***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background Cognitive remediation ( CR ) is an effective treatment for several psychiatric disorders . To date , there have been no published studies examining solely first-episode psychiatric cohorts , despite the merits demonstrated by early intervention CR studies . The current study aim ed to assess the effectiveness of CR in patients with a first-episode of either major depression or psychosis . Method Fifty-five patients ( mean age = 22.8 years , s.d . = 4.3 ) were r and omly assigned to either  CR  ( n = 28 ) or  treatment as usual ( TAU ; n = 27 ) . CR involved once-weekly 2-h sessions for a total of 10 weeks . Patients were comprehensively assessed before and after treatment . Thirty-six patients completed the study , and analyses were conducted using an intent-to-treat ( ITT ) approach with all available data . Results In comparison to TAU , CR was associated with improved immediate learning and memory controlling for diagnosis and baseline differences . Similarly , CR patients demonstrated greater improvements than TAU patients in psychosocial functioning irrespective of diagnosis . Delayed learning and memory improvements mediated the effect of treatment on psychosocial functioning at a marginal level . Conclusions CR  improves memory and psychosocial outcome in first-episode psychiatric out- patients for both depression and psychosis . Memory potentially mediated the functional gains observed . Future studies need to build on the current findings in larger sample s using blinded allocation and should incorporate longitudinal follow-up and assessment of potential moderators ( e.g. social cognition , self-efficacy ) to examine sustainability and the precise mechanisms of CR effects respectively Levels of the stress-sensitive hormone cortisol increase dramatically in the first 30 - 40min after waking , an effect known as the  cortisol awakening response ( CAR ) . There is considerable cross-sectional evidence that psychosocial stress is associated with an increased CAR , and the CAR has been found to be altered in the presence of stress-related diseases , including major depressive disorder ( MDD ) . To date , no prospect i ve longitudinal studies have examined whether individual differences in the CAR serve as a premorbid risk factor for MDD . In a sample of 230 late adolescents , clinical diagnoses of MDD were predicted from the CAR as well as other indicators of basal cortisol functioning gathered 1 year earlier , including : waking cortisol levels , bedtime cortisol levels , the size of the CAR , average cortisol , and the slope of the diurnal cortisol rhythm across the waking day . Age and gender , health and health behaviors , baseline neuroticism , exposure to stressful life events and past episodes of mood and anxiety disorders were included as covariates , to help ensure effects are attributable to the CAR rather than related variables . A higher baseline CAR was associated with a significantly increased risk of developing MDD by follow-up , even when excluding individuals with baseline MDD . No other baseline cortisol measures were significant prospect i ve predictors of MDD . In summary , the  CAR  is a significant prospect i ve risk factor for the development of MDD in young adults , providing some support for the possibility that a heightened CAR may play a role in the etiology of major depressive disorder BACKGROUND Previous studies suggest that people attempt suicide because they are cognitively inflexible , but past research suggesting a link between cognitive inflexibility and suicidal thoughts and behavior has been limited by cross-sectional design s. This study examined whether cognitive inflexibility differentially and prospect ively predicted suicidal ideation among young adults with and without a history of a suicide attempt . METHODS A sample of 45 young adults with ( n = 13 ) or without ( n = 32 ) a suicide attempt history completed the  Wisconsin Card Sorting Test ( WCST ) , a diagnostic interview , and self-report measures of hopelessness , depressive symptoms , and suicidal ideation  , and were followed up 6 months later to reassess suicidal ideation . RESULTS Cognitive inflexibility , as measured by perseverative errors on the WCST , predicted suicidal ideation at 6-month follow-up , among suicide attempters , but not among nonattempters , adjusting for the presence of a baseline mood or anxiety diagnosis , hopelessness , and baseline suicidal ideation . CONCLUSIONS Cognitive inflexibility may increase vulnerability to suicidal ideation over time among individuals with a previous suicide attempt history . Implication s for interventions with suicide attempters are discussed BACKGROUND Research suggests that alterations in gamma-aminobutyric acid receptor functioning have a role in depression . Paired-pulse transcranial magnetic stimulation ( TMS ) paradigms are noninvasive measures of cortical inhibitory and excitatory circuits . OBJECTIVE /HYPOTHESIS The present study examined pretreatment short-interval intracortical inhibition ( SICI ) , long-interval cortical inhibition ( LICI ) , and intracortical facilitation ( ICF ) in children and adolescents with major depressive disorder who were initiating fluoxetine treatment .  