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Introduction: Decreased plasma BDNF (pBDNF) levels have been proposed as a biomarker in illness phases of mood disorders. Serum cortisol (seC) levels are an index of energy mobilization and stress. The aim of this cross-sectional study was to evaluate pBDNF and seC levels in workers exposed to occupational stress and suffering from Adjustment Disorders (AD) compared to healthy workers., Methods: Plasma BDNF and seC levels were measured by means of specific immunoassays in 64 AD patients and 38 healthy controls. Perceived and occupational stress was evaluated in patients and controls using the Psychological Stress Measure (PSM) and the Job Content Questionnaire (JCQ). Psychopatological symptoms in patients were assessed using specific rating scales., Results: Plasma BDNF levels resulted significantly higher in patients than in controls, whereas no significant differences were found for seC levels. In patients but not in controls pBDNF levels showed a significant positive correlation with seC levels. Perceived stress levels were positively correlated with all psychopatological rating scales scores., Conclusions: BDNF could play a key role in the pathophysiology of stress-related disorders and its peripheral levels elevation could contribute to protect neurons under stress. Further research is needed focusing on biomarkers for stress-related disorders as a potential tool for the diagnosis and prevention of occupational diseases., (© 2019 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)

Mitochondrial dysfunction may result in a variety of diseases. The objectives here were to examine possible differences in mtDNA copy number between healthy controls and patients with depression, anxiety or stress- and adjustment disorders; the association between mtDNA copy number and disease severity at baseline; and the association between mtDNA copy number and response after an 8-week treatment (mindfulness, cognitive based therapy). A total of 179 patients in primary health care (age 20-64 years) with depression, anxiety and stress- and adjustment disorders, and 320 healthy controls (aged 19-70 years) were included in the study. Relative mtDNA copy number was measured using quantitative real-time PCR on peripheral blood samples. We found that the mean mtDNA copy number was significantly higher in patients compared to controls (84.9 vs 75.9, p<0.0001) at baseline. The difference in mtDNA copy number between patients and controls remained significant after controlling for age and sex (ß=8.13, p<0.0001; linear regression analysis). The mtDNA copy number was significantly associated with Patient Health Questionnaire (PHQ-9) scores (β=0.57, p=0.02) at baseline. After treatment, the change in mtDNA copy number was significantly associated with the treatment response, i.e., change in Hospital Anxiety and Depression Scale (HADS-D) and PHQ-9 scores (ß=1.00, p=0.03 and ß=0.65, p=0.04, respectively), after controlling for baseline scores, age, sex, BMI, smoking status, alcohol drinking and medication. Our findings show that mtDNA copy number is associated with symptoms of depression, anxiety and stress- and adjustment disorders and treatment response in these disorders., (Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.)

Objective: Childhood maltreatment leads to neuroendocrine changes, which may be associated with an increased vulnerability for psychopathology, such as depression and anxiety in later life. This study aimed to investigate the relationship between childhood maltreatment and orexin A levels in patients with depression and anxiety. The study consisted of 27 female outpatients who presented with depressive and/or anxiety symptoms, and 27 healthy female controls. Childhood trauma history was assessed using the childhood trauma questionnaire (CTQ-28) in patients and controls. Serum levels of orexin and cortisol were measured in all subjects. There were positive correlations between serum orexin levels and CTQ total score and between orexin levels and some CTQ subscale scores, such as physical and emotional neglect, in patients. Orexin levels in patients with a positive history of physical and emotional neglect were higher than those in patients with a negative history of them. In the controls, there was a positive correlation between emotional neglect score and serum orexin level. There were no differences in serum levels of orexin and cortisol between patients and controls. Orexin levels may be associated with childhood maltreatment per se, rather than psychopathology, such as depression or anxiety.

Objective: Patients with serious mental illnesses exhibit a reduced lifespan compared with the general population, a finding that can not solely rely on high suicide risk, low access to medical care and unhealthy lifestyle. The main causes of death are medical related pathologies such as type 2 diabetes mellitus and cardiovascular disease; however pharmacological treatment might play a role., Material and Methods: We compared a two hour glucose load in naïve patients at the onset of a serious mental illness (N=102) (84 patients with a first episode of schizophrenia and related disorders, 6 with a first episode of bipolar I disorder and 12 with a first episode of major depression disorder) with another psychiatric diagnose, adjustment disorder (N=17) and matched controls (N=98)., Results: Young patients with serious mental illness showed an increased two hour glucose load compared with adjustment disorder and the control group. Mean two hour glucose values [±standard deviation] were: for schizophrenia and related disorders 106.51mg/dL [±32.0], for bipolar disorder 118.33mg/dL [±34.3], for major depressive disorder 107.42mg/dL [±34.5], for adjustment disorder 79.06mg/dL[±24.4] and for the control group 82.11mg/dL [±23.3] (p<0.001)., Conclusions: Our results reflect an abnormal metabolic pathway at the onset of the disease before any pharmacological treatment or other confounding factors might have taken place. Our results suggest a similar glycemic pathway in serious mental illnesses and the subsequent need of primary and secondary prevention strategies., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background/aims: Increasing evidence suggests a link between brain-derived neurotrophic factor (BDNF) and suicidal behaviour (SB). Furthermore, decreased peripheral BDNF levels have been associated with clinical symptoms in various psychiatric disorders as well as with personality dimensions in healthy individuals. However, the relationship between BDNF and psychopathology is poorly investigated regarding SB., Methods: Plasma BDNF concentrations were analysed in 61 recent suicide attempters. Clinical symptoms were evaluated using the Comprehensive Psychopathological Rating Scale. Personality dimensions were assessed using the Marke-Nyman Temperament Scale., Results: Plasma BDNF correlated positively and significantly with the personality dimension Solidity but not with the other personality dimensions or with clinical symptoms., Conclusion: BDNF plays an important role in the regulation of neuroplasticity and neurogenesis in humans. Our results indicate that lower BDNF concentrations are associated with higher levels of impulsiveness and changeability (low scores on the Solidity scale). Furthermore, low plasma BDNF levels may be proposed as a trait marker rather than a state marker for attempted suicide., (© 2016 S. Karger AG, Basel.)

