Neurocognition and social cognition in youth and young adults at ultra-high-risk for psychosis and bipolar disorder.

BACKGROUND: Schizophrenia and bipolar disorder are associated with significant deficits in neurocognition and social cognition. Unlike the studies in chronic stages of these disorders, very limited information is available regarding neurocognitive and social-cognitive impairment before the onset of bipolar disorder. Our main aim was to investigate the differences in neurocognition and social cognition between individuals at ultra-high risk for psychosis (UHR-P) and bipolar disorder (UHR-BD). METHODS: This study included 152 help-seeking individuals identified as UHR-P (n = 78) and UHR-BD (n = 74), who were compared with a healthy control group (n = 43). A comprehensive neuropsychological battery was administered to all participants. RESULTS: UHR-P was associated with widespread deficits in all neurocognitive and social-cognitive domains. Effect sizes (Cohen's d) of these deficits ranged from -0.57 to -1.34. UHR-BD was associated with significant deficits in processing speed, executive functions, sustained attention and social cognition (d = -0.48 to-0.70, p < 0.05). UHR-P performed significantly worse than UHR-BD in social cognition, processing speed, verbal memory and executive function domains (d = -0.39 to-0.64, p < 0.05). Negative symptoms were associated with impaired social cognition in the UHR-P group and verbal memory deficits in the UHR-BD group. Cognitive impairment was associated with functional impairment in both groups. CONCLUSIONS: While UHR-P is associated with more widespread cognitive impairment, deficits in processing speed, executive functions, sustained attention and social cognition might be common features of both UHR groups. In early intervention services, cognition should be considered as a target for assessment and intervention not only for individuals at high risk for psychosis but also for bipolar disorder.

Social cognition and neurocognition in first-episode bipolar disorder and psychosis: The effect of negative and attenuated positive symptoms.

BACKGROUND: Schizophrenia and bipolar disorder are associated with neurocognitive and social-cognitive impairments. To date very few studies investigated social cognition in first-episode bipolar disorder (FEBD). Our main aim was to investigate the differences in social cognition and neurocognition between FEBD and first-episode psychosis (FEP). Another aim was to investigate neurocognitive correlates of negative symptoms and attenuated psychotic symptoms in FEBD. METHODS: This study included 55 FEBD, 64 FEP and 43 healthy controls. A comprehensive neuropsychological battery assessing social cognition, processing speed, verbal and visual memory, working memory, sustained attention, and executive functions was administered to all participants. RESULTS: Both FEBD and FEP were associated with widespread deficits in all neurocognitive domains and social cognition. Both FEP (d = -1.19) and FEBP (d = -0.88) were also impaired in social cognition. In FEP, effect sizes (Cohen's d) of neurocognitive deficits ranged from -0.71 to -1.56. FEBD was also associated with relatively milder but similar neurocognitive deficits (d = -0.61 to-1.17). FEBD group performed significantly better than FEP group in verbal and visual memory, processing speed, and executive function domains (d = -0.40 to-0.52). Negative symptoms and social functioning were associated with neuropsychological impairment in both groups. The severity of attenuated psychotic symptoms was associated with poorer verbal memory in FEBD (r = -0.39, p < 0.01). LIMITATIONS: The cross-sectional nature of the current study is the main limitation. CONCLUSIONS: Neurocognitive and social-cognitive deficits are evident in both FEBD and FEP. In FEBD, more severe memory deficits might be markers of clinical overlap and shared neurobiological vulnerability with psychotic disorders.

The effect of exercise on anxiety- and depression-like behavior of aged rats.

