Self-compassion and parenting efficacy among mothers who are breast cancer survivors: Implications for psychological distress.

Mothers who are breast cancer survivors may experience psychological distress in relation to diminished parenting efficacy. Self-compassion may protect mothers from psychological distress, yet little is known about self-compassion in this population. The extent to which self-warmth (self-kindness, mindfulness and sense of common humanity) and self-coldness (self-judgement, isolation and over-identification) dimensions of self-compassion moderate parenting efficacy in predicting depression, anxiety and stress was examined in a sample of 95 mothers who were breast cancer survivors. Independently, poorer parenting efficacy was associated with more depression and stress symptoms. Within regression models, self-coldness was a direct predictor of depression, anxiety and stress, while self-warmth moderated the relationship between parenting efficacy and stress. Self-warmth presents as a potential protective factor for stress associated with poor parenting efficacy, while self-coldness is a potential direct risk factor for psychological distress. Mothers who are breast cancer survivors may benefit from self-compassion focused psychosocial interventions.

Fear of cancer recurrence as a pathway from fatigue to psychological distress in mothers who are breast cancer survivors.

Fatigue is prevalent and pervasive among breast cancer survivors. Mothers are particularly susceptible to fatigue due to the ongoing demands of their caring role. While fatigue has been associated with psychological distress in prior research, the pathway by which fatigue translates into psychological distress is unclear. Given the theoretical and empirical links between fatigue, fear of cancer recurrence (FCR) and psychological distress, the role of FCR in mediating the relationship between fatigue and psychological distress in mothers who are breast cancer survivors was investigated. Ninety-two mothers who were breast cancer survivors completed the Depression, Anxiety and Stress Scale, PROMIS-Cancer Fatigue Short Form and Concerns About Cancer Recurrence scale in an online survey. Mediation analysis via PROCESS was used to examine whether fatigue predicted depression, anxiety or stress through FCR. Fear of cancer recurrence mediated the relationships between fatigue and anxiety and fatigue and stress, while fatigue directly predicted depression. This study highlights FCR as a potential pathway to anxiety and stress in response to ongoing fatigue, and as a mechanism of action to reduce psychological distress among mothers who are breast cancer survivors. Future research examining this pathway from fatigue to psychological distress should also explore the nature of mothers' fears about their cancer recurring.

Posttraumatic growth as a buffer and a vulnerability for psychological distress in mothers who are breast cancer survivors.

BACKGROUND: This study investigated the role of posttraumatic growth (PTG) in moderating the associations between parenting efficacy and psychological distress, and between fear of cancer recurrence (FCR) and psychological distress, in mothers who are breast cancer survivors. METHODS: In this cross-sectional study, mothers who were breast cancer survivors (N = 91) completed the Depression, Anxiety and Stress Scale (DASS-21), Cancer-Related Parenting Self-Efficacy (CaPSE), Concerns About Cancer Recurrence (CARS) and Posttraumatic Growth Inventory Short Form (PTGI-SF). Hierarchical multiple linear regressions and simple-slope tests were used to examine the main effects of the predictors (CaPSE and CARS) and moderator (PTGI-SF), and interaction effects of CaPSExPTGI-SF and CARSxPTGI-SF. The analyses were repeated for each outcome variable: Depression, Anxiety and Stress. RESULTS: Higher CARS significantly predicted higher Depression, Anxiety and Stress, and lower CaPSE significantly predicted higher Depression and Stress. Significant CaPSExPTGI-SF and CARSxPTGI-SF interactions predicted Depression. Simple-slopes tests indicated a significant positive association between CARS and Depression for mothers with high levels of PTG, but not with low levels of PTG. A negative association was indicated between CaPSE and Depression for mothers with low levels of PTGI-SF, though neither slope was significant. LIMITATIONS: Our results are only generalisable to mothers with similar socio-demographic backgrounds. CONCLUSIONS: PTG may serve as both a protective and a risk factor for depression in mothers who are breast cancer survivors. Debate remains whether PTG is best conceptualised as a perceived positive outcome or an ongoing coping mechanism in the face of parenting challenges and cancer-related threats such as FCR.

