Hypothalamus-pituitary-adrenal (HPA) axis parameters and neurocognitive evaluation in patients with bipolar disorder.

Bipolar disorder is associated with neurocognitive impairment but the etiology of such impairment remains largely unknown. The present study aimed at investigating the performance of bipolar patients in various neuropsychological tasks within the framework of HPA axis hyperactivity model and also the impact of disease characteristics on neuropsychological functioning. Cognitive performance of 60 bipolar-I patients and 30 healthy controls was evaluated by using tasks from the CANTAB battery targeting visual memory, executive function and inhibitory control. Current symptoms were evaluated via administration of the Hamilton Depression Rating Scale (HAMD) and Young Mania Rating Scale (YMRS) whereas assessment of functioning was performed with the Global Assessment of Functioning (GAF). Basal cortisol levels were determined and all patients were administered the Dexamethasone Suppression Test (DST). Statistically significant differences between patients and controls were found in visuo-spatial associative learning and memory, planning, attentional set shifting and inhibitory control. Worse performance in visuospatial associative memory correlated with longer duration of illness and higher levels of basal cortisol. Poorer attentional set shifting was related to higher number of manic episodes. We found no relationship of neurocognitive measures with DST suppression status, current symptom severity or history of psychosis. The results of our study confirm the presence of cognitive deficits in bipolar disorder and provide evidence on the relation of cortisol with neuropsychological functioning, especially visuo-spatial associative memory. Moreover, we have found that number of previous manic episodes and duration of illness is associated with worse cognitive performance. It is known that neurocognitive deficits are evident in many patients with bipolar disorder. These deficits are often a cause of considerable distress and can lead to impairment of psychosocial and occupational functioning. The role of HPA axis needs to be further examined in bipolar disorder. Nevertheless, the identification of factors affecting neurocognitive functioning, like basal cortisol and number of manic episodes, may contribute to the implementation of more appropriate prevention strategies.

Time-frequency analysis methods to quantify the time-varying microstructure of sleep EEG spindles: possibility for dementia biomarkers?

The time-varying microstructure of sleep EEG spindles may have clinical significance in dementia studies and can be quantified with a number of techniques. In this paper, real and simulated sleep spindles were regarded as AM/FM signals modeled by six parameters that define the instantaneous envelope (IE) and instantaneous frequency (IF) waveforms for a sleep spindle. These parameters were estimated using four different methods, namely the Hilbert transform (HT), complex demodulation (CD), matching pursuit (MP) and wavelet transform (WT). The average error in estimating these parameters was lowest for HT, higher but still less than 10% for CD and MP, and highest (greater than 10%) for WT. The signal distortion induced by the use of a given method was greatest in the case of HT and MP. These two techniques would necessitate the removal of about 0.4s from the spindle data, which is an important limitation for the case of spindles with duration less than 1s. Although the CD method may lead to a higher error than HT and MP, it requires a removal of only about 0.23s of data. An application of this sleep spindle parameterization via the CD method is proposed, in search of efficient EEG-based biomarkers in dementia. Preliminary results indicate that the proposed parameterization may be promising, since it can quantify specific differences in IE and IF characteristics between sleep spindles from dementia subjects and those from aged controls.

Sleep position and laterality of benign paroxysmal positional vertigo.

OBJECTIVE: The aim of this study was to investigate the frequency of posterior semicircular canal benign paroxysmal positional vertigo in each ear, and to assess the association between the ear affected by benign paroxysmal positional vertigo and the head-lying side during sleep onset. Based on a previous study which used objective methods to prove the preference of the elderly for the right head-lying side during sleep, we hypothesised that a predominance of the same head-lying side in benign paroxysmal positional vertigo patients may affect the pathophysiology of otoconia displacement. STUDY DESIGN: We conducted a prospective study of out-patients with posterior semicircular canal benign paroxysmal positional vertigo, confirmed by a positive Dix-Hallpike test. METHODS: One hundred and forty-two patients with posterior semicircular canal benign paroxysmal positional vertigo were interviewed about their past medical history, focusing on factors predisposing to benign paroxysmal positional vertigo. All patients included in the study were able to define a predominant, favourite head-lying side, right or left, during sleep onset. RESULTS: The Dix-Hallpike test was found to be positive on the right side in 82 patients and positive on the left side in 54; six patients were found to be positive bilaterally. During sleep onset, 97 patients habitually laid their head on the right side and the remaining 45 laid their head on the left. The association between the affected ear and the head-lying side during sleep onset was statistically significant (p < 0.001). CONCLUSIONS: Our study found a predominance of right-sided benign paroxysmal positional vertigo, a subjective preference amongst patients for a right head-lying position during sleep onset, and an association between the ear affected by benign paroxysmal positional vertigo and the preferred head-lying side during sleep onset. The clinical and therapeutical implications of this observation are discussed.

