Individual variation in brain network topology is linked to course of illness in major depressive disorder.

Major depressive disorder (MDD) is a chronic and highly recurrent disorder. The functional connectivity in depression is affected by the cumulative effect of course of illness. However, previous neuroimaging studies on abnormal functional connection have not mainly focused on the disease duration, which is seen as a secondary factor. Here, we used a data-driven analysis (multivariate distance matrix regression) to examine the relationship between the course of illness and resting-state functional dysconnectivity in MDD. This method identified a region in the anterior cingulate cortex, which is most linked to course of illness. Specifically, follow-up seed analyses show this phenomenon resulted from the individual differences in the topological distribution of three networks. In individuals with short-duration MDD, the connection to the default mode network was strong. By contrast, individuals with long-duration MDD showed hyperconnectivity to the ventral attention network and the frontoparietal network. These results emphasized the centrality of the anterior cingulate cortex in the pathophysiology of the increased course of illness and implied critical links between network topography and pathological duration. Thus, dissociable patterns of connectivity of the anterior cingulate cortex is an important dimension feature of the disease process of depression.

White matter fiber microstructure is associated with prior hospitalizations rather than acute symptomatology in major depressive disorder.

BACKGROUND: Eighty percent of all patients suffering from major depressive disorder (MDD) relapse at least once in their lifetime. Thus, understanding the neurobiological underpinnings of the course of MDD is of utmost importance. A detrimental course of illness in MDD was most consistently associated with superior longitudinal fasciculus (SLF) fiber integrity. As similar associations were, however, found between SLF fiber integrity and acute symptomatology, this study attempts to disentangle associations attributed to current depression from long-term course of illness. METHODS: A total of 531 patients suffering from acute (N = 250) or remitted (N = 281) MDD from the FOR2107-cohort were analyzed in this cross-sectional study using tract-based spatial statistics for diffusion tensor imaging. First, the effects of disease state (acute v. remitted), current symptom severity (BDI-score) and course of illness (number of hospitalizations) on fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity were analyzed separately. Second, disease state and BDI-scores were analyzed in conjunction with the number of hospitalizations to disentangle their effects. RESULTS: Disease state (pFWE < 0.042) and number of hospitalizations (pFWE< 0.032) were associated with decreased FA and increased MD and RD in the bilateral SLF. A trend was found for the BDI-score (pFWE > 0.067). When analyzed simultaneously only the effect of course of illness remained significant (pFWE < 0.040) mapping to the right SLF. CONCLUSIONS: Decreased FA and increased MD and RD values in the SLF are associated with more hospitalizations when controlling for current psychopathology. SLF fiber integrity could reflect cumulative illness burden at a neurobiological level and should be targeted in future longitudinal analyses.

Social capital and psychosis: a scoping review.

PURPOSE: Social capital has been studied as a risk factor for psychotic disorders. The purpose of this scoping review was to scope the literature and synthesize findings on the association between social capital and psychosis. METHODS: Three electronic databases were searched to identify relevant studies. Studies were included if they examined the association between social capital and either diagnosed psychotic disorders or symptoms of psychosis. RESULTS: Of 191 studies reviewed, 12 met the inclusion criteria. Ten studies measured social capital at the ecological level. Seven studies focused on risk of psychotic disorders or symptoms of psychosis, three studies focused on course of psychotic illness, and two studies focused on both risk and course of illness. A variety of social capital measures were used including scales, surveys, and census-based measures. The association between social capital and both the incidence of psychosis and patterns of service use varied based on measures used and study population. There was no association between social capital and recovery or duration of untreated illness. CONCLUSIONS: Prior literature has examined the impact of social capital on the incidence of psychotic disorders, as well as symptoms and course of illness. Based on the scant literature to date, it is difficult to make firm conclusions regarding the role of social capital in psychotic disorders. Heterogeneous measures of social capital make comparisons between studies challenging. Further specificity in measuring and defining dimensions of social capital is required for meaningful study of social capital and its association with psychotic disorders.

