Pituitary volume in teenagers with first-presentation borderline personality disorder

This study used magnetic resonance imaging to examine pituitary gland volume (PGV) in teenage patients with a first presentation of borderline personality disorder (BPD). No difference in PGV was observed between healthy controls (n=20) and the total BPD cohort (n=20). However, within the BPD cohort, those exposed to childhood trauma (n=9) tended to have smaller pituitaries (-18%) than those with no history of childhood trauma (n=10). These preliminary findings suggest that exposure to childhood trauma, rather than BPD, per se, might be associated with reduced PGV, possibly reflecting hypothalamic-pituitary-adrenal axis dysfunction.     

Do individuals with high functioning autism have the IQ profile associated with nonverbal learning disability?

Previously researchers have noted a high level of occurrence of the IQ profile associated with nonverbal learning disability (NLD) in Asperger syndrome (ASP) but not in high functioning autism (HFA). We examined the IQ profile scores of a large sample of children (n = 69) and adults (n = 77) with HFA, stringently diagnosed according to ADOS, ADI-R, and DSM-IV criteria, and a corresponding sample of typical child (n = 72) and adult controls (n = 107). At least one of the three primary components of the Wechsler pattern seen in NLD were found in 17–26% of the children and 20–32% of the adults with HFA. All three components occurred in slightly more than 5% of the children and adults with autism. Overall, the VIQ > PIQ profile seen in NLD occurred in 18% of the sample of individuals stringently diagnosed with HFA. Therefore, obtaining this IQ profile is not a valid clinical discriminator between NLD and HFA.     

The association of fetal and childhood growth with risk of schizophrenia. Cohort study of 720,000 Swedish men and women

Previous studies have shown that endogenous brain levels of kynurenic acid (KYNA), a glutamate receptor antagonist, are elevated in patients with schizophrenia. Here we analyse KYNA in the cerebrospinal fluid (CSF) from a large cohort, including male healthy controls (n = 49) and male patients with schizophrenia (n = 90). We found that male patients with schizophrenia had significantly higher levels of CSF KYNA compared to healthy male controls (1.45 nM ± 0.10 vs. 1.06 nM ± 0.06 in the control group). Furthermore, when the patients with schizophrenia were divided into subgroups we found that CSF KYNA levels were significantly elevated in drug-naïve, first episode patients (1.53 nM ± 0.19, n = 37) and in patients undergoing treatment with antipsychotic drugs (1.53 nM ± 0.17, n = 34) compared to healthy male controls. No elevated CSF KYNA levels were detected in drug-free patients with schizophrenia, i.e. patients previously undergoing antipsychotic medications but drug-free at time of sampling (1.16 nM ± 0.10, n = 19). Present results confirm that CSF KYNA concentration is elevated in patients with schizophrenia and are consistent with the hypothesis that KYNA contributes to the pathophysiology of the disease.     

Gender differences in prolactin elevation induced by olanzapine in Japanese drug-naïve schizophrenic patients

We investigated the effect of gender on plasma prolactin levels in 20 Japanese drug-naïve schizophrenic patients [10 male, 10 female, aged 25.4 ± 10.3 (mean ± S.D.), range = 12–46 years] treated with olanzapine. Plasma prolactin levels were measured at baseline, and weeks 3 and 8 after starting titration of olanzapine. Comparisons of plasma prolactin levels between baseline and week 3, and between baseline and week 8 were made by repeated analysis of variance (ANOVA) and paired t-test. Two-way ANOVA showed a significant difference in olanzapine-induced prolactin changes between male and female patients (P = 0.037). In male patients (n = 10), the plasma concentration of prolactin at week 3 was significantly higher than at baseline (P = 0.016), but there was no significant difference between the plasma concentration of prolactin at week 8 and at baseline or week 3 (P = 0.191). In female patients (n = 10), there was a significant change of prolactin between baseline and week 3 (P = 0.005), and between baseline and week 8 (P = 0.047). Our results indicate the possibility of gender differences in prolactin elevation induced by olanzapine in Japanese drug-naïve schizophrenic patients. These gender-based findings may be helpful for clinicians when deciding the frequency of follow-up visits once a patient starts olanzapine therapy.     

