Delineating the phenotype of 1p36 deletion in adolescents and adults.

1p36 deletion is the most common telomeric deletion syndrome, with an incidence of 1/5,000-1/10,000. A variety of clinical complications have been reported including seizures, hypotonia, heart malformations, cardiomyopathy, vision problems, and hearing loss. Approximately 90% are reported to have severe to profound intellectual disability and 75% to have absent expressive language. Little is known about long-term outcomes. The current literature suggests a poor prognosis for most patients. This study attempted to assess medical conditions and function of adolescent and adult patients with 1p36 deletion. A survey was distributed through three support groups to identify patients >12 years of age to assess functional status and medical problems in older patients with 1p36 deletion syndrome. 40 patients were identified between 12 and 46 years old. Among our survey sample, medical complications including seizures, hypotonia, structural heart defects, hearing loss, and vision problems, were similar to previous reports. However, functional skills were better than anticipated, with an overwhelming majority reported to independently sit, walk, and receive the majority of nutrition orally. Forty-four percent were reported to use complex speech abilities. While medical problems in patients with 1p36 deletion were similar to those that have been previously reported, we also demonstrated these same concerns persist into adolescence and adulthood. Additionally, patients were reported to have better functional skills than anticipated. Thus, quality of life and level of function appear to be better than anticipated from previous studies. © 2014 Wiley Periodicals, Inc.

Effects of risperidone and paliperidone pre-treatment on locomotor response following prenatal immune activation.

AIM: Limited data are available regarding pharmacological characteristics of effective interventions for psychosis prevention. Enrollment challenges in psychosis prevention trials impede screening diverse interventions for efficacy. Relevant animal models could help circumvent this barrier. We previously described prevention with risperidone of abnormal behavior following neonatal hippocampal lesion. We aimed to extend those findings evaluating risperidone and paliperidone following prenatal immune activation, a developmental model of a schizophrenia risk factor. We evaluated a later developmental time point to determine persistent effects of drug treatment. METHODS: Pregnant Sprague-Dawley rats were injected with poly I:C or saline on gestational day 14. Offspring of poly I:C and saline-treated dams received risperidone (0.45 mg/kg/d), paliperidone (0.05 mg/kg/d), or vehicle from postnatal days 35-70. Locomotor responses to novelty, saline injection, and amphetamine (1 and 5 mg/kg) were determined at three months, i.e., 21 days following antipsychotic discontinuation. RESULTS: Risperidone and paliperidone had persistent effects on behavioral response to amphetamine (1 mg/kg) at 3 months, ameliorating the impact of prenatal immune activation on offspring of poly I:C-treated dams. Risperidone, but not paliperidone, also exerted persistent effects in offspring of saline-treated dams on locomotor response to saline and amphetamine (5 mg/kg) injection. CONCLUSIONS: Risperidone and paliperidone pre-treatment of poly I:C offspring during peri-pubertal development stabilized response to amphetamine exposure persisting into early adulthood. Prenatal immune activation provides a model for evaluating effects of an environmental risk factor for schizophrenia, and has potential utility for identifying pharmacological approaches to early intervention.

Cerebellar ataxia in youths at risk for bipolar disorder.

OBJECTIVE: Structural, biochemical, and functional cerebellar abnormalities occur in individuals with or at-risk for developing bipolar disorder (BD), but the clinical implications of these abnormalities are unknown. The present study examined cerebellar function in youths who were at familial risk for BD by comparing ataxia battery scores of youths with a bipolar parent to those of healthy youths. METHODS: Trained raters administered an ataxia battery, consisting of three tasks, to children (aged 8-12 years) with at least one parent with BD type I (BDI) who themselves did not have BDI (at-risk or AR group, n = 21) and healthy comparison children (aged 8-12 years) with parents free of DSM-IV Axis I psychopathology (HC group, n = 23). RESULTS: AR youths performed worse than HC youths on the Sharpened Romberg test (subjects standing heel-to-toe) and standing on one foot with eyes open (p < 0.02). CONCLUSIONS: The results indicate that youths at familial risk for BD have more difficulty performing a Sharpened Romberg test than a HC group, suggesting that midline cerebellar dysfunction may be a biomarker for the future development of BD. Further studies examining the relationships among youths at risk for BD, coordination abnormalities, and cerebellar dysfunction are needed.

