Psychiatric symptoms and cerebrospinal fluid monoamine metabolites in primary hyperparathyroidism

This prospective study included 32 patients with primary hyperparathyroidism (HPT). As compared with a healthy reference group, the patients had pronounced psychiatric symptomatology [CPRS score 17.2 +/- 9.0 (SD) versus 4.4 +/- 2.0], which was mainly affective in character. The severity of symptoms was not related to the serum calcium or parathyroid hormone concentrations. The majority of the patients had low CSF concentrations of monoamine metabolites (5-HIAA, HVA, and MHPG) and, in particular, those with the most severe psychiatric symptoms had low values for 5-HIAA. At follow-up, 1 year after parathyroid surgery, the patients displayed a clear improvement in mental health (CPRS score 4.4 +/- 3.0) together with an increase in CSF concentrations of 5-HIAA and HVA. The study demonstrates that significant psychiatric disturbances, which can be improved/normalized by surgery, are common in patients with HPT and are possibly related to changes in the central nervous system turnover of monoamines.     

A case of primary hyperparathyroidism that had been treated under a diagnosis of depression for 10 years

Abstract A 66 year old man who had been treated under a diagnosis of depression for 10 years was referred to the Kyoto Prefectural University of Medicine, Kyoto because of general fatigue and appetite loss. The patient was diagnosed as having primary hyperparathyroidism (PHPT) based on the increased parathyroid hormone (PTH) and serum calcium levels. Computed tomography revealed solitary adenoma of parathyroid gland. The resection of this solitary adenoma improved the PTH and serum calcium concentrations to normal ranges, which resulted in an improvement in his depressive state. This case suggests that ionic calcium levels contribute to the mental symptoms associated with PHPT. As PHPT is curable, the possibility of PHPT should be taken into account when patients have depressive symptoms.     

Acute antidepressant effect of lithium is associated with fluctuation of calcium and magnesium in plasma. A double-blind study on the antidepressant effect of lithium and clomipramine

In a double-blind study on 22 patients with major depressive disorder the effects of lithium and clomipramine on signs and symptoms and on calcium and magnesium in plasma were compared. Ratings of antidepressant and side effects were performed by 2 psychiatrists at the end of a placebo period of 5-7 days and after treatment for 2 and 4 weeks. Psychopathology was rated by 15 reported and 4 observed items from the Comprehensive Psychopathological Rating Scale (CPRS). Eleven items present in 72-100% of the patients were used to evaluate the effect of the two drugs. After 2 weeks of treatment the rated scores dropped for more than half of the CPRS items. After 4 weeks the scores for all but one item were reduced in both groups. The sums of scores were significantly reduced after 2 weeks in both groups and after 4 weeks global scores were reduced as well. The drugs had notable and similar antidepressant effects. Lithium treatment was associated with fluctuations in calcium and magnesium levels in plasma not seen during clomipramine treatment. Serum prolactin increased during clomipramine treatment but was unaffected by lithium treatment. No correlations were found between the sum of rating scores and blood levels of drugs, prolactin, calcium or magnesium.     

Immunoreactive somatomedin B is increased in serum in patients with major depressive disorder

Serum levels of immunoreactive somatomedin B (RIA-B) were investigated in patients with major depressive disorder both in the acute state and during remission at 8 h and 22 h and at 22 h after the dexamethasone suppression test. Elevated levels of RIA-B at 8 h and at 22 h after the dexamethasone suppression test were found consistently in the patient group compared with the healthy controls. No indication was obtained that the patients' clinical condition or depressive symptomatology as revealed by their CPRS score, psychotropic medication or TSH, prolactin, melatonin or cortisol levels was significantly related to the RIA-B levels.     