Psychological distress, role, and identity changes in mothers following a diagnosis of cancer: A systematic review.

OBJECTIVE: To systematically review findings of the impact of cancer diagnosis and treatment on mothers' psychological well-being, roles, and identity and to explore the psychosocial factors that contribute to mothers' psychological well-being. METHODS: Six databases were searched for research articles and theses exploring the association between the impact of cancer diagnosis and treatment on mothers' psychological well-being, identity, and role, and the psychosocial factors contributing to mothers' psychological distress regardless of their cancer type and stage. The Mixed-Method Appraisal Bias Tool was used to assess the selected studies' methodological quality. RESULTS: A total of 30 qualitative, quantitative, and mixed-method studies were deemed eligible for inclusion. Most studies reported that mothers experienced significant psychological distress, changes to or loss of parenting efficacy, maternal identity, and role. Psychosocial factors that contributed to mothers' distress included mothers' young age, presence of metastases, lower parenting efficacy, fear of cancer recurrence, higher illness intrusiveness, and lack of appropriate support. Four main themes emerged from the qualitative studies: psychological impact of cancer on mothers, changes in maternal identity and role, relationship changes and concerns for their children, and meaning-making in cancer experience. CONCLUSIONS: Changes in mothers' psychological well-being, role, and identity occurred across cancer diagnoses, treatment, and recovery trajectories. The evidence suggests that mothers may benefit from continued and tailored psychosocial support to cope with these challenges, even after treatment is completed. Further studies with improved methodological quality are needed to explore these issues in depth.

The 23-Hour Observation Unit Admissions Within the Emergency Service at a National Tertiary Psychiatric Hospital: Clarifying Clinical Profiles, Outcomes, and Predictors of Subsequent Hospitalization.

OBJECTIVE: We examined health care utilization, clinical profiles (such as sociodemographic features, clinical severity), and outcomes (inpatient admission, revisit within 24 hours of discharge) of patients who were admitted to a 23-hour observation unit within the emergency service of a tertiary psychiatric hospital and hypothesized that a specific clinical profile (greater clinical severity, lower psychosocial functioning) predicted subsequent inpatient hospitalization. METHOD: The medical records of all patients admitted to the observation unit from February 5, 2007, to February 4, 2012 (N = 2,158) were assessed for relevant data. Clinical severity and level of psychosocial functioning were assessed using Clinical Global Impressions-Severity (CGI-S) and Global Assessment of Functioning (GAF) scales, respectively. RESULTS: Overall, the patients seen were predominantly Chinese males > 36 years old who had diagnoses including stress-related, anxiety, affective spectrum, and psychotic disorders. The clinical severity score (CGI-S) improved significantly following discharge from the observation unit (t 1,1848 = 23.316; P < .001). Logistic regression analyses revealed that self-referred (P = .001), older patients (P = .007) with past psychiatric history (P = .019), lower GAF scores (P = .025), and less improvement of CGI-S scores (P = .001) were associated with inpatient admission after a 23-hour stay in the observation unit. CONCLUSIONS: Our study findings affirmed our hypothesis and supported the utility of the observation unit in monitoring the overall clinical status of patients, which was linked with subsequent inpatient admissions. Better management of these patients at the outpatient level can potentially decrease unnecessary hospitalization and reduce health care cost as well as illness burden on patients and caregivers.

The impact of genome wide supported microRNA-137 (MIR137) risk variants on frontal and striatal white matter integrity, neurocognitive functioning, and negative symptoms in schizophrenia.

