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.

Hemispheric lateralization abnormalities of the white matter microstructure in patients with schizophrenia and bipolar disorder.

BACKGROUND: Hemispheric lateralization of the brain occurs during development and underpins specialized functions. It is posited that aberrant neurodevelopment leads to abnormal brain lateralization in individuals with psychotic illnesses. Here, we sought to examine whether white matter hemispheric lateralization is abnormal in individuals with the psychotic spectrum disorders of schizophrenia and bipolar disorder. METHODS: We examined the white matter microstructure lateralization in patients with schizophrenia, bipolar disorder with psychotic features and healthy controls by measuring the laterality indices of fractional anisotropy (FA) and mean diffusivity (MD). We also correlated the laterality indices with clinical measures. RESULTS: We included 150 patients with schizophrenia, 35 with bipolar disorder and 77 healthy controls in our analyses. Shared FA lateralization abnormalities in patients with schizophrenia and bipolar disorder were found in the cerebral peduncle and posterior limb of internal capsule, with more extensive abnormalities in patients with bipolar disorder than in those with schizophrenia. The shared MD lateralization abnormalities were more widespread, extending to the subcortical, frontal-occipital, limbic and callosal tracts, with patients with bipolar disorder showing greater abnormalities than patients with schizophrenia. While lateralization was decreased in patients with schizophrenia, the lateralization was reversed in those with bipolar disorder, underpinned by the more pronounced microstructural abnormalities in the right hemisphere. The loss of FA lateralization in patients with schizophrenia was associated with lower quality of life and psychosocial functioning. LIMITATIONS: Owing to the cross-sectional study design, we cannot confirm whether the lateralization abnormalities are neurodevelopmental or a consequence of psychosis onset or chronicity. CONCLUSION: Shared and distinct white matter lateralization abnormalities were found in patients with schizophrenia and bipolar disorder. In distinct regions of abnormalities, the lateralization was attenuated in patients with schizophrenia and reversed in those with bipolar disorder.

Shared and divergent neurocognitive impairments in adult patients with schizophrenia and bipolar disorder: Whither the evidence?

Recent data from genetic and brain imaging studies have urged rethinking of bipolar disorder (BD) and schizophrenia (SCZ) as lying along a continuum of major endogenous psychoses rather than dichotomous disorders. We systematically reviewed extant studies (from January 2000 to July 2015) that directly compared neurocognitive impairments in adults with SCZ and BD. Within 36 included studies, comparable neurocognitive impairments were found in SCZ and BD involving executive functioning, working memory, verbal fluency and motor speed. The extent and severity of neurocognitive impairments in patients with schizoaffective disorder, and BD with psychotic features occupy positions intermediate between SCZ and BD without psychotic features, suggesting spectrum of neurocognitive impairments across psychotic spectrum conditions. Neurocognitive impairments correlated with socio-demographic (lower education), clinical (more hospitalizations, longer duration of illness, negative psychotic symptoms and non-remission status), treatment (antipsychotics, anti-cholinergics) variables and lower psychosocial functioning. The convergent neurocognitive findings in both conditions support a continuum concept of psychotic disorders and further research is needed to clarify common and dissimilar progression of specific neurocognitive impairments longitudinally.

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.

Corpus callosum morphology in first-episode and chronic schizophrenia: combined magnetic resonance and diffusion tensor imaging study of Chinese Singaporean patients.

BACKGROUND: Abnormalities in the corpus callosum have been reported in patients with schizophrenia for over 30 years but the influence of inter-individual differences and illness characteristics remains to be fully elucidated. AIMS: To examine the influence of individual and illness characteristics on the corpus callosum in Chinese Singaporean patients with schizophrenia. METHOD: Using magnetic resonance and diffusion tensor imaging, mean corpus callosum area, volume and fractional anisotropy were investigated in 120 Chinese Singaporean patients (52 with chronic and 68 with first-episode schizophrenia) and compared with data from 75 matched healthy controls. RESULTS: Both area and volume were significantly reduced in patients relative to controls but no significant differences in corpus callosum existed between genders in either patients or controls. Differences in area and volume of the corpus callosum were greatest in patients whose condition was chronic relative to patients with a first episode and controls. Anterior callosum in patients, regardless of chronicity, was no different to that of controls. CONCLUSIONS: Morphological abnormalities in the corpus callosum may increase with illness progression.

Neurocognitive Functioning in Schizophrenia and Bipolar Disorder: Clarifying Concepts of Diagnostic Dichotomy vs. Continuum.

