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Introduction: There is an increasing rate of treatment resistance in severe psychiatric disorders (SPDs), which indicates the necessity for finding new therapeutic interventions, because of the significant negative impact these disorders have on the patient's quality of life, functionality, and other important parameters. In clinical practice, SPDs are estimated to represent up to 30-60% of all diagnosed cases. Schizophrenia spectrum disorders (SSD), major depressive disorder (MDD), and bipolar disorders (BDs) are associated with lower response to a large variety of therapeutic approaches. In this context, new technologies should be considered for SPDs, and non-invasive neuromodulation techniques can be explored as add-ons to ongoing therapeutic interventions. Objectives: A literature review was conducted to detect the available evidence to support recommendations for neuromodulation techniques in SPDs. Methods: Three electronic databases (PubMed, Cochrane, Google Scholar) were searched for papers corresponding to the keywords "treatment-resistant psychiatric disorders" and "neuromodulation" or "electroconvulsive therapy" (ECT) or "transcranial magnetic stimulation" (TMS) or "transcranial direct current stimulation" (tDCS), published from the beginning of the respective databases up to July 2023. Results: After the initial search, 1258 papers surfaced, but only 72 remained to be included in the analysis, after filtering them according to the inclusion and exclusion criteria. TMS may improve both depressive and manic symptoms, but also reports of polarity changes were found, indicating the need for careful monitoring of treatment-emergent affective switches (TEAS). TMS may also improve cognitive functions, although not sufficient evidence was found to support this observation clearly. The efficacy of temporoparietal TMS in schizophrenia has not been proven with certainty, although this intervention may improve positive symptoms. ECT was an effective and well-tolerated intervention for severe mood episodes, SSD, and BDs. Depressive symptoms responded to tDCS in bipolar/monopolar patients, but reports of TEAS in the BDs population have been reported. Conclusions: Non-invasive neuromodulation techniques may represent an efficient option in patients with SPD, but more good-quality trials are needed before this recommendation is formulated in clinical guidelines. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

Background: Recent developments in computational psychiatry have led to the hypothesis that mood represents an expectation (prior belief) on the likely interoceptive consequences of action (i.e. emotion). This stems from ideas about how the brain navigates its external world by minimising an upper bound on surprisal (free energy) of sensory information and echoes developments in other perceptual domains. Aims: In this paper we aim to present a simple partial observable Markov decision process that models mood updating in response to stressful or non-stressful environmental fluctuations while seeking to minimise surprisal in relation to prior beliefs about the likely interoceptive signals experienced with specific actions (attenuating or amplifying stress and pleasure signals). Method: We examine how, by altering these prior beliefs we can model mood updating in depression, mania and anxiety. Results: We discuss how these models provide a computational account of mood and its related psychopathology and relate it to previous research in reward processing. Conclusions: Models such as this can provide hypotheses for experimental work and also open up the potential modelling of predicted disease trajectories in individual patients. [ABSTRACT FROM AUTHOR]

Background: Healthcare decision makers require accurate long-term economic models to evaluate the cost-effectiveness of new mental health interventions.Aims: To assess the suitability of current patient-level economic models to estimate long-term economic outcomes in severe mental illness.Method: We undertook pre-specified systematic searches in MEDLINE, Embase and PsycINFO to identify reviews and stand-alone publications of economic models of interventions for schizophrenia, bipolar disorder and major depressive disorder (PROSPERO: CRD42020158243). We screened paper titles and abstracts to identify unique patient-level economic models. We conducted a structured extraction of identified models, recording the presence of key predefined model features. Model quality and validation were appraised using the 2014 ISPOR and 2016 AdViSHE model checklists.Results: We identified 15 unique patient-level models for psychosis and major depressive disorder from 1481 non-duplicate records. Models addressed schizophrenia (n = 6), bipolar disorder (n = 2) and major depressive disorder (n = 7). The predominant model type was discrete event simulation (n = 9). Model complexity and incorporation of patient heterogeneity varied considerably, and only five models extrapolated costs and outcomes over a lifetime horizon. Key model parameters were often based on low-quality evidence, and checklist quality assessment revealed weak model verification procedures.Conclusions: Existing patient-level economic models of interventions for severe mental illness have considerable limitations. New modelling efforts must be supplemented by the generation of good-quality, contemporary evidence suitable for model building. Combined effort across the research community is required to build and validate economic extrapolation models suitable for accurately assessing the long-term value of new interventions from short-term clinical trial data. [ABSTRACT FROM AUTHOR]

Background: The high cardiovascular (CV) morbidity and mortality reported for patients with psychiatric disorders may possibly be due to a poorer management of CV risk factors (CVRFs). However, these healthcare disparities remain poorly understood. In this paper, studies comparing the management of smoking, diabetes, hypertension and dyslipidaemia, in patients with and without depression, anxiety, schizophrenia, bipolar or personality disorder, were reviewed. Methods: Prospective studies comparing rates of screening, diagnosis, treatment and control of CVRFs were searched in PubMed, Embase, PsychInfo, Scopus and Web of Science (inception to January 2017). The Meta-analysis of Observational Studies in Epidemiology (MOOSE) criteria were used. Studies were assessed for quality. Wherever possible, meta-analyses were conducted to summarize the findings. Results: Twenty studies, out of the 18 333 references initially identified, were included. Most studies were heterogeneous in design. Two areas permitted meta-analyses: the pooled odds ratio for quitting smoking for those with depression was 0.64 (0.49–0.80) p < 0.001; the pooled difference of glycated haemoglobin for patients with type 2 diabetes and depression was 0.18 (0.06–0.31) p = 0.005. Individual studies showed associations between: schizophrenia and lower probability of having smoking habit recorded; schizoid personality disorder and higher probability of remaining non-smokers after quitting; anxiety and poorer control of type I diabetes; depression, anxiety or schizophrenia and lower probability of having a diagnosis of hypertension; schizophrenia or bipolar disorder and lower use of antihypertensive and lipid-lowering drugs. Conclusions: A proactive clinical management, together with further studies, are needed to reduce the CV morbidity and mortality of patients with psychiatric disorders. [ABSTRACT FROM AUTHOR]

