We examined the relationship of increasing prescription volume of newer antidepressants, introduced in Japan in 1999, to national rates of suicide.
The relationship between annual changes in rates of suicide (obtained from the Japanese Ministry of Health, Labor, and Welfare Vital Statistics Database) and prescription volume of the newer antidepressants paroxetine, fluvoxamine, and milnacipran (obtained from the database of IMS Japan K.K.), stratified by gender and age groups, was modeled statistically for the years 1999 through 2003. Effects of unemployment and alcohol consumption and the interaction of gender and age with antidepressant prescribing were assessed.
From 1999 through 2003 in Japan, total antidepressant prescriptions increased 57% among males and 50% among females. Approximately 80% of this increase involved the selective serotonin reuptake inhibitors (SSRIs). To reduce a limitation of ecological analysis, we compared annual change in prescription and suicide rates, which eliminates the effect of long-term (secular) linear trends. We found an inverse association between year-to-year changes in the suicide rate and prescription volume of newer antidepressants (fluvoxamine, paroxetine, and milnacipran) (β = −1.34, p = .008) and SSRIs specifically (fluvoxamine, paroxetine) (β = −1.41, p = .019). An increase of 1 defined daily dose of SSRI use/1000 population/day was associated with a 6% decrease in suicide rate. Exploratory analysis suggested a stronger association in males, who experienced a greater increase in antidepressant use. Changes in unemployment and alcohol consumption rates did not explain the association.
In Japan during 1999 through 2003, absent long-term linear trend effects, annual increases in prescribing of newer antidepressant medications, mainly SSRIs, were associated with annual decreases in suicide rates, particularly among males.
Elevated rates of psychopathology are noted among severely obese youth presenting for weight loss surgery. The role of mental health providers in this population is not well defined, and the selection of candidates is often the result of clinical judgment alone. The purpose of this study was to comprehensively evaluate psychiatric symptoms among a large sample of adolescents receiving laparoscopic adjustable gastric banding (LAGB) by: (1) examining changes in depressive symptoms and quality of life in the year following surgery, (2) evaluating the interaction between patterns of change in depression, quality of life, and weight post-surgery, and (3) identifying pre-surgical psychological predictors of initial weight change.
Participants were 101 severely obese adolescents aged 14 to 18. Measures of height, weight, depressive symptoms, and quality of life were obtained in the first year following surgery. Changes in the Beck Depression Inventory (BDI), Pediatric Quality of Life Inventory (PedsQL), and body mass index were analyzed using latent growth curve modeling.
Significant changes in total BDI [βslope=−0.885 SE=0.279, p<0.01; βquadratic=0.054 SE=0.021, p<.001] and PedsQL [βslope=−0.885 SE=0.279, p<0.001] scores were observed following LAGB, and comparable post-operative changes between psychosocial variables and body mass index were also noted [BDI: COV=0.21, SE=0.06, p<0.001; PedsQL: COV=−0.41, SE=0.10, p<0.01]. Two variables (family conflict/loss of control eating) were found to be significant predictors of weight change over the year following surgery (p<0.05).
Adolescents experienced notable improvements in initial depressive symptoms and quality of life after LAGB, and measures of pre-operative binge eating and family conflict affected post-surgery body mass index among youth.
To determine the risk for BP-I disorder in first-degree relatives of children with DSM-IV bipolar-I disorder (BP-I) via meta-analysis and expanded controlled study.
Data Sources and Extraction
We searched the Pubmed database for scientific articles published in the world literature in the English language through 2011. The key words searched were: bipolar disorder, first-degree relatives, family study, control. All online abstracts were reviewed and relevant full manuscripts were collected and reviewed. Citations were also examined for other potential relevant articles. We included only controlled family studies that examined rates of bipolar-I disorder in all first-degree relatives (parents and siblings) of pediatric bipolar-I probands and included only studies that had age and sex matched controls. Family history studies were excluded. Also excluded were studies that were not in English, did not report the rates of all first-degree relatives, and reported only bipolar spectrum rates. We also excluded family studies that included only adult probands. We conducted a meta-analysis of the five controlled family studies of pediatric BP-I probands that met our search criteria using the random effects model of DerSimonian and Laird.