The Kraepelinian dichotomy posits that patients with schizophrenia (SCZ) and bipolar disorder (BD) present as two separate psychotic entities such that they differ in terms of clinical severity including neurocognitive functioning. Our study aimed to specifically compare and contrast the level of neurocognitive functioning between SCZ and BD patients and identify predictors of their poor neurocognitive functioning. We hypothesized that patients with SCZ had a similar level of neurocognitive impairment compared with BD. About 49 healthy controls (HC), 72 SCZ, and 42 BD patients who were matched for age, gender, and premorbid IQ were administered the Brief Assessment of Cognition battery (BAC). Severity of psychopathology and socio-occupational functioning were assessed for both patients groups. Both BD and SCZ groups demonstrated similar patterns of neurocognitive deficits across several domains (verbal memory, working memory, semantic fluency, processing speed) compared with HC subjects. However, no significant difference was found in neurocognitive functioning between BD and SCZ patients, suggesting that both patient groups suffer the same degree of neurocognitive impairment. Patients with lower level of psychosocial functioning [F (1,112) = 2.661, p = 0.009] and older age [F (1,112) = -2.625, p = 0.010], not diagnosis or doses of psychotropic medications, predicted poorer overall neurocognitive functioning as measured by the lower BAC composite score. Our findings of comparable neurocognitive impairments between SCZ and BD affirm our hypothesis and support less the Kraepelinian concept of dichotomy but more of a continuum of psychotic spectrum conditions. This should urge clinicians to investigate further the underlying neural basis of these neurocognitive deficits, and be attentive to the associated socio-demographic and clinical profile in order to recognize and optimize early the management of the widespread neurocognitive deficits in patients with SCZ and BD.

Tracking cerebral white matter changes across the lifespan: insights from diffusion tensor imaging studies.

Delineating the normal development of brain white matter (WM) over the human lifespan is crucial to improved understanding of underlying WM pathology in neuropsychiatric and neurological conditions. We review the extant literature concerning diffusion tensor imaging studies of brain WM development in healthy individuals available until October 2012, summarise trends of normal development of human brain WM and suggest possible future research directions. Temporally, brain WM maturation follows a curvilinear pattern with an increase in fractional anisotropy (FA) from newborn to adolescence, decelerating in adulthood till a plateau around mid-adulthood, and a more rapid decrease of FA from old age onwards. Spatially, brain WM tracts develop from central to peripheral regions, with evidence of anterior-to-posterior maturation in commissural and projection fibres. The corpus callosum and fornix develop first and decline earlier, whilst fronto-temporal WM tracts like cingulum and uncinate fasciculus have protracted maturation and decline later. Prefrontal WM is most vulnerable with greater age-related FA reduction compared with posterior WM. Future large scale studies adopting longitudinal design will better clarify human brain WM changes over time.

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.

Arcuate fasciculus abnormalities and their relationship with psychotic symptoms in schizophrenia.

Disruption of fronto-temporal connections involving the arcuate fasciculus (AF) may underlie language processing anomalies and psychotic features such as auditory hallucinations in schizophrenia. No study to date has specifically investigated abnormalities of white matter integrity at particular loci along the AF as well as its regional lateralization in schizophrenia. We examined white matter changes (fractional anisotropy (FA), axial diffusivity (AD), asymmetry indices) along the whole extent of the AF and their relationship with psychotic symptoms in 32 males with schizophrenia and 44 healthy males. Large deformation diffeomorphic metric mapping and Fiber Assignment Continuous Tracking were employed to characterize FA and AD along the geometric curve of the AF. Our results showed that patients with schizophrenia had lower FA in the frontal aspects of the left AF compared with healthy controls. Greater left FA and AD lateralization in the temporal segment of AF were associated with more severe positive psychotic symptoms such as delusions and hallucinations in patients with schizophrenia. Disruption of white matter integrity of the left frontal AF and accentuation of normal left greater than right asymmetry of FA/AD in the temporal AF further support the notion of aberrant fronto-temporal connectivity in schizophrenia. AF pathology can affect corollary discharge of neural signals from frontal speech/motor initiation areas to suppress activity of auditory cortex that may influence psychotic phenomena such as auditory hallucinations and facilitate elaboration of delusional content.

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.

The brain's voices: comparing nonclinical auditory hallucinations and imagery.

Although auditory verbal hallucinations are often thought to denote mental illness, the majority of voice hearers do not satisfy the criteria for a psychiatric disorder. Here, we report the first functional imaging study of such nonclinical hallucinations in 7 healthy voice hearers comparing them with auditory imagery. The human voice area in the superior temporal sulcus was activated during both hallucinations and imagery. Other brain areas supporting both hallucinations and imagery included fronto temporal language areas in the left hemisphere and their contralateral homologues and the supplementary motor area (SMA). Hallucinations are critically distinguished from imagery by lack of voluntary control. We expected this difference to be reflected in the relative timing of prefrontal and sensory areas. Activity of the SMA indeed preceded that of auditory areas during imagery, whereas during hallucinations, the 2 processes occurred instantaneously. Voluntary control was thus represented in the relative timing of prefrontal and sensory activation, whereas the sense of reality of the sensory experience may be a product of the voice area activation. Our results reveal mechanisms of the generation of sensory experience in the absence of external stimulation and suggest new approaches to the investigation of the neurobiology of psychopathology.