Index depressive episode and antidepressant exposure were associated with illness characteristics of pediatric bipolar disorder.

OBJECTIVE: Pediatric bipolar disorder (PBD) is a serious, recurrent disorder leading to severe functional impairment. As a first mood episode, index episode could affect the long-term course of the illness. This study aimed to investigate the clinical characteristics of youth with PBD from our multicenter, nationwide, naturalistic follow-up samples and to identify (i) the effects of index mood episode and (ii) the effect of previous antidepressant treatments on the age at mania onset of PBD. METHOD: The study sample consisted of 271 youth with BD-I followed by the child and adolescent psychiatry clinics of seven different university hospitals and three research state hospitals, representing six geographic regions across Turkey. All diagnoses were made according to structured interviews, and all data were retrospectively obtained from clinical records by the clinicians. RESULTS: When patients with index depressive/mixed episodes (IDE, n=129) and patients with index (hypo)manic episodes (IME, n=142) were compared, the total number of mood episodes and rapid cycling feature were significantly higher in the IDE group than in the IME group. The Cox regression analysis adjusted for sociodemographic and illness characteristics revealed female adolescents in the IDE group treated with antidepressants were more likely to have an earlier onset of mania (hazard ratio=2.03, 95% confidence interval=1.31-3.12, p=0.001). CONCLUSION: This is the first large-scale nationwide follow-up study in Turkey that indicated prior antidepressant treatments were associated with an earlier onset of mania in youth, particularly in adolescent females. Larger prospective studies are needed to identify neurodevelopmental processes underlying PBD and initiate prevention approaches.

Characteristics of depression among offspring at high and low familial risk of bipolar disorder.

OBJECTIVES: Having a parent with bipolar disorder (BP) is a very strong risk factor for developing BP. Similarly, depression among youth is a clinical risk factor for subsequent BP. We evaluated whether mood symptomatology in depressed youth is different between those at high and low familial risk to develop BP. METHODS: The most severe major depressive episode in BP offspring (N=61) and community control offspring (N=20) was evaluated using expanded depression and mania rating scales derived from the Schedule for Affective Disorders and Schizophrenia for Children Present Version. The results were adjusted for any between-group significant demographic differences and for multiple comparisons. RESULTS: The severity of depressive symptoms and the percentage of offspring with severe depressive symptoms, especially atypical depressive features, were significantly higher in the depressed offspring of BP parents compared to the depressed controls (Ps <.05). The depressive symptoms were helpful to identify a high-risk group (e.g., odds ratio [OR] for hypersomnia: 22.4, 95% confidence interval [CI]: 1.3-404, P=.04). In addition, there were significantly more depressed offspring of BP parents with subsyndromal manic symptoms than controls (52.5% vs 20%, OR: 4.2, 95% CI: 1.2-14.7, P<.01). CONCLUSIONS: Depressed BP offspring had more severe depression including atypical depressive symptoms, and were more likely to have subsyndromal mixed manic symptoms than depressed control offspring. Prospective studies to evaluate whether these youth are at high risk to develop BP are warranted. If replicated, the results of this study have important clinical (e.g., treatment of depression in depressed offspring of BP parents) and research implications.

Dimensional psychopathology in offspring of parents with bipolar disorder.

OBJECTIVES: To compare the dimensional psychopathology in offspring of parents with bipolar disorder (BP) with offspring of community control parents as assessed by the Child Behavior Checklist (CBCL). METHODS: Offspring of parents with BP, who were healthy or had non-BP disorders (any psychiatric disorder other than BP; n = 319) or who had bipolar spectrum disorders (n = 35), and offspring of community controls (n = 235) ages 6-18 years were compared using the CBCL, the CBCL-Dysregulation Profile (CBCL-DP), and a sum of the CBCL items associated with mood lability. The results were adjusted for multiple comparisons and for any significant between-group demographic and clinical differences in both biological parents and offspring. RESULTS: With few exceptions, several CBCL (e.g., Total, Internalizing, and Aggression Problems), CBCL-DP, and mood lability scores in non-BP offspring of parents with BP were significantly higher than in offspring of control parents. In addition, both groups of offspring showed significantly lower scores in most scales when compared with offspring of parents with BP who had already developed BP. Similar results were obtained when analyzing the rates of subjects with CBCL T-scores that were two standard deviations or higher above the mean. CONCLUSIONS: Even before developing BP, offspring of parents with BP had more severe and higher rates of dimensional psychopathology than offspring of control parents. Prospective follow-up studies in non-BP offspring of parents with BP are warranted to evaluate whether these dimensional profiles are prodromal manifestations of mood or other disorders, and can predict those who are at higher risk to develop BP.

