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PubMed2000

Cytidinediphosphocholine (CDP choline) for cognitive and behavioural disturbances associated with chronic cerebral disorders in the elderly.

BACKGROUND: The prevalent use of this compound in the treatment of disorders of a cerebrovascular nature does not mean that a homogeneous and consistent application of this therapy has been applied. Dosage, method of administration, and selection criteria of patients have varied. The modalities of the studies, including length of observation, severity of disturbance, and methodology of the evaluation of the results were also heterogeneous. In spite of uncertainties about its efficacy, CDP-choline is a frequently prescribed drug for cognitive impairment in several European countries, especially when the clinical picture is predominantly one of cerebrovascular disease, hence the need for this review. OBJECTIVES: The objective is to assess the efficacy of CDP-choline (cytidinediphosphocholine) in the treatment of cognitive, emotional, and behavioural deficits associated with chronic cerebral disorders of the elderly. SEARCH STRATEGY: The CDCIG register of trials was searched for all relevant, non-animal randomised controlled trials using the terms CDP-choline/CDP, Citicoline, Cytidine Diphosphate Choline and Diphosphocholine. The Psychlit (1974-1996), Psychiatry (1980-1996) and MEDLINE electronic databases have been searched independently by the reviewers. The reviewers have also contacted manufacturers of CDP-choline. SELECTION CRITERIA: All relevant, non-animal, unconfounded, double-blind, placebo-controlled, randomised trials of CDP-choline in cognitive impairment due to chronic cerebral disorders will be considered for inclusion in the review. DATA COLLECTION AND ANALYSIS: Two reviewers independently reviewed the included studies, extracted the data, and pooled it when appropriate and possible. The pooled odd ratios (95% CI) or the average differences (95% CI) were estimated. No intention-to-treat data were available from the studies included. MAIN RESULTS: Seven of the included studies observed the subjects for a period between 20 to 30 days, one study was of 6 weeks duration, 2 studies used cycles extending over 2 and 3 months and one study observed continuous administration over 3 months. The studies were heterogeneous in dose, inclusion criteria for subjects, and outcome measures. Results are reported for the domains of attention, memory testing, behavioural rating scales, global clinical impression and tolerability. There was no significant evidence of a beneficial effect of CDP-choline on attention. There were modest, but significant, beneficial effects of CDP-choline on memory function and behaviour. For the outcome of clinical global impression, the odds ratio for improvement in the subjects treated with CDP-Choline as opposed to the subjects treated with placebo was 8.89 [5.19, 15.22]. The drug was well tolerated. REVIEWER'S CONCLUSIONS: There is some evidence that CDP Choline has a positive effect on memory and behaviour in at least the short term. The evidence of benefit from global impression is stronger, but is still limited by the duration of the studies. There is evidence that the effect of treatment is more homogeneous for patients with cognitive impairment secondary to cerebrovascular disorder. Other studies with a more appropriate length of treatment are recommended owing to the chronic and irreversible nature of the disorders for which this treatment is indicated.

Aged↗
PubMed2006

Models and theories of brain function in cognition within a framework of behavioral cognitive psychology.

The present article presents a nonexhaustive collection of contemporary models and theories on brain function and discusses these models and theories within a framework of explanatory formulations in behavioral cognitive psychology. Such a mission was accomplished by evaluating the cognitive implications in the explanatory formulations with respect to established laws/principles and models/theories of behavioral cognitive psychology. The article also points to problem areas of behavioral cognitive psychology for which the explanatory formulations have solutions to offer. The article shows that the cinematographic hypothesis, the new visual model, the synergetic model, and the theory of whole-brain-work emphasize various aspects of perception. The formulations on P300 theory emphasize attention and also working memory. The theory on cognits is a comprehensive account of memory. Characteristic to all of these explanatory formulations and also to that on the complexity and its evolution and that on neurocognitive networks is the emphasis on selective distribution, integration to the point of supersynergy, and dynamicity. Such a viewpoint was not only applied to the operations of the brain but also of cognition. With such a conceptualization, the explanatory formulations could account for cognitive processes other than the ones emphasized. A common aspect in a majority of the formulations is the utilization of the oscillatory activity as the valid activity of the brain. The article points out that a frontier in cognitive psychophysiology would be the study of the genetics of brain oscillations.

