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.

Clinical Characteristics, Comorbid Medical Diagnoses, and Causes of Death of Individuals with Severe Mental Illness Who Died During Follow-up in Community Mental Health Centers: A Multicenter, Retrospective Study. / Toplum Ruh Sagligi Merkezlerinde Takipleri Sirasinda Ölen Siddetli Ruhsal Hastaligi Olan Bireylerin Klinik Özellikleri, Ek Tibbi Tanilari ve Ölüm Nedenleri: Çok Merkezli, Geriye Dönük Bir Arastirma.

OBJECTIVE: In this study, it was aimed to define the clinical characteristics, causes of death, disease and treatment of patients who died while being followed for severe mental illness. METHOD: The study was carried out in ten community mental health centers from six provinces. The clinical characteristics, causes of death, course of the illness and treatment characteristics of the patients who had a death report from the date the community mental health centers were opened until the start date of the study were analyzed by retrospective file scanning method. RESULTS: In an average of 52 months, files of 3715 patients were examined. There were death declarations for 106 patients. The diagnosis of most patients with death declarations was schizophrenia (78%), most of them were male (66%), mean age was 57, mean disease duration was 24 years. The rate of multiple antipsychotic medication use was 61%. The most common comorbidities were metabolic syndrome (36%), hypertension (22%), diabetes (18%) and chronic obstructive pulmonary disease (15%). The most frequently reported causes of death were cardiovascular diseases (39%), infectious diseases (14%) and cancer (11%). CONCLUSION: Individuals with severe mental illness followed up in community mental health centers are mostly die due to preventable natural causes of death. Therefore, a sensitive approach should be taken to evaluate psychiatric and other medical conditions together. In our country, there is a need for natural follow-up studies investigating the average age of death and causes of death of individuals with severe mental illness.

Does clozapine really affect bone mineral density? An experimental study.

PURPOSE: The aim of this study was to investigate the effect of clozapine use on bone tissue by applying computerized tomography, dual-energy X-ray absorptiometry, and histological and biomechanical analyses in an experimental rat model. METHODS: Sixteen female Wistar Albino rats were included in this study. These animals were divided into two groups: the control group and the clozapine group. The animals in the clozapine group received 10 mg/kg clozapine, and the animals in the control group received tap water by oral gavage daily for 28 days. After sacrification, the femurs of the rats were used for radiologic, histologic, dual-energy X-ray absorptiometry, and biomechanical evaluations. RESULTS: Although the mean values of the clozapine group were higher in terms of histological, bone mineral density, and biomechanical evaluations, the statistical analyses were not significantly different. CONCLUSION: Clozapine use did not affect bone density in the rats. Clozapine can be the preferred treatment for patients with schizophrenia to avoid osteoporosis. It will be necessary to conduct further long-term follow-up and controlled studies in animals and humans to confirm these findings.

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.

Predictors of discontinuation and hospitalization during long-acting injectable antipsychotic treatment in patients with schizophrenia spectrum disorder.

The aim of this study was to evaluate discontinuation and hospitalization rates in patients with schizophrenia spectrum disorder who were treated with long-acting injectable (LAI) antipsychotics. We recorded clinical data about the period before the LAI treatment, when LAI treatment was initiated, and during the LAI treatment. Variables related to early (<8 weeks) and other LAI discontinuations and hospitalization were analyzed. Out of 452 patients, 14.4% of them discontinued their LAI treatment before 8 weeks, another 24.8% of the patients stopped their LAI by themselves later. Early discontinuers were younger, had shorter duration of illness, and less educated. Sixty-two (27.2%) of the patients were hospitalized under LAI treatment and 40% of the hospitalizations occurred in initial 6 months. Rate of hospitalization was 36.1% in the group who discontinued LAI after 8 weeks. In logistic regression analysis, younger age, history of combined antipsychotic treatment, number of hospitalizations before LAI, use of LAI for less than 6 months and alcohol abuse under LAI treatment were found related to hospitalization. Our findings suggested that discontinuation and hospitalization are still common among the patients who were treated with LAI antipsychotics.

Evaluation of the relationship between perceived social support, coping strategies, anxiety, and depression symptoms among hospitalized COVID-19 patients.

