Auditory P300 in borderline personality disorder and schizophrenia.

Using three sets of clinical criteria to define borderline personality disorder (BPD), P300 (P3) and other long-latency auditory event-related electroencephalographic potentials were measured in 22 subjects with BPD, 32 subjects with other personality disorders, 29 schizophrenics, 22 depressives, and 74 volunteer controls. The patients with BPD were found to differ from patients with nonborderline personality disorders, having a longer P3 latency and smaller P3 amplitude. Long-latency event-related potentials were similar in the BPD and schizophrenic groups and did not differentiate patients with BPD with a concurrent diagnosis of schizotypal personality disorder from those without schizotypal personality disorder. The P3 latency and amplitude changes distinguished the BPD and schizophrenic groups from normal controls, those with major depressive disorder, and those with nonborderline personality disorders. These findings suggest that though some patients with BPD may have depressive symptomatology, they share with schizophrenics a dysfunction of auditory neurointegration.

Auditory P300 does not differentiate borderline personality disorder from schizotypal personality disorder.

The P300 response to an auditory two-tone discrimination task has previously been reported to have prolonged latency and reduced amplitude in schizophrenia and borderline personality disorder. In this study, P300 was recorded from 23 subjects with borderline personality disorder, 12 subjects fulfilling criteria for both borderline and schizotypal personality, and 11 subjects with schizotypal personality. The mean P300 latency was similar in each of these groups and was significantly longer than in 32 patients with neuroses and other personality disorders and 74 nonpatient controls. These findings suggest that borderline and schizotypal patients share a similar abnormality in auditory stimulus evaluation and question whether or not these disorders are separate.

"Hidden" eating disorders in Scottish psychiatric inpatients.

The authors designed a study to determine the prevalence of "hidden" eating disorders among a large group of hospitalized psychiatric patients. Of 146 patients surveyed, 13.8% currently had eating disorders diagnosed according to DSM-III criteria: 7.3% had bulimia, 3.6% had anorexia nervosa, and 2.9% had an atypical disorder. Eighty percent of the bulimic patients and all of the patients with an atypical disorder had not been so identified by hospital diagnosis. Eating-disordered patients tended to have concurrent diagnoses of affective or personality disorders.

The prevalence of cyclothymia in borderline personality disorder.

Sixty patients with personality disorders were evaluated by several different diagnostic instruments to determine the prevalence of cyclothymia in borderline personality disorder (BPD) and in other personality disorders (OPD). Cyclothymia occurred more frequently in BPD than in OPD, regardless of which diagnostic system was used. In contrast, the prevalence of major, minor, and intermittent depression, hypomania, and bipolar disorder was not significantly different in BPD as compared with OPD. Cyclothymic borderlines and noncyclothymic borderlines could not be distinguished on behavioral or functional measures. These results have implications for the diagnostic validity of both BPD and cyclothymia.

Adolescent bipolar illness and personality disorder.

The relationship between adolescent bipolar illness and personality disorder has not been explored. Studies of adult bipolars suggest a bipolar illness/borderline personality disorder (BPD) association. Twenty euthymic bipolar teens were assessed using the Personality Disorders Examination. Thirty-five percent met DSM-III-R criteria for at least one personality disorder. Three of the 20 (15%) had a borderline personality disorder diagnosis. The bipolar illness with personality disorder group differed significantly from the bipolar illness without personality disorder group in terms of increased lithium unresponsiveness (p less than 0.05) and neuroleptic treatment at time of personality assessment (p less than 0.01), but not in terms of age, sex, age of illness onset, serum lithium level, rapid cycling, substance abuse history, alcohol abuse history, or number of suicide attempts. Issues regarding the study of personality disorder in adolescent bipolars are discussed.

Basal thyroid indices in adolescent depression and bipolar disorder.

