(Cd,Mg)Te crystals for picosecond-response optical-to-x-ray radiation detectors.

We demonstrate a photodetector sensitive to both optical and x-ray picosecond pulses based on our in-house grown cadmium magnesium telluride (Cd,Mg)Te single crystal. Specifically, we developed In-doped Cd0.96Mg0.04Te material and discuss its femtosecond optical photoresponse, as well as the detector performance, such as <100-pA dark current and up to 0.22-mA/W responsivity for 780-nm wavelength optical radiation. The detector exposed to Ti fluorescence (K alpha) x-ray pulses at 4.5 keV, generated by a free-electron laser beam with the central energy of 9.8 keV and <100 fs pulse width, exhibited readout-electronics-limited 200-ps full-width-at-half-maximum photoresponse, demonstrating that it is suitable for coarse timing in free-electron laser x-ray/optical femtosecond pump-probe spectroscopy applications.

The quality of mental health literacy measurement tools evaluating the stigma of mental illness: a systematic review.

AIMS: Stigma of mental illness is a significant barrier to receiving mental health care. However, measurement tools evaluating stigma of mental illness have not been systematically assessed for their quality. We conducted a systematic review to critically appraise the methodological quality of studies assessing psychometrics of stigma measurement tools and determined the level of evidence of overall quality of psychometric properties of included tools. METHODS: We searched PubMed, PsycINFO, EMBASE, CINAHL, the Cochrane Library and ERIC databases for eligible studies. We conducted risk-of-bias analysis with the Consensus-based Standards for the Selection of Health Measurement Instruments checklist, rating studies as excellent, good, fair or poor. We further rated the level of evidence of the overall quality of psychometric properties, combining the study quality and quality of each psychometric property, as: strong, moderate, limited, conflicting or unknown. RESULTS: We identified 117 studies evaluating psychometric properties of 101 tools. The quality of specific studies varied, with ratings of: excellent (n = 5); good (mostly on internal consistency (n = 67)); fair (mostly on structural validity, n = 89 and construct validity, n = 85); and poor (mostly on internal consistency, n = 36). The overall quality of psychometric properties also varied from: strong (mostly content validity, n = 3), moderate (mostly internal consistency, n = 55), limited (mostly structural validity, n = 55 and construct validity, n = 46), conflicting (mostly test-retest reliability, n = 9) and unknown (mostly internal consistency, n = 36). CONCLUSIONS: We identified 12 tools demonstrating limited evidence or above for (+, ++, +++) all their properties, 69 tools reaching these levels of evidence for some of their properties, and 20 tools that did not meet the minimum level of evidence for all of their properties. We note that further research on stigma tool development is needed to ensure appropriate application.

Improving Malawian teachers' mental health knowledge and attitudes: an integrated school mental health literacy approach.

BACKGROUND: Mental health literacy is foundational for mental health promotion, prevention, stigma reduction and care. Integrated school mental health literacy interventions may offer an effective and sustainable approach to enhancing mental health literacy for educators and students globally. METHODS: Through a Grand Challenges Canada funded initiative called 'An Integrated Approach to Addressing the Issue of Youth Depression in Malawi and Tanzania', we culturally adapted a previously demonstrated effective Canadian school mental health curriculum resource (the Guide) for use in Malawi, the African Guide: Malawi version (AGMv), and evaluated its impact on enhancing mental health literacy for educators (teachers and youth club leaders) in 35 schools and 15 out-of-school youth clubs in the central region of Malawi. The pre- and post-test study designs were used to assess mental health literacy - knowledge and attitudes - of 218 educators before and immediately following completion of a 3-day training programme on the use of the AGMv. RESULTS: Results demonstrated a highly significant and substantial improvement in knowledge (p < 0.0001, d = 1.16) and attitudes (p < 0.0001, d = 0.79) pertaining to mental health literacy in study participants. There were no significant differences in outcomes related to sex or location. CONCLUSIONS: These positive results suggest that an approach that integrates mental health literacy into the existing school curriculum may be an effective, significant and sustainable method of enhancing mental health literacy for educators in Malawi. If these results are further found to be sustained over time, and demonstrated to be effective when extended to students, then this model may be a useful and widely applicable method for improving mental health literacy among both educators and students across Africa.