Although genome wide association studies have highlighted MicroRNA 137 (MIR137) as a novel susceptibility gene for schizophrenia, the mechanisms by which MIR137 risk variants mediate the neurobiology of schizophrenia are not clear. Based on extant data linking MIR 137 gene with structural brain anomalies and functional brain activations in schizophrenia, we hypothesized that MIR137 risk variants rs1625579 and rs1198588 would be associated with reduced fractional anisotropy in frontostriatal brain regions, impaired neurocognitive functioning and worse psychotic symptoms in schizophrenia patients compared with healthy controls. A total of 147 Chinese participants (84 patients with DSM-IV diagnosis of schizophrenia (SCZ) and 63 healthy controls (HC)) were genotyped using blood samples and underwent diffusion tensor imaging. Neurocognitive domains and psychotic symptoms were assessed using The Brief Assessment of Cognition Battery for Schizophrenia and Positive and Negative Syndrome Scale respectively. We found significant diagnosis-genotype interactions in the right orbitofrontal regions (rs1625579: F = 5.44, P = 0.021; rs1198599: F = 7.55, P = 0.005), left striatum (rs1625579: F = 8.09, P=0.007; rs1198599: F=9.56, P = 0.002), and negative symptoms (rs1625579: t = 2.45, P = 0.016; rs1198588: t = 2.29, P = 0.024). Specifically, SCZ carrying the risk TT genotype had worse negative symptoms and decreased FA in the fronto-striatal regions compared to G and A allele carriers for rs1625579 and rs1198588 respectively, and worse attention and processing speed compared with G-allele for rs1625579. Our findings suggested that the MI137 risk variants were associated with decreased fronto-striatal brain white matter integrity which may underlie poorer attention, processing speed, and greater negative symptoms in schizophrenia.

CACNA1C genomewide supported psychosis genetic variation affects cortical brain white matter integrity in Chinese patients with schizophrenia.

OBJECTIVE: Recent genomewide association studies have implicated the calcium channel, voltage-dependent, L type, alpha 1C subunit (CACNA1C) genetic variant in schizophrenia, which is associated with functional brain changes and cognitive deficits in healthy individuals. However, the impact of CACNA1C on brain white matter integrity in schizophrenia remains unclear. On the basis of prior evidence of CACNA1C-mediated changes involving cortical brain regions, we hypothesize that CACNA1C risk variant rs1006737 is associated with reductions of white matter integrity in the frontal, parietal, and temporal regions and cingulate gyrus. METHOD: A total of 160 Chinese participants (96 DSM-IV-diagnosed patients with schizophrenia and 64 healthy controls) were genotyped by using blood samples and underwent structural magnetic resonance imaging and diffusion tensor imaging scans from 2008 to 2012. Two-way analysis of covariance was employed to examine CACNA1C-related genotype effects, diagnosis effects, and genotype × diagnosis interaction effects on fractional anisotropy (FA) of relevant brain regions. RESULTS: Significant diagnosis-genotype interactions were observed (left frontal lobe mean FA: F1,156 = 6.22, P = .014; left parietal lobe mean FA: F1,156 = 7.14, P = .008; left temporal lobe mean FA: F1,156 = 8.37, P = .004). Compared with patients who were A carriers, patients who were G homozygotes had lower mean FA in the left frontal lobe (F1,93 = 2.504, P = .014), left parietal lobe (F1,93 = 2.37, P = .020), and left temporal lobe (F1,93 = 3.01, P = .003), with standardized effect sizes of -1.43, -1.3, and -1.0, respectively. CONCLUSIONS: CACNA1C risk variant rs1006737 affects cortical white matter integrity in schizophrenia. Further imaging genetic investigations on the mediating effect of CACNA1C in schizophrenia can uncover brain circuitries involved in schizophrenia and suggest potential novel targets for intervention.

Effects of the neurogranin variant rs12807809 on thalamocortical morphology in schizophrenia.

Although the genome wide supported psychosis susceptibility neurogranin (NRGN) gene is expressed in human brains, it is unclear how it impacts brain morphology in schizophrenia. We investigated the influence of NRGN rs12807809 on cortical thickness, subcortical volumes and shapes in patients with schizophrenia. One hundred and fifty six subjects (91 patients with schizophrenia and 65 healthy controls) underwent structural MRI scans and their blood samples were genotyped. A brain mapping algorithm, large deformation diffeomorphic metric mapping, was used to perform group analysis of subcortical shapes and cortical thickness. Patients with risk TT genotype were associated with widespread cortical thinning involving frontal, parietal and temporal cortices compared with controls with TT genotype. No volumetric difference in subcortical structures (hippocampus, thalamus, amygdala, basal ganglia) was observed between risk TT genotype in patients and controls. However, patients with risk TT genotype were associated with thalamic shape abnormalities involving regions related to pulvinar and medial dorsal nuclei. Our results revealed the influence of the NRGN gene on thalamocortical morphology in schizophrenia involving widespread cortical thinning and thalamic shape abnormalities. These findings help to clarify underlying NRGN mediated pathophysiological mechanisms involving cortical-subcortical brain networks in schizophrenia.

