Subcortical brain structure and suicidal behaviour in major depressive disorder: a meta-analysis from the ENIGMA-MDD working group.

The aetiology of suicidal behaviour is complex, and knowledge about its neurobiological mechanisms is limited. Neuroimaging methods provide a noninvasive approach to explore the neural correlates of suicide vulnerability in vivo. The ENIGMA-MDD Working Group is an international collaboration evaluating neuroimaging and clinical data from thousands of individuals collected by research groups from around the world. Here we present analyses in a subset sample (n=3097) for whom suicidality data were available. Prevalence of suicidal symptoms among major depressive disorder (MDD) cases ranged between 29 and 69% across cohorts. We compared mean subcortical grey matter volumes, lateral ventricle volumes and total intracranial volume (ICV) in MDD patients with suicidal symptoms (N=451) vs healthy controls (N=1996) or MDD patients with no suicidal symptoms (N=650). MDD patients reporting suicidal plans or attempts showed a smaller ICV (P=4.12 × 10-3) or a 2.87% smaller volume compared with controls (Cohen's d=-0.284). In addition, we observed a nonsignificant trend in which MDD cases with suicidal symptoms had smaller subcortical volumes and larger ventricular volumes compared with controls. Finally, no significant differences (P=0.28-0.97) were found between MDD patients with and those without suicidal symptoms for any of the brain volume measures. This is by far the largest neuroimaging meta-analysis of suicidal behaviour in MDD to date. Our results did not replicate previous reports of association between subcortical brain structure and suicidality and highlight the need for collecting better-powered imaging samples and using improved suicidality assessment instruments.

Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group.

The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen's d=-0.14, % difference=-1.24). This effect was driven by patients with recurrent MDD (Cohen's d=-0.17, % difference=-1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen's d=-0.20, % difference=-1.85) and a trend toward smaller amygdala (Cohen's d=-0.11, % difference=-1.23) and larger lateral ventricles (Cohen's d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status.

Alcohol dependence and physical comorbidity: Increased prevalence but reduced relevance of individual comorbidities for hospital-based mortality during a 12.5-year observation period in general hospital admissions in urban North-West England.

PURPOSE: Alcohol dependence (AD) is associated with an increase in physical comorbidities. The effects of these diseases on general hospital-based mortality are unclear. Consequently, we conducted a mortality study in which we investigated if the burden of physical comorbidities and their relevance on general hospital-based mortality differs between individuals with and without AD during a 12.5-year observation period in general hospital admissions. METHODS: During 1 January 2000 and 30 June 2012, 23,371 individuals with AD were admitted at least once to seven General Manchester Hospitals. Their physical comorbidities with a prevalence≥1% were compared to those of 233,710 randomly selected hospital controls, group-matched for age and gender (regardless of primary admission diagnosis or specialized treatments). Physical comorbidities that increased the risk of hospital-based mortality (but not outside of the hospital) during the observation period were identified using multiple logistic regression analyses. RESULTS: Hospital-based mortality rates were 20.4% in the AD sample and 8.3% in the control sample. Individuals with AD compared to controls had a higher burden of physical comorbidities, i.e. alcoholic liver and pancreatic diseases, diseases of the conducting airways, neurological and circulatory diseases, diseases of the upper gastrointestinal tract, renal diseases, cellulitis, iron deficiency anemia, fracture neck of femur, and peripheral vascular disease. In contrast, coronary heart related diseases, risk factors of cardiovascular disease, diverticular disease and cataracts were less frequent in individuals with AD than in controls. Thirty-two individual physical comorbidities contributed to the prediction of hospital-based mortality in univariate analyses in the AD sample; alcoholic liver disease (33.7%), hypertension (16.9%), chronic obstructive pulmonary disease (14.1%), and pneumonia (13.3%) were the most frequent diagnoses in deceased individuals with AD. Multiple forward logistic regression analysis, accounting for possible associations of diseases, identified twenty-three physical comorbidities contributing to hospital-based mortality in individuals with AD. However, all these comorbidities had an equal or even lower impact on hospital-based mortality than in the comparison sample. CONCLUSION: The excess of in-hospital deaths in general hospitals in individuals with AD is due to an increase of multiple physical comorbidities, even though individual diseases have an equal or even reduced impact on general hospital-based mortality in individuals with AD compared to controls.

Alzheimer's disease and co-morbidity: increased prevalence and possible risk factors of excess mortality in a naturalistic 7-year follow-up.