We investigated the effects of exercise in multiple sessions on anxiety- and depression-like behavior during aging, and the role of serotonin and serotonin 1A receptors in this process. Both 24-month-old (aged) and 6-month-old (adult) female rats were divided into five groups; aged control, adult control, aged + serotonin re-uptake inhibitors (SSRIs), aged + exercise, and aged + SSRIs + exercise. After exercise, all groups were evaluated using the open field arena, elevated plus maze and forced swim tests. We assessed serum corticosterone levels; number of amygdala, hippocampus and prefrontal cortex cells; tissue serotonin and serotonin 1A (5-HT1A) levels. In the open field test, aged rats exhibited a significant increase in locomotor activity compared to the SSRIs and SSRIs + exercise groups. During the elevated plus maze test, aged rats were observed less frequently in the open arms of assembly compared to adults. The duration increased in the exercise group and remained unchanged in the SSRIs group. In the forced swim test, the aged rats were more immobile compared to adults; no change was observed in the immobility time between these groups. The tissue serotonin levels in amygdala and hippocampus were higher in SSRIs + exercise group compared to the aged, exercised and SSRIs groups. The number of cells in the hippocampus, prefrontal cortex and amygdala decreased in the aged group compared to adult rats; increased numbers of cell were observed in exercise, SSRIs and SSRIs + exercise groups compared to aged rats. Exercise in multiple sessions may increase the number of cells in the hippocampus, prefrontal cortex and amygdala, which may reduce senile anxiety and depression. Also, serotonin and serotonin 1A receptors may play role in depression-like behavior.

Dose dependent effects of oxytocin on cognitive defects and anxiety disorders in adult rats following acute infantile maternal deprivation stress.

Maternal deprivation at an early age is a powerful stressor that causes permanent alterations in cognitive and behavioral functions during the later stages of life. We investigated the effects of oxytocin on cognitive defects and anxiety disorders caused by acute infantile maternal deprivation in adult rats. We used 18-day-old Wistar albino rats of both sexes. The experimental groups included control (C), maternally deprived (MD), maternally deprived and treated with 0.02 µg/kg oxytocin (MD-0.02 µg/kg oxy), maternally deprived and treated with 2 µg/kg oxytocin (MD-2 µg/kg oxy). When the rats were 60 days old, the open field (OF) and elevated plus maze (EPM) behavioral tests, and the Morris water maze (MWM) test for spatial learning and memory were performed. In addition, the number of neurons in the hippocampus, prefrontal cortex (PFC) and amygdala were determined using quantitative histology. We also measured vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) levels in the PFC. In both sexes, the MD group failed the learning test and the MD-2 µg/kg oxy group failed in the memory test. The MD-0.02 µg/kg oxy group spent more time in the open arm of the EPM device and their locomotor activities were greater in the OF test. The VEGF and BDNF levels in the PFC were higher in the MD-0.02 µg/kg oxy groups than the other maternally deprived groups (oxytocin ±). The number of PFC neurons was low in all male maternally deprived (oxytocin ±) groups, while the number of amygdala neurons was low in both female and male maternally deprived (oxytocin ±) groups. Male rats were more affected by maternal deprivation; administration of oxytocin had dose-dependent biphasic effects on learning, memory and anxiety.

Effects of voluntary and involuntary exercise on cognitive functions, and VEGF and BDNF levels in adolescent rats.

Regular treadmill running during adolescence improves learning and memory in rats. During adolescence, the baseline level of stress is thought to be greater than during other periods of life. We investigated the effects of voluntary and involuntary exercise on the prefrontal cortex and hippocampus, vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF) levels, and spatial learning, memory and anxiety in adolescent male and female rats. The voluntary exercise group was given free access to a running wheel for 6 weeks. The involuntary exercise group was forced to run on a treadmill for 30 min at 8 m/min 5 days/week for 6 weeks. Improved learning was demonstrated in both exercise groups compared to controls. Neuron density in the CA1 region of the hippocampus, dentate gyrus and prefrontal cortex were increased. Hippocampal VEGF and BDNF levels were increased in both exercise groups compared to controls. In females, anxiety and corticosterone levels were decreased; BDNF and VEGF levels were higher in the voluntary exercise group than in the involuntary exercise group. The adolescent hippocampus is affected favorably by regular exercise. Although no difference was found in anxiety levels as a result of involuntary exercise in males, females showed increased anxiety levels, and decreased VEGF and BDNF levels in the prefrontal cortex after involuntary exercise.