Brain↗
PubMed2006

Kimberley Indigenous Cognitive Assessment tool (KICA): development of a cognitive assessment tool for older indigenous Australians.

BACKGROUND: Indigenous Australians have a unique cultural heritage dating back many thousands of years. Unfortunately, there is no validated tool to assess cognition in older indigenous Australians. This study was designed to address this deficiency. The Kimberley Indigenous Cognitive Assessment (KICA) was developed with Indigenous health and aged care organizations, and comprises cognitive, informant and functional sections. The psychometric properties of the cognitive assessment section (KICA-Cog) are described in this paper. METHODS: The KICA-Cog was tested in 70 indigenous subjects, of varying cognitive abilities and diagnoses, over 45 years of age. Subjects were interviewed using the KICA-Cog and then independently assessed by expert clinical raters using DSM-IV and ICD-10 criteria. Interrater and internal reliability were determined. RESULTS: The KICA-Cog score showed no systematic interrater difference; the mean was -0.07 (SD = 1.83). Interrater reliability for 16 individual questions from the cognitive section revealed a kappa-value > or = 0.6 and intraclass correlations for 12 questions. Internal consistency, as assessed by Cronbach's alpha, was 0.88. Three items on the cognitive score (pension week, recall and free recall) effectively discriminated 85-7% of dementia cases. Sensitivity and specificity were 90.6% and 92.6%, respectively, using a cut-off score of 31/32. CONCLUSIONS: The KICA-Cog appears to be a reliable assessment tool for cognitive impairment in an Australian older traditionally living indigenous population.

Adolescent↗
PubMed1991

Cognitive therapy with depressed inpatients: specific effects on dysfunctional cognitions.

Specificity of cognitive change following cognitive therapy for depression was assessed in 39 depressed inpatients who completed either a standard inpatient treatment (pharmacotherapy and milieu management) or the standard treatment plus cognitive therapy. Following treatment, patients in both groups endorsed fewer dysfunctional cognitions on 2 of 4 measures of cognitive distortion. Compared with patients receiving only the standard treatment, patients also receiving cognitive therapy reported less hopelessness and fewer cognitive biases at posttreatment and 6- and 12-month follow-up assessments and fewer dysfunctional attitudes at the 6-month follow-up. Treatment effects for dysfunctional cognitions were found even though the treatment groups did not differ in depression severity, suggesting that results did not reflect state-dependent differences between treatments secondary to difference in depression.

Adaptation, Psychological↗
PubMed2006

Methylmalonic acid and cognitive function in the Medical Research Council Cognitive Function and Ageing Study.

BACKGROUND: An elevated blood concentration of homocysteine is an established risk factor for cognitive impairment and dementia, but associations between cognition and methylmalonic acid (MMA), a related metabolic marker of vitamin B-12 deficiency, are less clear. OBJECTIVE: The aim was to determine the utility of serum MMA and holotranscobalamin as markers of vitamin B-12 status in relation to cognitive function and to investigate their association with discrete cognitive domains. DESIGN: This was a cross-sectional survey of 84 nondemented elderly participants (aged >69 y) from the Welsh cohort of the Medical Research Council's Cognitive Function and Ageing Study. Cognitive status was determined by Mini-Mental State Examination (MMSE) and the Cognitive Section of the Cambridge Mental Disorders of the Elderly Examination (CAMCOG). RESULTS: Nearly one-half (43%) of the persons selected had likely metabolically significant vitamin B-12 deficiency. Higher MMA concentrations were associated with lower MMSE scores independent of age and education (P = 0.007). MMA concentration correlated inversely with CAMCOG scores of ideational praxis (P < 0.05) and language comprehension (P < 0.05) and expression (P < 0.01). Serum folate correlated weakly but significantly with language (P < 0.05), remote memory (P < 0.05), and constructional and ideational praxis scores (P < 0.05 and P < 0.01, respectively). CONCLUSION: The high prevalence of likely metabolically significant vitamin B-12 deficiency in the elderly is associated with lower cognitive function scores and particularly with lower scores of language comprehension and expression.

Aged↗
PubMed2004

Effects of testosterone on behavior, depression, and cognitive function in older men with mild cognitive loss.