BACKGROUND: Subjects with late-onset Alzheimer's disease (AD) have to be sufficiently healthy to live long enough to experience and to be diagnosed with dementia in later life. In contrast, neurodegeneration and cognitive deficits in AD may increase the frequency of co-morbid disorders and their possible influence on mortality. Consequently, we investigated whether the pattern of co-morbidity and its relevance for later death differed between hospitalized AD and age-matched controls subjects. METHODS: Co-morbid diseases with a prevalence of more than 1% at hospital admission were compared between 634 hospitalized AD and 72,244 control subjects aged above 70 years admitted to the University of Birmingham NHS Trust between 1 January 2000 to 31 December 2007. Risk factors, i.e. co-morbid diseases that were predictors of mortality within the 7-year follow-up, were identified and compared. RESULTS: Subjects with AD suffer more eating disorders, infections, brain diseases and neck of femur fractures than other hospitalized elderly patients. In contrast, some cardiovascular diseases and diabetes mellitus were less prevalent in AD subjects in comparison with hospitalized controls. Diseases that might have contributed to later mortality in AD were pneumonia, ischemic heart disease and gastroenteritis, but there were no significant differences in their impact on mortality compared to other hospitalized elderly subjects with the same co-morbidities in multivariate logistic regression analyses. CONCLUSION: Patients with AD have a different pattern of co-morbidity, but die from the same diseases as other hospitalized patients. Infections including pneumonia and diseases that may occur secondary to neurodegeneration and cognitive decline may need special attention in patients with AD who may not be able to identify or report the early symptoms. Preventive measures may be helpful to reduce the high risk and fatal consequences of undetected disease in AD.

Type-2 diabetes mellitus in schizophrenia: increased prevalence and major risk factor of excess mortality in a naturalistic 7-year follow-up.

OBJECTIVE: Physical co-morbidity including type 2 diabetes mellitus is more prevalent in patients with schizophrenia compared to the general population. However, there is little consistent evidence that co-morbidity with diabetes mellitus and/or other diseases leads to excess mortality in schizophrenia. Thus, we investigated whether co-morbidity with diabetes and other somatic diseases is increased in schizophrenics, and if these are equally or more relevant predictors of mortality in schizophrenia than in age- and gender-matched hospitalised controls. METHODS: During 2000-2007, 679 patients with schizophrenia were admitted to University Hospital Birmingham NHS Trust. Co-morbidities were compared with 88,778 age- and gender group-matched hospital controls. Predictors of mortality were identified using forward Cox regression models. RESULTS: The prevalence of type 2 diabetes mellitus was increased in schizophrenia compared to hospitalised controls (11.3% versus 6.3%). The initial prevalence of type 2 diabetes mellitus was significantly higher in the 100 later deceased schizophrenic patients (24.0%) than in those 579 surviving over 7 years (9.2%). Predictors of mortality in schizophrenia were found to be age (relative risk [RR] = 1.1/year), type 2 diabetes mellitus (RR = 2.2), pneumonia (RR = 2.7), heart failure (RR = 2.9) and chronic renal failure (RR = 3.2). The impact of diabetes mellitus on mortality was significantly higher in schizophrenia than in hospital controls (RR = 2.2 versus RR = 1.1). In agreement, deceased schizophrenics had significantly suffered more diabetes mellitus than deceased controls (24.0 versus 10.5%). The relative risks of mortality for other disorders and their prevalence in later deceased subjects did not significantly differ between schizophrenia and controls. CONCLUSION: Schizophrenics have more and additionally suffer more from diabetes: co-morbidity with diabetes mellitus is increased in schizophrenia in comparison with hospital controls; type 2 diabetes mellitus causes significant excess mortality in schizophrenia. Thus, monitoring for and prevention of type 2 diabetes mellitus is of utmost relevance in hospitalised patients with schizophrenia.

[The 4-week prevalence of somatoform disorders and associated psychosocial impairment]. / 4-Wochen-Prävalenz somatoformer Störungen und assoziierte psychosoziale Beeinträchtigung.

In the course of a WHO study,we report on the prevalence of somatoform disorders (SFD) and the associated psychosocial impairment in five western German primary care settings. In accordance with ICD-10 classification, a 4-week prevalence of 28.5% was found for SFD (number of patients in the age between 18 and 60 with an SFD in the last 28 days). The accumulation of SFD was higher in female patients than in males (RR 1.7), in particular when the number of children was >1 (RR 1.8). The female-male difference was more marked in persistent somatoform pain disorder (RR 2.1) and unspecific somatization disorder (RR 5.0). Concerning other psychiatric disorders, neurasthenia occurred most frequently,with a 4-week prevalence of 8.2%. The 4-week prevalence of concomitant occurrence of SFD and other psychiatric disorders was 7.7%. Working capability was most severely impaired, with 22.5 days of absence from work during the last month, in male patients with hypochondriacal disorder. In comparison, somatization disorder resulted in a severe level of psychosocial impairment, with 10.3 days of absence in work during the last month in female patients. The coexistence of SFS with other psychiatric disorders resulted in a greater extent of psychosocial impairment.

Target predictability influences the distribution of coordinated eye-head gaze saccades in patients with homonymous hemianopia.

In hemianopic patients target predictability plays a differential role for the distribution of different types of initial saccades. A linear correlation was shown to exist between the adaptive state of reading capability and the probability of a correct initial eye-head gaze saccade that hit the target accurately. A constant target frequency of 0.8 Hz was found to be the optimum frequency for hemianopic patients to follow square step targets with an eccentricity of +/- 20 degrees. Variability of the compensatory eye movement velocity gain was lowest at this frequency. We were able to use this target frequency as a test for a clinical classification of the status of adaptation of hemianopic patients in combination with simple reading tests. The repetition of this manoeuvre could correct the synkinesis and the balance of the VOR during active gaze of hemianopic patients.