Cortisol to Dehydroepiandrosterone Sulphate Ratio and Executive Function in Bipolar Disorder.

INTRODUCTION: Bipolar disorder (BD) is associated with impairment in cognitive domains such as verbal memory and executive functions. Very few studies have assessed dehydroepiandrosterone sulphate (DHEA-S) in BD and its relation to cognitive functioning despite evidence showing its regulatory effects on glucocorticoid action. The aim of our study was to explore the association of cortisol, DHEA-S, and cortisol to DHEA-S ratio with visuospatial memory and executive functioning in BD. METHODS: Cognitive performance of 60 bipolar I patients and 30 healthy subjects was evaluated by using Cambridge Neuropsychological Test Automated Battery tasks targeting visuospatial memory (spatial recognition memory) and executive functions (planning [Stockings of Cambridge; SOC] and attentional set shifting [ID/ED]). Morning serum cortisol and DHEA-S levels were measured in patients. Main effects of cortisol, DHEA-S, and cortisol/DHEA-S ratio for each neurocognitive task were explored in multiple regression analyses correcting for demographic and clinical parameters as well as treatment-related factors (current use of antipsychotic and mood stabilizer medication). RESULTS: Bipolar patients showed poorer performance than healthy subjects in planning and attentional set shifting but not in visuospatial memory. Cortisol to DHEA-S ratio predicted worse performance in planning (SOC). CONCLUSIONS: This is the first study to assess memory and executive function in BD in relation to DHEA-S and cortisol to DHEA-S ratio. We report an association of cortisol to DHEA-S ratio with worse performance in planning in bipolar I patients, which warrants further investigation.

Clinical and treatment-related predictors of cognition in bipolar disorder: focus on visual paired associative learning.

Bipolar disorder (BD) is associated with impairment in cognitive domains such as verbal memory and executive functions. However, visual paired associative learning (PAL) has been far less researched. Neurocognitive dysfunction in BD patients has been related to several clinical factors, but data on the effect of medication are relatively scarce and inconsistent. The aim of our study was to explore the effect of clinical and treatment-related parameters on executive functions and visual memory/learning, including PAL, in BD. Cognitive performance of 60 bipolar I patients and 30 healthy subjects was evaluated by using CANTAB battery tasks targeting spatial recognition memory, PAL and executive functions (set shifting, planning, inhibitory control). Bipolar patients showed poorer performance in PAL, set shifting, planning and inhibitory control than healthy subjects; however, only differences in PAL and planning survived correction for multiple comparisons. Number of previous manic episodes and illness duration predicted worse performance in set shifting and PAL, respectively, whereas current treatment with valproate predicted better performance in PAL. This is one of the first studies to assess clinical and treatment-related predictors of PAL in BD. We report a possibly beneficial effect of valproate on PAL, which warrants further investigation.

Two Versus One High-Frequency Repetitive Transcranial Magnetic Stimulation Session per Day for Treatment-Resistant Depression: A Randomized Sham-Controlled Trial.

OBJECTIVES: High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has proven antidepressant effects, but the optimal frequency of sessions remains unclear. METHODS: We conducted a 3-week, sham-controlled trial to assess the antidepressant efficacy of 1 active HF-rTMS session per day (A1 group) compared with 2 per day (A2 group) and equivalent sham sessions (once a day, S1 group; twice a day, S2 group) in patients with treatment-resistant major depression with a subsequent 2-week follow-up period. One hundred seventy-seven patients were screened, of whom 105 met eligibility criteria and 98 consented and were randomized. The HF-rTMS (20 Hz) was targeted to the left prefrontal cortex in sessions of approximately 40 trains (2 seconds each) at 100% resting motor threshold with an intertrain interval of 1 minute. Treatment response was defined as a 50% or greater decrease in the Hamilton Depression Rating Scale (HDRS) score and/or Clinician Global Impressions-Severity of Illness (CGI-S) score of 3 or less. Remission was defined as HDRS score less than 8 and/or CGI-S score of 2 or less. RESULTS: Practically none of the subjects in either sham groups achieved remission. Increased odds of remission were present for CGI-S by stimulating twice rather than once per day (odds ratio [OR] = 1.5, P = 0.018), whereas there was a marginal result for HDRS (OR = 3.9, P = 0.066). Patients who had lower baseline HDRS (OR = 0.75, P = 0.014) and CGI-S scores (OR = 0.18, P = 0.001) were more likely to achieve remission. CONCLUSIONS: Twice per day active HF-rTMS might be more effective than once per day active HF-rTMS or sham stimulation.

Insomnia and PTSD one month after wildfires: evidence for an independent role of the "fear of imminent death".