Deficits in docosahexaenoic acid and associated elevations in the metabolism of arachidonic acid and saturated fatty acids in the postmortem orbitofrontal cortex of patients with bipolar disorder.

Previous antemortem and postmortem tissue fatty acid composition studies have observed significant deficits in the omega-3 fatty acid docosahexaenoic acid (DHA, 22:6n-3) in red blood cell (RBC) and postmortem cortical membranes of patients with unipolar depression. In the present study, we determined the fatty acid composition of postmortem orbitofrontal cortex (OFC, Brodmann area 10) of patients with bipolar disorder (n=18) and age-matched normal controls (n=19) by gas chromatography. After correction for multiple comparisons, DHA (-24%), arachidonic acid (-14%), and stearic acid (C18:0) (-4.5%) compositions were significantly lower, and cis-vaccenic acid (18:1n-7) (+12.5%) composition significantly higher, in the OFC of bipolar patients relative to normal controls. Based on metabolite:precursor ratios, significant elevations in arachidonic acid, stearic acid, and palmitic acid conversion/metabolism were observed in the OFC of bipolar patients, and were inversely correlated with DHA composition. Deficits in OFC DHA and arachidonic acid composition, and elevations in arachidonic acid metabolism, were numerically (but not significantly) greater in drug-free bipolar patients relative to patients treated with mood-stabilizer or antipsychotic medications. OFC DHA and arachidonic acid deficits were greater in patients plus normal controls with high vs. low alcohol abuse severity. These results add to a growing body of evidence implicating omega-3 fatty acid deficiency as well as the OFC in the pathoaetiology of bipolar disorder.

Temporal change in N-acetyl-aspartate concentrations in adolescents with bipolar depression treated with lithium.

OBJECTIVE: This proton magnetic resonance spectroscopy (1H MRS) study identified the in vivo effects of lithium on N-acetyl-aspartate (NAA) concentrations in adolescent bipolar depression. METHOD: Twenty eight adolescents with bipolar I disorder in a depressive episode received open-label lithium 30 mg/kg, adjusted to achieve serum levels of 1.0-1.2 mEq/L. Medial ventral and ventral lateral prefrontal NAA concentrations were measured at baseline, day 7, and day 42 of treatment. Temporal changes in NAA concentrations were analyzed and effect sizes (Cohen's d) were calculated. RESULTS: Medial ventral prefrontal NAA concentrations decreased over time (p = 0.03), with day-42 concentrations significantly lower than baseline concentrations (p = 0.01, d = 0.7). No significant time effects on NAA concentrations were observed in the left (p = 0.2) or right ventral lateral (p = 0.3) prefrontal cortices. CONCLUSIONS: In contrast with prior studies of bipolar adults, this study observes that ventral prefrontal NAA concentrations do not significantly increase from baseline following lithium treatment in adolescent bipolar depression. The results should be viewed in the context of the study's limitations, including the lack of a matched healthy control group. Additional longitudinal magnetic resonance imaging studies are warranted to understand better the role of NAA in the pathophysiology of bipolar disorder and neurochemical mechanisms by which lithium stabilizes mood.

Neuroanatomical characterization of child offspring of bipolar parents.