BACKGROUND: The role of sex hormones in the prevention of cognitive decline is uncertain. Animal studies suggest mechanisms for sex hormones including testosterone to maintain optimal cognitive function. But, there are studies to suggest that endogenous testosterone levels are associated with aggression in men with cognitive impairment. METHODS: In this pilot study, 11 men (mean age 80 +/- 5 years, range 73-87 years) with early cognitive decline and bioavailable testosterone levels below 128 ng/dl (lower limit for adult normal range) were randomized to receive intramuscular testosterone (200 mg every 3 weeks) or placebo for 12 weeks. Outcome measures included sex hormones (testosterone, bioavailable testosterone, sex hormone binding globulin, estradiol, and estrone), Behave AD Questionnaire, Katz Activities of Daily Living, Geriatric Depression Scale, Digit Span, Clock Face Drawing, Clock Face Perception, Verbal Fluency, Trail-Making B, and International Prostate Symptom Score at baseline, 4 weeks, and 10 weeks. RESULTS: All men completed the study. Total and bioavailable testosterone, estrone, and estradiol levels increased in men receiving testosterone, but no changes were detected in men receiving placebo. No significant changes were found in behavior following testosterone supplementation, nor was there evidence of change in depression or activities of daily living. No discernable changes were found in any of the cognitive tests. Symptoms of prostate hyperplasia remained unchanged in the testosterone (6.6 + 5.8 to 5.2 + 3.6; p =.39) and placebo (8.8 + 6.4 to 6.4 + 3.8; p =.15) groups, and prostate-specific antigen levels did not change significantly. CONCLUSION: No significant changes in behavior, function, depression, or cognitive performance occurred following 12 weeks of testosterone replacement in men with low testosterone levels and early-to-moderate cognitive impairment. This pilot work suggests that testosterone can be given to men with early cognitive impairment without significant concern about worsening aggressive or unwanted behaviors.

Aged↗
PubMed2005

Applying new approaches from cognitive neuroscience to enhance drug development for the treatment of impaired cognition in schizophrenia.

New approaches to the measurement of cognition in schizophrenia include the use of tasks from experimental cognitive psychology to examine the integrity of specific cognitive systems and the application of these tasks in noninvasive neuroimaging (e.g., functional magnetic resonance imaging [fMRI]) studies that directly measure the effects of drugs on cognition-related brain activity. These approaches offer many advantages, including the isolation of specific cognitive systems that may be conserved across species; controlling for the confounding effects of generalized performance deficits such as poor motivation, sedation, and so on; and providing a direct translational bridge from studies using animal models of cognition to patient-based research using fMRI. These developments have the potential to transform the early human phases of drug development and streamline the decision making at this critical point in the process. As was the case for the Measurement and Treatment Research to Improve Cognition in Schizophrenia initiative, optimizing the application of cognitive neuroscience to new drug development will require a major commitment by multiple investigators to task development and a thorough psychometric evaluation of both behavioral and neuroimaging measures.

Animals↗
PubMed2005

Distinguishing separable domains of cognition in human and animal studies: what separations are optimal for targeting interventions? A summary of recommendations from breakout group 2 at the measurement and treatment research to improve cognition in schizophrenia new approaches conference.

At the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) New Approaches Conference, a discussion group focused on directions for future research that are critical to enhancing our understanding of the distinctions among key cognitive domains that have relevance for the development of cognition-enhancing interventions. One set of recommendations emphasizes the need for examining and optimizing the psychometric properties of relevant measurement paradigms from cognitive psychology and cognitive neuroscience. This step is critical to translating many notable advances in these basic fields into measures that would be appropriate for clinical trials. A second set of recommendations focuses on key directions for the development and application of animal models of cognitive processes that would greatly aid the discovery and preclinical testing of potential cognition-enhancing agents. As part of this process, the group noted several existing animal paradigms that have particular promise as measures in the key cognitive domains in schizophrenia identified by the MATRICS Neurocognition Committee.

Animals↗
PubMed2006

A randomised controlled trial investigating the effect of n-3 long-chain polyunsaturated fatty acid supplementation on cognitive and retinal function in cognitively healthy older people: the Older People And n-3 Long-chain polyunsaturated fatty acids (OPAL) study protocol [ISRCTN72331636].

