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.

Sex-related variation of neurocognitive functioning in bipolar disorder: Focus on visual memory and associative learning.

Bipolar disorder (BD) is associated with cognitive deficits in attention, verbal memory and executive functions. However, only few studies have examined sex effects on cognition despite their clinical relevance. Given that visual memory/ learning has been understudied the aim of our study was to investigate sex-related variation in cognition (executive functions and visual memory/ learning) in BD. Cognitive performance of 60 bipolar-I patients and 30 healthy controls was evaluated by using CANTAB battery tasks targeting spatial memory (SRM), paired associative learning (PAL) and executive functions. We fitted a multivariate analysis of covariance (MANCOVA), followed by task-specific ANCOVAs. A significant diagnosis by sex interaction effect was detected (MANCOVA); specifically, diagnosis-specific sex effects were found for SRM and PAL, as healthy males outperformed healthy females but this pattern was attenuated in BD patients. Patients' clinicodemographic characteristics, current psychopathology or medication status did not differ across sexes and were, therefore, unlikely to explain detected sex effects. Our study is one of few studies to assess sex-related variation in cognition in BD and the first to record a diagnosis-specific sex effect for two tasks of visuo-spatial memory/ learning, indicating that sex-related variation in healthy subjects is disrupted in BD.

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.

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.

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.

Sleep EEG and spindle characteristics after combination treatment with clozapine in drug-resistant schizophrenia: a pilot study.

PURPOSE: Clozapine is an atypical neuroleptic agent, effective in treating drug-resistant schizophrenia. The aim of this work was to investigate overall sleep architecture and sleep spindle morphology characteristics, before and after combination treatment with clozapine, in patients with drug-resistant schizophrenia who underwent polysomnography. METHODS: Standard polysomnographic techniques were used. To quantify the sleep spindle morphology, a modeling technique was used that quantifies time-varying patterns in both the spindle envelope and the intraspindle frequency. RESULTS: After combination treatment with clozapine, the patients showed clinical improvement. In addition, their overall sleep architecture and, more importantly, parameters that quantify the time-varying sleep spindle morphology were affected. Specifically, the results showed increased stage 2 sleep, reduced slow-wave sleep, increased rapid eye movement sleep, increased total sleep time, decreased wake time after sleep onset, as well as effects on spindle amplitude and intraspindle frequency parameters. However, the above changes in overall sleep architecture were statistically nonsignificant trends. CONCLUSIONS: The findings concerning statistically significant effects on spindle amplitude and intraspindle frequency parameters may imply changes in cortical sleep EEG generation mechanisms, as well as changes in thalamic pacing mechanisms or in thalamo-cortical network dynamics involved in sleep EEG generation, as a result of combination treatment with clozapine. SIGNIFICANCE: Sleep spindle parameters may serve as metrics for the eventual development of effective EEG biomarkers to investigate treatment effects and pathophysiological mechanisms in schizophrenia.

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.

Indoleamine 2,3-dioxygenase and immune changes under antidepressive treatment in major depression in females.

BACKGROUND/AIM: Indoleamine 2, 3-dioxygenase (IDO) induction has been suggested as a mechanism by which immune activation affects tryptophan metabolism and serotonin synthesis in major depressive disorder (MDD). We investigated IDO and changes in inflammatory mediators in patients with MDD undergoing effective treatment. PATIENTS AND METHODS: Forty female patients with MDD and 40 controls were recruited. Serum IDO was assessed by enzyme-linked immunosorbent assay (ELISA). We also determined tumor necrosis factor-α (TNFα), interferon-γ (IFNγ), C-reactive protein (CRP) and serotonin concentrations. RESULTS: Patients' baseline concentrations of IDO and immune mediators were higher and serotonin concentrations were lower compared to controls. IDO and TNFα concentrations decreased under treatment and IDO changes were positively correlated with patient improvement. IFNγ and CRP concentrations remained unchanged. Serotonin concentration tended to increase. CONCLUSION: IDO might play an important role in the pathophysiology of MDD. Moreover, antidepressant therapy might reduce IDO production through an IFNγ-independent pathway. Finally, peripheral concentration of IDO assessed by ELISA might be a useful marker of MDD.

Differences in EEG delta frequency characteristics and patterns in slow-wave sleep between dementia patients and controls: a pilot study.

PURPOSE: To evaluate the modifications of EEG activity during slow-wave sleep in patients with dementia compared with healthy elderly subjects, using spectral analysis and period-amplitude analysis. METHODS: Five patients with dementia and 5 elderly control subjects underwent night polysomnographic recordings. For each of the first three nonrapid eye movement-rapid eye movement sleep cycles, a well-defined slow-wave sleep portion was chosen. The delta frequency band (0.4-3.6 Hz) in these portions was analyzed with both spectral analysis and period-amplitude analysis. RESULTS: Spectral analysis showed an increase in the delta band power in the dementia group, with a decrease across the night observed only in the control group. For the dementia group, period-amplitude analysis showed a decrease in well-defined delta waves of frequency lower than 1.6 Hz and an increase in such waves of frequency higher than 2 Hz, in incidence and amplitude. CONCLUSIONS: Our study showed (1) a loss of the dynamics of delta band power across the night sleep, in dementia, and (2) a different distribution of delta waves during slow-wave sleep in dementia compared with control subjects. This kind of computer-based analysis can highlight the presence of a pathologic delta activity during slow-wave sleep in dementia and may support the hypothesis of a dynamic interaction between sleep alteration and cognitive decline.