OBJECTIVE: To examine structural differences in selected anterior limbic brain regions between at-risk children of parents with bipolar I disorder and children with healthy parents. We hypothesized that at-risk (AR) children would exhibit abnormalities in brain regions that are involved in mood regulation. METHOD: Children (8-12 years old) of parents with bipolar I disorder (AR children, n = 21) and of parents without any DSM-IV Axis I disorder (healthy controls, n = 24) were evaluated using diagnostic assessments and brain magnetic resonance imaging. Morphometric analyses were used to examine group differences in the prefrontal cortical, thalamic, striatal, and amygdalar volumes. RESULTS: Nine (43%) of the AR children met DSM-IV-TR criteria for a nonbipolar mood disorder at the time of assessment. AR and healthy control children did not demonstrate statistically significant differences across regions of interest (Wilks lambda =.86, F4,39 = 1.64, p = .18; effect size, f = 0.19). Post hoc analyses of covariance showed the largest relative effect size was contributed by the prefrontal cortex (f = 0.26). CONCLUSIONS: Eight- to 12-year-old children with a familial risk for mania do not exhibit any statistically significant volumetric differences in the prefrontal cortex, thalamus, striatum, or amygdala as compared with age-matched children of parents without any psychopathology. Longitudinal studies examining whether structural changes over time may be associated with vulnerability for developing subsequent bipolar disorder are needed to clarify the underlying pathophysiology of this disorder.

Females with Fabry disease frequently have major organ involvement: lessons from the Fabry Registry.

Fabry disease (FD) is an X-linked lysosomal storage disease caused by alpha-galactosidase A deficiency. The Fabry Registry is a global clinical effort to collect longitudinal data on FD. In the past, most "carrier" females were usually thought to be clinically unaffected. A systematic effort has been made to enroll all FD females, regardless of symptomology. Of the 1077 enrolled females in the Registry, 69.4% had symptoms and signs of FD. The median age at symptom onset among females was 13 years, and even though 84.1% had a positive family history, the diagnosis was not made until a median age of 31 years. Twenty percent experienced major cerebrovascular, cardiac, or renal events, at a median age of 46 years. Among adult females with estimated glomerular filtration rate (eGFR) data (N=638), 62.5% had an eGFR <90 ml/min/1.73 m2 and 19.0% had eGFR <60 ml/min/1.73 m2. Proteinuria 300 mg/day was present in 39.0% of females, and 22.2% had >1 gram/day. Quality of life (QoL), as measured by the SF-36((R)) survey, was impaired at a later age than in males, but both genders experience significantly impaired QoL from the third decade of life onward. Thus, females with FD have a significant risk for major organ involvement and decreased QoL. Females should be regularly monitored for signs and symptoms of FD, and considered for enzyme replacement therapy.

Emotional eating and emotional eating alternatives in subjects undergoing bariatric surgery.

BACKGROUND: The purpose of this study was to characterize emotional eating and its alternatives in obese patients undergoing bariatric surgery. METHODS: The medical charts of 178 consecutive patients who had laparoscopic Roux-en-Y gastric bypass provided by a multidisciplinary bariatric program were reviewed. Data from patients who had emotional eating, reported strategies to overcome their urges to emotionally eat, and had their 6 months follow-up after surgery (N=50) were further analyzed in terms of weight history, medical co-morbidity prior to surgery, weight loss after surgery, and lifetime psychiatric status. RESULTS: 38.7% of the 178 bariatric surgery patients reported emotional eating. Patients reported using three main types of behaviors (oral, sedentary and physical activity) to overcome urges to eat emotionally. Most patients (42%) experiencing emotional eating chose sedentary behaviors to overcome urges to eat in response to emotion. The three groups did not differ in any of the examined variables. CONCLUSIONS: While patients using different coping mechanisms to overcome urges to eat emotionally did not differ before and 6 months after surgery, further research is needed to examine the frequency and long-term effects of emotional eating in bariatric surgery patients.

Body mass indexes and lipid profiles in hospitalized children and adolescents exposed to atypical antipsychotics.