The number of individuals with age-related cognitive impairment is rising dramatically in the UK and globally. There is considerable interest in the general hypothesis that improving the diet of older people may slow the progression of cognitive decline. To date, there has been little attention given to the possible protective role of n-3 long-chain polyunsaturated fatty acids (n-3 LCPs) most commonly found in oily fish, in age-related loss of cognitive function. The main research hypothesis of this study is that an increased dietary intake of n-3 LCPs will have a positive effect on cognitive performance in older people in the UK. To test this hypothesis, a double-blind randomised placebo-controlled trial will be carried out among adults aged 70-79 years in which the intervention arm will receive daily capsules containing n-3 LCP (0.5 g/day docosahexaenoic acid and 0.2 g/day eicosapentaenoic acid) while the placebo arm will receive daily capsules containing olive oil. The main outcome variable assessed at 24 months will be cognitive performance and a second major outcome variable will be retinal function. Retinal function tests are included as the retina is a specifically differentiated neural tissue and therefore represents an accessible window into the functioning of the brain. The overall purpose of this public-health research is to help define a simple and effective dietary intervention aimed at maintaining cognitive and retinal function in later life. This will be the first trial of its kind aiming to slow the decline of cognitive and retinal function in older people by increasing daily dietary intake of n-3 LCPs. The link between cognitive ability, visual function and quality of life among older people suggests that this novel line of research may have considerable public health importance.

Aged↗
PubMed1998

A prospective study of cognitive function and onset of dementia in cognitively healthy elders.

OBJECTIVE: To examine the earliest cognitive changes associated with the onset of dementia as well as changes associated with normal aging. DESIGN: Longitudinal evaluation of participants with annual clinical and psychometric examinations for up to 15 1/2 years. SETTING AND PARTICIPANTS: Elderly volunteers (n = 82) enrolled with a Clinical Dementia Rating of 0 (cognitively intact) in longitudinal studies. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Clinical Dementia Rating and results of a 1 1/2-hour psychometric battery. RESULTS: As estimated with survival analysis, 40% of participants had a Clinical Dementia Rating greater than 0 (cognitive decline) within 12 years of enrollment; 59% of these were judged to have dementia of the Alzheimer type or incipient dementia. Participants with poorer performance on psychometric testing at enrollment were at higher risk for cognitive decline subsequently. The rate of change in psychometric performance before clinically detectable cognitive change occurred was not significantly different between those who eventually developed dementia and those who remained stable, except for performance on the Logical Memory subtest of the Wechsler Memory Scale. When subtle cognitive decline was clinically detected, however, an abrupt deterioration in performance on independently administered psychometric tests was observed. CONCLUSIONS: Cognitively healthy elderly people maintain stable cognitive performance when measured longitudinally by both careful clinical evaluation and repeated psychometric testing. This stability is maintained unless and until they develop a dementing illness, at which time a sharp decline in performance is observed.

Aged↗
PubMed2004

Effects of modafinil on cognitive and meta-cognitive performance.

The stimulant modafinil has proved to be an effective treatment modality for narcolepsy and related sleep disorders and is also being studied for use during sustained military operations to ameliorate the effects of fatigue due to sleep loss. However, a previous study reported that a relatively large, single dose of modafinil (300 mg), administered to already sleep-deprived individuals, caused participants to overestimate their cognitive abilities (i.e. 'overconfidence'). Because the predominant application of modafinil is in otherwise healthy, non-sleep-deprived individuals, the present study investigated the generality of modafinil-induced overconfidence in a group of 18 healthy, non sleep-deprived adults. The design involved a double-blind, placebo controlled, fully within-subjects manipulation of placebo and modafinil (4 mg/kg: approximately 300 mg, on average) over three 50-min cognitive testing sessions (i.e. before drug ingestion, and at 90 and 180 min after drug ingestion). The cognitive task battery included subjective assessments of mood, fatigue, affect, vigor and motivation, and cognitive assessments of serial reaction time, logical reasoning, visual comparison, mental addition and vigilance. In addition, trial-by-trial confidence judgements were obtained for two of the cognitive tasks and more global, task level assessments of performance were obtained for four of the cognitive tasks. Relative to placebo, modafinil improved fatigue levels, motivation, reaction time and vigilance. In terms of self-assessments of cognitive performance, both the placebo and modafinil conditions were 'well calibrated' on trial-by-trial confidence judgements, showing neither marked over- nor under-confidence. Of note, the modafinil condition displayed a non-significant tendency towards 'overconfidence' for task-level assessments of performance. The present findings highlight the need for continued research on the many complex interactions involving fatigue states, occasional versus long-term stimulant use, and subjective assessments of fatigue and cognitive performance.