Sertraline in generalized anxiety disorder: efficacy in treating the psychic and somatic anxiety factors.

OBJECTIVE: The objective was to study the efficacy of sertraline on symptoms of psychic and somatic anxiety in patients suffering from moderate-to-severe generalized anxiety disorder (GAD). METHOD: Out-patients with DSM-IV GAD were randomized to 12 weeks of double-blind treatment with placebo. The psychic and somatic anxiety factors of the Hamilton Anxiety Rating Scale (HAM-A) and the Quality of Life, Enjoyment, and Satisfaction Questionnaire were analyzed. RESULTS: Treatment with sertraline resulted in significantly greater last observation carried forward (LOCF)-endpoint improvement than placebo on both the HAM-A psychic and somatic anxiety factors. At LOCF-endpoint, all items on the HAM-A psychic factor were more improved on sertraline than placebo, as were three of seven items on the somatic factor. Reduction of secondary depressive symptoms was more correlated with endpoint improvement in quality of life than either psychic- or somatic anxiety. CONCLUSION: Sertraline treatment demonstrated efficacy for both the psychic and somatic anxiety symptoms of GAD.

The characteristics of asymptomatic female adolescents at high risk for depression: the baseline assessment from a prospective 8-year study.

OBJECTIVES: This longitudinal 8-year study assesses potential predictors of major depressive disorder (MDD) in a cohort of healthy adolescent females at high familial risk for MDD. The objective of this study was to ascertain whether risk factors for female onset MDD would differentiate youth at high or usual risk for MDD, prior to the onset of depressive symptomology. METHODS: Subjects (ages 12-15 years) were assigned to a high (n=43) or usual (n=40) risk group according to maternal history of MDD. Depressive symptomatology (Beck Depression Inventory, Hamilton Rating Scale for Depression), pubertal development (Pubertal Developmental Staging Questionnaire), social support (Social Support Scale), and cognitive vulnerability (Depressive Experiences Questionnaire) were assessed. RESULTS: High risk and usual risk group demonstrated no significant differences in demographic variables such as age, body mass index, and grade. Significantly more youth in the high risk group (n=40, 93%) had started menstruation, compared to youth in the usual risk group (n=31, 77.5%). There were no significant differences between the groups on measures of dysphoric cognitive style, perceived overall number of social supports, or satisfaction with social support. CONCLUSIONS: Females at high familial risk for the onset of depression have significant differences in pubertal development, but not in demographics, depressive symptoms, social supports, or dysphoric cognitive style, when compared to females at usual risk for depression. These findings suggest that in prevention trials for depression in asymptomatic young women no non-biological risk factors for MDD aid in identifying females at higher risk for MDD.

A pilot study of loading versus titration of valproate in the treatment of acute mania.

OBJECTIVE: This double-blind pilot study compares the effectiveness and incidence of adverse effects of oral loading versus titration schedules of valproate in acute mania. METHOD: Consecutive new admissions for an acute manic episode were prescribed either an oral loading dose (20 mg/kg/day; n = 5; mean age = 33.4) or slower titration dose (10 mg/kg/day, n = 6. mean age = 30.6) of valproate for 7 days without other psychotropic agents. with the exception of benzodiazepines. Daily outcome measures included: serum valproic acid levels, the Young Mania Rating Scale (YMRS), the Brief Psychiatry Rating Scale (BPRS), the Clinical Global Impression Scale (CGI) and the Adverse Effect Rating Scale. RESULTS: The mean serum valproic acid levels were significantly higher in the loading group when compared with the titration group after 1 and 2 days following the initiation of treatment (p < 0.05). After 3 days of treatment there was a trend for the group that received the loading regimen to have slightly more improvement in YMRS scores compared with the titration group. Side-effects were minor for both treatments, however, a higher incidence of side-effects was reported in the titration group, with 50% of patients reporting sedation most likely because of increased use of benzodiazepines. CONCLUSION: This suggests that a loading dose of valproate is likely safe and may provide an earlier onset of antimanic effects in patients with bipolar disorder. Future studies with larger sample sizes are indicated.

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.

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.

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.

Clinical guidelines for the treatment of depressive disorders. VI. Special populations.

