To examine the association between childhood trauma and work functioning, and to elucidate to what extent this association can be accounted for by depression and/or anxiety.

Data of 1,649 working participants were derived from the Netherlands Study of Depression and Anxiety (NESDA, n = 2,981). Childhood trauma (emotional neglect, psychological, physical, and sexual abuse before age 16) was assessed with a structured interview and work functioning, in terms of absenteeism and presenteeism, with the Health and Labor Questionnaire Short Form (SF-HLQ) and the World Health Organization Disability Assessment Schedule II (WHODAS-II), respectively. Depressive and/or anxiety disorders were assessed with the Composite Interview Diagnostic Instrument (CIDI). Mediation analyses were conducted.

At baseline, 44.8% reported to have experienced childhood trauma. Workers with the highest childhood trauma level showed significantly (p < 0.001) more absenteeism as well as more presenteeism. Mediation analyses revealed that indirect effects between the childhood trauma index and both work indices were significantly mediated by current depressive disorder (p = 0.023 and p < 0.001, respectively) and current comorbid depression-anxiety (p = 0.020 and p < 0.001, respectively), with the latter accounting for the largest effects (PM = 0.23 and PM = 0.29, respectively). No significant mediating role in this relationship was found for current anxiety disorder and remitted depressive and/or anxiety disorder.

Persons with childhood trauma have significantly reduced work functioning in terms of absenteeism and presenteeism. This seems to be largely accounted for by current depressive disorders and current comorbid depression-anxiety.

Impairments in social and nonsocial cognition have been demonstrated in both patients suffering from bipolar disorder (BD) and their unaffected relatives and might therefore represent a heritable marker of risk. This study investigated the relevance of emotional intelligence (EI) as part of the emotion processing domain of social cognition in this regard.

A total of 54 outpatients suffering from BD, 54 unaffected siblings, and 80 control subjects were investigated using the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) and the Brief Assessment of Cognition in Schizophrenia (BACS). Analyses of covariance (ANCOVAs) were performed with adjustment for the BACS composite score. The three groups were compared by one-way analysis of variance or chi-square test, depending on the variable type. As the three groups differed significantly in their level of education, additional ANCOVAs with adjustment for education were performed.

Patients achieved significantly lower levels of overall EI and overall nonsocial cognitive functioning compared to unaffected siblings and controls, whereas performance of the latter two groups was comparable in both domains.

Due to comparable levels of EI in unaffected siblings of patients suffering from BD and control subjects, EI assessed by means of the MSCEIT does not represent an endophenotype for BD.

This study aimed to identify clinical and cognitive factors associated with increased risk for difficult-to-treat depression (DTD) or treatment-resistant depression (TRD).

A total of 229 adult outpatients with major depression were recruited from the mental health unit at a public hospital. Participants were subdivided into resistant and nonresistant groups according to their Maudsley Staging Model score. Sociodemographic, clinical, and cognitive (objective and subjective measures) variables were compared between groups, and a logistic regression model was used to identify the factors most associated with TRD risk.

TRD group patients present higher verbal memory impairment than the nonresistant group irrespective of pharmacological treatment or depressive symptom severity. Logistic regression analysis showed that low verbal memory scores (odds ratio [OR]: 2.02; 95% confidence interval [CI]: 1.38–2.95) together with high depressive symptom severity (OR: 1.29; CI95%: 1.01–1.65) were associated with TRD risk.

Our findings align with neuroprogression models of depression, in which more severe patients, defined by greater verbal memory impairment and depressive symptoms, develop a more resistant profile as a result of increasingly detrimental neuronal changes. Moreover, our results support a more comprehensive approach in the evaluation and treatment of DTD in order to improve illness course. Longitudinal studies are warranted to confirm the predictive value of verbal memory and depression severity in the development of TRD.

Patients with schizophrenia display experiential anomalies in their feelings and cognitions arising in the domain of their lived body. These abnormal bodily phenomena (ABP) are not part of diagnostic criteria for schizophrenia. One of the reasons is the difficulty to assess specific ABP for schizophrenia spectrum disorders. The present study aimed to explore the presence in patients with schizophrenia of specific ABP.

