Neuroanatomical correlates of aggressiveness: a case-control voxel- and surface-based morphometric study.

Aggression occurs across the population ranging on a symptom continuum. Most previous studies have used magnetic resonance imaging in clinical/forensic samples, which is associated with several confounding factors. The present study examined structural brain characteristics in two healthy samples differing only in their propensity for aggressive behavior. Voxel- and surface-based morphometry (SBM) analyses were performed on 29 male martial artists and 32 age-matched male controls. Martial artists had significantly increased mean gray matter volume in two frontal (left superior frontal gyrus and bilateral anterior cingulate cortex) and one parietal (bilateral posterior cingulate gyrus and precuneus) brain clusters compared to controls (whole brain: p < 0.001, cluster level: family-wise error (FWE)-corrected). SBM analyses revealed a trend for greater gyrification indices in martial artists compared to controls in the left lateral orbital frontal cortex and the left pars orbitalis (whole brain: p < 0.001, cluster level: FWE-corrected). The results indicate brain structural differences between martial artists and controls in frontal and parietal brain areas critical for emotion processing/inhibition of emotions as well as empathic processes. The present study highlights the importance of studying healthy subjects with a propensity for aggressive behavior in future structural MRI research on aggression.

Patterns of risk-Using machine learning and structural neuroimaging to identify pedophilic offenders.

Background: Child sexual abuse (CSA) has become a focal point for lawmakers, law enforcement, and mental health professionals. With high prevalence rates around the world and far-reaching, often chronic, individual, and societal implications, CSA and its leading risk factor, pedophilia, have been well investigated. This has led to a wide range of clinical tools and actuarial instruments for diagnosis and risk assessment regarding CSA. However, the neurobiological underpinnings of pedosexual behavior, specifically regarding hands-on pedophilic offenders (PO), remain elusive. Such biomarkers for PO individuals could potentially improve the early detection of high-risk PO individuals and enhance efforts to prevent future CSA. Aim: To use machine learning and MRI data to identify PO individuals. Methods: From a single-center male cohort of 14 PO individuals and 15 matched healthy control (HC) individuals, we acquired diffusion tensor imaging data (anisotropy, diffusivity, and fiber tracking) in literature-based regions of interest (prefrontal cortex, anterior cingulate cortex, amygdala, and corpus callosum). We trained a linear support vector machine to discriminate between PO and HC individuals using these WM microstructure data. Post hoc, we investigated the PO model decision scores with respect to sociodemographic (age, education, and IQ) and forensic characteristics (psychopathy, sexual deviance, and future risk of sexual violence) in the PO subpopulation. We assessed model specificity in an external cohort of 53 HC individuals. Results: The classifier discriminated PO from HC individuals with a balanced accuracy of 75.5% (sensitivity = 64.3%, specificity = 86.7%, P 5000 = 0.018) and an out-of-sample specificity to correctly identify HC individuals of 94.3%. The predictive brain pattern contained bilateral fractional anisotropy in the anterior cingulate cortex, diffusivity in the left amygdala, and structural prefrontal cortex-amygdala connectivity in both hemispheres. This brain pattern was associated with the number of previous child victims, the current stance on sexuality, and the professionally assessed risk of future sexual violent reoffending. Conclusion: Aberrant white matter microstructure in the prefronto-temporo-limbic circuit could be a potential neurobiological correlate for PO individuals at high-risk of reoffending with CSA. Although preliminary and exploratory at this point, our findings highlight the general potential of MRI-based biomarkers and particularly WM microstructure patterns for future CSA risk assessment and preventive efforts.

Deep brain stimulation of the nucleus accumbens in treatment-resistant alcohol use disorder: a double-blind randomized controlled multi-center trial.