Easily available biomarkers for suicidality would be valuable for the identification of individuals at risk. Oxytocin has been shown to be associated with mental illness. We assessed basal oxytocin plasma levels of patients with (SA, n=41) and without (NSA, n=40) a 1-year history of attempted suicide. SA and NSA groups did not differ with respect to oxytocin levels. Plasma oxytocin may not be a biological suicide marker candidate., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Hypokalemia is not an isolated disease but an associated finding in a number of different diseases. It is also a commonly neglected condition among patients with acute acetaminophen overdose., Objectives: This study intended to determine the prevalence of hypokalemia and its clinical correlates in acute psychiatric illness among hypokalemic and normokalemic patients after acetaminophen overdose., Methods: This is a retrospective cohort study of hospital admissions for acute acetaminophen overdose conducted over a period of 5 years from 1 January 2004 to 31 December 2008. Demographic data and different types of psychiatric illness were compared between hypokalemic and normokalemic patients. Hypokalemia was predefined by a serum concentration <3.5 mmol/L. Statistical Package for Social Sciences (SPSS) 15 was used for data analysis., Results: Two hundred and eighty patients out of 305 admissions were studied. Hypokalemia was found in 63.6% of patients with a higher prevalence in the presence of psychiatric illness (67.7%). Hypokalemic patients were significantly associated with the presence of major depression (p = .04), adjustment disorder (p < .001), anxiety (p = .01), and suicidal attempts (p = .04)., Conclusion: Hypokalemia was common among patients with psychiatric illness and acute acetaminophen overdose.

Psychopathological factors associated with metabolic control in juvenile insulin-dependent diabetes mellitus (IDDM) deserve further investigation. This study assessed the relationship among specific psychopathological dimensions, coping mechanisms, and metabolic control in a Croatian clinical sample of adolescents with IDDM. One-hundred and one adolescents (aged 11-18) with IDDM filled out the youth self report (YSR) assessing psychopathological dimension and the scale of coping with stress (SCS). Glycemic control was estimated by the percentage of glycated hemoglobin (HbA1c). Subjects were divided into three groups according to HbA1C values: "optimal", "suboptimal control", and "at high risk". Subjects in optimal glycemic control presented with significantly lower scores in most of YSR scales compared to subjects at high risk. Moreover, they had significantly lower scores in avoidance and emotional reactivity and significantly higher scores in cognitive restructuring and problem solving SCS subscales. Regression models revealed that both internalizing and externalizing YSR scores, as well as emotional reactivity coping scores, independently contributed to explain variability of HbA1C values. Both internalizing and externalizing psychopathological dimensions, as well as emotion-oriented coping strategies, are independently associated with poor metabolic control in both boys and girls with IDDM, thus representing potential interest targets of psychotherapeutic interventions aimed at improving glycemic control in this population.

Aim: Today the most important problem in the work place is psychological abuse, which may affect the health because of high levels of stress and anxiety. There is evidence that most psychiatric disorders are associated with increased oxidative stress but nothing is reported about the presence of oxidative stress in mobbing victims., Methods: This study has been carried out in a group of 19 patients affected by workplace mobbing-due adjustment disorders, in comparison with 38 healthy subjects, to evaluate whether oxidative stress may be induced by mobbing., Results: Serum levels of protein carbonyl groups and of nitrosylated proteins, biological markers of oxidative stress conditions, were higher than those measured in healthy subjects., Conclusions: These findings may contribute to a better understanding of the redox homeostasis dysregulation occurring in victims of workplace mobbing.

Objective: Evidence based on controlled studies is still limited for treatment strategies that prevent recurrence of suicide attempts. Findings from observational as well as meta-analytic studies strongly suggest that lithium may have suicide-protective properties., Method: Patients with a recent suicide attempt in the context of an affective spectrum disorder (n = 167) were treated with either lithium or placebo during a 12-month period., Results: Survival analysis showed no significant difference of suicidal acts between lithium and placebo-treated individuals (adjusted hazard ratio 0.517; 95% CI 0.18-1.43). However, post hoc analysis revealed that all completed suicides had occurred in the placebo group accounting for a significant difference in incidence rates (P = 0.049)., Conclusion: Results indicate that lithium treatment might be effective in reducing the risk of completed suicide in adult patients with affective disorders. Our findings contribute to the growing body of evidence suggesting a specific antisuicidal effect of lithium.

Therapeutic drug monitoring studies of selective serotonin reuptake inhibitor (SSRI) antidepressants thus far failed to identify a clear concentration-response relationship in major depression. Majority of the previous studies defined clinical response as 50% or greater reduction from baseline in depression rating scale scores. Because many patients who meet these criteria still present symptoms associated with functional impairment, there is a need to consider "remission" as an alternative end point in concentration-response analyses of SSRIs. The present 12-week prospective study investigated the relationship between fluvoxamine (an SSRI) plasma concentration and remission in outpatients with depression. We used a flexible dose titration study designed to mimic clinical practice within the therapeutic dose range of fluvoxamine (25-200 mg/d). Receiver operating characteristics (ROC) curve was computed to determine the optimal fluvoxamine plasma concentration for remission using 269 concentration data obtained from 80 patients. Analysis of the ROC curve from the entire study sample did not reveal a fluvoxamine concentration significantly predicting remission. By contrast, ROC analysis specifically in patients with moderate to severe depression (N = 51; baseline 17-item Hamilton Rating Scale for Depression score > or = 20) found a fluvoxamine concentration of 61.4 ng/mL as a significant predictor of remission. In conclusion, therapeutic drug monitoring may be useful for rational titration and individualization of fluvoxamine dose and predicting remission in patients with moderate to severe depression, who may presumably display lesser placebo component in pharmacodynamic response.