BACKGROUND: The Canadian Psychiatric Association and the Canadian Network for Mood and Anxiety Treatments partnered to produce clinical guidelines for psychiatrists for the treatment of depressive disorders. METHODS: A standard guidelines development process was followed. Relevant literature was identified using a computerized Medline search supplemented by review of bibliographies. Operational criteria were used to rate the quality of scientific evidence, and the line of treatment recommendations included consensus clinical opinion. This section, "Special Populations," is 1 of 7 articles that were drafted and reviewed by clinicians. Revised drafts underwent national and international expert peer review. RESULTS: This section reports on the prevalence, course, and outcome of depression for specific populations. Psychological, pharmacologic, and other biological treatment options for these populations--children and adolescents, the elderly, women at times of increased risk within the reproductive cycle, and specific ethnocultural groups--are critically evaluated. CONCLUSIONS: Major depressive disorder (MDD) is prevalent across the lifespan. In general, clinical presentations are more similar than different across age, sex, and cultural divides. Although less evidence is available for the efficacy of treatments in these subpopulations than in mid-life patients, comparable rates of response for pharmacotherapies, electroconvulsive therapy (ECT), and, in some cases, evidence-based psychotherapies have been reported.

The 'dalhousie serotonin cocktail' for treatment-resistant major depressive disorder.

We describe the successful treatment of five patients with treatment-resistant major depressive disorder (TR-MDD) with a combination pharmacotherapy of pindolol, tryptophan and nefazodone. Five TR-MDD outpatients who had previously not responded to at least four different antidepressant medication trials were initiated on 300 mg/day of nefazodone, 7.5 mg/day of pindolol and 1 g/day of tryptophan. Pindolol doses remained the same throughout the 20 weeks, while tryptophan and nefazodone dosages were gradually increased to 8 g/day and 450 mg/day, respectively. The Hamilton Depression Rating Scale (HAM-D) was used to evaluate outcome. By week 4, all cases demonstrated at least 50% decrease in HAM-D scores. At the end of the trial, the group mean HAM-D score had significantly decreased from 26.8 (+/- 1.9) to 1.8 (+/- 0.8) (p < 0.001). No significant adverse effects were reported. These results suggest that if serotonin availability and release is further enhanced by tryptophan in the presence of nefazodone and pindolol, an antidepressant effect may be produced in patients who are otherwise treatment-resistant. Due to limited sample size, an open design and an 'unusually' high successful efficacy rate of this preliminary study, controlled studies are required to confirm the efficacy of this treatment strategy.

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.

Diagnosis and measurement of adolescent depression: a review of commonly utilized instruments.

We surveyed 160 recent studies of adolescent depression (publication dates ranged from March 1996 to August 2000) and identified 33 different diagnostic and symptom measurement instruments being used by various investigators. We also found that more than one in three of the studies measuring depressive symptom severity in adolescents relied on instruments designed for use with adults. We then reviewed in detail the design features and psychometric properties of the 12 instruments most commonly used in studies of adolescent depression and attempted to characterize their strengths and weaknesses. Our main conclusions are as follows: Too many different instruments are being used by investigators, presumably due to a lack of consensus as to which are the most valid and reliable tools. Instruments designed for use in adults and never validated in adolescent populations are frequently used with no evidence for their developmental sensitivity. Many studies are using instruments that demonstrate substantial weaknesses in validity and/or reliability. The need for a parsimonious, easily administered, valid, and reliable tool(s) to diagnose and measure symptom severity in adolescent depression has not yet been met.

Measures of attention and hyperactivity symptoms in a high-risk sample of children of bipolar parents.

BACKGROUND: To determine whether significant symptoms of inattention were present among the offspring of well-characterized bipolar parents. METHODS: We included 53 offspring of 30 parents meeting DSM-IV criteria for bipolar disorder diagnosed by consensus on the basis of a SADS-L interview and a wealth of longitudinal clinical data. The unaffected parent had no lifetime history of a major psychiatric illness. Offspring, prospectively followed for up to 5 years, completed psychometric measures of attention and mood when judged to be at a good level of functioning (well, remitted or treated). RESULTS: Those offspring with any lifetime psychiatric diagnosis endorsed more subjective problems with attention. However, there was no measurable difference on tasks of sustained attention between those with and those without a lifetime psychiatric illness including affective disorder. There was a significant association between self-reported symptoms of depression and inattention, but no association between either self-report measure and an objective measure of sustained attention. LIMITATIONS: This study was not intended to be a comprehensive neuropsychological investigation of at risk offspring. CONCLUSIONS: In this high-risk population, subjective difficulty with attention appeared to be state-dependent, associated with the degree of subjective distress related to an underlying psychiatric illness.

