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.

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.

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).

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 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.

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.

Vitamin B12 and hepatic enzyme serum levels correlate with interleukin-6 in alcohol-dependent individuals without liver disease.

Alcohol abuse is a major cause of liver cirrhosis as well as chronic liver disease. The aim of the present study was to investigate the possible correlation, between liver dysfunction biological markers and vitamin B12, with interleukin-6, in the serum of alcohol-dependent individuals without liver disease (AWLD). In a sample of 43 alcohol abusing/dependent subjects (33 males and 10 females) treated on an inpatient basis according to a standard detoxification protocol, the serum activities of the hepatic enzymes (ASAT, ALAT, gamma-GT), as well as the concentration of B12 and IL-6, were determined on admission. A strong positive correlation has been observed between IL-6 and B12, ASAT, ALAT, and gamma-GT at the beginning of the detoxification period. The results confirmed that in alcohol-dependent individuals, the median serum concentration of IL-6, before the beginning of the treatment, had a significant positive correlation with the liver dysfunction biological markers and B12. In conclusion, IL-6 might be used as an additional diagnostic marker for the degree of liver dysfunction in alcohol dependent individuals.

Changes in LORETA and conventional patterns of P600 after steroid treatment in multiple sclerosis patients.

OBJECTIVE: The P600 component of event-related potentials (ERPs) reflecting the 'rule-governed sequence of information processing', has been associated with multiple sclerosis (MS)-related cognition. The present study aimed at examining the effects of methylprednisolone treatment in MS patients on cognition as reflected by the low-resolution brain electromagnetic tomography (LORETA) of the P600 as well as its conventional constituents (amplitudes and latencies) recorded during a working memory (WM) test. METHOD: A paired LORETA comparison was performed in the P600 component of ERPs elicited during a (WM) test in 18 MS patients suffering from the relapsing-remitting form, before and after 1 week treatment with methylprednisolone. The P600 component was also evaluated in 16 healthy controls matched to the patients on age and educational level. RESULTS: When pre- and post-treatment recordings of LORETA were compared all patients as a group showed significantly different patterns of current density activation located at right frontal lobe. The treatment was accompanied by an increase of the amplitude of P600 at the right frontoparietal area. In the post-treatment phase the patients exhibited significant improvement of the memory performance as compared to themselves before treatment. As a result both the P600 amplitudes and memory performance at post-treatment were closer to those exhibited by normal controls. CONCLUSION: These findings support the notion that steroid treatment in relapsing-remitting MS patients, may exert a beneficial effect in 'rule-governed sequence of information processing'.

Refractory psychosis and prominent cognitive deficits in a patient with mega-cisterna magna.

We present a case of refractory psychosis with prominent cognitive deficits in a patient with 'mega-cisterna magna', a congenital defect within the 'Dandy-Walker Complex' continuum. The 21-year-old female had a 3-year history of refractory psychotic symptoms despite adequate antipsychotic treatment. CT and MRI scans disclosed 'mega-cisterna magna'. Thorough neuropsychological testing recorded extensive deficits. Treatment with amisulpride 1200 mg/day resulted in a 30% decrease in PANSS score within 2 months. Then galantamine 8 mg/day was added and PANSS score decreased further by 27% within 2 weeks. Cognitive and social functioning was overall much improved. The effect was sustained in a 24 months follow-up. It is postulated that even a less extended cerebellar lesion, such as mega-cisterna magna, can be associated with psychosis, and in some cases with treatment refractoriness or cognitive dysfunction. Adjuvant galantamine may improve cognitive and psychosocial functioning in these patients.

Non-pharmacological treatments in the management of rapid cycling bipolar disorder.

BACKGROUND: Rapid cycling (RC) bipolar disorder is often treatment-resistant to pharmacotherapy. Non-pharmacological methods, however, are reasonable considerations in treatment refractory cases of bipolar patients. Thus, such methods may be useful in the management of RC, especially when drugs are not shown to be effective. METHOD: This review is based on studies of all major non-pharmacological methods which are used in the management of bipolar disorder, by focusing on data regarding patients with a RC pattern of the illness. RESULTS: Regarding biological treatments, for electroconvulsive therapy and sleep deprivation, there exists some evidence that they might be efficacious in RC patients for acute treatment as well as for prophylaxis from recurrences. Light therapy has not been shown to be efficacious in RC, while no published data exist for transcranial magnetic stimulation and vagus nerve stimulation. The non-biological treatments include psychotherapeutic and psychosocial interventions; these have not been tried particularly on RC patients, but their use should be expected to contribute to the overall management of the RC pattern as it does to that of mood disorder in general. LIMITATIONS: Many data on which this review is based are drawn from case reports or non-randomised trials. CONCLUSIONS: Non-pharmacological methods, either biological or non-biological (psychotherapies and psychoeducation), may be applied in the management of RC patients. These methods might be used in combination with the administration of drug treatment, based on the clinical experience of the physician and the individual characteristics of the patient.

Circadian rhythms and sleep patterns in urban Greek couples.

A convenience sample of 14 adults (seven couples) who intentionally nap regularly was recruited to describe circadian rhythms and sleep patterns in a culture in which afternoon naps are routine. Participants wore a wrist actigraph for 48 hr during May to obtain two peaks and troughs of activity data. Peak activity, estimated by cosinor analysis (acrophase), occurred at 1542 hours for men and at 1600 hours for women. Compared to their male partners, women had a later acrophase and a significantly stronger 24-hr rhythm, despite similar nap and nighttime sleep schedules. Men had more awakenings during the night and slightly shorter naps than did women. For the 24-hr period, men averaged 6.8 +/- 1.0 hr of sleep and women averaged 7.4 +/- 1.1 hr. Results indicate that Greek adults delay sleep onset at night and awaken early in the morning. Among this small group, naps are an accepted cultural behavior.