We greatly expanded our previous sample of DSM-IV BP-I probands using structured diagnostic interviews. Our new study included 239 children satisfying full with DSM-IV diagnostic criteria for BP-I (n=726 first-degree relatives), 162 ADHD (without BP-I) probands (n=511 first-degree relatives), and 136 healthy control (without ADHD or BP-I) probands (n=411 first-degree relatives). We used the Kaplan-Meier cumulative failure function to calculate survival curves and cumulative, lifetime risk in relatives. Cox proportional hazard models were used to calculate the risk of BP-I in relatives.
The pooled odds ratio for BP-I disorder in relatives was estimated to be 6.96 (95% Confidence Interval (CI): 4.8 to 10.1). We also found first-degree relatives of BP-I probands to be significantly more likely than first-degree relatives of both ADHD (Hazards Ratio: 3.02; 95% CI: 1.85 to 4.93; p<0.001) and control probands (HR: 2.83; 1.65 to 4.84; p<0.001) to have bipolar-I disorder.
Our results document an increased familial risk for BP-I disorder in relatives of pediatric probands with DSM-IV BP-I.
A subset of patients undergoing initial antidepressant treatment experience worsening of symptoms, including thoughts of suicide or suicidal behavior. The present study explores whether this subset of patients is also more likely to experience recurrence or worsening of these symptoms during a second treatment trial with a different antidepressant.
We examined data collected between July 2001 and September 2006 from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, a multicenter effectiveness study of outpatients with major depressive disorder diagnosed by a DSM-IV checklist. In that study, subjects who did not remit with citalopram treatment were randomized among next-step treatment options. The main outcome measure for this post hoc analysis, presence of suicidal thoughts and behaviors, was assessed using the suicide item on the 16-item Quick Inventory of Depressive Symptomatology—Self-Rated. Logistic regression was used to examine association between emergence or worsening of these symptoms with the first-step (level 1) citalopram treatment and emergence or worsening with next-step (level 2) pharmacologic or psychosocial treatment, including augmentation with bupropion or buspirone; switch to sertraline, venlafaxine, or bupropion; or addition of or switch to cognitive therapy.
Of 1,240 subjects entering level 2 with a score less than 3 on the suicide item, 102 (8.2%) experienced emergence or worsening of suicidal thoughts or behaviors. Emergence or worsening at level 1 was strongly associated with reemergence or worsening at level 2 (crude OR=4.00 [95% CI, 2.45–6.51], adjusted OR=2.95 [95% CI, 1.76–4.96]). Overall magnitude of risk was similar among next-step pharmacologic augmentation versus switching.
These results suggest that individuals who experience emergence or worsening of suicidal thoughts or behaviors with one antidepressant treatment may warrant closer follow-up during the next-step treatment, as these symptoms may recur regardless of which modality is selected.
Establishing the minimum clinically important difference (MCID) in the Positive and Negative Syndrome Scale (PANSS) is important to the interpretation of the research and clinical work conducted with this scale.
This study employed both anchor-based and distributive methods to estimate the MCID for the PANSS using data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Schizophrenia trial, a large, multicenter trial for patients with schizophrenia. Data from 1442 individuals linked PANSS scores with both clinician and patient ratings on the Clinical Global Impressions Scale (CGI) using an equipercentile method. Data were also used to investigate the magnitude of the standard error measurement (SEM), offering another estimate of the MCID.
Cross-sectional clinician rated CGI scores of 1 through 7 linked to PANSS scores of 32.4, 42.2, 57.5, 74.5, 93.0, 110.9, and 131.0 respectively. The MCID for PANSS scores using this scale equaled a 15.3 point (34.0%) change from baseline. A 1.96 SEM on the PANSS corresponded to a 16.5 point (36.2%) change from baseline. The MCID for a subsample with above-median baseline PANSS scores was 38% higher than a sample with lower baseline scores. With the patient-rated CGI as the anchor, PANSS scores were higher for CGI scores of 1 through 4 and the MCID was lower, 11.2 points (24.6%).
MCID estimates from a longer-term effectiveness trial were consistent with previous efforts from shorter-term efficacy trials. MCID estimates can help clinicians and researchers design future studies and interpret treatment change in future research and clinical work.
Psychiatric Status Rating Scales; Schizophrenia; Severity of Illness Index; Treatment Outcome; Research Design; Clinical Trials as Topic
This study examined the potential effects of antidepressant exposure in pregnancy on early infant neurobehavioral outcomes.
