Differential effects of high-fat diet on endocrine, metabolic and depressive-like behaviors in male and female rats.

The complications of obesity extend beyond the periphery to the central nervous system (CNS) and include an increased risk of developing neuropsychiatric co-morbidities like depressive illness. Preclinical studies support this concept, including studies that have examined the effects of a high-fat diet (HFD) on depressive-like behaviors. Although women are approximately two-fold more likely to develop depressive illness compared to men, most preclinical studies have focused on the effects of HFD in male rodents. Accordingly, the goal of this study was to examine depressive-like behaviors in male and female rats provided access to a HFD. In agreement with prior studies, male and female rats provided a HFD segregate into an obesity phenotype (i.e., diet-induced obesity; DIO) or a diet resistant (DR) phenotype. Upon confirmation of the DR and DIO phenotypes, behavioral assays were performed in control chow, DR, and DIO rats. In the sucrose preference test, male DIO rats exhibited significant decreases in sucrose consumption (i.e., anhedonia) compared to male DR and male control rats. In the forced swim test (FST), male DIO rats exhibited increases in immobility and decreases in climbing behaviors in the pre-test sessions. Interestingly, male DR rats exhibited these same changes in both the pre-test and test sessions of the FST, suggesting that consumption of a HFD, even in the absence of the development of an obesity phenotype, has behavioral consequences. Female rats did not exhibit differences in sucrose preference, but female DIO rats exhibited increases in immobility exclusively in the test session of the FST, behavioral changes that were not affected by the stage of the estrous cycle. Collectively, these studies demonstrate that access to a HFD elicits different behavioral outcomes in male and female rats.

Impact of mood stabilizers on creativity.

OBJECTIVE: While a DSM-5 criterion for both hypomania and mania is impaired functioning, the majority of those with a bipolar condition report improved functioning. When offered a mood stabilizer, many express concerns about any impact on their creativity. This piece seeks to address the question and attendant issues. METHOD: Reference is made to the impact of differing mood stabilizers on cognitive performance and the limited data on any specific impact on creativity, while some personal observations are offered. RESULTS: There appears to be a distinctive gradient in the cognitive impacts of differing mood stabilizers, with lithium offering the highest risk, carbamazepine and valproate providing a slight risk, and lamotrigine seemingly without cognitive side-effects. CONCLUSIONS: The question not only invites a nuanced response from the clinician but argues for close observation of any cognitive side-effects when lithium is introduced.

A structural basis for lithium and substrate binding of an inositide phosphatase.

Inositol polyphosphate 1-phosphatase (INPP1) is a prototype member of metal-dependent/lithium-inhibited phosphomonoesterase protein family defined by a conserved three-dimensional core structure. Enzymes within this family function in distinct pathways including inositide signaling, gluconeogenesis, and sulfur assimilation. Using structural and biochemical studies, we report the effect of substrate and lithium on a network of metal binding sites within the catalytic center of INPP1. We find that lithium preferentially occupies a key site involved in metal-activation only when substrate or product is added. Mutation of a conserved residue that selectively coordinates the putative lithium-binding site results in a dramatic 100-fold reduction in the inhibitory constant as compared with wild-type. Furthermore, we report the INPP1/inositol 1,4-bisphosphate complex which illuminates key features of the enzyme active site. Our results provide insights into a structural basis for uncompetitive lithium inhibition and substrate recognition and define a sequence motif for metal binding within this family of regulatory phosphatases.

A neuropsychological study on Leonhard's nosological system.

