Neuromelanin-sensitive MRI (NM-MRI) purports to detect the content of neuromelanin (NM), a product of dopamine metabolism that accumulates with age in dopamine neurons of the substantia nigra (SN). ...Interindividual variability in dopamine function may result in varying levels of NM accumulation in the SN; however, the ability of NM-MRI to measure dopamine function in non-neurodegenerative conditions has not been established. Here, we validated that NM-MRI signal intensity in postmortem midbrain specimens correlated with regional NM concentration even in the absence of neurodegeneration, a prerequisite for its use as a proxy for dopamine function. We then validated a voxelwise NM-MRI approach with sufficient anatomical sensitivity to resolve SN subregions. Using this approach and a multimodal dataset of molecular PET and fMRI data, we further showed the NM-MRI signal was related to both dopamine release in the dorsal striatum and resting blood flow within the SN. These results suggest that NM-MRI signal in the SN is a proxy for function of dopamine neurons in the nigrostriatal pathway. As a proof of concept for its clinical utility, we show that the NM-MRI signal correlated to severity of psychosis in schizophrenia and individuals at risk for schizophrenia, consistent with the well-established dysfunction of the nigrostriatal pathway in psychosis. Our results indicate that noninvasive NM-MRI is a promising tool that could have diverse research and clinical applications to investigate in vivo the role of dopamine in neuropsychiatric illness.
We examined neuroimaging-derived hippocampal biomarkers in subjects at clinical high risk (CHR) for psychosis to further characterize the pathophysiology of early psychosis. We hypothesized that ...glutamate hyperactivity, reflected by increased metabolic activity derived from functional magnetic resonance imaging in the CA1 hippocampal subregion and from proton magnetic resonance spectroscopy–derived hippocampal levels of glutamate/glutamine, represents early hippocampal dysfunction in CHR subjects and is predictive of conversion to syndromal psychosis.
We enrolled 75 CHR individuals with attenuated positive symptom psychosis-risk syndrome as defined by the Structured Interview for Psychosis-risk Syndromes. We used optimized magnetic resonance imaging techniques to measure 3 validated in vivo pathologies of hippocampal dysfunction—focal cerebral blood volume, focal atrophy, and evidence of elevated glutamate concentrations. All patients were imaged at baseline and were followed for up to 2 years to assess for conversion to psychosis.
At baseline, compared with control subjects, CHR individuals had high glutamate/glutamine and elevated focal cerebral blood volume on functional magnetic resonance imaging, but only baseline focal hippocampal atrophy predicted progression to syndromal psychosis.
These findings provide evidence that CHR patients with attenuated psychotic symptoms have glutamatergic abnormalities, although only CHR patients who develop syndromal psychosis exhibit focal hippocampal atrophy. Furthermore, these results support the growing evidence that hippocampal dysfunction is an early feature of schizophrenia and related psychotic disorders.
Deficits in mismatch negativity (MMN) generation are among the best-established biomarkers for cognitive dysfunction in schizophrenia and predict conversion to schizophrenia (Sz) among individuals at ...symptomatic clinical high risk (CHR). Impairments in MMN index dysfunction at both subcortical and cortical components of the early auditory system. To date, the large majority of studies have been conducted using deviants that differ from preceding standards in either tonal frequency (pitch) or duration. By contrast, MMN to sound location deviation has been studied to only a limited degree in Sz and has not previously been examined in CHR populations. Here, we evaluated location MMN across Sz and CHR using an optimized, multi-deviant pattern that included a location-deviant, as defined using interaural time delay (ITD) stimuli along with pitch, duration, frequency modulation (FM) and intensity deviants in a sample of 42 Sz, 33 CHR and 28 healthy control (HC) subjects. In addition, we obtained resting state functional connectivity (rsfMRI) on CHR subjects. Sz showed impaired MMN performance across all deviant types, along with strong correlation between MMN deficits and impaired neurocognitive function. In this sample of largely non-converting CHR subjects, no deficits were observed in either pitch or duration MMN. By contrast, CHR subjects showed significant impairments in location MMN generation particularly over right hemisphere and significant correlation between impaired location MMN and negative symptoms including deterioration of role function. In addition, significant correlations were observed between location MMN and rsfMRI involving brainstem circuits. In general, location detection using ITD stimuli depends upon precise processing within midbrain regions and provides a rapid and robust reorientation of attention. Present findings reinforce the utility of MMN as a pre-attentive index of auditory cognitive dysfunction in Sz and suggest that location MMN may index brain circuits distinct from those indexed by other deviant types.
