Depression is associated with higher rates of premature mortality in people with physical comorbidities, such as type 2 diabetes. Conceptually, the successful treatment of depression in people with type 2 diabetes could prevent premature mortality.

To investigate the association between antidepressant prescribing and the rates of all-cause and cause-specific (endocrine, cardiovascular, respiratory, cancer, unnatural) mortality in individuals with comorbid depression and type 2 diabetes.

Using UK primary care records between years 2000 and 2018, we completed a nested case–control study in a cohort of people with comorbid depression and type 2 diabetes who were starting oral antidiabetic treatment for the first time. We used incident density sampling to identify cases who died and matched controls who remained alive after the same number of days observation. We estimated incidence rate ratios for the association between antidepressant prescribing and mortality, adjusting for demographic characteristics, comorbidities, medication use and health behaviours.

We included 5222 cases with a recorded date of death, and 18 675 controls, observed for a median of 7 years. Increased rates of all-cause mortality were associated with any antidepressant prescribing during the observation period (incidence rate ratio 2.77, 95% CI 2.48–3.10). These results were consistent across all causes of mortality that we investigated.

Antidepressant prescribing was highly associated with higher rates of mortality. However, we suspect that this is not a direct causal effect, but that antidepressant treatment is a marker of more severe and unsuccessfully treated depression.

Women have a greater lifetime risk of developing Alzheimer’s disease (AD) dementia than men, a sex/gender disparity that cannot be explained by female longevity alone. There is substantial evidence for sex differences in the effects of APOE £4 on risk for AD. While APOE e4 increases AD risk in both sexes, women who carry APOE e4 are disproportionately vulnerable to cognitive impairment and AD compared to their counterpart men. In contrast to APOE e4, APOE £2 is associated with slower cognitive decline and a lower risk of AD. Although a less robust literature, APOE e2 may also have sex-specific effects. Because APOE e2 is the rarest major APOE allele, well-powered studies are needed to examine sex-specific effects. The objective of the present study was to examine sex-specific associations of APOE e2 carriage with longitudinal cognitive decline in a large cohort of clinically unimpaired adults.

We used observational data from two sources: the National Alzheimer’s Coordinating Center (NACC) and the Rush Alzheimer’s Disease Center (ROS/MAP/MARS) studies. We included data from clinically unimpaired adults who were >50 years old at baseline who self-identified as non-Hispanic White (NHW) or non-Hispanic Black (NHB). Participants were categorized as APOE £2, £4, or £3/e3 carriers. APOE e2/e4 carriers were excluded. The same battery of neuropsychological tests was used to assess global cognition in participants from both data sources. Linear mixed models examined interactive associations of genotype (£2 or £4 vs. £3/£3), sex, and time on longitudinal cognition in NHW and NHB participants separately. Analyses were first performed in a pooled sample of NACC and ROS/MAP/MARS participants and if significant they were repeated separately in each data source.

Across both data sources, 9,766 NHW (mean (SD) age=73.0(9.00) years, mean (SD) education=16.3(2.83) years, n(%) women=6,344(65.0)) and 2,010 NHB participants (mean(SD) age=71.3(7.59) years, mean(SD) education=14.9(3.10) years, n(%) women=1,583(78.8)) met inclusion criteria. Sex modified the association between APOE £2 and cognitive decline in NHW (ß=0.097, 95% CI: 0.023-0.172, pint=.01) but not NHB participants (ß=-0.011, 95% CI: -0.153-0.131, pint=.9). In sex-stratified analyses of NHW participants, APOE £2 (vs. £3/£3) carriage was associated with attenuated cognitive decline in men (ß=0.096, 95% CI: 0.037-0.155, p=.001), but not women (ß=-0.001, 95% CI: -0.044-0.043, p=.97). In analyses comparing men and women APOE £2 carriers, men exhibited slower cognitive decline than women (ß=0.120, 95% CI: 0.051-0.190, p=.001). Analyses performed separately in NACC and ROS/MAP revealed the same pattern of male-specific APOE £2 protection in NHW participants in both data sources.

In light of the longstanding view that APOE £2 protects against AD and dementia, our results provide evidence that APOE £2 is associated with attenuated cognitive decline in men but not women among NHW adults. This male-specific protection may contribute to sex differences in AD-related cognitive decline. Our findings have important implications for understanding the biological drivers of sex differences in AD risk, which is crucial for developing sex-specific strategies to prevent and treat AD dementia.

High cognitive activity possibly reduces the risk of cognitive decline and dementia.

To investigate associations between an individual's need to engage in cognitively stimulating activities (need for cognition, NFC) and structural brain damage and cognitive functioning in the Dutch general population with and without existing cognitive impairment.