The dopamine transporter gene and the impulsivity phenotype in attention deficit hyperactivity disorder: a case-control association study in a Korean sample

The dopamine transporter gene (DAT1) has been extensively studied as one of the candidate genes in attention-deficit/hyperactivity disorder (ADHD). Several studies have reported on the association between the DAT1 10-repeat allele and cognitive variables in ADHD. However, few studies have been designed to ascertain the association between DAT1 genotypes other than the 10-repeat allele and cognitive endophenotypes in ADHD. The aim of this study was to examine the relationship between the DAT1 genotypes and the candidate endophenotypes, inattention and impulsivity symptoms, as measured by the continuous performance test (CPT), in a Korean sample of 85 children diagnosed with DSM-IV ADHD. Compared to the normal control group, the frequencies of the 9/10 genotype were significantly higher in the ADHD probands (χ² = 13.45, p = 0.02, OR = 4.12, 95% CI: 2.21–12.34) and parents of probands (χ² = 11.60, p = 0.03). The 9-repeat allele frequencies were significantly higher in the ADHD probands (χ² = 11.55, p = 0.03, OR = 4.43, 95% CI: 1.55–11.78) and parents of probands (χ² = 12.70, p = 0.03) than the normal control group. Compared to the ADHD probands without the 9-repeat allele (n = 74), the mean T-score, with regard to the commission errors of the CPT, was significantly higher (p < 0.05) in the ADHD probands with the 9-repeat allele (n = 11). Compared to the ADHD probands with other DAT1 genotypes, the mean T-score, with respect to the commission errors of the CPT, was significantly higher in the ADHD probands with the 9/10 genotype (p < 0.05). The results of this study suggest the possibility of an association between the DAT1 9-repeat allele and the impulsivity phenotype of ADHD.     

The Brief Adherence Rating Scale (BARS) validated against electronic monitoring in assessing the antipsychotic medication adherence of outpatients with schizophrenia and schizoaffective disorder

Among outpatients with schizophrenia, antipsychotic non-adherence is common, grossly under-detected by patients and their prescribers, and is associated with poor clinical outcomes. Using electronic monitoring (EM) as the reference standard we evaluated the reliability and validity as well as the sensitivity and specificity of a recently developed, brief, pencil-paper, clinician-administered adherence instrument [the Brief Adherence Rating Scale (BARS)] to assess the oral antipsychotic medication adherence of outpatients with schizophrenia and schizoaffective disorder. EM and BARS adherence and symptom severity ratings were gathered at baseline and prospectively at 6 monthly visits in 61 participants (n = 35 with schizophrenia; n = 26 with schizoaffective disorder). A significant positive relationship was found between mean BARS and EM adherence (β = 0.98; r_s = 0.59, p < 0.0001). Cronbach's coefficient alpha revealed very high internal reliability for the BARS ( = 0.92). A moderate-to-strong degree of test–retest reliability was also found for the BARS (β ranged from 0.53 to 0.92 and r_s ranged from 0.46 to 0.86). Regarding concurrent validity of the BARS, greater mean BARS adherence was significantly related to lower mean PANSS total scores (β = − 0.40; r_s = − 0.39, p = 0.002) and to lower mean Positive symptom sub-scale scores (β = − 0.08, p = .007; r_s = − 0.28, p = .02). An initial 3-month monitoring period with the BARS also demonstrated good sensitivity (73%) and specificity (74%) in identifying non-adherent outpatients (defined as < 70% mean EM adherence). Relative to EM, the BARS appears to provide valid, reliable, sensitive, and specific estimates of antipsychotic medication adherence of outpatients with schizophrenia and schizoaffective disorder. The BARS appears to be a promising candidate as a brief adherence assessment instrument for feasible use in community-based settings.     

