L15 Flashcards
Schizophrenia is characterized by episodic ____ ___ or ____ symptoms that are commonly (but not necessarily) accompanied by persistent negative symptoms such as ____ ___, impaired attention, social ____, and ____ impairment.
positive psychotic, disorganization, flattened affect, withdrawal, cognitive
The symptoms of schizophrenia have been attributed to the ___ and ____ of NT systems in the ________ circuits
disruption, imbalance, mesocorticolimbic
The dopamine hypothesis of schizophrenia states that ___ of DA signalling in the mesolimbic pathway via ___ receptors, contributes to the positive symptoms, while hypoactivity of DA signalling in the ___ pathway via ___ receptors, contributes to the negative symtpoms
hyperactivity, D2, mesocortical, D1
Sex / gender differences exist in the _____, ___ and ___ of schizophrenia. There is slightly ____ prevalence in men than women (but no difference in ____). Men also have a ___ year earlier onset than women, and women have another spike for onset at the start of _____. Men with schizophrenia experience more _____ symptoms and ____ clinical features, particularly social ____, ____ abuse, and blunted affect. Women with schizophhrenia present more _____ disturbances, and _____ / _____ symptoms. With a late onset, there tends to be less severe ___ symptoms, and more severe positive psychotic symptoms. Female patients show better ___ ___ than men and have ___% less hospitalizations.
prevalence, manifestation, onset, higher, incidence, 5, menopause, negative, severe, withdrawal, substance, mood, depressive, affective, negative, treatment response, 50
____ are hypothesized to have therapeutic and _______ properties against schizophrenia. The symptoms of SZ are worse when they are low, such as ___ and _____. Exogenous estrogens enhance _____ drug effectiveness. Additionally, higher ____ estradiol provides a antipsychotic effect for women. Symptoms of SZ also fluctuate across the ____ _____, with phases with lower estrogen like ____ and the ____ phase having increased symptoms, and phases with higher estrogens like _____ and the _______ phase having decreased symptoms. In female patients with chronic SZ, higher estrogen levels are associated with better ____ ability.
estrogens, neuroprotective, menopause, postpartum, antipsychotic, circulating, menstrual cycle, menses, luteal, follicular, ovulation, cognitive
Estrogens may act within the mesocorticolimbic system to protect against sz _______. Estrogen increases presynaptic ____ ______ transporters, which limits the DA left in the ___ _____, and decreases ______.
pathology, DA reuptake, synaptic cleft, D2R
There are inconsistent finding with ____, some showing protective, and some showing ____ effects on SZ.
progesterone, deleterious
In one experiment, autoradiography was used to look for ___, ___ and ____ density in the NAcc, __ ___, and cingulate cortex. Female rats were ___ and administered saline or ___ for ___ weeks. They found that ovariectomy ____ DAT in the Nacc, an effect that is ____ by estradiol treatment. They found no effects on ____. They found that ovariectomy increased ____ density in the Nacc and caudate nucleus, and _____ density when ovariectomy was paired with estradiol. In conclusion, estradiol acts on DA in the ____ pathway to protect against SZ
DAT, D1R, D2R, caudate nucleus, ovariectomized, estradiol, 4-5, reduced, rescued, D1R, D2R, decreased, mesolimbic
Major depressive disorder is more than ____x more common in young women than in men, but the ____ of the prevalence discrepancy ____ with age. Studies find no difference in the prevalence rates in _____, or if they do, it is higher in ___ than girls. Similar prevalence ratios were found globally, suggesting that the sex / gender gap is primarily drive by ___ ____ ____ and less dependent on socioeconomic factors. A contributing factor for men may be T decline at age ____, and for women, ____ at age 50-55
- magnitude, diminishes, prepubescence, boys, biological sex differences, 40, menopause
In MDD, there is a higher risk for ___ in men than women, and depressed men exhibit more ____ ____, aggression, ____ use, ___ and escape behaviours. Depressed women show ____ disturbance, impaired ____, difficulty in ____, low ___, irritability and depressed mood that is higher in ___ and ____. Compared to men, depressed women also experience more _____ depressive episodes, and higher rates of ___ symptoms such as excessive ____, overeating and oversleeping, anxiety and ____.
suicide, anger attacks, substance, risk-taking, appetite, sleep, decision-making, energy, frequency, intensity, frequent, atypical, fatigue, somatization
Most of the behaviours reported in depressed men do not fit the ____ __ ___ for MDD, which is more in line with what ____ experience. This may partially explain the sex/gender gap in ____
DSM diagnostic criteria, women, prevalence
men respond better to ____ ____ compared to women, while women show better response to ____. this may be due to sex differences in drug ___ and ___, as well sex steroids that interfere with the ___ __ ___ of antidepressants
tricyclic antidepressants, SSRIs, metabolism, distribution, mechanism of action
There are two cytoplasmic estrogen receptors: the _____ receptor or the ____ receptor, as well as a membrane bound _____ receptor.