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.

Independent component analysis for source localization of EEG sleep spindle components.

Sleep spindles are bursts of sleep electroencephalogram (EEG) quasirhythmic activity within the frequency band of 11-16 Hz, characterized by progressively increasing, then gradually decreasing amplitude. The purpose of the present study was to process sleep spindles with Independent Component Analysis (ICA) in order to investigate the possibility of extracting, through visual analysis of the spindle EEG and visual selection of Independent Components (ICs), spindle "components" (SCs) corresponding to separate EEG activity patterns during a spindle, and to investigate the intracranial current sources underlying these SCs. Current source analysis using Low-Resolution Brain Electromagnetic Tomography (LORETA) was applied to the original and the ICA-reconstructed EEGs. Results indicated that SCs can be extracted by reconstructing the EEG through back-projection of separate groups of ICs, based on a temporal and spectral analysis of ICs. The intracranial current sources related to the SCs were found to be spatially stable during the time evolution of the sleep spindles.

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).

Tiagabine augmentation to fluvoxamine-risperidone combination in the treatment of obsessive-compulsive disorder.

Despite the recent progress in the pharmacological treatment of obsessive-compulsive disorder (OCD)--especially with high doses of serotonin reuptake inhibitors, alone or in combination with low doses of antipsychotics--a non-negligible proportion of patients remains refractory to it. For these patients augmentation tactics with drugs from other chemical classes, including antiepileptic drugs, seems advisable. We report on the case of a female inpatient with OCD, whereby the adjunction of tiagabine, a selective GABA reuptake inhibitor at 15 mg/day, to a fluvoxamine (400 mg/day)-risperidone (1 mg/day) combination led to the patient's marked improvement as reflected in the reduction by almost 47% of her score on the Yale-Brown Obsessive Compulsive Scale. With respect to tiagabine's specifically anti-OCD mechanism of action, we note that enhanced inhibitory GABAergic neurotransmission slows down excitatory glutamatergic transmission in the cortico-striato-thalamic system, which presumably constitutes the core pathophysiological mechanism of OCD symptoms.

Bilateral ankle oedema in a patient taking escitalopram.

Escitalopram (ESC) is the S-isomer of the racemic compound citalopram, and has been shown to be an efficacious treatment for major depressive disorder. Several studies or case reports are available describing its side effects, none of which however refer to its potential to induce ankle oedema. We report the case of a 69-year-old female depressed patient who, after approximately 1 month of therapy with ESC, progressively titrated up to 30 mg/day, developed a bilateral ankle oedema, which resolved completely within the first week following its discontinuation.

Reversible tremor and myoclonus associated with topiramate-fluvoxamine coadministration.

The antiepileptic agent topiramate has proved its efficacy in a variety of other conditions as well, including several kinds of tremor and migraine prophylaxis. We report on the case of a 42-year-old depressive female patient with comorbid migraine attacks, whereby the adjunction of topiramate as an antimigraine agent at the dosage of 50 mg/d to her antidepressive treatment with fluvoxamine at 300 mg/d triggered--the prima facie paradoxical for topiramate--side effects of tremor and myoclonus. Topiramate was immediately discontinued, and patient's abnormal movements subsided completely within 24 to 72 hours. Topiramate was possibly the cause of patient's abnormal movements enhanced by fluvoxamine's potential to induce also tremor and myoclonus. Therefore, clinicians should be aware of the potentially severe adverse reactions that might occur during concomitant treatment with fluvoxamine and topiramate.

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.

Remission of migraine attacks in a patient with depression who is taking pregabalin.

Antiepileptic drugs (AED) are increasingly used in the treatment of migraine. Pregabalin (PGB) is an AED that has been used in the treatment of partial seizures, of various types of pain, and of certain anxiety disorders, but to the best of our knowledge, there has been no report on the use of PGB in the treatment of migraine. We report the case of a 60-year-old female inpatient with depression, long experiencing migraine, whose migraine symptoms improved markedly after receiving PGB in combination with escitalopram administered for her depression. The PGB mechanism of action in conjunction with its structural similarity with gabapentin, already successfully tested in the treatment of migraine, provide additional supportive evidence, theoretical and clinical, respectively, for PGB potential to alleviate migraine symptoms. However, only carefully randomized, controlled studies, or at the very least, open-label series of large patient samples treated in a similar fashion could establish the efficacy of PGB in migraine treatment.