OBJECTIVE: Abnormalities of the thyroid axis are documented in adult mood disorders. The most consistent findings have been observed in major depressive disorder with elevations of thyroxine (T4) or free-T4 (fT4) within the euthyroid range that decrease with treatment. The literature on adolescents is limited, and it is unknown whether similar findings might be present in this population. METHOD: First admissions to a university hospital adolescent psychiatry unit were reviewed. Fourteen depressed and 13 manic patients satisfied inclusion and exclusion criteria. None had a history of thyroid illness or medical illness or were taking medications known to affect thyroid function. Basal serum thyrotropin, T4, fT4, triiodothyronine (T3), reverse-T3, free thyroxine index (FTI), and T3 resin uptake levels were compared with those of a group of adolescent normal controls. RESULTS: T4 (but not fT4) was elevated in depressed and manic patients compared with controls (p < .05). In manic patients, T3 was decreased and reverse-T3 was increased (p < .05). There were no significant differences in relation to age, sex, or suicidality. CONCLUSIONS: We observed significant differences in basal thyroid hormone levels in depressed and manic adolescents. Our results suggest the presence of abnormalities of thyroid function in adolescent mood disorders similar to those described in mood-disordered adults.

Efficacy of paroxetine in the treatment of adolescent major depression: a randomized, controlled trial.

OBJECTIVE: To compare paroxetine with placebo and imipramine with placebo for the treatment of adolescent depression. METHOD: After a 7- to 14-day screening period, 275 adolescents with major depression began 8 weeks of double-blind paroxetine (20-40 mg), imipramine (gradual upward titration to 200-300 mg), or placebo. The two primary outcome measures were endpoint response (Hamilton Rating Scale for Depression [HAM-D] score < or = 8 or > or = 50% reduction in baseline HAM-D) and change from baseline HAM-D score. Other depression-related variables were (1) HAM-D depressed mood item; (2) depression item of the Schedule for Affective Disorders and Schizophrenia for Adolescents-Lifetime version (K-SADS-L); (3) Clinical Global Impression (CGI) improvement scores of 1 or 2; (4) nine-item depression subscale of K-SADS-L; and (5) mean CGI improvement scores. RESULTS: Paroxetine demonstrated significantly greater improvement compared with placebo in HAM-D total score < or = 8, HAM-D depressed mood item, K-SADS-L depressed mood item, and CGI score of 1 or 2. The response to imipramine was not significantly different from placebo for any measure. Neither paroxetine nor imipramine differed significantly from placebo on parent- or self-rating measures. Withdrawal rates for adverse effects were 9.7% and 6.9% for paroxetine and placebo, respectively. Of 31.5% of subjects stopping imipramine therapy because of adverse effects, nearly one third did so because of adverse cardiovascular effects. CONCLUSIONS: Paroxetine is generally well tolerated and effective for major depression in adolescents.

Changes in thyroid hormone levels associated with desipramine response in adolescent depression.

1. The authors recently reported that acutely ill depressed adolescents have elevated plasma T4 and fT4 compared to controls. Studies in adult depression suggest antidepressant response is associated with decreases in these elevated levels. The effect of antidepressant treatment on adolescent thyroid indices has not been examined. 2. Thyroid indices were examined in 12 adolescent patients (4 male, 8 female; age 14-19y) in the active treatment arm of a double-blind, placebo-controlled desipramine trial (200 mg/day for 6 weeks). Antidepressant responders had higher pre-treatment levels of T4 and larger decreases were observed responders vs. nonresponders. 3. These results replicate findings observed in adult depressed patients and suggest similar alterations in the hypothalamic-pituitary-thyroid (HPT) axis function in adolescent depression.

Parameters of adolescent depression. A review.

Recent advances in adolescent depression are reviewed, including diagnosis, epidemiology, comorbidity, personality disturbance, course and outcome, biology, and treatment. Issues regarding various aspects are critically discussed, and directions for future studies are suggested.

The pharmacotherapy of anxiety disorders in children and adolescents.

Psychopharmacologic agents may offer potentially effective treatment of child and adolescent anxiety disorders. Much further research, however, remains to be done to determine medication specificity, dosages, duration of treatment, and the optimal relationship between pharmacologic and nonpharmacologic therapies.

Impact of early onset bipolar disorder on family functioning: adolescents' perceptions of family dynamics, communication, and problems.