Objectives: Evidence in the literature suggests stress-related changes of hypothalamus-pituitary-adrenal (HPA) axis in mobbing. We investigated the association between HPA activity and psychological profiles in mobbing, using a multidisciplinary approach., Design: Forty-eight victims of mobbing were evaluated by a working group of the Departments of Occupational Medicine, Psychiatry and Internal Medicine. After an informed consent, a detailed occupational history, a psychiatric interview with Minnesota Multiphasic Personality Inventory 2 (MMPI-2) administration and a blood sample (8:00 AM) for the determination of basal adrenocorticotropin (ACTH), cortisol and dehydroepiandrosterone sulphate (DHEAS) plasma levels were collected. Twenty-six patients received an overnight dexamethasone (dex) test., Results: Mean ACTH, cortisol and DHEAS levels were within normal ranges. The dex-test response was normal, with a significant hormone suppression (ACTH p<0.001, cortisol p<0.001, DHEAS p<0.001). The correlations between basal hormones and the psychometric scales of MMPI-2 revealed that cortisol was significantly and negatively related to Psychasthenia (Pt, p=0.003) and Depression (D, p=0.006), while DHEAS showed a significant negative correlation to Hysteria (Hy, p=0.008). Basal ACTH levels were not significantly related to psychometric scales., Conclusion: A significant inverse correlation between morning plasma cortisol levels and psychometric parameters in victims of mobbing with adjustment disorders was observed. A larger group of patients is necessary to identify and validate a cut-off cortisol level that may become an innovative biological parameter for the diagnosis and follow-up in victims of mobbing.

Introduction: Autogenic training is a widely recognised psychotherapy technique. The British School of Autogenic Training cites a large list of disorders, states, and changes, where autogenic training may prove to be of help. We wanted to explore the application of autogenic training as a therapy for adjustment disorder in adults. Our sample consisted of a homogeneous group of 35 individuals, with an average age of 39.3 +/- 1.6 years, who were diagnosed with adjustment disorder, F 43.2, in accordance with ICD 10 search criteria., Aim: The aim of our study was to research the effectiveness of autogenic training as a therapy for adjustment disorder in adults, by checking the influence of autogenic training on the biophysical and biochemical indicators of adjustment disorder., Method: We measured the indicators of adjustment disorder and their changes in three phases: before the beginning, immediately after the beginning, and six months after the completion, of a practical course in autogenic training. We measured systolic and diastolic arterial blood pressure, brachial pulse rate as well as the levels of cortisol in plasma, of cholesterol in blood, and of glucose. During that period, autogenic training functioned as the sole therapy., Results: The study confirmed our preliminary assumptions. The measurements we performed demonstrated that arterial blood pressure, pulse rate, concentration of cholesterol and cortisol, after the application of autogenic training among the subjects suffering from adjustment disorder, were lower in comparison to the initial values. These values remained lower even six months after the completion of the practical course in autogenic training., Conclusion: Autogenic training significantly decreases the values of physiological indicators of adjustment disorder, diminishes the effects of stress in an individual, and helps adults to cope with stress, facilitating their recuperation.

Introduction: Autogenic training is a widespread technique used in psychotherapy. The British school of autogenic training cites a large list of diseases, health states, and life changes, in which autogenic training can be of help. We wanted to explore the application of autogenic training as a therapy for adjustment disorder in adolescents. The sample consisted of a homogeneous group of 31 individuals, with an average age of 17.3 +/- 0.2 years, who were diagnosed with adjustment disorder, F 43.2, in accordance with ICD 10 search criteria., Objective: The aim of our work was to figure out the influence of autogenic training on adjustment disorder, through biophysical and biochemical indicators, and to research the efficiacy of autogenic training as a therapy for adjustment disorder in adolescents., Method: We observed adjustment disorder indicators and their changes in three phases, using initial, final, and control values, which we measured immediately before the beginning, immediately after the completion, and six months after the completion, of the practical course in autogenic training. We measured systolic and diastolic arterial blood pressure, brachial pulse rates, cortisol levels in plasma, cholesterol levels in blood, as well as glucose concentrations. During that period, autogenic training was employed as the sole therapy., Results: The study confirmed our preliminary assumptions. The measurements we performed showed that arterial blood pressure, pulse rates, cholesterol and cortisol concentrations, after the application of autogenic training among adolescents suffering from adjustment disorder, were lower than the initial values. They remained lower even six months after the completion of the practical course in autogenic training., Conclusion: We concluded that autogenic training significantly decreases the values of physiological indicators of adjustment disorder, diminishes the effects of stress in an individual, and eases the adaptation of adolescents to stress, helping with recovery.

Fear is a common behavioral problem in dogs. In this paper, we studied the association between behavioral and physiological responses in two potentially fear-eliciting situations. The aim was to establish whether it is possible to separate dogs of the collie breed that are fearful of floors and gunshots from those that are not by studying changes in heart rate and hematocrit, plasma cortisol, progesterone, testosterone, vasopressin, and beta-endorphin concentrations. Thirteen privately owned male dogs of the collie breed were studied during a floor test, using different types of floors, and a subsequent gunshot test. Seven of the dogs were identified as being fearful of floors and six were declared as fearless. Out of the 13 dogs, seven were fearful of gunshots and six were fearless of gunshots. Since fear of floors did not always occur concomitantly with fear of gunshots, there were consequently four different groups of dogs. The heart rate increased during the floor test in all groups, but dogs that were fearful of floors had higher heart rates than dogs that were fearless of floors. Dogs that were fearful of gunshots had higher heart rates, higher hematocrit levels and higher plasma concentrations of cortisol, progesterone, vasopressin, and beta-endorphins during the gunshot test than did dogs that were found to be fearless of gunshots. Plasma cortisol and progesterone increased drastically during the gunshot test in dogs identified as being fearful of gunshots. In fearful dogs, the testosterone concentration increased after completion of the floor test and before the gunshot test started, but there were no significant differences in testosterone between the groups. Since dogs fearful of gunshots had increased levels of several physiological parameters, the results demonstrated that this fear is a serious stress for the individual, a fear which it is possible to register with physiological variables.