Phenotype validation of endogenous psychosis is a problem that remains to be solved. This study investigated the neuropsychological performance of endogenous psychosis subtypes according to Wernicke-Kleist-Leonhard's classification system (WKL). The participants included consecutive admissions of patients with schizophrenia spectrum disorder or mood disorder with psychotic symptoms (N = 98) and healthy comparison subjects (N = 50). The patients were assessed by means of semi-structured interviews and diagnosed through the WKL system into three groups: a manic-depressive illness and cycloid psychosis group (MDC), unsystematic schizophrenia (USch) and systematic schizophrenia (SSch). All the participants completed a comprehensive neuropsychological battery. The three Leonhard's psychosis subtypes showed a common neuropsychological profile with differences in the severity of impairment relative to healthy controls. MDC patients showed better performance on premorbid intelligence, verbal memory and global cognitive index than USch and SSch patients, and they showed better performance on processing speed, and working memory than SSch patients. USch patients outperformed SSch patients in verbal memory, working memory and global cognitive index. Neuropsychological performance showed a modest accuracy for classification into the WKL nosology. Our results suggest the existence of a common profile of cognitive impairment cutting across WKL subtypes of endogenous psychosis but with significant differences on a severity continuum. In addition, classification accuracy in the three WKL subtypes by means of neuropsychological performance was modest, ranging between 40 and 64% of correctly classified patients.

Co-occurrence across time and space of drug- and cannabinoid- exposure and adverse mental health outcomes in the National Survey of Drug Use and Health: combined geotemporospatial and causal inference analysis.

BACKGROUND: Whilst many studies have linked increased drug and cannabis exposure to adverse mental health (MH) outcomes their effects on whole populations and geotemporospatial relationships are not well understood. METHODS: Ecological cohort study of National Survey of Drug Use and Health (NSDUH) geographically-linked substate-shapefiles 2010-2012 and 2014-2016 supplemented by five-year US American Community Survey. Drugs: cigarettes, alcohol abuse, last-month cannabis use and last-year cocaine use. MH: any mental illness, major depressive illness, serious mental illness and suicidal thinking. DATA ANALYSIS: two-stage, geotemporospatial, robust generalized linear regression and causal inference methods in R. RESULTS: 410,138 NSDUH respondents. Average response rate 76.7%. When drug and sociodemographic variables were combined in geospatial models significant terms including tobacco, alcohol, cannabis exposure and various ethnicities remained in final models for all four major mental health outcomes. Interactive terms including cannabis were related to any mental illness (ß-estimate = 1.97 (95%C.I. 1.56-2.37), P <  2.2 × 10- 16), major depressive episode (ß-estimate = 2.03 (1.54-2.52), P = 3.6 × 10- 16), serious mental illness (SMI, ß-estimate = 2.04 (1.48-2.60), P = 1.0 × 10- 12), suicidal ideation (ß-estimate = 1.99 (1.52-2.47), P <  2.2 × 10- 16) and in each case cannabis alone was significantly associated (from ß-estimate = - 3.43 (- 4.46 - -2.42), P = 3.4 × 10- 11) with adverse MH outcomes on complex interactive regression surfaces. Geospatial modelling showed a monotonic upward trajectory of SMI which doubled (3.62 to 7.06%) as cannabis use increased. Extrapolated to whole populations cannabis decriminalization (4.26%, (4.18, 4.34%)), Prevalence Ratio (PR) = 1.035(1.034-1.036), attributable fraction in the exposed (AFE) = 3.28%(3.18-3.37%), P < 10- 300) and legalization (4.75% (4.65, 4.84%), PR = 1.155 (1.153-1.158), AFE = 12.91% (12.72-13.10%), P < 10- 300) were associated with increased SMI vs. illegal status (4.26, (4.18-4.33%)). CONCLUSIONS: Data show all four indices of mental ill-health track cannabis exposure across space and time and are robust to multivariable adjustment for ethnicity, socioeconomics and other drug use. MH deteriorated with cannabis legalization. Cannabis use-MH data are consistent with causal relationships in the forward direction and include dose-response and temporal-sequential relationships. Together with similar international reports and numerous mechanistic studies preventative action to reduce cannabis use is indicated.

'My insanity in the year 1783', by C.S. Andresen (1801).

The literature of the past has included self-reports by the mentally ill since before Roy Porter reminded us that their views and experiences constitute an important document for historians of psychiatry. The value of these self-reports can be enhanced if their potential biases and informational power are duly determined. This Classic Text concerns a self-report of a form of periodic madness written by an eighteenth-century Danish vicar. It shows how the same document can be presented in a more or less neutral fashion by a medical historian (Maar) or used as 'evidence' for some 'ontological' view of madness by a clinician (Rasmussen).