[A study of irritability in menopausal women].

Despite the fact that irritability is frequently the main presenting complaint of perimenopausal and postmenopausal women, studies specifically researching irritability in this population are scant. One hundred sixty three (163) peri- and postmenopausal women non-HT users, attending a menopause clinic, were included in this cross-sectional study. The investigation focused on whether the occurrence of inward and outward irritability in menopause is associated with various menopausal parameters, such as vasomotor symptoms, insomnia, menopausal status, hormone levels, and with the presence of chronic disease. Furthermore, we examined the possible association of inward and outward irritability with measures of anxiety and depression. Outward and inward irritability of peri- and postmenopausal women seem to be related to chronic disease, a factor that may be partially influenced by the older age of menopausal women. Outwardly directed irritability is found to be related to FSH and LH levels, independently of specific menopausal symptoms, such as vasomotor symptoms or insomnia. Outward irritability was found to be positively correlated with depressive symptomatology, whereas inward irritability correlated with both anxiety and higher depressive symptomatology.

Potential dementia biomarkers based on the time-varying microstructure of sleep EEG spindles.

The time-varying microstructure of sleep EEG spindles may have clinical significance in dementia studies. In this work, the sleep spindle is modeled as an AM-FM signal and parameterized in terms of six parameters, three quantifying the instantaneous envelope (IE) and three quantifying the instantaneous frequency (IF) of the spindle model. The IE and IF waveforms of sleep spindles from patients with dementia and normal controls were estimated using the time-frequency technique of Complex Demodulation (CD). Sinusoidal curve-fitting using a matching pursuit (MP) approach was applied to the IE and IF waveforms for the estimation of the six model parameters. Specific differences were found in sleep spindle instantaneous frequency dynamics between spindles from dementia subjects and spindles from controls.

Sublingual use of olanzapine in combination with alprazolam to treat agitation in a terminally ill patient receiving parenteral nutrition.

This paper reports the case of a 64-year-old man who was receiving parenteral nutrition after repeated operations due to stomach cancer. Olanzapine (orally disintegrating tablets) in combination with alprazolam was used successfully to relieve this terminally ill patient's anxiety and tension improving his relationship with his physicians and his daily life.

Set shifting deficits in melancholic vs. non-melancholic depression: preliminary findings.

Twenty-two patients with major depressive disorder, 11 of them with melancholic features, and 11 controls were investigated with CANTAB subtests focusing in visual memory/learning and executive functions. Melancholic patients performed worse than the other groups in all tasks and manifested a significant impairment in set shifting. The results are discussed in association with prefrontal dysfunction.

Hip dysplasia following a case of olanzapine exposed pregnancy: a questionable association.

This is a case report of a 33 year old woman with a history of psychosis, who presented to the women's mental health clinic for consultation at the 12(th) week of gestation, having already received olanzapine throughout the first trimester. She was followed from that point on at our clinic and remained on small doses of olanzapine for the rest of her pregnancy, which was uncomplicated. She gave birth to a healthy female, which at the age of three months was diagnosed with developmental dysplasia of the hip and subsequently received appropriate treatment with favorable outcome. The possibility of the association of this congenital dysplasia with the use of olanzapine during pregnancy is further discussed in this paper.

Switching to amisulpride monotherapy for treatment-resistant schizophrenia.

The objective of this study was to assess switching to amisulpride (AMS) in treatment-resistant schizophrenia. Seven male subjects were switched to AMS and followed for 8 weeks. PANSS scores improved from 123 to 66 over this period. We conclude that AMS is of interest in the treatment of refractory schizophrenia.

Modeling the time-varying microstructure of simulated sleep EEG spindles using time-frequency analysis methods.

The time-varying microstructure of sleep spindles may have clinical significance and can be quantified and modeled with a number of techniques. In this paper, sleep spindles were regarded as AM-FM signals modeled by six parameters. The instantaneous envelope (IE) and instantaneous frequency (IF) waveforms were estimated using four different methods, namely Hilbert Transform (HT), Complex Demodulation (CD), Wavelet Transform (WT) and Matching Pursuit (MP). The six model parameters were subsequently estimated from the IE and IF waveforms. The average error, taking into account the error for each model parameter, was lowest for HT, higher but still less than 10% for CD and MP, and highest (greater than 10%) for WT, for three different spindle model examples. The amount of distortion induced by the use of a given method is also important; distortion was the greatest (0.4 sec) in the case of HT. Therefore, in the case of real spindles, one could utilize CD and MP and, if the spindle duration is more than 1 sec, HT as well.