The longitudinal course of schizophrenia: testosterone and progression of the negative symptoms.

Background: The longitudinal course of schizophrenia shows a high level of heterogeneity with testosterone as a possible factor in the variety of clinical outcomes.Aim: Evaluation of the course of schizophrenia in male patients over an eight-year period and of the possible testosterone effects on changes in clinical features.Subjects and methods: The initial study population consisted of 120 male schizophrenic patients (aged 18-40) hospitalized in the University Psychiatric Hospital Vrapce in 2009. Patients were classified into nonaggressive (control, n = 60) and aggressive (n = 60) groups. In 2017, we reassessed 85 patients (67,5%) from the initial sample. Symptoms of schizophrenia were determined using the Positive and Negative Syndrome Scale (PANSS) and compared with the total serum testosterone level taken at the inclusion in the study. The distribution of values for individual variables was determined using the Smirnov-Kolmogorov test; for all further analyses, the appropriate non-parametric test was used.Results: The control group showed a statistically significant negative correlation between testosterone and negative PANSS. The initial PANSS scores, compared to those at the follow-up, showed a statistically significant reduction in positive and general symptoms in all groups, with the greatest reduction in the control group.Conclusion: We found a reduction in positive and general symptoms of schizophrenia among all patients and no changes in negative symptoms. Inverse correlation between testosterone and negative symptoms was found only in the control group, but there was no testosterone influence on the progression of any PANSS subscales.

Neurobiology of the major psychoses: a translational perspective on brain structure and function-the FOR2107 consortium.

Genetic (G) and environmental (E) factors are involved in the etiology and course of the major psychoses (MP), i.e. major depressive disorder (MDD), bipolar disorder (BD), schizoaffective disorder (SZA) and schizophrenia (SZ). The neurobiological correlates by which these predispositions exert their influence on brain structure, function and course of illness are poorly understood. In the FOR2107 consortium, animal models and humans are investigated. A human cohort of MP patients, healthy subjects at genetic and/or environmental risk, and control subjects (N = 2500) has been established. Participants are followed up after 2 years and twice underwent extensive deep phenotyping (MR imaging, clinical course, neuropsychology, personality, risk/protective factors, biomaterials: blood, stool, urine, hair, saliva). Methods for data reduction, quality assurance for longitudinal MRI data, and (deep) machine learning techniques are employed. In the parallelised animal cluster, genetic risk was introduced by a rodent model (Cacna1c deficiency) and its interactions with environmental risk and protective factors are studied. The animals are deeply phenotyped regarding cognition, emotion, and social function, paralleling the variables assessed in humans. A set of innovative experimental projects connect and integrate data from the human and animal parts, investigating the role of microRNA, neuroplasticity, immune signatures, (epi-)genetics and gene expression. Biomaterial from humans and animals are analyzed in parallel. The FOR2107 consortium will delineate pathophysiological entities with common neurobiological underpinnings ("biotypes") and pave the way for an etiologic understanding of the MP, potentially leading to their prevention, the prediction of individual disease courses, and novel therapies in the future.

Implicit affectivity in clinically depressed patients during acute illness and recovery.