We used a semistructured interview—the Abnormal Bodily Phenomena questionnaire (ABPq), an instrument devised to detect and measure ABP specific to patients with schizophrenia. Fifty-one outpatients affected by schizophrenia and 28 euthymic outpatients affected by bipolar disorder type I with psychotic features (BD-pf-e) were recruited. Before assessing the specificity for schizophrenia of the observed ABP, we tested the internal consistency and the convergent validity of the ABPq in patients with schizophrenia. Specificity was assessed by examining potential differences in ABPq among the patients with schizophrenia in remission (SCZ-r) and BD-pf-e.

The ABPq shows strong internal consistency and convergent validity. As to the specificity, ABP measured by ABPq were more frequent and severe in SCZ-r than in BD-pf-e. In particular, all ABPq dimensions, except “Coherence,” had at least mild severity in over 50% of SCZ-r, while dimensions with at least mild severity were observed in 5–10% of the BD-pf-e.

These findings can contribute to establish more precise phenomenal boundaries between schizophrenia and bipolar disorder, to explore the borders between nonpsychotic and psychotic forms of ABP, between ABP and negative and disorganized symptoms, and to enlighten core aspects of schizophrenia.

Mood instability and sleep disturbance are common symptoms in people with mental illness. Both features are clinically important and associated with poorer illness trajectories. We compared clinical outcomes in people presenting to secondary mental health care with mood instability and/or sleep disturbance with outcomes in people without either mood instability or sleep disturbance.

Data were from electronic health records of 31,391 patients ages 16–65 years presenting to secondary mental health services between 2008 and 2016. Mood instability and sleep disturbance were identified using natural language processing. Prevalence of mood instability and sleep disturbance were estimated at baseline. Incidence rate ratios were estimates for clinical outcomes including psychiatric diagnoses, prescribed medication, and hospitalization within 2-years of presentation in persons with mood instability and/or sleep disturbance compared to individuals without either symptom.

Mood instability was present in 9.58%, and sleep disturbance in 26.26% of patients within 1-month of presenting to secondary mental health services. Compared with individuals without either symptom, those with mood instability and sleep disturbance showed significantly increased incidence of prescription of any psychotropic medication (incidence rate ratios [IRR] = 7.04, 95% confidence intervals [CI] 6.53–7.59), and hospitalization (IRR = 5.32, 95% CI 5.32, 4.67–6.07) within 2-years of presentation. Incidence rates of most clinical outcomes were considerably increased among persons with both mood instability and sleep disturbance, relative to persons with only one symptom.

Mood instability and sleep disturbance are present in a wide range of mental disorders, beyond those in which they are conventionally considered to be symptoms. They are associated with poor outcomes, particularly when they occur together. The poor prognosis associated with mood instability and sleep disorder may be, in part, because they are often treated as secondary symptoms. Mood instability and sleep disturbance need better recognition as clinical targets for treatment in their own right.

Aberrant activity of the subcallosal cingulate (SCC) is a common theme across pharmacologic treatment efficacy prediction studies. The functioning of the SCC in psychotherapeutic interventions is relatively understudied, as are functional differences among SCC subdivisions. We conducted functional connectivity analyses (rsFC) on resting-state functional magnetic resonance imaging (fMRI) data, collected before and after a course of cognitive behavioral therapy (CBT) in patients with major depressive disorder (MDD), using seeds from three SCC subdivisions.

Resting-state data were collected from unmedicated patients with current MDD (Hamilton Depression Rating Scale-17 > 16) before and after 14-sessions of CBT monotherapy. Treatment outcome was assessed using the Beck Depression Inventory (BDI). Rostral anterior cingulate (rACC), anterior subcallosal cingulate (aSCC), and Brodmann’s area 25 (BA25) masks were used as seeds in connectivity analyses that assessed baseline rsFC and symptom severity, changes in connectivity related to symptom improvement after CBT, and prediction of treatment outcomes using whole-brain baseline connectivity.