OBJECTIVE: This research investigated the impact of adolescent onset bipolar illness on perceived family functioning in stabilized bipolar I (B) and unipolar (U) probands, and normal controls (C). METHOD: Sample N=119: 44 bipolar 1(17 M, 27 F), 30 unipolar (9 M, 21 F), and 45 controls (19 M, 26 F). Mean ages: 19.9, 18.5 and 18.2 years, respectively. INSTRUMENTS: Family Adaptability and Cohesion Scale (FACES II), Parent-Adolescent Communication Scales (PACS), Social Adjustment Inventory for Children and Adolescents (SAICA). RESULTS: There were no significant group or sex differences between controls and mood disordered youth--assessed intermorbidly--in ratings of relationship with either parent. Bipolars acknowledged significantly more minor conflicts with parents than either unipolars or controls. Ratings by mood disordered subjects were significantly less positive in terms of shared activities and communication with siblings. Mood disordered youth and controls were not differentiated on the basis of family adaptability, and all family cohesion scores were within population norms. No significant group differences were observed in communication with parents. LIMITATIONS: This self-report study was conducted intermorbidly, does not include objective measures of family functioning, nor does it assess the effect of psychiatric illness in other family members on family functioning. CONCLUSIONS: Assessed intermorbidly, bipolar adolescents' perceptions of family dynamics do not seem to diverge significantly from controls. Further research is needed to investigate the impact of adolescent bipolar illness on family life during acute phases of the illness, as well as the effect on family functioning of psychiatric disorders in other family members.

A Canadian multicentre placebo-controlled study of a fixed dose of brofaromine, a reversible selective MAO-A inhibitor, in the treatment of major depression.

In a 6-week double-blind study, 220 patients with major depression (mostly outpatients) were randomly assigned to receive a fixed dose of brofaromine 150 mg daily (n = 111) or placebo (n = 109) after a 1-week single-blind placebo washout. Except for the HAM-D sleep items, brofaromine was superior to placebo on measures of depression as determined by the four methods of assessing drug efficacy: (1) psychiatric symptom rating (HAM-D 17-item less the three sleep items); (2) self-rating scale (Beck Depression Inventory); (3) Clinical Global Assessment of Efficacy; and (4) drop-out rate due to lack of efficacy. Most commonly reported adverse events with brofaromine were: headache, nausea, dizziness and sleep disturbance. Brofaromine was found to be an effective antidepressant, superior to placebo with a good tolerability profile.

High-dose vitamin E plus vitamin B6 treatment of risperidone-related neuroleptic malignant syndrome.

We present a case of a 74-year-old patient with schizoaffective disorder, who developed risperidone-related neuroleptic malignant syndrome. This patient responded satisfactorily to the supportive management and vit E plus vit B6.

Brofaromine in depression: a Canadian multicenter placebo trial and a review of standard drug comparative studies.

Brofaromine is a new, reversible, and selective type-A monoamine oxidase inhibitor (MAOI) that also has serotonin reuptake inhibitory properties. Its dual pharmacologic effects offer promise in the treatment of a wide spectrum of depressed patients while producing less severe anticholinergic side effects in comparison with standard drugs. A multicenter, double-blind, placebo-controlled study including 220 patients was undertaken to evaluate the efficacy and safety of brofaromine in major depression. This study of a fixed-dose design and 6 weeks' duration found that brofaromine was significantly better than placebo on the Overall Evaluation of Efficacy, Beck self-rating scale, HAM-D Bech subscale, HAM-D total 14 items (minus the three sleep items), HAM-D depressed mood item and retardation factor, and worse than placebo on the insomnia items of HAM-D. Significantly more patients on placebo than on brofaromine did not complete the trial due to lack of efficacy. In comparative controlled studies (n = 899), brofaromine was found to be at least as efficacious as tricyclic antidepressants (imipramine) and standard MAOIs (tranylcypromine and phenelzine). Reductions of at least 50% in the HAM-D total score were seen in 58-66% of patients treated with either brofaromine or imipramine (n = 609). Brofaromine also was found to be of comparable efficacy to tranylcypromine in two clinical trials (n = 132), one of which included patients considered to have a treatment-resistant depression (n = 39). In another double-blind study that compared brofaromine (150 mg/day) to phenelzine (45 mg/day) (n = 158), there was no difference between brofaromine and phenelzine.

Life events and mania: a case-controlled study.

Life events were evaluated in 14 patients with bipolar affective disorder in the year preceding a mania as well as in 14 patients with bipolar affective disorder without a mania matched for age, sex, and time of recall. There were a significantly greater number of uncontrolled and unanticipated life events in the patients with as compared to those without a mania. However, neither the total number of life events nor measures of distress and stress distinguished bipolar patients with as compared to those without mania.

Nocturnal melatonin and 24-hour 6-sulphatoxymelatonin levels in various phases of bipolar affective disorder.