In this prospective, naturalistic study, neurobehavioral assessments using the Brazelton Neonatal Behavioral Assessment Scale (BNBAS) were completed by blinded raters between March 2001 and August 2005 on 64 infants who were born to mothers in 1 of 3 categories: (1) women with a history of DSM-IV-diagnosed major depressive disorder (MDD) who were treated with antidepressants during pregnancy, (2) women with a history of DSM-IV-diagnosed MDD who discontinued or chose not to be treated with antidepressants during pregnancy, and (3) a nonpsychiatric control group. Summary scores for the BNBAS were obtained within the first week of life and at 6 to 8 weeks of age.
No significant differences were observed between groups at either the first week after delivery or at 6 to 8 weeks of age on any of the summary scores for the 7 major clusters of the BNBAS.
Antidepressant exposure during pregnancy does not appear to have major adverse effects on indices of early infant neurobehavioral development during the first 2 months of life as assessed by the BNBAS. While this finding is encouraging, further studies with larger samples and longer follow-up are needed.
Patients with bipolar disorder are prone to suicidal behavior, yet possible protective mechanisms are rarely studied. We investigated a possible protective role for moral or religious objections to suicide against suicidal ideation and attempts in depressed bipolar patients.
A retrospective case control study of 149 depressed bipolar patients (DSM-III-R criteria) in a tertiary care university research clinic was conducted. Patients who reported religious affiliation were compared with 51 patients without religious affiliation in terms of sociodemographic and clinical characteristics and history of suicidal behavior. The primary outcome measure was the moral or religious objections to suicide subscale of the Reasons for Living Inventory (RFLI).
Religiously affiliated patients had more children and more family-oriented social networks than nonaffiliated patients. As for clinical variables, religiously affiliated patients had fewer past suicide attempts, had fewer suicides in first-degree relatives, and were older at the time of first suicide attempt than unaffiliated patients. Furthermore, patients with religious affiliation had comparatively higher scores on the moral or religious objections to suicide subscale of the RFLI, lower lifetime aggression, and less comorbid alcohol and substance abuse and childhood abuse experience. After controlling for confounders, higher aggression scores (P = .001) and lower score on the moral or religious objections to suicide subscale of the RFLI (P < .001) were significantly associated with suicidal behavior in depressed bipolar patients. Moral or religious objections to suicide mediated the effects of religious affiliation on suicidal behavior in this sample.
Higher score on the moral or religious objections to suicide subscale of the RFLI is associated with fewer suicidal acts in depressed bipolar patients. The strength of this association was comparable to that of aggression scores and suicidal behavior, and had an independent effect. A possible protective role of moral or religious objections to suicide deserves consideration in the assessment and treatment of suicidality in bipolar disorder.
A recent meta-analysis has indicated that, in patients with dementia, the use of atypical antipsychotics is associated with an excess mortality. Later observational studies have suggested that conventional antipsychotics may pose an even greater risk of death. None of these studies could evaluate the risk associated with single antipsychotics nor could they provide any conclusive evidence concerning the risk among nursing home residents. We conducted a retrospective cohort study to compare the risk of death associated with atypical and conventional antipsychotics in a large population of nursing home residents with dementia.
We identified 6,524 new users of atypical antipsychotics and 3,205 new users of conventional antipsychotics living in 1,581 Medicare- or Medicaid-certified nursing homes in 5 US states during the years 1998–2000. The outcome measure was all-cause mortality, which was determined during 6-months of follow-up.
After adjusting for potential confounders relative to users of atypicals, the rate of death was increased for users of conventional antipsychotics (hazard ratio [HR], 1.26; 95% CI, 1.13–1.42). Relative to risperidone, a higher rate of death was documented for haloperidol (HR, 1.31; 95% CI, 1.13–1.53), phenothiazines (HR, 1.17; 95% CI, 1.00–1.38) and other conventional medications (HR, 1.32; 95% CI, 0.99–1.80). No atypical antipsychotic was associated with a differential risk relative to risperidone.
Conventional antipsychotics are associated with a higher risk of all-cause mortality than atypical agents. It seems advisable that they are not used in substitution for atypical antipsychotics among nursing home residents with dementia even when short-term therapy is being prescribed.
