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Obesity is highly prevalent and disabling, especially in individuals with severe mental illness including bipolar disorders (BD). The brain is a target organ for both obesity and BD. Yet, we do not understand how cortical brain alterations in BD and obesity interact.
We obtained body mass index (BMI) and MRI-derived regional cortical thickness, surface area from 1231 BD and 1601 control individuals from 13 countries within the ENIGMA-BD Working Group. We jointly modeled the statistical effects of BD and BMI on brain structure using mixed effects and tested for interaction and mediation. We also investigated the impact of medications on the BMI-related associations.
BMI and BD additively impacted the structure of many of the same brain regions. Both BMI and BD were negatively associated with cortical thickness, but not surface area. In most regions the number of jointly used psychiatric medication classes remained associated with lower cortical thickness when controlling for BMI. In a single region, fusiform gyrus, about a third of the negative association between number of jointly used psychiatric medications and cortical thickness was mediated by association between the number of medications and higher BMI.
We confirmed consistent associations between higher BMI and lower cortical thickness, but not surface area, across the cerebral mantle, in regions which were also associated with BD. Higher BMI in people with BD indicated more pronounced brain alterations. BMI is important for understanding the neuroanatomical changes in BD and the effects of psychiatric medications on the brain.
Decreased hippocampal volume reported in neuropsychiatric and endocrine disorders is considered a result of putative neuronal damage mediated by corticosteroids. This is the first prospective study of hippocampal volume and function in patients treated with corticosteroids.
14 subjects treated systemically with prednisone or betamethasone for dermatological or rheumatic disorders underwent prospective neurocognitive testing (Auditory Verbal Learning Test—AVLT, Trail Making Test—TMT, Digit Span—DS) and nine of them also repeated magnetic resonance volumetry.
The mean duration of treatment between the first and the second assessment was 73 ± 38 days with mean daily dose of 37 ± 17 mg prednisone and 193 ± 29 days, with mean daily dose of 24 ± 15 mg prednisone between the first and the third assessment. There was a trend towards decreases in total AVLT scores and an improvement in the TMT and DS, but no significant changes in the volumes of the right or the left hippocampi between the assessments. Prednisone dose did not correlate with the hippocampal volume change.
We observed a trend for decline in verbal memory despite improvement in psychomotor speed, attention/working memory and no macroscopic hippocampal volume changes during 36–238 days of treatment with therapeutic doses of corticosteroids.
Previous studies have suggested altered structural and functional asymmetry of the brain in schizophrenia.
Functional MRI was used to assess differences in cortical activation during a verbal task in Broca's area and its contralateral homologue in four pairs of right-handed monozygotic (MZ) twins discordant and concordant for schizophrenia with low and high familial loading for the illness and four healthy control MZ twin pairs.
Pooled data from all subjects with schizophrenia showed increased activation in the right homologue of Broca's area in contrast to healthy individuals. Concordant twins (i.e. high familial loading group) showed prominent between co-twin differences in lateralization index within given region of interest. Intra-pair differences in lateralization index were significantly higher in concordant twins compared to the controls (0.69 ± 0.4 vs. 0.13 ± 0.13, P < 0.03), albeit no significant differences in the variable were shown between the discordant and control groups.
This study provides evidence of reduced cerebral dominance for language processing in patients with schizophrenia. The findings further suggest the need for additional research on relative proportion of genetic and environmental factors underlying deviations of functional asymmetry in schizophrenia.
T1 and T2 relaxation times were examined in four pairs of monozygotic (MZ) twins discordant and concordant for schizophrenia with low and high genetic loading for the illness and five healthy control MZ twin pairs. Patients with schizophrenia (n = 11) showed significant prolongation in T1 relaxation times in the globus pallidus (GP) bilaterally (P < 0.005, Bonferroni corrected) when compared to 14 healthy MZ twins.
It has been suggested that offspring of parents with bipolar disorder are at increased risk for disruptive mood dysregulation disorder (DMDD), but the specificity of this association has not been established.
We examined the specificity of DMDD to family history by comparing offspring of parents with (a) bipolar disorder, (b) major depressive disorder and (c) a control group with no mood disorders.
We established lifetime diagnosis of DMDD using the Schedule for Affective Disorders and Schizophrenia for School Aged Children for DSM-5 in 180 youth aged 6–18 years, including 58 offspring of parents with bipolar disorder, 82 offspring of parents with major depressive disorder and 40 control offspring.
Diagnostic criteria for DMDD were met in none of the offspring of parents with bipolar disorder, 6 of the offspring of parents with major depressive disorder and none of the control offspring. DMDD diagnosis was significantly associated with family history of major depressive disorder.
Our results suggest that DMDD is not specifically associated with a family history of bipolar disorder and may be associated with parental depression.
Residual symptoms and cognitive impairment are among important sources of disability in patients with bipolar disorder. Methylene blue could improve such symptoms because of its potential neuroprotective effects.
We conducted a double-blind crossover study of a low dose (15 mg, ‘placebo’) and an active dose (195 mg) of methylene blue in patients with bipolar disorder treated with lamotrigine.
Thirty-seven participants were enrolled in a 6-month trial (trial registration: NCT00214877). The outcome measures included severity of depression, mania and anxiety, and cognitive functioning.
