The role of microbiota and inflammation in self-judgement and empathy: implications for understanding the brain-gut-microbiome axis in depression.

RATIONALE: The gut-brain axis includes bidirectional communication between intestinal microbiota and the central nervous system. Bifidobacterium and Lactobacillus spp. have been implicated in psychological health, such as depression, through various pathways (e.g. inflammation). Research needs a better understanding of direct and indirect effects through examination of psychological factors that make people susceptible to, or offer protection against, depression. OBJECTIVE: This study investigated the relationships between gut microbiota, inflammation and psychological risk and resilience factors for depression. METHODS: Forty participants (13 m/27 f) recruited from the general population completed self-report questionnaires for depression, self-judgement, over-identification and affective and cognitive empathy. Faecal and blood samples were taken to assay microbiota (Bifidobacterium; Lactobacillus spp.) and pro-inflammatory molecules (C-reactive protein, CRP and interleukin-6, IL-6), respectively. RESULTS: Hierarchical regression analyses (controlling for sex, age and the shared variance of risk and resilience factors) showed that (i) cognitive depression was significantly predicted by negative self-judgement and reduced cognitive empathy; (ii) abundance of Lactobacillus spp. was directly related to positive self-judgement but only indirectly to cognitive depression and lower affective empathy (both through self-judgement); and (iii) CRP was the strongest predictor of reduced cognitive empathy, with suppression effects seen for age (negative) and IL-6 (positive) after controlling for CRP. CONCLUSIONS: Findings suggest that lactobacilli and inflammation may be differentially associated with mood disorder via brain mechanisms underpinning self-judgement and cognitive empathy, respectively. Further trials investigating interventions to increase Lactobacillus spp. in depression would benefit from direct measures of self-judgement and affective empathic distress, whilst those that aim to reduce inflammation should investigate cognitive empathy.

Reduced thalamic volume in men with antisocial personality disorder or schizophrenia and a history of serious violence and childhood abuse.

OBJECTIVE: Violent behaviour has been associated with presence of certain mental disorders, most notably antisocial personality disorder (ASPD) and schizophrenia, childhood abuse, and multiple brain abnormalities. This study examined for the first time, to the authors' knowledge, the role of psychosocial deprivation (PSD), including childhood physical and sexual abuse, in structural brain volumes of violent individuals with ASPD or schizophrenia. METHODS: Fifty-six men (26 with ASPD or schizophrenia and a history of serious violence, 30 non-violent) underwent magnetic resonance imaging and were assessed on PSD. Stereological volumetric brain ratings were examined for group differences and their association with PSD ratings. PSD-brain associations were examined further using voxel-based-morphometry. RESULTS: The findings revealed: reduced thalamic volume in psychosocially-deprived violent individuals, relative to non-deprived violent individuals and healthy controls; negative association between thalamic volume and abuse ratings (physical and sexual) in violent individuals; and trend-level negative associations between PSD and hippocampal and prefrontal volumes in non-violent individuals. The voxel-based-morphometry analysis detected a negative association between PSD and localised grey matter volumes in the left inferior frontal region across all individuals, and additionally in the left middle frontal and precentral gyri in non-violent individuals. CONCLUSIONS: Violent mentally-disordered individuals with PSD, relative to those with no or minimal PSD, suffer from an additional brain deficit, i.e., reduced thalamic volume; this may affect sensory information processing, and have implications for management, of these individuals. PSD may have a stronger relationship with volumetric loss of stress-linked regions, namely the frontal cortex, in non-violent individuals.

Cognitive functioning in siblings discordant for schizophrenia.

OBJECTIVE: The objective of this study was to investigate neuropsychological impairment as a genetically mediated risk indicator for schizophrenia while accounting for prevalence of schizotypy signs/symptoms in siblings. METHOD: Cognitive functioning in 25 individuals with schizophrenia, 25 unaffected siblings and 25 unrelated healthy controls, was assessed using neuropsychological tests of sustained attention, memory and learning, executive function, visual-spatial ability and psychomotor performance. RESULTS: Unaffected siblings demonstrated better performance than patients on some measures of memory and learning and executive function. Patients and siblings demonstrated impaired Full Scale IQ and verbal fluency, otherwise siblings performed similarly to healthy controls. Controlling for differences in IQ, the shared deficit in verbal fluency disappeared. CONCLUSION: Patients with schizophrenia and unaffected siblings (without schizotypy personality disorder) shared a neuropsychological deficit in verbal fluency. This deficit appeared to be mediated by IQ. Deficits, which differentiated patients from controls, may not be inherited and perhaps are related to the manifestation or treatment of schizophrenia.