OBJECTIVE: The purpose of this study was to examine body mass indexes (BMI) and lipid profiles of children and adolescents hospitalized for a psychiatric illness and exposed to an atypical antipsychotic. METHOD: Medical records of children and adolescents (ages of 5-18 years) with an inpatient psychiatric hospitalization between July 1, 2004, and June 30, 2005, were reviewed. Subjects were required to have been treated with at least one atypical antipsychotic during the month prior to admission. Height, weight, and fasting lipid values completed upon admission were collected. Prevalences of overweight (sex-specific BMI for age>or=the 95th percentile) and at risk for overweight (sex-specific BMI for age between the 85th and 94.9th percentiles) were determined and compared to estimates from the 2001-2002 National Health and Nutrition Examination Survey (NHANES) data. The prevalence of abnormal lipid profiles was also evaluated using widely accepted criteria specific for pediatric patients. Exploratory multiple linear regression models were fit to examine relationships of demographic and clinical variables with BMI z-scores and lipid profiles. RESULTS: Of 95 inpatients (mean age 14 years, 43% female, and 60% white) evaluated, 16% (n=15) were at risk for overweight and 53% (n=50) were overweight. Fifty-one percent (n=48) and 48% (n=46) of the sample had elevated triglycerides (TG) levels and low high-density lipoprotein (HDL) levels, respectively. CONCLUSION: The prevalence of overweight among hospitalized children and adolescents with exposure to atypical antipsychotics is triple that of national norms. Dyslipidemia was also common in this inpatient sample. Future studies should assess the development of overweight, the factors contributing to it, and related comorbidities in youths with mental illness.

A 12-week single-blind trial of quetiapine for the treatment of mood symptoms in adolescents at high risk for developing bipolar I disorder.

OBJECTIVE: To investigate the effectiveness and tolerability of quetiapine for the treatment of adolescents at high risk for developing bipolar I disorder. METHOD: Twenty adolescents (aged 12-18 years) with mood symptoms that did not meet DSM-IV-TR criteria for bipolar I disorder and who had at least one first-degree relative with bipolar I disorder were recruited from August 2003 to June 2005 to participate in a single-blind, 12-week prospective study of quetiapine. Subjects were diagnosed using the Washington University in St. Louis Kiddie Schedule of Affective Disorders and Schizophrenia and were symptomatic, defined by a Young Mania Rating Scale (YMRS) score > or = 12 or a Childhood Depression Rating Scale-Revised Version (CDRS-R) score > or = 28 at baseline. The primary effectiveness measure was an endpoint Clinical Global Impressions-Improvement scale (CGI-I) score < or = 2 ("much" or "very much" improved). Secondary efficacy measures included change from baseline to endpoint in YMRS and CDRS-R scores. RESULTS: Mood disorder diagnoses in the adolescents consisted of bipolar disorder not otherwise specified (N = 11), dysthymia (N = 3), bipolar II disorder (N = 3), cyclothymia (N = 2), and major depressive disorder (N = 1). The majority of patients (N = 12, 60%) were non-responders to previous trials of psychotropic agents. Fifteen subjects (75%) completed all study visits. Eighty-seven percent of patients were responders (CGI-I < or = 2) to quetiapine at week 12 (mean +/- SD endpoint dose = 460 +/- 88 mg/day). YMRS scores decreased from 18.1 +/- 5.5 at baseline to 8.7 +/- 7.9 at endpoint (p < .0001), and CDRS-R scores decreased from 38.2 +/- 9.8 to 27.7 +/- 9.3, (p = .0003). The most frequently reported adverse events were somnolence, headache, musculoskeletal pain, and dyspepsia. No subjects discontinued study participation due to adverse events. CONCLUSION: Although these findings are limited by the small sample size and open-label treatment, the results suggest that quetiapine may be an effective treatment for mood symptoms in adolescents with a familial risk for developing bipolar I disorder.

Health-related quality of life in adolescents with bipolar I disorder.

OBJECTIVE: To examine abnormalities in health-related quality of life (HRQOL) and to determine whether pharmacological intervention with divalproex or quetiapine alters HRQOL abnormalities in bipolar adolescents. METHOD: Parents of 23 adolescents diagnosed with a manic or mixed episode associated with bipolar I disorder were asked to rate their child's health using the Child Health Questionnaire-Parental Form 50 (CHQ-PF 50) at baseline, prior to receiving medication and then at 28 days later. RESULTS: Manic adolescents exhibited significantly worse HRQOL than national norms at baseline on all subscales of the CHQ-P50 except for those assessing physical well-being. Twenty eight days later, similar results were obtained for the divalproex group. Significant improvements in HRQOL, particularly on the psychosocial subscales, occurred for both groups. CONCLUSIONS: HRQOL for bipolar youth improves following pharmacological treatments. However, distinct effects of specific treatments may exist, and impairment in several domains persists.

