Aberrant emotion regulation has been posited as a putative endophenotype of bipolar disorder (BD). We therefore aimed to compare the neural responses during voluntary down-regulation of negative emotions in a large functional magnetic resonance imaging study of BD, patients' unaffected first-degree relatives (URs), and healthy controls (HCs).

We compared neural activity and fronto-limbic functional connectivity during emotion regulation in response to aversive v. neutral pictures in patients recently diagnosed with BD (n = 78) in full/partial remission, their URs (n = 35), and HCs (n = 56).

Patients showed hypo-activity in the left dorsomedial, dorsolateral, and ventrolateral prefrontal cortex (DMPFC and DLPFC) during emotion regulation while viewing aversive pictures compared to HCs, with URs displaying intermediate neural activity in these regions. There were no significant differences between patients with BD and HCs in functional connectivity from the amygdala during emotion regulation. However, exploratory analysis indicated that URs displayed more negative amygdala–DMPFC coupling compared with HCs and more negative amygdala-cingulate DLPFC coupling compared to patients with BD. At a behavioral level, patients and their URs were less able to dampen negative emotions in response aversive pictures.

The findings point to deficient recruitment of prefrontal resources and more negative fronto-amygdala coupling as neural markers of impaired emotion regulation in recently diagnosed remitted patients with BD and their URs, respectively.

Few studies have reported real-life data on socio-economic functioning in patients with bipolar disorder and their unaffected first-degree relatives.

We used Danish nation-wide population-based longitudinal register linkage to investigate socio-economic functioning in 19 955 patients with bipolar disorder, their 13 923 siblings and 20 sex, age and calendar-matched control individuals from the general population. Follow-up was from 1995 to 2017.

Patients with a diagnosis of bipolar disorder had lower odds of having achieved the highest educational level [OR 0.75 (95% confidence interval (CI) 0.73–0.77)], being employed [OR 0.16 (95% CI 0.159–0.168)], having achieved the 80% highest quartile of income [OR 0.33 (95% CI 0.32–0.35)], cohabitating [OR 0.44 (95% CI 0.43–0.46)] and being married [OR 0.54 (95% CI 0.52–0.55)] at first contact to hospital psychiatry as inpatient or outpatient compared with control individuals from the general population. Similarly, siblings to patients with bipolar disorder had a lower functioning within all five socio-economic areas than control individuals. Furthermore, patients and partly siblings showed substantially decreased ability to enhance their socio-economic functioning during the 23 years follow-up compared to controls.

Socio-economic functioning is substantially decreased in patients with bipolar disorder and their siblings and does not improve during long-term follow-up after the initial hospital contact, highlighting a severe and overlooked treatment gap.

Morphological abnormalities of the anterior cingulate (AC) occur in patients with schizophrenia and in symptomatic high-risk individuals, and may be predictive of subsequent psychosis. We investigated AC sulcal morphology in the Edinburgh High Risk Study cohort to see if such abnormalities are evident and predict psychosis in patients’ relatives. We also investigated the association of the cingulate sulcus (CS) and paracingulate sulcus (PCS) variants with intelligence quotient (IQ).

We compared cingulate and paracingulate sulcal anatomy, using reliable standardised measurements, blind to group membership, in those at high genetic risk (n = 146), first episode patients (n = 34) and healthy controls (n = 36); and compared high-risk subjects who did (n = 17) or did not develop schizophrenia.

Interruptions of the cingulate sulcus were more common in high-risk individuals and in those with schizophrenia, in both hemispheres, compared to controls. When separated by gender, these results were only present in males in the left hemisphere and only in females in the right hemisphere. A well-formed paracingulate sulcus was less common in high-risk participants and patients with schizophrenia, compared to controls; but this association was only present in males. These morphological variants of the paracingulate sulcus and the continuous cingulate sulcus were also associated with the higher IQ in male high-risk individuals.

An interrupted cingulate sulcus pattern in both males and females and paracingulate morphology in males are associated with increased genetic risk of schizophrenia. Associations between cingulate and paracingulate morphology and premorbid IQ scores provide evidence that intellectual ability could be related to particular cytoarchitectural brain regions. Given that these sulci develop in early fetal life, such findings presumably reflect early neurodevelopmental abnormalities of genetic origin, although environmental effects and interactions cannot be ruled out.

Neuropsychological impairment, including deficits in social cognition is evident in subjects at genetic high-risk for psychosis. However, findings in youth at genetic risk to bipolar disorder (BP) have been suggested to be less supportive of premorbid deficits. We aimed to conduct a meta-analysis of cognitive deficits in youth with familiar risk for bipolar disorder (FHR-BD).

A novel meta-analysis of FHR-BD (mean age 10–25), including 18 studies (786 offsprings/siblings of patients with BD and 794 healthy controls), was conducted.