To determine whether borderline personality disorder (BPD) and bipolar II disorder can be differentiated from each other and from major depressive disorder (MDD) by comparing depression severity, impulsiveness, and hostility in mood disorder patients with and without BPD.
One hundred seventy-three patients with either MDD or bipolar II disorder were enrolled from a larger sample admitted to a multisite project on mood disorders and suicidal behavior conducted from June 1996 through June 2006. Patients were divided into 4 groups: MDD with BPD, MDD without an Axis II diagnosis, bipolar II disorder with BPD, and bipolar II disorder without an Axis II diagnosis. All diagnoses were based on DSM-IV criteria. Depression was assessed using the 17-item Hamilton Rating Scale for Depression (HAM-D) and the self-rated Beck Depression Inventory (BDI). Impulsiveness was assessed using the Barratt Impulsiveness Scale, and hostility was assessed using the Buss-Durkee Hostility Inventory.
Patients with BPD reported higher levels of impulsiveness (p = .004) and hostility (p = .001), independent of Axis I diagnosis. Bipolar II patients reported greater attentional impulsiveness (p = .008) than MDD patients, independent of BPD status, while BPD patients reported greater nonplanning impulsiveness than patients without BPD, independent of Axis I diagnosis (p = .02). For motor impulsiveness, there was a main effect for Axis I diagnosis (p = .05) and Axis II diagnosis (p = .002). The bipolar II + BPD group scored the highest, suggesting a compound effect of comorbidity. There were no differences in depression severity when measured with the HAM-D, although the BPD groups reported more severe depression on the BDI, independent of their Axis I diagnosis (p = .05). The BPD groups scored higher on the cognitive factor (p = .01) and anxiety factor (p = .03) of the HAM-D.
Results suggest that there is a unique symptom and trait profile associated with BPD that distinguishes the diagnosis from bipolar II disorder. Results also suggest that impulsiveness is an important aspect of both disorders and that there is a compounding effect associated with a diagnosis of bipolar II disorder with comorbid BPD.
Determining risk for a suicide attempt in psychiatric patients requires assessment of multiple risk factors and knowledge of their relative importance. Classification and regression tree (CART) analysis generates decision trees that select the variables that perform best in identifying the group of interest and model clinical decision making. Hypothetical decision trees to identify recent and remote suicide attempters, weighted to increase sensitivity, were generated for psychiatric patients using correlates of past suicidal behavior.
Correlates of past suicide attempts were identified in 408 patients with mood, schizophrenia spectrum, or personality disorders (DSM-IV). Correlated variables were entered into recursive partitioning statistical models to generate equally weighted and unequally weighted hypothetical decision trees for distinguishing recent (≤ 30 days prior to study) and remote (> 250 days prior to study) suicide attempters from nonattempters. The study was conducted from December 1989 to November 1998.
In equally weighted trees, a recent past suicide attempt was best predicted by current suicidal ideation (sensitivity = 56%, specificity = 91%, positive predictive value = 69%), and no adequate model was found for remote attempts. In unequally weighted models, recent attempters were identified by suicidal ideation and comorbid borderline personality disorder (sensitivity = 73%, specificity = 80%, positive predictive value = 58%). Remote attempters were identified by lifetime aggression and current subjective depression (sensitivity = 89%, specificity = 36%, positive predictive value = 44%).
Current suicidal ideation is the best indicator of a recent suicide attempt in psychiatric patients. Indicators of a remote attempt are aggressive traits and current depression. Weighted decision trees can improve sensitivity and miss fewer attempters but with a cost in specificity.
Little is known about predictors of recovery from bipolar depression or moderators of treatment response. In the present study we investigated attributional style (a cognitive pattern of explaining the causes of life events) as a predictor of recovery from episodes of bipolar depression and as a moderator of response to psychotherapy for bipolar depression.
106 depressed outpatients with DSM-IV bipolar I or II disorder enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) were randomized to intensive psychotherapy for depression (n=62), or collaborative care (n=44), a minimal psychoeducational intervention. The primary outcome was recovery status at each study visit as measured by the Clinical Monitoring Form. Attributional style was measured at baseline using the Attributional Style Questionnaire. Data were collected between 1998 and 2005.
