNCH), Dublin, Ireland. Our study population included all patients who had at least one serum lithium measurement from January 1st 2000 to December 31st 2014 inclusive. RESULTS: A total of 580 patients were included in the study. Among our study group, 70 patients (12.1%) had 1 toxic lithium measurement (lithium level >1.2 mmol/l). 27.8% (n > 161) of patients developed stage 3 Chronic kidney Disease (CKD) or higher, which was commoner in those patients who developed toxic lithium levels (P < 0.0001) and in those who developed hypernatraemia (P > 0.0001). 16.2% of patients (n > 94) had one serum sodium >145 mmol/l during follow up. 60 patients(10.3%) had a TSH >10 mU/l, while complete suppression of TSH (<0.05 mU/l) was observed in 22 patients (3.8%) during follow-up. 4% (n > 37) of the study population had ≥1 serum corrected calcium level > 2.55 mmol/l, and 4 patients had biochemical confirmation of primary hyperparathyroidism but PTH levels were only performed in 2.8% (n > 16) of the studypopulation. CONCLUSION: Stage 3 CKD is common in patients receiving lithium therapy. Lithium toxicity is associated with CKD and hypernatraemia. Thyroid dysfunction and hypercalcaemia are common in patients receiving lithium therapy. Patients receiving lithium therapy require surveillance of renal, thyroid and bone biochemistry.

Anxiety or agitation in mood disorder with mixed features: A review with a focus on validity as a dimensional criterion.

BACKGROUND: The diagnostic validity of mixed features, excluding anxiety or psychomotor agitation in mood disorders, has not yet been fully examined. METHOD: PubMed and relevant English-language literature (regardless of year) were searched. Keywords were mixed or mixed state or mixed features or mixed episode and anxious or anxiety or agitation and bipolar disorder or depressive disorder or mood disorder or affective disorder. RESULTS: Most studies on anxiety or psychomotor agitation have included a significant correlation relevant to the "with mixed features" specifier, although it is common in both poles of mood episodes regardless of the predominant polarity. There is some confusion between the characteristic of classical mixed states and the definition of the mixed features specifier with the newly added anxious distress specifier in DSM-5, specifically, whether to include anxiety and agitation as significant characteristics. This change is of concern because a large proportion of patients with mixed features are now unspecified, and this may influence treatment planning and prognosis. CONCLUSIONS: The findings of our review suggest that anxiety and psychomotor agitation can be core symptoms in mood episodes with mixed features and important clinical clues for prediction of treatment effects and disease course.

Associations between comorbid health conditions and the use of mental health services among adults with bipolar disorder.

Using a nationally representative sample, this study examined to what extent the number of comorbid health conditions was associated with various mental health service utilization among people with bipolar disorder. The results of logistic regression models indicate that a greater number of comorbid medical conditions were associated with higher odds of using specialty mental health service, while they were not associated with utilization of services provided by general health care providers. The type of bipolar disorder, functional impairment, and marital status were found to be associated with the use of a specialty service, while ethnicity was the only covariate significantly related to general health care use.

Efficiency of Umbilical Cord Blood Cells in Patients with Treatment-Resistant Depressions.

We studied the efficacy of umbilical cord blood cells in the therapy of treatment-resistant depressive states in women. Concentrated umbilical cord blood cells were administered in a dose of 250 millions cells (4 injections at 1-week intervals). The control group received placebo. In both groups, reduction of depressive disorders and the decrease in hypothymia severity were observed. Infusions of cell concentrate contributed to delayed correction of treatment resistance and reduced the severity of depression to moderate. In the main group, significant, persistent, and long-term positive dynamics was observed in the cognitive sphere. The therapeutic potential of umbilical cord blood cell concentrate can be used to overcome treatment resistance formed in depressive patients.

Recurrent unipolar mania: A comparative, cross-sectional study.

