Impaired striatal glutamate/GABA regulation in violent offenders with antisocial personality disorder and psychopathy.

Men with antisocial personality disorder (ASPD) with or without psychopathy (+/-P) are responsible for most violent crime in society. Development of effective treatments is hindered by poor understanding of the neurochemical underpinnings of the condition. Men with ASPD with and without psychopathy demonstrate impulsive decision-making, associated with striatal abnormalities in functional neuroimaging studies. However, to date, no study has directly examined the potential neurochemical underpinnings of such abnormalities. We therefore investigated striatal glutamate: GABA ratio using Magnetic Resonance Spectroscopy in 30 violent offenders (16 ASPD-P, 14 ASPD + P) and 21 healthy non-offenders. Men with ASPD +/- P had a significant reduction in striatal glutamate : GABA ratio compared to non-offenders. We report, for the first time, striatal Glutamate/GABA dysregulation in ASPD +/- P, and discuss how this may be related to core behavioral abnormalities in the disorders.

Differential sensitivity to the acute psychotomimetic effects of delta-9-tetrahydrocannabinol associated with its differential acute effects on glial function and cortisol.

BACKGROUND: Cannabis use has been associated with psychosis through exposure to delta-9-tetrahydrocannabinol (Δ9-THC), its key psychoactive ingredient. Although preclinical and human evidence suggests that Δ9-THC acutely modulates glial function and hypothalamic-pituitary-adrenal (HPA) axis activity, whether differential sensitivity to the acute psychotomimetic effects of Δ9-THC is associated with differential effects of Δ9-THC on glial function and HPA-axis response has never been tested. METHODS: A double-blind, randomized, placebo-controlled, crossover study investigated whether sensitivity to the psychotomimetic effects of Δ9-THC moderates the acute effects of a single Δ9-THC dose (1.19 mg/2 ml) on myo-inositol levels, a surrogate marker of glia, in the Anterior Cingulate Cortex (ACC), and circadian cortisol levels, the key neuroendocrine marker of the HPA-axis, in a set of 16 healthy participants (seven males) with modest previous cannabis exposure. RESULTS: The Δ9-THC-induced change in ACC myo-inositol levels differed significantly between those sensitive to (Δ9-THC minus placebo; M = -0.251, s.d. = 1.242) and those not sensitive (M = 1.615, s.d. = 1.753) to the psychotomimetic effects of the drug (t(14) = 2.459, p = 0.028). Further, the Δ9-THC-induced change in cortisol levels over the study period (baseline minus 2.5 h post-drug injection) differed significantly between those sensitive to (Δ9-THC minus placebo; M = -275.4, s.d. = 207.519) and those not sensitive (M = 74.2, s.d. = 209.281) to the psychotomimetic effects of the drug (t(13) = 3.068, p = 0.009). Specifically, Δ9-THC exposure lowered ACC myo-inositol levels and disrupted the physiological diurnal cortisol decrease only in those subjects developing transient psychosis-like symptoms. CONCLUSIONS: The interindividual differences in transient psychosis-like effects of Δ9-THC are the result of its differential impact on glial function and stress response.

Brain imaging in catatonia: systematic review and directions for future research.

BACKGROUND: Catatonia is a frequent, complex and severe identifiable syndrome of motor dysregulation. However, its pathophysiology is poorly understood. METHODS: We aimed to provide a systematic review of all brain imaging studies (both structural and functional) in catatonia. RESULTS: We identified 137 case reports and 18 group studies representing 186 individual patients with catatonia. Catatonia is often associated with brain imaging abnormalities (in more than 75% of cases). The majority of the case reports show diffuse lesions of white matter, in a wide range of brain regions. Most of the case reports of functional imaging usually show frontal, temporal, or basal ganglia hypoperfusion. These abnormalities appear to be alleviated after successful treatment of clinical symptoms. Structural brain magnetic resonance imaging studies are very scarce in the catatonia literature, mostly showing diffuse cerebral atrophy. Group studies assessing functional brain imaging after catatonic episodes show that emotional dysregulation is related to the GABAergic system, with hypoactivation of orbitofrontal cortex, hyperactivation of median prefrontal cortex, and dysconnectivity between frontal and motor areas. CONCLUSION: In catatonia, brain imaging is abnormal in the majority of cases, and abnormalities more frequently diffuse than localised. Brain imaging studies published so far suffer from serious limitations and for now the different models presented in the literature do not explain most of the cases. There is an important need for further studies including a better clinical characterisation of patients with catatonia, functional imaging with concurrent catatonic symptoms and the use of novel brain imaging techniques.

Cognitive deficits in people who have recovered from COVID-19.

BACKGROUND: There is growing concern about possible cognitive consequences of COVID-19, with reports of 'Long COVID' symptoms persisting into the chronic phase and case studies revealing neurological problems in severely affected patients. However, there is little information regarding the nature and broader prevalence of cognitive problems post-infection or across the full spread of disease severity. METHODS: We sought to confirm whether there was an association between cross-sectional cognitive performance data from 81,337 participants who between January and December 2020 undertook a clinically validated web-optimized assessment as part of the Great British Intelligence Test, and questionnaire items capturing self-report of suspected and confirmed COVID-19 infection and respiratory symptoms. FINDINGS: People who had recovered from COVID-19, including those no longer reporting symptoms, exhibited significant cognitive deficits versus controls when controlling for age, gender, education level, income, racial-ethnic group, pre-existing medical disorders, tiredness, depression and anxiety. The deficits were of substantial effect size for people who had been hospitalised (N = 192), but also for non-hospitalised cases who had biological confirmation of COVID-19 infection (N = 326). Analysing markers of premorbid intelligence did not support these differences being present prior to infection. Finer grained analysis of performance across sub-tests supported the hypothesis that COVID-19 has a multi-domain impact on human cognition. INTERPRETATION: Interpretation. These results accord with reports of 'Long Covid' cognitive symptoms that persist into the early-chronic phase. They should act as a clarion call for further research with longitudinal and neuroimaging cohorts to plot recovery trajectories and identify the biological basis of cognitive deficits in SARS-COV-2 survivors. FUNDING: Funding. AH is supported by the UK Dementia Research Institute Care Research and Technology Centre and Biomedical Research Centre at Imperial College London. WT is supported by the EPSRC Centre for Doctoral Training in Neurotechnology. SRC is funded by a Wellcome Trust Clinical Fellowship 110,049/Z/15/Z. JMB is supported by Medical Research Council (MR/N013700/1). MAM, SCRW and PJH are, in part, supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London.