All analyses were by intention to treat. Extreme attributions predicted a lower likelihood of recovery (p=.01, OR=0.93, 95% CI=.88-.98) and longer time until recovery (p<.01, OR=0.96, 95% CI=.93-.99), independent of the effects of initial depression severity. Among individuals with more pessimistic attributional styles, initial depression severity predicted a lower likelihood of recovery (p=.01, OR=0.64, 95% CI=.45-.91) and longer time until recovery (p<.001, OR=0.76, 95% CI=.66-.88). There was no difference in recovery rates between intensive psychotherapy and collaborative care (OR=0.90, 95% CI=0.40-2.01) in the full sample.
These results suggest that extreme, rigid attributions may be associated with a more severe course of depression, and that evaluating attributional style may help clinicians to identify patients who are at risk for experiencing a more severe course of depression.
The true benefit of pharmacological intervention to improve cognition in schizophrenia may not be evident without regular cognitive enrichment. Clinical trials assessing the neurocognitive effects of new medications may require engagement in cognitive remediation exercises to stimulate the benefit potential. However, the feasibility of large-scale multi-site studies using cognitive remediation at clinical trials sites has not been established.
Patients with DSM-IV schizophrenia from nine sites were randomized to a cognitive remediation condition that included the Posit Science Brain Fitness auditory training program with weekly NEAR ‘bridging groups,’ or a control condition of computer games and weekly healthy lifestyles groups. Patients were expected to complete 3–5 one-hour sessions weekly for 40 sessions or 12 weeks, whichever came first.
The primary outcomes were feasibility results as measured by rate of enrollment, retention, and completion rate of primary outcome measures. Within the 3-month enrollment period, 53 of a projected 54 patients were enrolled and 47 completed the study. Thirty-one patients completed all 40 sessions and all patients completed all primary outcome measures. Preliminary efficacy results indicated that after 20 sessions, patients in the cognitive remediation condition demonstrated mean MCCB composite score improvements that were 3.7 (95% CI: 7.34, 0.05) T-score points greater than in patients in the computer games control group (F=4.16, df=1,46, p=0.047). At the end of treatment, a trend favoring cognitive remediation was not statistically significant (F=2.26, df=1,47, p=0.14).
Multi-site clinical trials of cognitive remediation using the Posit Science auditory training program with the NEAR method of weekly bridging groups in traditional clinical sites appear feasible.
Few studies have examined the correlates of psychosis in children and adolescents with Bipolar Disorder (BPD). We examined psychiatric comorbidity, familiality, and psychosocial functioning in multiple domains in BPD children and adolescents with and without psychotic features.
As part of two ongoing family-based studies of children and adolescents with BPD, we compared youth and their families with psychotic symptoms (BPD+P) and without psychotic symptoms (BPD−P). All youth and family members were assessed by structured psychiatric interviews in a blinded manner. One study was conducted from January 2000 through December 2004, and the other study was conducted from February 1997 through September 2006.
Of the 226 youth with BPD, 33% manifested psychotic symptoms, as defined by the presence of hallucinations or delusions. We found that BPD+P had a greater number of BPD episodes, more psychiatric hospitalizations, and significantly higher rates of psychiatric comorbidity compared to BPD−P. Additionally, a higher percentage of BPD+P had a family history of psychosis. There was a lower processing speed and lower arithmetic scaled score in BPD+P youth, but no other meaningful differences in cognitive variables were identified between the two BPD groups. Psychosis in BPD was also associated with decreased family cohesion and poorer overall global functioning.
In children and adolescents with BPD, those who manifest psychotic features have higher rates of comorbid psychopathology, family history of psychosis, and poorer overall functioning in multiple domains than BPD children without psychosis. Future studies should examine neuroimaging correlates, medication response, and longitudinal course of BPD children and adolescents who manifest psychosis as part of their clinical picture.
Pediatric Bipolar Disorder; Psychosis; Comorbidity; Subtype
This multisite randomized trial addressed risks and benefits of staying on long-acting injectable haloperidol or fluphenazine versus switching to long-acting injectable risperidone microspheres.
