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This chapter describes the physiological mechanisms that underpin the varying effects of different types of breath practices inherent in the yoga tradition and ultimately the role that breathing techniques play in person and public health. Concurrently, the script elucidates how different practices alter psycho-physiological states clarifying why and how they may be employed with specific health populations, how they may enhance and or maintain well-being, and clear guidance regarding precautions and contraindications.

This study advances the chemical research community toward the goal of replacing toxic cadmium-containing quantum dots (QDs) with environmentally benign InP QDs. The InP QD synthesis uniquely combines the previously reported use of InP magic-sized clusters (MSCs) as a single-source precursor for indium and phosphorus to form InP QDs, with zinc incorporation and subsequent ZnS shelling, to form InPZn/ZnS QDs with luminescence properties comparable to those of commonly used cadmium-containing luminescent QDs. The resulting InPZn/ZnS QDs have an emission quantum yield of about 50% across a broad range of emission peak wavelengths and emission peaks averaging 50 nm fwhm. The emission peak wavelength can be easily tuned by varying the Zn/In ratio in the reaction mixture. The strategy of using zinc stearate to tune the emission properties is advantageous as it does not lead to a loss of emission quantum yield or emission peak broadening. Although the initial optical properties of InP and InPZn/ZnS QDs are promising, thermal stability measurements of InPZn QDs show significant degradation in the absence of a shell compared to the CdSe QDs particularly at increased temperature in the presence of oxygen, which is indicative of thermal oxidation. There is no significant difference in the degradation rate of InP QDs made from molecular precursors and from MSCs. Additionally, the emission intensity and quantum yield of InPZn/ZnS QDs when purified and diluted in organic solvents under ambient conditions decrease significantly compared to those of CdSe/ ZnS QDs. This indicates instability of the ZnS shell when prepared by common literature methods. This must be improved to realize high-quality, robust Cd-free QDs with the capability of replacing CdSe QDs in QD technologies.

Background Yoga interventions offer promise for the treatment of major depressive disorder (MDD), yet their safety and potential impact on suicidal ideation (SI) have not been well documented. This study evaluated the safety of a randomized controlled dose-finding trial of Iyengar yoga plus coherent breathing for individuals with MDD, as well as the potential effects of the intervention on SI without intent. Methods Participants with Beck Depression Inventory-II (BDI-II) scores ≥14 and a diagnosis of MDD (using DSM-IV criteria) were randomized to either a low dose group (LDG) or high dose group (HDG) and received a 12-week manualized intervention. The LDG included two 90-min yoga classes plus three 30-min homework sessions weekly. The HDG offered three 90-min classes plus four 30-min homework sessions weekly. Results Thirty-two individuals with MDD were randomized, of which 30 completed the protocol. At screening, SI without intent was endorsed on the BDI-II by 9 participants; after completing the intervention, 8 out of 9 reported resolution of SI. There were 17 adverse events possibly-related and 15 definitely-related to the intervention. The most common protocol-related adverse event was musculoskeletal pain, which resolved over the course of the study. Conclusions The Iyengar yoga plus coherent breathing intervention was associated with the resolution of SI in 8 out of 9 participants, with mild side effects that were primarily musculoskeletal in nature. This preliminary evidence suggests that this intervention may reduce SI without intent and be safe for use in those with MDD.

Objective A systematic review on S-adenosylmethionine (SAMe) for treatment of neuropsychiatric conditions and comorbid medical conditions. Data sources Searches were conducted in PubMed, EMBASE, PsycINFO, Cochrane Library, CINAHL, and Google Scholar databases between July 15, 2015, and September 28, 2016, by combining search terms for SAMe (s-adenosyl methionine or s-adenosyl-l-methionine) with terms for relevant disease states (major depressive disorder, MDD, depression, perinatal depression, human immunodeficiency virus, HIV, Parkinson's, Alzheimer's, dementia, anxiety, schizophrenia, psychotic, 22q11.2, substance abuse, fibromyalgia, osteoarthritis, hepatitis, or cirrhosis). Additional studies were identified from prior literature. Ongoing clinical trials were identified through clinical trial registries. Study selection Of the 174 records retrieved, 21 were excluded, as they were not original investigations. An additional 21 records were excluded for falling outside the scope of this review. Of the 132 studies included in this review, 115 were clinical trials and 17 were preclinical studies. Data extraction A wide range of studies was included in this review to capture information that would be of interest to psychiatrists in clinical practice. Results This review of SAMe in the treatment of major depressive disorder found promising but limited evidence of efficacy and safety to support its use as a monotherapy and as an augmentation for other antidepressants. Additionally, preliminary evidence suggests that SAMe may ameliorate symptoms in certain neurocognitive, substance use, and psychotic disorders and comorbid medical conditions. Conclusions S-adenosylmethionine holds promise as a treatment for multiple neuropsychiatric conditions, but the body of evidence has limitations. The encouraging findings support further study of SAMe in both psychiatric and comorbid medical illnesses.