INTRODUCTION: A significant number of patients experience recurrent episodes of mania without depressive episodes. Evidence from the available literature suggests that these patients differ from typical "bipolar" or "manic-depressive" patients, but results have been inconsistent. The current study aims to add to this literature by comparing the demographic, clinical and risk factor profiles of patients with recurrent mania with and without depression. METHODS: 66 patients with a diagnosis of bipolar I disorder were divided into "unipolar mania" (recurrent mania alone, MA) and "bipolar" (both mania and depression, MD) sub-groups. Comorbid diagnoses were assessed using the Mini International Neuropsychiatric Interview (MINI), and genetic and environmental risk factors were explored using the Diagnostic Interview for Genetic Studies (DIGS), Childhood Trauma Questionnaire (CTQ), and an additional questionnaire designed for the purpose of the study. Differences between the MA and MD groups in terms of demographic variables, clinical profile, comorbidities and antecedent risk factors were explored. RESULTS: Patients with both mania and depression had higher frequencies of lifetime suicide attempts, antidepressant treatment, and catatonic symptoms. There was some evidence of an association between overcrowding in childhood and the presence of depressive episodes. No other differences in demographic, clinical or risk factor variables could be found between the two groups. DISCUSSION: Our results are consistent with the view that unipolar mania is not a distinctive disorder, or even a distinctive subtype of bipolar disorder. However, this conclusion is provisional as it is based only on clinical and demographic data.

Model approach for stress induced steroidal hormone cascade changes in severe mental diseases.

INTRODUCTION: Stress was described by Cushing and Selye as an adaptation to a foreign stressor by the anterior pituitary increasing ACTH, which stimulates the release of glucocorticoid and mineralocorticoid hormones. The question is raised whether stress can induce additional steroidal hormone cascade changes in severe mental diseases (SMD), since stress is the common denominator. METHODS: A systematic literature review was conducted in PubMed, where the steroidal hormone cascade of patients with SMD was compared to the impact of increasing stress on the steroidal hormone cascade (a) in healthy amateur marathon runners with no overtraining; (b) in healthy well-trained elite soldiers of a ranger training unit in North Norway, who were under extreme physical and mental stress, sleep deprivation, and insufficient calories for 1 week; and, (c) in soldiers suffering from post traumatic stress disorder (PTSD), schizophrenia (SI), and bipolar disorders (BD). RESULTS: (a) When physical stress is exposed moderately to healthy men and women for 3-5 days, as in the case of amateur marathon runners, only few steroidal hormones are altered. A mild reduction in testosterone, cholesterol and triglycerides is detected in blood and in saliva, but there was no decrease in estradiol. Conversely, there is an increase of the glucocorticoids, aldosterone and cortisol. Cellular immunity, but not specific immunity, is reduced for a short time in these subjects. (b) These changes are also seen in healthy elite soldiers exposed to extreme physical and mental stress but to a somewhat greater extent. For instance, the aldosterone is increased by a factor of three. (c) In SMD, an irreversible effect on the entire steroidal hormone cascade is detected. Hormones at the top of the cascade, such as cholesterol, dehydroepiandrosterone (DHEA), aldosterone and other glucocorticoids, are increased. However, testosterone and estradiol and their metabolites, and other hormones at the lower end of the cascade, seem to be reduced. 1) The rate and extent of reduction of the androgen metabolites may cause a decrease of cellular and specific immunity which can lead to viral and bacterial infections; joint and stomach inflammation; general pain; and allergic reactions. 2) The decrease in testosterone, and estradiol in SMD may have detrimental effects in cell repair as the estradiol metabolite, 2-methoxy-estradiol (2ME2), helps to transforms stem cells into functional cells. As dopamine and 2ME2 are inversely metabolized via various forms of catechol-O-methyl transferase (COMT), well-being and hypertension may be related. 2ME2 is related to vascular endothelial growth factor (VEGF), which regulates blood capillary growth and O2 supply. As reduced O2 is a key marker of stress, the increase of glucocorticoids in all forms of mental and physical stress cannot counterbalance the reduced 2ME2 in cellular and mental stress. The increased cholesterol and triglycerides are related to stroke and infarction, contributing to a reduced life expectancy in SMD between 14 and 20 years. The increase of aldosterone leads to increases in anxiety, edema, and lung infections. DISCUSSION: Increasing mental and physical stress is related to systematic deviations in the steroidal hormone cascade in the non-psychotic state, which then may cause life threatening co-morbidities in PTSD, SI, and BD.