BACKGROUND: Clinical depression is characterized by high levels of negative affect (NA) and attenuated positive affect (PA). Psychological and pharmacological treatments have been shown to reduce NA and to enhance PA in depressed patients. Following dual-process models, two types of affect can be distinguished: explicit (or self-reported) affect, which is formed by conscious reflections, and implicit affect, which relates to automatic affective reactions. The present study was conducted to examine, for the first time, both implicit and explicit affectivity in patients suffering from acute depression. Moreover, changes in patients' implicit and explicit affectivity were investigated over the course of inpatient treatment. METHODS: Thirty-nine patients suffering from major depression and 39 healthy individuals participated in the study. Implicit affectivity was assessed using the Implicit Positive and Negative Affect Test. The explicit state and trait affectivity were measured by the Positive and Negative Affect Schedule. The level of depressive symptoms was assessed with the Beck Depression Inventory. Tests were administered to patients after admission and after 7 weeks of therapy, whereas healthy controls were investigated only once. We examined whether either comorbidity or antidepressant medication has an effect on affectivity. RESULTS: Patients with acute depression had lower implicit and explicit PA scores and higher implicit and explicit NA scores than the healthy controls. After treatment, patients' level of depression decreased significantly. At posttreatment, patients exhibited heightened implicit and explicit PA and diminished explicit trait NA. Independent of antidepressant medication and comorbidity, no significant change in implicit NA was observed over the course of treatment. Implicit NA was correlated with explicit NA in acute depression but not during recovery. CONCLUSIONS: Acute depression appears to be characterized by decreased implicit and explicit PA and increased implicit and explicit NA. After 7 weeks of treatment, depressed patients' implicit and explicit PA increased, and explicit trait NA decreased. No decrease in implicit NA and explicit state NA occurred over the course of treatment. Finally, it seems that in the state of acute depression, the interplay between the automatic and reflective systems could be increased for negative affectivity.

Chronic obsessive-compulsive disorder: prognostic factors.

BACKGROUND: The course of illness in obsessive-compulsive disorder (OCD) varies significantly between patients. Little is known about factors predicting a chronic course of illness. The aim of this study is to identify factors involved in inducing and in maintaining chronicity in OCD. METHODS: The present study is embedded within the Netherlands Obsessive Compulsive Disorder Association (NOCDA) study, an ongoing multicenter naturalistic cohort study designed to identify predictors of long-term course and outcome in OCD. For this study, 270 subjects with a current diagnosis of OCD were included. Chronicity status at 2-year follow-up was regressed on a selection of baseline predictors related to OCD, to comorbidity and to stress and support. RESULTS: Psychotrauma [odds ratio (OR) 1.98, confidence interval (CI) 1.22-3.22, p = 0.006], recent negative life events (OR 1.42, CI 1.01-2.01, p = 0.043), and presence of a partner (OR 0.28, CI 0.09-0.85, p = 0.025) influenced the risk of becoming chronic. Longer illness duration (OR 1.46, CI 1.08-1.96, p = 0.013) and higher illness severity (OR 1.09, CI 1.03-1.16, p = 0.003) increased the risk of remaining chronic. CONCLUSIONS: External influences increase the risk of becoming chronic, whereas the factors involved in maintaining chronicity are illness-related. As the latter are potentially difficult to modify, treatment should be devoted to prevent chronicity from occurring in the first place. Therapeutic strategies aimed at alleviating stress and at boosting social support might aid in achieving this goal.

Sex similarities and differences in risk factors for recurrence of major depression.

BACKGROUND: Major depression (MD) occurs about twice as often in women as in men, but it is unclear whether sex differences subsist after disease onset. This study aims to elucidate potential sex differences in rates and risk factors for MD recurrence, in order to improve prediction of course of illness and understanding of its underlying mechanisms. METHODS: We used prospective data from a general population sample (n = 653) that experienced a recent episode of MD. A diverse set of potential risk factors for recurrence of MD was analyzed using Cox models subject to elastic net regularization for males and females separately. Accuracy of the prediction models was tested in same-sex and opposite-sex test data. Additionally, interactions between sex and each of the risk factors were investigated to identify potential sex differences. RESULTS: Recurrence rates and the impact of most risk factors were similar for men and women. For both sexes, prediction models were highly multifactorial including risk factors such as comorbid anxiety, early traumas, and family history. Some subtle sex differences were detected: for men, prediction models included more risk factors concerning characteristics of the depressive episode and family history of MD and generalized anxiety, whereas for women, models included more risk factors concerning early and recent adverse life events and socioeconomic problems. CONCLUSIONS: No prominent sex differences in risk factors for recurrence of MD were found, potentially indicating similar disease maintaining mechanisms for both sexes. Course of MD is a multifactorial phenomenon for both males and females.