The authors investigated the impact of the CYP2D6 genotype on steady-state concentrations of nortriptyline (NT) and its metabolites, trans-10-hydroxynortriptyline (EHNT) and cis-10-hydroxynortriptyline in a Japanese population of psychiatric patients. Forty-one patients (20 men and 21 women) were orally administered nortriptyline hydrochloride. The allele frequencies of the CYP2D6*5 and CYP2D6*10 were 4.9% and 34.1%, respectively. Significant differences in NT concentrations corrected for dose and weight were observed between the subjects with no mutated alleles and those with one mutated allele (mean +/- SD for no mutated alleles vs. one mutated allele: 70.3 +/- 25.4 vs. 98.4 +/- 36.6 ng/mL x mg(-1) x kg(-1); t = 2.54, dcf = 33, p < 0.05) and between the subjects with no mutated alleles and two mutated alleles (no mutated alleles vs. two mutated alleles: 70.3 +/- 25.4 vs. 147 +/- 31.1 ng/mL x mg(-1) x kg(-1); t = 5.87, df = 19, p < 0.0001). Also, a significant difference in the NT/EHNT ratio, which is representative of the hydroxylation ratio of NT, was observed between the subjects with no mutated alleles and those with two mutated alleles (no mutated alleles vs. two mutated alleles: 0.82 +/- 0.30 vs. 2.71 +/- 0.84; t = 7.86, df = 19, p < 0.0001). Multiple regression analysis showed that the number of mutated alleles of CYP2D6, which was the only significant factor, accounted for 41% and 48% of the variability in log(NT corrected for dose and weight) and log(NT/EHNT), respectively.

Suicidality has been found to be associated with low pre- and postsynaptic serotonin functioning. The purpose of this study was to examine whether in acutely suicidal psychiatric inpatients, the blood serotonin concentration was related to the underlying psychiatric disorder and whether it was associated with changes in the affinity (dissociation constant, KD) or in the maximal binding capacity (Bmax) of the platelet serotonin2A receptor. We therefore determined the blood serotonin concentrations and the platelet serotonin2A receptor activities of 45 suicidal psychiatric patients and 20 healthy subjects. We found that the blood serotonin concentrations were significantly lower in suicidal patients compared to healthy subjects. In all diagnostic categories (affective disorder, schizophrenia and adjustment disorder) we noted a significantly higher maximal binding capacity of the platelet serotonin2A receptor. These findings support the notion that a reduction in the availability of serotonin and an upregulation of the serotonin2A receptors in psychiatric patients are associated with a loss of control over suicidal impulses.

Recently, there were some reports that major depression may be accompanied by alterations in serum total cholesterol, cholesterol ester and omega 3 essential fatty acid levels and by an increased C20: 4 omega 6/C20: 5 omega 3, i.e., arachidonic acid/eicosapentaenoic, ratio. The present study aimed to examine fatty acid composition of serum cholesteryl esters and phospholipids in 36 major depressed, 14 minor depressed and 24 normal subjects. Individual saturated (e.g., C14:0; C16:0, C18:0) and unsaturated (e.g., C18:1, C18:2, C20:4) fatty acids in phospholipid and cholesteryl ester fractions were assayed and the sums of the percentages of omega 6 and omega 3, saturated, branched chain and odd chain fatty acids, monoenes as well as the ratios omega 6/omega 3 and C20:4 omega 6/C20:5 omega 3 were calculated. Major depressed subjects had significantly higher C20:4 omega 6/C20:5 omega 3 ratio in both serum cholesteryl esters and phospholipids and a significantly increased omega 6/omega 3 ratio in cholesteryl ester fraction than healthy volunteers and minor depressed subjects. Major depressed subjects had significantly lower C18:3 omega 3 in cholesteryl esters than normal controls. Major depressed subjects showed significantly lower total omega 3 polyunsaturated fatty acids in cholesteryl esters and significantly lower C20:5 omega 3 in serum cholesteryl esters and phospholipids than minor depressed subjects and healthy controls. These findings suggest an abnormal intake or metabolism of essential fatty acids in conjunction with decreased formation of cholesteryl esters in major depression.