Neuropsychological dysfunction is a well-established finding in individuals with bipolar disorder type I (BP-I), even during euthymic periods; however, it is less clear whether this also pertains to bipolar disorder type II (BP-II) or those with subthreshold states (SBP; subthreshold bipolar disorder), such as bipolar not otherwise specified (BP-NOS). Herein, we compare the literature regarding neuropsychological performance in BP-II vs BP-I to determine the extent of relative impairment, and we present and review all related studies on cognition in SBP. After systematically searching PubMed, Medline, PsycINFO, and The Cochrane Library, we found 17 papers that comprise all the published studies relevant for this review. The areas that are consistently found to be impaired in BP are executive function, verbal memory, visual spatial working memory, and attention. More studies than not show no significant difference between BP-I and BP-II, particularly in euthymic samples. Preliminary evidence suggests that patients experiencing major depressive episodes who also meet criteria for SBP show similar profiles to BP-II; however, these results pertain only to a depressed sample. SBP were found to perform significantly better than both MDD and healthy controls in a euthymic sample. A consensus on mood state, patient selection, and neuropsychological testing needs to be agreed on for future research. Furthermore, no studies have used the most recent DSM-5 criteria for SBP; future studies should address this. Finally, the underlying bases of cognitive dysfunction in these diagnostic groups need to be further investigated. We suggest recommendations on all of the above current research challenges.

This issue contains a review on child-onset bipolar disorder. Other sets of papers examine various aspects of bipolar disorder, depression and suicide, anxiety, and chronic fatigue, and four individual papers examine a variety of topics. [ABSTRACT FROM AUTHOR]

Introduction: Many clinicians are reluctant to use traditional mood-stabilizing agents, especially lithium, in children and adolescents. This review examined the evidence for lithium's safety and efficacy in this population., Methods: A systematic review was conducted on the use of lithium in children and adolescents with bipolar disorder (BD). Relevant papers published through June 30 th 2018 were identified searching the electronic databases MEDLINE, Embase, PsycINFO and the Cochrane Library., Results: 30 articles met inclusion criteria, including 12 randomized controlled trials (RCTs). Findings from RCTs demonstrate efficacy for acute mania in up to 50% of patients, and evidence of long-term maintenance efficacy. Lithium was generally safe, at least in the short term, with most common side effects being gastrointestinal, polyuria, or headache. Only a minority of patients experienced hypothyroidism. No cases of acute kidney injury or chronic kidney disease were reported., Conclusions: Though the available literature is mostly short-term, there is evidence that lithium monotherapy is reasonably safe and effective in children and adolescents, specifically for acute mania and for prevention of mood episodes., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

In 1800, mania was conceptualized as an agitated psychotic state. By 1900, it closely resembled its modern form. This paper reviews the descriptions of mania in Western psychiatry from 1880 to 1900, when Kraepelin was training and developing his concept of manic-depressive illness. Psychiatric textbooks published 1900-1960 described 22 characteristic manic symptoms/signs the presence of which were recorded in 25 psychiatric textbooks and three other key documents published 1880-1900. Descriptions of mania in these nineteenth century textbooks closely resembled those in the twentieth century, recording a mean (s.d.) of 15.9 (2.3) and 17.0 (2.3) of the characteristic symptoms, respectively (p = 0.12). The frequency with which individual symptoms were reported was substantially correlated in these two periods (r = +0.64). Mendel's 1881 monograph, Kraepelin's first description of mania in 1883 and the entry for mania in Tuke's Dictionary of Psychological Medicine (1892) described a mean (s.d.) of 19 (1.7) of these characteristic symptoms. These descriptions of mania often contained phenomenologically rich descriptions of euphoria, hyperactivity, grandiosity, flight of ideas, and poor judgment. They also emphasized several features not in DSM criteria including changes in character, moral standards and physical appearance, and increased sense of humor and sexual drive. Fifteen authors described key symptoms/signs of mania most reporting elevated mood, motoric hyperactivity and accelerated mental processes. By 1880, the syndrome of mania had been largely stabilized in its modern form. In the formation of his concept of manic-depressive illness, Kraepelin utilized the syndrome of mania as described in the psychiatric community in which he was trained.

Evidence from the literature suggests that, on average, 27% of patients with a bipolar disorder (BD) experience a continuous cycling course (CCC) and that this subgroup differs significantly from patients with a noncontinuous cycling course (N-CCC) with respect to sociodemographic characteristics and clinical presentation. The aim of the present paper is to review the studies that evaluated short- and long-term treatment responses in BD patients with CCC. The retrieved studies indicate that CCC is a significant predictor of poor response to long-term treatment with lithium (the odds of a response in the CCC group were 57% less than in the N-CCC group; p<0.01), as well as to polytherapies including lithium and/or an antiepileptic augmented, when necessary, with an antipsychotic and/or antidepressant. The percentage of patients without new episodes during follow-up was significantly lower in the CCC group compared with the N-CCC group (15.4 vs. 37.6% , p<0.01). Compared with patients in the N-CCC group, members of the CCC group had a poorer response and lower remission rates after 12-week antidepressant treatments for a major depressive episode (82.3 vs. 50%, p =0.002; 69.6 vs. 40.9%, p=0.013). These findings, underlining that CCC is a predictor of poor response to short- and long-term treatment in BD, should be interpreted considering the limitations of the reviewed studies (the small sample sizes, the small number of trials and their observational nature, the lack of randomization or placebo controls, and the unblinded nature of the outcomes). Clinical trials and observational studies with larger samples are warranted to confirm the conclusions of our review.