Clinical and functional outcomes of cannabis use among individuals with anxiety disorders: A 3-year population-based longitudinal study.

BACKGROUND: Cannabis use has been reported to negatively affect the course and outcome of various psychiatric disorders, yet little is known on its effect on rates of remission from anxiety disorders and associated clinical and functional outcomes. METHODS: In this study, data were drawn from Waves 1 and 2 of the National Epidemiologic survey on Alcohol and Related Conditions, focusing on individuals who qualified for a diagnosis of any anxiety disorder (social anxiety, panic disorder, generalized anxiety disorder, and specific phobias) at Wave 1 (N = 3,723). Cannabis users and individuals with cannabis use disorders (CUDs) throughout a 4-year period were compared to nonusers in rates of remission, suicidality, general functioning, and quality of life at Wave 2, while controlling for baseline confounders. RESULTS: Although rates of remission decreased with level of cannabis use, this was not maintained in adjusted models. Aside from specific outcomes (individuals with CUDs were significantly more prone to report breaking up from a romantic relationship; adjusted odds ratio [AOR] = 3.85, 95% confidence interval [CI] = 1.66-8.97) and repeatedly quitting school (AOR = 6.02, 95% CI = 2.65-13.66)), following adjustment no additional differences were found in outcome measures. CONCLUSIONS: These findings add to previous reports suggesting that poorer outcome of anxiety disorders among cannabis users may be attributed mainly to differences in baseline factors and not cannabis use.

Rates and predictors of remission, recurrence and conversion to bipolar disorder after the first lifetime episode of depression--a prospective 5-year follow-up study.

BACKGROUND: In depression, non-remission, recurrence of depressive episodes after remission and conversion to bipolar disorder are crucial determinants of poor outcome. The present study aimed to determine the cumulative incidences and clinical predictors of these long-term outcomes after the first lifetime episode of depression. METHOD: A total of 301 in- or out-patients aged 18-70 years with a validated diagnosis of a single depressive episode were assessed from 2005 to 2007. At 5 years of follow-up, 262 patients were reassessed by means of the life chart method and diagnostic interviews from 2011 to 2013. Cumulative incidences and the influence of clinical variables on the rates of remission, recurrence and conversion to bipolar disorder, respectively, were estimated by survival analysis techniques. RESULTS: Within 5 years, 83.3% obtained remission, 31.5% experienced recurrence of depression and 8.6% converted to bipolar disorder (6.3% within the first 2 years). Non-remission increased with younger age, co-morbid anxiety and suicidal ideations. Recurrence increased with severity and treatment resistance of the first depression, and conversion to bipolar disorder with treatment resistance, a family history of affective disorder and co-morbid alcohol or drug abuse. CONCLUSIONS: The identified clinical characteristics of the first lifetime episode of depression should guide patients and clinicians for long-term individualized tailored treatment.

Obsessive-compulsive disorder in pregnancy and the postpartum period: course of illness and obstetrical outcome.

The study aimed to examine the course of obsessive-compulsive disorder (OCD) across pregnancy and its impact on obstetric and neonatal outcomes. Women enrolled prior to 20-week gestation in a prospective, observational study. The Structured Clinical Interview for DSM-IV was completed to obtain lifetime Axis I diagnoses. A total of 56 women with OCD were followed at 1 to 3-month intervals through 52 weeks postpartum. Each visit, the Yale-Brown Obsessive Compulsive Scale (YBOCS), clinical assessment, and medication/exposure tracking were performed. Obstetric and neonatal data were abstracted from the medical record. In subjects with OCD, associations between perinatal obsessive-compulsive symptoms (OCSs) and outcomes were examined. Additionally, outcomes were compared to 156 matched psychiatric patients without OCD. Maternal age inversely correlated with the YBOCS scores across the study period (ß = -0.5161, p = .0378). Cesarean section was associated with increased OCSs in the postpartum period compared to vaginal delivery (ß = 5.3632, p = 0.043). No associations were found between severity of perinatal obsessions or compulsions and any specific obstetric or neonatal complications. Subjects without OCD had higher frequency of fetal loss compared to mothers with OCD (χ (2) = 4.03, p = 0.043). These novel prospective data fail to identify an association of OCSs with adverse outcomes. In contrast, there is an association of delivery method and younger maternal age with increased postnatal symptoms of OCD. Psychiatric subjects without OCD may have a higher risk of miscarriage and intrauterine fetal demise compared to subjects with OCD.