Interleukin-6 attenuates hyperthermia-induced seizures in developing rats

Previous studies indicated that several cytokines influenced the seizure propensity in convulsive disorders and were the cause of encephalopathies in childhood. We studied the role of one inflammatory cytokine, interleukin-6 (IL-6), in hyperthermia-induced seizures in developing rats. Twenty-four male Lewis rats (23–28 days old) were divided into three groups (n = 8/IL-6 (500 ng), IL-6 (50 ng), and saline control groups). We applied human recombinant IL-6 intra-nasally to developing rats 1 h before seizures induced by moist heated air (50 °C). The seizure latency was defined as the time from hyperthermia onset until the appearance of continuous seizure discharges on electroencephalography (EEG), and the seizure duration as the duration of continuous spike and wave discharges on EEG. Five of the eight rats in the IL-6 (500 ng) group, two in the IL-6 (50 ng) group, and one in the control group exhibited no seizure discharges during the 360 s heating period. In these cases, the seizure latency time was regarded as 360 s and the seizure duration time as 0 s. The median seizure latency for the IL-6 (500 ng) group, 360 s (range: 256–360), was significantly longer than that for the control one, 249 (121–360) (P < 0.05). The seizure duration for the IL-6 (500 ng) group, 0 s (0–20), was significantly shorter than that for the control one, 33 (0–76) (P < 0.025). Also, the adenosine receptor antagonist, aminophylline, prevented these effects of IL-6 on hyperthermia-induced seizures. These results indicate that IL-6 plays an anti-convulsive role through the adenosine system in hyperthermia-induced seizures, which might be relevant as to human febrile seizures.     

Validation of the electronic Visual Analogue Scale of Anxiety

Currently, the use of electronic scales is increasing rapidly, which is not surprising considering its accuracy, the ease of use and the increased compliance. The value of Visual Analogue Scales as a mean to objectify subjective variables has long been recognised. The current study aimed to validate the electronic Visual Analogue Scale of Anxiety (eVAAS).

Seventy-one subjects, control subjects (n = 46) and Panic Disorder patients (n = 25), filled out the paper VAAS and the eVAAS in a randomised order. Panic was provoked using 35% CO₂ inhalation allowing us to include maximal scores in our analyses.

The correlation between eVAAS and pVAAS was very strong and highly significant (r = 0.98, p < 0.001). pVAAS scores were slightly higher than eVAAS scores (p < 0.001), but this difference is clinically unimportant.

The VAAS established on a tablet PC is a useful and valid measure of anxiety and holds intrinsic benefits for anxiety assessment.     

Effects of acute metabolic stress on the dopaminergic and pituitary-adrenal axis activity in patients with schizophrenia, their unaffected siblings and controls

A genetically mediated abnormal sensitivity to stress is thought to play a role in the onset, exacerbation and relapse of schizophrenia. In a double blind, placebo-controlled crossover study, peak increases in plasma ACTH (ΔACTH) and homovanillic-acid, a dopamine metabolite, (ΔHVA) following exposure to a metabolic stressor(2DG) were studied in unaffected siblings of patients with schizophrenia (n = 15), their patient relatives (n = 15) and healthy controls (n = 14). Siblings showed a stress response (both ΔACTH and ΔHVA) that was significantly greater compared to controls and significantly less pronounced compared to patients. The results suggest that the genetic risk for schizophrenia may be characterized by an enhanced sensitivity to stress.     

Metformin plus sibutramine for olanzapine-associated weight gain and metabolic dysfunction in schizophrenia: a 12-week double-blind, placebo-controlled pilot study

Metformin (850-1700 mg) plus sibutramine (10-20 mg, n = 13) or placebo (n = 15) was administered for 12 weeks in olanzapine-treated chronic schizophrenia patients. Weight loss was similar in both groups: - 2.8 ± 3.2 kg vs. - 1.4 ± 2.6 kg. Except for preventing a triglyceride increase, the drug combination lacked efficacy for metabolic control in this clinical population.     