To assess relationships of total plasma cholesterol (TC) and triglyceride (TG) values to suicide, suicide ideation, and hospitalization for psychiatric disease, we studied 220 children, ages 5 to 18 y, hospitalized with affective, adjustment, disruptive, anxiety, schizophrenic, other, and organic psychiatric disorders. The 135 male and 85 female patients had higher TG values (p = 0.0001 and 0.0003, respectively) and higher Quetelet Indices (p = 0.0001 and 0.003, respectively) than the 732 male and 316 female schoolchild controls; male patients had higher TC values than male controls (p = 0.014). Substance abuse in patients was an independent inverse determinant of TC value (p = 0.05); TG value correlated positively with alcohol use (p < or = 0.1) and substance abuse (p < 0.05). After covariance adjustment for age, race, sex, and Quetelet, children having adjustment disorders with depression had much lower covariance-adjusted TC value than control schoolchildren (3.91 versus 4.29 mmol/L, p = 0.003), whereas those with disruptive behavior with oppositional defiant disorder had much higher adjusted TC value (5.09 mmol/L, p = 0.0001). After covariance adjusting for age, race, sex, Quetelet, cigarette smoking, alcohol use, and substance abuse, children having adjustment disorders with concomitant depression had the highest group suicide tendencies (attempts and ideation) and the lowest covariance-adjusted TC value (4.03 mmol/L). Conversely, children having disruptive behavior with attention deficit hyperactivity disorder or disruptive behavior with oppoistional defiant disorder had 50% lower suicide index than those with adjustment disorders with concomitant depression and higher adjusted TC levels (4.45 and 5.12 mmol/L, p = 0.0003).(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of prolonged psychological stress on hormonal secretion was investigated in 84 East Germany refugees suffering from psychiatric disorders within 6 weeks of their arrival in West Berlin shortly before or after the fall of the Berlin Wall. Before leaving the German Democratic Republic, these patients had already experienced prolonged stress, which continued after migration. In most cases, the diagnosis was anxious-depressive syndrome with vegetative complaints and symptoms of increased arousal. Their formal DSM-III-R diagnoses (American Psychiatric Association, 1987) included adjustment disorders, depressive disorders, and anxiety disorders (the latter including posttraumatic stress disorder). Serum levels of thyroid stimulating hormone (TSH) and thyroid hormones (thyroxine, free thyroxine, triiodothyronine, and reverse triiodothyronine) were measured and compared with those of 20 healthy control subjects. TSH and all thyroid hormone concentrations were significantly reduced in the patient group. Fifty-two of the patients (62%) were in the hypothyroid range but did not show any clinical signs of hypothyroidism. These disturbances in hormonal secretion were not correlated to any psychiatric diagnosis or to the severity of acute or chronic stress. The marked abnormalities in the hypothalamic-pituitary-thyroid axis seen in these refugees differ from those reported in depression and would seem to reflect severe chronic stress rather than specific psychiatric disorders. The underlying neurochemical mechanisms remain to be investigated.

[3H] Imipramine binding to platelets and plasma cortisol levels were measured in nine Israeli civilians before, during, and after repeated missile attacks. Hamilton Anxiety Rating Scale (HARS), and Beck Depression Inventory (BDI) were similar before and during the war and decreased significantly after the war. A trend toward increase in platelet imipramine binding values was observed during the war when compared with the postwar values (19%; p = 0.056), and/or when compared with prewar values (26%; p = 0.063). However, one-way analysis of variance with repeated measures did not reveal a significant statistical difference [F (2,6) = p = 2.07; NS] among the three time points. A significant correlation was found between HARS score, but not BDI, and imipramine binding values in the prewar and postwar time points (r = 0.87; 0.71, respectively). Plasma cortisol levels did not alter significantly during the study period.

Recently, some researchers noted significant positive relationships between postdexamethasone serum cortisol and prolactin levels, whilst endogenous depressives exhibited a significantly lower suppression of prolactin by dexamethasone than non-endogenous patients or normal controls. To ascertain the extent of prolactin responses to dexamethasone in severely depressed patients, we measured 8 a.m. pre- and postdexamethasone prolactin levels in 104 depressed and 42 normal subjects. Serum cortisol levels were also determined in depressed patients before and after dexamethasone administration. We found a significant suppressive effect of dexamethasone on prolactin levels. There were no significant differences either in pre- or postdexamethasone prolactin, or in actual dexamethasone-induced decrements in prolactin between normal controls, melancholics, simple major or minor depressed subjects. We have not found any significant relationships between cortisol and prolactin, either under baseline or postdexamethasone conditions.

Several authors have shown that the availability of L-tryptophan (L-TRP) in the serum is lower in patients with major depression than in controls. It has recently been reported that the administration of a dose of dexamethasone sufficient to cause cortisol suppression also caused significant decrements in the availability of L-TRP. In order to elucidate the putative pathophysiological mechanisms underlying this decreased L-TRP disposition, the authors examined 37 depressed women categorized according to the DSM-III. L-TRP, the sum of five competing amino acids (CAA), the L-TRP/CAA ratio, and insulin and free fatty acid (FFA) levels were determined both before and after oral administration of 1 mg dexamethasone. The availability of L-TRP was significantly lower in depressed women with melancholia compared with simple major and minor depressives. The baseline disposal of L-TRP was related neither to insulin nor to FFA concentrations Dexamethasone administration significantly reduced the L-TRP and L-TRP/CAA values and increased FFA and insulin levels. Postdexamethasone L-TRP and FFA levels were significantly and positively correlated.

To determine if serum prolactin levels were correlated with the level of depression in an ambulatory medical clinic population, prolactin was measured by immunoassay in all new medical patients completing the Langer Scale and the Popoff Index of Depression. Thirty-four of 71 patients (48%) were found to be depressed with a positive Popoff Scale. There was no difference in the prolactin levels in the depressed and nondepressed patients, who were matched for age and sex. Thus, depression, as seen in an ambulatory medical population, is not associated with increased prolactin release.

The growth hormone (GH) response to clonidine was measured in 10 patients meeting standardized criteria for 'endogenous' depression and in 10 patients individually matched for age and sex but meeting the corresponding criteria for 'reactive' depression. In a paired comparison of patients with reactive and endogenous depression (matched for age and sex), the GH response to clonidine was less in the endogenous member of the pair in 8 out of 10 cases. These findings are interpreted as evidence of a defect at alpha 2 adrenoceptors in neuroendocrine systems in endogenous as compared with reactive depression.

Platelet MAO activity was found to be elevated in primary depressive illness, and the severity to correlate positively with MAO activity. The reactive depression subgroup's mean platelet MAO activity was not significantly different from that of the controls. The endogenous group's unipolar and bipolar subgroups had significantly different platelet MAO activity, respectively high and low. The differences in MAO activity between unipolar and bipolar patients appeared to persist in the well state, but not after lithium carbonate therapy. These differences in MAO activity were apparent with the substrate tyramine but not with benzylamine. Altered MAO activity in patients with affective disorders may be determined through genetic mechanisms.