Serum melatonin in relation to clinical variables in patients with major depressive disorder and a hypothesis of a low melatonin syndrome

Maximum nocturnal serum melatonin level (MTmax) in relation to some clinical variables was studied in 32 patients with a major depressive episode and in 33 healthy subjects with reference to the outcome of the dexamethasone suppression test (DST). Significant regressions were found between MTmax levels and clinical rating scores in CPRS, interpreted as retardation symptoms. Four healthy subjects with disposition for dysthymic reactions had subnormal MTmax levels, which differed from MTmax levels in subjects without such disposition. Patients but not the healthy subjects, who reported parental loss before 17 years of age, had subnormal MTmax levels and differed from patients with no reported parental loss. Patients with no reported suicidal behaviour in clinical history had significantly lower MTmax levels than patients with reported suicide attempts. No relations were found between low MTmax levels and diagnoses, duration of illness, reported inheritance for depressive illness or sleep disturbances. A hypothetical low melatonin syndrome in depression is proposed: low nocturnal melatonin, abnormal dexamethasone suppression test, disturbed 24-h rhythm of cortisol, less pronounced daily and annual cyclic variation in depressive symptomatology.     

Affective disorder subtyped by psychomotor symptoms, monoamine oxidase, melatonin and cortisol: identification of patients with latent bipolar disorder

A multivariate approach using pattern recognition method was applied on a multivariable data set from patients with affective disorders comprising biological and clinical variables. The depressed patients were rated according to 23 items of the comprehensive psychopathological rating scale (CPRS). Variables of importance were selected and clusters of patients were found by combining monoamine oxidase, melatonin and post-dexamethasone cortisol with symptoms of psychomotor retardation and agitation. Patients were distributed with high scores of agitation in the extreme of one direction and with high scores of retardation in the opposite direction. By using the combined clinical and biological variables, a diagnostic subcategory with latent bipolar disorder was identified. Two clusters of unipolar patients, one with low melatonin and low psychomotor retardation scores, and one with high melatonin and high psychomotor retardation scores, were found. Identification of a patient group with latent bipolar disorder may have potential therapeutic value since bipolar patients should be taken care of by a specialist in psychiatry, avoid tricyclic antidepressant therapy and may be candidates for lithium treatment. Received: 14 October 1997 / Accepted: 19 January 1998     

Inverse correlation between hallucinations and serum prolactin in patients with non-affective psychoses

Serum prolactin (PRL) was correlated with clinical symptomatology in 17 drug-free patients suffering from non-affective psychoses. A clear-cut negative correlation was found between the Comprehensive Psychiatric Rating Scale (CPRS) items assessing hallucinations and serum PRL levels (r=-6.14, P=0.009). No correlation was observed between clinical measures (total CPRS score, schizophrenia subscale score or depression and anxiety subscale score) and serum PRL.     

A new self-rating scale for depression and anxiety states based on the Comprehensive Psychopathological Rating Scale

Self-assessment scales have long been used in psychiatric research even if their validity has often been questioned, one reason being poor the concordance of expert ratings. In clinical practice the use of rating scales is restricted, since they are considered to be time-consuming and perhaps even to disrupt the clinician's rapport with the patient. In the present study, a self-assessment scale, the CPRS Self-rating Scale for Affective Syndromes (CPRS-S-A), was constructed by re-phrasing in a self-rating format 19 items from the original Comprehensive Psychopathological Rating Scale (CPRS) and covering depression, anxiety and obsessional symptoms. In a group of 30 patients with depression syndromes and anxiety syndromes, the CPRS-S-A and the original CPRS were both used on 2 occasions. The patient's Global Assessment of Functioning scores ranged from 30 to 76 (mean 58), which suggests a moderate severity of illness, as does the fact that the majority were outpatients. There was a high degree of concordance between the instruments for most items and for the scores on the subscales for both diagnostic groups (i.e., the Montgomery-Åsberg Depression Rating Scale and the Brief Anxiety Scale, which are both subscales drawn from the CPRS). The time taken to complete the CPRS-S-A varied from 5 to 30 min (mean 19 min for depressive and 16 min for anxiety patients on the first occasion, 13 min for both groups on the second), and the self-rating procedure was readily accepted by both groups of patients. The CPRS-S-A would thus seem to be a promising instrument for quantitative rating of symptoms in ambulatory patients, both in clinical practice and in research.     