Time to rehospitalization of clozapine versus risperidone in the naturalistic treatment of comorbid alcohol use disorder and schizophrenia

Clozapine is known to be effective in treating schizophrenia patients with comorbid alcohol use disorders (AUD). However, few prospective studies have examined the effect of clozapine on community survival of the patient, which is one of the most important indicators of success for patients with schizophrenia. In this prospective, naturalistic, observational, community-survival-analysis study, we compared the effect of clozapine and risperidone on two-year psychiatric hospitalization rate and time to hospitalization in the treatment of patients with schizophrenia and comorbid AUD. We found that the clozapine treated patients were readmitted to hospital significantly later (mean survival = 526.5 days, n = 25 patients) than the risperidone treated patients (mean survival = 420.4 days, n = 36 patients). The survival curve for the clozapine-treated patients was significantly different from that of the risperidone treated patients (log-rank test, df = 1, p = .045). At the end of the two-year study period, 75% of the risperidone treated patients had been admitted to the hospital, compared to only 48% of the clozapine treated patients. These findings suggest that clozapine should be considered for the treatment of schizophrenia patients with comorbid AUD. However, due to the limitations of this study, further studies will be required to confirm these findings.     

Plasma cortisol-dehydroepiandrosterone (DHEA) ratios in schizophrenia and bipolar disorder

Hypercortisolaemia is a feature of many severe psychiatric illnesses and has been suggested to be both a causal and exacerbating factor of clinical symptoms and neurocognitive impairment. The adrenal steroid dehydroepiandrosterone (DHEA) has antiglucocorticoid properties that may have regulatory effects on glucocorticoid action in the brain. However, there is a paucity of data on these steroids and their ratio in schizophrenia and bipolar disorder. We therefore sought to assess cortisol and DHEA levels and the cortisol-DHEA ratio in patients with schizophrenia (n = 20) and bipolar disorder (n = 20), on stable medication for a minimum of 6 weeks, and healthy age- and sex-matched control subjects (n = 20). Steroid levels were measured from plasma samples collected at 30 min intervals from 1:00 p.m. to 4:00 p.m. Cortisol levels were found to be significantly elevated in both patient groups compared with controls. DHEA levels were elevated in schizophrenic patients compared with bipolar patients and controls, but there was no evidence of a difference in the cortisol-DHEA ratio of the groups. These data suggest that afternoon hypercortisolaemia is evident in symptomatic bipolar and schizophrenic patients compared to controls. However, an elevation in DHEA levels may represent a specific endocrine marker in schizophrenia.     

A prospective study of the psychological effects of "person under train" incidents on drivers

Previous studies have shown that person under train (PUT) accidents cause psychological distress to drivers during the first year following the incident. Our aims were to assess the psychological consequences of PUT accidents on drivers prospectively, and to identify risk factors for psychological effects. In this prospective, one-year, follow-up study, a consecutive series of PUT drivers (n = 202) were compared with a group of matched control drivers (n = 186). Psychological state was assessed 15 days, 3 months and 1 year after the event, using the GHQ-28 questionnaire and a standardised diagnostic interview (the v4.4 MINI). Fifteen days after the event, PUT drivers had significantly higher GHQ-28 scores (p < 0.0001) and more acute stress disorder (p = 0.008) than control drivers. No significant differences were found 3 months and 1 year after the accident. Significant explicative variables were the presence of acute and chronic psychosocial stressors (OR = 3.30 and 3.68) and the availability of immediate help (OR = 0.46). We thus confirm previous findings that train drivers who have experienced a PUT accident experience acute psychological disturbances. Our results also highlight the utility of the systematic prevention programme provided.     

Neuropsychological task performance in bipolar spectrum illness: genetics, alcohol abuse, medication and childhood trauma