Pretreatment BDI negatively correlated with pretreatment rACC ~ dorsolateral prefrontal cortex and aSCC ~ lateral prefrontal cortex rsFC. In a region-of-interest longitudinal analysis, rsFC between these regions increased post-treatment (p < 0.05FDR). In whole-brain analyses, BA25 ~ paracentral lobule and rACC ~ paracentral lobule connectivities decreased post-treatment. Whole-brain baseline rsFC with SCC did not predict clinical improvement.

rsFC features of rACC and aSCC, but not BA25, correlated inversely with baseline depression severity, and increased following CBT. Subdivisions of SCC involved in top-down emotion regulation may be more involved in cognitive interventions, while BA25 may be more informative for interventions targeting bottom-up processing. Results emphasize the importance of subdividing the SCC in connectivity analyses.

Aberrant emotional reactivity is a putative endophenotype for bipolar disorder (BD), but the findings of behavioral studies are often negative due to suboptimal sensitivity of the employed paradigms. This study aimed to investigate whether visual gaze patterns and facial displays of emotion during emotional film clips can reveal subtle behavioral abnormalities in remitted BD patients.

Thirty-eight BD patients in full or partial remission and 40 healthy controls viewed 7 emotional film clips. These included happy, sad, and neutral scenarios and scenarios involving winning, risk-taking, and thrill-seeking behavior of relevance to the BD phenotype. Eye gaze and facial expressions were recorded during the film clips, and participants rated their emotional reactions after each clip.

BD patients showed a negative bias in both facial displays of emotion and self-rated emotional responses. Specifically, patients exhibited more fearful facial expressions during all film clips. This was accompanied by less positive self-rated emotions during the winning and happy film clips, and more negative emotions during the risk-taking/thrill-related film clips.

These findings suggest that BD is associated with trait-related abnormalities in subtle behavioral displays of emotion processing. Future studies comparing patients with BD and unipolar depression are warranted to clarify whether these differences are specific to BD. If so, assessments of visual gaze and facial displays of emotion during emotional film clips may have the potential to be implemented in clinical assessments to aid diagnostic accuracy.

Cognitive impairment associated with lifetime major depressive disorder (MDD) is well-supported by meta-analytic studies, but population-based estimates remain scarce. Previous UK Biobank studies have only shown limited evidence of cognitive differences related to probable MDD. Using updated cognitive and clinical assessments in UK Biobank, this study investigated population-level differences in cognitive functioning associated with lifetime MDD.

Associations between lifetime MDD and cognition (performance on six tasks and general cognitive functioning [g-factor]) were investigated in UK Biobank (N-range 7,457–14,836, age 45–81 years, 52% female), adjusting for demographics, education, and lifestyle. Lifetime MDD classifications were based on the Composite International Diagnostic Interview. Within the lifetime MDD group, we additionally investigated relationships between cognition and (a) recurrence, (b) current symptoms, (c) severity of psychosocial impairment (while symptomatic), and (d) concurrent psychotropic medication use.

Lifetime MDD was robustly associated with a lower g-factor (β = −0.10, PFDR = 4.7 × 10−5), with impairments in attention, processing speed, and executive functioning (β ≥ 0.06). Clinical characteristics revealed differential profiles of cognitive impairment among case individuals; those who reported severe psychosocial impairment and use of psychotropic medication performed worse on cognitive tests. Severe psychosocial impairment and reasoning showed the strongest association (β = −0.18, PFDR = 7.5 × 10−5).

Findings describe small but robust associations between lifetime MDD and lower cognitive performance within a population-based sample. Overall effects were of modest effect size, suggesting limited clinical relevance. However, deficits within specific cognitive domains were more pronounced in relation to clinical characteristics, particularly severe psychosocial impairment.

The efficacy of antidepressant treatment is fair, but the efficacy is considerably lower in patients failing two or more trials underscoring the need for new treatment options. Our study evaluated the augmenting antidepressant effect of 8-weeks transcranial pulsed electromagnetic field (T-PEMF) therapy in patients with treatment-resistant depression.

A multicenter 8-week single-arm cohort study conducted by the Danish University Antidepressant Group.