GRIN2B gene and associated brain cortical white matter changes in bipolar disorder: a preliminary combined platform investigation.

Abnormalities in glutamate signaling and glutamate toxicity are thought to be important in the pathophysiology of bipolar disorder (BD). Whilst previous studies have found brain white matter changes in BD, there is paucity of data about how glutamatergic genes affect brain white matter integrity in BD. Based on extant neuroimaging data, we hypothesized that GRIN2B risk allele is associated with reductions of brain white matter integrity in the frontal, parietal, temporal, and occipital regions and cingulate gyrus in BD. Fourteen patients with BD and 22 healthy controls matched in terms of age, gender and handedness were genotyped using blood samples and underwent diffusion tensor imaging. Compared to G allele, brain FA values were significantly lower in BD patients with risk T allele in left frontal region (P = 0.001), right frontal region (P = 0.002), left parietal region (P = 0.001), left occipital region (P = 0.001), right occipital region (P < 0.001), and left cingulate gyrus (P = 0.001). Further elucidation of the interactions between different glutamate genes and their relationships with such structural, functional brain substrates will enhance our understanding of the link between dysregulated glutamatergic neurotransmission and neuroimaging endophenotypes in BD.

Evidence-based options for treatment-resistant adult bipolar disorder patients.

OBJECTIVES: Many patients diagnosed with bipolar disorder (BD) respond incompletely or unsatisfactorily to available treatments. Given the potentially devastating nature of this prevalent disorder, there is a pressing need to improve clinical care of such patients. METHODS: We performed a literature review of the research findings related to treatment-resistant BD reported through February 2012. RESULTS: Therapeutic trials for treatment-resistant bipolar mania are uncommon, and provide few promising leads other than the use of clozapine. Far more pressing challenges are the depressive-dysthymic-dysphoric-mixed phases of BD and long-term prophylaxis. Therapeutic trials for treatment-resistant bipolar depression have assessed anticonvulsants, modern antipsychotics, glutamate [N-methyl-D-aspartate (NMDA)] antagonists, dopamine agonists, calcium-channel blockers, and thyroid hormones, as well as behavioral therapy, sleep deprivation, light therapy, electroconvulsive therapy (ECT), transcranial magnetic stimulation, and deep brain stimulation-all of which are promising but limited in effectiveness. Several innovative pharmacological treatments (an anticholinesterase, a glutamine antagonist, a calcium-channel blocker, triiodothyronine, olanzapine and topiramate), ECT, and cognitive-behavior therapy have some support for long-term treatment of resistant BD patients, but most of trials of these treatments have been methodologically limited. CONCLUSIONS: Most studies identified were small, involved supplementation of typically complex ongoing treatments, varied in controls, randomization, and blinding, usually involved brief follow-up, and lacked replication. Clearer criteria for defining and predicting treatment resistance in BD are needed, as well as improved trial design with better controls, assessment of specific clinical subgroups, and longer follow-up.

Genome-wide supported psychosis risk variant in ZNF804A gene and impact on cortico-limbic WM integrity in schizophrenia.