Background: More knowledge about positive outcomes for people with first-episode psychosis (FEP) is needed. An FEP 10-year follow-up study investigated the rate of personal recovery, emotional wellbeing, and clinical recovery in the total sample and between psychotic bipolar spectrum disorders (BD) and schizophrenia spectrum disorders (SZ); and how these positive outcomes overlap. Methods: FEP participants (n = 128) were re-assessed with structured clinical interviews at 10-year follow-up. Personal recovery was self-rated with the Questionnaire about the Process of Recovery-15-item scale (total score ⩾45). Emotional wellbeing was self-rated with the Life Satisfaction Scale (score ⩾5) and the Temporal Experience of Pleasure Scale (total score ⩾72). Clinical recovery was clinician-rated symptom-remission and adequate functioning (duration minimum 1 year). Results: In FEP, rates of personal recovery (50.8%), life satisfaction (60.9%), and pleasure (57.5%) were higher than clinical recovery (33.6%). Despite lower rates of clinical recovery in SZ compared to BD, they had equal rates of personal recovery and emotional wellbeing. Personal recovery overlapped more with emotional wellbeing than with clinical recovery (χ2). Each participant was assigned to one of eight possible outcome groups depending on the combination of positive outcomes fulfilled. The eight groups collapsed into three equal-sized main outcome groups: 33.6% clinical recovery with personal recovery and/or emotional wellbeing; 34.4% personal recovery and/or emotional wellbeing only; and 32.0% none. Conclusions: In FEP, 68% had minimum one positive outcome after 10 years, suggesting a good life with psychosis. This knowledge must be shared to instill hope and underlines that subjective and objective positive outcomes must be assessed and targeted in treatment. [ABSTRACT FROM AUTHOR]

Background: One potential cause of comorbidity is the direct causal effect of one disorder – A – on risk for subsequent onset of disorder B. Could genetic risk scores be utilized to test for such an effect? If disorder A causally impacts on risk for disorder B, then genetic risk for disorder A should be lower in cases of disorder A with v. without a prior onset of B. Methods: In all individuals (n = 905 736) born in Sweden from 1980 to 1990, from six psychiatric and drug use disorders (major depression, anxiety disorders, alcohol use disorder, drug use disorder, bipolar disorder, and schizophrenia), we formed 14 pairs of disorders A and B. In these pairs, we compared, using Cox proportional hazards models, the predictive effect of the familial-genetic risk score (FGRS) for disorder B in those who had v. had not had a prior onset of disorder A. Results: In all pairs, the impact of the FGRS for disorder B was significantly stronger in cases without v. with a prior history of disorder A. These effects were similar across sex, stable across levels of FGRS and not likely due to clinician bias. In many of our disorder pairs, previous clinical studies suggest a mechanism for a causal effect of disorder A on B. Conclusions: Our findings provide indirect evidence that the occurrence of one psychiatric or substance use disorder often has a causal effect on risk for subsequent disorders. This mechanism may substantially contribute to the widespread comorbidity among psychiatric conditions. [ABSTRACT FROM AUTHOR]

Background: The N100, an early auditory event-related potential, has been found to be altered in patients with psychosis. However, it is unclear if the N100 is a psychosis endophenotype that is also altered in the relatives of patients. Methods: We conducted a family study using the auditory oddball paradigm to compare the N100 amplitude and latency across 243 patients with psychosis, 86 unaffected relatives, and 194 controls. We then conducted a systematic review and a random-effects meta-analysis pooling our results and 14 previously published family studies. We compared data from a total of 999 patients, 1192 relatives, and 1253 controls in order to investigate the evidence and degree of N100 differences. Results: In our family study, patients showed reduced N100 amplitudes and prolonged N100 latencies compared to controls, but no significant differences were found between unaffected relatives and controls. The meta-analysis revealed a significant reduction of the N100 amplitude and delay of the N100 latency in both patients with psychosis (standardized mean difference [s.m.d.] = −0.48 for N100 amplitude and s.m.d. = 0.43 for N100 latency) and their relatives (s.m.d. = − 0.19 for N100 amplitude and s.m.d. = 0.33 for N100 latency). However, only the N100 latency changes in relatives remained significant when excluding studies with affected relatives. Conclusions: N100 changes, especially prolonged N100 latencies, are present in both patients with psychosis and their relatives, making the N100 a promising endophenotype for psychosis. Such changes in the N100 may reflect changes in early auditory processing underlying the etiology of psychosis. [ABSTRACT FROM AUTHOR]

Background: Although diagnostic instability in first-episode psychosis (FEP) is of major concern, little is known about its determinants. This very long-term follow-up study aimed to examine the diagnostic stability of FEP diagnoses, the baseline predictors of diagnostic change and the timing of diagnostic change. Methods: This was a longitudinal and naturalistic study of 243 subjects with FEP who were assessed at baseline and reassessed after a mean follow-up of 21 years. The diagnostic stability of DSM-5 psychotic disorders was examined using prospective and retrospective consistencies, logistic regression was used to establish the predictors of diagnostic change, and survival analysis was used to compare time to diagnostic change across diagnostic categories. Results: The overall diagnostic stability was 47.7%. Schizophrenia and bipolar disorder were the most stable diagnoses, with other categories having low stability. Predictors of diagnostic change to schizophrenia included a family history of schizophrenia, obstetric complications, developmental delay, poor premorbid functioning in several domains, long duration of untreated continuous psychosis, spontaneous dyskinesia, lack of psychosocial stressors, longer duration of index admission, and poor early treatment response. Most of these variables also predicted diagnostic change to bipolar disorder but in the opposite direction and with lesser effect sizes. There were no significant differences between specific diagnoses regarding time to diagnostic change. At 10-year follow-up, around 80% of the diagnoses had changed. Conclusions: FEP diagnoses other than schizophrenia or bipolar disorder should be considered as provisional. Considering baseline predictors of diagnostic change may help to enhance diagnostic accuracy and guide therapeutic interventions. [ABSTRACT FROM AUTHOR]