The primary objective was to examine the relationship of these measures with subsequent treatment response . It was hypothesized that alterations in pretreatment GABA and glutamate mediated neurotransmission , would be associated with fluoxetine nonresponse . METHODS Sixteen children and adolescents with major depressive disorder underwent paired-pulse TMS testing before beginning fluoxetine treatment . Response was prospect ively characterized by scores of 1 or 2 on the Clinical Global Impression Scale and less than 40 on the Children 's Depression Rating Scale-Revised after 6 weeks of fluoxetine treatment ( 20 - 40 mg/day ) . RESULTS Eight patients responded to treatment . Least-squares mean LICI values were consistently higher bilaterally for treatment nonresponders . Higher LICI values indicate less inhibition and impaired GABAB functioning . There was no significant effect of treatment response on the measures of SICI and ICF . CONCLUSIONS Our findings suggest that deficits in pretreatment GABAB may be related to fluoxetine nonresponse in depressed youth . This is congruent with prior work demonstrating that GABAB interneurons have serotonergic input and antidepressants modulate GABAB receptors . These findings also show that TMS paradigms have utility in study ing the neurophysiology and treatment of childhood mood disorders . REGISTRATION S Cortical Excitability and Inhibition in Children and Adolescents With Major Depressive Disorder , http://www . clinical trials.gov/ct2/show/NCT00896090?term=cortical+excitability+ and + inhibition&rank=2 , NCT00896090 ; Sequential Treatment of Pediatric MDD to Increase Remission and Prevent Relapse , http://www . clinical trials.gov/ct2/show/NCT00612313?term=Sequential+Treatment+ and + MDD&rank=1 , NCT00612313 Prior work suggests that major depression is associated with abnormal startle blink responses ; however , only chronic or recurrent depression appears to be associated with this effect . The current study tested this hypothesis directly by examining whether recurrent major depression accounted for the anomalous startle seen in major depression using a sample of 515 female twins from the Minnesota Twin Family Study .  Blink responses recorded at the age of 20 were examined in relation to number of episodes of depression prospect ively assessed from ages 11 to 20 . Results showed that only subjects who had experienced multiple episodes of depression showed abnormal startle responses . Subjects who had experienced just one episode of depression in their lifetime did not differ from controls . This lends additional support to the idea that recurrent depression may have a different etiological basis than nonrecurrent depression Fluoxetine is associated with substantial objective and subjective sleep disturbance in adults with major depressive disorders . In this preliminary report , the effects of fluoxetine on sleep electroencephologram ( EEG ) are described in 6 children and adolescents with nonpsychotic major depression .  Fluoxetine increased light Stage 1 sleep , the number of arousals and rapid eye movement ( REM ) density . REM latency was largely unaffected . Oculomotor abnormalities were also evident on treatment , accompanied by an increase in myoclonic activity . Subjective sleep was also disturbed on treatment . These results are in keeping with those observed in depressed adults treated with fluoxetine Background It is an open question as to whether differential developmental trajectories , potentially representing underlying pathophysiological processes , can form the basis of a more useful typology in young persons who present for mental health care . Methods A cohort of 605 young people was recruited from youth mental health services that target the early phases of anxiety , mood or psychotic disorders . Participants were assigned to one of three clinical sub-types ( anxious-depression ; mania-fatigue ; developmental-psychotic ) according to putative developmental trajectories . Results The distribution of subtypes was : 51 % anxiety-depression , 25 % mania-fatigue and 24 % developmental-psychotic , with key differences in demographic , clinical , family history and neuropsychological characteristics . When analyses were limited to 286 cases with ‘ attenuated ’ or sub-threshold syndromes , the pattern of differences was similar . Multinomial