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The American Journal of Psychiatry Oct 2023Maternal psychological stress during pregnancy is a common risk factor for psychiatric disorders in offspring, but little is known about how heterogeneity of stress...
OBJECTIVE
Maternal psychological stress during pregnancy is a common risk factor for psychiatric disorders in offspring, but little is known about how heterogeneity of stress trajectories during pregnancy affect brain systems and behavioral phenotypes in infancy. This study was designed to address this gap in knowledge.
METHODS
Maternal anxiety, stress, and depression were assessed at multiple time points during pregnancy in two independent low-risk mother-infant cohorts (N=115 and N=2,156). Trajectories in maternal stress levels in relation to infant negative affect were examined in both cohorts. Neonatal amygdala resting-state functional connectivity MRI was examined in a subset of one cohort (N=60) to explore the potential relationship between maternal stress trajectories and brain systems in infants relevant to negative affect.
RESULTS
Four distinct trajectory clusters, characterized by changing patterns of stress over time, and two magnitude clusters, characterized by severity of stress, were identified in the original mother-infant cohort (N=115). The magnitude clusters were not associated with infant outcomes. The trajectory characterized by increasing stress in late pregnancy was associated with blunted development of infant negative affect. This relationship was replicated in the second, larger cohort (N=2,156). In addition, the trajectories that included increasing or peak maternal stress in late pregnancy were related to stronger neonatal amygdala functional connectivity to the anterior insula and the ventromedial prefrontal cortex in the exploratory analysis.
CONCLUSIONS
The trajectory of maternal stress appears to be important for offspring brain and behavioral development. Understanding heterogeneity in trajectories of maternal stress and their influence on infant brain and behavioral development is critical to developing targeted interventions.
Topics: Infant; Infant, Newborn; Female; Humans; Pregnancy; Amygdala; Prefrontal Cortex; Mothers; Magnetic Resonance Imaging; Affect
PubMed: 37670606
DOI: 10.1176/appi.ajp.21111176 -
Journal Francais D'ophtalmologie Feb 2016Lacrimal system injuries represent a significant part of ocular emergencies and mainly affect males of various ages including very young children. The most frequent... (Review)
Review
Lacrimal system injuries represent a significant part of ocular emergencies and mainly affect males of various ages including very young children. The most frequent presentations are canalicular laceration with a palpebral wound medial to the lacrimal punctum. The inferior canaliculus is the most commonly affected but bilateral injuries or injuries affecting both canaliculi can occur. The main causes are dog bites in children, scuffles in young adults and falls in elderlies. Antitetanic and antirabic measures have to be considered for open cases. The diagnosis is easily made by inspection and can be confirmed by probing. Other lesions can be associated and require proper identification, especially eyeball laceration requiring surgical repair within 6 hours. Otherwise, isolated canalicular wounds are to be repaired within 48 hours by an anastomotic suture with or without mono- or bi-canalicular silicone intubation. Other lacrimal tract injuries involving the lacrimal sac or the nasolacrimal duct are rare, commonly associated with blunt craniofacial trauma or iatrogenic after some surgical procedures.
Topics: Adult; Animals; Dogs; Eye Injuries; Female; Humans; Lacrimal Apparatus; Lacrimal Apparatus Diseases; Male
PubMed: 26847220
DOI: 10.1016/j.jfo.2015.10.002 -
Progress in Neuro-psychopharmacology &... Apr 2020Negative Symptoms (blunted affect, alogia, anhedonia, avolition and asociality) are observed in schizophrenia but also in depressive disorders. (Review)
Review
BACKGROUND
Negative Symptoms (blunted affect, alogia, anhedonia, avolition and asociality) are observed in schizophrenia but also in depressive disorders.
OBJECTIVE
To gather cognitive, neuroanatomical, neurofunctional and neurobiological knowledge of negative symptoms in studies on schizophrenia, depressive disorder, and transnosographic studies.
RESULTS
Blunted affect in schizophrenia is characterized by amygdala hyperactivation and frontal hypoactivation, also found in depressive disorder. Mirror neurons, may be related to blunted affect in schizophrenia. Alogia may be related to cognitive dysfunction and basal ganglia area impairments in schizophrenia. Data surrounding alogia in depressive disorder is scarce; wider speech deficits are often studied instead. Consummatory Anhedonia may be less affected than Anticipatory Anhedonia in schizophrenia. Anhedonia is associated with reward impairments and altered striatal functions in both diagnostics. Amotivation is associated with Corticostriatal Hypoactivation in both disorders. Anhedonia and amotivation are transnosographically associated with dopamine dysregulation. Asociality may be related to oxytocin.