Exercise and mental health literacy in an Australian adult population.

BACKGROUND: Exercise is a well-established treatment for depression, and its use in clinical care is supported by consumers and clinicians. However, whether public health messages regarding the benefits of exercise for depression have translated to public knowledge remains unknown. This study aims to examine the community's mental health literacy, and views regarding exercise delivery for people with depression. METHODS: A vignette was presented as part of the telephone-based 2017 National Social Survey (n = 1,265). Interviewees identified what (if anything) was wrong with the person described, who they should seek help from, whether exercise might be beneficial, and how exercise should be delivered for the person described in the vignette. Results are reported using descriptive statistics. RESULTS: From 1,265 respondents (response rate = 24%, n = 598 males, mean age 54.7 years [range 18-101]), almost two-thirds correctly identified the condition described in the vignette as depression. There was widespread support for seeking help from a general practitioner. Exercise was well supported in the treatment of the person described in the vignette, with general practitioners and accredited exercise physiologists highlighted as persons to consult regarding exercise. Views regarding the type of program were consistent with current best practice recommendations. CONCLUSIONS: Australian adults demonstrate a high level of exercise and mental health literacy. The high level of support for accredited exercise physiologists is evidence of the effectiveness of health promotion campaigns from peak exercise professional agencies.

Max Scheler's influence on Kurt Schneider.

Kurt Schneider (1887-1967) met Max Scheler (1874-1928) in 1919 when he enrolled in the latter's philosophy seminars at the University of Cologne. Kurt Schneider was then a junior psychiatrist and Max Scheler a renowned philosophy professor and co-founder of the phenomenological movement in philosophy. We uncover the facts about their intellectual and personal relationship, summarize the main articles and books that they wrote and consider whether Max Scheler did influence the young Kurt Schneider. We conclude that Scheler's philosophy of emotion impressed Schneider, and that the latter's notion of 'vital depression' as the core element in melancholia was essentially applied Schelerian philosophy. Schneider's more celebrated contributions to psychiatry - his notion of first rank symptoms of schizophrenia - owed nothing to Scheler or any other philosopher.

Max Scheler's theory of the hierarchy of values and emotions and its relevance to current psychopathology.

The philosopher Max Scheler (1874-1928) set out a hierarchical theory of values and emotions in the early twentieth century. This inspired Kurt Schneider to distinguish two sorts of depressive illness, each conforming to a Störung (disorder) in different levels of Scheler's hierarchy. No other psychopathologist, except Stanghellini, gave the matter much attention. I believe that Scheler's theory is a rich source of insight into psychopathology, general and neuropsychiatric. I therefore give an account of Scheler's scheme, review its extant applications (Schneider's, Stanghellini's), and present suggestions as to its continuing potential relevance in a wide range of psychopathological conditions.

Bipolar disorder and its outcomes: two cohorts, 1875-1924 and 1994-2007, compared.

We compared admission rates and outcomes for bipolar disorder patients using the medical records of patients with a first hospital admission in 1875-1924 retrospectively diagnosed based on International Classification of Diseases (ICD)-10 criteria, and patients with a first admission in 1994-2007. The incidences of first admissions in the historical and contemporary periods are comparable: 1.2 and 1.3 per hundred thousand per year, respectively. Manic episodes constituted a greater proportion of admissions historically, while depressive episodes made up more in the contemporary sample. There is no evidence for a reduction in the mean inter-admission intervals with duration of illness. This study suggests that modern treatments may have decreased lengths of stay in hospital, but at a cost of contributing to more admissions. It also points to a shift in the threshold for admissions.

Correlates of depressive illness among the elderly in a mixed urban community in Lagos, Nigeria.