The relationship between the plasma levels of amitriptyline and its metabolite nortriptyline, as well as their side-effects and clinical response, were studied in 102 depressed female in-patients, treated with different dosages of amitriptyline. For 50 and 100 mg dosages, significant positive correlations were found between amitriptyline concentration and the Hamilton amelioration scores, as well as between Hamilton final values and side effects. For depressive neurosis and involutional melancholia best therapeutic responses were yielded at a dosage of 50 mg, while in the treatment of manic-depressive illness, comparable results occurred at a 150 mg dosage. In the depressive neurosis and in the involutional melancholia the upper plasma concentration limits for the therapeutic effect of nortriptyline were identified. The lower plasma concentration limits of amitriptyline and nortriptyline in the treatment of manic-depressive illness were also pointed out.

The plasma cortisol (PC) level at 08.00 a.m. was assessed in 250 unselected psychiatric inpatients suffering from various disorders, assorted in 8 diagnostic groups. Endogenously depressive patients showed a significantly higher rate of cortisol hypersecretion (PC greater than 560 nmol/l = 20 micrograms/dl) than the neurotically or reactively depressed patients and than schizophrenics or paranoid psychotics. The PC level after the midnight dose of 1 mg dexamethasone was examined in 125 patients at 08.00 a.m. (group I) and in 125 patients at 04.00 p.m. (group II). There was no statistical difference in the rate of dexamethasone test (DST) nonsuppressors (PC greater than 140 nmol/l = 5 micrograms/dl) in the separate diagnostic groups between group I and II, but in the postdexamethasone blood samples at 04.00 p.m., significantly more DST nonsuppressors were detected than in the samples at 08.00 a.m. in the total number of all patients, regardless of their diagnosis. DST nonsuppressors were found in all of our diagnostic groups with the exception of manic syndrome, and their various rates will be discussed and compared with the results of previous studies. The DST shows a high sensitivity in endogenous depression, but its diagnostic value is limited as a result of its relative lack of specificity.

Using radioimmunoassay the authors studied the patterns of plasma levels of cortisol, insulin, triiodothyronine, and thyroxine in patients with acute and protracted reactive depressions. The patients had higher cortisol levels and lower immunoreactivity of the other three hormones as compared to a group of healthy donors. Patients with acute depressions had higher values of cortisol than those with protracted ones. The treatment tended to normalize the hormonal parameters which was parallelled by positive clinical dynamics. Patients with protracted reactive depressions were more resistant to the conducted therapy. Concentrations of plasma hormones (with the exception of insulin) at the end of the treatment remained altered as compared to those in healthy subjects.

We studied recently bereaved individuals with the corticotropin-releasing hormone (CRH) stimulation test. Subjects with a bereavement complicated by a depressive illness (n = 9) had significantly higher basal plasma cortisol levels and smaller plasma adrenocorticotropic hormone (ACTH) responses to CRH than either subjects with an uncomplicated bereavement (n = 19) or normal controls (n = 34). Subjects with depressed bereavement showed ACTH responses to CRH similar to those of depressed patients (n = 30). Bereaved subjects who had received psychotropic medications in the past (n = 13), compared with those who had not (n = 15), showed significantly smaller plasma ACTH responses to CRH. Significantly more subjects with bereavement complicated by depression, as compared to subjects whose bereavement was uncomplicated, had a past history of treatment for depression. These results suggest that predisposed individuals may respond to the stress of bereavement with a depressive illness accompanied by dysregulation of the hypothalamic-pituitary-adrenal axis.

Neuroendocrine strategies in affective disorders have explored both resting values of hormones and hormonal responses to stimuli such as hypoglycemia, TRH, LHRH, dexamethasone, methadone and morphine. The abnormalities established to date have involved growth hormone, cortisol and TSH responses in particular. Prolactin has not been investigated to the same extent. We therefore describe several prolactin studies exemplifying selected neuroendocrine strategies. Our studies of prolactin responses included acute cases of either primary or secondary depression, stabilized bipolar patients, and healthy controls both off and on lithium. We found prolactin response to hypoglycemia significantly reduced in primary but not secondary depressions. Lithium administration led to flattened prolactin responses to hypoglycemia in stabilized bipolar patients but not in healthy controls. The flattened response in patients was observed already after 3 weeks of lithium, and remained flattened after years of treatment. The findings suggest a greater degree of prolactin response reduction in those patients showing most pronounced stability on lithium treatment.

Several pharmacological stimulation tests of the pituitary-hypothalamic system have been used to investigate psychiatric disorders. This study introduces amphetamine sulfate as a stimulus for human growth hormone (HGH) release in various psychiatric patients. Peak HGH release after a single intravenous administration of amphetamine sulfate, 0.1 mg/kg, was significantly lower in nine "endogenous" depressives (P = .01) and significantly higher in seven "reactive" depressives (P less than .05) as compared to normal subjects, whereas peak HGH release in eight schizophrenics and six chronic alcoholics did not differ significantly from that in normal subjects.

This study examines the utility of the dexamethasone suppression test (DST) in identifying a clinically meaningful subtype of depression. Forty-nine inpatients who met research diagnostic criteria for major depressive disorder underwent DSTs and standard clinical assessments and ratings. Half of those with primary depression showed escape from dexamethasone suppression and are referred to as nonsuppressors, while few of those with secondary depression had this response. Most of the nonsuppressors were rated as having a good response to treatment, while only one third of the suppressors were rated as having a good response to treatment. These data suggest that pituitary adrenal disinhibition as assessed by the DST is selectively associated with primary depression. The DST may be a marker of a depressive subtype with a specific pathophysiology or pathogenesis.