Mania profile in a community sample of prepubertal children in Turkey.

BACKGROUND: Mania in youth is increasingly recognized and accompanied by substantial psychiatric and psychosocial morbidity. There are no data on prepubertals in the general population and we aimed to search for mania symptoms and its clinical correlations in a community sample of prepubertal Turkish children. METHODS: Among all children (n = 56,335) aged 7-11 in Adana, Turkey, 2,468 children (48% girls) were randomly included. Parents completed Child Behavior Checklist (CBCL) 4-18 and Parent-Young Mania Rating Scale (P-YMRS). Cut-off scores of 17 and 27 on total P-YMRS were defined as efficient (probable-mania group) and specific (mania group), respectively, for bipolar profile. We searched for clinical correlations and used logistic regression to show how well each CBCL subscale predicted the presence of mania and probable-mania, after adjusting for any demographic differences. RESULTS: Parent-Young Mania Rating Scale scores were > or =17 but <27 (probable-mania) in 155 (6.3%) children and > or =27 (mania) in 32 (1.3%) children. Elevated mood, increased activity levels, and poor insight were the most frequent manic symptoms in our sample. Children with probable-mania and mania had higher scores on all CBCL subscales and the CBCL-Pediatric Bipolar Disorder (CBCL-PBD) profile (sum of attention, aggression, and anxiety/depression subscales). Logistic regression analysis revealed only thought problems on CBCL that predicted probable-mania and mania. CONCLUSION: Our study shows that mania profile is common in the community sample of Turkish prepubertal children and does not support the thought that mania is rare outside the US. We need further population-based studies that will use diagnostic interviews and multiple informants.

Adjunctive Bright Light Therapy for Bipolar Depression: A Randomized Double-Blind Placebo-Controlled Trial.

OBJECTIVE: Patients with bipolar disorder have recurrent major depression, residual mood symptoms, and limited treatment options. Building on promising pilot data, the authors conducted a 6-week randomized double-blind placebo-controlled trial to investigate the efficacy of adjunctive bright light therapy at midday for bipolar depression. The aims were to determine remission rate, depression symptom level, and rate of mood polarity switch, as well as to explore sleep quality. METHOD: The study enrolled depressed adults with bipolar I or II disorder who were receiving stable dosages of antimanic medication (excluding patients with hypomania or mania, mixed symptoms, or rapid cycling). Patients were randomly assigned to treatment with either 7,000-lux bright white light or 50-lux dim red placebo light (N=23 for each group). Symptoms were assessed weekly with the Structured Interview Guide for the Hamilton Depression Scale With Atypical Depression Supplement (SIGH-ADS), the Mania Rating Scale, and the Pittsburgh Sleep Quality Index. Remission was defined as having a SIGH-ADS score of 8 or less. RESULTS: At baseline, both groups had moderate depression and no hypomanic or manic symptoms. Compared with the placebo light group, the group treated with bright white light experienced a significantly higher remission rate (68.2% compared with 22.2%; adjusted odds ratio=12.6) at weeks 4-6 and significantly lower depression scores (9.2 [SD=6.6] compared with 14.9 [SD=9.2]; adjusted ß=-5.91) at the endpoint visit. No mood polarity switches were observed. Sleep quality improved in both groups and did not differ significantly between them. CONCLUSIONS: The data from this study provide robust evidence that supports the efficacy of midday bright light therapy for bipolar depression.

Differentiating major depressive disorder in youths with attention deficit hyperactivity disorder.