ER-alpha, ER-beta, GPER1
allopregnanolone is a _____ metabolite and a ____ ___ ___ of GABA-A receptors and ____ ___ autoreceptors. It increases ____ mediated inhibition, and ____ DA release. It also triggers an initial ____ of glutamate, which depolarizes ____ receptors, triggers ____ influx, and thus upregulates release of ____ (learning and memory).
progesterone, positive allosteric modulator, presynaptic, D2, GABA-A, decreases, burst, MDMA, Ca2+, BDNF
Exogenous progesterone in ___ ______ decreased endogenous progesterone, and exogenous progesterone does not break down into ____. This means a reduction in ___ signalling and higher levels of ____.
oral contraceptives, ALLO, GABA, anxiety
For androgens, Testosterone is first converted to ______ by _____. This then binds to receptors and leads to ___ ____.
DHT, 5-alpha-reductase, signalling cascades
Increased depression symptoms in females are associated with decreased ____ gene expression in the __ ____, and _____, gene polymorphisms of ER-alpha, _____, _____ and ____.
ER-alpha, medial amygdala, hypothalamus, CYP1A1, 17HSD, aromatase
Increase depression symptoms in males are associated with decreased ____ receptor gene expression or activity and gene ____ of ARs
androgens, polymorphisms
Increased depressed symptoms for both males and females were associated with decreased _____ expression, ___ concentration, or ____.
GPER1, protein, activity
Antidepressant effects in females are associated with _____ ER-alpha activation in the _____, as well as increased ____ concentrations in the same area. It is also associated with increased ______ expression or activation
increased, hippocampus, ALLO, GPER1
Antidepressant effects in males are associated with ___ ____ ____ when basal levels are low due to age or ____
T replacement therapy, hypogonadism
Antidepressant effects in both males and females are associated with increased _____ and _____ signalling, increased ___ activation, stimulation of ____, and increased ____ release
BDF, TrKB, D2R, glutamate, Ca2+
Inflammation induces changes in ____ state and ____ behaviours, many of which are similar to depressive symptoms, such as ___, ___ disturbances, low ___ and _____. Patients with MDD also exhibit increased levels of ____ biomarkers, and this is also higher in patients who are _______ _____.
motivational, sickness, fatigue, sleep, mood, anhedonia, pro-inflammatory, antidepressant-treatment resistant.
Though apparent in both men and women, the relationship between ___ and depression might have more clinical relevance in ____. Baseline ___ predicts long term depression in ___ but not in men, in other words, a higher IL-6 baseline meant that these individuals were more likely to have depression ___ years later.
inflammation, women. IL-6, women, 6
Different inflammatory profiles are associated with different ____ of depression. Pro-inflammatory states are associated with ____ depression. Reduced _____ ______ _____ is associated with non-melancholic depression. _____ protein, a biomarker of increased inflammation, is associated with greater symptom ___ in MDD. Low grade inflammation is associated with _____ depression and poor ___ ____ to antidepressants.
components, melancholic, pro-inflammatory cytokine production, c-reactive, severity, treatment-resistant, treatment response
pro-inflammatory cytokines can target NT systems and reduce availability of ____, ___ and ___ (catecholamines)
NE, 5-HT, DA
Neuroinflammation increases the ___ and function of _____ ____ ____. It also decreases monoamine ____ such as tryptophan. Inflammatory cytokines can also decrease the expression or function of ______, and/or increase expression / function of ____, reducing DA levels.
expression, presynaptic reuptake transporters, precursors, VMAT2, DAT
Reduced dopamine levels are associated with reduced ____ in the mesocortical regions resulting in ____, reduced __ ____ and ____. Cytokines also affect DA pathways by inhibiting corticostriatal circuits involving the ___ ____, ____, and subgenual and dorsal _____, affecting reward, motivation and ____ drive
connectivity, anhedonia, cognitive capacity, fatigue, basal ganglia, vmPFC, ACC, hedonic
Cytokines activate circuits regulating ___, ____ ___ and fear, including the amygdala, ___, ______, and insula. Proinflammatory cytokines including type I and II. _____, ______ and ___ ___ ___ can reduce the availability of 5-HT.