Combined treatment: impact of optimal psychotherapy and medication in bipolar disorder.

OBJECTIVES: The current study investigated the longitudinal course of symptoms in bipolar disorder among individuals receiving optimal treatment combining pharmacotherapy and psychotherapy, as well as predictors of the course of illness. METHODS: A total of 160 participants with bipolar disorder (bipolar I disorder: n = 115; bipolar II disorder: n = 45) received regular pharmacological treatment, complemented by a manualized, evidence-based psychosocial treatment - that is, cognitive behavioral therapy or psychoeducation. Participants were assessed at baseline and prospectively for 72 weeks using the Longitudinal Interval Follow-up Evaluation (LIFE) scale scores for mania/hypomania and depression, as well as comparison measures (clinicaltrials.gov identifier: NCT00188838). RESULTS: Over a 72-week period, patients spent a clear majority (about 65%) of time euthymic. Symptoms were experienced more than 50% of the time by only a quarter of the sample. Depressive symptoms strongly dominated over (hypo)manic symptoms, while subsyndromal symptoms were more common than full diagnosable episodes for both polarities. Mixed symptoms were rare, but present for a minority of participants. Individuals experienced approximately six significant mood changes per year, with a full relapse on average every 7.5 months. Participants who had fewer depressive symptoms at intake, a later age at onset, and no history of psychotic symptoms spent more weeks well over the course of the study. CONCLUSIONS: Combined pharmacological and adjunctive psychosocial treatments appeared to provide an improved course of illness compared to the results of previous studies. Efforts to further improve the course of illness beyond that provided by current optimal treatment regimens will require a substantial focus on both subsyndromal and syndromal depressive symptoms.

Longitudinal Comparison of PNES spell and ASM reduction in PNES Patients with and without Epilepsy Discharged from an Epilepsy Monitoring Unit.

OBJECTIVE: To examine trends of Antiseizure Medication (ASM) reduction and discontinuation, as well as Psychogenic Non-Epileptic Seizure (PNES) spell reduction and resolution in patients with PNES, with and without comorbid epileptic seizures (ES). METHODS: A retrospective analysis was conducted on data from 145 patients with PNES, including 109 with PNES alone and 36 with PNES plus comorbid epilepsy. Patients were admitted to the Epilepsy Monitoring Unit (EMU) between May 2000 and April 2008, with follow-up clinical data collected until September 2015. Clinical records were thoroughly examined, encompassing the period preceding the PNES diagnosis until either loss to follow-up or September 2015. A subsequent chart review was conducted by two neurologists, covering the period following the diagnosis of PNES until either loss to follow-up or September 2015, which ever came first. RESULTS: Patients with PNES alone had higher rates of ASM reduction for all variables of ASM reduction measured compared to those with comorbid epilepsy (all at p < 001). Among patients with PNES alone, reductions in ASMs were observed after EMU discharge, but an uptick and plateau were seen in later follow-up years (100% of patients free of ASMs at years 2-3, 20% on at least one ASM by year 7). This pattern differs greatly in PNES + ES patients, in which the only time point at which any patient was able to discontinue all ASMs was at EMU discharge (4.5% of patients), with all patients taking at least one ASM for every other follow-up time point. Reductions in PNES spell frequency did not differ significantly between the two groups (for example PNES spells reduced at final FU 47.2% vs 42.9%, p = 0.65). In both groups, despite an initial drop in variables of PNES spell reduction and resolution in the early years post discharge, there is an eventual rebound and plateau (for example in PNES only patients, 33.9% of patients having no resolution in 1st year FU, which rises to 78% at years 4-5, and plateus around 52.8% at more than 7 years follow-up.) SIGNIFICANCE: This study contributes to the growing body of research focused on improving the current approach to management and prognostic outlook of PNES. Although PNES only patients had higher rates of ASM reduction, the uptick and plateau observed in later years highlights the challenges in managing PNES. Similarly, the continued persistence and rebound of PNES spells underline the continued poor prognostic outcomes associated with this condition.