Protracted acute stress reaction following an earthquake.

OBJECTIVE: To verify the official criteria of ICD-10 diagnosis of acute stress reaction (ASR) among earthquake victims. METHOD: Data on psychosocial variables and the diagnosis of ASR were collected from 91 subjects. RESULTS: The diagnosis of ASR was made in 70% of the sample. However, the restrictive duration criterion (i.e. symptoms not exceeding the first 48 h) was fulfilled only in 10%; in the remaining 60% the symptoms lasted for about another week. Thus, 60% of the sample constituted a group with protracted ASR (PASR) and 40% a group without it (n-PASR). Medical history was more frequent among PASR than n-PASR; PASR showed higher anxiety levels (both pre- and post-disaster) than n-PASR; finally, the persistence of ASR related positively to the fear of death at the time of the earthquake and pre-disaster anxiety levels. CONCLUSION: As in the vast majority of earthquake victims the ASR is protracted beyond 48 h, a revision of ICD-10 guidelines should be considered.

Athens Insomnia Scale: validation of an instrument based on ICD-10 criteria.

OBJECTIVES: To describe and validate the Athens Insomnia Scale (AIS). METHODS: The AIS is a self-assessment psychometric instrument designed for quantifying sleep difficulty based on the ICD-10 criteria. It consists of eight items: the first five pertain to sleep induction, awakenings during the night, final awakening, total sleep duration, and sleep quality; while the last three refer to well-being, functioning capacity, and sleepiness during the day. Either the entire eight-item scale (AIS-8) or the brief five-item version (AIS-5), which contains only the first five items, can be utilized. The validation of the AIS was based on its administration to 299 subjects: 105 primary insomniacs, 144 psychiatric patients and 50 non-patient controls. RESULTS: Regarding internal consistency, for both versions of the scale, the Cronbach's alpha was around 0. 90 and the mean item-total correlation coefficient was about 0.70. Moreover, in the factor analysis, the scale emerged as a sole component. The test-retest reliability correlation coefficient was found almost 0.90 at a 1-week interval. As far as external validity is concerned, the correlations of the AIS-8 and AIS-5 with the Sleep Problems Scale were 0.90 and 0.85, respectively. CONCLUSION: The high measures of consistency, reliability, and validity of the AIS make it an invaluable tool in sleep research and clinical practice.

Sleep spindle incidence dynamics: a pilot study based on a Markovian analysis.

Results are reported, based on 5 healthy subjects, concerning patterns in the dynamics of the sequential arrangement of spindles in human stage 2 sleep. Specifically, the conditional probability of incidence of successive spindle lengths and successive inter-spindle intervals is investigated. The results show that successive spindle lengths may be statistically independent. However, their distribution (histogram) may be similar for two different stage 2 periods, one in the first third and another in the second third of the night sleep record. In contrast to the finding about spindle lengths, results show that successive inter-spindle intervals may not be statistically independent. Furthermore, the overall dynamics of the sequential arrangement of inter-spindle intervals may be similar for the two sleep periods. These findings are discussed in the context of the "sleep maintenance" role of spindles.

Tolerance and rebound insomnia with rapidly eliminated hypnotics: a meta-analysis of sleep laboratory studies.

Differences in development of tolerance and occurrence of rebound insomnia have been well established between rapidly and slowly eliminated benzodiazepine hypnotics. Based on meta-analytic methodology, this study assesses whether there are such differences among the rapidly eliminated benzodiazepine and benzodiazepine-like hypnotics (brotizolam, midazolam, triazolam, zolpidem and zopiclone). All sleep laboratory studies of these drugs (n = 137) published from 1966 to 1997 were obtained, mainly through a MEDLINE search. Rigorous selection criteria resulted in the inclusion of 75 studies employing 1276 individuals (804 insomniacs and 472 healthy volunteers). Using a mixed effects regression model, reliable estimation of the effects on insomniacs of the recommended dose of each drug could be obtained. All five rapidly eliminated hypnotics showed statistically significant initial efficacy. Tolerance with intermediate and long-term use was clearly developed with triazolam and was only marginal with midazolam and zolpidem; it could not be estimated for brotizolam or zopiclone because of insufficient data. Rebound insomnia on the first withdrawal night was intense with triazolam and mild with zolpidem; data were unavailable for brotizolam and inadequate for midazolam and zopiclone. In conclusion, there are differences among the rapidly eliminated hypnotics with respect to tolerance and rebound insomnia suggesting that, in addition to short elimination half-life, other pharmacological properties are implicated in the mechanisms underlying these side-effects.