Blood platelet serotonin levels were measured in unmedicated 12 manic and 74 depressive patients with 118 normal control subjects employed. Blood platelets were separated by multiple centrifugation in the medium of Na2-EDTA solution, and the loss of serotonin during collecting procedures was about 11%. The mean value of blood platelet serotonin levels in depressed patients was 594 +/- 288 ng/mg platelet protein (+/- S.D.), which was significantly lower than that for normal controls, 780 +/- 253 ng/mg protein (p less than 0.001). Age does not account for the reduction of serotonin levels both in depressed and in normal population. Unipolar and involutional depressed patients exhibited to have the most pronounced reduced levels of serotonin of various subtypes of depression, while bipolar depressed patients, neurotic and chronic characterological depressed patients as well as patients with first-episode depression had the values which were comparable with those in normal controls. Manic patients did not show enhancement but did reduction of serotonin levels, the mean being 580 +/- 152 ng/mg protein, which made a contrast with their clinical manifestations of exhilaration and hyperactivity. Changes in blood platelet serotonin levels were determined before, during and after administration of L-5-HTP with a maintenance dose of 300 mg daily in nine depressed patients. Serotonin levels in all subjects were lifted to normal levels during the L-5-HTP treatment, while clinical symptoms were not improved with the treatment. Reduction of blood platelet serotonin levels in depressed patients may be due to their psychobiological distinction, which involves abnormal biogenic amine metabolism in the brain.

Admission thyroid function tests were reviewed in 115 euthyroid patients with depression (66), depression and alcohol abuse (30), or alcohol abuse (19). Estimated free thyroxine (EFT) levels ranged from 0.7 to 2.7 ng/100 ml (normal, 1.0 to 2.1). Levels above 2.1 ng/100 ml were associated with agitation and values under 1.1 with alcohol abuse. Mean EFT levels differed significantly among six diagnostic subgroups and paralleled rank order for severity of depression (none, secondary, reactive, single uncategorized, recurrent, psychotic). Alcohol abuse negatively affected EFT: there was a significant decrease of mean EFT level from nonabusers to abusers and, further, to intoxicated abusers. A positive association between EFT level and severity of depression, and a negative one with alcohol use, were significant when other variables considered were controlled. These two factors accounted from 28.2% of variability in EFT levels, with a minimal additional contribution of medication effect.

We examined the effects of the serotonin antagonist pizotifene (4 mg daily for 3 days orally), and the opiate antagonist naloxone-HCI (0.8 mg intravenously) on the TRH-induced thyrotropin (TSH), growth hormone (GH), and prolactin (PRL) response in female psychiatric inpatients with adjustment disorder or alcohol abuse. All the patients were free from interfering endocrine and metabolic illness and had not received major psychotropic medication before the investigation. Pizotifene caused a small but significant decrease of the TRH-induced TSH response in 8 patients, two of them changed their responses from normal (i.e. above 5 mU/l) to blunted. Neither GH nor PRL changed significantly after pizotifene. Naloxone-HCI, 30 min before the TRH challenge, did not produce any significant change in the TSH, GH or PRL responses, nor did it cause any significant change in the plasma level of these hormones by itself. The hormonal responses to TRH remained unaltered in ten other patients who had repeated tests without any drug treatment between the two occasions. The results suggest that serotonin deficiency may play a role in the blunted TSH response to TRH, while opiate mechanisms do not appear to have a primary influence on these endocrine effects of TRH.

TRH and LHRH were simultaneously infused into a group of five male patients with primary unipolar depression and four male secondary depressed patients. Blood samples were measured for LH and TSH just before and two hours following infusion. Six healthy male subjects matched for age were similarly studied. Our results showed: 1) that basal levels of TSH and LH were not different in any of the three groups of subjects, 2) TSH responses in the three groups were not significantly different, and 3) the LH response was significantly greater in the secondary depressed patients than the primary unipolar depression and normal controls at all time intervals after infusion. Our results add to the existing evidence for an abnormality in the hypothalamo-pituitary regulation of pituitary hormones-in particular LH. Such an abnormalit has not been reported in the literature to our knowledge. Our results tend to suggest a biological difference in the two subtypes of depression studied. Neuroendocrine studies would appear to be a useful diagnostic procedure in the differentiation of these subtypes of depression.

The serum glycoproteins represented by the individual protein-bound carbohydrate components and glycosaminoglycans represented by the hexuronic acid contents were determined in the sera of black and Caucasian normal children and children with diagnoses of schizophrenia, conduct disorder, and adjustment disorder. There were no race-related or sex-related differences in glycoproteins and glycosaminoglycans in the sera of normal children. Although the serum glycosaminogltents were determined in the sera of black and Caucasian normal children and children with diagnoses of schizophrenia, conduct disorder, and adjustment disorder. There were no race-related or sex-related differences in glycoproteins and glycosaminoglycans in the sera of normal children. Although the serum glycosaminogltents were determined in the sera of black and Caucasian normal children and children with diagnoses of schizophrenia, conduct disorder, and adjustment disorder. There were no race-related or sex-related differences in glycoproteins and glycosaminoglycans in the sera of normal children. Although the serum glycosaminoglycans were significantly elevated in children with a diagnosis of schizophrenia, the levels were in normal range in children with conduct and adjustment disorders. All of the protein-bound carbohydrates were elevated in schizophrenic children. However, only arabinose and galactosamine were significantly elevated in children with a diagnosis of conduct disorder, while only galactosamine was elevated in children with adjustment disorder. The presence of arabinose in serum glycoprotein was confirmed by chemical ionization-mass spectrometry. The possible causes of the differential elevation of the glycoconjugates in psychiatric disorders in relation to the effect of stress and environment are discussed.