Both general cognition (d = 0.29, CI = 0.15–0.44) and social cognition (d = 0.23, CI = 0–0.45) were impaired in FHR-BD. In comparison to controls, FHR-BD had significant deficits in several cognitive domains, including visual memory (d = 0.35), verbal memory (d = 0.21), processing speed (d = 0.26) and sustained attention (d = 0.36). There was no significant difference between FHR-BD and controls in planning and working memory.

Cognitive deficits are evident in individuals who are at genetic high-risk for developing BD. Neurodevelopmental abnormalities are likely playing a role not only in schizophrenia but also in BD.

Identifying factors that influence the functional outcome is an important goal in schizophrenia research. The 22q11.2 deletion syndrome (22q11DS) is a unique genetic model with high risk (20–25%) for schizophrenia. This study aimed to identify potentially targetable domains of neurocognitive functioning associated with functional outcome in adults with 22q11DS.

We used comprehensive neurocognitive test data available for 99 adults with 22q11DS (n = 43 with schizophrenia) and principal component analysis to derive four domains of neurocognition (Verbal Memory, Visual and Logical Memory, Motor Performance, and Executive Performance). We then investigated the association of these neurocognitive domains with adaptive functioning using Vineland Adaptive Behavior Scales data and a linear regression model that accounted for the effects of schizophrenia status and overall intellectual level.

The regression model explained 46.8% of the variance in functional outcome (p < 0.0001). Executive Performance was significantly associated with functional outcome (p = 0.048). Age and schizophrenia were also significant factors. The effects of Executive Performance on functioning did not significantly differ between those with and without psychotic illness.

The findings provide the impetus for further studies to examine the potential of directed (early) interventions targeting Executive Performance to improve long-term adaptive functional outcome in individuals with, or at high risk for, schizophrenia. Moreover, the neurocognitive test profiles may benefit caregivers and clinicians by providing insight into the relative strengths and weaknesses of individuals with 22q11DS, with and without psychotic illness.

Negative bias and aberrant neural processing of emotional faces are trait-marks of depression but findings in healthy high-risk groups are conflicting.

Healthy middle-aged dizygotic twins (N = 42) underwent functional magnetic resonance imaging (fMRI): 22 twins had a co-twin history of depression (high-risk) and 20 were without co-twin history of depression (low-risk). During fMRI, participants viewed fearful and happy faces while performing a gender discrimination task. After the scan, they were given a faces dot-probe task, a facial expression recognition task and questionnaires assessing mood, personality traits and coping.

Unexpectedly, high-risk twins showed reduced fear vigilance and lower recognition of fear and happiness relative to low-risk twins. During face processing in the scanner, high-risk twins displayed distinct negative functional coupling between the amygdala and ventral prefrontal cortex and pregenual anterior cingulate. This was accompanied by greater fear-specific fronto-temporal response and reduced fronto-occipital response to all emotional faces relative to baseline. The risk groups showed no differences in mood, subjective state or coping.

Less susceptibility to fearful faces and negative cortico-limbic coupling during emotional face processing may reflect neurocognitive compensatory mechanisms in middle-aged dizygotic twins who remain healthy despite their familial risk of depression.

War and conflict are known to adversely affect mental health, although their effects on risk symptoms for psychosis development in youth in various parts of the world are unclear. The Rwandan genocide of 1994 and Civil War had widespread effects on the population. Despite this, there has been no significant research on psychosis risk in Rwanda. Our goal in the present study was to investigate the potential effects of genocide and war in two ways: by comparing Rwandan youth born before and after the genocide; and by comparing Rwandan and Kenyan adolescents of similar age.

A total of 2255 Rwandan students and 2800 Kenyan students were administered the Washington Early Recognition Center Affectivity and Psychosis (WERCAP) Screen. Prevalence, frequency and functional impairment related to affective and psychosis-risk symptoms were compared across groups using univariate and multivariate statistics.

Rwandan students born before the end of the genocide and war in 1994 experienced higher psychotic and affective symptom load (p’s < 0.001) with more functional impairment compared with younger Rwandans. 5.35% of older Rwandan students met threshold for clinical high-risk of psychosis by the WERCAP Screen compared with 3.19% of younger Rwandans (χ 2 = 5.36; p = 0.02). Symptom severity comparisons showed significant (p < 0.001) group effects between Rwandan and Kenyan secondary school students on affective and psychotic symptom domains with Rwandans having higher symptom burden compared with Kenyans. Rwandan female students also had higher rates of psychotic symptoms compared with their male counterparts – a unique finding not observed in the Kenyan sample.

These results suggest extreme conflict and disruption to country from genocide and war can influence the presence and severity of psychopathology in youth decades after initial traumatic events.

Previous reviews have reported cognitive and motor deficits in childhood and adolescence among individuals who later develop schizophrenia. However, these reviews focused exclusively on studies of individuals with affected relatives or on population/birth cohorts, incorporated studies with estimated measures of pre-morbid intelligence, or included investigations that examined symptomatic at-risk participants or participants 18 years or older. Thus, it remains unclear whether cognitive and motor deficits constitute robust antecedents of schizophrenia. Meta-analyses were conducted on published studies that examined cognitive or motor function in youth aged 16 years or younger who later developed schizophrenia or a schizophrenia spectrum disorder (SSD) and those who did not.