OBJECTIVE: We aimed to evaluate the relationship between perceived social support, coping strategies, anxiety, and depression symptoms among hospitalized COVID-19 patients by comparing them with a matched control group in terms of age, gender, and education level. METHOD: The patient group (n = 84) and the healthy controls (HCs, n = 92) filled in the questionnaire including the socio-demographic form, Hospital Anxiety Depression Scale, Multidimensional Perceived Social Support Scale, and Brief Coping Orientation to Problems Experienced through the online survey link. RESULTS: The COVID-19 patients had higher perceived social support and coping strategies scores than the HCs. However, anxiety and depression scores did not differ significantly between the two groups. In logistic regression analysis performed in COVID-19 patients, the presence of chest CT finding (OR = 4.31; 95% CI = 1.04-17.95) was a risk factor for anxiety and the use of adaptive coping strategies (OR = 0.86; 95% CI = 0.73-0.99) had a negative association with anxiety. In addition, the use of adaptive coping strategies (OR = 0.89; 95% CI = 0.79-0.98) and high perceived social support (OR = 0.97; 95% CI = 0.93- 0,99) had a negative association with depression symptoms. CONCLUSIONS: Longitudinal studies involving the return to normality phase of the COVID-19 pandemic are needed to investigate the effects of factors such as coping strategies and perceived social support that could increase the psychological adjustment and resilience of individuals on anxiety and depression.

Examination of Patients' Regular Participation at an Obesity Center to Evaluate the Effects on Mental Status and Blood Parameters.

BACKGROUND: Obesity is the main cause of type 2 diabetes, coronary artery disease, musculoskeletal disorders, some cancers, and mental disorders, and many other diseases leading to mortality. The aim of this study was to determine the effects of participation in an obesity center on patient mental status and blood parameters within 3 months and to show the relationship of this participation with depression, anxiety, and other parameters. METHODS: This was a descriptive and cross-sectional study. Of 2,591 patients admitted to an obesity center between November 1, 2018 and November 1, 2019, 317 met the inclusion criteria. This study was a descriptive and cross-sectional study of the data from those 317 patients. RESULTS: Of the patients enrolled in the study, 90.5% were female and 9.5% were male. Weight, occupation, body mass index, body fat percentage, waist circumference, hip circumference, glycosylated hemoglobin (HbA1c), Beck Depression Scale, and Beck Anxiety Scale were important determinants in our univariate analyses associated with the regular receipt of center education. HbA1c (odds ratio, 1.661; 95% confidence interval, 1.140-2.421; P=0.008) was shown to be multivariate predictors of amount of participation in center education. CONCLUSION: These results support that regular participation in obesity center education has a positive effect on patients mental status, blood parameters, and anthropometric measurements. Thus, increasing the number of obesity centers is of great importance in treating obesity and improving obese patient mental status.

A Case of Gitelman Syndrome Diagnosed with Anorexia Nervosa in a Psychiatry Clinic. / Psikiyatri Kliniginde Tani Konulan Anoreksiya Nervoza Görünümlü Gitelman Sendromu.

Anorexia nervosa is a disorder that is characterized by excessive preoccupation with body weight and shape, and conscious attempts to stay in low weight due to fear of weight gain. Vomiting, one of the METHODS used by anorexia nervosa patients to stay in low weight, is one of the most important causes of hypokalemia. Diuretics and diarrhea are other common causes of hypokalemia. If hypokalemia is chronic and resistant to treatment, eating disorders and other metabolic conditions should be investigated. One of the rare causes of hypokalemia, an electrolyte imbalance that can cause fatal outcomes, is Gitelman syndrome. Gitelman Syndrome is a genetically inherited disease of the distal tubules which causes hypokalemia, metabolic alkalosis, hypocalcemia, hypomagnesemia and vomiting. It is a syndrome usually diagnosed during adolescence, however it sometimes remains asymptomatic throughout life. Severe symptoms such as tetanus, rhabdomyolysis, and paralysis can also be seen. A case of Gitelman syndrome which was diagnosed as anorexia nervosa due to physical appearance of the patient, low body mass index (BMI), and frequent vomiting and in which the other medical pathologies have not been adequately investigated is presented in this article. Assessments to exclude the medical conditions that may be associated with symptoms are necessary before a diagnosis of a psychiatric disorder is made.

Correlation between vaspin and PANSS scores in schizophrenia patients with obesity.