Objectives: The aims of this study were to assess the effects of an intervention of Iyengar yoga and coherent breathing at five breaths per minute on depressive symptoms and to determine optimal intervention yoga dosing for future studies in individuals with major depressive disorder (MDD). Methods: Subjects were randomized to the high-dose group (HDG) or low-dose group (LDG) for a 12-week intervention of three or two intervention classes per week, respectively. Eligible subjects were 18–64 years old with MDD, had baseline Beck Depression Inventory-II (BDI-II) scores ≥14, and were either on no antidepressant medications or on a stable dose of antidepressants for ≥3 months. The intervention included 90-min classes plus homework. Outcome measures were BDI-II scores and intervention compliance. Results: Fifteen HDG (Mage = 38.4 ± 15.1 years) and 15 LDG (Mage = 34.7 ± 10.4 years) subjects completed the intervention. BDI-II scores at screening and compliance did not differ between groups (p = 0.26). BDI-II scores declined significantly from screening (24.6 ± 1.7) to week 12 (6.0 ± 3.8) for the HDG (–18.6 ± 6.6; p 50% decrease in BDI-II scores; p = 0.65) for the HDG (13/15 subjects) and LDG (11/15 subjects) or remission (i.e., number of subjects with BDI-II scores

Objective: To determine if a 12-week yoga intervention (YI) was associated with increased gamma aminobutyric acid (GABA) levels and decreased depressive symptoms in participants with major depressive disorder (MDD). Methods: Subjects were randomized to a high-dose group (HDG) of three YIs a week and a low-dose group (LDG) of two YIs a week. Thalamic GABA levels were obtained using magnetic resonance spectroscopy at Scan-1 before randomization. After the assigned 12-week intervention, Scan-2 was obtained, immediately followed by a YI and Scan-3. Beck Depression Inventory II (BDI-II) scores were obtained before Scan-1 and Scan-3. Settings/Location: Screenings and interventions occurred at the Boston University Medical Center. Imaging occurred at McLean Hospital. Subjects: Subjects met criteria for MDD. Intervention: Ninety minutes of Iyengar yoga and coherent breathing at five breaths per minute plus homework. Outcome measures: GABA levels and the BDI-II. Results: BDI-II scores improved significantly in both groups. GABA levels from Scan-1 to Scan-3 and from Scan-2 to Scan-3 were significantly increased in the LDG (n = 15) and showed a trend in the total cohort. Post hoc, participants were divided into two groups based on having an increase in GABA levels at Scan-2. Increases in Scan-2 GABA levels were observed in participants whose mean time between their last YI and Scan-2 was 3.93 ± 2.92 standard deviation (SD) days, but not in those whose mean time between their last YI and Scan-2 was 7.83 ± 6.88 SD. Conclusions: This study tentatively supports the hypothesis that one of the mechanisms through which yoga improves mood is by increasing the activity of the GABA system. The observed increase in GABA levels following a YI that was no longer observed 8 days after a YI suggests that the associated increase in GABA after a YI is time limited such that at least one YI a week may be necessary to maintain the elevated GABA levels.

Evidence suggests that yoga may be an effective treatment for major depressive disorder (MDD). Studies evaluating the "dosing" of yoga treatment and efficacy for MDD are needed. The goal of this study was to assess the effects of an intervention combining Iyengar yoga and coherent breathing in participants with MDD and determine the optimal intervention dose.Thirty-two participants (18 to 65 y of age) diagnosed with MDD were randomized to a high-dose group (HDG) or a low-dose group (LDG) of yoga and coherent breathing for 12 weeks. The HDG (n=15) involved three 90-minute yoga classes and four 30-minute homework sessions per week. The LDG (n=15) involved two 90-minute yoga classes and three 30-minute homework sessions per week. Participants were evaluated at baseline, week 4, week 8, and week 12 with the following instruments: Positivity Self-Test, Spielberger State Anxiety Inventory, Patient Health Questionnaire-9, Pittsburgh Sleep Quality Index, and Exercise-induced Feeling Inventory. Data were analyzed using intent-to-treat methods.Significant improvements in all outcome measures were found for both groups, with acute and cumulative benefits. Although the HDG showed greater improvements on all scales, between-group differences did not reach significance, possibly due to lack of power because of the small sample size. Cumulative yoga minutes were correlated with improvement in outcome measures.This dosing study did not include a non-yoga control.Improvement in psychological symptoms correlated with cumulative yoga practice. Both interventions reduced symptoms of depression and anxiety and increased feelings of positivity. The time commitment for yoga practice needs to be weighed against benefits when designing yoga interventions.