Psychiatric and metabolic characteristics of childhood versus adult-onset obesity in patients seeking weight management.

The purpose of the study was to examine whether childhood-onset obesity differed from adult-onset obesity in lifetime prevalence of mood and eating disorders, and metabolic abnormalities, in currently obese adults seeking weight loss. A subgroup of childhood-onset obesity participants (N=44) was compared with a subgroup with adult-onset obesity (N=69) on a number of clinical and metabolic features. The results showed high lifetime prevalence rates of mood (78%) and eating (81%) disorders, and metabolic syndrome (45%), in the group as a whole. However, patients with childhood-onset obesity had a significantly higher lifetime prevalence of eating disorders in general, and of bulimia nervosa in particular, than patients with adult-onset obesity. Our results support findings of substantial comorbidity among obesity, mood and eating disorders, and metabolic syndrome in weight loss seeking populations. Early recognition and attention to eating and mood dysregulation, including, but not limited to binge eating disorder and bulimia nervosa, in some persons, might help reduce their lifetime risk for obesity.

Gabapentin in the treatment of fibromyalgia: a randomized, double-blind, placebo-controlled, multicenter trial.

OBJECTIVE: To assess the efficacy and safety of gabapentin in patients with fibromyalgia. METHODS: A 12-week, randomized, double-blind study was designed to compare gabapentin (1,200-2,400 mg/day) (n=75 patients) with placebo (n=75 patients) for efficacy and safety in treating pain associated with fibromyalgia. The primary outcome measure was the Brief Pain Inventory (BPI) average pain severity score (range 0-10, where 0=no pain and 10=pain as bad as you can imagine). Response to treatment was defined as a reduction of >or=30% in this score. The primary analysis of efficacy for continuous variables was a longitudinal analysis of the intent-to-treat sample, with treatment-by-time interaction as the measure of effect. RESULTS: Gabapentin-treated patients displayed a significantly greater improvement in the BPI average pain severity score (P=0.015; estimated difference between groups at week 12=-0.92 [95% confidence interval -1.75, -0.71]). A significantly greater proportion of gabapentin-treated patients compared with placebo-treated patients achieved response at end point (51% versus 31%; P=0.014). Gabapentin compared with placebo also significantly improved the BPI average pain interference score, the Fibromyalgia Impact Questionnaire total score, the Clinical Global Impression of Severity, the Patient Global Impression of Improvement, the Medical Outcomes Study (MOS) Sleep Problems Index, and the MOS Short Form 36 vitality score, but not the mean tender point pain threshold or the Montgomery Asberg Depression Rating Scale. Gabapentin was generally well tolerated. CONCLUSION: Gabapentin (1,200-2,400 mg/day) is safe and efficacious for the treatment of pain and other symptoms associated with fibromyalgia.

Genetic service providers' practices and attitudes regarding adolescent genetic testing for carrier status.

PURPOSE: To characterize current practices and attitudes regarding testing adolescents for carrier status. METHODS: Electronic survey of 294 genetic service providers from various professional organizations. Testing for predisposition and presymptomatic conditions was excluded from this study. RESULTS: Eighty-three percent of providers had received requests to test adolescents for carrier status. Of these, 84% have performed testing. Providers cited adolescent desire, sexual activity/pregnancy, and adolescent competence as the main reasons for testing. Some providers who performed testing found the current guidelines unhelpful. CONCLUSION: Testing adolescents for carrier status is common for at least some conditions. The guidelines regarding genetic testing of adolescents may need to be updated to reflect current concerns and practices.

Psychopathology in children of bipolar parents.

