Exploratory study of ultraviolet B (UVB) radiation and age of onset of bipolar disorder.

BACKGROUND: Sunlight contains ultraviolet B (UVB) radiation that triggers the production of vitamin D by skin. Vitamin D has widespread effects on brain function in both developing and adult brains. However, many people live at latitudes (about > 40 N or S) that do not receive enough UVB in winter to produce vitamin D. This exploratory study investigated the association between the age of onset of bipolar I disorder and the threshold for UVB sufficient for vitamin D production in a large global sample. METHODS: Data for 6972 patients with bipolar I disorder were obtained at 75 collection sites in 41 countries in both hemispheres. The best model to assess the relation between the threshold for UVB sufficient for vitamin D production and age of onset included 1 or more months below the threshold, family history of mood disorders, and birth cohort. All coefficients estimated at P ≤ 0.001. RESULTS: The 6972 patients had an onset in 582 locations in 70 countries, with a mean age of onset of 25.6 years. Of the onset locations, 34.0% had at least 1 month below the threshold for UVB sufficient for vitamin D production. The age of onset at locations with 1 or more months of less than or equal to the threshold for UVB was 1.66 years younger. CONCLUSION: UVB and vitamin D may have an important influence on the development of bipolar disorder. Study limitations included a lack of data on patient vitamin D levels, lifestyles, or supplement use. More study of the impacts of UVB and vitamin D in bipolar disorder is needed to evaluate this supposition.

Association between polarity of first episode and solar insolation in bipolar I disorder.

OBJECTIVE: Circadian rhythm disruption is commonly observed in bipolar disorder (BD). Daylight is the most powerful signal to entrain the human circadian clock system. This exploratory study investigated if solar insolation at the onset location was associated with the polarity of the first episode of BD I. Solar insolation is the amount of electromagnetic energy from the Sun striking a surface area of the Earth. METHODS: Data from 7488 patients with BD I were collected at 75 sites in 42 countries. The first episode occurred at 591 onset locations in 67 countries at a wide range of latitudes in both hemispheres. Solar insolation values were obtained for every onset location, and the ratio of the minimum mean monthly insolation to the maximum mean monthly insolation was calculated. This ratio is largest near the equator (with little change in solar insolation over the year), and smallest near the poles (where winter insolation is very small compared to summer insolation). This ratio also applies to tropical locations which may have a cloudy wet and clear dry season, rather than winter and summer. RESULTS: The larger the change in solar insolation throughout the year (smaller the ratio between the minimum monthly and maximum monthly values), the greater the likelihood the first episode polarity was depression. Other associated variables were being female and increasing percentage of gross domestic product spent on country health expenditures. (All coefficients: P ≤ 0.001). CONCLUSION: Increased awareness and research into circadian dysfunction throughout the course of BD is warranted.

Variations in seasonal solar insolation are associated with a history of suicide attempts in bipolar I disorder.

BACKGROUND: Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries. METHODS: Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun's electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries). RESULTS: This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p < 0.01. CONCLUSION: A large change in solar insolation, both between winter and summer and between the minimum and maximum monthly values, may increase the risk of suicide attempts in bipolar I disorder. With frequent circadian rhythm dysfunction and suicidal behavior in bipolar disorder, greater understanding of the optimal roles of daylight and electric lighting in circadian entrainment is needed.

Periodic Catatonia: Long-term Treatment With Lamotrigine: A Case Report.

Periodic catatonia is a rare form of catatonia, characterized by episodes occurring in a cyclic pattern with clinical features of combined stupor and excitement, with intervals of remission. Although periodic catatonia is not common, it is an urgent condition, requiring hospitalization for evaluation and treatment. The management of periodic catatonia is quite challenging, mainly because of the unknown pathophysiological mechanisms involved in the onset of this clinical entity, which are less clear than in other forms of catatonia. Although positive trials of several medications in the acute phase of periodic catatonia have been published, available literature concerning the prevention of recurrent catatonic episodes is scarce. Here, we present the case of a patient with periodic catatonia in which long-term treatment with lamotrigine appears to have acted prophylactically in reducing the occurrence and severity of new catatonic episodes. A better understanding of the mechanisms involved in the pathophysiology of periodic catatonia and increasing psychiatrists' and physicians' awareness of the presentation of this clinical entity could be of benefit in shedding light on the most appropriate treatment approach. However, further clinical studies are needed before any firm recommendations can be made.

Psychiatric admission as a risk factor for posttraumatic stress disorder.