Although anxiety is not always the most obvious symptom in complex cases, it must be recognized and addressed. The following four cases represent unrecognized atypical presentations of anxiety disorders and posttraumatic stress disorder (PTSD) in patients who did not respond well to conventional psychotropic medications. In these cases, affective, cognitive, and behavioral symptoms significantly improved with integrative treatments combining medicinal herbs, nootropics, other complementary approaches, and in some cases prescription psychotropic medications. When stress-related physical symptoms, such as dystonias, become the focus of treatment, the anxiety underlying the physical condition may escape notice. Patients who do not respond well to conventional medications or who have drug sensitivities are often mislabeled as “treatment-resistant.” The urgent need for behavioral control of patients with developmental disorders, learning disabilities, and communication impairments often leads to the overuse of sedating major tranquilizers that miss the real target symptoms and exacerbate underlying cognitive and coordination dysfunctions. The treatment of anxiety, depression, and mild cognitive impairment in elderly patients with mild herbal formulas can significantly improve quality of life. Patients who do not respond adequately to prescription psychotropics and those who are sensitive to medication side effects are a large subgroup of people who benefit most from integrative and complementary approaches.

Complementary and alternative medicine (CAM) in psychiatry or integrative psychiatry covers a wide range of biological, psychological and mind-body treatments that enhance standard medical practices and patient outcomes. While CAM approaches are popular amongst patients in their practice as well as in self-report because of their ease of use, health professionals have received limited education in these interventions and often are unaware of their patients' use of CAM treatments.This overview highlights evidence-based CAM treatments for attention deficit hyperactivity disorder (ADHD) including dietary interventions, phytomedicines, mind-body practices and neurofeedback.While conventional treatments are the mainstays for ADHD, there are a large number of available treatments that can be used to enhance treatment response.With improved education and further scientific and clinical research, validated integrative treatments will provide more effective, lower risk and lower cost care for patients with ADHD.

Background Menopausal women are challenged by the adverse effects of estrogen loss on energy, mood, cognitive function, and memory. These stresses are compounded by increased risks for cardiovascular disease, osteoporosis, and cancer. Known to have neuroprotective, cardio-protective, anti-oxidative and anti-carcinogenic effects, Rhodiola rosea extracts have also been shown to improve energy, mood, cognitive function and memory. Purpose We propose that R. rosea be investigated for use as a potential selective estrogen receptor modulator (SERM) in the prevention and treatment of menopause-related fatigue, stress, depression, cognitive decline, memory impairment, cardiovascular disease, osteoporosis and cancer. Method This paper briefly reviews the relationship between estrogen decline and menopause-related health risks, the molecular mechanisms underlying estrogenic effects on health, and the evidence indicating beneficial effects of R. rosea extracts on these mechanisms and health risks. Mechanisms include non-genomic and genomic effects, for example: activation of intra-cellular signal transduction pathways by binding to estrogen receptors, ERα-mediated activation of endothelial nitric oxide synthase with increased nitric oxide release; and anti-inflammatory effects, counteracting TNFα by inhibiting nuclear factor-Kappa-B (NF- K B) and protection of osteoblasts from hydrogen peroxide. A clinical case illustrating treatment of a menopausal woman with R. rosea is presented. Risks, benefits, gaps in knowledge, and future directions are discussed. Conclusion Numerous lines of evidence indicate that R. rosea should be investigated as a potential selective estrogen receptor modulator (SERM) to prevent, delay or mitigate menopause-related cognitive, psychological, cardiovascular and osteoporotic conditions.