BACKGROUND: Few studies have examined the psychopathological profiles of child offspring of bipolar parents. Such investigations are useful as a first step to identifying potential prodromal manifestations of bipolar disorder. METHODS: The presence of psychopathology in 37 children with at least one parent with bipolar I disorder and 29 demographically matched children with parents free of any DSM-IV Axis I psychopathology was evaluated using the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia (WASH-U KSADS). RESULTS: Twenty-nine (78%) of 37 high-risk children were diagnosed with at least one DSM-IV Axis I diagnosis as compared to seven (24%) of 29 children of healthy control parents (Fisher's exact test, p < 0.0001, odds ratio=11, 95% CI=3.33, 33). Sixteen percent (N=6) of high-risk offspring met DSM-IV criteria for bipolar I disorder as compared to none of the healthy control offspring (Fisher's exact test, p < 0.03). High-risk offspring also had statistically significant elevations in rates of other affective and disruptive behavior disorders as well as subsyndromal manifestations of psychopathology. CONCLUSIONS: Children of bipolar parents had an elevated risk for developing bipolar and other psychiatric disorders. The study of children of bipolar parents who are at high risk for developing bipolar disorder themselves is essential to identify potential prodromal manifestations of the disorder and to eventually establish targeted early intervention strategies. Longitudinal studies to confirm the prodromal manifestations of bipolar disorder and risk factors associated with the development of specific diagnoses in children are needed.

Open-label aripiprazole in the treatment of acute bipolar depression: a prospective pilot trial.

BACKGROUND: Increasing evidence indicates that some second-generation antipsychotics are efficacious in bipolar depression, but there are few data on this illness for the novel agent aripiprazole. METHODS: Aripiprazole response was prospectively assessed for 8 weeks with the Montgomery-Asberg Depression Rating Scale (MADRS), the Clinical Global Impression Scale Modified for Bipolar Illness (CGI-BP), and the Young Mania Rating Scale (YMRS) in 31 bipolar patients with acute depression inadequately responsive to 1 mood stabilizer. Side effects and body weight were also evaluated. Outcome measures were analyzed with repeated measures ANOVAs. RESULTS: Patients showed a significant decrease in mean MADRS total and CGI-BP-Depression Severity scores, but only 14 (45%) completed the 8-week trial. Thirteen (42%) patients met criteria for response (> or =50% reduction in MADRS total score), 11 (35%) patients met criteria for remission (final MADRS total score < or =12), and 9 (29%) patients discontinued aripiprazole for side effects, most commonly akathisia (N=4). As a group, patients showed statistically insignificant weight gain (0.8+/-2.5 kg) over the 8-week trial. CONCLUSION: Aripiprazole was associated with beneficial effects on mood in some patients with bipolar depression, but also had a high discontinuation rate, primarily due to side effects. Double-blind, placebo-controlled studies are necessary to determine aripiprazole's efficacy, tolerability, and safety in bipolar depression.

Abnormalities in the fatty acid composition of the postmortem orbitofrontal cortex of schizophrenic patients: gender differences and partial normalization with antipsychotic medications.

Previous studies have observed significant abnormalities in the fatty acid composition of peripheral tissues from drug-naïve first-episode schizophrenic (SZ) patients relative to normal controls, including deficits in omega-3 and omega-6 polyunsaturated fatty acids, which are partially normalized following chronic antipsychotic treatment. We hypothesized that postmortem cortical tissue from patients with SZ would also exhibit deficits in cortical docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA; 20:4n-6) relative to normal controls, and that these deficits would be greater in drug-free SZ patients. We determined the total fatty acid composition of postmortem orbitofrontal cortex (OFC) (Brodmann area 10) from drug-free and antipsychotic-treated SZ patients (n=21) and age-matched normal controls (n=26) by gas chromatography. After correction for multiple comparisons, significantly lower DHA (-20%) concentrations, and significantly greater vaccenic acid (VA) (+12.5) concentrations, were found in the OFC of SZ patients relative to normal controls. Relative to age-matched same-gender controls, OFC DHA deficits, and elevated AA:DHA, oleic acid:DHA and docosapentaenoic acid (22:5n-6):DHA ratios, were found in male but not female SZ patients. SZ patients that died of cardiovascular-related disease exhibited lower DHA (-31%) and AA (-19%) concentrations, and greater OA (+20%) and VA (+17%) concentrations, relative to normal controls that also died of cardiovascular-related disease. OFC DHA and AA deficits, and elevations in oleic acid and vaccenic acid, were numerically greater in drug-free SZ patients and were partially normalized in SZ patients treated with antipsychotic medications (atypical>typical). Fatty acid abnormalities could not be wholly attributed to lifestyle or postmortem tissue variables. These findings add to a growing body of evidence implicating omega-3 fatty acid deficiency as well as the OFC in the pathoaetiology of SZ, and suggest that abnormalities in OFC fatty acid composition may be gender-specific and partially normalized by antipsychotic medications.