OBJECTIVE: The relationship of insomnia with Post-Traumatic Stress Disorder (PTSD) one month after wildfires and more specifically with the experience of 'fear of imminent death' were investigated. METHODS: Ninety-two randomly chosen victims of wildfires in the Greek province of Ilia, were assessed through a specifically designed semi-structured psychiatric interview comprising of questionnaires and scales to measure psychopathology, as well as psychosocial and environmental parameters. PTSD was set according to ICD-10 research diagnostic criteria, while insomnia was assessed with the Athens Insomnia Scale (AIS). RESULTS: The presence of insomnia was identified in 63.0% of the victims. 46.7% of the participants were diagnosed with PTSD in the first post-disaster month, while 51.1% of the total sample experienced 'fear of imminent death'. The majority of sleep complaints were significantly more frequent in subjects with PTSD. Female gender, PTSD, older age, and 'fear of imminent death' were independently associated with insomnia. CONCLUSIONS: The findings of the present study indicate that the diagnosis of insomnia, as well as, certain specific insomnia complaints were more frequent in female victims of wildfires who have experienced 'fear of imminent death' and have developed PTSD.

Baseline heartbeat perception accuracy and short-term outcome of brief cognitive-behaviour therapy for panic disorder with agoraphobia.

BACKGROUND: Increased heartbeat perception accuracy (HBP-accuracy) may contribute to the pathogenesis of Panic Disorder (PD) without or with Agoraphobia (PDA). Extant research suggests that HBP-accuracy is a rather stable individual characteristic, moreover predictive of worse long-term outcome in PD/PDA patients. However, it remains still unexplored whether HBP-accuracy adversely affects patients' short-term outcome after structured cognitive behaviour therapy (CBT) for PD/PDA. AIM: To explore the potential association between HBP-accuracy and the short-term outcome of a structured brief-CBT for the acute treatment of PDA. METHOD: We assessed baseline HBP-accuracy using the "mental tracking" paradigm in 25 consecutive medication-free, CBT-naive PDA patients. Patients then underwent a structured, protocol-based, 8-session CBT by the same therapist. Outcome measures included the number of panic attacks during the past week, the Agoraphobic Cognitions Questionnaire (ACQ), and the Mobility Inventory-Alone subscale (MI-alone). RESULTS: No association emerged between baseline HBP-accuracy and posttreatment changes concerning number of panic attacks. Moreover, higher baseline HBP-accuracy was associated with significantly larger reductions in the scores of the ACQ and the MI-alone scales. CONCLUSION: Our results suggest that in PDA patients undergoing structured brief-CBT for the acute treatment of their symptoms, higher baseline HBP-accuracy is not associated with worse short-term outcome concerning panic attacks. Furthermore, higher baseline HBP-accuracy may be associated with enhanced therapeutic gains in agoraphobic cognitions and behaviours.

The potential of biomarkers for diagnosing insomnia: Consensus statement of the WFSBP Task Force on Sleep Disorders.

OBJECTIVES: Thus far, the diagnosis of insomnia is based on purely clinical criteria. Although a broad range of altered physiological parameters has been identified in insomniacs, the evidence to establish their diagnostic usefulness is very limited. Purpose of this WFSBP Task Force consensus paper is to systematically evaluate a series of biomarkers as potential diagnostic tools for insomnia. METHODS: A newly created grading system was used for assessing the validity of various measurements in establishing the diagnosis of insomnia; these measurements originated from relevant studies selected and reviewed by experts. RESULTS: The measurements with the highest diagnostic performance were those derived from psychometric instruments. Biological measurements which emerged as potentially useful diagnostic instruments were polysomnography-derived cyclic alternating pattern, actigraphy, and BDNF levels, followed by heart rate around sleep onset, deficient melatonin rhythm, and certain neuroimaging patterns (mainly for the activity of frontal and pre-frontal cortex, hippocampus and basal ganglia); yet, these findings need replication, as well as establishment of commonly accepted methodology and diagnostic cut-off points. Routine polysomnography, EEG spectral analysis, heart rate variability, skin conductance, thermoregulation, oxygen consumption, HPA axis, and inflammation indices were not shown to be of satisfactory diagnostic value. CONCLUSIONS: Apart from psychometric instruments which are confirmed to be the gold standard in diagnosing insomnia, six biomarkers emerge as being potentially useful for this purpose.

Differential association of cortisol with visual memory/learning and executive function in Bipolar Disorder.