Effects of carbon dioxide exposure on early brain development in rats.

The developing brain is vulnerable to environmental factors. We investigated the effects of air that contained 0.05, 0.1 and 0.3% CO2 on the hippocampus, prefrontal cortex (PFC) and amygdala. We focused on the circuitry involved in the neurobiology of anxiety, spatial learning, memory, and on insulin-like growth factor-1 (IGF-1), which is known to play a role in early brain development in rats. Spatial learning and memory were impaired by exposure to 0.3% CO2 air, while exposure to 0.1 and 0.3% CO2 air elevated blood corticosterone levels, intensified anxiety behavior, increased superoxide dismutase (SOD) enzyme activity and MDA levels in hippocampus and PFC; glutathione peroxidase (GPx) enzyme activity decreased in the PFC with no associated change in the hippocampus. IGF-1 levels were decreased in the blood, PFC and hippocampus by exposure to both 0.1 and 0.3% CO2. In addition, apoptosis was increased, while cell numbers were decreased in the CA1 regions of hippocampus and PFC after 0.3% CO2 air exposure in adolescent rats. A positive correlation was found between the blood IGF-1 level and apoptosis in the PFC. We found that chronic exposure to 0.3% CO2 air decreased IGF-1 levels in the serum, hippocampus and PFC, and increased oxidative stress. These findings were associated with increased anxiety behavior, and impaired memory and learning.

Anxiety- and depression-like behavior are correlated with leptin and leptin receptor expression in prefrontal cortex of streptozotocin-induced diabetic rats.

Anxiety and depression are common in diabetics. Diabetes also may cause reduced leptin levels in the blood. We investigated the relation between diabetes induced anxiety- and depression-like behavior, and leptin and leptin receptor expression levels in diabetic rats. The anxiety- and depression-like behaviors of rats were assessed 4 weeks after intraperitoneal injection of streptozotocin. Diabetic rats exhibited greater anxiety-like behavior; they spent more time in closed branches of the elevated plus maze test and less time in the center cells of the open field arena. Increased depression-like behavior was observed in diabetic rats using the Porsolt swim test. Prefrontal cortex (PFC), blood leptin levels and PFC neuron numbers were decreased, and leptin receptor expression and apoptosis were increased in diabetic rats. Blood corticosterone levels also were increased in diabetic rats. These results indicate that reduction of leptin up-regulates leptin receptor expression and may affect PFC neurons, which eventually triggers anxiety- and depression-like behaviors in diabetic rats.

Effects of exercise and poor indoor air quality on learning, memory and blood IGF-1 in adolescent mice.

It is known that regular aerobic exercise enhances cognitive functions and increases blood insulin-like growth factor 1 (IGF-1) levels. People living in urban areas spend most of their time indoors and indoor air quality can affect health. We investigated the effects of aerobic exercise in poor and good air quality environments on hippocampus and prefrontal cortex (PFC) neurons, anxiety, and spatial learning and memory in adolescent mice. Poor air quality impaired spatial learning and memory; exercise did not affect learning or memory impairment. Exercise in a good air quality environment improved spatial learning and memory. Poor air quality increased apoptosis in the hippocampus and PFC. Both exercised and sedentary groups living in a poor air quality environment had lower serum IGF-1 levels than those living in a good air quality environment. Living in a poor air quality environment has negative effects on the hippocampus, PFC and blood IGF-1 levels in adolescent mice, but exercise did not alter the negative effects of poor air quality.

The protective effects of carnosine in alcohol-induced hepatic injury in rats.