Obstetrical complications in children at high risk for bipolar disorder.

OBJECTIVE: To examine obstetrical complications as a risk factor for developing bipolar disorder (BPD). We hypothesized that children with a bipolar parent would be at greater risk for obstetrical complications than demographically matched children of healthy adults. Additionally, within this "at-risk" (AR) sample, we hypothesized that obstetrical complications would be associated with the development of psychiatric disorders. METHODS: The Washington University in St. Louis Kiddie-Schedule for Affective Disorders and Schizophrenia (WASH-U KSADS) was administered to children (AR) who had at least one parent with BPD (N=36) and children of healthy parents (HC) (N=27), by raters who were blind to diagnostic category. To assess obstetrical risk history, the Rochester Research Obstetrical Scale (ROS) was administered to parents of AR and HC children. RESULTS: Children at familial risk for BPD had greater total (p=0.02) and prenatal (p=0.006) obstetrical complication scores than children of healthy parents. However, obstetrical complications were not associated with the development of affective, anxiety, or disruptive behavioral disorders within the at-risk group. CONCLUSION: Our data suggest that compared with children of families without BPD, children of parents with BPD may be at greater risk for obstetrical complications, particularly those that occur during the prenatal period; however, at this early follow-up period factors other than obstetrical complications appear to contribute to the differences in rates of psychiatric disorders between these groups.

Child behavior checklist profiles of children and adolescents with and at high risk for developing bipolar disorder.

In order to recognize behavioral patterns in children and adolescents at risk for developing bipolar disorder, this study examined Child Behavior Checklist (CBCL) profiles of bipolar offspring both with (BD group) and without ("at-risk" or AR group) bipolar disorder themselves. The BD youth had three CBCL subscale T scores > or = 70 (attention problems, delinquent behavior, and aggression) and scored significantly higher than healthy comparison youth on all CBCL subscales. AR youth did not have any T scores > or = 70; however, they scored higher than healthy comparisons in the anxiety/depression, attention problems, aggression, and withdrawal subscales. AR and BD youth differed significantly on all scales except somatic complaints and anxiety/depression.

Selective deficits in the omega-3 fatty acid docosahexaenoic acid in the postmortem orbitofrontal cortex of patients with major depressive disorder.

BACKGROUND: Epidemiological surveys and peripheral tissue (red blood cells/plasma) fatty acid composition studies suggest that omega-3 fatty acid deficiency is associated with major depressive disorder (MDD) and suicide. It was hypothesized that patients with MDD would exhibit lower frontal cortical concentrations of docosahexaenoic acid (DHA), the principal omega-3 fatty acid in brain, relative to normal controls. METHODS: We determined the total fatty acid composition of postmortem orbitofrontal cortex (Brodmann's Area 10) from patients with DSM-IV-defined MDD (n = 15) and age-matched normal controls (n = 27) by gas chromatography. RESULTS: After correction for multiple comparisons, the omega-3 fatty acid DHA was the only fatty acid that was significantly different (-22%) in the postmortem orbitofrontal cortex of MDD patients relative to normal controls. Deficits in DHA concentrations were greater in female MDD patients (-32%) than in male MDD patients (-16%), and could not be wholly attributed to lifestyle factors or postmortem tissue variables. CONCLUSIONS: These results demonstrate a selective deficit in the omega-3 fatty acid DHA in the orbitofrontal cortex of patients with MDD. This finding adds to a growing body of evidence implicating omega-3 fatty acid deficiency as well as the orbitofrontal cortex in the pathophysiology and potentially pathogenesis of MDD.