Objective: The electroencephalogram (EEG) can be a useful tool in determining differences in general neural activity and specific waveforms in individuals with a number of psychiatric disorders. This paper aims to outline and discuss significant findings in EEG and event-related potential (ERP) research into bipolar disorder (BD). Methods: A literature review was performed through searches of MedLine, EMBASE, CINAHL and PsycInfo medical research databases for papers published from 1985 onwards. References of selected articles were also examined for other relevant studies. Results: Differences in general EEG data were found in subjects with BD, namely increased theta and delta and decreased alpha wave bands. Changes in EEG were also found in euthymic BD subjects and those undergoing medication programmes. ERP studies commonly report prolonged latencies and reduced amplitudes in the P300 component. Hyperfunctioning of the right hemisphere in BD was also reported in some studies, although further confirmation of this finding is required. Finally, the effects of medication and the role that genetics plays in EEG still remain unclear. Conclusions: The literature reviewed demonstrates supporting evidence for the presence of significant differences in EEG and ERP data in subjects with BD. However, methodological considerations such as varying mood states and medication status of the patients need to be followed more stringently for future research to bring about a robust model of the cognitive deficits of BD. [ABSTRACT FROM AUTHOR]

Lithium is a mood stabilizer rarely associated with drug-induced parkinsonism (DIP). We present a case of an elderly woman with bipolar disorder who developed parkinsonian symptoms after chronic lithium administration despite therapeutic serum levels. Upon evaluation, classic parkinsonian signs of muscle rigidity, tremor, bradykinesia, freezing of gait, and cognitive decline were observed. Initially, she was diagnosed with Parkinson's disease (PD); however, DaTscan SPECT imaging clarified the diagnosis as DIP. As the daily lithium dosage was reduced, the patient's motor symptoms improved. This report emphasizes close monitoring of lithium levels in geriatric populations and the need to consider lithium-induced parkinsonism when PD symptoms appear in chronic lithium users. [ABSTRACT FROM AUTHOR]

Background: Two established staging models outline the longitudinal progression in bipolar disorder (BD) based on episode recurrence or inter-episodic functioning. However, underlying neurobiological mechanisms and corresponding biomarkers remain unexplored. This study aimed to investigate if global and (sub)cortical brain structures, along with brain-predicted age difference (brain-PAD) reflect illness progression as conceptualized in these staging models, potentially identifying brain-PAD as a biomarker for BD staging. Methods: In total, 199 subjects with bipolar-I-disorder and 226 control subjects from the Dutch Bipolar Cohort with a high-quality T1-weighted magnetic resonance imaging scan were analyzed. Global and (sub)cortical brain measures and brain-PAD (the difference between biological and chronological age) were estimated. Associations between individual brain measures and the stages of both staging models were explored. Results: A higher brain-PAD (higher biological age than chronological age) correlated with an increased likelihood of being in a higher stage of the inter-episodic functioning model, but not in the model based on number of mood episodes. However, after correcting for the confounding factors lithium-use and comorbid anxiety, the association lost significance. Global and (sub)cortical brain measures showed no significant association with the stages. Conclusions: These results suggest that brain-PAD may be associated with illness progression as defined by impaired inter-episodic functioning. Nevertheless, the significance of this association changed after considering lithium-use and comorbid anxiety disorders. Further research is required to disentangle the intricate relationship between brain-PAD, illness stages, and lithium intake or anxiety disorders. This study provides a foundation for potentially using brain-PAD as a biomarker for illness progression. [ABSTRACT FROM AUTHOR]

Background: Data on trends in the epidemiological burden of bipolar disorder are scarce. Aims: To provide an overview of trends in bipolar disorder burden from 1990 to 2019. Method: Revisiting the Global Burden of Disease Study 2019, we analysed the number of cases, calculated the age-standardised rate (per 100 000 population) and estimated annual percentage change (EAPC) of incidence, prevalence and years lived with disability (YLDs) for bipolar disorder from 1990 to 2019. The independent effects of age, period and cohort were estimated by the age–period–cohort modelling. Results: Globally, the bipolar disorder-related prevalent cases, incident cases and number of YLDs all increased from 1990 to 2019. Regionally, the World Health Organization Region of the Americas accounted for the highest estimated YLD number and rate, with the highest age-standardised prevalence rate in 1990 and 2019 and highest EAPC of prevalence. By sociodemographic index (SDI) quintiles, all five SDI regions saw an increase in estimated incident cases. Nationally, New Zealand reported the highest age-standardised rate of incidence, prevalence and YLDs in 1990 and 2019. The most prominent age effect on incidence rate was in those aged 15–19 years. Decreased effects of period on incidence, prevalence and YLD rates was observed overall and in females, not in males. The incidence, prevalence and YLD rates showed an unfavourable trend in the younger cohorts born after 1990, with males reporting a higher cohort risk than females. Conclusions: From 1990 to 2019, the overall trend of bipolar disorder burden presents regional and national variations and differs by age, sex, period and cohort. [ABSTRACT FROM AUTHOR]

This editorial presents a serious call to arms for clinicians to consider their own prescribing practices, ensure they are aware of regulatory requirements around valproate prescription and always address the risk of harm in anyone for whom pregnancy is biologically possible. The risks associated with using sodium valproate in pregnancy have been well established for over a decade. Clozapine was associated with a reduced risk of developing substance use disorder compared with antipsychotic polytherapy, and clozapine was associated with lower relapse rates in patients with both diagnoses. [Extracted from the article]

B I recall the awful news footage of emotionally abandoned children in Romanian orphanages following the fall of Ceausescu's regime in the late 80s. b I was a child myself at the time, and I remember in particular the feeling of sadness hearing about some babies who had learned to no longer cry, as it evoked no response. B Finally, German DJ Tomcraft imprinted my 20s with his track "Loneliness": considering psychosis, how much is it affected by this social blight (isolation, not underground techno-trance anthems)? During this time, participants underwent repeated measurements of IQ, physical growth, brain activity via electroencephalographs, and evaluation for various types of psychopathology. [Extracted from the article]