Consumption of alcohol leads to oxidative stress in liver by inducing lipid peroxidation. The aim of this study was to investigate the effects of carnosine (CAR) in alcohol-induced liver injury by biochemical and histomorphological evaluations. The rats were divided into four groups, namely, control group, alcohol (AL) group, CAR group and AL + CAR group. Three doses of ethanol (5 g/kg, 25% (v/v) in distilled water) were given by nasogastric catheter for twice-a-day. CAR (100 mg/kg) was given 1 h before the administration of ethanol using the same method. Levels of alanine aminotransferase, aspartate aminotransferase, myeloperoxidase and malondialdehyde were significantly increased in the AL group compared with control, CAR and AL + CAR groups. Glutathione level was significantly decreased in the AL group, while it was increased in the AL + CAR group. Immunoreactivity of caspase-3 and bax increased in the hepatocytes of AL group when compared with control and AL + CAR groups. Expression of bcl-2 was decreased in AL group than AL + CAR group. Under electron microscopy, dense mitochondria, accumulation of lipid, sinusoidal dilatation, vacuolization and decrease in the number of microvilli were observed in AL group, while these findings were markedly less in the AL + CAR group. In conclusion, pretreatment of CAR is effective for recovering biochemical alterations and morphologic damage in the liver of rats treated with ethanol.

Progesterone treatment decreases traumatic brain injury induced anxiety and is correlated with increased serum IGF-1 levels; prefrontal cortex, amygdala, hippocampus neuron density; and reduced serum corticosterone levels in immature rats.

Traumatic brain injury (TBI) may cause neuropsychiatric problems, such as anxiety disorder, that have negative effects on cognitive functions and behavior. We investigated the effects of progesterone on traumatic brain injury induced anxiety in 7-day-old rat pups subjected to contusion injury. Progesterone treatment decreased TBI induced anxiety and serum corticosterone levels, and increased serum IGF-1 levels. Moreover, progesterone treatment increased amygdala, prefrontal cortex and hippocampal neuron density. We found a negative correlation between serum corticosterone levels and anxiety tests, and a positive correlation between serum IGF-1 levels and anxiety tests. In addition, progesterone treatment decreased serum corticosterone compared to the controls and sham. Our results indicate that single dose progesterone may be effective for treating anxiety caused by TBI.

A case series of Turkish children and adolescents with bipolar spectrum disorder: a naturalistic clinical phenomenological follow-up.

AIM: The main objectives of this a naturalistic, prospective follow-up study were to describe the clinical presentation and predictors of treatment response in Turkish children and adolescents with bipolar disorder (BD) and to document their response to available treatment regimes. METHODS: The study sample consisted of 27 consecutive admissions to the Child and Adolescent Psychiatry Clinic between 2002 and 2006. Washington University at St. Louis -Kiddie and Young Adult Schedule for Affective Disorders and Schizophrenia (WASH-U-KSADS) was administered to mothers for an assessment of the problem of their children and to children about themselves. Subjects were phenomenologically re-examined to ascertain whether they met the Leibenluft criteria for the narrow, intermediate, or broad phenotypes of juvenile mania. All patients were also rated with Children Global Assessment Scale (CGAS) and Young Mania Rating Scale (YMRS). Treatment response was documented using the Clinical Global Impression (CGI) and the YMRS. RESULTS: The mean age was 12.95+/-3.8 years and the mean follow-up period was 24+/-9.2 months. Nineteen (70.3%) patients continued their treatment for 20.6+/-12.47 months. A large number of patients responded to mood stabilizers and antipsychotic agents (89.5%). When treatment endpoint scores of CGAS were compared between patients with age at onset =or>13 and <13, functionality of group with age at onset =or>13 was significantly greater than early onset group at the end of the treatment(z:-2.014, P=0.044). CONCLUSION: Compared to non-episodic patients, episodic patients were more likely to have psychotic features and to have a later age of onset. Mood stabilizers and atypical antipsychotic combination was required in many cases (73.7%). Long term follow-up clinical phenomenological and treatment efficacy studies are needed in the future.