Background This study evaluated the effects of the Breath-Body-Mind Workshop (BBMW) (breathing, movement, and meditation) on psychological and physical symptoms and inflammatory biomarkers in inflammatory bowel disease (IBD). Methods Twenty-nine IBD patients from the Jill Roberts IBD Center were randomized to BBMW or an educational seminar. Beck Anxiety Inventory, Beck Depression Inventory, Brief Symptom Inventory 18, IBD Questionnaire, Perceived Disability Scale, Perceived Stress Questionnaire, Digestive Disease Acceptance Questionnaire, Brief Illness Perception Questionnaire, fecal calprotectin, C-reactive protein, and physiological measures were obtained at baseline and weeks 6 and 26. Results The BBMW group significantly improved between baseline and week 6 on Brief Symptom Inventory 18 (P = 0.02), Beck Anxiety Inventory (P = 0.02), and IBD Questionnaire (P = 0.01) and between baseline and week 26 on Brief Symptom Inventory 18 (P = 0.04), Beck Anxiety Inventory (P = 0.03), Beck Depression Inventory (P = 0.01), IBD Questionnaire (P = 0.01), Perceived Disability Scale (P = 0.001), and Perceived Stress Questionnaire (P = 0.01) by paired t tests. No significant changes occurred in the educational seminar group at week 6 or 26. By week 26, median C-reactive protein values decreased significantly in the BBMW group (P = 0.01 by Wilcoxon signed-rank test) versus no significant change in the educational seminar group. Conclusions In patients with IBD, participation in the BBMW was associated with significant improvements in psychological and physical symptoms, quality of life, and C-reactive protein. Mind-body interventions, such as BBMW, which emphasize Voluntarily Regulated Breathing Practices, may have significant long-lasting benefits for IBD symptoms, anxiety, depression, quality of life, and inflammation. BBMW, a promising adjunctive treatment for IBD, warrants further study.

Yogic breathing is a unique method for balancing the autonomic nervous system and influencing psychologic and stress-related disorders. Part I of this series presented a neurophysiologic theory of the effects of Sudarshan Kriya Yoga (SKY). Part II will review clinical studies, our own clinical observations, and guidelines for the safe and effective use of yoga breath techniques in a wide range of clinical conditions. Although more clinical studies are needed to document the benefits of programs that combine pranayama (yogic breathing) asanas (yoga postures), and meditation, there is sufficient evidence to consider Sudarshan Kriya Yoga to be a beneficial, low-risk, low-cost adjunct to the treatment of stress, anxiety, post-traumatic stress disorder (PTSD), depression, stress-related medical illnesses, substance abuse, and rehabilitation of criminal offenders. SKY has been used as a public health intervention to alleviate PTSD in survivors of mass disasters. Yoga techniques enhance well-being, mood, attention, mental focus, and stress tolerance. Proper training by a skilled teacher and a 30-minute practice every day will maximize the benefits. Health care providers play a crucial role in encouraging patients to maintain their yoga practices.

The use of complementary and alternative medicine (CAM) has increased tremendously over the past 10 years. As a result of the increase physicians must understand both the factual information about CAM practices and the psychologic reasons patients seek out such treatments. A particular concern is the use of CAM by patients without the knowledge of their physicians, which may lead to complications resulting from interactions, or adverse effects from treatments of which the physician is unaware. This paper reviews research concerning the use of CAM by patients, explores some of the psychodynamic factors in CAM use, and suggests means of integrating that use into the patient's therapy. Specific information about herbal and other alternative products is provided.

The choice of nutrients for review is based on clinical evidence of efficacy in neuropsychiatric disorders and biochemical effects that are neuroprotective or reparative. Vitamins, minerals, amino acids, and metabolites have been shown to augment antidepressants, improve symptoms in anxiety disorders, depression, neurodegenerative diseases, brain injury, ADHD, and schizophrenia, and to reduce medication side effects. Detection and correction of vitamin and mineral deficiencies can be essential for recovery. Generally low in adverse effects when taken in therapeutic doses, nutrients can be combined for greater benefits. Further studies are warranted to validate these promising treatments.

Neurophysiological studies may explain how breathing techniques normalize stress response, emotion regulation, and autonomic and neuroendocrine system function. Breath practices have been shown to reduce symptoms of stress, anxiety, insomnia, post-traumatic stress disorder, mass disasters, depression, and attention deficit disorder. Technology-assisted breathing interventions facilitate therapeutic breathing by using either static cues such as a breath pacer or real-time feedback based on physiological parameters such as heart rate variability. The empirical literature indicates that technology-assisted breathing can be beneficial in mental health treatment, though it may not be appropriate for all individuals. Initial in-person training and evaluation can improve results.