Psychiatric hospitalization poses a risk for Posttraumatic Stress Disorder (PTSD), partly because of coercion. However, the role of legal status is less clear, while factors like insight, exposure to violence and affective disorders have not been addressed adequately. The present study aims at assessing PTSD rates after hospitalization and evaluating the potential role of these factors. 98 inpatients were assessed for PTSD, insight, main diagnosis, adverse events during hospitalization and legal status. Assessment took place at discharge (T1) and three months later (T2). Three months after discharge, 74.2% of patients with affective disorders met symptom-criteria for PTSD. Voluntarily hospitalized patients had more severe PTSD-symptoms. This relation vanished after controlling for affective disorders. The latter, as well as exposure to violence were the most significant risk factors at T2. Female gender, marital status (not married) and employment status (not employed), were additional risk factors at T1, while involuntary medication had a negative effect on PTSD-symptoms. Voluntarily hospitalized patients are more vulnerable to PTSD, due to higher rates of affective disorders. Females suffering from affective disorders who are not married and not employed should be monitored for PTSD symptoms during and after hospitalization, especially if exposed to violence.

Association between solar insolation and a history of suicide attempts in bipolar I disorder.

In many international studies, rates of completed suicide and suicide attempts have a seasonal pattern that peaks in spring or summer. This exploratory study investigated the association between solar insolation and a history of suicide attempt in patients with bipolar I disorder. Solar insolation is the amount of electromagnetic energy from the Sun striking a surface area on Earth. Data were collected previously from 5536 patients with bipolar I disorder at 50 collection sites in 32 countries at a wide range of latitudes in both hemispheres. Suicide related data were available for 3365 patients from 310 onset locations in 51 countries. 1047 (31.1%) had a history of suicide attempt. There was a significant inverse association between a history of suicide attempt and the ratio of mean winter solar insolation/mean summer solar insolation. This ratio is smallest near the poles where the winter insolation is very small compared to the summer insolation. This ratio is largest near the equator where there is relatively little variation in the insolation over the year. Other variables in the model that were positively associated with suicide attempt were being female, a history of alcohol or substance abuse, and being in a younger birth cohort. Living in a country with a state-sponsored religion decreased the association. (All estimated coefficients p < 0.01). In summary, living in locations with large changes in solar insolation between winter and summer may be associated with increased suicide attempts in patients with bipolar disorder. Further investigation of the impacts of solar insolation on the course of bipolar disorder is needed.

Indication of Disrupted Temporal Structure in the Case of Thought Blocks in Schizophrenia: The Role of the Metastable Balance.

This study is aimed at investigating probable disruption of the metastable balance relevant to a disruption of the mental processes observed in the neurophenomenal level. This disruption was found to occur under dense auditory verbal hallucinations (AVHs) which are accompanied by thought blocking (TB) phenomena. The entropy that quantifies the complexity of the spontaneous coupling has been used to describe the observed transitions. According to our findings, the high synchrony-derived entropy (SE) defines a metastable state, where formations of cortical areas are able to coordinate transiently under the demands of stimulus-oriented processes or other internal cognitive associations. It was also found that the disruption of the sensitive balance to the side of oversynergy (overconnectedness) rather than the side of independence (coincidental coupling) is relevant with functional fixations under the specific symptom of schizophrenia. An introduced measure relative to the persistence of coupling indicated that the overcoupled brain areas exhibit a kind of "stiffness" in processing incoherent phasic components. Our consideration enhances the understanding of the role the metastability plays in the interpretation of deeply subjective phenomena, such as AVHs and TBs that affect the normal information routing in the brain.

Brain Oscillations Elicited by the Cold Pressor Test: A Putative Index of Untreated Essential Hypertension.

OBJECTIVE: Essential hypertension is associated with reduced pain sensitivity of unclear aetiology. This study explores this issue using the Cold Pressor Test (CPT), a reliable pain/stress model, comparing CPT-related EEG activity in first episode hypertensives and controls. METHOD: 22 untreated hypertensives and 18 matched normotensives underwent 24-hour ambulatory blood pressure monitoring (ABPM). EEG recordings were taken before, during, and after CPT exposure. RESULTS: Significant group differences in CPT-induced EEG oscillations were covaried with the most robust cardiovascular differentiators by means of a Canonical Analysis. Positive correlations were noted between ABPM variables and Delta (1-4 Hz) oscillations during the tolerance phase; in high-alpha (10-12 Hz) oscillations during the stress unit and posttest phase; and in low-alpha (8-10 Hz) oscillations during CPT phases overall. Negative correlations were found between ABPM variables and Beta2 oscillations (16.5-20 Hz) during the posttest phase and Gamma (28.5-45 Hz) oscillations during the CPT phases overall. These relationships were localised at several sites across the cerebral hemispheres with predominance in the right hemisphere and left frontal lobe. CONCLUSIONS: These findings provide a starting point for increasing our understanding of the complex relationships between cerebral activation and cardiovascular functioning involved in regulating blood pressure changes.