The Hamilton Depression Rating Scale (HDRS) score and plasma cortisol values were measured in 100 depressed patients at 8 a.m., 4 p.m. and 11 p.m. after oral administration of 1 mg dexamethasone the previous night. The patients were categorized according to DSM-III as suffering from either minor depression (including dysthymic disorder, 300.40; adjustment disorder with depressed mood, 309.00; atypical depression, 296.82) or major depression (without melancholia, 296.X2; with melancholia, 296.X3; with psychotic features, 296.X4). Plasma cortisol levels of greater than or equal to 3.5 micrograms/dl at 8 a.m. were found to be the most sensitive (56.9%) and specific (94.3%) discriminator between minor and major depression. Plasma cortisol levels at 4 p.m. and 11 p.m. or the combination of several cortisol values also differentiated between minor and major depression; however, the results were not so conclusive. According to the ratings on the Hamilton Depression Scale the patients with major depression were more severely depressed (P less than 0.001) than patients suffering from minor depression. Cortisol values at 8 a.m., 4 p.m., 11 p.m. and the highest levels were significantly (P less than 0.001) correlated with the HDRS score. A maximum of 20.2% of the score variance could be explained by the correlation with the highest cortisol value observed. Severity of illness does not exclusively account for the biological differences between minor and major depression.

Cerebrospinal fluid (CSF) cortisol levels were examined in a total group of 65 patients. Those who were not depressed (ND), and those suffering from depressive neuroses (DN) had marginally elevated values. Patients with unipolar depression (UD) and bipolar depression (BD) had levels twice as high as the ND and DN patients. Psychotic UD and BD patients had the highest values, three to four times as high as the ND and DN subjects. A significant reduction of CSF cortisol levels was observed following treatment and recovery. Manic patients had moderately elevated CSF cortisol values. The CSF results were in good agreement with plasma total cortisol levels and with urinary free cortisol excretion. Age and sex effects were not responsible for the observed differences; similar results were found in patient subgroups studied in Australia and in the United States. Preliminary equilibrium dialysis data are presented for plasma and CSF cortisol binding. CSF cortisol was 20% bound and 80% free. Plasma free cortisol levels were in good agreement with CSF free cortisol values. Depressed patients have increased tissue and central nervous system (CNS) exposure to free, physiologically active glucocorticoids. The appearance of severe depressive symptoms which manifest a diurnal rhythm may be determined in part by excesssve CNS exposure to glucocorticoids.

Biochemical analyses of brain samples of an Animal Model of Depression indicate the state of motionlessness observed in response to a conditioned stimulus was due to an excess in functional activity of serotonin. An excess functional activity of serotonin may be directly responsible for human depressive illness. This conflicting conclusion to the currently popular theories of serotonin deficiency was discussed with reference to the animal and clinical data in the literature which are consistent with the conclusion.

Endogenous depression (ED) is regarded as a psychiatric disease with a biological pathogenesis. Consequently patients with ED respond favourably to somatic treatment, whereas for non-endogenously depressed patients drug-treatment would be often inappropriate. Until now, psychopathologists have failed to define precisely the endogenous subtype of depression on clinical features alone. It is well established that a subgroup of depressed patients shows hypersecretion of cortisol and consequently inadequate suppression of cortisol after a test dose of dexamethasone. This dexamethasone suppression test (DST) was introduced as a laboratory marker, specifically identifying endogenously depressed individuals. This survey illustrates the present dispute about the diagnostic confidence and clinical value of the DST in a psychiatric population, and related biochemical aspects. The following conclusions are stated: (a) use of the DST to validate a theory of nosology is premature. (b) Influence of psychoactive drug medication, diet and weight loss have to be established. (c) Preliminary data suggest that abnormal DST results frequently normalize before clinical recovery and abnormal DST results may be observed before a relapse into depression is clinically apparent. From this it was concluded that the DST might be useful as predictor of clinical outcome. (d) From the association of depressive episodes with disinhibited HPA-activity, a causative role of corticotropin and glucocorticoids in the development of psychiatric illness can be hypothesized. Beside some pharmacological data no supportive evidence for this hypothesis is available. (e) Multisteroid analysis after dexamethasone has provided promising results indicating increased sensitivity of the test when based upon cortisol/11-deoxycortisol ratios and disturbed mineralocorticosteroid secretion in endogenously depressed patients.

The relationship between clinical effect of imipramine (IP) in 39 depressed patients and biochemical distinction, serum drug levels, and diagnostic classification was investigated retrospectively. Based on pretreatment plasma ratios of tryptophan and tyrosine to competing amino acids, which reflect the availability of the precursor amino acids to the brain, the patient sample was separated in two halfparts. The one group with low net availability of tryptophan and tyrosine improved significantly more than the other group with comparable mean serum drug levels. In the former group there was no association between clinical improvement and serum drug levels, whereas in the latter group the patients with serum IP plus desipramine (DMI) above 180 ng/ml improved significantly more than patients with lower levels. There was an indication that a serum ratio of IP:DMI below 0.2 was associated with a poor response. Patients classified as nonendogenous depressives by means of the Newcastle II scale showed about the same response pattern as endogenous depressives with comparable plasma amino acid profiles and serum drug levels. Based on amino acid patterns and serum drug levels only half of the patients received an optimal therapy on the applied schematic dosage schedule. Thus, biochemical classification rather than diagnostic may be a useful remedy for the adjustment of serum IP plus DMI to appropriate levels in individual depressives.

L-tryptophan (L-TRP), the competing amino acids (CAA) valine and leucine and the cortisol levels taken at 8 a.m. after administration of dexamethasone on the previous day, were determined in 160 patients suffering from depression. The ratio between the L-TRP values and the sum of the competing amino acids was calculated. The clinical relevance of the L-TRP/CAA ratio in the case of major depression (DSM-III) versus minor depression (dysthymic disorder, atypical depression and adaptation disorder with depressive mood) was studied in comparison with the DST. Patients suffering from major depression showed a significantly decreased (p = 0.0006) L-TRP/CAA ratio. The combination of a decreased L-TRP/CAA ratio (cut off point less than or equal to 0.130) or an abnormal DST (cut off point greater than or equal to 3.5 micrograms/dl) is the best criterion which allows 59.0% of the patients suffering from major depression to be identified correctly with a specificity of 90.9%; the above-mentioned criterion permits 70.0% of the patients to be classified correctly into their actual group.