Serotonin abnormalities have been reported in the brain of suicide victims. Evidence of a serotonin deficiency in suicide attempters is less consistent. We hypothesized that a serotonin deficiency may be present in suicide attempters whose attempt behavior more closely approximates completed suicide.Sixty-seven (67) drug-free depressed inpatients (46 suicide attempters, 21 nonattempters) underwent research clinical assessments and a lumbar puncture. Cerebrospinal fluid (CSF) monoamine metabolites were assayed. Degree of medical damage and intent of the most recent suicide attempt were rated.CSF amine metabolites did not differentiate suicide attempters as a group from nonattempters. However, reduced serotonergic activity, as indicated by lower levels of CSF-5-hydroxyindoleacetic acid (5-HIAA) was associated with a history of planned suicide attempts and with suicide attempts that resulted in greater medical damage. Other monoamine metabolites did not correlate with seriousness of suicidal behavior, except for low CSF homovanillic acid and higher medical damage. No correlation was found with violent method.Planned and more medically damaging suicide attempts appear to be associated specifically with low serotonergic activity and, therefore, resemble completed suicide both behaviorally and biochemically. It remains to be determined whether low levels of CSF 5-HIAA can predict greater medical damage in future suicide attempts.

Multi-Component Yoga Breath Program for Vietnam Veteran Post Traumatic Stress Disorder: Randomized Controlled Trial It is appropriate to acknowledge that despite treatment, Post Traumatic Stress Disorder (PTSD) continually debilitates many Vietnam veterans. Although therapies have been developed, remission is hard to obtain with either pharmacotherapy or psychotherapy. Evidence has suggested that some forms of yoga may reduce sympathetic overactivity and increase parasympathetic activity, thereby improving stress resilience.

The Behavioral Syndromes Scale for Dementia (BSSD) is a new instrument that showed strong internal consistency and interrater reliability in an outpatient sample of 106 patients with probable Alzheimer's disease. Factor analysis provided support for a priori symptom groupings, particularly the syndromes of disinhibition and apathy-indifference. Dependency (87%), denial of illness (63%), and motor agitation (55%) were common, while sexual disinhibition (2.9%) and self-destructive behaviors (2.9%) were rare. Virtually all symptoms were predominantly minimal to mild in severity. Patients with longer illness duration were more apathetic. Disinhibited behaviors and apathy-indifference increased with greater severity of dementia. Catastrophic reactions, aggression, and agitation were associated with greater functional impairment. There was great heterogeneity in symptom presentation. In Alzheimer's disease, several behavioral changes might be direct manifestations of underlying brain pathology, rather than being solely secondary to cognitive impairment.

Although a multitude of pharmaceutical agents are available for the treatment of mood disorders, anxiety and insomnia, many patients have difficulty tolerating the side effects, do not respond adequately, or eventually lose their response. Many therapeutic herbs and nutrients have far fewer side effects and may provide an alternative treatment or can be used to enhance the effect of prescription medications. In the article, the authors review the quality of the evidence supporting the clinical effects of a number of commonly used types of complementary/alternative medicine (CAM) for mood disorders, anxiety, and insomnia. They review data on the use of St. John's Wort, S-adenosyl-methionine (SAM-e), B vitamins, inositol, omega-3 fatty acids, and choline for mood disorders; data on the use of kava and other herbal agents and fish extract for anxiety and insomnia; and data on valerian and melatonin for insomnia. The authors also discuss the use of CAM to treat migraines, which may be comorbid with mood and anxiety disorders, and obesity, which can occur as a side effect of psychotropic medications. They consider the data on feverfew and butterbur for migraines and on chromium picolinate and the combination of ephedrine and caffeine for obesity. The authors also review issues related to comorbid medical illness, side effects, drug interactions, dosage, and brand selection.

Mind-body interventions are beneficial in stress-related mental and physical disorders. Current research is finding associations between emotional disorders and vagal tone as indicated by heart rate variability. A neurophysiologic model of yogic breathing proposes to integrate research on yoga with polyvagal theory, vagal stimulation, hyperventilation, and clinical observations. Yogic breathing is a unique method for balancing the autonomic nervous system and influencing psychologic and stress-related disorders. Many studies demonstrate effects of yogic breathing on brain function and physiologic parameters, but the mechanisms have not been clarified. Sudarshan Kriya yoga (SKY), a sequence of specific breathing techniques (ujjayi, bhastrika, and Sudarshan Kriya) can alleviate anxiety, depression, everyday stress, post-traumatic stress, and stress-related medical illnesses. Mechanisms contributing to a state of calm alertness include increased parasympathetic drive, calming of stress response systems, neuroendocrine release of hormones, and thalamic generators. This model has heuristic value, research implications, and clinical applications.