Antipsychotic Treatment of 22q11.2 Deletion Syndrome-Related Psychoses.

In the recent study by Verhoeven and Egger, 2015 and the recent letter to the editor by Boot et al. 2015 an emphasis is given to the best possible pharmacological treatment of 22q11-2 Deletion-Syndrome related psychoses. We would like to present the case of a 23-year old Cypriot patient with 22q11.2 deletion syndrome who fulfilled criteria for treatment resistant schizophrenia (TRS). He was sequentially treated with aripiprazole, risperidone, olanzapine, haloperidol and a combination treatment with olanzapine and haloperidol. Clozapine was the only antipsychotic medication that has improved his condition.

Aristotle Meets Zeno: Psychophysiological Evidence.

This study, a tribute to Aristotle's 2400 years, used a juxtaposition of valid Aristotelian arguments to the paradoxes formulated by Zeno the Eleatic, in order to investigate the electrophysiological correlates of attentional and /or memory processing effects in the course of deductive reasoning. Participants undertook reasoning tasks based on visually presented arguments which were either (a) valid (Aristotelian) statements or (b) paradoxes. We compared brain activation patterns while participants maintained the premises / conclusions of either the valid statements or the paradoxes in working memory (WM). Event-related brain potentials (ERPs), specifically the P300 component of ERPs, were recorded during the WM phase, during which participants were required to draw a logical conclusion regarding the correctness of the valid syllogisms or the paradoxes. During the processing of paradoxes, results demonstrated a more positive event-related potential deflection (P300) across frontal regions, whereas processing of valid statements was associated with noticeable P300 amplitudes across parieto-occipital regions. These findings suggest that paradoxes mobilize frontal attention mechanisms, while valid deduction promotes parieto-occipital activity associated with attention and/or subsequent memory processing.

Enduring financial crisis in Greece: prevalence and correlates of major depression and suicidality.

PURPOSE: A series of repeated cross-sectional surveys conducted in 2008, 2009, 2011 and 2013 were conducted with the aim of estimating the prevalence of major depression and suicidality as well as of investigating its risk factors. The present report concentrates on the 2013 survey. METHODS: A random and representative sample of 2.188 people was telephone interviewed with regard to various socio-economic indicators and the presence of major depression and suicidality, which were assessed with the germane module of the Structured Clinical Interview. RESULTS: Findings suggest a rise in 1-month prevalence of major depression (12.3 %) and a decline in prevalence of suicidality (2.8 %). Female gender, residence in rural area, low educational attainment, unemployment and economic hardship were found to increase the odds of suffering from major depression. The influence of economic hardship and unemployment on suicidality was also substantial and independent of major depression. CONCLUSIONS: Results stress the imperative need for the design and implementation of social policies and interventions that would offset the dire impact of the sustained recession in Greece.

Preoperative neuropsychological presentation of patients with refractory frontal lobe epilepsy.

BACKGROUND: This study investigated whether certain cognitive deficits are associated with frontal lobe epilepsy (FLE) aiming to contribute with localization data to the preoperative assessment of epilepsy surgery candidates. METHODS: We evaluated 34 patients with refractory FLE, 37 patients with refractory medial temporal lobe epilepsy (MTLE), and 22 healthy individuals in attention, psychomotor speed, motor function, verbal memory span, verbal fluency, response inhibition/interference, concept formation and set shifting, anticipation and planning, global memory. RESULTS: Neuropsychological performances of FLE and MTLE were similar, with the only exception the WCST-number of categories index, measuring mental flexibility, in which MTLE patients performed significantly worse than FLE patients. Left-FLE patients presented more perseverative responding compared to both other patient groups and healthy controls (HCs), while left-MTLE patients showed worse sorting abilities than the other epilepsy groups. CONCLUSIONS: Our findings suggest a weak cognitive differentiation between FLE and MTLE, probably attributed to the intricate nature of fronto-temporal connectivity frequently resulting in overlapping deficits as well as the confounding effects of seizure-related variables. In clinical practice, a highly individualized (idiographic) neuropsychological approach along with the inclusion of concurrent EEG recordings (e.g., interictal coupling) may be of help for neuropsychologists in identifying FLE patients from those with medial temporal pathology presenting frontal dysfunction as a secondary cognitive symptom.

The persistent and broadly distributed EEG synchronization might inhibit the normal processing capability of the human brain.