Treatment resistance in alcohol use disorders (AUD) is a major problem for affected individuals and for society. In the search of new treatment options, few case studies using deep brain stimulation (DBS) of the nucleus accumbens have indicated positive effects in AUD. Here we report a double-blind randomized controlled trial comparing active DBS ("DBS-EARLY ON") against sham stimulation ("DBS-LATE ON") over 6 months in n = 12 AUD inpatients. This 6-month blind phase was followed by a 12-month unblinded period in which all patients received active DBS. Continuous abstinence (primary outcome), alcohol use, alcohol craving, depressiveness, anxiety, anhedonia and quality of life served as outcome parameters. The primary intention-to-treat analysis, comparing continuous abstinence between treatment groups, did not yield statistically significant results, most likely due to the restricted number of participants. In light of the resulting limited statistical power, there is the question of whether DBS effects on secondary outcomes can nonetheless be interpreted as indicative of an therapeutic effect. Analyses of secondary outcomes provide evidence for this, demonstrating a significantly higher proportion of abstinent days, lower alcohol craving and anhedonia in the DBS-EARLY ON group 6 months after randomization. Exploratory responder analyses indicated that patients with high baseline alcohol craving, depressiveness and anhedonia responded to DBS. The results of this first randomized controlled trial are suggestive of beneficial effects of DBS in treatment-resistant AUD and encourage a replication in larger samples.

Reduced anterior insular cortex volume in male heroin addicts: a postmortem study.

We and others have observed reduced volumes of brain regions, including the nucleus accumbens, globus pallidus, hypothalamus, and habenula in opioid addiction. Notably, the insular cortex has been under increasing study in addiction, and a smaller anterior insula has been found in alcohol-addicted cases. Here, we have investigated whether similar effects occur in heroin addicts compared to healthy controls. Volumes of the anterior and posterior insula in heroin addicts (n = 14) and controls (n = 13) were assessed by morphometry of Nissl-myelin-stained serial whole-brain coronal sections. The mean relative volume of the anterior insular cortex was smaller than in non-addicted controls (3010 ± 614 *10-6 versus 3970 ± 1306 *10-6; p = 0.021). However, no significant differences in neuronal cell counts were observed. Therefore, the observed volume reduction appears to be a consequence of damaged connecting structures such as neuropil and glial cells. The findings were not confounded by age or duration of autolysis. Our results provide further evidence of structural deficits in key hubs of the addiction circuitry in heroin-dependent individuals and warrant further research in this area.

Changes in leukocytes and CRP in different stages of major depression.

BACKGROUND: We recently reported increased levels of neutrophils, monocytes and C-reactive protein (CRP) correlated with symptom severity in acute schizophrenia. Here, we investigated if a similar pattern of innate immune system activation occurs in major depression (MD). METHODS: We assessed differential blood counts, CRP, depression symptoms (HAMD-21) and psychosocial functioning (GAF) in controls (n = 129) and patients with first (FEMD: n = 82) or recurrent (RMD: n = 47) disease episodes of MD at baseline (T0; hospital admission) and after 6-weeks treatment (T6). RESULTS: Considering smoking, BMI and gender as covariates, neutrophils (FEMD: p = 0.034, RMD: p = 0.034) and CRP (FEMD: p < 0.001, RMD: p = 0.021) were higher, and eosinophils (FEMD: p = 0.005, RMD: p = 0.004) lower in patients versus controls at T0. Baseline lymphocyte counts were elevated in RMD (p = 0.003) but not FEMD. Results were confirmed by analyses of nonsmokers. At follow-up, eosinophils rose significantly in FEMD (p = 0.011) but no significant changes were observed in RMD. Improvement in HAMD-21 correlated with T0-T6 changes of neutrophil counts in FEMD (r = 0.364, p = 0.024). Compared with our previous schizophrenia study, raised baseline neutrophil and reduced eosinophil counts in MD had smaller effect sizes and treatment had a weaker association with T0-T6 changes in neutrophils. In addition, lymphocytes were elevated at T0 in recurrent MD but not in schizophrenia patients. CONCLUSIONS: These findings suggest that innate immunity may be involved in early stages of MD, and adaptive immunity may be involved in chronic disease. Thus, further studies may lead to new disease stage-dependent MD treatment strategies targeting different aspects of immune system activation.