We report a pilot study of S-adenosyl-methionine (SAM) in 13 depressed patients with Parkinson's disease. All patients had been previously treated with other antidepressant agents and had no significant benefit or had intolerable side effects. SAM was administered in doses of 800 to 3600 mg per day for a period of 10 weeks. Eleven patients completed the study, and 10 had at least a 50% improvement on the 17-point Hamilton Depression Scale (HDS). One patient did not improve. Two patients prematurely terminated participation in the study because of increased anxiety. One patient experienced mild nausea, and another two patients developed mild diarrhea, which resolved spontaneously. The mean HDS score before treatment was 27.09 +/- 6.04 (mean +/- standard deviation) and was 9.55 +/- 7.29 after SAM treatment (p < 0.0001). Although uncontrolled and preliminary, this study suggests that SAM is well tolerated and may be a safe and effective alternative to the antidepressant agents currently used in patients with Parkinson's disease.

We report a patient treated with paroxetine and sumatriptan who developed severe persistent paroxysmal dyskinesias that included dystonia, chorea, and athetosis. This movement disorder responded partially to treatment with anticholinergic medications and benzodiazepines; and completely to clozapine, an atypical antipsychotic that has previously been shown to be beneficial for the treatment of tardive movement disorders (Casey 1989). Extrapyramidal symptoms (EPS) have traditionally been associated with neuroleptic exposure; however, there is a growing literature of EPS as a rare but important adverse effect of selective serotonin (5-HT) reuptake inhibitors (SSRIs) (Bacher and Ruskin 1991; Baldwin et al 1991; Black and Uhde 1992; Bouchard et al 1989; Budman and Bruun 1991; Dave 1992; Fallon and Liebowitz 1991; Hamilton and Opler 1992; Me ltzer et al 1979; Anonymous 1993; Reccoppa et al 1990; Shihabuddin and Rapport 1994; Stein 1991; Stoukides and Stoukides 1991; Tate 1989). Only three of these reports are of tardive or other persistent dyskinesias, all of which were associated with fluoxetine treatment (Bacher and Ruskin 1991; Budman and Bruun 1991; Stein 1991). Persistent paroxysmal dyskinesias are intermittent episodes of dystonia and/or choreoathetosis that are 20 min to 2 hours in

We measured regional cerebral blood flow with the xenon 133 inhalation technique in 41 patients with major depressive disorder and 40 matched, normal controls during an eyes-closed, resting condition. The depressed group had a marked reduction in global cortical blood flow. To examine topographic abnormalities, traditional multivariate analyses were applied, as well as a new scaled subprofile model developed to identify abnormal functional neural networks in clinical samples. Both approaches indicated that the depressed sample had an abnormality in topographic distribution of blood flow, in addition to the global deficit. The scaled subprofile model identified the topographic abnormality as being due to flow reduction in the depressed patients in selective frontal, central, superior temporal, and anterior parietal regions. This pattern may reflect dysfunction in the parallel distributed cortical network involving frontal and temporoparietal polymodal association areas. The extent of this topographic abnormality, as revealed by the scaled subprofile model, was associated with both patient age and severity of depressive symptoms.

To investigate the effect of treatment modality on length of hospital stay, the authors retrospectively studied 86 admissions of 74 patients with major depression. All 19 patients who received ECT recovered, in contrast to only 27 (49%) of 55 patients given tricyclic antidepressants or other medication. The 28 patients who had not responded to antidepressants recovered after treatment with ECT. Treatment modality had a highly significant effect on length of hospital stay: patients given ECT stayed a mean of 13 fewer days, saving more than $6,400 per patient at current rates. These findings of significant economic and therapeutic benefits in the use of ECT raise issues about treatment selection for depressed inpatients.

Selected transistors and diodes have been irradiated by various types and energies of dislocating radiation. Irradiation by protons of 10-Mev, neutrons of a reactor spectrum, electrons of 5, 10, and 25-Mev, gamma rays from cobalt-60, and bremsstrahlung from stopping of 5-Mev electrons are discussed. Passive and dynamic monitoring of permanent radiation damage was performed for exposures ranging from "threshold" to failure doses, utilizing various exposure rates. Changes in transistor forward current gain and changes in diode lifetime are presented in terms of integrated "particle" flux. From such analysis, the feasibility of ascribing an equivalence of radiation particles for aermanent damage in transistors and diodes has been successfully shown. Comparative damage curves, correlations of operational degradation with defect densities, and preliminary equivalences are presented.