The active dose of methylene blue significantly improved symptoms of depression both on the Montgomery–Åsberg Depression Rating Scale and Hamilton Rating Scale for Depression (P = 0.02 and 0.05 in last-observation-carried-forward analysis). It also reduced the symptoms of anxiety measured by the Hamilton Rating Scale for Anxiety (P = 0.02). The symptoms of mania remained low and stable throughout the study. The effects of methylene blue on cognitive symptoms were not significant. The medication was well tolerated with transient and mild side-effects.
Methylene blue used as an adjunctive medication improved residual symptoms of depression and anxiety in patients with bipolar disorder.
Little is known about the impact of insulin resistance on bipolar
To examine the relationships between insulin resistance, type 2 diabetes
and clinical course and treatment outcomes in bipolar disorder.
We measured fasting glucose and insulin in 121 adults with bipolar
disorder. We diagnosed type 2 diabetes and determined insulin resistance.
The National Institute of Mental Health Life Chart was used to record the
course of bipolar disorder and the Alda scale to establish response to
prophylactic lithium treatment.
Patients with bipolar disorder and type 2 diabetes or insulin resistance
had three times higher odds of a chronic course of bipolar disorder
compared with euglycaemic patients (50% and 48.7% respectively
v. 27.3%, odds ratio (OR) = 3.07, P
= 0.007), three times higher odds of rapid cycling (38.5% and 39.5%
respectively v. 18.2%, OR = 3.13, P =
0.012) and were more likely to be refractory to lithium treatment (36.8%
and 36.7% respectively v. 3.2%, OR = 8.40,
P<0.0001). All associations remained significant
after controlling for antipsychotic exposure and body mass index in
Comorbid insulin resistance may be an important factor in resistance to
treatment in bipolar disorder.
The landscape of north-western Bohemia covers the area between the towns of Duchcov, Most and Bílina and its immense historical value could hardly be overestimated. Unfortunately the landscape was heavily hit by the industrial era of coal mining (especially on the surface) and it was exfoliated on a large scale. Mining is in decline, and we are facing the task of restoring almost annihilated landscapes, including their memory traces. It is important to summarize the possibilities and methods of recalling, or ‘re-creating’ landscape memory, and even to search for new ones.
The paper works with the symbols of a specific predicative value – ‘minor landscape monument’, e.g. crosses, statues, small wayside chapels, etc. These widely disappeared because of brown-coal mining in the mining area of Bílina, and thus are endowed with extended symbolic strength. The leading idea of this project of preservation and recalling of memory traces in an industrial landscape is that of regarding small landscape monuments as the main source of historical identity and an equally essential tool for re-creating it. This project was worked out as a case study investigating the decayed small monuments as well as their re-calling in the strip-mine area of Bílina. The retrieval of information regarding essential cultural, historical, and natural values as well as a general development plan were implemented on the basis of multi-disciplinary cooperation including philosophy, cultural heritage theory, landscape architecture, landscape planning and horticulture. As a result ‘the principles of preservation and recalling of memory traces’ themselves were proposed as the general attitude to the preservation and recalling of historically precious areas within industrial, deeply changed landscapes afflicted by aberrations of modernity.
A methodical procedure has been thus evolved to be used for a wide range of landscapes of high historical value that have been roughly modified by industrial activities.
Middle Ages, modernity, post-modernity, landscape memory, minor landmark (small landscape monuments), cultural heritage theory, industrial landscape, landscape planning
The north Bohemian brown-coal basin covers the area between the Krušné hory mountains (Erzgebirge) and České středohoří (Central Czech Highlands).
We studied the course of major mood disorders in the offspring of parents with well-characterised bipolar disorder prospectively for up to 15 years. All consenting offspring were assessed annually or anytime symptomatic. The participants began to develop major mood episodes in adolescence and not before. The index major mood episode was almost always depressive, as were the first few recurrences. Onsets and recurrences continued throughout the observation period into adulthood. We did not find evidence of pre-pubertal mania. In summary, adolescence marks the beginning of the high-risk period for major mood episodes related to bipolar disorder.
La disminución del volumen del hipocampo comunicada en trastornos neuropsiquiátricos y endocrinos se considera resultado de un daño neuronal putativo mediado por corticoesteroides. Éste es el primer estudio prospectivo del volumen y la función del hipocampo en pacientes tratados con corticoesteroides.
Se sometió a 14 sujetos tratados sistémicamente con prednisona o betametasona por trastornos dermatológicos o reumáticos a pruebas neurocognitivas prospectivas (Prueba de Aprendizaje Verbal Auditivo [AVLT], Prueba del Trazo [TMT], Amplitud de dígitos [AD]) y nueve de ellos repitieron también una volumetría de resonancia magnética.
La duración media del tratamiento entre la primera evaluación y la segunda fue 73 ± 38 días con dosis diaria media de 37 ± 17 mg de prednisona y 193 ± 29 días, con dosis diaria media de 24 ± 15 mg de prednisona, entre la primera evaluación y la tercera. Hubo una tendencia a disminuciones en las puntuaciones totales de la AVLT y una mejoría en la TMT y la AD, pero ausencia de cambios significativos en el volumen de los hipocampos derecho o izquierdo entre las evaluaciones. La dosis de prednisona no correlacionaba con el cambio de volumen del hipocampo.
Observamos una tendencia a la disminución en la memoria verbal a pesar de la mejora en la velocidad psicomotriz, la atención/memoria operativa y una ausencia de cambios del volumen macroscópico del hipocampo durante los 36-238 días de tratamiento con dosis terapéuticas de corticoesteroides.
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