Twenty-three studies fulfilled the following inclusion criteria: (1) written in English; (2) prospective investigations of birth or genetic high-risk cohorts, or follow-back investigations of population samples; (3) objective measures of cognitive or motor performance at age 16 or younger; (4) results provided for individuals who did and who did not develop schizophrenia/SSD later in life; and (5) sufficient data to calculate effect sizes. Four domains of function were examined: IQ; Motor Function; General Academic Achievement; and Mathematics Achievement.

Meta-analyses showed that, by age 16, individuals who subsequently developed schizophrenia/SSD displayed significant deficits in IQ (d=0.51) and motor function (d=0.56), but not in general academic achievement (d=0.25) or mathematics achievement (d=0.21). Subsidiary analysis indicated that the IQ deficit was present by age 13.

These results demonstrate that deficits in IQ and motor performance precede the prodrome and the onset of illness.

Few studies have examined religiosity as a protective factor using a longitudinal design to predict resilience in persons at high risk for major depressive disorder (MDD).

High-risk offspring selected for having a depressed parent and control offspring of non-depressed parents were evaluated for psychiatric disorders in childhood/adolescence and at 10-year and 20-year follow-ups. Religious/spiritual importance, services attendance and negative life events (NLEs) were assessed at the 10-year follow-up. Models tested differences in relationships between religiosity/spirituality and subsequent disorders among offspring based on parent depression status, history of prior MDD and level of NLE exposure. Resilience was defined as lower odds for disorders with greater religiosity/spirituality in higher-risk versus lower-risk offspring.

Increased attendance was associated with significantly reduced odds for mood disorder (by 43%) and any psychiatric disorder (by 53%) in all offspring; however, odds were significantly lower in offspring of non-depressed parents than in offspring of depressed parents. In analyses confined to offspring of depressed parents, those with high and those with average/low NLE exposure were compared: increased attendance was associated with significantly reduced odds for MDD, mood disorder and any psychiatric disorder (by 76, 69 and 64% respectively) and increased importance was associated with significantly reduced odds for mood disorder (by 74%) only in offspring of depressed parents with high NLE exposure. Moreover, those associations differed significantly between offspring of depressed parents with high NLE exposure and offspring of depressed parents with average/low NLE exposure.

Greater religiosity may contribute to development of resilience in certain high-risk individuals.

Numerous longitudinal studies have identified risk factors for the onset of most eating disorders (EDs). Identifying women at highest risk within a high-risk sample would allow for focusing of preventive resources and also suggests different etiologies.

A longitudinal cohort study over 3 years in a high-risk sample of 236 college-age women randomized to the control group of a prevention trial for EDs. Potential risk factors and interactions between risk factors were assessed using the methods developed previously. Main outcome measures were time to onset of a subthreshold or full ED.

At the 3-year follow-up, 11.2% of participants had developed a full or partial ED. Seven of 88 potential risk factors could be classified as independent risk factors, seven as proxies, and two as overlapping factors. Critical comments about eating from teacher/coach/siblings and a history of depression were the most potent risk factors. The incidence for participants with either or both of these risk factors was 34.8% (16/46) compared to 4.2% (6/144) for participants without these risk factors, with a sensitivity of 0.75 and a specificity of 0.82.

Targeting preventive interventions at women with high weight and shape concerns, a history of critical comments about eating weight and shape, and a history of depression may reduce the risk for EDs.

Exploration of complicated grief focusing on the relationship of post-traumatic stress disorder (PTSD) and complicated grief in a population of women at high risk for developing breast cancer. Special reference is made to women who have experienced a material death.

We reflected on the clinical attributes of the Revlon UCLA High Risk Clinic population in terms of their own perceived risk of developing breast cancer. For part of our population, their perceived risk was coupled with their reactions to the loss of their mothers to breast cancer. We compared and contrasted this pattern of reactions to those described by Licihtenthal et al. (2004) in their developmental review of complicated grief as a distinct disorder.

We concluded that our population of women differed from Lichtenthal et al.'s (2004) model for complicated grief. Lichtenthal's group postulated that the key element of complicated grief involves the protracted nature of separation anxiety and distress and excludes PTSD. In our populations, the daughter with complicated grief experiences a combination of separation anxiety and a type of PTSD involving anxiety over the perceived certainty of her own future diagnosis of breast cancer. It was noteworthy that Lichtenthal's model population was composed of individuals caring for terminally ill spouses. Significantly, the spousal caretakers did not have an ongoing genetic link to their partners whereas our population is genetically linked. We postulate that this accounts for the unique presentation of complicated grief and PTSD in our population.

We submit that this combination of complicated grief and PTSD requires a cognitive reframing of thier perceived inevitability of developing breast cancer and desensitization techniques to help high risk women pursue preventative health care rather than avoiding it.