Neuroimaging of sexual arousal: research and clinical utility.

The treatment of sexual dysfunction or deviancy requires an understanding of the underlying neural substrates. Neuroimaging techniques offer insight into brain regions involved in sexual arousal and inhibition. The development of robust paradigms has implications for the assessment and treatment of sexual disorder in men and women.

Magnetic resonance imaging of the thalamus in first-episode psychosis.

OBJECTIVE: There is some evidence of thalamic abnormalities in schizophrenia. This study investigated thalamic volumes in patients experiencing their first episode of psychosis and nonpsychotic comparison subjects. METHOD: Magnetic resonance imaging scans were obtained for 38 patients and 29 comparison subjects. Patients' symptoms were rated by research psychiatrists using the Positive and Negative Syndrome Scale. RESULTS: Thalamic volumes were smaller in patients than in comparison subjects. There were no significant correlations between thalamic volumes and symptom scores. CONCLUSIONS: Thalamic abnormalities are present close to the onset of psychosis.

Third ventricle enlargement and developmental delay in first-episode psychosis: preliminary findings.

BACKGROUND: Third rather than lateral ventriculomegaly may be a more specific finding in psychosis. The relevance of ventricular abnormality remains unclear. AIMS: To investigate the developmental correlates of ventricular enlargement. METHOD: Information on childhood development and magnetic resonance images in 1.5-mm contiguous sections were collected on 21 patients experiencing a first episode of psychosis. RESULTS: Patients (n = 21) had significantly less whole brain volume and enlarged third and lateral ventricles compared to controls (n = 25). Third ventricle (r = 0.48, P < 0.03) and lateral ventricle (r = 0.65, P < 0.01) volumes correlated with developmental score. Patients with developmental delay had significantly larger third and lateral ventricles than those without. CONCLUSIONS: Enlargement of both third and lateral ventricles is found in first-episode psychosis and is related to developmental delay in childhood. Insult to periventricular areas is relevant to the neurobiology of the disease. These findings support the view that schizophrenia involves disturbance of neurodevelopmental processes in some patients.

Features of structural brain abnormality detected in first-episode psychosis.

OBJECTIVE: Structural magnetic resonance imaging (MRI) studies that focus on first-episode psychosis avoid some common confounds, such as chronicity of illness, treatment effects, and long-term substance abuse. However, such studies may select subjects with poor short-term treatment response or outcome. In this study, the authors focus on structural brain abnormalities in never or minimally treated patients who underwent MRI scanning early in their first episode of psychosis. METHOD: The authors examined 37 patients (13 medication naive, 24 previously treated) who were experiencing their first episode of psychosis; the mean duration of symptoms was short (31 weeks). These patients were comparable in age, gender, handedness, ethnicity, and parental socioeconomic status to a group of 25 healthy comparison subjects. A three-dimensional, inversion recovery prepared, fast spoiled gradient/recall in the steady state scan of the whole brain that used 1.5-mm contiguous sections was performed to acquire a T(1)-weighted data set. Human ratings of volumetric measurement of brain structures were performed with stereological techniques on three-dimensional reconstructed MRIs. RESULTS: The patient group had significant deficits in cortical gray matter, temporal lobe gray matter, and whole brain volume as well as significant enlargement of the lateral and third ventricles. Structural deviations were found in both treatment-naive and minimally treated subjects. No relationships were found between any brain matter volumes and positive or negative symptoms. CONCLUSIONS: Structural brain abnormalities were distributed throughout the cortex with particular decrement evident in gray matter. This feature is consistent with altered cell structure and disturbed neuronal connectivity, which accounts for the functional abnormality of psychosis.

Spatial orienting controlled without awareness: a semantically based implicit learning effect.

Three experiments tested whether spatial attention can be influenced by a predictive relation between incidental information and the location of target events. Subjects performed a simple dot detection task; 600 msec prior to each target a word was presented briefly 5 degrees to the left or right of fixation. There was a predictive relationship between the semantic category (living or non-living) of the words and target location. However, subjects were instructed to ignore the words, and a post-experiment questionnaire confirmed that they remained unaware of the word-target relationship. In all three experiments, given some practice on the task, response times were faster when target appeared at likely ( p = 0.8 ), compared to unlikely ( p = 0.2 ) locations, in relation to lateral word category. Experiments 2 and 3 confirmed that this effect was driven by semantic encoding of the irrelevant words, and not by repetition of individual stimuli. Theoretical implications of this finding are discussed.