BACKGROUND: Youths with attention deficit hyperactivity disorders (ADHD) frequently have comorbid major depressive disorders (MDD) sharing overlapping symptoms. Our objective was to examine which depressive symptoms best discriminate MDD among youths with ADHD. METHODS: One-hundred-eleven youths with ADHD (5.2-17.8 years old) and their parents completed interviews with the K-SADS-PL and respective versions of the child or the parent Mood and Feelings Questionnaire (MFQ-C, MFQ-P). Controlling for group differences, logistic regression was used to calculate odds ratios reflecting the accuracy with which various depressive symptoms on the MFQ-C or MFQ-P discriminated MDD. Stepwise logistic regression then identified depressive symptoms that best discriminated the groups with and without MDD, using cross-validated misclassification rate as the criterion. RESULTS: Symptoms that discriminated youths with MDD (n=18) from those without MDD (n=93) were 4 of 6 mood/anhedonia symptoms, all 14 depressed cognition symptoms, and only 3 of 11 physical/vegetative symptoms. Mild irritability, miserable/unhappy moods, and symptoms related to sleep, appetite, energy levels and concentration did not discriminate MDD. A stepwise logistic regression correctly classified 89% of the comorbid MDD subjects, with only age, anhedonia at school, thoughts about killing self, thoughts that bad things would happen, and talking more slowly remaining in the final model. LIMITATIONS: Results of this study may not generalize to community samples because subjects were drawn largely from a university-based outpatient psychiatric clinic. CONCLUSIONS: These findings stress the importance of social withdrawal, anhedonia, depressive cognitions, suicidal thoughts, and psychomotor retardation when trying to identify MDD among ADHD youths.

Fluoxetine in posttraumatic eating disorder in two-year-old twins.

Feeding disorders of infancy or early childhood are relatively uncommon in the pediatric population. In posttraumatic eating disorder, the infant demonstrates food refusal after a traumatic event or repeated traumatic events to the oropharynx or esophagus. We present case reports of 24-month-old twin girls, A and B, who presented to our clinic with food refusal and fear of feeding. Several invasive gastrointestinal procedures were performed when they were 3 months old, and they started to refuse all solid food and some liquids soon after hospitalization. Fluoxetine 0.3 mg/kg per day (5 mg/day) was started to target their anxiety and fear about feeding. In the second month of weekly follow up, the children began to be fed without a nasogastric catheter. A significant decrease in anxiety and fear was observed during feeding. Although the use of serotonin-selective reuptake inhibitors (SSRIs) in preschool children is controversial due to the lack of empirical data in this age group, we observed clinical improvements in anxiety in these two cases. Furthermore, fluoxetine was well tolerated and no side effects were observed.

Distinguishing Bipolar Depression from Unipolar Depression in Youth: Preliminary Findings.

OBJECTIVES: To identify mood symptoms that distinguishes bipolar disorder (BP) depression versus unipolar depression in youth during an acute depressive episode. METHODS: Youth with BP (N = 30) were compared with youth with unipolar depression (N = 59) during an acute depressive episode using the depression and mania items derived from the Schedule for Affective Disorders and Schizophrenia for Children (K-SADS)-Present Version. The results were adjusted for multiple comparisons, and any significant between-group differences in demographic, nonmood comorbid disorders, and psychiatric family history. RESULTS: In comparison with unipolar depressed youth, BP depressed youth had significantly higher scores in several depressive symptoms and all subsyndromal manic symptoms, with the exception of increased goal-directed activity. Among the depressive symptoms, higher ratings of nonsuicidal physical self-injurious acts and mood reactivity, and lower ratings of aches/pains, were the symptoms that best discriminated BP from unipolar depressed youth. Subsyndromal manic symptoms, particularly motor hyperactivity, distractibility, and pressured speech, were higher in BP depressed youth and discriminated BP depressed from unipolar depressed youth. CONCLUSIONS: The results of this study suggest that it is possible to differentiate BP depression from unipolar depression based on depressive symptoms, and in particular subsyndromal manic symptoms. If replicated, these results have important clinical and research implications.

Risperidone-induced obsessive-compulsive symptoms in two children.

OBJECTIVE: To present two cases of rapid-onset obsessive-compulsive symptoms in children treated with risperidone. CASES: "A" was an 8-year-old boy with attention deficit and chronic tic disorder who developed obsessive-compulsive symptoms within 2 weeks of starting risperidone. When the dose of 0.5 mg tid was discontinued, the obsessive-compulsive symptoms resolved with no return over 8 months of follow-up. "B" was an 11-year-old girl with mild mental retardation and aggression who was treated with risperidone 1 mg per day. Obsessive-compulsive symptoms suddenly emerged 10 days after starting risperidone and resolved within 3 days of discontinuation. In both cases, streptococcal pharyngitis was ruled out. CONCLUSION: Although the mechanism is not clear, these cases add to several other reports concerning the sudden emergence of obsessive-compulsive symptoms and anxiety symptoms in children treated with atypical antipsychotics. Clinicians should be alert to the possibility of these adverse effects in children treated with these drugs.