The association of cortisol with cognition has been understudied in Bipolar Disorder (BD); available evidence is inconsistent while it is unknown whether cortisol's effects vary across neurocognitive domains implicating different brain structures. This study aimed to examine the association of cortisol with two cognitive tasks targeting visual memory and executive function (planning) in BD, related to the hippocampus and prefrontal lobe, respectively. Cambridge Neuropsychological Test Automated Battery (CANTAB) tasks targeting paired associative learning (PAL) and planning (Stockings of Cambridge; SOC) were administered to 60 BD type I patients. Basal serum cortisol was also measured. Higher cortisol was associated with worse performance in PAL, but not SOC, after controlling for gender, education, illness duration and treatment with mood stabilizers. This is the first study to examine the association of cortisol with neurocognitive function in BD while controlling for clinicodemographic and treatment-related factors. We found a significant association of cortisol with hippocampal-related visual memory/learning but not with prefrontal lobe-related executive function, suggesting domain-specific underlying mechanisms of cognitive dysfunction in BD. Future studies should further explore cortisol's brain structure-specific effects on cognitive functioning in BD.

Education in mental health promotion and its impact on the participants' attitudes and perceived mental health.

BACKGROUND: Although the promotion of mental health (MHP) through education and training is widely accepted, there is scarce evidence for its effectiveness in the literature from outcome studies worldwide. The present study aimed to assess the effect of a three-semester MHP educational program on the recipients' opinions towards mental illness and on their own self-assessed health. METHODS: Respondents were 78 attendees who completed the assessment battery at the first (baseline) and the last session (end) of the training course. They were primary care physicians or other professionals, or key community agents, working in the greater Athens area. The course consisted of 44 sessions (4 h each), over a 3-semester period, focusing on the principles and methods of mental health promotion, the main aspects of major psychiatric disorders, and on relevant to health skills. Assessment instruments included the Opinion about Mental Illness (OMI) scale and the General Health Questionnaire (GHQ-28). RESULTS: The mean scores of three OMI factors, that is, social discrimination, social restriction and social integration, and the two GHQ-28 subscales, that is, anxiety/insomnia and social dysfunction, were significantly improved by the end of the training course. CONCLUSIONS: The results of this study provide evidence, with limitations, for the short-term effectiveness of the implemented educational MHP program on an adult group of recipients-key agents in their community. Because interventions for strengthening positive opinions about mental illness and enhancing self-assessed health constitute priority aims of mental health promotion, it would be beneficial to further investigate the sustainability of the observed positive changes. In addition it would be useful to examine (a) the possible interplay between the two outcome measures, that is, the effect of opinions of recipients about mental health on their perceived health, and (b) the applicability of this intervention in individuals with different sociodemographic profiles.

Insomnia and its correlates in a representative sample of the Greek population.

BACKGROUND: Insomnia is a major public health concern affecting about 10% of the general population in its chronic form. Furthermore, epidemiological surveys demonstrate that poor sleep and sleep dissatisfaction are even more frequent problems (10-48%) in the community. This is the first report on the prevalence of insomnia in Greece, a southeastern European country which differs in several socio-cultural and climatic aspects from the rest of European Community members. Data obtained from a national household survey (n = 1005) were used to assess the relationship between insomnia symptoms and a variety of sociodemographic variables, life habits, and health-related factors. METHODS: A self-administered questionnaire with questions pertaining to general health and related issues was given to the participants. The Short Form-36 (Mental Health subscale), the Athens Insomnia Scale (AIS) as a measure of insomnia-related symptoms, and the International Physical Activity Questionnaire (IPAQ) were also used for the assessment. RESULTS: The prevalence of insomnia in the total sample was 25.3% (n = 254); insomnia was more frequent in women than men (30.7% vs. 19.5%) and increased with age. Multiple regression analysis revealed a significant association of insomnia with low socio-economical status and educational level, physical inactivity, existence of a chronic physical or mental disease and increased number of hospitalizations in the previous year. CONCLUSIONS: The present study confirms most findings reported from other developed countries around the world regarding the high prevalence of insomnia problems in the general population and their association with several sociodemographic and health-related predisposing factors. These results further indicate the need for more active interventions on the part of physicians who should suspect and specifically ask about such symptoms.

Depressive symptomatology in high school students: the role of age, gender and academic pressure.

To clarify the prevalence of depressive symptomatology in high school students in Athens and to evaluate risk factors for depressive symptomatology the CES-D scale was administered to 713 students (age 15-18). Demographic, school performance and extracurricular activities data were collected. A high prevalence (26.2%) of depressive symptomatology (CES-D cut-off score >28) was found. Regression analysis showed depressive symptomatology to be associated to gender (girls had higher scores than boys), school record (students with a better record had lower scores) and the interaction of gender and grade (males were found to have higher depressive symptomatology scores as they grew older).