Little is known about the success of the insanity defense in homicide cases involving posthumous dismemberment. Such seemingly bizarre conduct may suggest, at first glance, aberrant mental states. ...Drawing from a larger study of cases of single or repeat homicide followed by dismemberment on at least one occasion, we examined 38 in which offenders pleaded the insanity defense. These were compared to 30 cases in which no posthumous dismemberment was observed. Cases were drawn from print and online sources, as well as the Radford/Florida Gulf Coast Universities Serial Killer Database (SKD). Various motivations for both homicide and posthumous dismemberment among defendants who attempted to plead Not Guilty by Reason of Insanity (NGRI) were analyzed.
The most common style of mutilation and dismemberment observed was aggressive, occurring in the context of excessive emotion, such as rage or acute psychosis. Among those in the dismemberment group, 52.6% of the NGRI cases proved successful. In comparison, 33.3% of the NGRI cases were successful among those in the non-dismemberment group. A relationship between NGRI outcomes and motive for homicide was observed in both comparison groups.
Our findings suggest that posthumous dismemberment may be an important characterological description in homicide offending, representing murderous impulses that may help to identify a sub-group of homicide offenders. Examination of posthumous dismemberment vis-a-vis NGRI verdicts also helps elucidate the degree to which posthumous dismemberment is, at least in some cases, a psychopathology-driven action.
•The Aggressive style of dismemberment was the most common style displayed from our sample.•A significant relationship was observed between dismemberment style and motives for murder.•In the dismemberment group, 75% of successful NGRI cases involved motives associated with the offenders’ mental status and wellbeing.•In comparison, 47% of cases which were motivated by emotions or anger were not successful.•While 92% of the offenders displayed either aggressive or offensive styles of dismemberment, only about 52% successfully pled insanity.
Genetic tests for schizophrenia could introduce both risks and benefits. Little is known about the hopes and expectations of young adults at clinical high-risk for psychosis concerning genetic ...testing for schizophrenia, despite the fact that these youth could be among those highly affected by such tests. We conducted semistructured interviews with 15 young adults at clinical high-risk for psychosis to ask about their interest, expectations, and hopes regarding genetic testing for schizophrenia. Most participants reported a high level of interest in genetic testing for schizophrenia, and the majority said they would take such a test immediately if it were available. Some expressed far-reaching expectations for a genetic test, such as predicting symptom severity and the timing of symptom onset. Several assumed that genetic testing would be accompanied by interventions to prevent schizophrenia. Participants anticipated mixed reactions on finding out they had a genetic risk for schizophrenia, suggesting that they might feel both a sense of relief and a sense of hopelessness. We suggest that genetic counseling could play an important role in counteracting a culture of genetic over-optimism and helping young adults at clinical high-risk for psychosis understand the limitations of genetic testing. Counseling sessions could also invite individuals to explore how receiving genetic risk information might impact their well-being, as early evidence suggests that some psychological factors help individuals cope, whereas others heighten distress related to genetic test results.
Abstract Background Schizophrenia, a neurodevelopmental disorder, involves abnormalities in functional connectivity (FC) across distributed neural networks, which are thought to antedate the ...emergence of psychosis. In a cohort of adolescents and young adults at clinical high risk (CHR) for psychosis, we applied data-driven approaches to resting-state fMRI data so as to systematically characterize FC abnormalities during this period and determine whether these abnormalities are associated with psychosis risk and severity of psychotic symptoms. Methods Fifty-one CHR participants and 47 matched healthy controls (HCs) were included in our analyses. Twelve of these CHR participants developed psychosis within 3.9 years. We estimated one multivariate measure of FC and studied its relationship to CHR status, conversion to psychosis and positive symptom severity. Results Multivariate analyses revealed between-group differences in whole-brain connectivity patterns of bilateral temporal areas, mostly affecting their functional connections to the thalamus. Further, more severe positive symptoms were associated with greater connectivity abnormalities in the anterior cingulate and frontal cortex. Conclusions Our study demonstrates that the well-established FC abnormalities of the thalamus and temporal areas observed in schizophrenia are also present in the CHR period, with aberrant connectivity of the temporal cortex most associated with psychosis risk.