Background: Subthreshold psychotic and bipolar experiences are common in major depressive disorder (MDD). However, it is unknown if effectiveness of psychotherapy is altered in depressed patients who display such features compared with those without. The current paper aimed to investigate the impact of the co-presence of subclinical psychotic experiences and subclinical bipolar symptoms on the effectiveness of psychological treatment, alone or in combination with pharmacotherapy., Method: In a naturalistic study, patients with MDD (n = 116) received psychological treatment (cognitive behavioural therapy or interpersonal psychotherapy) alone or in combination with pharmacotherapy. Depression and functioning were assessed six times over 2 years. Lifetime psychotic experiences and bipolar symptoms were assessed at the second time point., Results: Subclinical psychotic experiences predicted more depression over time (β = 0.20, p < 0.002), non-remission [odds ratio (OR) 7.51, p < 0.016] and relapse (OR 3.85, p < 0.034). Subthreshold bipolar symptoms predicted relapse (OR 1.16, p < 0.037)., Conclusions: In general, subclinical psychotic experiences have a negative impact on the course and outcome of psychotherapy in MDD. Effects of subclinical bipolar experiences were less prominent.

Background: Although numerous studies have examined the latent structure of major depression, less attention has focused on mania. This paper presents the first investigation outside the USA to evaluate the psychometric properties of the DSM-IV criterion B mania symptoms using item response theory (IRT)., Method: Data were drawn from the Australian 2007 National Survey of Mental Health and Well-Being (NSMHWB, n = 8841). The psychometric performance of the mania symptoms was evaluated using a two-parameter logistic model. Because substance use disorders (SUDs) frequently co-occur with mania and can influence manic symptom expression, differential item functioning (DIF) between mania respondents with/without a SUD diagnosis was also assessed., Results: Factor analysis supported a unidimensional trait underlying mania. The grandiosity symptom displayed the highest discrimination whereas discrimination was lowest for decreased need for sleep. Relatively speaking, grandiosity tapped the severe end and increased goal-oriented activities tapped the mild end of the mania severity continuum. The symptoms generally performed equivalently between those with/without a SUD diagnosis, with one exception; the activities with painful consequences symptom was endorsed at lower levels of severity, and hence more frequently, by those with a SUD diagnosis versus those without a SUD diagnosis., Conclusions: Accurate conceptualization of latent structure has crucial theoretical, statistical and clinical implications. The symptoms generally performed well in distinguishing between respondents with differing levels of liability, but others did not, suggesting modification is warranted to ensure optimal use in epidemiological samples. Given the dearth of psychometric evaluation studies of mania, further research replicating these results is necessary.

Background: Allostatic load (AL) relates to the neural and bodily "wear and tear" that emerge in the context of chronic stress. This paper aims to provide clinicians with a comprehensive overview of the role of AL in patophysiology of bipolar disorder (BD) and its practical implications., Methods: PubMed searches were conducted on English-language articles published from 1970 to June 2011 using the search terms allostatic load, oxidative stress, staging, and bipolar disorder cross-referenced with cognitive impairment, comorbidity, mediators, prevention., Results: Progressive neural and physical dysfunction consequent to mood episodes in BD can be construed as a cumulative state of AL. The concept of AL can help to reconcile cognitive impairment and increased rates of clinical comorbidities that occur over the course of cumulative BD episodes., Conclusions: Data on transduction of psychosocial stress into the neurobiology of mood episodes converges to the concept of AL. Mood episodes prevention would not only alleviate emotional suffering, but also arrest the cycle of AL, cognitive decline, physical morbidities and, eventually, related mortality. These objectives can be achieved by focusing on effective prophylaxis from the first stages of the disorder, providing mood-stabilizing agents and standardized psychoeducation and, potentially, addressing cognitive deficits by the means of specific medication and neuropsychological interventions., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Background: To clarify, in a national sample, associations between risk for seven psychiatric and substance use disorders and five key transitions in Sweden's public educational system. Methods: Swedish-born individuals (1972–1995, N = 1 997 910) were followed through 12-31-2018, at mean age 34.9. We predicted, from these educational transitions, risk for major depression (MD), obsessive-compulsive disorder (OCD), bipolar disorder (BD), schizophrenia (SZ), anorexia nervosa (AN), alcohol use disorder (AUD), and drug use disorder (DUD), assessed from Swedish national registers, by Cox regression, censoring individuals with onsets ⩽17. We also predicted risk from the deviation of grades from family-genetic expectations (deviation 1) and from changes in grades from ages 16 to 19 (deviation 2). Results: We observed four major risk patterns across transitions in our disorders: (i) MD and BD, (ii) OCD and SZ, (iii) AUD and DUD, and (iv) AN. Failing early educational transitions had the greatest impact on risk for OCD and SZ while for other disorders, not progressing from basic to upper high school had the largest effect. Completing vocational v. college-prep upper high school was strongly associated with risk for AUD and DUD, had little relation with MD, OCD, BD, and SZ risk, and was protective for AN. Deviation 1 predicted risk most strongly for SZ, AN, and MD. Deviation 2 predicted risk most strongly for SZ, AUD, and DUD. Conclusions: The pattern of educational transitions and within family and within person development deviations are strongly and relatively specifically associated with future risk for seven psychiatric and substance-use disorders. [ABSTRACT FROM AUTHOR]

Background: Neurocognitive dysfunction in schizophrenia (SZ), bipolar (BD) and related disorders represents a core feature of these illnesses, possibly a marker of underlying pathophysiology. Substantial overlap in domains of neuropsychological deficits has been reported among these disorders after illness onset. However, it is unclear whether deficits follow the same longitudinal pre- and post-morbid course across diagnoses. We examine evidence for neurocognitive dysfunction as a core feature of all idiopathic psychotic illnesses, and trace its evolution from pre-morbid and prodromal states through the emergence of overt psychosis and into chronic illness in patients with SZ, BD and related disorders., Method: Articles reporting on neuropsychological functioning in patients with SZ, BD and related disorders before and after illness onset were reviewed. Given the vast literature on these topics and the present focus on cross-diagnostic comparisons, priority was given to primary data papers that assessed cross-diagnostic samples and recent meta-analyses., Results: Patients with SZ exhibit dysfunction preceding the onset of illness, which becomes more pronounced in the prodrome and early years following diagnosis, then settles into a stable pattern. Patients with BD generally exhibit typical cognitive development pre-morbidly, but demonstrate deficits by first episode that are amplified with worsening symptoms and exacerbations., Conclusions: Neuropsychological deficits represent a core feature of SZ and BD; however, their onset and progression differ between diagnostic groups. A lifetime perspective on the evolution of neurocognitive deficits in SZ and BD reveals distinct patterns, and may provide a useful guide to the examination of the pathophysiological processes underpinning these functions across disorders.