Substance abuse patterns and their association with psychopathology and type of hostility in male patients with borderline and antisocial personality disorder.

The aim of this study was to investigate the prevalence of substance use disorder in young adult patients with borderline personality disorder (BPD) and antisocial personality disorder (APD) and to ascertain the specific substances each of these groups choose to abuse. An additional aim was to assess whether alcohol and drug abuse in the patients related to their psychopathology and hostility. The study subjects were 41 hospitalized patients with BPD and 44 hospitalized patients with APD. The diagnoses of personality disorders and substance use disorders were made using DSM-III criteria. Psychopathology patterns were assessed using the Brief Psychiatric Rating Scale, Hamilton Depression Rating Scale, and State-Trait Anxiety Inventory. Hostility was assessed using the Hostility and Direction of Hostility Questionnaire. Abuse of one or more substances was reported by 76% of BPD patients and 95% of APD patients. There was no difference between the two groups in terms of alcohol abuse, but certain substances (such as benzodiazepines, anticholinergics, cannabis, and opioids) were abused more than twice as often by APD patients versus BPD patients. APD patients were more likely than BPD patients to be multiusers. In BPD patients, the number of substances abused showed a negative association with depression, while in APD patients it was positively related to state anxiety. In both patient groups, there was no correlation of the number of abused substances with the degree of extroverted or introverted hostility.

Growth hormone secretion during sleep in male depressed patients.

1. Growth hormone (GH) secretion during sleep was studied in ten male patients with major depression according to DSM III and eight normal controls. 2. Samples were collected through a continuous blood withdrawal pump while sleep was recorded in the laboratory. 3. The results showed a marked decrease in the GH secretion mainly during the first three hours of sleep in depressed patients as compared to normal controls. DST and TRH tests were also administered to the same patients but no correlation was observed between a positive test and a blunted GH secretion, suggesting that the various neuroendocrinological disturbances do not coexist in all depressed patients. 4. This disturbance in GH secretion during sleep, along with reduced slow wave sleep (SWS), gives support to the theory that GHRH is the common stimulus of SWS and GH release and that the ratio of GHRH and its counterpart CRH plays a major role in the pathophysiology of disturbed endocrine activity during sleep in depression.

Discriminating borderline from antisocial personality disorder in male patients based on psychopathology patterns and type of hostility.

Dimensions of psychopathology and patterns of hostility, as well as the relationship of hostility to psychopathology, were studied in 85 male young adults: 41 with borderline personality disorder (BPD) and 44 with antisocial personality disorder (APD). Diagnoses were based on DSM-III. The following instruments were also used: Brief Psychiatric Rating Scale, Hamilton Depression Rating scale, State-Trait Anxiety Inventory, and Hostility and Direction of Hostility Questionnaire. BPD patients compared with APD patients showed higher levels of overall psychopathology and depression, whereas both groups had equally high anxiety. Total hostility was quite high in both groups. However, BPD patients had more introverted hostility and APD patients had more extroverted hostility. In BPD patients, introverted hostility was related to overall psychopathology, depression, and trait anxiety, whereas in APD patients, no significant relationship of any type of hostility to various dimensions of psychopathology was observed. In conclusion, when comprehensively assessed, BPD patients can be discriminated from APD patients based on certain dimensions of psychopathology and differences in the direction of their hostility. Moreover, the relationship between psychopathology and hostility patterns suggests that the direction of patients' hostility plays an important role in the development of disorder-specific symptomatology.

Low and high melatonin excretors among healthy individuals.

To meet the need of establishing firm normative data regarding the secretion/excretion of human melatonin, nighttime urinary melatonin of 16 healthy volunteers was measured in samples collected monthly over a period of 1 year. Low melatonin excretors (N = 8) were distinguished from high melatonin excretors (N = 8), based on a cut-off mean melatonin value of 0.25 nmol/l. There was no overlap in any of the monthly melatonin values between the two groups, while their annual rhythms of melatonin excretion were not different in shape. Since no obvious factors (age, sex, height, weight, etc.) were responsible for the observed differences, the distinction between low and high nocturnal excretion and by inference secretion of melatonin most likely reflects genetically determined variable levels of the noradrenergic secretory drive and/or variable N-acetyltransferase/hydroxyindole-O-methyltransferase enzymatic activity during the night.