In total, 58 participants (20 men and 38 women) with a moderate to severe depression as part of a depressive disorder according to ICD-10 who fulfilled criteria for treatment resistance were included, with 19 participants being nonresponders to electroconvulsive therapy during the current depressive episode. Fifty-two participants completed the study period. Scores on the Hamilton Depression Scale 17-items version (HAM-D17) decreased significantly from baseline (mean = 20.6, SD 4.0) to endpoint (mean = 12.6, SD 7.1; N = 58). At endpoint, utilizing a Last Observation Carried Forward analysis, 49 and 28% of those participants with, respectively, a nonchronic current episode (≤2 years; N = 33) and a chronic current episode (>2 years; N = 25) were responders, that is, achieved a reduction of 50% or more on the HAM-D17 scale. At endpoint, respectively, 30 and 16% obtained remission, defined as HAM-D17 ≤ 7. On the Hamilton Scale 6-item version (HAM-D6), respectively, 51 and 16% obtained remission, defined as HAM-D6 ≤ 4.

The findings indicate a potential beneficial role of T-PEMF therapy as an augmentation treatment to ongoing pharmacotherapy in treatment-resistant depression.

The mechanisms linking cardiovascular disease (CVD) and depression are still not established. We investigated the impact of mental vulnerability on the relationship between CVD and depression.

A total of 19,856 individuals from five cohorts of random samples of the background population in Copenhagen were followed from baseline (1983–2011) until 2017 in Danish registries. Additive hazard and Cox proportional hazard models were used to analyze the effects of confounding by mental vulnerability as well as interactions between mental vulnerability and CVD on the risk of depression.

During follow-up, 15.3% developed CVD, while 18.1% experienced depression. A strong positive association between CVD and depression (hazard ratio: 3.60 [95% confidence intervals (CI): 3.30; 3.92]) corresponding to 35.4 (95% CI: 31.7; 39.1) additional cases per 1,000 person-years was only slightly attenuated after adjustment for mental vulnerability in addition to other confounders. Synergistic interaction between CVD and mental vulnerability was identified in the additive hazard model. Due to interaction between CVD and mental vulnerability, CVD was associated with 50.9 more cases of depression per 1,000 person-years among individuals with high mental vulnerability compared with individuals with low mental vulnerability.

Mental vulnerability did not explain the strong relationship between CVD and depression. CVD was associated with additional cases of depression among individuals with higher mental vulnerability indicating that this group holds the greatest potential for intervention, for example, in rehabilitation settings.

Studying offspring of schizophrenia (SZo) and bipolar disorder patients (BDo) provides important information on the putative neurodevelopmental trajectories underlying development toward severe mental illnesses. We compared intracranial volume (ICV), as a marker for neurodevelopment, and global and local brain measures between SZo or BDo and control offspring (Co) in relation to IQ and psychopathology.

T1-weighted magnetic resonance imaging (MRI) brain scans were obtained from 146 participants (8–19 years; 40 SZo, 66 BDo, 40 Co). Linear mixed models were applied to compare ICV, global, and local brain measures between groups. To investigate the effect of ICV, IQ (four subtests Wechsler Intelligence Scale for Children/Wechsler Adult Intelligence Scale-III) or presence of psychopathology these variables were each added to the model.

SZo and BDo had significantly lower IQ and more often met criteria for a lifetime psychiatric disorder than Co. ICV was significantly smaller in SZo than in BDo (d = −0.56) and Co (d = −0.59), which was largely independent of IQ (respectively, d = −0.54 and d = −0.35). After ICV correction, the cortex was significantly thinner in SZo than in BDo (d = −0.42) and Co (d = −0.75) and lateral ventricles were larger in BDo than in Co (d = 0.55). Correction for IQ or lifetime psychiatric diagnosis did not change these findings.

Despite sharing a lower IQ and a higher prevalence of psychiatric disorders, brain abnormalities in BDo appear less pronounced (but are not absent) than in SZo. Lower ICV in SZo implies that familial risk for schizophrenia has a stronger association with stunted early brain development than familial risk for bipolar disorder.

Schizoaffective disorder, bipolar type (SAD) and bipolar disorder I (BD) present a large clinical overlap. In a 1-year follow-up, we aimed to evaluate days to hospitalization (DTH) and predictors of relapse in a SAD-BD cohort of patients.