BackgroundThere are insufficient data from nationwide surveys on the prevalence of specific psychotic disorders and associated co-morbidities.MethodThe 2010 Australian national psychosis survey used a two-phase design to draw a representative sample of adults aged 18–64 years with psychotic disorders in contact with public treatment services from an estimated resident population of 1 464 923 adults. This paper is based on data from 1642 participants with an International Classification of Diseases (ICD)-10 psychotic disorder. Its aim is to present estimates of treated prevalence and lifetime morbid risk of psychosis, and to describe the cognitive, physical health and substance use profiles of participants.ResultsThe 1-month treated prevalence of psychotic disorders was 3.10 cases per 1000 population aged 18–64 years, not accounting for people solely accessing primary care services; lifetime morbid risk was 3.45 per 1000. Mean premorbid intelligence quotient was approximately 0.5 s.d.s below the population mean; current cognitive ability (measured with a digit symbol coding task) was 1.6 s.d.s below the population mean. For both cognitive tests, higher scores were significantly associated with better independent functioning. The prevalence of the metabolic syndrome was high, affecting 60.8% of participants, and pervasive across diagnostic groups. Of the participants, two-thirds (65.9%) were current smokers, 47.4% were obese and 32.4% were sedentary. Of the participants, half (49.8%) had a lifetime history of alcohol abuse/dependence and 50.8% lifetime cannabis abuse/dependence.ConclusionsOur findings highlight the need for comprehensive, integrative models of recovery to maximize the potential for good health and quality of life for people with psychotic illness. [ABSTRACT FROM PUBLISHER]

ObjectiveSchizophrenia (SCZ) and bipolar disorder (BD) are common psychotic disorders, which show some overlaps in genetic aetiology. Researchers have conducted a number of studies to investigate the relationship between SCZ and the 1354C/T genetic polymorphism of 5-hydroxytryptamine receptor 2A (HTR2A–1354C/T), as well as the associations between BD and the HTR2A–1354C/T polymorphism. However, the results were conflicting. To provide a more robust estimate about the effects of the HTR2A–1354C/T polymorphism on the risk of these two psychotic disorders, we performed this meta-analysis.MethodsWe used the pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) to investigate the relationships between SCZ and the 1354C/T polymorphism of HTR2A, as well as the associations between BD and HTR2A–1354C/T. Publication bias was tested by Begg's test and inverted funnel plot, and heterogeneity was checked by Cochran's Q statistic and the inconsistency index (I2).ResultsEight studies were concerned with SCZ, analysing a cumulative total of 2953 cases and 3153 controls; six papers studied BD, using a total of 923 cases and 928 controls. There was no significant association found between HTR2A–1354C/T and SCZ in the overall population (T allele vs. C allele, OR = 1.035, 95% CI 0.912–1.175, p = 0.596) or in the subgroups Caucasian population and Asian population. Moreover, there was no significant association between the HTR2A–1354C/T polymorphism and BD in the overall population (T allele vs. C allele, OR = 1.038, 95% CI = 0.607–1.772, p = 0.892).ConclusionOn the basis of these results, the HTR2A–1354C/T polymorphism is unlikely to be a risk factor for SCZ and BD. [ABSTRACT FROM PUBLISHER]

Background: The extant major psychiatric classifications, DSM-IV and ICD-10, are purportedly atheoretical and largely descriptive. Although this achieves good reliability, the validity of a medical diagnosis is greatly enhanced by an understanding of both risk factors and clinical history. In an effort to group mental disorders on the basis of risk factors and clinical manifestations, five clusters have been proposed. The purpose of this paper is to consider the position of bipolar disorder (BPD), which could be either with the psychoses, or with emotional disorders, or in a separate cluster., Method: We reviewed the literature on BPD, unipolar depression (UPD) and schizophrenia in relation to 11 validating criteria proposed by the DSM-V Task Force Study Group, and then summarized similarities and differences between BPD and schizophrenia on the one hand, and UPD on the other., Results: There are differences, often substantial and never trivial, for 10 of the 11 validators between BPD and UPD. There are also important differences between BPD and schizophrenia., Conclusion: BPD has previously been classified together with UPD, but this is the least justifiable place for it. If it is to be recruited to a 'psychotic cluster', there are several important respects in which it differs from schizophrenia, so the cluster would have a division within it. The alternative would be to allow it to be in an intermediate position in a cluster of its own.

Background: Previous work suggests that impairments in executive function and verbal memory in particular may persist in euthymic bipolar patients and serve as an indicator of genetic risk (endophenotype)., Method: A systematic review of the literature was undertaken. Effects sizes were extracted from selected papers and pooled using meta-analytical techniques., Results: In bipolar patients, large effect sizes (d>0.8) were noted for executive functions (working memory, executive control, fluency) and verbal memory. Medium effect sizes (0.5

Objective: To review the diagnostic validity and utility of mixed depression, i.e. co-occurrence of depression and manic/hypomanic symptoms., Methods: PubMed search of all English-language papers published between January 1966 and December 2006 using and cross-listing key words: bipolar disorder, mixed states, criteria, utility, validation, gender, temperament, depression-mixed states, mixed depression, depressive mixed state/s, dysphoric hypomania, mixed hypomania, mixed/dysphoric mania, agitated depression, anxiety disorders, neuroimaging, pathophysiology, and genetics. A manual review of paper reference lists was also conducted., Results: By classic diagnostic validators, the diagnostic validity of categorically-defined mixed depression (i.e. at least 2-3 manic/hypomanic symptoms) is mainly supported by family history (the current strongest diagnostic validator). Its diagnostic utility is supported by treatment response (negative effects of antidepressants). A dimensionally-defined mixed depression is instead supported by a non-bi-modal distribution of its intradepression manic/hypomanic symptoms., Discussion: Categorically-defined mixed depression may have some diagnostic validity (family history is the current strongest validator). Its diagnostic utility seems supported by treatment response.