From December 2004 until March 2008, adult outpatients with a SCID diagnosis of schizophrenia or schizoaffective disorder who were taking haloperidol decanoate (n=40) or fluphenazine decanoate (n=22) were randomly assigned to Stay on current long-acting injectable medication or Switch to risperidone microspheres and followed for 6 months under study protocol and an additional 6 months naturalistic follow-up. Kaplan-Meier and Cox regression analyses were used to examine the primary outcome, time-to-treatment-discontinuation, and random regression models were used to examine secondary outcomes.
Groups did not differ in time-to-treatment-discontinuation through 6 months of protocol-driven treatment. When the 6 month naturalistic follow-up period was included, time-to-treatment-discontinuation was significantly shorter for individuals assigned to Switch than for individuals assigned to Stay (10% of Stayers discontinued versus 31% of Switchers; p =.01). Groups did not differ with respect to psychopathology, hospitalizations, sexual side effects, new-onset TD, or new onset EPS. However, those randomized to Switch to long-acting injectable risperidone microspheres had greater increases in body mass (increase of 1.0 BMI versus decrease of −0.3 BMI ; p=.00) and prolactin (maximum increase to 23.4 ng/ml versus decrease to 15.2 ng/ml, p=.01) compared to those randomized to Stay.
Switching from haloperidol decanoate or fluphenazine decanoate to risperidone microspheres resulted in more frequent treatment discontinuation as well as significant weight gain and increases in prolactin.
Clinical trials have demonstrated that pharmacotherapies can safely treat ADHD in adulthood. Eligibility criteria in these trials may significantly limit their external validity by excluding a significant portion of adults with ADHD in the general population. In particular, exclusion criteria may frequently exclude individuals with comorbid mental health conditions, which are common in the adult ADHD population.
The authors addressed the representativeness of clinical trials by comparing 146 adult Clinical Trial participants with DSM-IV ADHD, and a Community Sample comprised of 124 adults with DSM-IV ADHD and 123 non-ADHD controls. Subjects were compared on socioeconomic status, Hollingshead Occupational code, cognitive measures, lifetime psychopathology and global assessment of function (GAF) ratings.
Adults with ADHD in the Community Sample had higher rates of lifetime psychiatric comorbidity, lower GAF, and lower occupational codes than those in the Clinical Trial. The clinical trial eligibility criteria would have excluded 61% of Community Sample ADHD adults. This excluded portion of the Community sample had higher rates of lifetime psychiatric comorbidity and lower GAF than clinical trial participants.
Adults with ADHD participating in the Clinical Trial had less evidence of functional impairment and endorsed less psychiatric comorbidity than the majority of Community Sample subjects with ADHD. This suggests that findings from clinical trials may have limited external validity for adults with ADHD in the general population, particularly for those adults with ADHD with the greatest burden of comorbid psychopathology.
To critically review the literature on topiramate in the treatment of substance related disorders.
A PubMed search of human studies published in English through January 2009.
26 articles were identified and reviewed; these studies examined topiramate in disorders related to alcohol, nicotine, cocaine, methamphetamine, opioids, ecstasy, and benzodiazepines.
Study design, sample size, topiramate dose and duration, and study outcomes were reviewed.
There is compelling evidence for the efficacy of topiramate in the treatment of alcohol dependence. Two trials show trends for topiramate’s superiority over oral naltrexone in alcohol dependence, while one trial suggests topiramate is inferior to disulfiram. Despite suggestive animal models, evidence for topiramate in treating alcohol withdrawal in humans is slim. Studies of topiramate in nicotine dependence show mixed results. Human laboratory studies that used acute topiramate dosing show that topiramate actually enhances the pleasurable effects of both nicotine and methamphetamine. Evidence for topiramate in the treatment of cocaine dependence is promising, but limited by small sample size. The data on opioids, benzodiazepines, and ecstasy are sparse.
Topiramate is efficacious for the treatment of alcohol dependence, but side effects may limit widespread use. While topiramate’s unique pharmacodynamic profile offers a promising theoretical rationale for use across multiple substance related disorders, heterogeneity both across and within these disorders limits topiramate’s broad applicability in treating substance related disorders. Recommendations for future research include exploration of genetic variants for more targeted pharmacotherapies.
Topiramate; substance abuse; substance related disorders; critical review
Anorexia nervosa is characterized by self-induced starvation and associated with severe bone and fat loss. Oxytocin is a peptide hormone involved in appetite and energy homeostasis. Recent data show that oxytocin has an anabolic effect on bone and stimulates osteoblast function. There is limited information about oxytocin levels or its relationship to decreased bone mineral density (BMD) in anorexia nervosa. Our objective was to investigate the relationship between oxytocin levels, BMD and body composition in women with anorexia nervosa.