Appetitive aggression is associated with lateralized activation in nucleus accumbens.

Aggression can have a hedonistic aspect in predisposed individuals labeled as appetitive aggression. The present study investigates the neurobiological correlates of this appetitive type of aggression in non-clinical samples from community. Applying functional magnet resonance imaging (fMRI), we tested whether 20 martial artists compared to 26 controls had a higher activation in the nucleus accumbens (NAcc), a central part of the dopaminergic, mesolimbic reward system. Subjects had to watch violent vs. neutral pictures representing appetitive aggression. The affinity towards hedonistic violence was assessed by the Appetitive and Facilitative Aggression Scale (AFAS). Furthermore, the subjects rated all the pictures with regard to how pleasant and violent they were. The martial artists reported a higher AFAS-score and a more positive perception of violent pictures. On the neural level, across all subjects, there was a significant positive correlation between the AFAS-score and the activation in the left NAcc and an inverse association with the activation of the right NAcc when watching violent compared to neutral pictures. This lateralization effect indicates a different processing of hedonistic aspects of aggression in the two hemispheres.

Altered expression of costimulatory molecules in dementias.

Although the expression of co-stimulatory molecules plays an important role in the immune system, only little is known about their regulation in dementias. Therefore, we determined the expression of CD28, ICOS (CD278) and CTLA-4 (CD152) by CD4 + and CD8 + T cells in the peripheral blood of patients with mild cognitive impairment (MCI; N = 19), Alzheimer's disease (AD; N = 51), vascular dementia (VD; N = 21) and frontotemporal dementia (FTD; N = 6) at the point in time of diagnosis compared to 19 non-demented elderly persons. The expression of CD28 and ICOS by CD4 + and CD8 + T cells was not changed in AD, FTD or VD patients. The expression of the negative regulator CTLA-4 was increased by CD4 + T cells from AD and FTD patients and by CD8 + T cells from VD patients. The classification of the AD patients according to the severity of the disorder showed stage-dependent alterations of CD28, ICOS and CTLA-4 expression. In AD patients, the correlation analysis showed an association between the decline in CD28 + T cells and the increase in CTLA-4 + T cells with cognitive decline, measured by the mini-mental state examination (MMSE), tau proteins and Amyloid-ß, important AD biomarkers in cerebrospinal fluid (CSF). In FTD patients, a positive association between Q Albumin, a marker for blood-CSF-barrier function, and CD28 and a negative correlation between Q Albumin and ICOS expression were determined. Our data suggest a dysregulated balance between the expression of negative and positive co-stimulatory molecules by T cells in AD patients, which might contribute to chronic inflammation observed in dementia.

Reduced GABAergic neuropil and interneuron profiles in schizophrenia: Complementary analysis of disease course-related differences.

BACKGROUND: GABAergic interneuron dysfunction has been implicated in the pathophysiology of schizophrenia. Expression of glutamic acid decarboxylase (GAD), a key enzyme in GABA synthesis, may also be altered. Here, we have simultaneously evaluated GAD-immunoreactive (GAD-ir) neuropil and cell profiles in schizophrenia-relevant brain regions, and analysed disease-course related differences. METHODS: GAD65/67 immunoreactivity was quantified in specific brain regions for profiles of fibres and cell bodies of interneurons by automated digital image analysis in post-mortem brains of 16 schizophrenia patients from paranoid (n = 10) and residual (n = 6) diagnostic subgroups and 16 matched controls. Regions of interest were superior temporal gyrus (STG) layers III and V, mediodorsal (MD) and laterodorsal (LD) thalamus, and hippocampal CA1 and dentate gyrus (DG) regions. RESULTS: A reduction in GAD-ir neuropil profiles (p < 0.001), particularly in STG layer V (p = 0.012) and MD (p = 0.001), paralleled decreased GAD-ir cell profiles (p = 0.029) in schizophrenia patients compared to controls. Paranoid schizophrenia patients had lower GAD-ir neuron cell profiles in STG layers III (p = 0.007) and V (p = 0.001), MD (p = 0.002), CA1 (p = 0.001) and DG (p = 0.043) than residual patients. There was no difference in GAD-ir neuropil profiles between paranoid and residual subgroups (p = 0.369). CONCLUSIONS: These results support the hypothesis of GABAergic dysfunction in schizophrenia. They show a more prominent reduction of GAD-ir interneurons in paranoid versus residual patients, suggestive of more pronounced GABAergic dysfunction in the former. Fully automated analyses of histological sections represent a step towards user-independent assessment of brain structure.