Obsessive-Compulsive Disorder as an Epiphenomenon of Comorbid Bipolar Disorder? An Updated Systematic Review.

BACKGROUND: Bipolar disorder (BD) and obsessive-compulsive disorder (OCD) comorbidity is an emerging condition in psychiatry, with relevant nosological, clinical, and therapeutic implications. METHODS: We updated our previous systematic review on epidemiology and standard diagnostic validators (including phenomenology, course of illness, heredity, biological markers, and treatment response) of BD-OCD. Relevant papers published until (and including) 15 October 2023 were identified by searching the electronic databases MEDLINE, Embase, PsychINFO, and Cochrane Library, according to the PRISMA statement (PROSPERO registration number, CRD42021267685). RESULTS: We identified 38 new articles, which added to the previous 64 and raised the total to 102. The lifetime comorbidity prevalence ranged from 0.26 to 27.8% for BD and from 0.3 to 53.3% for OCD. The onset of the two disorders appears to be often overlapping, although the appearance of the primary disorder may influence the outcome. Compared to a single diagnosis, BD-OCD exhibited a distinct pattern of OC symptoms typically following an episodic course, occurring in up to 75% of cases (vs. 3%). Notably, these OC symptoms tended to worsen during depressive episodes (78%) and improve during manic or hypomanic episodes (64%). Similarly, a BD course appears to be chronic in individuals with BD-OCD in comparison to patients without. Additionally, individuals with BD-OCD comorbidity experienced more depressive episodes (mean of 8.9 ± 4.2) compared to those without comorbidity (mean of 4.1 ± 2.7). CONCLUSIONS: We found a greater likelihood of antidepressant-induced manic/hypomanic episodes (60% vs. 4.1%), and mood stabilizers with antipsychotic add-ons emerging as a preferred treatment. In line with our previous work, BD-OCD comorbidity encompasses a condition of greater nosological and clinical complexity than individual disorders.

Are personality disorders in bipolar patients more frequent in the US than Europe?

OBJECTIVE: Bipolar patients in the United States (US) compared to those from the Netherlands and Germany (here abbrev. as "Europe") have more Axis I comorbidities and more poor prognosis factors such as early onset and psychosocial adversity in childhood. We wished to examine whether these differences also extended to Axis II personality disorders (PDs). METHODS: 793 outpatients with bipolar disorder diagnosed by SCID gave informed consent for participating in a prospective longitudinal follow up study with clinician ratings at each visit. They completed detailed patient questionnaires and a 99 item personality disorder inventory (PDQ-4). US versus European differences in PDs were examined in univariate analyses and then logistic regressions, controlling for severity of depression, age, gender, and other poor prognosis factors. RESULTS: In the univariate analysis, 7 PDs were more prevalent in the US than in Europe, including antisocial, avoidant, borderline, depressive, histrionic, obsessive compulsive, and schizoid PDs. In the multivariate analysis, the last 4 of these PDs remained independently greater in the US than Europe. CONCLUSIONS: Although limited by use of self report and other potentially confounding factors, multiple PDs were more prevalent in the US than in Europe, but these preliminary findings need to be confirmed using other methodologies. Other poor prognosis factors are prevalent in the US, including early age of onset, more childhood adversity, anxiety and substance abuse comorbidity, and more episodes and rapid cycling. The interactions among these variables in relationship to the more adverse course of illness in the US than in Europe require further study.