Growth hormone, cortisol and prolactin responses to physical exercise: higher prolactin response in depressed patients

This study was designed to compare growth hormone, cortisol and prolactin responses to physical exercise in depressed patients and healthy comparison subjects. Patients fulfilled the DSM-IV diagnostic criteria for current major depressive disorder; subjective depressive symptoms were rated with Montgomery-Asberg Depression Rating Scale (MADRS) immediately before the experiment. Growth hormone, cortisol and prolactin were measured before and immediately after physiologically stressful bicycle cardiopulmonary exercise test. After exercise, there were three additional hormone measurements, with 30-min intervals. No significant difference was found in baseline growth hormone, cortisol or prolactin levels between patients and the control group. Plasma growth hormone and cortisol levels increased significantly during physical exercise in both patients and controls and returned to baseline in 90 min. There was no significant difference in growth hormone or cortisol responses to physical exercise between the two groups. However, prolactin levels increased only in the depressed patients group during the exercise. We hypothesize that acute exercise may have a stronger effect on serotonin (5-HT) release in depressed patients, which is reflected in increased plasma prolactin concentration.     

Effect of TRH on TSH and prolactin levels in affective disorders

The thyrotropin-releasing hormone (TRH) test was studied in 32 patients with acute major depressive disorder, 16 patients with recurrent unipolar (n = 8) or bipolar (n = 8) affective disorder in remission, and 22 healthy control subjects. Twenty-six of the 32 acutely ill patients were also studied when in remission. Outcome in these patients was correlated to serum levels of triiodothyronine (T3), 3,3',5'triiodothyronine (reverse T3), thyroxine (T4), thyroid-stimulating hormone (TSH), prolactin (PRL), melatonin, dexamethasone suppression test (DST) results, and clinical symptoms assessed by the Comprehensive Psychopathological Rating Scale (CPRS). The TSH response to TRH (delta TSH) was decreased in the acutely ill patients, but no difference was found between patients in remission and controls. The delta TSH was correlated to TSH but not to T3 and T4 levels in both acutely ill and control subjects. In the acutely ill group, delta TSH did not distinguish between patients with normal and abnormal DST results. Thus, abnormalities in the hypothalamic-pituitary-thyroid (HPT) axis are not correlated to abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis. Moreover, delta TSH did not differentiate between melancholic (DSM-III) and nonmelancholic patients or between patients with primary and secondary depression. No correlation was found between delta TSH and CPRS scores. Patients with observable agitation greater than 0.25 points (item range 0-3) had higher levels of delta TSH than patients with lower levels. No significant correlation was found between delta TSH and seven specific symptom clusters on the CPRS. However, there was a possible relation between low delta TSH and violent suicide attempts or suicide. PRL levels did not distinguish acutely ill patients from controls. Finally, there was no significant regression between delta TSH and melatonin levels. The decrease in delta TSH seen in the acutely ill patients was too small to be of diagnostic value as a laboratory measure differentiating acutely ill and healthy subjects. The mechanism underlying the HPT alterations in acute major depressive disorder may be a desensitization of the TRH receptor in the thyrotrophs secondary to an increased endogenous TRH stimulation.     

Psychosis resulting in suicide in a patient with primary hyperparathyroidism

A case is reported of a patient presenting to the psychiatric unit of our hospital with symptoms of depression and found to have an organic psychosis. On routine SMA-12 investigation (12 channel auto analyzer), elevated serum calcium was detected on admission leading to the diagnosis of primary hyperparathyroidism (PHPT). The surgical removal of a parathyroid adenoma was followed by a rapid return of biochemical abnormalities to normal ranges. In spite of appropriate psychiatric management and fluctuations in the patient's clinical condition, the organic psychosis was unaltered and culminated in suicide 4 months after admission.     