Reduced habenular volumes and neuron numbers in male heroin addicts: a post-mortem study.

The Habenula is increasingly being investigated in addiction. Reduced volumes of other relevant brain regions in addiction, such as nucleus accumbens, globus pallidus and hypothalamus have been reported. Reduced volumes of the habenula as well as reduced neuronal cell count in the habenula have also been reported in mood disorders and an overlap between mood disorders and addiction is clinically widely recognized. Thus, our aim was to investigate possible volume and neuronal cell count differences in heroin addicts compared to healthy controls. Volumes of the medial (MHB) and lateral habenula (LHB) in heroin addicts (n = 12) and healthy controls (n = 12) were assessed by morphometry of 20 µm serial whole brain sections. Total brain volume was larger in the heroin group (mean 1466.6 ± 58.5 cm3 vs. mean 1331.5 ± 98.8 cm3), possibly because the heroin group was about 15 years younger (p = 0.001). Despite larger mean whole brain volume, the mean relative volume of the MHB was smaller than in healthy non-addicted controls (6.94 ± 2.38 × 10-6 vs.10.64 ± 3.22 × 10-6; p = 0.004). A similar finding was observed regarding relative volumes of the LHB (46.62 ± 10.90 × 10-6 vs. 63.05 ± 16.42 × 10-6 p = 0.009). In parallel, neuronal cell numbers were reduced in the MHB of heroin-addicted subjects (395,966 ± 184,178 vs. 644,149 ± 131,140; p < 0.001). These findings were not significantly confounded by age and duration of autolysis. Our results provide further evidence for brain-structural deficits in heroin addiction.

Increased densities of T and B lymphocytes indicate neuroinflammation in subgroups of schizophrenia and mood disorder patients.

An increasing number of clinical, epidemiological and genetic studies as well as investigations of CSF and blood suggests that neuroinflammation plays an essential role in the etiology of schizophrenia and mood disorders. However, direct neuropathological evidence of inflammation within the brain tissue remains sparse and the regional distribution of lymphocytes as surrogate markers of blood-brain barrier (BBB) impairment has not yet been investigated in this context. Densities of T and B lymphocytes were assessed in coronal whole brain sections of 22 patients with schizophrenia and 20 patients suffering from major depression or bipolar disorder, compared to 20 individuals without neuropsychiatric disorders from the Magdeburg Brain Collection. Cell densities were determined by immunohistochemical staining (anti-CD3 for T cells, anti-CD20 for B cells), followed by automated microscopic image acquisition and analysis. Hierarchical clustering and detailed cluster analysis were performed to detect possible subgroups of patients. Regional distribution was assessed by analysis of color coded mappings based on microsopic scans. Elevated lymphocyte density was found in 7 out of 20 mood disorder patients (adj. p = 0.022; Fisher's exact test, FET), 9 out of 22 schizophrenic patients (adj. p = 0.014; FET) and in 1 of 20 controls (p < 0.005; FET). Several cases showed different patterns of infiltration affecting cortical regions or subcortical white matter, while some presented diffuse infiltration. In two thirds of patients, no increased lymphocyte density could be found. The current findings indicate that lymphocyte infiltration occurs in a greater proportion of schizophrenia and mood disorder patients as compared to healthy controls. Under healthy conditions lymphocytes rarely cross the BBB. Thus, higher densities are considered indicators of neuroinflammation associated with an impairment of the BBB.