logistic regression demonstrated that compared to the developmental-psychotic subtype , both the mania-fatigue and anxiety-depression subtypes were younger and more depressed at presentation , but less functionally impaired . Other discriminating variables between the developmental-psychotic and mania-fatigue sub-types were that the latter were significantly more likely to have a family history of bipolar disorder but have less likelihood of impaired verbal learning ; whilst the anxious-depression group were more anxious , more likely to have a family history of depression , and had a higher premorbid IQ level . Conclusions This cross-sectional evaluation provides preliminary support for differing developmental trajectories in young persons presenting for mental health care . Prospect i ve follow-up is needed to examine the predictive validity of this approach and its relationships to underlying pathophysiological mechanisms This study examined the hypothesis that depressed adolescents with a history of childhood maltreatment will show greater cortisol reactivity to psychological stress challenge than those without , and this relation will be moderated by level of depression severity . Seventy-one adolescents were exposed to the Trier Social Stress Test .  Salivary cortisol was assessed at baseline , immediately before the challenge , after the challenge , and during an extended recovery period . Childhood maltreatment was assessed with a rigorous context ual interview and rating system . Adolescents with a history of maltreatment produced higher and more prolonged levels of cortisol in response to the challenge than did adolescents with no maltreatment , but only among those with a mild/moderate level of depression severity . Those with moderate/severe depression exhibited a blunted cortisol response regardless of child maltreatment history . These findings indicate that depression is a heterogeneous syndrome , and that both depression severity and child maltreatment history should be considered in studies examining biological stress reactivity BACKGROUND Knowledge about the natural history of self-harm is scarce , especially during the transition from adolescence to young adulthood , a period characterised by a sharp rise in self-inflicted deaths . From a repeated measures cohort of a representative sample , we describe the course of self-harm from middle adolescence to young adulthood . METHODS A stratified , r and om sample of 1943 adolescents was recruited from 44 schools across the state of Victoria , Australia , between August , 1992 , and January , 2008 . We obtained data pertaining to self-harm from question naires and telephone interviews at seven waves of follow-up , commencing at mean age 15·9 years ( SD 0·49 ) and ending at mean age 29·0 years ( SD 0·59 ) . Summary adolescent measures ( waves three to six ) were obtained for cannabis use , cigarette smoking , high-risk alcohol use , depression and anxiety , antisocial behaviour and parental separation or divorce . FINDINGS 1802 participants responded in the adolescent phase , with 149 ( 8 % ) reporting self-harm , More girls ( 95/947 [ 10 % ] ) than boys ( 54/855 [ 6 % ] ) reported self-harm ( risk ratio 1·6 , 95 % CI 1·2 - 2·2 ) . We recorded a substantial reduction in the frequency of self-harm during late adolescence . 122 of 1652 ( 7 % ) participants who reported self-harm during adolescence reported no further self-harm in young adulthood , with a stronger continuity in girls ( 13/888 ) than boys ( 1/764 ) . During adolescence , incident self-harm was independently associated with symptoms of depression and anxiety ( HR 3·7 , 95 % CI 2·4 - 5·9 ) , antisocial behaviour ( 1·9 , 1·1 - 3·4 ) , high-risk alcohol use ( 2·1 , 1·2 - 3·7 ) , cannabis use ( 2·4 , 1·4 - 4·4 ) , and cigarette smoking ( 1·8 , 1·0 - 3·1 ) . Adolescent symptoms of depression and anxiety were clearly associated with incident self-harm in young adulthood ( 5·9 , 2·2 - 16 ) . INTERPRETATION Most self-harming behaviour in adolescents resolves spontaneously . The early detection and treatment of common mental disorders during adolescence might constitute an important and hitherto unrecognised component of suicide prevention in young adults . FUNDING National Health and Medical Research Council , Australia 
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Conclusions Despite the predominance of studies that solely examine the clinical syndrome of young people the literature also provides evidence of distinct associations among objective measures ( indexing various aspects of brain circuitry ) and other functional domains .
We suggest that a shift in focus towards characterising the mechanisms that underlie and /or mediate multiple functional domains will optimise personalised interventions and improve illness trajectories