Introduction:  Impaired executive and memory function is a putative genetic trait marker of bipolar I disorder (BPD I). Although executive/memory function has been posited to be an endophenotype of BPD I, it is unclear whether this extends to bipolar spectrum illness. It is also unclear to what extent non-genetic factors such as childhood abuse, alcoholism and medication influence neurocognitive function. We assessed the neuropsychological performance of a large cohort of bipolar disorder probands and their affectively ill and healthy family members, while controlling for self-reported childhood sexual and emotional abuse, emotional neglect, alcohol abuse and medication.
Methods:  A total of 230 largely euthymic participants from 47 families, comprising 49 subjects with BPD I, 19 with bipolar II disorder (BPD II), 44 with recurrent major depression (MDE-R), 33 with a single lifetime episode of depression (MDE-S), 20 with other DSM-IV diagnoses and 65 unaffected relatives, were assessed with a battery of neuropsychological tasks.
Results:  Sexual abuse, emotional abuse and emotional neglect scores were associated with poorer cognitive performance. After controlling for childhood trauma, the BPD I group performed worse than unaffected relatives on tests of visual recall memory as well as verbal recall and recognition memory. In contrast, individuals with BPD II and bipolar spectrum illness did not differ significantly from unaffected relatives. Treatment with lithium and antipsychotic medication was associated with reduced executive and verbal recognition memory function. After controlling for medication and other covariates, only verbal recall memory was significantly impaired in the BPD I cohort.
Conclusions:  Verbal recall deficits may be one manifestation of a genetically driven dysfunction of frontal-striatal cortical networks in BPD I.     

Effects of sad mood on facial emotion recognition in Chinese people

This study examined the influence of sad mood on the judgment of ambiguous facial emotion expressions among 47 healthy volunteers who had been induced to feel sad (n = 13), neutral (n = 15), or happy (n = 19) emotions by watching video clips. The findings suggest that when the targets were ambiguous, participants who were in a sad mood tended to classify them in the negative emotional categories rather than the positive emotional categories. Also, this observation indicates that emotion-specific negative bias in the judgment of facial expressions is associated with a sad mood. The finding argues against a general impairment in decoding facial expressions. Furthermore, the observed mood-congruent negative bias was best predicted by spatial perception. The findings of this study provide insights into the cognitive processes underlying the interpersonal difficulties experienced by people in a sad mood, which may be predisposing factors in the development of clinical depression.     

Corpus callosum abnormalities associated with greater externalizing behaviors in subjects at high risk for alcohol dependence

Subjects at high risk for alcoholism have a greater propensity for externalizing behaviors and brain volume reductions of possible neurodevelopmental origin. Morphometric deficits in the corpus callosum (CC), which might reflect this neurodevelopmental abnormality, have been reported in other externalizing disorders such as attention deficit hyperactivity disorder, but not in subjects at high risk for alcoholism. The objective of the current study was to evaluate the CC morphometry in subjects at high risk for alcoholism. Magnetic resonance images of the CC in high-risk subjects (n = 20) were compared with those of low-risk subjects matched to the high-risk subjects for age, sex, and handedness (n = 20). Mid-sagittal areas of the CC, genu, body, isthmus and splenium were measured based on Witelson's method with good inter- and intra-rater reliability. Externalizing behaviors were assessed using the Semi-Structured Assessment for Genetics of Alcoholism-II. Total CC, genu and isthmus areas were significantly smaller in high-risk than low-risk subjects after controlling for age and intracranial area. The total externalizing symptoms score had a significant negative correlation with genu and isthmus areas. Smaller CC areas and their negative association with externalizing behaviors may represent yet another marker of susceptibility to alcoholism in high-risk subjects.     

Executive functioning in anorexia nervosa: exploration of the role of obsessionality, depression and starvation

Cognitive deficits related to executive functioning have been previously identified in anorexia nervosa (AN). Currently, there is limited knowledge about the degree to which other variables related to AN or executive function may influence the observed relationships. The present study examined three groups of participants, women with AN (n = 22), and two control groups: women who were high in obessionality (n = 20) and women who were low in obsessionality (n = 21). Women reporting disordered eating over the previous 4 weeks were screened out of the control groups. Executive function was measured using the Wisconsin card sorting test (WCST) and the uses of common objects test (UCOT). In addition, depression, obsessionality and body mass index were measured. Initial analyses showed no significant differences between the groups on executive function, but moderate effect sizes were obtained for performance on UCOT total perseverations and WCST total trials. When controlling for either depression or obsessionality, the group differences on the UCOT total perseverations became significant and in the case of depression attained a large effect size. Both the AN and high obsessional groups showed significantly more perseverations than the low obsessional group. Depression appeared to suppress variance that was irrelevant to the prediction of perseverance thus enhancing the importance of group membership. It is recommended that variables strongly associated with AN be investigated in future research as this may clarify the relationship between AN and executive function.     