We studied 36 women, mean age 27.6±1.3 years: 17 with anorexia nervosa (AN) and 19 healthy controls (HC) in a cross-sectional study. Oxytocin levels were determined from pooled serum samples obtained every 20 minutes from 8pm to 8am. Fasting leptin levels were measured. BMD at the anterior-posterior (AP) and lateral spine and hip, and body composition were assessed by dual energy X-ray absorptiometry.
Mean oxytocin levels (14.3±1.5 vs. 31.8±5.1 pg/mL, p=0.003), leptin levels (2.7±0.5 vs. 11.4±1.1 ng/mL, p<0.0001), BMD (AP spine: 0.83±0.02 vs. 1.04±0.03; lateral spine: 0.63±0.02 vs. 0.81±0.02; total hip: 0.79±0.03 vs. 0.97±0.03 g/cm2, <0.0001), and fat mass (8.8±0.6 vs. 19.7±0.9 kg, p<0.0001) were lower in AN vs. HC. Oxytocin levels were associated with BMD at the AP (r=0.40, p=0.02) and lateral (r=0.36, p=0.04) spine, fat mass (r=0.42, p=0.01), and leptin levels (r=0.55, p=0.001).
Overnight secretion of oxytocin in AN is decreased compared with healthy women. Low oxytocin levels are associated with decreased BMD and body fat and may contribute to anorexia nervosa-induced bone loss.
Anorexia Nervosa; Oxytocin; Bone; Fat; Leptin
Anxiety Disorders; glutamate; obsessive-compulsive disorder; OCD; ketamine; NMDA
Bereavement-related depression is excluded from a diagnosis of major depressive episode (MDE) in DSM-IV unless the syndrome is prolonged or complicated. The objective of this study is to assess the validity of the bereavement exclusion by comparing characteristics of bereavement-related episodes that are excluded from a diagnosis, and bereavement-related episodes that qualify for a diagnosis (complicated bereavement), to MDE.
We used data from two waves of the National Epidemiologic Survey on Alcohol and Related Conditions to compare bereavement-excluded depression and complicated bereavement to MDE with respect to indicators of pre-existing risk for psychopathology (antecedent indicators) and indicators of disorder severity (consequent indicators).
Compared to individuals with MDE, individuals with bereavement-excluded depression had lower risks of pre-existing psychiatric disorders (e.g., 0.44 lower odds of social phobia, P=0.006), fewer depressive episodes (recurrence rate 0.37 times lower, P<0.001), less impairment, an 0.18 times lower odds of seeking treatment (P<0.001), and a lower risk of psychiatric disorders during a 3-year follow-up period. Unexpectedly, this same pattern of differences was observed between individuals with complicated bereavement and MDE.
Despite the presence of a clinically significant depressive episode, bereavement-excluded depression is in many ways less indicative of psychopathology than MDE. However, complicated bereavement was more similar to bereavement-excluded depression than to MDE. We therefore question whether the DSM-IV criteria validly distinguish between non-disordered loss reactions (bereavement-excluded depression), pathological loss reactions (complicated bereavement), and non-loss related MDE.
Depression; bereavement; validity
We examined the predictive power of the self-harm subscale of the Schedule for Nonadaptive and Adaptive Personality (SNAP) to identify suicide attempters in the Collaborative Longitudinal Study of Personality Disorders (CLPS).
The SNAP, a self-report personality inventory, was administered to 733 CLPS participants at baseline, of whom 701 (96%) had at least 6 months of follow-up data. Cox proportional hazards regression analyses were performed to examine the SNAP–self-harm subscale (SNAP-SH) in predicting the 129 suicide attempters over 8 years of follow-up. Possible moderators of prediction were examined, including borderline personality disorder, major depressive disorder (MDD), and substance use disorder. We also compared baseline administration of the SNAP-SH to subsequent administrations more proximal to the suicide attempt, and to a higher-order SNAP-negative temperament (SNAP-NT) subscale. Receiver operating characteristic analyses were conducted using suicide attempts (n = 58) over the first year of follow-up to provide reference points for sensitivity and specificity.