Synchrony in the brain functioning describes the mode that the components are interacted and reflect the collective behaviour of neuronal assemblies. Nevertheless, the excessive and prolonged coupling among brain sites is relevant with disturbed information routing. In the present study we investigated the possibility that the sustained oscillatory states and the common mode in which several brain sites vary their functional connectivity inhibit the ability of the brain in perceiving and processing information. The hypothesis, that in many interacting systems, greater regularity-rhythmicity corresponds to grater component self-organization and isolation, is investigated in the case of thought blocks (under persistent auditory verbal hallucinations) and epileptic absences (under spike wave discharges). Our findings indicate that the observed common mode of coupling significantly restrains the normal flow of mental processes. This erroneous "connectivity mode" in the presence of symptoms such as thought blocks and absences respectively, was found to eliminate the spontaneous synchrony variability, essentially needed for the information processing, by fixating the functional specificity of the respected brain sites.

Episodic Visual Learning/Memory and Attentional Flexibility in Patients With Major Depressive Disorder After Clinically Effective Electroconvulsive Therapy.

OBJECTIVES: This study is a follow-up of a previous one reporting that the neuropsychological profile of pharmacoresistant patients with major depressive disorder referred for electroconvulsive therapy (ECT, ECT group) contrasted with that of their pharmacorespondent counterparts (NECT group). The NECT group exhibited severe visuospatial memory and minor executive deficits; the ECT group presented the reverse pattern. In that same ECT group, the current follow-up study examined the effects of clinically effective ECT on both cognitive domains 2 months later. METHODS: Fifteen ECT patients were administered Hamilton Depression (HAMD-24), Hamilton Anxiety (HAMA), Mini-Mental State Examination Scales and 5 tests of Cambridge Neuropsychological Test Automated Battery at intake (pre-ECT), end of ECT course (post-ECT), and 2 months thereafter (follow-up). RESULTS: Electroconvulsive therapy was effective in relieving clinical depression. After a post-ECT decline, the patients exhibited significant improvement in both Cambridge Neuropsychological Test Automated Battery, paired associate learning, and Stockings of Cambridge. By contrast, their major pre-ECT deficit in intra/extradimensional set shifting remained virtually unaffected. CONCLUSIONS: Our findings suggest that attentional flexibility deficits may constitute a neuropsychological trait-like feature of pharmacoresistant, ECT-referred major depressive disorder patients. However, this deficit does not seem generalized, given patient improvement in episodic visual learning/memory and some indication of improvement in spatial planning after ECT.

Influence of light exposure during early life on the age of onset of bipolar disorder.

BACKGROUND: Environmental conditions early in life may imprint the circadian system and influence response to environmental signals later in life. We previously determined that a large springtime increase in solar insolation at the onset location was associated with a younger age of onset of bipolar disorder, especially with a family history of mood disorders. This study investigated whether the hours of daylight at the birth location affected this association. METHODS: Data collected previously at 36 collection sites from 23 countries were available for 3896 patients with bipolar I disorder, born between latitudes of 1.4 N and 70.7 N, and 1.2 S and 41.3 S. Hours of daylight variables for the birth location were added to a base model to assess the relation between the age of onset and solar insolation. RESULTS: More hours of daylight at the birth location during early life was associated with an older age of onset, suggesting reduced vulnerability to the future circadian challenge of the springtime increase in solar insolation at the onset location. Addition of the minimum of the average monthly hours of daylight during the first 3 months of life improved the base model, with a significant positive relationship to age of onset. Coefficients for all other variables remained stable, significant and consistent with the base model. CONCLUSIONS: Light exposure during early life may have important consequences for those who are susceptible to bipolar disorder, especially at latitudes with little natural light in winter. This study indirectly supports the concept that early life exposure to light may affect the long term adaptability to respond to a circadian challenge later in life.

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.

Relationship between sunlight and the age of onset of bipolar disorder: an international multisite study.

BACKGROUND: The onset of bipolar disorder is influenced by the interaction of genetic and environmental factors. We previously found that a large increase in sunlight in springtime was associated with a lower age of onset. This study extends this analysis with more collection sites at diverse locations, and includes family history and polarity of first episode. METHODS: Data from 4037 patients with bipolar I disorder were collected at 36 collection sites in 23 countries at latitudes spanning 3.2 north (N) to 63.4 N and 38.2 south (S) of the equator. The age of onset of the first episode, onset location, family history of mood disorders, and polarity of first episode were obtained retrospectively, from patient records and/or direct interview. Solar insolation data were obtained for the onset locations. RESULTS: There was a large, significant inverse relationship between maximum monthly increase in solar insolation and age of onset, controlling for the country median age and the birth cohort. The effect was reduced by half if there was no family history. The maximum monthly increase in solar insolation occurred in springtime. The effect was one-third smaller for initial episodes of mania than depression. The largest maximum monthly increase in solar insolation occurred in northern latitudes such as Oslo, Norway, and warm and dry areas such as Los Angeles, California. LIMITATIONS: Recall bias for onset and family history data. CONCLUSIONS: A large springtime increase in sunlight may have an important influence on the onset of bipolar disorder, especially in those with a family history of mood disorders.