Bipolar disorders are frequently not diagnosed until long after their onset, leaving patients with no or correspondingly inadequate treatment. The course of the disorder is all the more severe and the negative repercussions for those affected all the greater. Concerted research effort is therefore going into learning how to recognize bipolar disorders at an early stage. Drawing on current research results, this paper presents considerations for an integrative Early Symptom Scale with which persons at risk can be identified and timely intervention initiated. This will require prospective studies to determine the predictive power of the risk factors integrated into the scale.

Bipolar disorder (BPD) has received increasing attention from public and professional sources. Although pharmacologic treatments are considered the sine qua non in the treatment of youth with BPD, psychosocial interventions are critical to assist the child and family cope with symptoms that carry with them significant morbidity and mortality. Treatments developed to date are few in number; all are psychoeducationally based, using cognitive-behavioral and family systems interventions within a biopsychosocial framework. This paper reviews possible mediators of outcome, including caregiver concordance, children's social skills, hopelessness, and family stress. The author has developed two family-based psychoeducational interventions for the treatment of youth with BPD: multifamily psychoeducation groups (MFPG) and individual family psychoeducation (IFP). These treatments are both described and the results from a previously published randomized clinical trial (RCT) of MFPG are summarized. Then, new findings from an RCT of IFP are presented, along with preliminary pilot data from an expanded version of IFP. The paper concludes with recommendations for future research.

The goal of this paper is to review assessment research of bipolar disorder in children and adolescents. The review addresses numerous themes: the benefits and costs of involving clinical judgment in the diagnostic process, particularly with regard to diagnosis and mood severity ratings; the validity of parent, teacher, and youth self-report of manic symptoms; how much cross-situational consistency is typically shown in mood and behavior; the extent to which a parent's mental health status influences their report of child behavior; how different measures compare in terms of detecting bipolar disorder, the challenges in comparing the performance of measures across research groups, and the leading candidates for research or clinical use; evidence-based strategies for interpreting measures as diagnostic aids; how test performance changes when a test is used in a new setting and what implications this has for research samples as well as clinical practice; the role of family history of mood disorder within an assessment framework; and the implications of assessment research for the understanding of phenomenology of bipolar disorder from a developmental framework.

There is a great need for discovery of biological markers that could be used diagnostically for pediatric onset disorders, particularly those with potentially confusing phenomenology such as pediatric-onset bipolar disorder (BD). Obtaining these markers would help overcome current subjective diagnostic techniques of relying on parent and child interview and symptomatic history. Brain imaging may be the most logical choice for a diagnostic tool, and certain neurobiological abnormalities have already been found in pediatric BD. However, much work remains to be done before neuroimaging can be used reliably to diagnose this disorder, and because of the nature of BD and the limitations of imaging technology and technique, neuroimaging will likely at most be only a diagnostic aide in the near future. In this paper we discuss the characteristics of pediatric BD that complicate the use of biological markers as diagnostic tools, how neuroimaging techniques have been used to study pediatric BD so far, and the limitations and potential of such techniques for future diagnostic use.

Interpersonal and social rhythm therapy (IPSRT) is a manual-based adjunctive psychotherapy specific to the treatment of bipolar disorder. This paper reviews the theoretical rationale and empirical evidence for the efficacy of IPSRT in combination with pharmacotherapy for adults with bipolar I disorder. We then provide an overview of the developmental modifications being made to IPSRT to increase its relevance to adolescents with bipolar disorder.

The aim of this paper is to highlight the importance of the sleep-wake cycle in children and adolescents with bipolar disorder. After presenting an overview of the measurement and function of human sleep, we describe changes in sleep and circadian functioning across the life cycle. We then review evidence that, in adults, sleep and/or circadian rhythms are of considerable influence in the multifactorial causal chain implicated in relapse in bipolar disorder, discussing relevant mechanisms. The latter include abnormalities in the amount and timing of sleep, the role of social zeitgebers, and the importance of sleep in regulating emotional responses and mood. We next present preliminary data indicating considerable sleep disturbance among children and adolescents with bipolar disorder. Given the considerable sleep disturbance evident among children and adolescents with bipolar disorder along with a key role for sleep in emotion regulation and learning, we conclude that sleep among children and adolescents with bipolar disorder is a critical domain for future research. An agenda for future research is presented that includes descriptive studies, investigations of causality, and treatment development research.

Background: Previous work suggests that subthreshold depression and subthreshold (hypo)mania are common, although little is known about the prognosis in terms of transition to clinical disorder. This paper presents data on the temporal relationship between subthreshold and clinical expression of mood phenotypes., Method: In a random general population sample of 7076 individuals, symptoms of depression and (hypo)mania were measured with the Composite International Diagnostic Interview (CIDI) at baseline, after 1 year, and 2 years later., Results: At baseline, the lifetime prevalences of depressive and (hypo)manic symptoms were 17.2% and 1.2% respectively. Predictive values of mood symptoms for a DSM-III-R mood disorder ranged from 14.3% to 50%. (Hypo)manic mood symptoms had much higher predictive values than unipolar manifestations, not only for bipolar disorder but also for major depression., Conclusions: The subthreshold expressions of depression and (hypo)mania are prevalent and continuous with more severe clinical states. The cross-prediction of mood symptoms may support a continuum from depressive to (hypo)manic symptoms. The high predictive value of (hypo)manic symptoms for mood disorders suggests that the experience of (hypo)manic symptoms is a stronger indicator of vulnerability for mood dysregulation than the experience of depressive symptoms.