Adolescent↗
PubMed2004

Applied cognitive psychology: Implications of cognitive psychology for clinical psychology and psychotherapy.

Cognitive psychology has made numerous contributions to clinical psychology, and these contributions are considered especially with reference to the anxiety disorders. It is argued that there are four major contributions that can be identified. First, the cognitive approach has led to the development of complex models showing the main cognitive processes and structures of relevance to an understanding of anxiety disorders. Second, controlled laboratory studies permit a more detailed investigation of cognitive biases in anxious patients than generally is feasible in more naturalistic settings. Third, the cognitive approach provides relevant evidence with respect to the issue of whether cognitive biases play a role in the development and maintenance of anxiety disorders. Fourth, the enhanced understanding of the anxiety disorders that has arisen from the cognitive approach has had beneficial effects on therapeutic practice in a number of significant ways. In sum, it is claimed that clinical psychology has benefited considerably from cognitive theory and research.

Anxiety↗
PubMed1999

[Postoperative cognition disorders in elderly patients. The results of the "International Study of Postoperative Cognitive Dysfunction" ISPOCD 1)].

OBJECTIVE: Cognitive dysfunction is a known problem after operations and may be especially relevant in the elderly. The aim of this international multicentre study was to investigate short- and long-term cognitive dysfunction in elderly patients and to elucidate the relevance of hypoxaemia and hypotension as causative factors. METHODS: 1218 patients aged 60 years and older and scheduled for major non-cardiac surgery under general anaesthesia were investigated. Oxygen saturation was measured by continuous pulse oximetry before surgery and throughout the day of and the first 3 nights after surgery. Blood pressure was recorded every 3 minutes during the operation and every 15-30 min for the rest of that day and night. Cognitive testing was performed before and 1 week and 3 months after the operation. Cognitive dysfunction was identified with neuropsychological tests compared with controls recruited from the UK (n = 176) and the same countries as study centres (n = 145). RESULTS: Postoperative cognitive dysfunction was present in 25.8% of patients 1 week after surgery and in 9.9% 3 months after surgery, compared with 3.4% and 2.8%, respectively, of the UK controls. Increasing age and duration of anaesthesia, little education, a second operation, postoperative infections, and respiratory complications were the risk factors for early postoperative cognitive dysfunction, but only age was a risk factor for long-term postoperative cognitive dysfunction. Hypoxaemia and hypotension were not significant risk factors at any time. CONCLUSION: With this investigation long-term cognitive dysfunction could be proven definitively for elderly patients after major operations under general anaesthesia. No factors with prophylactic or therapeutic influence were detectable so that aetiology and pathophysiology of POCD could not be further determined.

Aged↗
PubMed2005

Examination of the use of cognitive domains in postoperative cognitive dysfunction after coronary artery bypass graft surgery.

BACKGROUND: Cognitive domain summary scores have been used to examine postoperative cognitive dysfunction in a number of influential studies. To successfully examine cognitive dysfunction in this way, the domains need to be consistent during the assessment time points or the results are distorted. The current study examines two methods of determining cognitive domains and examines their temporal stability during serial cognitive assessments after coronary artery bypass graft surgery. METHODS: Two hundred and four coronary artery bypass graft patients and 80 matched healthy control subjects 55 years or older completed a battery of neuropsychological assessments at baseline and at 7 days and 3 months. Domains were determined in two ways. The first was based on precedence, and neuropsychological tests were allocated to commonly attributed cognitive domains. The second method was to conduct principal components analysis to statistically determine the domains at each time. The stability of these factors was then assessed over time by conducting repeated analysis. RESULTS: There were discrepancies between the two methods used to determine decline, and among the factors in the control and surgical groups. Stability with time was not evident as the factors varied within the groups. CONCLUSIONS: The assessment of postoperative cognitive dysfunction would be best served by the use of individual test results with efforts made to minimize false-positive classification as the extracted cognitive domains do not appear to be temporally consistent, and were sample specific.