Measurement of ACTH and prolactin in the dexamethasone suppression test

Plasma concentrations of ACTH and prolactin were measured in psychiatric inpatients at 8 a.m. and 4 p.m. before and after the standard 1 mg overnight Dexamethasone Suppression Test (DST). Plasma concentrations of cortisol were measured at 8 a.m. and 4 p.m., and 11 p.m. before and after 1 mg dexamethasone. Dexamethasone suppressed plasma concentrations of ACTH, prolactin and cortisol in the subject group as a whole. "Cut Points" obtained using Fisher's Exact Test identified plasma ACTH values at 8 a.m. baseline, 4 p.m. baseline and 8 a.m. post-dexamethasone and plasma prolactin values at all four times that significantly differentiated patients with bipolar depressive disorder and major depressive disorder from other psychiatric patients. There were no cut points found at any of the six times for plasma levels of cortisol that significantly differentiated between these two diagnostic groups. Of interest in this subject population, basal (pre-dexamethasone) plasma concentrations were of more diagnostic information than post-dexamethasone values. These pilot findings suggest that monitoring plasma prolactin and ACTH concentrations before and after dexamethasone might increase the sensitivity and specificity of this laboratory test for depression.     

Depression and anxiety inventories, and the dexamethasone suppression test

Twenty-one psychiatric inpatients with prominent depressive symptoms underwent dexamethasone suppression tests and assessment with observer-rated and self-rated anxiety, depression, and somatic symptom inventories. This was done to test the hypothesis that anxiety, more than depression, was related to cortisol nonsuppression seen in psychiatric patients including those diagnosed as having major depressive disorders. Nonsuppressors were significantly more depressed but not more anxious on the symptom inventories. In addition, it was noted retrospectively that the depression symptom inventory scores predicted nonsuppression. Several individual items from the symptom scales which correlated with post-dexamethasone cortisol levels were also identified.     

Psychopathology in treated Wilson's disease determined by means of CPRS expert and self-ratings

OBJECTIVE: To examine the occurrence and severity of psychopathological symptoms in patients with treated Wilson's disease (WD) and to evaluate the clinical utility of a self-assessment. METHOD: Twenty-six consecutive patients with confirmed WD were investigated using the Comprehensive Psychopathological Rating Scale (CPRS) and the CPRS Self-rating Scale. RESULTS: The total CPRS scores ranged from 2.5 to 59.0 (mean 29.4 +/- 15.5). Most common symptoms were: autonomic disturbances, observed muscular tension, fatiguability, reduced sexual interest, lack of appropriate emotion, concentration difficulties, reduced sleep, aches and pains, hostile feelings, apparent sadness and failing memory. Agreement between interview-based ratings and self-ratings was low. CONCLUSION: The patients with treated WD have prominent psychopathology in the same range as in patients with moderate to severe depressive disorders. A specific symptom profile has been identified. If confirmed, the identification of the typical symptom profile might be of great importance. The patients with WD tend to underestimate the presence of psychopathological symptoms.     

The association of nocturnal serum melatonin levels with major depression in patients with acute multiple sclerosis

The association of nocturnal serum melatonin levels was investigated in acute multiple sclerosis (MS) patients with major depression (MD). The sample comprised 13 patients with MD and 12 with no psychiatric disorders admitted to our clinic due to acute MS attacks. Psychiatric evaluation was performed with the Structured Clinical Interview for DSM-IV (SCD-I). The level of depressive symptoms was assessed with the Beck Depression Scale (BDS). Blood samples were taken from the patients to determine melatonin level at 03.30 h and 10.00 h before steroid treatment started. Melatonin levels were determined using the ELISA test. Nocturnal serum melatonin levels (21.2+/-17.1 pg/ml) of the patients with MD were significantly lower than those (51.5+/-18.3 pg/ml) of the patients without MD. A significant negative correlation was found between BDS scores and nocturnal serum melatonin levels. These findings suggest that a melatonin deficiency may be among the factors involved in the occurrence of depression in MS patients.     

Circadian rhythms of melatonin,cortisol and prolactin in patients with obsessive-compulsive disorder

Plasma melatonin, cortisol and prolactin (PRL) levels were measured over a 24-h period in 13 drug-free patients with obsessive-compulsive disorder and in matched healthy subjects. The circadian profiles of melatonin and PRL were altered in patients; the circadian rhythm of cortisol was preserved, although at a higher level compared with normal controls. These changes were significantly related to the severity of the obsessive-compulsive symptoms. Further studies need to clarify the state- or trait-dependent character of these abnormalities.     