The SNAP-SH demonstrated good predictive power for suicide attempts (hazard ratio = 1.28, P < .001) and appeared relatively consistent across borderline personality disorder, MDD, and substance use disorder diagnoses. Using more proximal scores did not increase predictive power. The SNAP-SH compared favorably to the predictive power of the higher-order SNAP-NT. Receiver operating characteristic analyses indicate several cutoff scores on the SNAP-SH that yield moderate to high sensitivity and specificity for predicting suicide attempts over the first year of follow-up.
The SNAP-SH may be a useful screening instrument for risk of suicide attempts in nonpsychotic psychiatric patients.
This randomized, 24-week, flexible-dose study compared changes in glucose metabolism in patients with schizophrenia receiving initial exposure to olanzapine, quetiapine, or risperidone.
The hypothesized primary endpoint was change (baseline to Week 24) in area under the curve 0-2h plasma glucose during oral glucose tolerance test (OGTT); primary analysis: olanzapine versus quetiapine. Secondary endpoints included change in AUC 0-2h plasma insulin, insulin sensitivity index (ISI), and fasting lipids.
Mean weight change (kg) over 24 weeks was +3.7 (quetiapine), +4.6 (olanzapine), and +3.6 (risperidone). Based on data from 395 patients (quetiapine n=115 [mean 607.0 mg/day], olanzapine n=146 [15.2 mg/day], and risperidone n=134 [5.2 mg/day]), change in AUC 0-2h glucose (mg/dL×h) at Week 24 was significantly lower for quetiapine versus olanzapine (t=1.98; DF=377; p=0.048). Increases in AUC 0-2h glucose were statistically significant with olanzapine (+21.9 mg/dL, 95% CI 11.5, 32.4) and risperidone (+18.8, CI 8.1, 29.4), but not quetiapine (+9.1, CI −2.3, 20.5). AUC 0-2h insulin increased statistically significantly with olanzapine, but not quetiapine or risperidone. Reductions in ISI were statistically significant with olanzapine and risperidone, but not quetiapine. Total cholesterol and LDL increased statistically significantly with olanzapine and quetiapine, but not risperidone. Statistically significant increases in triglycerides, cholesterol/HDL, and triglyceride/HDL ratios were observed with olanzapine only.
The results indicate a significant difference in the change in glucose tolerance during 6 months’ treatment with olanzapine versus quetiapine, with significant reductions on olanzapine and risperidone, but not quetiapine; these differential changes were largely explained by changes in insulin sensitivity.
glucose; insulin; lipids; olanzapine; quetiapine; risperidone; schizophrenia
It is currently not possible to determine which individuals with unipolar depression are at highest risk for a manic episode. This study investigates clinical and psychosocial risk factors for mania among individuals with major depressive disorder (MDD), indicating diagnostic conversion from MDD to bipolar I disorder.
We fitted logistic regression models to predict the first onset of a manic episode among 6,214 cases of lifetime MDD according to DSM-IV criteria in the National Epidemiologic Survey on Alcohol and Related Conditions.
Approximately 1 in 20 individuals with MDD transitioned to bipolar disorder during the study's 3-year follow-up period. Demographic risk factors for the transition from MDD to bipolar disorder included younger age, Black race/ethnicity, and less than high school education. Clinical characteristics of depression (e.g., age at first onset, presence of atypical features) were not associated with diagnostic conversion. However, prior psychopathology was associated with the transition to bipolar disorder: history of social phobia (Odds Ratio=2.20; 95% Confidence Interval=1.47, 3.30) and generalized anxiety disorder (OR=1.58; CI=1.06, 2.35). Lastly, we identified environmental stressors over the life course that predicted the transition to bipolar disorder: these include a history of child abuse (OR=1.26; CI=1.12, 1.42) and past-year problems with one's social support group (OR=1.79; CI=1.19, 2.68). The overall predictive power of these risk factors based on a receiver operating curve analysis is modest.
A wide range of demographic, clinical, and environmental risk factors were identified that indicate a heightened risk for the transition to bipolar disorder. Additional work is needed to further enhance the prediction of bipolar disorder among cases of MDD, and to determine whether interventions targeting these factors could reduce the risk of bipolar disorder.
unipolar; bipolar; depression; mania; epidemiology