Perceived Course of Illness on the Desire for Social Distance From People Suffering From Symptoms of Schizophrenia in India.

Background: Stigmatization of people with schizophrenia remains a highly relevant topic worldwide, particularly in low- and middle-income countries like India. It is crucial to identify the determinants of the desire for social distance as a proxy for discriminatory behavior in a socio-cultural context to indicate ways to reduce stigma. This study aims to explore whether the public perception of the perceived course of an illness concerning people with symptoms of schizophrenia has an impact on the desire for social distance. Subjects and Methods: Data collection took place in five cities in India. The sample (N = 447) was stratified for gender, age, and religion. Desire for social distance was sampled based on a self-reported questionnaire using unlabelled vignettes for schizophrenia. First, factor analysis was conducted to identify the main factors underlying the perception of the perceived course of the illness. Subsequently, a regression analysis was conducted to examine the impact of the perception of those prognostic factors on the desire for social distance. Results: Factor analysis revealed two independent factors of the perceived course of an illness: (1) life-long dependency on others and loss of social integration and functioning and (2) positive expectations toward treatment outcome. This second factor was significantly associated with a less desire for social distance toward persons with schizophrenia. Conclusion: The desire for social distance toward people with schizophrenia reduces with the expectation of positive treatment outcomes which underlines the need to raise public mental health awareness and provide psychoeducation for affected people and their family members in India. Help-seeking behaviors can be promoted by directing those needing treatment toward locally available, affordable and credible community-based services rather than facility-based care. Strikingly, lifelong dependency and the inability to socially integrate do not increase the desire for social distance, reflecting the Indian nation's socio-relational values and insufficiency of public mental health services. This indicates the suitability of systemic therapy approaches in public mental healthcare services to support the family's involvement and family-based interventions in caregiving for mentally ill people across the lifespan.

Early Course of Symptom Development in Anorexia Nervosa.

PURPOSE: Anorexia nervosa (AN) commonly begins in adolescence; however, detailed knowledge of symptom trajectories, including their temporal sequence, is less well elucidated. The purpose of the present study is to describe the onset and duration of disordered eating behaviors prior to a diagnosis of AN, examine concordance between child and parent report, and examine the relationships between timing of symptom onset and illness severity. METHODS: Seventy-one adolescents (ages 12-18 years) and their parents were interviewed about dieting, restriction, loss of control/binge eating, purging, excessive/compulsive exercise, weight history, and amenorrhea. Body mass index percentiles were calculated, and adolescents completed the Eating Disorder Examination-Questionnaire. RESULTS: Restriction, being underweight, dieting, and excessive exercise were reported by most of the sample; purging, loss-of-control eating, and having been overweight were reported by less than a third. Dieting typically emerged first, on average around age 14; the remainder of behaviors tended to emerge between ages 14 and 14½; and average age of formal diagnosis was slightly over 15 years. Dyads had good agreement regarding presence and timing of all behaviors except for dieting, for which children reported about 6 months earlier onset/longer duration, compared to parents. Although older age at interview was associated with lower body mass index percentile and higher EDE-Q score, neither age of onset nor duration was associated with severity when controlling for current age. DISCUSSION: Teens and parents describe a similar sequence of behavior changes leading up to a diagnosis of AN that typically begins with dieting and occurs over an approximate 1- to 1½-year period. Querying teens and parents about eating behavior changes may aid in identification and early intervention in AN; adolescents with normal weight who engage in persistent dieting or restrictive eating may warrant more frequent weight monitoring.

Impact of clozapine on disability and course of illness in patients with schizophrenia: A study from North India.