anxiety, arousal, alarm, dACC, hippocampus, interferons, interleukin-1beta, tumor necrosis factor
many cytokines also activate the enzyme ________ _______, which breaks down tryptophan, the primary precursor for serotonin, into _____. The activated _____ convert this into ____ ___, which binds to ______ receptors, stimulating ____ release. They also block glutamate ____ by ____, all of which converge on _____. The glutamate excess causes reduced _____ as well, which particularly in the ____, can have a fundamental effect on neurogenesis and thus affect __ and ___.
indoleamine 2,3-dioxygenase, kynurenine, microglia, quinolinic acid, NMDA, glutamate, reuptake, astrocytes, excitotoxicity, BNDF, hippocampus, learning memory
In general, females have more ___ ___ ___ and higher ____ markers than males. The female typical immune system depends on ____, age, and ___ ____. Immune cells have ___ ___ ___ and can respond directly to changes in their concentration.
innate adaptive immune cells, pro-inflammatory, chromosomes, sex steroids, sex steroid receptors
___ and ___ sex steroids generally have anti-inflammatory properties
testosterone, progesterone
___ concentrations of estradiol are typically pro-inflammatory, while ____ concentrations are typically anti-inflammatory
low, high
female prominent microglia are the ___ type, have higher ____ capacity, higher expression of phagocytosis ____, and higher expression of ___ ___ and inflammatory __ ____. Together with pro-inflammatory cytokines, they increase inflammation, ___ and ___ ____.
M1, phagocytosis, receptor, cellular repair, control genes, neurotoxicity, immune activation
male predominant microglia are the ___ type, have higher ____ capacity, are more ____, have larger ____, and higher ___, ___ and ___ expression. Together with anti-inflammatory cytokines, they increase ___ __, _____ and ____.
M2, migration, reactive, somas, MCHI, MCHII, P2Y12, wound healing, neuroprotection, immunosuppression
Lombardo et al. performed a systematic review to study how sex steroids interact with the immune system to produce ___ ____.
affective disorders
the systemic review included criteria that it had to be written in ___, used adult, ____ subjects, had at least one sex hormone measured in ___ or ___ and/or at least one ___ sex hormone administered, had at least one ____ _____, and included affective disorder ____ or depressive symptoms.
english, human, blood, saliva, exogenous, inflammatory biomarker, diagnosis
There was a very big gap in literature, only ___% of screened articles focused on the interplay between inflammatory and sex hormones and were highly ____.
2, inconsistent
A study by eisenberg et al, 2009, used healthy subjects, and used ____ (endotoxin), vs a placebo to induce increase in ____. The endotoxin induced increase in IL-6 was positively correlated with ___ __ in females but not in males
LPS, IL-6, negative affect
An fMRI study showed that witnessing ___ ___ induced a higher neural activity in the dorsal _____, and ___ ___, which was positively correlated with increased IL-6 in ___ ____. The increased neural activity was positively correlated with negative affect in ___ but not in males.
social exclusion, ACC, anterior insula, both sexes, females
A study found that menstrual markers such as baseline __ and ___ levels before a ____ / placebo administration did not affect the association between ___ and depressed mood. this shows that sex differences were likely not driven by ___ ____ of sex steroids.
E2, progesterone, endotoxin, IL-6, activational effects
A study by Haenisch et al., 2015, found that male and female patients diagnosed with ___ disorder currently in a ___ state, showed higher __ and ____ levels than healthy controls. This showed that in BP, these hormones may mediate the ___ ____
bipolar, manic, insulin, progesterone, manic symptoms
Keshri et al., 2018 found that in male subjects with bipolar disorder, _____ a pro-inflammatory cytokine, was negatively correlated with ___ levels and positively correlated with __ ____. No correlation was found with ___ _____. This showed that testosterone has an ___ role in protecting against ___ ___ bipolar disorder in men
IL-17, testosterone, disease duration, symptom severity, anti-inflammatory, long term
Stephenson et al., 2013 recruited women who were ____, ___ had surgical removal of ____ or had cessation of ovarian function due to _____. Hormone replacement therapy treatment in these women induced an increase in __ and ___ that coincided with a decrease in ___ and ____, and an increase in quality of life (decrease in menopause symptoms). This showed that women with low ____ E and P, hormone treatment could ___ symptoms and decrease bioinflammatory markers.
perimenopausal, menopausal, ovaries, chemotherapy, estrogen, progesterone, IL-6, CRP, basal, ameliorate
Finally, Sha et al, 2020 recruited ___ women who were either experiencing depression or not. estrogen and progesterone both negatively correlated with _____. Estrogen positively correlated with ____ (pro-inflammatory), and progesterone negatively correlated with ____ (anti-inflammatory). Progesterone and estrogen levels did not differ between women with ___ and those without, which means this was not likely due to the interplay between __ __ and the immune system
postpartum, kynurenine, IL-6, IL-1, PPD, sex steroids