Selective serotonin reuptake inhibitors in children and adolescents.

This article will review the tolerability, side effects, and effectiveness of selective serotonin reuptake inhibitors (SSRIs) in children and adolescents. We aimed to familiarise the readers with the available data on the pharmacological treatment of childhood psychiatric disorders, especially of depressive disorder and obsessive compulsive disorder. Tricyclic antidepressants (TCAs) have questionable efficacy, definite problems with safety (e.g., cardiotoxicity, lethality in overdose, anticholinergic side effects), and compliance issues. Therefore it is suggested suggest that SSRIs should be the first-line treatment for these disorders in children and adolescents. Studies have shown a significant clinical response to SSRIs and their efficiency has been demonstrated in open and controlled trials. It is often recommended that clinicians should start low and go slow when using SSRIs, and maintain the patient in a symptom-free state for at least six months. The side effects of SSRIs are generally mild, manageable, and seldom require discontinuation of treatment. Children should be monitored closely for infrequent side effects such as gastrointestinal upset, headache, and behavioural activation which may be as severe as mania. There is a great need for controlled trials in childhood psychiatric disorders, especially in anxiety disorders.

Fluoxetine-induced extrapyramidal symptoms in an adolescent: a case report.

We present a 15-year-old girl with depression, an obsessive compulsive disorder and conduct disorder, who developed EPS (torticollis, bradykinesia and cogwheel rigidity) while on fluoxetine. No other cause of EPS was present. The patient responded well to benztropine but re-experienced EPS when benztropine was stopped. Fluoxetine and benztropine were used concomitantly for 21.2 months and the patient has been off medication for 2 months without EPS. This case report shows that EPS can and does occur in youth with SSRI. Clinicians should be aware of the SSRIs as a potential causative factor for EPS.

Panic disorder in children and adolescents.

Panic disorder (PD) in children and adolescents is a disabling and chronic condition, which is accompanied by psychosocial and academic difficulties both during adolescence and into adulthood. In this article, the prevalence, clinical characteristics, risk factors, comorbid states, differential diagnosis, and treatment of PD are reviewed. Although PD was thought to be rare in children and adolescents, the prevalence of PD in community samples ranges between 0.5% and 5.0, and in pediatric psychiatric clinics from 0.2% to 10%. Panic attacks are reported to be equally prevalent in males and females. Clinical studies have shown that the majority of the PD pediatric patients receiving consultation in clinics are older adolescents, Caucasian, female, and middle class. Up to 90% of children and adolescents with PD have other anxiety disorders (generalized anxiety disorder/overanxious disorder, separation anxiety disorder, social phobia or agoraphobia), or mood disorders (major depressive disorder or bipolar disorder). PD patients can be misdiagnosed or having neurologic, cardiovascular, pulmonary, or gastrointestinal illness. Psychoeducation and psychosocial treatments are recommended, and it appears that selective serotonin reuptake inhibitors (SSRIs) are a safe and promising treatment for children and adolescents with PD. The clinical characteristics, long-term course, and treatment of PD in children and adolescents needs to be further assessed by well-designed studies.

Pharmacotherapy and regional cerebral blood flow in children with obsessive compulsive disorder.

While regional cerebral blood flow (rCBF) studies on adults involving the caudate, prefrontal, orbitofrontal, and cingulated areas have been reported, no such published data on children exist. In this study, we aimed to determine the significance of pre- and post-treatment regional cerebral blood flow (rCBF) differences in children with obsessive compulsive disorder (OCD) and compared them with healthy controls. Eighteen drug-free obsessive compulsive children, aged 11 to 15, without comorbid states except for anxiety disorders--participated in this study. The control group consisted of 12 children, aged 11 to 15, with no medical or psychiatric illnesses. Using SPECT (Single Photon Emission Computerized Tomography) scans with Technetium-99m-HMPAO-hexamethly propyleneamine oxime (Tc99mHMPAO), the rCBF was calculated in 15 regions of the control group according to a standard protocol, while in the study group, it was measured at baseline and after 12 weeks of treatment with a fixed dose of paroxetine (20 mg qd). We compared the resulting pre- and post-treatment CBF values for the control group and study group. The right and left caudates, right and left dorsolateral prefrontals, and cingulate had significantly higher rCBF in children with obsessive compulsive disorder than in the control group. These areas, in addition to the right anteromedial temporal, showed significant rCBF reduction after treatment with paroxetine. The mean percentage of change in obsession scores during the treatment correlated significantly with the baseline and post- treatment rCBF level of the right caudate, post-treatment left caudate, and baseline left caudate. Our findings on children are consistent with adult studies and support the theory of a cortical-striatal-thalamic-cortical loop disturbance in OCD.