The relationship between chronotype and mood fluctuation in the general population.

There is a lack of evidence for the relationship between chronotype and subthreshold mood fluctuation. The present study aims to investigate the relationship between chronotypes and mood fluctuation in the general population. Participants (n=302) who have had no experience of major mood episodes were included. The Korean version of the Composite Scale of Morningness (CSM) was used to classify participants according to three chronotypes. Mood fluctuation was measured using the Mood Disorder Questionnaire (MDQ) and the Bipolar Spectrum Diagnostic Scale (BSDS). Mean scores achieved by the three chronotype groups on the MDQ and the BSDS were compared. There were no significant differences in the frequency of positive responses on the MDQ for the three chronotype groups. However, there was a significant group difference in total BSDS scores. The eveningness group had significantly higher BSDS-D scores than did either the morningness or the intermediate group have. In addition, the eveningness group had significantly higher BSDS-M scores than the morningness group. After adjusting for age by the analysis of covariance (ANCOVA), there were still significant group differences in total BSDS scores. The present results suggest that eveningness may be more related to mood fluctuation than morningness. The eveningness may be an important factor related to soft bipolarity or mood fluctuation.

Rating scales measuring the severity of psychotic depression.

OBJECTIVE: Unipolar psychotic depression (PD) is a severe and debilitating syndrome, which requires intensive monitoring. The objective of this study was to provide an overview of the rating scales used to assess illness severity in PD. METHOD: Selective review of publications reporting results on non-self-rated, symptom-based rating scales utilized to measure symptom severity in PD. The clinical and psychometric validity of the identified rating scales was reviewed. RESULTS: A total of 14 rating scales meeting the predefined criteria were included in the review. These scales grouped into the following categories: (i) rating scales predominantly covering depressive symptoms, (ii) rating scales predominantly covering psychotic symptoms, (iii) rating scales covering delusions, and (iv) rating scales covering PD. For the vast majority of the scales, the clinical and psychometric validity had not been tested empirically. The only exception from this general tendency was the 11-item Psychotic Depression Assessment Scale (PDAS), which was developed specifically to assess the severity of PD. CONCLUSION: In PD, the PDAS represents the only empirically derived rating scale for the measurement of overall severity of illness. The PDAS should be considered in future studies of PD and in clinical practice.

ERBB4 polymorphism and family history of psychiatric disorders on age-related cortical changes in healthy children.

Genetic variations in ERBB4 were associated with increased susceptibility for schizophrenia (SCZ) and bipolar disorders (BPD). Structural imaging studies showed cortical abnormalities in adolescents and adults with SCZ or BPD. However, less is known about subclinical cortical changes or the influence of ERBB4 on cortical development. 971 healthy children (ages 3-20 years old; 462 girls and 509 boys) were genotyped for the ERBB4-rs7598440 variants, had structural MRI, and cognitive evaluation (NIH Toolbox ®). We investigated the effects of ERBB4 variants and family history of SCZ and/or BPD (FH) on cortical measures and cognitive performances across ages 3-20 years using a general additive model. Variations in ERBB4 and FH impact differentially the age-related cortical changes in regions often affected by SCZ and BPD. The ERBB4-TT-risk genotype children with no FH had subtle cortical changes across the age span, primarily located in the left temporal lobe and superior parietal cortex. In contrast, the TT-risk genotype children with FH had more pronounced age-related changes, mainly in the frontal lobes compared to the non-risk genotype children. Interactive effects of age, FH and ERBB4 variations were also found on episodic memory and working memory, which are often impaired in SCZ and BPD. Healthy children carrying the risk-genotype in ERBB4 and/or with FH had cortical measures resembling those reported in SCZ or BPD. These subclinical cortical variations may provide early indicators for increased risk of psychiatric disorders and improve our understanding of the effect of the NRG1-ERBB4 pathway on brain development.