A 1–year, prospective, naturalistic cohort study considering DTH as primary outcome and incidence of direct and indirect measures of psychopathological compensation as secondary outcomes. Kaplan-Meyer survival analysis with Log-rank Mantel-Cox test compared BD/SAD subgroups as to DTH. After bivariate analyses, Cox regression was performed to assess covariates possibly associated with DTH in diagnostic subgroups.

Of 836 screened patients, 437 were finally included (SAD = 105; BD = 332). Relapse rates in the SAD sample was n = 26 (24.8%) vs. n = 41 (12.3%) in the BD sample (p = 0.002). Mean ± SD DTH were 312.16 ± 10.6 (SAD) vs. 337.62 ± 4.4 (BD) days (p = 0.002). Patients with relapses showed more frequent suicide acts, violent behaviors, and changes in pharmacological treatments (all p < 0.0005) in comparison to patients without relapse. Patients without relapses had significantly higher mean number of treatments at T0 (p = 0.010). Cox regression model relating the association between diagnosis and DTH revealed that BD had higher rates of suicide attempts (HR = 13.0, 95%CI = 4.0–42.0, p < 0.0005), whereas SAD had higher rates of violent behavior during psychotic episodes (HR = 12.0, 95%CI =.3.3-43.5, p > 0.0005).

SAD patients relapse earlier with higher hospitalization rates and violent behavior during psychotic episodes whereas bipolar patients have more suicide attempts. Psychiatric/psychological follow-up visits may delay hospitalizations by closely monitoring symptoms of self- and hetero-aggression.

Depression and chronic inflammatory medical conditions have been linked to impaired cognitive ability. However despite frequent comorbidity, their combined association with cognitive ability has rarely been examined.

This study examined associations between self-reported depression and chronic inflammatory diseases and their interaction with cognitive performance in 456,748 participants of the UK Biobank, adjusting for sociodemographic and lifestyle factors. Numbers with available data ranged from 94,899 to 453,208 depending on the cognitive test.

Self-reported depression was associated with poorer performance compared to controls in several cognitive tests (fully adjusted models, reaction time: B = 6.08, 95% CI = 5.09, 7.07; pairs matching: incidence rate ratio = 1.02, 95% CI = 1.02, 1.03; Trail Making Test B: B = 1.37, 95% CI = 0.88, 1.87; Digit Symbol Substitution Test (DSST): B = −0.35, 95% CI = −0.44, −0.27). Self-reported chronic inflammatory conditions were associated with slower reaction time (B = 3.79, 95% CI = 2.81, 4.78) and lower DSST scores (B = −0.21, 95% CI = −0.30, −0.13). No interaction effects were observed.

In this large, population-based study we provide evidence of lower cognitive performance in both depression and a comprehensive category of chronic inflammatory conditions. Results are consistent with additive effects of both types of disorder on cognitive ability. Clinicians should be aware of such effects, particularly as cognitive impairment is linked to poorer disease outcomes and quality of life.

Life expectancy of people with depression is on average 15 years less than that of the general population. This excess of mortality is largely attributed to a deteriorated physical health. Evidence about the association between major depressive disorder (MDD) and physical health is still lacking in some areas. The aim of this study was to explore the association between MDD and physical health-related variables in southern Spain.

The PISMA-ep is a cross-sectional study based on community-dwelling adult population. Our main outcome was current prevalence of MDD. Independent variables explored were: lifetime prevalence of twenty-one chronic physical conditions (CPCs), anthropometric measures (height, weight, body max index, and hip and waist circumferences), general health status, and medication use.

MDD was significantly associated with any CPC (OR = 2.60; 95% CI: 2.01–3.35; p < 0.001). Increases in BMI were associated with MDD in women (OR=1.08; 95% CI: 1.05–1.11; p < 0.001), but not in men (OR=0.99; 95% CI: 0.95–1.05; p = 0.916). Variables associated with MDD in the multivariate model were: female gender, obesity, general health status, cancer, peptic ulcer, tinnitus and vertigo. 21.4% of participants with MDD received antidepressant treatment.

MDD is associated with CPCs, obesity, and increased use of medication. The high rates of comorbidity between MDD and CPCs call for a more holistic management of patients in the clinical practice. The low rate of antidepressant use may be indicating underdiagnosis. Anthropometric variables were differently associated with MDD depending on gender, suggesting a strong influence of psychosocial factors.