Association between altered hippocampal oligodendrocyte number and neuronal circuit structures in schizophrenia: a postmortem analysis.

In schizophrenia, decreased hippocampal volume, reduced oligodendrocyte numbers in hippocampal cornu ammonis (CA) subregions and reduced neuron number in the dentate gyrus have been reported; reduced oligodendrocyte numbers were significantly related to cognitive deficits. The hippocampus is involved in cognitive functions and connected to the hypothalamus, anterior thalamus, and cingulate cortex, forming the Papez circuit, and to the mediodorsal thalamus. The relationship between the volume of these interconnected regions and oligodendrocyte and neuron numbers in schizophrenia is unknown. Therefore, we used stepwise logistic regression with subsequent multivariate stepwise linear regression and bivariate correlation to analyze oligodendrocyte and neuron numbers in the posterior hippocampal subregions CA1, CA2/3, CA4, dentate gyrus, and subiculum and volumes of the hippocampal CA region, cingulum, anterior and mediodorsal thalamus and hypothalamus in postmortem brains of 10 schizophrenia patients and 11 age- and gender-matched healthy controls. Stepwise logistic regression identified the following predictors for diagnosis, in order of inclusion: (1) oligodendrocyte number in CA4, (2) hypothalamus volume, (3) oligodendrocyte number in CA2/3, and (4) mediodorsal thalamus volume. Subsequent stepwise linear regression analyses identified the following predictors: (1) for oligodendrocyte number in CA4: (a) oligodendrocyte number in CA2/3, (b) diagnostic group, (c) hypothalamus volume, and (d) neurons in posterior subiculum; (2) for hypothalamus volume: (a) mediodorsal thalamus volume; (3) for oligodendrocyte number in CA2/3: oligodendrocyte number (a) in posterior CA4 and (b) in posterior subiculum; (4) for mediodorsal thalamus volume: volumes of (a) anterior thalamus and (b) hippocampal CA. In conclusion, we found a positive relationship between hippocampal oligodendrocyte number and the volume of the hypothalamus, a brain region connected to the hippocampus, which is important for cognition.

Autoimmune psychosis: an international consensus on an approach to the diagnosis and management of psychosis of suspected autoimmune origin.

There is increasing recognition in the neurological and psychiatric literature of patients with so-called isolated psychotic presentations (ie, with no, or minimal, neurological features) who have tested positive for neuronal autoantibodies (principally N-methyl-D-aspartate receptor antibodies) and who have responded to immunotherapies. Although these individuals are sometimes described as having atypical, mild, or attenuated forms of autoimmune encephalitis, some authors feel that that these cases are sufficiently different from typical autoimmune encephalitis to establish a new category of so-called autoimmune psychosis. We briefly review the background, discuss the existing evidence for a form of autoimmune psychosis, and propose a novel, conservative approach to the recognition of possible, probable, and definite autoimmune psychoses for use in psychiatric practice. We also outline the investigations required and the appropriate therapeutic approaches, both psychiatric and immunological, for probable and definite cases of autoimmune psychoses, and discuss the ethical issues posed by this challenging diagnostic category.

Innate Immune Cells and C-Reactive Protein in Acute First-Episode Psychosis and Schizophrenia: Relationship to Psychopathology and Treatment.