Cross-sectional data were used from the population-based cohort of the Maastricht Study. NFC was measured using the Need For Cognition Scale. Cognitive functioning was tested in three domains: verbal memory, information processing speed, and executive functioning and attention. Values 1.5 s.d. below the mean were defined as cognitive impairment. Standardised volumes of white matter hyperintensities (WMH), cerebrospinal fluid (CSF) and presence of cerebral small vessel disease (CSVD) were derived from 3T magnetic resonance imaging. Multiple linear and binary logistic regression analyses were used adjusted for demographic, somatic and lifestyle factors.

Participants (n = 4209; mean age 59.06 years, s.d. = 8.58; 50.1% women) with higher NFC scores had higher overall cognition scores (B = 0.21, 95% CI 0.17–0.26, P < 0.001) and lower odds for CSVD (OR = 0.74, 95% CI 0.60–0.91, P = 0.005) and cognitive impairment (OR = 0.60, 95% CI 0.48–0.76, P < 0.001) after adjustment for demographic, somatic and lifestyle factors. The association between NFC score and cognitive functioning was similar for individuals with and without prevalent cognitive impairment. We found no significant association between NFC and WMH or CSF volumes.

A high need to engage in cognitively stimulating activities is associated with better cognitive functioning and less presence of CSVD and cognitive impairment. This suggests that, in middle-aged individuals, motivation to engage in cognitively stimulating activities may be an opportunity to improve brain health.

Late-life depression has been associated with volume changes of the hippocampus. However, little is known about its association with specific hippocampal subfields over time.

We investigated whether hippocampal subfield volumes were associated with prevalence, course and incidence of depressive symptoms.

We extracted 12 hippocampal subfield volumes per hemisphere with FreeSurfer v6.0 using T1-weighted and fluid-attenuated inversion recovery 3T magnetic resonance images. Depressive symptoms were assessed at baseline and annually over 7 years of follow-up (9-item Patient Health Questionnaire). We used negative binominal, logistic, and Cox regression analyses, corrected for multiple comparisons, and adjusted for demographic, cardiovascular and lifestyle factors.

A total of n = 4174 participants were included (mean age 60.0 years, s.d. = 8.6, 51.8% female). Larger right hippocampal fissure volume was associated with prevalent depressive symptoms (odds ratio (OR) = 1.26, 95% CI 1.08–1.48). Larger bilateral hippocampal fissure (OR = 1.37–1.40, 95% CI 1.14–1.71), larger right molecular layer (OR = 1.51, 95% CI 1.14–2.00) and smaller right cornu ammonis (CA)3 volumes (OR = 0.61, 95% CI 0.48–0.79) were associated with prevalent depressive symptoms with a chronic course. No associations of hippocampal subfield volumes with incident depressive symptoms were found. Yet, lower left hippocampal amygdala transition area (HATA) volume was associated with incident depressive symptoms with chronic course (hazard ratio = 0.70, 95% CI 0.55–0.89).

Differences in hippocampal fissure, molecular layer and CA volumes might co-occur or follow the onset of depressive symptoms, in particular with a chronic course. Smaller HATA was associated with an increased risk of incident (chronic) depression. Our results could capture a biological foundation for the development of chronic depressive symptoms, and stresses the need to discriminate subtypes of depression to unravel its biological underpinnings.

To fully comprehend and appreciate the impact of psychosurgery on treatment-resistant depression it is pertinent to review its initial development and subsequent history. By reviewing previous studies of psychosurgery, we can build a narrative of what was, what currently is and what might be. Assessing the complex philosophical dilemma of the mind and the impact this has on individuals’ concept of psychosurgery has helped to bridge the gap between Neurosurgery and Psychiatry.

We aimed to examine this question, starting at the very beginnings of our concept of mind, working through to modern-day thinking, how we approach both neurosurgery and psychiatry and help to bridge the two.

A narrative review of the current literature concerning neurosurgery for mental disorders and said applications to modern psychiatry was conducted. Emphasis on philosophical thought processing in conjunction with the neurosurgical intervention was noted.

Psychosurgery has its roots in the early philosophy of mind, concerned with distinguishing whether the mind is a physical entity or immaterial. Psychosurgery is reliant on a physical concept of the mind, or at the very least that the mind supervenes the physical brain. History has shown us examples of this, with the archetype of this being the story of Phineas Gage. Since its onset psychosurgery has moved in and out of vogue. After being met with early scepticism it later went on to be performed thousands of times to help cure schizophrenia. In the 1800s, Gottlieb Burkhardt pioneered initial surgical interventions on the brain with intended psychiatric outcomes, moving on to work from Egas Moniz and the development of leucotomies and famously lobotomies, to modern medical techniques of Deep Brain Stimulation.

Psychosurgery has faced much opposition throughout history due to the uniquely invasive nature of not just affecting us physically but also mentally and the implications that this has for us as humans and our understanding of ourselves. As both medical and cultural views of mental health have changed over time, so has our understanding of psychosurgery and its potential applications. It is possible that early attempts to implement psychosurgery, before the advent of modern medicine, did more harm to psychosurgery’s reputation than good. However, without those early forays, we may never have progressed to the modern techniques we now utilise.

None Declared