OBJECTIVE: Metabolic abnormalities such as diabetes, dyslipidemia, abdominal obesity, metabolic syndrome, and abnormal levels of plasma adipokines have been observed in patients with schizophrenia. This study aimed to investigate the differences and correlations of plasma vaspin levels with metabolic parameters in patients with schizophrenia and to compare with healthy controls. METHOD: We measured plasma levels of vaspin and metabolic parameters of 100 patients with schizophrenia and 95 healthy controls. Patients with schizophrenia were evaluated with the Positive and Negative Syndrome Scale (PANSS) and The Global Assessment of Functioning. RESULTS: Mean levels of body mass index, waist circumference, triglyceride, and low-density lipoprotein cholesterol of the patients were statistically higher than those of the healthy controls (p = 0.002, p < 0.001, p = 0.03, and p = 0.002, respectively). Plasma levels of vaspin were 0.96 ± 0.73 ng/ml in patients with schizophrenia and 0.29 ± 0.15 ng/ml in the healthy controls (p < 0.001). Plasma vaspin levels were statistically higher in patients with schizophrenia than healthy controls both in groups with and without metabolic syndrome and obesity (p < 0.001). Plasma vaspin levels showed a positive correlation with triglyceride in patients with schizophrenia (r = 0.26, p = 0.007). There were positive correlations between vaspin and PANSS scores in schizophrenia patients with obesity (PANSS Positive: r = 0.42, p = 0.01; PANSS Negative: r = 0.42, p = 0.01; PANSS General: r = 0.43, p = 0.01; PANSS Total: r = 0.47, p = 0.006). CONCLUSIONS: Our study showed a significant relationship and positive correlation between vaspin and PANSS scores in schizophrenia patients with obesity. Vaspin may play an important role in the metabolic processes of patients with schizophrenia.

The relationship between serum clozapine concentrations and hematological parameters by a validated mass spectrometric method.

OBJECTIVE: Clozapine is one of the most effective drugs for resistant schizophrenia, but its severe metabolic and hematological side effects limit the use of clozapine. It has been reported that clozapine blood concentrations should be maintained between 350-600 ng/mL. Our aim was to develop a determination method for clozapine and its main metabolites norclozapine and clozapine-N-oxide, to perform validation studies and to investigate the change of various biochemical parameters in patients using clozapine. METHODS: A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for clozapine measurement. Thus, blood samples were collected from 38 patients with schizophrenia and 32 healthy volunteers. Biochemical and hematological parameters were measured by Beckman-Coulter AU 5800 (Beckman Coulter, Brea, USA) and Beckman Coulter LH 780 analyzer (Beckman Coulter, Miami, FL, USA), respectively. Hormone levels were analyzed using Cobas 6000 analyzer (Roche Diagnostics, Germany). RESULTS: The LCMS/MS method was linear between 1.22-2500 ng/mL (r2 = 0.9971) for clozapine. The retention times of clozapine, norclozapine and clozapine-N-oxide were 0.92, 0.89 and 0.95, respectively. Blood glucose (GLU) (p = 0.025), low density lipoprotein (LDL-cholesterol) (p = 0.015), triglyseride (TG) (p = 0.042) and total cholesterol (TC) (p = 0.024) levels were higher; hemoglobin (HGB) (0.015), mean corpuscular hemoglobin (MCH) (0.036), red blood cell count (RBC) (0.020), neutrophil (NEU) (0.034), and platelet (PLT) (P = 0.005) levels were lower in the clozapine group. CONCLUSIONS: This LC-MS/MS method was rapid, simple, cost-effective and suitable for the routine clozapine monitoring. Furthermore, norclozapine and clozapine-N-oxide were also determined. Monitoring of metabolic and hematological parameters with clozapine levels is very important. However, the limitations of the study were that the method was not validated for norclozapine and clozapine-N-oxide, so the validation parameters were not evaluated for these two metabolites.

Neutrophil/lymphocyte ratio, monocyte/lymphocyte ratio, and mean platelet volume as systemic inflammatory markers in different states of bipolar disorder.

Background: Currently, increasing evidence supports the hypothesis that alterations in the immune-inflammatory system are critical for the pathophysiology of bipolar disorder (BD). Neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), and mean platelet volume (MPV) have recently been investigated as inexpensive and simple inflammatory markers. Aims: The aim of this study is to compare NLR, PLR, MLR, and MPV in depressive, manic, and euthymic patients with BD and healthy controls, and to evaluate whether values of NLR, PLR, MLR, and MPV are possible state or trait biomarkers in BD. Methods: This retrospective study was conducted with 341 patients with BD (100 patients in a depressive state, 141 patients in a manic state, and 100 patients in a euthymic state) and 114 healthy controls. Results: We found that patients with BD in manic states had higher levels of MPV, NLR, and MLR, and patients with BD in depressive states had higher levels of MPV than the controls. Moreover, MPV predicted all states of BD, while NLR and MLR predicted the manic state of BD. Conclusions: NLR, MLR, and MPV obtained from simple and inexpensive blood tests were significantly higher in patients with BD than in healthy controls, which each imply low-grade inflammation. MPV may serve as a possible trait biomarker of BD, while NLR and MLR may both serve as possible state biomarkers of the manic state.