Many authors report that patients with psychotic and nonpsychotic major depressions differ in their response to somatic treatment. Psychotic depression is less responsive to tnicyclic antidepressants (1) and often requires a combined regimen of antipsychotics and antidepressants (2) on ECT (3). The nosological status of psychotic depression remains in question. Is psychotic depression best considered as a severe variant of major depression on as a separate entity with a characteristic pattern of demographic and symptom features, family history, course, biochemical profile, and response to treatment? There are limited and inconsistent data on this issue, but some differences between psychotic and nonpsychotic depression have been suggested. Nelson and Bowers (2) reported more psychomotor disturbance and previous episodes in psychotic depressive patients than in nonpsychotic depressive patients. In contrast Glassman and Roose (4) found more psychomotor retardation, less placebo responsiveness, and fewer previous episodes in psychotic depressive patients. Several preliminary biochemical and physiological findings seem to distinguish psychotic from nonpsychotic depressive patients. Meltzen and associates (5) reported that psychotic patients had increased serum creatinine phosphokinase and aldolase, skeletal musdc abnormalities, and lower serum dopamine 3-hydroxylase. Sweeney and associates (6) reported lower urine 3-methoxy-4-hydroxyphenethylene glycol and higher CSF homovanillic acid. These authors all used the Research Diagnostic Criteria (RDC) definition of psychotic major depressive disorder in defining their cohorts. Mendels and associates used a clinical judgment definition of psychotic depfession and found decreased CSF 5-hydnoxyindoleacetic acid (7) and decreased stage 4 and REM sleep (8). If psychotic depression is no more than a severe variant of nonpsychotic major depression, it should, aside from the presence of the psychotic symptoms, have similar clinical features. Guze and associates (9) studied 1 15 variables in 253 patients with primary and secondary affective disorder and found that delusional unipolan patients were distinguished only by more frequent psychiatric hospitalization. Most ofthe vania

This retrospective study compared the treatment responses of 34 primary, unipolar depressives without psychotic features and 30 with psychotic features. Patients were diagnosed by Research Diagnostic Criteria and received trials of tricyclic antidepressants, antipsychotics, the combination of the two, electroconvulsive therapy, or placebo and psychotherapy. Only three of 18 psychotic patients vs. 17 of 23 nonpsychotic patients responded to antidepressants alone. Electroconvulsive therapy and the combination of antipsychotic and antidepressant medication gave better responses. These data suggest that major depressive disorder with psychotic features is best considered as a distinct subtype rather than a severe variant of major depression.

The classical monoamine hypotheses of depressive illness have postulated a deficiency of norepinephrine and/or serotonin at functionally important receptors in the central nervous system (CNS).1,2 An alternative “receptor hypothesis” would explain reduced transmission by a deficiency in signal amplification by the receptor complex. This focus on the receptor gained impetus from studies showing that virtually all effective somatic antidepressant treatment modalities shared the common effect of down-regulation and/or desensitization of β-adrenergic receptor complexes.3,4 Moreover, a significant number of antidepressants down-regulate 5- HT2 (serotonin; 5-hydroxytryptamine) receptors, although, in contrast, electroconvulsive shock up-regulates 5-HT2 receptors.4,5

Although they have not yet profoundly affected the clinical practice of psychiatry, five new imaging techniques--computed tomography, brain electrical activity mapping, cerebral blood flow techniques, positron emission tomography, and nuclear magnetic resonance--show promise for furthering knowledge of the pathophysiology, diagnosis, and treatment of psychiatric patients. Through a survey of the literature, the authors discuss the applicability of each technique to the study of certain mental disorders, such as schizophrenia; the latest research findings produced by studies using the techniques; the advantages and disadvantages, if any, of each technique; and the potential role for each technique in the field of psychiatry.