Tc-99m-ECD SPECT brain imaging in children with Tourette's syndrome.

We undertook this study to assess the patterns of regional cerebral perfusion (RCP) with SPECT using Technetium- 99m-ethyl cysteinate dimer (Tc-99m-ECD) in children with Tourette's Syndrome (TS), and to compare these with the patterns in a group of normal controls. The study sample consisted of 38 children (7 to 14 years) who met the ICD-10 and DSM/IV criteria for Tourette's Syndrome, and a control group of 18 children (9 to 14 years). The Children's Depression Inventory and Maudsley Obsessional-Compulsive Questionnaire were used for assessment, and the severity of motor and vocal tics were assessed using the Goetz Rating Scale. The RCP values were significantly lower in the TS group in left caudate, cingulum, right cerebellum, left dorsolateral prefrontal, and the left orbital frontal region. A positive correlation was found between the severity of vocal tics and blood flow of mid-cerebellum, right dorsolateral prefrontal and left dorsolateral prefrontal regions. Although no depressive or obsessive patients were included in the study, the depression and obsession scores were found to be negatively correlated with all RCP values, especially in the temporal regions. Further studies are needed to explore the relationship between the hypoperfusion of certain brain areas and the underlying neurophysiology and neurobiology of patients with TS. Additional disturbances such as obsessive-compulsive symptoms and depressive symptoms should also be assessed

A cytogenetic study in 120 Turkish children with intellectual disability and characteristics of fragile X syndrome.

We review the evidence for the frequency of the fragile X syndrome (FXS), other X-linked abnormalities, and other chromosomal disabilities of Turkish pediatric psychiatry outpatients with intellectual disability. Reported clinical features and genetic findings were used in cytogenetic screenings to estimate the prevalence of the fragile X (fra X) and other chromosomal aberrations in 120 patients with mental retardation, language disorders, attention deficit hyperactivity, or developmental delay, in comparison with 30 healthy children. Data on the clinical, intellectual and behavioral findings in 14 fra X positive children (11.7%) is presented. Ten of the 120 patients (8.3%) had enlargement of the heterochromatin region of chromosome 9. Other chromosomal aberrations and autosomal fragile sites (FS) were also observed. There was a statistically significant difference in the autosomal and X-linked FS between the study and control groups (p < 0.05). The tests for the fra X chromosome are likely to be of diagnostic benefit in young children with autism or developmental delay, particularly in speech, and who have large and prominent ears.

Differential Anterior Cingulate Activity during Response Inhibition in Depressed Adolescents with Bipolar and Unipolar Major Depressive Disorder.

OBJECTIVE: Cognitive control deficits are commonly seen in Depression of Bipolar Disorder (BDd) and Unipolar Major Depressive Disorder (UDd). Because failure to differentiate BDd from UDd has significant clinical consequences we aimed to identify differential patterns of neural activity in BDd versus UDd underlying response inhibition and motor control in adolescents. METHODS: Functional MRI was used to compare 12 BDd adolescents (mean age= 15.5±1.2) with age- and sex-matched ten UDd and ten healthy control (HC) adolescents during the performance of well-validated Go/NoGo task. NoGo response inhibition versus Go motor control blocks was used in whole-brain analysis and results were corrected for multiple comparisons. RESULTS: There were no significant behavioral or neuroimaging findings between adolescents with BDd and UDd. However, both groups relative to HC showed significantly higher left superior temporal and left caudate activity during the NoGo condition. Moreover, left anterior cingulate (ACC) activity relative to HC was significantly higher only in BDd - not UDd - adolescents during the NoGo condition, and left caudate activity was higher only in UDd - not BDd - adolescents during the Go condition. In addition, several neural regions including dorsolateral prefrontal (DLPFC) were positively correlated with increased reaction time in UDd - not BDd - adolescents. CONCLUSIONS: Despite some similarities, neural correlates of depression are different in BDd and UDd relative to HC, and greater recruitment of ACC resources during response inhibition can help distinguish BDd.