OBJECTIVES: Little is known about the factors associated with depression among elderly Nigerians despite research evidence suggesting that some correlates of depression may be important in early detection, treatment and prognosis. This study aimed to determine the correlates of depression among a community based elderly population. METHODS: The study population made up of 350 consenting participants was selected using multistage stratified random sampling technique. Face-to-face interviews were conducted among the participants using a research instrument consisting of two parts: a self-designed questionnaire to elicit their socio-demographic profile, level of social support as well as their health status and the 30-item Geriatric Depression Scale to diagnose depression using cut-off score ≥11. Both the English and Yoruba versions of the study instruments were used depending on the level of education of the participants. RESULTS: Depression was found to be associated with being younger old (χ(2) = 6.19, p = 0.045), prolonged stay in current residence (χ(2) = 6.62, p = 0.01), living in less developed area of the community and not having children (χ(2) = 0.03, p = 0.01), while higher social support (χ(2) = 4.19, p = 0.041) seems protective. However, only low social support (odds ratio [OR] = 0.573; 95% confidence interval [CI], 0.330-0.994; p = 0.048), living in less developed area (OR = 5.342; 95% CI = 1.027, 27.776; p = 0.046) and prolonged stay in current residence (OR = 0.407; 95% CI = 0.205, 0.806; p = 0.01) independently predicted depression in participants. CONCLUSION: To enhance early detection and treatment of depressive disorders in the elderly, physicians should be alert to the diagnosis of depression in late life, especially among the younger old, elderly not having children, those with low social support as well as prolonged stay in a residence and living in less developed parts of the community. Further research is needed to shed light on the intriguing link between depression and associated factors in geriatric population.

Prevalence of depression, quality of life and antidepressant treatment in the Danish General Suburban Population Study.

BACKGROUND: The Danish General Suburban Population Study (GESUS), the objective of which is to facilitate epidemiological and genetic research, has included the Major Depression Inventory (MDI) and the WHO-Five Well-Being Index (WHO-5) among the medical health questionnaires. We were thus in a position to compare the 2-week prevalence of ICD-10 depression in the period from 2010 to 2012 with our previous Danish general population study from 2003, in which the MDI was also included. AIMS: The aim of our analysis was not only to evaluate the point prevalence of ICD-10 depression but also to describe the prevalence of antidepressants received by the respondents in the GESUS study and the correspondence to their subjective well-being on the WHO-5 questionnaire. METHODS: To evaluate the validity (scalability) of the MDI and the WHO-5 in the GESUS study we performed the non-parametric Mokken analysis. The scalability of the MDI and the WHO-5 was quite acceptable. RESULTS: In total, 14,787 respondents were available from a response rate of 50%. The 2-week prevalence of ICD-10 depression was 2.3%, which is rather similar to the 2.8% in our 2003 study. The rate of people receiving antidepressants increased consistently with increasing severity of ICD-10 depression. CONCLUSION: This study has confirmed that the use of the MDI to obtain an ICD-10 depression diagnosis gives rather conservative estimates of the 2-week prevalence of depression in the Danish general population. The prescription of antidepressants depends on the severity of the ICD-10 depression diagnosis.

Confluence of Challenges: A Case Report of Superior Mesenteric Artery Syndrome Coexisting With Depressive Illness, Severe Weight Loss, and an Incidental Adnexal Cyst.

In the case of a 24-year-old woman experiencing depressive illness, weight loss, vomiting, and hypoglycemia, initial suspicion of gastroenteritis shifted to reveal compensated metabolic acidosis and electrolyte imbalances. A subsequent CT scan revealed both superior mesenteric artery (SMA) syndrome and an incidental adnexal cyst, leading to treatment involving electrolyte correction and laparoscopic duodenojejunostomy, ultimately facilitating her recovery.

An Evaluation of the Effectiveness of Repetitive Transcranial Magnetic Stimulation (rTMS) for the Management of Treatment-Resistant Depression with Somatic Attributes: A Hospital-Based Study in Oman.