Similarities between borderline personality disorder and post traumatic stress disorder: Evidence from resting-state meta-analysis.

Borderline personality disorder (BPD) and post-traumatic stress disorder (PTSD) are common psychiatric disorders. The nature of the relationship between BPD and PTSD remains controversial, but it has been suggested that these disorders should brought closer because of their many similarities. We thus performed a quantitative meta-analysis of resting-state functional imaging to assess similarities in the brain activation across BPD and PTSD diagnostic groups. Overlap analyses revealed decreased activation in the left and right precuneus of both BPD and PTSD groups when compared to control subjects. BPD showed significant increased, but PTSD showed decreased activation, relative to control subjects, in the anterior cingulate/paracingulate gyri and in the left superior frontal gyrus. Complementary overlap analyses on a subgroup of studies with similar sex and age distribution partially confirmed the main results as the same pattern of functional activation in the anterior cingulate and in the left superior frontal gyrus were found. Our findings are in agreement with the hypothesis that BPD and PTSD share common neuropathological pathways.

Glutamatergic hypofunction in medication-free major depression: Secondary effects of affective diagnosis and relationship to peripheral glutaminase.

BACKGROUND: There is uncertainty as to whether alterations in glutamatergic function in affective disorders differ between unipolar and bipolar disorders and between depressive and euthymic states. Additionally, there are currently no available blood-based markers of central glutamatergic function to support clinical diagnosis and aid brain based investigations. METHODS: In this study, we measured levels of glutamate in the dorsal anterior cingulate cortex in-vivo using 1H-Magnetic Resonance Spectroscopy in medication free unipolar and bipolar patients (n = 29, 20 unipolar and 9 bipolar) experiencing a major depressive episode, in comparison with a group of matched healthy controls (n = 20). We also analysed peripheral glutaminase measured in serum to examine the relationship between central and peripheral measures. RESULTS: Anterior cingulate glutamate levels were reduced in both unipolar and bipolar depression groups relative to healthy controls, although this only reached significance in the unipolar group. Peripheral glutaminase levels did not differentiate bipolar from unipolar depression and a positive correlation with central glutamate levels did not reach statistical significance. LIMITATIONS: The sample of bipolar disorder patients was relatively small due to the difficulties involved in finding medication-free patients experiencing a depressive episode. CONCLUSIONS: These results suggest that glutamatergic hypofunction might represent a state marker for a depressive episode irrespective of diagnosis. Peripheral glutaminase did not index central glutamate levels in this study, which could potentially reflect a small magnitude of the effect requiring larger samples for detection.

Elucidating neuroanatomical alterations in the at risk mental state and first episode psychosis: a combined voxel-based morphometry and voxel-based cortical thickness study.

Previous studies have reported alterations in grey matter volume and cortical thickness in individuals at high risk of developing psychosis and patients in the early stages of the disorder. Because these studies have typically focused on either grey matter volume or cortical thickness separately, the relationship between these two types of alterations is currently unclear. In the present investigation we used both voxel-based cortical thickness (VBCT) and voxel-based morphometry (VBM) to examine neuroanatomical differences in 21 individuals with an At Risk Mental State (ARMS) for psychosis, 26 patients with a First Episode of Psychosis (FEP) and 24 healthy controls. Statistical inferences were made at P<0.05 after correction for multiple comparisons. Cortical thinning in the right superior temporal gyrus was observed in both individuals at high risk of developing psychosis and patients with a first episode of the disorder, and therefore is likely to represent a marker of vulnerability. In contrast, the right posterior cingulate cortex showed cortical thinning in FEP patients relative to individuals at high risk, and therefore appears to be implicated in the onset of the disease. These neuroanatomical differences were expressed in terms of cortical thickness but not in terms of grey matter volume, and therefore may reflect specific cortical atrophy as opposed to variations in sulcal and gyral morphology.

Storage of verbal associations is sufficient to activate the left medial temporal lobe.

Neuroimaging studies have shown that memory encoding activates the medial temporal lobe (MTL). Many believe that these activations are related to novelty but it remains unproven which is critical - novelty detection or the rich associative encoding it triggers. We examined MTL activation during verbal associative encoding using functional magnetic resonance imaging. First, associative encoding activated left posterior MTL more than single word encoding even though novelty detection was matched, indicating not only that associative encoding activates the MTL particularly strongly, but also that activation does not require novelty detection. Moreover, it remains to be convincingly shown that novelty detection alone does produce such activation. Second, repetitive associative encoding produced less MTL activation than initial associative encoding, indicating that priming of associative information reduces MTL activation. Third, re-encoding familiar associations in a well-established way had a minimal effect on both memory and MTL activation, indicating that MTL activation reflects storage of associations, not merely their initial representation.