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.

Selective serotonin reuptake inhibitor discontinuation syndrome: proposed diagnostic criteria.

OBJECTIVE: To establish specific criteria by which selective serotonin reuptake inhibitor (SSRI) discontinuation syndrome may be identified. DATA SOURCES: MEDLINE and PSYCHLIT databases were searched for case reports published from 1986 to 1997 inclusive, and references of relevant articles were also searched. STUDY SELECTION: Forty-six case reports of symptoms following the discontinuation of fluoxetine, fluvoxamine, paroxetine or sertraline were selected. Three studies of SSRI discontinuation were also reviewed. DATA EXTRACTION: Demographic and treatment information, as well as the timing, duration, number, nature and frequency of dicontinuation symptoms. DATA SYNTHESIS: Paroxetine was most frequently implicated. The drug had been tapered in half of the cases. In some cases, symptom onset began during taper, whereas, in most cases, symptoms began within 1 to 3 days of drug discontinuation. Fifty-three different symptoms were reported, with dizziness being the most common. Other common symptoms were nausea or emesis, fatigue, headache, gait instability and insomnia. Shock-like sensations, paresthesia and visual disturbances were the most rare. Without intervention, symptoms persisted for more than a week in half of the cases. In cases in which the SSRI was restarted, symptoms resolved within 72 hours. In some cases, withdrawal symptoms recurred when the same SSRI was again discontinued. CONCLUSIONS: Findings were used to construct diagnostic criteria for the SSRI discontinuation syndrome. These criteria are 2 or more of the following symptoms developing within 1 to 7 days of discontinuation or reduction in dosage of an SSRI after at least 1 month's use, when these symptoms cause clinically significant distress or impairment and are not due to a general medical condition or recurrence of a mental disorder: dizziness, light-headedness, vertigo or feeling faint; shock-like sensations or paresthesia; anxiety; diarrhea; fatigue; gait instability; headache; insomnia; irritability; nausea or emesis; tremor; and visual disturbances.

Practical clinical issues regarding child and adolescent psychopharmacology.

The psychotropic treatment of child and adolescent psychiatric disorders is becoming increasingly common. In many cases, its clinical use outstrips its demonstrated scientific validity. Pharmacologic compounds need to be properly utilized, effectively prescribed, and appropriately monitored. This entails a detailed knowledge of various psychotropic agents, their pharmacokinetics and pharmacodynamics, and a high degree of psychotherapeutic sophistication in terms of the patient-family-physician relationship.

Smoking, nicotine and psychiatric disorders: evidence for therapeutic role, controversies and implications for future research.

Researchers interested in investigating the possible therapeutic effects and the mechanisms of action of nicotine in neuropsychiatric disorders face a social-scientific-ethical dilemma. This dilemma comprises three components: (1) the known addictive potential of nicotine makes careful evaluation of the therapeutic potential of this compound socially unattractive; (2) the potential misuse of scientifically determined data by the tobacco 'lobby' creates ethical concerns; and (3) the possible confusion between the differential effects of nicotine in human smokers versus non-smokers creates difficulties in study designs in voluntary human subjects. Therefore, it is imperative that, at the onset of this review, the authors stress that they do not advocate cigarette-smoking as a route of nicotine intake under any circumstances on the basis that controlled dosing of nicotine may be of potential benefit in some neuropsychiatric disorders. In this article, we review the psychopharmacology of nicotine and its effects in a variety of neuropsychiatric disorders including schizophrenia, depression, anxiety and Tourette's syndrome. Possible mechanisms of action of nicotine directly or indirectly via its interaction with other neurotransmitter systems (i.e. serotonin, dopamine and noradrenaline) in relation to its potential role in these disorders are discussed. It is postulated that new drugs may need to be developed that selectively interact with nicotinic receptors without addiction potential.