Electroconvulsive therapy (ECT) is a highly effective treatment for severe psychiatric disorders. Despite its high efficacy, the use of ECT would be greater if the risk of cognitive side effects were reduced. Over the last 20 years, developments in ECT technique, including improvements in the dosing methodology and modification of the stimulus waveform, have allowed for improved treatment methods with reduced adverse cognitive effects. There is increasing evidence that the electrode placement is important for orienting the electrical stimulus and therefore modifying treatment outcomes, with potential for further improvement of the placements currently used in ECT.

We used computational modelling to perform an in-depth examination into regional differences in brain excitation by the ECT stimulus for several lesser known and novel electrode placements, in order to investigate the potential for an electrode placement that may optimise clinical outcomes.

High resolution finite element human head models were generated from MRI scans of three subjects. The models were used to compare regional differences in average electric field (EF) magnitude among a total of thirteen bipolar ECT electrode placements, i.e. three conventional placements as well as ten lesser known and novel placements.

In this exploratory study on a systemic comparison of thirteen ECT electrode placements, the EF magnitude at regions of interest (ROIs) was highly dependent upon the position of both electrodes, especially the ROIs close to the cortical surface. Compared to conventional right-unilateral (RUL) ECT using a temporo-parietal placement, fronto-parietal and supraorbito-parietal RUL also robustly stimulated brain regions considered important for efficacy, while sparing regions related to cognitive functions, and may be a preferrable approach to the currently used placement for RUL ECT. The simulations also found that regional average EF magnitude varied between individual subjects, due to factors such as head size, and results also depended on the size of the defined ROI.

we aimed to compare socio-demographic and clinical differences between patients with versus without current RC in order to detect clinical factors that may favor early diagnosis and personalized treatment.

A total of 1675 patients (males: n = 714 and females: n = 961; bipolar 1: n = 1042 and bipolar 2: n = 633) from different psychiatric clinics were grouped and compared according to the current presence of RC in terms of socio-demographic and clinical variables. Chi-squared tests for qualitative variables and Student’s t tests for quantitative variables were executed for group comparison, and multivariable logistic regressions were performed, considering the current presence of RC as dependent variable, and socio-demographic/clinical factors as independent variables.

Female gender (male versus female: OR = 0.64, p = 0.04), unidentifiable prevalent polarity (versus depressive polarity: OR = 1.76, p = 0.02; versus manic polarity: OR: 2.86, p < 0.01) and hospitalization in the last year (no versus yes: OR = 0.63, p = 0.02) were found to be associated with RC in the final multivariable regression analysis.

RC in BD seems to be more prevalent in female gender and associated with some unfavorable clinical features, such as an increased risk of hospitalization. These aspects should be taken into account in the management and monitoring of RC versus non-RC patients.

Lifestyles are involved in the pathogenesis of depression and many of these factors can be modified for the potential prevention of depression. Our aim was to assess the association between a healthy-lifestyle score, that includes some less-studied lifestyle indicators, and the risk of depression.

We followed 14,908 participants initially free of any history of depression in the “Seguimiento Universidad de Navarra” (SUN) cohort. Information was collected biennially from 1999 to December 2016. We calculated a healthy-lifestyle score (0–10 points), previously associated with cardioprotection, by giving one point to each of the following components: never smoking, physical activity (> 20 METs-h/week), Mediterranean diet adherence (≥ 4 points), healthy body mass index (≤ 22 kg/m2), moderate alcohol consumption (women 0.1–5 g/d; men 0.1–10 g/d of ethanol), avoidance of binge drinking (never more than 5 alcoholic drinks in a row), low television exposure (≤ 2 h/d), short afternoon nap (≤ 30 min/day), time spent with friends (>1 h/d) and working at least 40 h/week.

During a median follow-up of 10.4 years, we observed 774 new cases of major depression among participants initially free of depression. The highest category (8–10 factors) showed a significant inverse association with a 32% relative risk reduction for depression compared to the lowest category (0–3 factors) (multivariable-adjusted hazard ratio: 0.68; 95% CI:0.49-0.95) (p for trend = 0.010).