CONCLUSION
Pathophysiological hypotheses are specific to each dimension of negative symptoms and overlap across diagnostic boundaries, possibly underpinning the observed clinical continuum.
Topics: Anhedonia; Apathy; Aphasia; Brain; Cognition; Depressive Disorder; Humans; Schizophrenia; Schizophrenic Psychology
PubMed: 31927053
DOI: 10.1016/j.pnpbp.2020.109862 -
Journal of Psychiatric Research Mar 2021Affect dynamics reflect individual differences in how emotional information is processed, and may provide insights into how depressive episodes develop. To extend prior...
Affect dynamics reflect individual differences in how emotional information is processed, and may provide insights into how depressive episodes develop. To extend prior studies that examined affect dynamics in currently depressed individuals, the present study tested in 68 non-depressed young adults whether three well-established risk factors for major depressive disorder (MDD) - (a) past episodes of MDD, (b) family history of MDD, and (c) reduced neurophysiological responses to reward - predicted mean levels, instability, or inertia (i.e., inflexibility) of positive affect (PA) and/or negative affect (NA). Momentary PA and NA were assessed up to 6 times per day for 14 days (mean number of surveys completed = 45.89). MDD history and family history of MDD were assessed via semi-structured interview, and neurophysiological responses to reward were indexed using the Reward Positivity, an event-related potential related to depression. After adjusting for current depressive symptoms, results indicated that (a) past episodes of MDD predicted higher mean levels of NA, (b) family history of MDD predicted greater PA inertia, and (c) blunted reactivity to reward predicted greater NA inertia. Collectively, these results suggest that elevated mean levels of NA and inflexibility of PA and NA may be potential mechanisms that confer risk for depression.
Topics: Affect; Depression; Depressive Disorder, Major; Ecological Momentary Assessment; Humans; Risk Factors; Young Adult
PubMed: 33450467
DOI: 10.1016/j.jpsychires.2021.01.007 -
Progress in Neuro-psychopharmacology &... Jan 2005This study investigated changes in cerebral activation related to emotion processing in schizophrenia patients with blunted or flat affect (FA+) during treatment with... (Clinical Trial)
Clinical Trial
This study investigated changes in cerebral activation related to emotion processing in schizophrenia patients with blunted or flat affect (FA+) during treatment with quetiapine. Using functional magnetic resonance imaging (fMRI), brain activation in 12 FA+ schizophrenia patients during passive viewing of sad film excerpts was studied before and after a median of 5.5-months treatment with quetiapine. Random-effects 'paired sample t-test' analyses of brain activation before quetiapine (contrast=sad-neutral, before-after) revealed significant activation in the brainstem (pons, medulla). After quetiapine, the same contrast showed significant prefrontal activation (BA 9, 10 and 11). Activation of key prefrontal areas involved in emotion processing and significant symptoms improvement as measured by the subjective rating scale and PANSS suggests the potential effect of quetiapine in improving blunted affect related symptoms (i.e., passive withdrawal, emotional withdrawal, social avoidance) in schizophrenia.
Topics: Adult; Affect; Antipsychotic Agents; Dibenzothiazepines; Echo-Planar Imaging; Emotions; Female; Frontal Lobe; Humans; Magnetic Resonance Imaging; Male; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology
PubMed: 15610941
DOI: 10.1016/j.pnpbp.2004.08.015 -
Psychoneuroendocrinology Jul 2021Sleep disturbances and insufficient sleep are highly prevalent. Both clinical sleep disorders and multiple forms of experimental sleep loss predict heightened... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Sleep disturbances and insufficient sleep are highly prevalent. Both clinical sleep disorders and multiple forms of experimental sleep loss predict heightened inflammation. As such, it is necessary to investigate potential protective factors. Given that trait positive affect (PA) is associated with reduced inflammation, and buffers the proinflammatory effects of stress, it is possible that high trait positive affect might protect individuals from an inflammatory response to sleep disruption. The present study tested this hypothesis in an experimental sleep disruption paradigm with assessment of cellular inflammation.
METHODS
Data were drawn from good sleeping adults (n = 79) who participated in a randomized, within-subjects crossover experiment comparing the effects of two nights of sleep disruption versus two nights of uninterrupted sleep. Stimulated monocytic production of intracellular proinflammatory cytokines tumor necrosis factor (TNF) and interleukin-6 (IL-6) were assayed using flow cytometric methods and indexed as the percentage of monocytes expressing TNF, IL-6, or co-expressing both. Hypotheses were evaluated using linear mixed effects models.