Nine bipolar patients (2 men and 7 women) and 12 healthy control subjects completed overnight sampling for serum melatonin (MT) and urinary 6-sulphatoxymelatonin (aMT6s). The patients were investigated during manic, depressed, and/or euthymic states. Although serum MT levels did not differ significantly across the bipolar groups, in all cases serum MT levels were significantly lower than in control subjects. Differences in MT levels were also present between bipolar patients who were in a depressed phase and control subjects. There were no statistically significant differences in urinary aMT6s levels among the patients and control subjects, although in all cases nocturnal aMT6s levels were significantly higher than daytime levels. This study provides tentative evidence for decreased serum MT as a trait but not a state marker in bipolar affective disorder.

Psychological, topographic EEG, and CT scan correlates of frontal lobe function in schizophrenia.

This study examined frontal lobe function in a group of 20 patients with schizophrenia, on and off medication, compared to 20 normals matched for age, sex, handedness, intelligence, and educational level. Schizophrenic patients generally did not perform as well as normals on the Wisconsin Card Sorting Test (WCST). Patients off medication performed less well on this test than those on medication. Those on medication did not perform as well as those off medication on the design and word fluency tests, which suggested that medications may affect various aspects of frontal lobe function differently. During the WCST, normal subjects demonstrated an increase in beta mean frequency of the electroencephalogram in frontal and centrotemporal regions which was not statistically significant in either schizophrenic group. This shift in beta mean frequency was found to correlate positively with performance on the WCST in normals, but not in patients. Patients with more negative symptoms tended to show a smaller increase in beta mean frequency during the WCST. Performance on the WCST was correlated negatively with ventricle-brain ratio in all subjects, suggesting that frontal lobe function might be related to computed tomographic measures in the normal population as well as in schizophrenic patients. There was no correlation with performance on the WCST and length of illness.

Update and recommendations for the use of antipsychotics in early-onset psychoses.

A review was undertaken of studies evaluating the efficacy and tolerability of antipsychotic medications for the management of psychosis in children and adolescents. All identified published and unpublished studies from 1996 onward were included for review. The search located one randomized control trial, seven open-label trials, six retrospective chart reviews, and nine case reports. The studies assessed the use of haloperidol, clozapine, risperidone, olanzapine, and quetiapine in the management of psychosis in children and adolescents. Most studies reported reasonable treatment response; however, extrapyramidal side effects, sedation, and weight gain are concerning. This points to the need for appropriate baseline assessments prior to initiating treatment with these agents. Particular attention should be given to assessment of the extrapyramidal system as well as to baseline weight, lipid profile, and blood glucose. Further study is needed to refine the use of antipsychotic medications in children and adolescents in order to minimize adverse effects while conferring an optimum therapeutic response. The importance of instituting effective early treatment in youth with psychoses is an important goal that may serve to lessen the long-term morbidity of the illness.

An exploratory approach to the serotonergic hypothesis of depression: bridging the synaptic gap.

In this exploratory review, we attempt to integrate pre and post synaptic theories of the biochemical basis of depression--in particular with regard to 5-HT. We will be providing evidence that in major depressive disorder, there is a continuity of dysfunction of neural function, i.e. pre and post synaptic serotonergic symptoms are affected. Furthermore, we will also be providing the implications of this approach for normal treatments for depressive disorder.

An exploratory approach to the serotonin syndrome: an update of clinical phenomenology and revised diagnostic criteria.

Serotonin-related adverse side-effects of psychotropic drugs were first recorded in humans in 1960. However, since 1991, these related cases have been diagnosed as 'serotonin syndrome (SS)' according to the criteria reported by Sternbach. In this article, we have reviewed and further explored the validity of these criteria. The clinical profile of 24 cases of the SS published between 1991 and 1995 has been analysed in detail and compared with the symptomatology of 38 previous cases which were also further analysed. Mainly Medline and references from other reports were used to review these cases. The general concept put forward by Sternbach has been approved. On the basis of the severity of overall clinical presentation, it appeared that there is a need to further classify SS into three main groups as: (1) mild state of serotonin-related symptoms; (2) serotonin syndrome (full-blown form); (3) toxic states. Furthermore, the detailed analysis of the SS cases published so far suggests that 'the diagnostic criteria for SS' also require further revision, and these are presented here. We also review, present and discuss the guidelines for the management and treatment of SS.