Sleep disturbances in relation to fatigue in major depression.

OBJECTIVE: This study aimed to investigate the independent correlations of subjective sleep disturbances (insomnia and daytime sleepiness) with the severity of fatigue in patients with major depression. METHODS: Eighty-one currently depressed patients (70 females and 11 males), aged between 23 and 65 years, with a DSM-IV diagnosis of major depressive disorder were studied. Patients with physical diseases or other conditions associated with prominent fatigue were excluded. The 17-item Hamilton Depression Rating Scale (HDRS), the Athens Insomnia Scale (AIS), and the Epworth Sleepiness Scale (ESS) were used for the cross-sectional assessment of the severity of depression, insomnia, and sleepiness, respectively. Severity of fatigue was measured with the Fatigue Severity Scale (FSS). Pearson's and Spearman's coefficients were used in bivariate correlations between FSS score and the independent variables (age, gender, inpatient/outpatient status, HDRS score, AIS total score, AIS individual item scores, and ESS score). A stepwise multiple regression analysis was then performed, with FSS score as the dependent variable. RESULTS: The severity of fatigue was significantly correlated with female sex, HDRS score, AIS total score, awakenings during the night (AIS item 2), compromised sleep quality (AIS item 5), and ESS score. Sleep quality (AIS item 5) and daytime sleepiness (ESS) were the only significant predictors of the severity of fatigue in the multiple regression analysis. CONCLUSIONS: Both sleep quality and daytime sleepiness correlate independently with fatigue severity, as measured with the FSS, in patients with major depression. The FSS does not appear to be a 'pure' measure of fatigue in depressed patients, a finding with potential implications for the choice of appropriate fatigue measures in this population.

Combination therapy with amisulpride and antidepressants: clinical observations in case series of elderly patients with psychotic depression.

Psychotic depression is classified as a clinical subtype of major depressive disorder. The combination of an antidepressant with an antipsychotic agent has been demonstrated to be efficacious for the treatment of psychotic depression. However, in elderly patients with psychotic depression, little information is available on the efficacy of such combinations. Therefore, we have evaluated combination treatment for 5 weeks with amisulpride and antidepressants in non-demented elderly patients with psychotic depression. Eleven patients were treated with either citalopram 20-40 mg/day (n=5) or mirtazapine 30-60 mg/day (n=6), and amisulpride 75-100 mg/day for 5 weeks. Clinical status was evaluated at baseline and after 3 and 5 weeks using the Brief Psychiatric Rating Scale (BPRS), the Hamilton Depression Rating Scale--17 items (HDRS) and the Clinical Global Impression Scale (CGI-S). In 5 of the 11 patients there was remission of depression, while in another 5 patients there was partial remission of depression and in one patient there was no remission. Finally, there was resolution of psychotic symptoms in all the patients involved. One patient developed tremor and rigidity but insisted on continuing with the drug since her psychopathology has improved considerably after the addition of amisulpride to antidepressant treatment. In conclusion, some of the elderly patients with psychotic depression may benefit from the combination of amisulpride and antidepressant pharmacotherapy.

Pregabalin in the discontinuation of long-term benzodiazepine use: a case-series.

Tolerance, dependence, and adverse effects on cognitive functions are well known consequences of long-term use of benzodiazepines (BDZ), especially at high doses; this raises thorny therapeutic problems in their discontinuation. One promising pharmacological agent in BDZ discontinuation might be the newer antiepileptic, pregabalin (PGB), which has already successfully been tested in the treatment of anxiety disorders. We report on a series of four women with long-term, high-dose dependence on BDZ, who were treated with PGB at doses of 225-600 mg. All four patients discontinued BDZ successfully in 3-7 weeks. Moreover, they had an impressive reduction of their previous anxiety levels under BDZ. In addition, the patients showed a clinically significant amelioration in their cognitive functioning. The side effects of PGB were mild and transient, persisting only during the first 2 weeks of treatment. Although our findings are preliminary, they suggest that PGB might be one of the most promising of the newer agents in the treatment of BDZ dependence.

Jacksonian seizure in a manic patient treated with rTMS.

This is a report of a jacksonian seizure in a non-psychotic manic patient who was treated with right prefrontal high frequency rTMS concomitant to pharmacotherapy.

Levetiracetam in the treatment of antipsychotics-resistant Tourette syndrome.