It has been suggested that there are altered levels of norepinephrine or other neurotransmitters at functionally important receptors in patients with depressive disorders. This hypothesis is difficult to study in the human central nervous system. However, noradrenergic function can be assessed indirectly with peripheral-blood lymphocytes used as a model of the beta-adrenergic receptor complex. We found that drug-free inpatients with endogenous depression had lower isoproterenol-stimulated cyclic AMP levels in intact lymphocytes than did healthy control subjects (3.9 +/- 0.5 vs. 7.4 +/- 1.0 pmol per 10(6) cells, P less than 0.01). The density and affinity of beta-adrenergic receptors were similar in controls and depressed subjects (beta-receptor number, 5.4 +/- 0.7 and 5.3 +/- 0.8 fmol per 10(6) cells; binding affinity, 106 +/- 7.6 vs. 99.2 +/- 11.4 pM, respectively). When the depressed patients were subdivided by psychomotor manifestations, binding characteristics were indistinguishable among the subgroups. However, a significant reduction in beta-adrenergic responsiveness was observed in patients with psychomotor agitation, as compared with controls (2.6 +/- 0.5 vs. 7.4 +/- 1.0 pmol per 10(6) cells, P less than 0.01), but not in patients with psychomotor retardation (5.8 +/- 1.1 pmol per 10(6) cells, P less than 0.05). Thus, the desensitization of beta-adrenergic receptors was correlated more closely with the severity of psychomotor agitation than with the overall severity of depression.

Previous studies of peripheral blood mononuclear cells isolated from drug-free, hospitalized patients with endogenous major depression have demonstrated a diminished adenosine 3',5'-monophosphate (cyclic AMP) response to single concentrations of isoproterenol as compared with that obtained from normal control subjects. We now report results of isoproterenol dose-response studies that indicate lower basal levels of cyclic AMP as well as diminished cyclic AMP levels in response to isoproterenol stimulation at concentrations ranging from 10(-10) to 10(-5) mol/L in drug-free, hospitalized patients with endogenous depression. The major factor responsible for the diminished cyclic AMP production in the depressed patients was a loss of receptor sites capable of cyclic AMP production. Taken together with our previously reported finding that beta-adrenergic antagonist binding was normal in peripheral blood mononuclear cells obtained from depressed patients, the results of the dose-response studies suggest a loss of receptor function (desensitization) rather than a diminished number of receptor binding sites (down-regulation) as the underlying mechanism. Potential explanations for beta-adrenergic desensitization and its implications for the catecholamine hypothesis of depressive disorders are discussed.

Ten depressed patients treated with trazodone developed edema and weight gain that was promptly reversed by reduction or discontinuation of trazodone. This suggests a dose-dependent effect. None of the patients had an active medical problem that might predispose to edema formation. Summary data on all 10 cases and three case histories are presented to alert physicians to this side effect.

To the Editor.— In the Oct 10, 1986, issue ofJAMA, there was the following question1: "A 43-year-old woman with well-documented peptic ulcer disease complained of frequent and annoying nocturnal awakening due to pain, despite the use of ranitidine, sucralfate, and antacids. The nocturnal pain disappeared completely when she was given a nighttime dose of amitriptyline hydrochloride; however, she suffered from jitteriness, constipation, and... weight gain while taking the tricyclic agent." Suggestions were sought as to how to proceed with the therapy. The answer mentioned possible explanations of the effects of tricyclic antidepressants, which include sedative effects and an acid antisecretory effect due to anticholinergic properties. However, the property of tricyclic antidepressants as histamine2-receptor blockers was not mentioned. Tricyclic antidepressants are both histamine1-and histamine2-receptor blocking agents.2-4 Controlled clinical trials using 50 mg/d of trimipramine (as the maleate salt) showed it to be superior to a placebo

It is unclear why delusional depressives respond poorly to usual doses of tricyclic antidepressants alone. Seventeen elderly, delusional depressives were treated with high doses of imipramine or desmethylimipramine while monitoring plasma levels in an open study. Four of seven patients who received an adequate trial responded, but over half of the total sample had to be dropped due to intolerable side effects or worsening clinical condition. Antidepressants in high doses may be effective for part of the delusional depression sample, but this potentially effective pharmacologic therapy is not feasible in a large percentage of elderly or agitated patients.

Since formal seniority policies are established to provide orderly and equitable administration of layoffs, recalls, and promotions, it is incongruous, as is remarked in this article, that they should be the source of frequent disputes. Two difficulties are involved in seniority programs: (1) too simple a policy may be inadequate to meet the complexities of the plant situation, but (2) a more complicated policy may be difficult to administer. This article describes the technique adopted in a large firm to provide the accurate and current information needed for administration of a relatively complex seniority policy. (Author's abstract courtesy EBSCO.)