OBJECTIF: Les déficits de contrôle cognitif sont souvent observés dans la dépression du trouble bipolaire (dTB) et dans le trouble dépressif majeur unipolaire (dTU). Parce que ne pas différencier entre la dTB et la dTU a des conséquences cliniques significatives, nous avons cherché à identifier les modèles différentiels d'activité neurale dans la dTB comparativement à la dTU en ce qui concerne l'inhibition sous-jacente de la réponse et le contrôle moteur chez les adolescents. MÉTHODES: L'imagerie par résonance magnétique fonctionnelle (IRMf) a servi à comparer 12 adolescents souffrant de dTB (âge moyen = 15,5±1,2) avec 10 adolescents souffrant de dTU appariés selon l'âge et le sexe, et dix adolescents témoins en santé (TS) durant la performance d'une tâche Go/NoGo bien validée. L'inhibition de la réponse à NoGo par opposition aux blocs de contrôle moteur de GO a été utilisée dans une analyse du cerveau en entier et les résultats ont été corrigés pour de multiples comparaisons. RÉSULTATS: Il n'y avait pas de résultats de comportement ou de neuroimagerie significatifs entre les adolescents souffrant de dTB et de dTU. Cependant, les deux groupes comparés aux TS montraient une activité temporale gauche supérieure et caudale gauche significativement plus élevée durant la condition NoGo. En outre, l'activité du cortex cingulaire antérieur (CCA) gauche, en comparaison avec les TS, était significativement supérieure seulement chez les adolescents souffrant de dTB ­ et non de dTU ­ durant la condition NoGo, et l'activité caudale gauche était plus élevée seulement chez les adolescents souffrant de dTU ­ et non de dTB ­ durant la condition NoGo. De plus, plusieurs régions neurales, dont le cortex préfrontal dorsolatéral (CPFDL), étaient positivement corrélées à un temps de réaction accru chez les adolescents souffrant de dTU ­ et non de dTB. CONCLUSIONS: Malgré certaines similitudes, les corrélats neuraux de la dépression sont différents dans la dTB et la dTU comparativement aux TS, et un meilleur recrutement des ressources du CCA durant l'inhibition de la réponse peut contribuer à distinguer la dTB.

Neural correlates of treatment response in depressed bipolar adolescents during emotion processing.

Depressive mood in adolescents with bipolar disorder (BDd) is associated with significant morbidity and mortality, but we have limited information about neural correlates of depression and treatment response in BDd. Ten adolescents with BDd (8 females, mean age = 15.6 ± 0.9) completed two (fearful and happy) face gender labeling fMRI experiments at baseline and after 6-weeks of open treatment. Whole-brain analysis was used at baseline to compare their neural activity with those of 10 age and sex-matched healthy controls (HC). For comparisons of the neural activity at baseline and after treatment of youth with BDd, region of interest analysis for dorsal/ventral prefrontal, anterior cingulate, and amygdala activity, and significant regions identified by wholebrain analysis between BDd and HC were analyzed. There was significant improvement in depression scores (mean percentage change on the Child Depression Rating Scale-Revised 57 % ± 28). Neural activity after treatment was decreased in left occipital cortex in the intense fearful experiment, but increased in left insula, left cerebellum, and right ventrolateral prefrontal cortex in the intense happy experiment. Greater improvement in depression was associated with baseline higher activity in ventral ACC to mild happy faces. Study sample size was relatively small for subgroup analysis and consisted of mainly female adolescents that were predominantly on psychotropic medications during scanning. Our results of reduced negative emotion processing versus increased positive emotion processing after treatment of depression (improvement of cognitive bias to negative and away from positive) are consistent with the improvement of depression according to Beck's cognitive theory.

Neural correlates of treatment in adolescents with bipolar depression during response inhibition.