RESULTS
Controlling for negative affect, body mass index, age, and sex, PA significantly moderated the associations between sleep condition and stimulated monocyte production of IL-6 (b = -1.03, t = -2.02, p = .048) and its co-expression with TNF (b = -0.93, t = -2.00, p = .049), such that inflammatory responses were blunted among those high in PA with increases principally among those low in PA. The effect on TNF was similar in terms of effect size, but marginally significant.
CONCLUSIONS
Activation of cellular inflammation in response to sleep disruption is buffered by PA independent of negative affect. Interventions that promote PA might protect persons from the inflammatory activation following sleep loss, with the potential to mitigate the adverse health consequences of sleep disturbance.
Topics: Adult; Affect; Cross-Over Studies; Female; Happiness; Humans; Inflammation; Interleukin-6; Male; Monocytes; Pleasure; Protective Factors; Sleep; Sleep Deprivation; Tumor Necrosis Factor-alpha
PubMed: 33975149
DOI: 10.1016/j.psyneuen.2021.105240 -
Canadian Journal of Psychiatry. Revue... Dec 2005There have been reports that patients with schizophrenia have decreased activity in the prefrontal cortex during emotion processing. However, findings have been...
OBJECTIVE
There have been reports that patients with schizophrenia have decreased activity in the prefrontal cortex during emotion processing. However, findings have been confounded by sample nonspecificity and explicit cognitive task interference with emotion processing. We aimed to further investigate this by examining the ventrolateral prefrontal cortex (VLPFC) activation in response to the passive viewing of sad film excerpts.
METHODS
We presented film excerpts depicting sad and neutral social situations to 25 schizophrenia patients (14 with blunted affect [BA+] and 11 without blunted affect [BA-]) in an implicit perception task to evoke prefronto-limbic activity illustrated by blood oxygenation level-dependent functional magnetic resonance imaging.
RESULTS
A random-effects analysis (2-sample t test) using statistical parametric mapping indicated that BA+ patients differed from BA- patients at a 0.05 level (P corrected for multiple comparisons). Consistent with our a priori hypothesis, BA- patients (relative to BA+ patients) showed significant activation in the right VLPFC. An exploratory analysis revealed the following loci of activation: caudate nucleus, VLPFC, middle prefrontal cortex, medial prefrontal cortex, anterior cingulate cortex, and anterior temporal pole in the BA- group; and hippocampus, cerebellum, anterior temporal pole, and midbrain in the BA+ group.
CONCLUSIONS
We observed not only hypofrontality in the BA+ group but also dysfunctional circuitry distributed throughout the brain. The temporal and midbrain activation seen in the BA+ group may indicate that these brain regions were working harder to compensate for inactivation in other regions. These distributed dysfunctional circuits may form the neural basis of blunted affect through impairment of emotion processing in the brain that prevents it from processing input efficiently and producing output effectively, thereby leading to symptoms such as blunted affect.
Topics: Adult; Affect; Brain; Diagnostic and Statistical Manual of Mental Disorders; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Oxygen; Schizophrenia; Severity of Illness Index; Social Environment
PubMed: 16494260
DOI: 10.1177/070674370505001405 -
Brain : a Journal of Neurology Jun 2020Major depressive disorder is a leading cause of disability and significant mortality, yet mechanistic understanding remains limited. Over the past decade evidence has...
Major depressive disorder is a leading cause of disability and significant mortality, yet mechanistic understanding remains limited. Over the past decade evidence has accumulated from case-control studies that depressive illness is associated with blunted reward activation in the basal ganglia and other regions such as the medial prefrontal cortex. However it is unclear whether this finding can be replicated in a large number of subjects. The functional anatomy of the medial prefrontal cortex and basal ganglia has been extensively studied and the former has excitatory glutamatergic projections to the latter. Reduced effect of glutamatergic projections from the prefrontal cortex to the nucleus accumbens has been argued to underlie motivational disorders such as depression, and many prominent theories of major depressive disorder propose a role for abnormal cortico-limbic connectivity. However, it is unclear whether there is abnormal reward-linked effective connectivity between the medial prefrontal cortex and basal ganglia related to depression. While resting state connectivity abnormalities have been frequently reported in depression, it has not been possible to directly link these findings to reward-learning studies. Here, we tested two main hypotheses. First, mood symptoms are associated with blunted striatal reward prediction error signals in a large community-based sample of recovered and currently ill patients, similar to reports from a number of studies. Second, event-related directed medial prefrontal cortex to basal ganglia effective connectivity is abnormally increased or decreased related to the severity of mood symptoms. Using a Research Domain Criteria approach, data were acquired from a large community-based sample of subjects who participated in a probabilistic reward learning task during event-related functional MRI. Computational modelling of behaviour, model-free and model-based functional MRI, and effective connectivity dynamic causal modelling analyses were used to test hypotheses. Increased depressive symptom severity was related to decreased reward signals in areas which included the nucleus accumbens in 475 participants. Decreased reward-related effective connectivity from the medial prefrontal cortex to striatum was associated with increased depressive symptom severity in 165 participants. Decreased striatal activity may have been due to decreased cortical to striatal connectivity consistent with glutamatergic and cortical-limbic related theories of depression and resulted in reduced direct pathway basal ganglia output. Further study of basal ganglia pathophysiology is required to better understand these abnormalities in patients with depressive symptoms and syndromes.