Suicide attempts and related factors in schizophrenia patients.

OBJECTIVES: To investigate the relationship between suicide attempts and demographic-clinical variables and to assess the methods used in suicide attempts by comparing schizophrenia patients with and without suicide attempts. METHODS: A retrospective study with a total of 223 schizophrenia patients aged 18-65 years that were admitted to the Department of Psychiatry, Selcuk University and the Beyhekim Psychiatric Clinic Konya Training and Research Hospital, Konya, Turkey, between January 2014 and January 2018. The data collection forms created by researchers were completed using hospital medical records. Results: It was determined that 40.8% of schizophrenia patients attempted suicide at least once and that 39.6% of schizophrenia patients who attempted suicide had recurrent suicide attempts. Those with suicide attempts had a significantly longer mean duration of untreated psychosis and a higher total number of hospitalizations compared to those without suicide attempts. In addition, the use of depot antipsychotic drugs was significantly lower in those with suicide attempts. There was a statistically significant difference in the presence of traumatic life events between those with and without suicide attempts. Conclusion: Suicidal behavior is an important problem in schizophrenia. Identifying risk factors and high-risk individuals will guide us in the development of preventive interventions.

Continuing clozapine treatment with lithium in schizophrenic patients with neutropenia or leukopenia: brief review of literature with case reports.

OBJECTIVE: Clozapine is a second-generation antipsychotic used for treatment-resistant schizophrenia. Despite its effectiveness, clozapine is largely underused due to serious side effects such as leukopenia or neutropenia. We aimed to review whether to continue, discontinue or rechallenge clozapine treatment after such haematological side effects. METHODS: We reviewed and summarized the literature on the use of clozapine, how to deal with its side effects, and suitable options in case of any haematological problems. Then, we described several cases successfully treated with clozapine and lithium after development of neutropenia or leukopenia. RESULTS: We present three patients with treatment-resistant schizophrenia. While they had demonstrated poor response to multiple antipsychotic trials, clozapine was started. Clozapine induced neutropenia; or leukopenia developed in some cases that was successfully reversed after lithium onset. Increased serious side effects related with coprescription of lithium and clozapine were not observed. CONCLUSION: Lithium increases neutrophil and total white blood cell count as a side effect that may be useful in patients who develop neutropenia or leukopenia while being treated with clozapine.

Injury patterns and psychological traits of patients with self-inflicted wounds produced by punching glass.

BACKGROUND: Self-inflicted injuries are among the preventable forms of hand injury. Psychologic factors underlying these injuries have not been studied sufficiently. This study aims to reveal the extent of injury and the morbidity as well as the psychologic factors in a population of patients who intentionally injured themselves by punching glass. METHODS: Patients seen and treated for glass punching injuries during a 4.5-year period were reviewed. The demographic data included the extent of injury, postoperative hospitalization time, and full recovery time. Their psychologic traits were analyzed by two questionnaires (Symptom Distress Check List and State-Trait Anger Expression Inventory) and through a psychiatric interview. The results were compared with a sex- and age-matched control group with accidental hand injuries. RESULTS: The study group consisted of 36 patients. Mean age was 24.7 years. Most were men (n = 28), not married (n = 28), and living with their families. Half of them were unemployed. Twelve had only skin lacerations. The remaining 24 patients had a total of 45 tendon, 15 nerve, and 9 artery injuries. On an average, 46 days were required for full recovery. A second attempt of self-infliction was not reported. Twenty-one patients underwent questionnaires and psychiatric interview. The study group felt significantly higher levels of psychologic distress and hostility (p = 0.018 and p = 0.002, respectively). They also had higher levels of anger in daily life (p = 0.002). Clinical psychiatric evaluation failed to reveal any significant psychiatric disorder. CONCLUSION: Self-inflicted hand injuries increase the workload of emergency services and clinics involved in the treatment. Prevention is very difficult, especially when alcohol is not an underlying cause. A typical patient has hostile and disobedient characteristics and who easily expresses his anger. Happily, having suffered enough during their treatment these patients do not attempt a second self-infliction.