ABSTRACTIndividuals with psychotic symptoms often report low global self-esteem (GSE). However, it remains unclear whether the low GSE is linked to the presence of psychotic symptoms or it is present ...before the onset of psychosis. In addition, the specific subdomains of GSE in these populations are unknown. To address this question, we conducted a cross-sectional study comparing global and SE elements among individuals at clinical high risk for psychosis (CHR; n = 36), individuals with schizophrenia (SCZ; n = 43), and healthy controls (HCs; n = 40). We then examined among CHR individuals the association between GSE, subdomains, and symptoms. CHR individuals displayed significantly lower GSE compared to HCs, at a level comparable with those for individuals with SCZ. The low GSE was driven primarily by self-perceptions of work and interpersonal relationships abilities. Lower GSE was associated with overall negative and disorganized symptoms severity, but not positive ones. The authors discuss the implications of the findings to intervention development.
Abstract
Background
Individuals with psychotic symptoms often report low global self-esteem (GSE).
However, it remains unclear whether the low GSE is linked to the presence of psychotic symptoms or ...it is present prior to the onset of psychosis. Additionally, the specific subdomains of GSE in these populations are unknown.
Methods
To address this question, we conducted a cross-sectional study comparing global and SE elements among individuals at clinical high-risk for psychosis (CHR; n=36), individuals with schizophrenia (SCZ; n=43), and healthy controls (HC; n=40). We then examined among CHR individuals the association between GSE, subdomains, and symptoms.
Results
CHR individuals displayed significantly lower GSE compared to HC, at a level comparable to individuals with SCZ. The low GSE was driven primarily by self-perceptions of work and interpersonal relationships abilities, in the sub-domains of provider (r=.53, p<.001), physical appearance (r=.37, p=.026), sense of humor (r=.45, p=.006), intimate relations (r=.45, p=.006), and job competence (r=.39, p=.018). Lower GSE was associated with overall negative (p<0.01) and disorganized (p<0.05) symptoms severity, but not positive ones.
Discussion
This investigation demonstrates that low self-esteem, which is prevalent in SCZ, is also present to a comparable degree of severity in CHR individuals. Our findings help to better understand the CHR period and may suggest targets for early psychosocial treatments aimed at improving social and occupational functioning, as such domains appear to play an important role in determining GSE in this population. The examination of different dimensions of self-esteem in the assessment of CHR populations may contribute to a better understanding of the phenomenology of prodromal symptoms, and thus, may have implications for finding successful early therapeutic approaches, rehabilitation, and social integration for a condition that is accompanied by considerable suffering and risk of suicide.
Cannibalism is a practice that has been present in numerous cultures. Personal cause or criminal cannibalism is arguably one of the most unfathomable acts which an individual might perpetrate. This ...study examined the patterns of those who engage in cannibalism in comparison to those who posthumously dismember or mutilate their victims but do not consume their flesh. Cases were extracted from the Serial Killer Database, as well as media sources, and assessed for characteristics of the perpetrators. An informational form was developed and used to establish quantitative parameters and objectively extract pertinent information that could be used for comparison and pattern analysis. Variables including motives, styles, and level of organization during the crime were examined for each case. The majority of the cannibalism cases were consistent with an offensive style (56.7%), while cases in the dismemberment-only group were marked by a defensive style (66.7%). Whereas the majority of dismemberment/mutilation cases have the ultimate goal of disposing of evidence, the dataset demonstrated that cannibal cases are primarily planned, organized and driven by sadism. The findings support two primary patterns among cannibalistic offenders: ‘psychosis-driven, disorganized and aggressive’ and ‘sadism-driven, organized and offensive’.
Attributes and behavioral patterns of female homicide offenders have been less explored than those of males, particularly in crimes that involve aggravating factors such as dismemberment and ...mutilation. This study explored the patterns of female murderers who engage in postmortem dismemberment and/or mutilation of victims, contrasting these with the patterns of males who display these same behaviors. Cases were obtained from Radford‐Florida Gulf Coast University Database and public sources, and then analyzed for specific characteristics of the crimes. An informational form was used to derive quantitative parameters. Statistical significance between sex and variables such as motive, dismemberment/mutilation style, and level of organization during the crime were examined. The majority of the cases were consistent with a defensive style. However, 23% of the cases involving females followed an offensive style compared to 33% among males. The nature of prior relationships between offenders and their victims was noteworthy, with the victims of males being largely strangers and the victims of females being primarily known to them. In comparison to males, females were markedly organized. These differences may emphasize aspects of psychological drives and pleasure‐seeking that was more commonly seen among men, who often targeted strangers and were motivated by sadism in 25% of the cases. Dismemberment perpetrated by women primarily followed a defensive style that aimed to dispose of evidence, which would be congruent with the assumption that the murder occurred within a prior background of interpersonal partner violence toward the female perpetrator or other family members.
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