AIM: The aim of this study was to evaluate the impact of long-term use of clozapine on disability and course of illness among patients with treatment-resistant schizophrenia. MATERIALS AND METHODS: 102 participants who have been receiving clozapine for a mean duration of 5 years were evaluated on Positive and Negative Syndrome Scale (PANSS) rating, Clinical Global Impression (CGI) severity rating, and Indian Disability Evaluation and Assessment Scale (IDEAS) and the scores were compared with the scores on the same scales at the time of starting clozapine. RESULTS: There was a significant reduction in both CGI-severity scores and scores in all the four domains of IDEAS, alongside a significant reduction on all three subscales of PANSS with clozapine treatment. The CGI global improvement subscale was rated as very much improved for 80 patients. In terms of course of symptoms, at 6 months of clozapine use, three-fourth of the patients were rated as having partial recovery with no relapse of symptoms, but with passage of time, the proportion of patients in the category of "complete recovery" was found to be increasing. Higher CGI severity at the follow-up, lower CGI global improvement, and poorer efficacy index were associated with higher disability at the follow-up. CONCLUSIONS: The present study suggests that clozapine has a significant beneficial impact on disability and course of illness among patients with treatment-resistant schizophrenia.

The course and concomitants of depression in first-episode schizophrenia spectrum disorders: A 24-month longitudinal study.

Depressive symptoms are common in schizophrenia and have been associated with both favourable and unfavourable outcomes. We studied the longitudinal course of depressive symptoms and explored their temporal relationships with other manifestations of the illness and its treatment. This longitudinal cohort study included 126 antipsychotic naïve or only briefly treated patients with first-episode schizophrenia spectrum disorders treated with a long-acting antipsychotic over 24 months. Depressive symptoms were assessed at three monthly intervals using the Calgary Depression Scale for Schizophrenia and changes over time were assessed using linear mixed-effect models for continuous repeated measures. Depressive symptoms were most prominent at baseline with highly significant reductions during the first three months of treatment and maintenance of improvement thereafter. Most improvement occurred with antipsychotic treatment alone, with few patients requiring additional antidepressants. We also found that depressive symptoms were associated with positive symptoms, better insight and poorer quality of life, but not with negative symptoms, extrapyramidal symptoms, substance use or cumulative antipsychotic dose.There were few differences between patients who met criteria for depression during the acute phase of treatment and those in the post-acute phase.

Trajectories of symptoms of anxiety and depression among people on sick leave with mood or anxiety disorders: Secondary analysis from a randomized controlled trial.

BACKGROUND: Depression and anxiety are heterogenous disorders often combined into one entity in studies. Few studies have compared trajectories of depression and anxiety among clinically ill. We aimed to identify specific trajectories of depression, and anxiety and predictors of trajectory membership. METHODS: Latent growth mixture modelling was carried out on data from the IPS-MA trial (n = 261), a supported employment intervention for people with mood or anxiety, to identify trajectories of depression and anxiety. Logistic regression was used to estimate predictors for trajectory membership. Associations between trajectory class and remission of comorbid depression or anxiety and return to work were also tested. RESULTS: We identified three trajectories of depression and anxiety symptoms respectively; moderate-decreasing (60%), moderate-stable (26%), and low-stable (14%) depression and mild-decreasing (59%), moderate-decreasing (33%), and moderate-stable (8%) anxiety. The depression model showed low precision in class separation (entropy 0.66), hence, predictors of class membership were not estimated. For anxiety, lower age and higher levels of depressive symptoms were associated with a less desirable trajectory. Remission of comorbid depressive symptoms after two years differed significantly between classes (p < 0.000). Fewer had returned to work in the two moderate classes compared to the mild-decreasing anxiety class. LIMITATIONS: Depression model not reliable. Only 80% of participants from original study included. Not able to distinguish between anxiety disorders. CONCLUSION: Trajectories of anxiety confirm that, even after two years, a rather large proportion in the moderate-stable class had symptoms of moderate anxiety, moderate comorbid depressive symptoms, and less probability of having returned to work. TRIAL REGISTRATION: ClinicalTrials.govNCT01721824.