Depressive illnesses in non-Western societies are often masked by somatic attributes that are sometimes impervious to pharmacological agents. This study explores the effectiveness of repetitive transcranial magnetic stimulation (rTMS) for people experiencing treatment-resistant depression (TRD) accompanied by physical symptoms. Data were obtained from a prospective study conducted among patients with TRD and some somatic manifestations who underwent 20 sessions of rTMS intervention from January to June 2020. The Hamilton Rating Scale for Depression (HAMD) was used for clinical evaluation. Data were analysed using descriptive and inferential techniques (multiple logistic regression) in SPSS. Among the 49 participants (mean age: 42.5 ± 13.3), there was a significant reduction in posttreatment HAMD scores compared to baseline (t = 10.819, p < 0.0001, and 95% CI = 8.574-12.488), indicating a clinical response. Approximately 37% of the patients responded to treatment, with higher response rates among men and those who remained in urban areas, had a history of alcohol use, and were subjected to the standard 10 HZ protocol. After adjusting for all extraneous variables, the rTMS protocol emerged as the only significant predictor of response to the rTMS intervention. To our knowledge, this is the first study to examine the effectiveness of rTMS in the treatment of somatic depression.

Measurement of Noradrenaline and Serotonin Metabolites With Internal Jugular Vein Sampling: An Indicator of Brain Monoamine Turnover in Depressive Illness and Panic Disorder.

In research spanning three decades we have estimated brain monoamine turnover (approximately equating with synthesis rate) with sampling from the internal jugular veins and measurement of trans-cerebral plasma monoamine metabolite concentration gradients. Here we report indices of brain noradrenaline and serotonin turnover in patients with major depressive illness (MDD) and panic disorder (PD). Brain noradrenaline turnover was assessed from the combined flux into the internal jugular veins of the metabolites dihydroxyphenylglycol (DHPG) and 3-hydroxy-4-methoxyphenylglycol (MHPG), and brain serotonin turnover from the overflow of the primary metabolite, 5-hydroxyindole acetic acid (5HIAA). Comparison was made with matched healthy research participants. In both MD and PD the estimate of brain noradrenaline turnover provided by metabolite overflow was unremarkable. In contrast, in both patient groups the estimate of brain serotonin turnover provided by 5HIAA overflow was increased 3-4-fold (P < 0.01). This neurotransmitter abnormality was normalized in MDD and PD in clinical remission, during selective serotonin reuptake blocker (SSRI) dosing. We cannot be sure if the brain serotonergic abnormality we find in MDD and PD is causal or a correlate. Measurements in PD were not made during a panic attack. The increased estimated serotonin turnover here may possibly be a substrate for panic attacks; serotonergic raphe nuclei participate in anxiety responses in experimental animals. It is puzzling that the findings were identical in MDD and PD, although it may be pertinent that these psychiatric diagnoses are commonly comorbid. It is unlikely that activation of brain serotonergic neurons is driving the sympathetic nervous activation present, which contributes to cardiovascular risk, persistent sympathetic activation in MDD and episodic activation in PD during panic attacks. We have previously demonstrated that the mechanism of activation of human central sympathetic outflow in other contexts (hypertension, heart failure) is activation of noradrenergic brainstem neurons projecting to the hypothalamus and amygdala.

Prevalence and factors associated with depressive illness in patients with tuberculosis in Mulago hospital, Kampala- Uganda: A cross sectional study.

BACKGROUND: Depression is a major cause of the global disease burden and globally affects 350-400 million persons making it the largest contributor to years lived with disability. Among of patients with chronic physical illnesses like tuberculosis, depression affects up to 25-33% of individuals. There are limited studies on the comorbidity of depressive illness and tuberculosis in the Ugandan setting. Our aim was to determine the prevalence and factors associated with depressive illness in patients with tuberculosis in Mulago Hospital, Uganda. METHODS: This was a cross sectional study involving 308 consecutively sampled participants aged 18 years and above diagnosed with tuberculosis attending the tuberculosis clinic in Mulago Hospital, Uganda. Consecutive sampling was done for a sample size of 308 participants. Participants had the following instruments administered to them; the Socio-demographic questionnaire, the Mini Neuropsychiatric Interview (MINI) to diagnose depressive illness and the Patient Health Questionnaire- 9 to rate the severity of depression. Data was entered using Epi-Data. Descriptive, bivariate and multivariate analyses were done with the Statistical Package for Social Sciences (SPSS). RESULTS: the prevalence of depressive illness was 23.7% (95% confidence interval 19.3-28.9). Depressive illness was independently associated with low education level (AOR = 0.39, 95%CI = 0.21-0.72, p = 0.003), being in the intensive phase of TB treatment (AOR = 2.34, 95%CI = (1.27-4.33), p = 0.007) and family history of depressive illness (AOR = 5.42, 95%CI = 2.02-14.54, p = 0.001). On the PHQ, 60.3% had moderate to severe depression. CONCLUSION: Depressive illnesses should be screened and managed among patients with TB. RECOMMENDATION: Depression should be routinely screened and managed among patients with Tuberculosis.