A new depression scale designed for use with adults with mental retardation

A sample of 51 mentally retarded adults with DSM-III-R criteria for depressive disorders, and 41 without depressive disorders but a high rate of other psychiatric disorders were rated on 27 items from the Comprehensive Psychopathological Rating Scale (CPRS). The newly developed CPRS depression subscale consists of nine items which can also be assessed in almost all of the people with severe or profound mental retardation in the sample. The scale is able to distinguish between depressive and non–depressive cases, and between subgroups of depression. The two factors derived from factor analysis were open to clear interpretation.     

Changes in cortisol and DHEA plasma levels after psychotherapy for PTSD

Post-traumatic stress disorder (PTSD) has been associated with dysregulation of the neuroendocrine system. In this study we examine the effects of psychotherapy in 21 PTSD patients, with and without coexisting depression, on the levels of six stress-related hormones: cortisol, dehydroepiandrosterone (DHEA), and dehydroepiandrosterone-sulfate (DHEA-S), prolactin, thyrotropin (TSH) and free thyroxin (fT4). The results show that after brief eclectic psychotherapy (BEP) significant changes occurred in levels of cortisol and DHEA. Responders showed an increase in cortisol and DHEA levels, while in non-responders both hormone levels decreased. Differences were only found after controlling for depressive symptoms. In conclusion, effective psychotherapy for PTSD may alter dysregulations in the Hypothalamus-pituitary-adrenal (HPA)-axis, but comorbid depressive symptoms should be taken into account.     

Melatonin and cortisol secretion profile in patients with pineal cyst before and after pineal cyst resection

A pineal cyst is a benign affection of the human pineal gland on the borderline between pathology and normality. Only a small percentage of patients present with symptoms and a surgical treatment is indicated in highly selected cases. A melatonin secretion in patients with a pineal cyst before and after a pineal cyst resection has not been studied yet and the effect of surgery on human metabolism is unknown. The present study examined melatonin, cortisol and blood glucose secretion profiles perioperatively in a surgical group of 4 patients. The control group was represented by 3 asymptomatic patients with a pineal cyst. For each patient, 24-h circadian secretion curves of melatonin, cortisol and glycemia were acquired. An analysis of melatonin profiles showed an expected diurnal pattern with the night peak in patients before the surgery and in the control group. In contrast, melatonin levels in patients after the surgery were at their minimum throughout the whole 24-h period. The cortisol secretion was substantially increased in patients after the surgery. Blood glucose sampling showed no statistically significant differences. Clinical results demonstrated statistically significant headache relief measured by Visual Analogue Scale in patients after the surgery. Despite the small number of examined patients, we can conclude that patients with a pineal cyst preserved the physiological secretion of the hormone melatonin while patients who underwent the pineal cyst resection experienced a loss of endogenous pineal melatonin production, which equated with pinealectomy. Surprisingly, cortisol secretion substantially increased in patients after the surgery.     

Association among serum cortisol,dehydroepiandrosterone-sulfate levels and psychiatric symptoms in men with chronic schizophrenia

PurposeThe purpose of this study was to examine possible associations of serum levels of cortisol and dehydroepiandrosterone-sulfate (DHEA-S) with psychiatric symptoms in men with chronic schizophrenia.MethodsThis retrospective study involved 162 men with schizophrenia and 138 age-matched healthy controls, for whom data were collected on demographic characteristics, age at disease onset, disease duration, positive and negative syndrome scale (PANSS) scores, and history of atypical antipsychotic treatment. Serum levels of cortisol and DHEA-S were calculated, as well as the ratios of the two levels. Possible correlations were explored between these levels and psychiatric symptoms before and after antipsychotic treatment.ResultsSerum levels of cortisol and DHEA-S levels as well as the ratios of cortisol to DHEA-S levels were higher in patients than in controls (p < 0.01). Among patients, serum levels of cortisol and DHEA-S were significantly lower after treatment than before (p < 0.01), although the ratios of cortisol to DHEA-S levels remained similar. Serum levels of cortisol, DHEA-S and the ratios of the two levels were positively correlated with the negative symptoms score on the PANSS.ConclusionsThe pathophysiology of schizophrenia may involve in the spread levels of cortisol and DHEA-S. These levels may serve as biomarkers for diagnosing schizophrenia and monitoring treatment efficacy.