Innate immunity has been linked to initiation of Alzheimer's disease and multiple sclerosis. Moreover, risk of first-episode psychosis (FEP) and schizophrenia (Sz) is increased after various infections in predisposed individuals. Thus, we hypothesized an analogous role of innate immunity with increased C-reactive protein (CRP) in non-affective psychosis. Differential blood count, CRP, neutrophil and monocyte-macrophage activation markers, cortisol and psychotic symptoms (Positive and Negative Syndrome Scale [PANSS]) were assessed in controls (n = 294) and acutely ill unmedicated FEP (n = 129) and Sz (n = 124) patients at baseline and after 6 weeks treatment. Neutrophils, monocytes, and CRP were increased in patients vs controls at baseline (P < .001), and neutrophil and monocyte counts correlated positively with activation markers. Eosinophils were lower at baseline in FEP (P < .001) and Sz (P = .021) vs controls. Differences in neutrophils (P = .023), eosinophils (P < .001), and CRP (P < .001) were also present when controlling for smoking and cortisol, and partially remitted after antipsychotic treatment. FEP patients with high neutrophils (P = .048) or monocytes (P = .021) had higher PANSS-P scores at baseline but similar disease course. CRP correlated with PANSS-P at baseline (ρ = 0.204, P = .012). Improvement of positive symptoms after treatment correlated with declining neutrophils (ρ = 0.186, P = .015) or CRP (ρ = 0.237, P = .002) and rising eosinophils (ρ = -0.161, P = .036). In FEP, normalization of neutrophils (ρ = -0.231, P = .029) and eosinophils (ρ = 0.209, P = .048) correlated with drug dosage. In conclusion, innate immune system activation correlated with PANSS-P, supporting the immune hypothesis of psychosis. Neutrophil and monocyte counts and CRP levels may be useful markers of disease acuity, severity, and treatment response.

Neurobiological correlates of violence perception in martial artists.

OBJECTIVES: The direct exertion as well as the visual perception of violence can have a hedonistic effect and elicit positive arousal in predisposed individuals. This appetitive aspect of aggression in healthy subjects has been neglected in psychiatric research so far. METHODS: Using functional magnetic resonance imaging, we tested whether subjects trained in sports with a violent component (martial arts) show altered brain responses in reward-associated brain areas when compared to controls. Sixteen martial artists (e.g., boxing, mixed martial arts) and 24 controls watched violent versus neutral pictures while performing a cognitive cover task. Subjects' aggressiveness was assessed by the aggressiveness factors questionnaire (FAF). RESULTS: While watching violent pictures, martial artists had a stronger activation in the left amygdala than controls. Within the martial artist group however, there was an inverse correlation between activation in the left amygdala and degree of aggressiveness. CONCLUSIONS: Higher amygdala activation while watching violent pictures might reflect that perception of violence conveys increased salience to martial artists as compared to controls. The inverse correlation between amygdala activation and aggressiveness within the martial artist group might be explained by the assumption that the more aggressive martial artists may be more accustomed to violent situations leading to a down-modulation of amygdala activation. Appetitive aggression should be taken into account as a factor contributing to violence.

The hypothalamus and neuropsychiatric disorders: psychiatry meets microscopy.

The past decades have witnessed an explosion of knowledge on brain structural abnormalities in schizophrenia and depression. Focusing on the hypothalamus, we try to show how postmortem brain microscopy has contributed to our understanding of mental disease-related pathologic alterations of this brain region. Gross anatomical abnormalities (volume changes of the third ventricle, the hypothalamus, and its nuclei) and alterations at the cellular level (loss of neurons, increased or decreased expression of hypothalamic peptides such as oxytocin, vasopressin, corticotropin-releasing hormone, and other regulatory factors as well as of enzymes involved in neurotransmitter and neuropeptide metabolism) have been reported in schizophrenia and/or depression. While histologic research has mainly concentrated on neurons, little is currently known about the impact of non-neuronal cells for hypothalamus pathology in mental disorders. Their study would be a rewarding task for the future.

Reduced volumes of the external and internal globus pallidus in male heroin addicts: a postmortem study.