Genome-wide association, case association genetic and meta-analytic studies have highlighted ZNF804A as a robust genome-wide supported susceptibility gene for schizophrenia (SCZ). In view of the possible involvement of ZNF804A gene in early neurodevelopment and cellular processes including oligodendrocyte proliferation and differentiation, we examined the effect of ZNF804A on brain WM (WM) integrity in patients with SCZ. Based on extant data in healthy controls (HC), we hypothesized that ZNF804A risk variant rs1344706 is associated with lower fractional anisotropy (FA) in brain regions within cortico-limbic circuits, namely frontal, parietal, medial temporal lobes, and cingulate gyri in SCZ. A total of 200 Chinese participants (125 patients with DSM-IV diagnosis of SCZ and 75 controls) were genotyped using blood samples, a subset of 153 participants (89 patients with DSM-IV diagnosis of SCZ and 64 controls) underwent structural magnetic resonance imaging and diffusion tensor imaging (DTI). There are significant effects of diagnosis (left cingulate gyrus: Adjusted F(1,149) = 9.36, P = 0.003) and diagnosis-genotype interactions (left parietal lobe: Adjusted F(1,147) = 7.39, P = 0.007; right parietal lobe: Adjusted F(1,147) = 6.95, P = 0.009; right medial temporal lobe: Adjusted F(1,147) = 8.79, P = 0.004; left cingulate gyrus: Adjusted F(1,147) = 8.02, P = 0.005). Specifically, we found that patients with SCZ who are risk T homozygotes have lower FA in bilateral parietal lobes, and left cingulate gyrus compared with G carriers. Compared with risk T homozygotes in HC, patients with SCZ who are risk T homozygotes have decreased FA in bilateral parietal lobes, and left cingulate gyrus as well as right medial temporal lobe. Our findings suggest that ZNF804A risk variant influence WM integrity involving cortico-limbic brain regions in SCZ and highlight the importance of investigating the impact of genome-wide supported risk factors on intermediate phenotypes with potential to shed light on the neurobiology of SCZ.

Diffusion tensor imaging findings of white matter changes in first episode schizophrenia: a systematic review.

Earlier structural magnetic resonance imaging in schizophrenia have noted smaller white matter volumes in diverse brain regions and recent diffusion tensor imaging (DTI) studies have allowed better elucidation of changes in brain white matter integrity within the illness. As white matter abnormalities have been reported to occur early in the course of schizophrenia, we systematically review extant DTI studies of anomalies of white matter integrity in first episode schizophrenia (FES) up till October 2011. Overall, disruptions of white matter integrity were found in the cortical, subcortical brain regions and white matter associative and commissural tracts, suggesting that changes of cortical-subcortical white matter integrity were found at an early stage of the disorder. These changes in white matter integrity were correlated with specific cognitive deficits (verbal and spatial working memory) as well as psychopathology (positive more than negative symptoms) in patients with FES. The correlation of these white matter integrity changes with cognitive and phenomenological factors may shed light on neurobiological substrates underlying these clinical manifestations. Future studies need to validate these findings in larger samples of subjects and in different populations as well as chart the progress of these cerebral white matter changes over time so as to better appreciate their trajectory with illness course, treatment and chronicity.

Neurocognitive-genetic and neuroimaging-genetic research paradigms in schizophrenia and bipolar disorder.

Studies examining intermediate phenotypes such as neurocognitive and neuroanatomical measures along with susceptibility genes are important for improving our understanding of the neural basis of schizophrenia (SZ) and bipolar disorder (BD). In this paper, we review extant studies involving neurocognitive-genetic and neuroimaging-genetic perspectives and particularly related to catechol-O-methyltransferase (COMT), brain-derived neurotrophic factor (BDNF) and neuregulin-1 (NRG1) genes in SZ and BD. In terms of neurocognitive-genetic investigations, COMT and BDNF are the two most studied candidate genes especially in patients with SZ. Whereas BDNF Met carriers perform worse on verbal working memory, problem solving and visuo-spatial abilities, COMT Met carriers perform better in working memory, attention, executive functioning with evidence of genotype by diagnosis interactions including high-risk individuals. In terms of genetic-structural MRI studies, patients with SZ are found to have reductions in the frontal, temporal, parietal cortices, and limbic regions, which are associated with BDNF, COMT, and NRGI genes. Genetic-functional MRI studies in psychotic disorders are sparse, especially with regard to BD. These neurocognitive and neuroimaging findings are associated with genes which are implicated in functional pathways related to neuronal signaling, inter-neuronal communication and neuroplasticity.