Levetiracetam, an anti-epileptic agent that enhances GABAergic neurotransmission, is one of the newest alternative treatments of Tourette syndrome (TS). We present the case of a 23-year-old female patient suffering from TS since the age of 7, who exhibited poor response to a variety of agents (haloperidol, pimozide, clonidine and various adjunctive agents) and had four hospitalizations during the previous 2 years due to the deterioration of her clinical state. On her last admission, in addition to clonidine 600 microg/day (already part of her regimen for the previous 4 years), levetiracetam was prescribed, up to 2000 mg/day, progressively titrated over a 3-week period. The patient presented a significant improvement on her TS symptomatology (the score on the Yale Global Tic Severity Scale dropped from 70 at admission, to 25 five weeks later, at discharge), which was preserved during the subsequent 4 months, without any serious side-effect.

The psychological impact of a catastrophic earthquake: a retrospective study 50 years after the event.

Aim of the present study was to retrospectively assess the impact of a catastrophic earthquake in a sample of 121 survivors, 50 years after the event. Mean age +/- SD of the responders was 72.2 +/- 6.1 years. The majority of the victims (78%) acknowledged a strong overall impact of the earthquake on their lives, and almost all of them had intense recollection of the event at its anniversary. The most frequent symptom during the 6 months after the earthquake was persistent remembering or "reliving" of the event; women had considerably more often recurrent dreams of the earthquake and distress than did men. Women and young adults at the time of the earthquake appear to be the most vulnerable groups regarding the psychological effects of the event.

Comparison of cognitive performance among different age groups in patients with obstructive sleep apnea.

The aim of this study was to evaluate the effect of obstructive sleep apnea syndrome on the cognitive performance of young and middle-aged patients. Patients were divided into two groups, one consisting of 30 patients less than 50 years of age and the other consisting of 28 patients 50 years and over. Normal subjects were similarly divided into two groups, composed of 17 younger and 24 older controls. Patients and controls were examined with all-night polysomnography and subsequently underwent cognitive testing via attention-alertness tests. Comparing young to middle-aged patients, there were statistically significant differences in cognitive performance, especially in attention tests. Younger patients' cognitive performance was similar to their age-matched controls, while middle-aged patients showed cognitive decline in comparison with their age-matched controls. Although we studied only two age groups using 50 years of age as a cut-off, we could demonstrate that cognitive deterioration of untreated sleep apnea patients is age dependent, and several factors may contribute to this effect including brain hypoxia, sleep fragmentation, or comorbidities. Aging patients with sleep apnea demonstrate cognitive decline, while younger patients with the same disease severity are (somehow) able to compensate for this effect.

The impact of stressful life events on risk of relapse in women with multiple sclerosis: a prospective study.

PURPOSE: The aims of this study were first, to examine the general relation between stressful life events (SLEs) and clinical relapses in women with multiple sclerosis (MS) and second, to investigate the relations of the specific stressor attributes of duration, type, and severity on MS exacerbations. METHODS: Twenty six ambulating women with relapsing-remitting MS were followed-up for a mean of 56.3 weeks. Patients documented SLEs weekly in self report diaries which were then collected at regular pre-scheduled clinic visits every 4 weeks. SLEs were classified as short-term if they had subjectively no lasting effect and long-term if they had a subjectively felt psychological impact that lasted at least 10-14 days after the event. The severity of SLEs was determined using the Recent Life Change Questionnaire. RESULTS: Experiencing three or more SLEs, during a 4-week period, was associated with a 5-fold increase of MS relapse rate (95% CI 1.7-16.4, p=0.003). The presence of at least one long-term SLE was associated with three times (95% CI 1.01-9.13, p<0.05) the rate of MS exacerbation during the following 4 weeks. There was no significant association between the severity (95% CI 0.99-1.01, p>0.05) or the type (chi2=7.29, df=5, p>0.05) of stressor and the risk for relapse. CONCLUSION: Ambulatory women with relapsing-remitting MS who experience cumulative SLEs may be at a greater risk for relapse. Duration is the only stress attribute that seems to increase the risk for relapsing in contrast to stress type and stress severity that were not found to interact with MS exacerbation.

The safety of the electroconvulsive therapy-aripiprazole combination: four case reports.

In clinical practice, a proportion of patients with psychotic or mood disorders are treated with electroconvulsive therapy (ECT) while receiving concomitantly antipsychotic and/or other psychotropic agents. Aripiprazole is a second-generation antipsychotic that seems to have a favorable side-effect profile. However, to the best of our knowledge, there are, as yet, no available reports on the safety of ECT-aripiprazole combination. We report the cases of 4 female inpatients--3 suffering from major depression and 1 from schizophrenia--who underwent ECT--1 of them twice--while receiving aripiprazole (10-15 mg/d), as part of their regimen. In all cases, the combination was well tolerated and only minimal side effects were reported.