Deep brain stimulation (DBS) of the globus pallidus internus was recently proposed as a potential new treatment target for opioid addiction. DBS requires computer-assisted-3D planning to implant the stimulation electrode precisely. As volumes of brain regions may differ in addiction compared to healthy controls, our aim was to investigate possible volume differences in addicts compared to healthy controls. Volumes of the globus pallidus externus (PE) and internus (PI) in heroin addicts (n = 14) and healthy controls (n = 12) were assessed using morphometry of serial whole-brain sections. Total brain volume was larger in the heroin group (mean 1479 ± 62 cm3 vs. mean 1352 ± 103 cm3), as the heroin group was more than 10 years younger (p = 0.001). Despite larger mean whole brain volume, the mean relative volume of the PE and PI was smaller in addicted subjects compared to healthy controls (PE 0.658 ± 0.183 × 10-3 vs. 0.901 ± 0.284 × 10-3; ANOVA F(1, 24) = 6.945, p = 0.014, η2 = 0.224; PI 0.253 ± 0.095 × 10-3 vs. 0.345 ± 0.107 × 10-3; ANOVA F(1, 24) = 5.374, p = 0.029, η2 = 0.183). These findings were not significantly confounded by age, duration of autolysis, and fixation time. Our results provide further evidence for structural and not only functional deficits of the globus pallidus in addiction. In the context of previous studies, our findings support the idea of shared pathophysiological processes between comorbid depression and impulsivity in opioid addiction.

Aggressiveness of martial artists correlates with reduced temporal pole grey matter concentration.

Perception and practice of violence have hedonistic aspects associated with positive arousal (appetitive aggression). Earlier studies have mainly investigated the aetiology of aggressive behaviour in forensic/psychiatric patients. The present study examined structural brain characteristics in healthy people practicing violent sports (martial artists) compared to controls not showing violent behaviour. Aggressiveness was assessed in 21 male healthy martial artists and 26 age-matched male healthy controls using the aggressivity factors questionnaire (FAF). Participants underwent structural T1-weighted MRI. Grey matter (GM) differences were analysed using voxel-based morphometry. Whole-brain analyses of the main effects of group and aggressiveness and their interaction were computed. An interaction effect between group and aggressiveness was evident in a brain cluster comprising the left temporal pole and left inferior temporal gyrus. In martial artists, aggressiveness was inversely related to mean GM concentration in this cluster while in controls the opposite pattern was evident. Since these temporal brain regions are relevant for emotion/aggression regulation and threat appraisal, the increased GM concentration in aggressive controls might reflect a stronger cognitive top-down inhibition of their aggressiveness. Lower GM concentration in more aggressive martial artists may indicate a reduced need of inhibitory cognitive control because of their improved self-regulation skills.

Allostatic load is associated with psychotic symptoms and decreases with antipsychotic treatment in patients with schizophrenia and first-episode psychosis.

Current pathophysiological models of schizophrenia suggest that stress contributes to the etiology and trajectory of the disorder. We investigated if allostatic load (AL), an integrative index of neuroendocrine, immune and metabolic dysregulation in response to chronic stress, is elevated in patients with schizophrenia (SCZ) and first-episode psychosis (FEP) and related to psychotic symptoms and social and occupational functioning. Additionally, we assessed the temporal dynamics of AL in response to treatment with second-generation antipsychotics. AL, psychotic symptoms and psychosocial functioning were assessed in a longitudinal design in patients with SCZ (n = 28), FEP (n = 28), and healthy controls (n = 53) at baseline and 6 and 12 weeks after commencement of antipsychotic therapy. AL at baseline was higher in patients with SCZ and FEP relative to controls, but not different between patients with SCZ and FEP. Adjusting for age and smoking, we found that positive symptoms were positively correlated with AL and psychosocial functioning was negatively correlated with AL at trend level. Linear mixed model analysis demonstrated that AL decreased after treatment was commenced in patients with SCZ and FEP between the baseline assessment and the 6 and 12-week follow-up. AL was not predictive of treatment response or symptomatic remission. Our data provide evidence for cumulative physiological dysregulation in patients with SCZ and FEP that is linked to the experience of current positive psychotic symptoms. AL could be a useful tool to monitor biological signatures related to chronic stress and unhealthy behaviors in schizophrenia.