Aged↗
PubMed2004

An integrated cognitive model of panic disorder: the role of positive and negative cognitions.

One reason for the neglect of the role of positive factors in cognitive-behavioural therapy (CBT) may relate to a failure to develop cognitive models that integrate positive and negative cognitions. Bandura [Psychol. Rev. 84 (1977) 191; Anxiety Res. 1 (1988) 77] proposed that self-efficacy beliefs mediate a range of emotional and behavioural outcomes. However, in panic disorder, cognitively based research to date has largely focused on catastrophic misinterpretation of bodily sensations. Although a number of studies support each of the predictions associated with the account of panic disorder that is based on the role of negative cognitions, a review of the literature indicated that a cognitively based explanation of the disorder may be considerably strengthened by inclusion of positive cognitions that emphasize control or coping. Evidence to support an Integrated Cognitive Model (ICM) of panic disorder was examined and the theoretical implications of this model were discussed in terms of both schema change and compensatory skills accounts of change processes in CBT.

Adaptation, Psychological↗
PubMed2005

Cognitive reactivity and vulnerability: empirical evaluation of construct activation and cognitive diatheses in unipolar depression.

Cognitive vulnerability is a central concept in cognitive theories of unipolar depression. This idea suggests that negative cognitive factors emerge during stressful situations, and that this cognitive reactivity is critical for the onset, relapse, and recurrence of depression. The number of empirical investigations that model the diathesis-stress nature of cognitive reactivity has substantially increased within the last decade. This review examines this literature, with a focus on priming and longitudinal designs. Extant research supports the concept of cognitive vulnerability to depression among adults, and support is accruing for the validity of this concept among children. Research that examines direct links between cognitive vulnerability and depression onset, relapse, and recurrence and the attachment origins of cognitive vulnerability is also accruing, although at a slower pace.

Cognition Disorders↗
PubMed2000

Informant ratings of cognitive decline in old age: validation against change on cognitive tests over 7 to 8 years.

BACKGROUND: Informant questionnaires on cognitive decline are increasingly used as screening tests for dementia. Informants can provide a longitudinal perspective that is not possible with cognitive screening tests administered at one point in time. However, there are limited data on the validity of such questionnaires when judged against longitudinal change on cognitive tests. METHODS: A community sample of elderly people aged > or = 70 was assessed on cognitive tests at baseline and after a follow-up of 7-8 years. The participants were given the Mini-Mental State Examination and tests of episodic memory and mental speed. At follow-up, the short-form of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) was completed by informants for 287 of the participants. RESULTS: Elderly people who were rated by informants as having moderate or severe decline had declined significantly on cognitive tests. The IQCODE correlated as highly with cognitive test change scores as these change scores correlated with each other. CONCLUSIONS: The IQCODE is a valid way of assessing cognitive decline when assessment can be carried out only at one point in time.

Age Factors↗
PubMed2006

A cognitive vulnerability-stress perspective on bipolar spectrum disorders in a normative adolescent brain, cognitive, and emotional development context.

Why is adolescence an "age of risk" for onset of bipolar spectrum disorders? We discuss three clinical phenomena of bipolar disorder associated with adolescence (adolescent age of onset, gender differences, and specific symptom presentation) that provide the point of departure for this article. We present the cognitive vulnerability-transactional stress model of unipolar depression, evidence for this model, and its extension to bipolar spectrum disorders. Next, we review evidence that life events, cognitive vulnerability, the cognitive vulnerability-stress combination, and certain developmental experiences (poor parenting and maltreatment) featured in the cognitive vulnerability-stress model play a role in the onset and course of bipolar disorders. We then discuss how an application of the cognitive vulnerability-stress model can explain the adolescent age of onset, gender differences, and adolescent phenomenology of bipolar disorder. Finally, we further elaborate the cognitive vulnerability-stress model by embedding it in the contexts of normative adolescent cognitive (executive functioning) and brain development, normative adolescent development of the stress-emotion system, and genetic vulnerability. We suggest that increased brain maturation and accompanying increases in executive functioning along with augmented neural and behavioral stress-sensitivity during adolescence combine with the cognitive vulnerability-stress model to explain the high-risk period for onset of bipolar disorder, gender differences, and unique features of symptom presentation during adolescence.

Adolescent↗