Self-assessment of functional status in schizophrenia

With new treatments targeting features of schizophrenia associated with functional disability, there is a need to evaluate the validity of ratings of everyday outcomes. It is unknown whether patients can validly self-report on aspects of their functional status, which would be a potentially economical method for obtaining outcome data. In this study, 67 older schizophrenia outpatients provided self-ratings of everyday real-world functioning using the specific levels of functioning scale (SLOF). They were also administered assessments of neuropsychological performance, performance-based measures of functional capacity and social skills, clinical symptoms, and quality of life. Case managers, unaware of other ratings, also generated SLOF ratings. Based on discrepancy scores, participants were categorized as accurate raters (n = 24), underestimators (n = 16), or overestimators (n = 27) of their functional status as compared to case managers’ ratings. Patients’ self-rated functional status was correlated with their subjective quality of life, but remarkably unassociated with case manager ratings of functional status or their own performance on functional capacity or social skills measures. Case manager ratings, however, were highly correlated with performance on functional capacity and social skills measures. Patients who underestimated their real world performance had better cognitive skills and greater self-rated depression than those who overestimated. Accurate raters demonstrated greater social skills than both overestimators and underestimators, while overestimators were most cognitively and functionally impaired. Accurate ratings of everyday outcomes in schizophrenia may require systematic observation of real world outcomes or performance-based measures, as self-reports were inconsistent with objective information.     

Serum BDNF levels and weight gain in schizophrenic patients on long-term treatment with antipsychotics

Several lines of evidence suggest that central brain-derived neurotrophic factor (BDNF) modulates food intake, metabolism, and increases in body weight. Reports have also shown that serum BDNF is altered in schizophrenic patients treated with antipsychotics. This study aimed to determine if there was a relationship between BDNF and antipsychotic-induced weight gain in patients with chronic schizophrenia. Serum BDNF was measured in 124 schizophrenia patients chronically treated with clozapine (n = 57), risperidone (n = 23) or typical antipsychotics (n = 44) and 50 healthy control subjects. To further assess group differences in serum BDNF, additional analyses were performed in a subset of patients and controls individually matched for body mass index (BMI). BDNF levels were lower in patients with schizophrenia than normal controls. However, this difference was not present when controlling for current BMI. In the individually BMI-matched sample, no differences in serum BDNF levels were observed in schizophrenic patients compared to BMI-matched healthy controls. BDNF levels negatively correlated with BMI gain in female but not in male patients when gender was considered. Antipsychotic class exerted differential effects over BDNF levels and BMI gain. Our findings suggest that decreased BDNF levels may be associated with weight gain in female schizophrenic patients on long-term antipsychotic treatment.     

Serum brain-derived neurotrophic factor response to aerobic exercise in multiple sclerosis

Brain-derived neurotrophic factor (BDNF) and insulin-like growth factor (IGF)-1, support brain health through protective, regenerative and adaptive neural processes. In this study, we investigated whether exercise and exercise training would alter circulating BDNF and IGF-1 in people with multiple sclerosis (MS) and matched controls. Twenty-two volunteers (MS (n = 11) and controls (n = 11)) matched in age, weight, body fatness and aerobic capacity (VO_2peak) completed the study. Subjects cycled at 60% of VO_2peak, three times per week for 8 weeks. Serum was analyzed for BDNF and IGF-1 at rest and BDNF after a standardized exercise bout at weeks 0, 4 and 8. Resting BDNF levels were lower in MS compared to controls at week 0 (p = 0.03) and only tended to be lower at week 8 (p = 0.07). BDNF increased at week 4 in MS subjects (p = 0.04) and returned to baseline at week 8. With acute exercise, BDNF decreased in both groups during the 3-hour post-exercise recovery period. Resting IGF-1 concentration was not significantly different between groups before or after training. Our study provides preliminary evidence that exercise may influence BDNF regulation in humans. Further research is needed to elucidate the impact of exercise on neurotrophin production, secretion and target tissue responses in humans.