OBJECTIVE: Abnormal prefrontal and subcortical activity during cognitive control tasks is identified in non-depressed adolescents with bipolar disorder (BD); however, little is known about the neural correlates of bipolar adolescents in a depressed state (BDd). We aimed to investigate baseline versus after-treatment patterns of neural activity underlying motor response and response inhibition in adolescents with BDd. METHODS: In this functional magnetic resonance imaging (fMRI) study, 10 adolescents with BDd relative to 10 age- and sex-matched healthy controls (HC) completed a well-validated go/no go block-design cognitive control task at baseline and after 6 weeks of naturalistic treatment. We used whole-brain analysis and controlled our results for multiple comparisons. RESULTS: There was significant improvement in depression scores (mean change: 57%±28). There was no behavioral difference in BDd baseline versus HC and after treatment. BDd adolescents relative to HC had higher baseline cortical, but not subcortical, neural activity (e.g., bilateral ventrolateral prefrontal during both the go [motor control] and the no go [response inhibition] conditions, and left superior temporal during the no go condition). However, after-treatment activity relative to baseline neural activity during response inhibition was significantly increased in subcortical (e.g., right hippocampus and left thalamus), but not cortical, regions. In addition, at baseline, lower left thalamus activity was correlated with higher depression scores. CONCLUSIONS: Adolescents with BDd had baseline prefrontal and temporal hyperactivity underlying motor control and response inhibition that did not change after treatment in contrast to relatively decreased baseline subcortical activity underlying response inhibition associated with the depressive state that was increased after the treatment.

Neural activity to intense positive versus negative stimuli can help differentiate bipolar disorder from unipolar major depressive disorder in depressed adolescents: a pilot fMRI study.

Failure to distinguish bipolar depression (BDd) from the unipolar depression of major depressive disorder (UDd) in adolescents has significant clinical consequences. We aimed to identify differential patterns of functional neural activity in BDd versus UDd and employed two (fearful and happy) facial expression/ gender labeling functional magnetic resonance imaging (fMRI) experiments to study emotion processing in 10 BDd (8 females, mean age=15.1 ± 1.1) compared to age- and gender-matched 10 UDd and 10 healthy control (HC) adolescents who were age- and gender-matched to the BDd group. BDd adolescents, relative to UDd, showed significantly lower activity to both intense happy (e.g., insula and temporal cortex) and intense fearful faces (e.g., frontal precentral cortex). Although the neural regions recruited in each group were not the same, both BDd and UDd adolescents, relative to HC, showed significantly lower neural activity to intense happy and mild happy faces, but elevated neural activity to mild fearful faces. Our results indicated that patterns of neural activity to intense positive and negative emotional stimuli can help differentiate BDd from UDd in adolescents.

Psychosocial functioning in offspring of parents with bipolar disorder.

BACKGROUND: Offspring of parents with bipolar disorder are at increased risk for a range of psychopathology, including bipolar disorder. It is not clear if they also have impairments in their psychosocial functioning. METHODS: We compared the psychosocial functioning of three groups of children enrolled in the Pittsburgh Bipolar Offspring Study (BIOS): offspring of probands with bipolar disorder (n=388), offspring of probands with other types of psychopathology (n=132), and offspring of healthy probands (n=118). Psychosocial functioning was assessed at study intake using the schedule of the Adolescent Longitudinal Interval Follow-Up Evaluation (A-LIFE), the Child Behavior Check List (CBCL) and the Children's Global Assessment Scale (CGAS). RESULTS: Offspring of probands with bipolar disorder exhibited impairments in various aspects of psychosocial functioning. On all measures, they had worse functioning in comparison with offspring of healthy probands. Offspring of probands with bipolar disorder generally exhibited more impairment than offspring of probands with nonbipolar psychopathology. After adjusting for proband parent functioning and the child's Axis I psychopathology, functioning of offspring of probands with bipolar disorder was similar to that of offspring of healthy probands. LIMITATIONS: Data are cross-sectional and therefore do not allow for causal conclusions about the association between parental psychopathology, child psychopathology and offspring psychosocial functioning. CONCLUSIONS: Offspring of parents with bipolar disorder exhibit impairments in psychosocial functioning which appear largely attributable to proband parent functional impairment and the child's own psychopathology. As such, interventions to improve parental functioning, as well as early interventions to treat the child's psychopathology may help reduce the risk for long-term functional impairment in offspring.