Topics: Adult; Affect; Basal Ganglia; Brain Mapping; Computational Biology; Connectome; Corpus Striatum; Depression; Depressive Disorder, Major; Female; Humans; Magnetic Resonance Imaging; Male; Models, Theoretical; Motivation; Nucleus Accumbens; Prefrontal Cortex; Reward
PubMed: 32385498
DOI: 10.1093/brain/awaa106 -
European Neuropsychopharmacology : the... Aug 2015A significant body of epidemiological evidence has linked psychotic symptoms with both acute and chronic use of cannabis. Precisely how these effects of THC are mediated... (Review)
Review
A significant body of epidemiological evidence has linked psychotic symptoms with both acute and chronic use of cannabis. Precisely how these effects of THC are mediated at the neurochemical level is unclear. While abnormalities in multiple pathways may lead to schizophrenia, an abnormality in dopamine neurotransmission is considered to be the final common abnormality. One would thus expect cannabis use to be associated with dopamine signaling alterations. This is the first systematic review of all studies, both observational as well as experimental, examining the acute as well as chronic effect of cannabis or its main psychoactive ingredient, THC, on the dopamine system in man. We aimed to review all studies conducted in man, with any reported neurochemical outcomes related to the dopamine system after cannabis, cannabinoid or endocannabinoid administration or use. We identified 25 studies reporting outcomes on over 568 participants, of which 244 participants belonged to the cannabis/cannabinoid exposure group. In man, there is as yet little direct evidence to suggest that cannabis use affects acute striatal dopamine release or affects chronic dopamine receptor status in healthy human volunteers. However some work has suggested that acute cannabis exposure increases dopamine release in striatal and pre-frontal areas in those genetically predisposed for, or at clinical high risk of psychosis. Furthermore, recent studies are suggesting that chronic cannabis use blunts dopamine synthesis and dopamine release capacity. Further well-designed studies are required to definitively delineate the effects of cannabis use on the dopaminergic system in man.
Topics: Brain; Cannabinoids; Cannabis; Dopamine; Endocannabinoids; Humans; Psychotropic Drugs
PubMed: 26068702
DOI: 10.1016/j.euroneuro.2015.03.011 -
Annals of Neurology Jan 1998Autism is a behaviorally defined, life-long static developmental disorder of the brain that is poised for neurobiological investigation. It affects at least 1 or 2 in... (Review)
Review
Autism is a behaviorally defined, life-long static developmental disorder of the brain that is poised for neurobiological investigation. It affects at least 1 or 2 in 1000 persons and has a broad range of severity. It has multiple causes, with genetics playing a major role. According to the DSM-IV, defining features are impaired sociability, language and communication, and range of interests and activities. Mental deficiency is frequent but by no means universal. The cognitive profile is characteristic, occasionally with a superior but narrow talent. Perseveration, concreteness, affective blunting, and lack of insight into other persons' thinking may be conspicuous. The neurological basis of autism's many sensorimotor features, including stereotypies, is unknown. Attention and sleep are affected, and one third of individuals experience epilepsy by adulthood. Whether subclinical epilepsy plays a role in the developmental regression of the one third of the toddlers who lose their language skills and become autistic remains to be determined. Clinical neuroimaging and biochemical investigations are generally unremarkable. Fewer than 35 brains have been examined pathologically, none with modern techniques. The findings thus far suggest subtle prenatal neuronal maldevelopment in the cerebellum and certain limbic structures. Abnormalities in distributed networks involving serotonin and perhaps other neurotransmitters require further documentation.
Topics: Autistic Disorder; Brain; Environment; Humans; Magnetic Resonance Imaging; Prevalence
PubMed: 9450763
DOI: 10.1002/ana.410430106