In a previous paper, the authors found that impairment on the Wisconsin Card Sorting Test (WCST) in adolescence was predictive of bipolar disorder in young adulthood among offspring of mothers with bipolar illness. In the present study, the authors explore the contribution of maternal characteristics, beyond maternal mood disorder, to the prediction of offspring dysfunction on the WCST. Results showed that maternal bipolar disorder and maternal negativity were both predictive of impaired performance on the WCST during adolescence. The contribution of maternal negativity to offspring WCST impairment was not better explained by maternal personality disorder, mother's functional impairment, family loading for bipolar disorder, or offspring disruptive behavioral disturbance. Findings did not support a moderator model. However, support was found for a mediation model in which maternal negativity contributed to risk for offspring bipolar disorder through its negative association with apparent frontal lobe functioning, as measured by the WCST. Findings are discussed from the perspective of a vulnerability-stress model. In addition, the authors consider the possibility that maternal negativity and offspring impairment on the WCST may be reflective of a common heritable trait.

Both typical and atypical antipsychotic psychotropics have been reported to cause ischemic priapism presumptively secondary to alpha1-adrenergic blockade. This condition is a urologic emergency for if not evaluated and treated appropriately, long-term sequelae include erectile dysfunction and impotence. This paper addresses the first reported case of priapism requiring surgical intervention presumed to be secondary to ziprasidone. Increased clinician and patient education regarding priapism is required in order to minimize this adverse event and to maximize immediate treatment.

Biomarkers for diagnosis and treatment of Bipolar Disorder: hope or hype? Professor Allan Young, Centre for Affective Disorders, IoPPN, KCL London, SE5 8AF. allan.young@kcl.ac.uk The use of "biomarkers" (biological markers) in basic and clinical research as well as in clinical practice has become so commonplace in many areas of medicine that their presence as primary endpoints in clinical trials is now widely accepted. In clinical disciplines where specific biomarkers have been well characterized and repeatedly shown to correctly predict relevant clinical outcomes across a variety of treatments and populations, this use is entirely justified and appropriate. However, the validity of biomarkers in most psychiatric disorders continues to be evaluated. This lecture will review the current conceptual status of biomarkers as clinical and diagnostic tools for bipolar disorder and as surrogate endpoints in clinical research in bipolar disorder. The conceptual background in terms of current diagnostic categories and research domain criteria will be discussed and the various approaches with putative value (e.g., brain imaging, genetics, and neuroendocrinology) reviewed (1, 2). The lecture will end with a discussion of approaches to evaluating biomarkers of lithium response (3). [ABSTRACT FROM AUTHOR]

Background: Despite increasing adoption of clinical practice guidelines in psychiatry, there is little measurement of provider implementation of these recommendations, and the resulting impact on clinical outcomes. The current study describes one effort to measure these relationships in a cohort of public sector out-patients with bipolar disorder., Method: Participants were enrolled in the algorithm intervention of the Texas Medication Algorithm Project (TMAP). Study methods and the adherence scoring algorithm have been described elsewhere. The current paper addresses the relationships between patient characteristics, provider experience with the algorithm, provider adherence, and clinical outcomes. Measurement of provider adherence includes evaluation of visit frequency, medication choice and dosing, and response to patient symptoms. An exploratory composite 'adherence by visit' score was developed for these analyses., Results: A total of 1948 visits from 141 subjects were evaluated, and utilized a two-stage declining effects model. Providers with more experience using the algorithm tended to adhere less to treatment recommendations. Few patient factors significantly impacted provider adherence. Increased adherence to algorithm recommendations was associated with larger decreases in overall psychiatric symptoms and depressive symptoms over time, but did not impact either immediate or long-term reductions in manic symptoms., Conclusions: Greater provider adherence to treatment guideline recommendations was associated with greater reductions in depressive symptoms and overall psychiatric symptoms over time. Additional research is needed to refine measurement and to further clarify these relationships.

Background: The German National Health Interview and Examination Survey (GHS) is the first government mandated nationwide study to investigate jointly the prevalence of somatic and mental disorders within one study in the general adult population in Germany. This paper reports results from its Mental Health Supplement (GHS-MHS) on 4-week 12-month, and selected lifetime prevalence of a broad range of DSM-IV mental disorders, their co-morbidity and correlates in the community., Methods: The sample of the GHS-MHS (n=4181; multistage stratified random sample drawn from population registries; conditional response rate: 87.6%) can be regarded as representative for the German population aged 18-65. Diagnoses are based on fully structured computer assisted clinical interviews (M-CIDI), conducted by clinically trained interviewers., Results: 12-month prevalence for any DSM-IV study disorder is 31% (lifetime: 43%; 4-week: 20%) with anxiety disorders, mood disorders and somatoform syndromes being the most frequent diagnoses. Retrospective age of onset information reveals that most disorders begin early in life. Co-morbidity rates among mental disorders range from 44% to 94%. Correlates of increased rates of mental disorders and co-morbidity were: female gender (except for substance disorders), not being married, low social class, and poor somatic health status. Health care utilization for mental disorders depended on co-morbidity (30% in 'pure', 76% in highly co-morbid cases) and varied from 33% for substance use disorders to 75% for panic disorder., Conclusions: Results confirm and extend results from other national studies using the same assessment instruments with regard to prevalence, co-morbidity and sociodemographic correlates, covering a broader range of DSM-IV disorders [i.e. somatoform disorders, all anxiety disorders (except PTSD), mental disorders due to substance or general medical factor, eating disorders]. Intervention rates were higher than in previous studies, yet still low overall.

AbstractThis paper provides a selected review of recent studies highlighting key aspects of mood disorders research. Cognitive models and clinical trials of cognitive therapy of depression are evolving and adapting to increase applicability to the spectrum of depressive symptoms and syndromes experienced by clients, as well exploring beyond acute phase treatment to relapse prevention. In contrast, cognitive models of bipolar disorders and the effectiveness of the therapy are unclear and there are more questions than answers for researchers in this area. [ABSTRACT FROM AUTHOR]