Mixed States: Historical Impact and Evolution of the Concept.

Mixed states have been discussed for more than 2 millennia. The theoretic conception of the coexistence of presumably opposite symptoms of mood or of different psychic domains is well established, although obscured by the presumed separation between bipolar and depressive disorders. Moreover, the lack of response to treatments and severe psychopathology raise important issues requiring urgent solution. The aim of this article was to review the development of the concept of mixed states from the classic literature to modern nosologic systems and to claim for the need of a new paradigm to address the still-open issues about mixed states.

Pharmacological interventions for prevention of depression in high risk conditions: Systematic review and meta-analysis.

BACKGROUND: Background Depressive disorders account for almost half of all Disability Adjusted Life Years caused by psychiatric disorders but efficacy of pharmacological interventions to prevent depressive disorders is not known. We aimed to assess efficacy of pharmacological treatments in prevention of depression. METHODS: We searched PubMed, Psych Info, EMBASE, and CINHAL from 1980 to January 2020 and bibliographies of relevant systematic reviews. We selected randomised controlled trials (RCTs) that used a pharmacological intervention to prevent the onset of the new depressive episode in adult population. Study selection, data extraction and reporting was done following PRISMA guidelines. Data were pooled using random-effects meta-analysis. RESULTS: 28 trials (2745 participants) were included in meta-analysis. Antidepressants (22 studies), Selenium, Hormone Replacement Therapy Omega-3 fatty acids and Melatonin were used to prevent depression, mostly in physical conditions associated with high risk of depression. All pharmacological interventions [pooled Odds Ratios (OR) 0.37 CI (0.25-0.54)], and antidepressants (OR 0.29, 95% CI: 0.18, 0.46) were significantly more effective than placebo in preventing depression. Antidepressants were significantly better than placebo in trials that had low risk of bias (n = 16; OR 0.43 [0.30, 0.60]), in preventing post stroke depression (OR = 0.16, 95% CI: 0.05, 0.55) and depression associated with Hepatitis C (OR = 0.56, 95% CI: 0.31, 1.02). Limitations include small number of studies focussed only on high risk conditions and short follow up in most studies. CONCLUSIONS: Prevention of depression may be possible in patients who have high-risk conditions such as stroke but the strategy requires complete risk and benefits analysis before it can be considered for clinical practice.

Psychosocial correlates of medication adherence in patients with depressive illness.

INTRODUCTION: Nonadherence to medication is common in depressive illness and the same may lead to increased risk of relapse, morbidity, burden of care, and avoidable health cost. Factors which may cause nonadherence are multiple. METHODOLOGY: A study was undertaken to appreciate the role of various psychosocial factors in adherence to various antidepressant medication in the patients of depressive disorder. One hundred and fifty patients after due consent were subjected to medico-psychosocial-structured per forma, Beck's Depression Inventory, The Belief About Medicines Questionnaire, and the Morisky Medication Adherence Scale. RESULTS: Nonadherence to antidepressant medication in our study was 73.33%. Characteristics of the disease, disease therapies, patient-associated aspects including beliefs, and social and economic support did affect medication adherence. CONCLUSION: Nonadherence to medication was common in patients with depressive illness. Finding emphasizes the need to sensitize the patients about the importance of proper adherence.