Adopting a healthy-lifestyle was associated with a lower risk of incident depression in the SUN cohort. This index, including ten simple healthy lifestyle habits, may be useful for a more integrative approach to depression prevention.

In mental health research, functional recovery is increasingly valued as an important outcome in addition to symptomatic remission.

Course types of functional limitations among depressed older patients and its relation with symptomatic remission were explored in a naturalistic cohort study (Netherlands Study of Depression in Older persons). 378 depressed older patients (≥60 years) and 132 non-depressed persons were included. Depressive disorders were assessed with Composite International Diagnostic Interview at baseline and two-year follow-up. Functional limitations were assessed every 6 months with the World Health Organization Disability Assessment II.

Depressed patients had more functional limitations compared to their non-depressed counterparts. Growth Mixture Modeling among depressed patients identified two trajectories of functional limitations, both starting at a high disability level. The largest subgroup (81.2%) was characterized by a course of high disability levels over time. The smaller subgroup (18.8%) had an improving course (functional recovery). After two years, the main predictor of functional recovery was the remission of depression. Among symptomatic remitted patients, female sex, higher level of education, higher gait speed, and less severe depression were associated with no functional recovery. Non-remitted patients without functional recovery were characterized by the presence of more chronic somatic diseases, a lower sense of mastery, and a higher level of anxiety.

1 in 5 depressed older patients have a course with functional recovery. Combining functional and symptomatic recovery points to a subgroup of older patients that might profit from more rigorous psychiatric treatment targeted at psychiatric comorbidity and a group of frail depressed older patients that might profit from integrated geriatric rehabilitation.

Sleep alterations are frequent occurrence in Bipolar Disorder (BD), both in acute and interepisodic phases. Sleep alterations have been also described both long before BD onset, as aspecific risk syndromes, or as immediate prodromes of BD onset. The aim of the present study is to systematically review the relationship between sleep alterations anticipating for the full-blown onset of BD, both in general and according to specific polarities of onset.

A systematic literature research according to PRISMA statement and considering: 1. prospective studies about BD patients’ offspring with sleep alterations who later developed BD. 2. prospective studies assessing patients with sleep disorders who later developed BD. 3. retrospective studies on BD patients where sleep alterations before BD onset of the disease were reported.

A total of 16 studies were included in this review. Sleep disturbances may frequently appear 1 year before the onset of BD or more, often during childhood or adolescence. A decreased need for sleep may precede the onset of the illness, specially a manic episode, while insomnia appears to anticipate either a manic or a depressive episode. Hypersomnia seems to precede bipolar depressive episodes.

Sleep alterations frequently appear long before the onset of BD, and appear to be related specifically to the polarity of the index episode. The detection and treatment of sleep alterations in special high risk populations may help achieving an earlier detection of the illness.

The hippocampus is not a uniform structure, but rather consists of multiple, functionally specialized subfields. Few studies have explored hippocampal subfield volume difference in the same sample of major depressive disorder (MDD) and bipolar disorder (BD) cases. We aimed to investigate the difference of hippocampal subfield volume between patents with MDD and BD and healthy controls (HCs).

A total of 102 MDD and 55 BD patients and 135 HCs were recruited and underwent T1-weighted image. Hippocampal subfield volume was calculated by automated segmentation and volumetric procedures developed by Iglesias et al. and implemented in FreeSurfer. Volume differences between the groups were analyzed using the analysis of covariance and controlling for age, sex, and total intracranial cavity volume.

Patients with MDD had significantly reduced volumes in the bilateral cornu ammonis 1 (CA1), CA4, the granule cell layer (GCL), molecular layer (ML), whole hippocampus, the left CA2/3, and right presubiclum and subiculum. Patients with BD had significantly reduced volumes in the right CA1, GCL, and the whole hippocampus as compared to HCs. No significant volume differences were observed between the MDD and BD groups. Illness duration was negatively correlated with volumes of the left CA1, CA4, ML, presubiculum, subiculum, and the whole hippocampus in patients with BD.

We observed hippocampal subfield volume reductions in both MDD and BD, a finding which more prominent in MDD. The inverse correlation between BD illness duration and hippocampal subfield volume may evidence the neuroprogressive nature of BD.