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NEUROBIOLOGY OF DEPRESSION As opposed to anxiety, which focuses on complex circuits throughout the brain, the neurobiology of depression is characterized by dysfunction and abnormali-ties of neurotransmitter and neuroendocrine (hormonal) systems, The primary neurotransmitters studied for depression are norepinephrine, serotonin, and acetylcholine (Kowatch et al., 2006). Studies of medications such as selective-serotonin reuptake inhibitors (SSRI) indicate insufficient norepinephrine and serotonin are associated with depression. Abnormal functioning of the hypo-thalamic-pituitary-adrenal (HPA) axis has been associated with depression. Specifically, the HPA axis is activated in times of stress and results in instruc-tions to the hypothalamus to produce corticotrophin-releasing factor (CRT) that results in elevations of the hormone cortisol (Miller, 1998). Chronically elevated cortisol levels result in increased sensitivity to future stress, leading to an open feedback loop Of increasing cortisol levels. Recent studies have revealed that prolonged, intense maternal stress during pregnancy increases cortisol levels and can alter functioning of the [IPA axis in both the mother and fetus. Such alterations are associated with structural changes in the hippocampus, amyg-dala, and frontal cortex (Weinstock, 2008). Such changes can have systemic influence because the frontal lobe is the largest of the brain's lobes and performs diverse functions. Along with planning appropriate behavioral responses and working memory, it functions with other parts of the brain in regard to learning, memory, motivation, and attention. The frontal cortex integrates perceptual information from the parietal and temporal lobes, as well as the sensory and motor areas during learning (Buchsbaum, 2004). These findings correlate with the course of depression described above in which the time between depressive episodes and the stress needed to activate a depressive episode decrease over time. Soares and Mann (1997) conducted a review of existing morphological neuroimaging studies and found consistent evidence for decreased volume of the frontal lobe, cerebellum, caudate, and putamen in adults with depression. These findings have not been replicated in children due to difficulties with conducting MRI studies with children (Kowatch et al., 2006). However, the limited functional neuroimaging studies of cerebral blood flow have pointed to abnormalities in the limbic-thalamic-cortical network (Drevets et al., 1992; Soares & Mann, 1997). NFUROCOGNJTIVE DEFICITS ASSOCIATED WITH INTERNALIZING DISORDERS SENSORY-MOTOR DEFICITS Baron (2004) pointed out that sensory-motor assessments have been minimized or marginalized in the typical child neuropsychological evaluation. This is evidenced by the very minimal information about sensory-motor functioning in the empirical literature base. Nevertheless, Baron concluded that sensory-motor assessment should be routine in child neuropsychological evaluations. For example, Hale and Fiorello (2004) report that right hemisphere dysfunction has been associated with internalizing disorders. Therefore, it would be important to assess hemispheric laterality through lateral dominance testing to assist in the interpretation of other assessment data. Depression has been associated with psychomotor retardation, which would likely impact sensory-motor tasks. In a study with adults, Zarrinpar, Deldin, and Kosslyn (2006) found that individuals with major depression evidence slower response times for visual-spatial tasks. They concluded that psychomotor retardation associated with depression may he a stimulus-encoding or motor-output deficit rather than a cognitive deficit. Replication studies are necessary to extend this finding to children, but the findings do suggest children may exhibit longer response times for visual-spatial tasks while in a depressive episode. ATTENTIONAI, PROCESSING DEFICITS Inattention is often observed during the early childhood period of children who later become depressed. In fact, the DSM-IV-TR indicates that Major Depression in young children is often comorbid with attention-deficit dis-orders (American Psychiatric Association, 2000). Throughout the develop-mental period there is substantial evidence for the co-occurrence of Attention-Deficit/Hyperactivity Disorder (ADHD) and Major Depression (Ostrander, Crystal, & August, 2006). Despite the early appearance of inattention as a prodromal symptom in very young children, inattention may not be the primary attentional problem in school-aged children. Blackman, Ostrander, and Herman (2005) compared depressed and non-depressed school-age children to determine if the depressed children exhibited higher rates of ADHD inattentive type than combined type. They found no difference in rates of inattentive type and combined type compared to the control subjects suggesting that children with depression and ADHD may present either as inattentive or as overactive/impulsive. On the other hand, Hurtig and colleagues (2007) studied 457 adolescents with ADHD and found that those with primarily inattentive symptoms had increased probability of comorbid Major Depression. Blackman et al. (2005) further found that children with ADHD and depression exhibit great social impairment than normal controls. VISUAL-SPATIAL PROCESSING DEFICITS
As with sensory-motor deficits, visual-spatial deficits in children with inter-nalizing disorders are not frequently reported in the literature. In a non-clinical sample of 66 children ages 6 to 13 years, Aronen, Vuontela, Steenari, Salmi, and Carlson (2005) found that children with internalizing symptoms performed poorly on visual working memory tasks. Additionally, there was a positive correlation between anxious/depressed symptoms and the number of incorrect, multiple, and missed responses on the visual working memory tasks. McClure, Rogeness, and Thompson (1997) found subtle differences between subclinically depressed adolescent females and nondepressed peers in terms of visuospatial perception and organization.
LANGUAGE DEFICITS
When examining the relatioilship between language deficits and internalizing disorders, if is difficult to determine if neuropsychological dysfunction accounts for the development of both language deficits and internalizing disorders or if the stigma from having difficulty speaking results in increased levels of anxiety or depression. It does appear, however that increased rates of both anxiety and depression as well as other internalizing disorders are strongly correlated with language disorders such as combined speech language disorder, stuttering, selective mutism, and Tourette syndrome. General SpeechlLangziage Disorders Vallance, Cummings, and Humphries (1998) studied school-aged students diagnosed with language learning dis-orders (LLD) who were found to have lower social discourse than the control students. The Test of Language Development (TOLD-2: Hammitt & Newcomer, 1988) was used to measure expressive and receptive language, while the Test of Language Competence—Expanded Edition (TLC-E: Wiig & Secord, 1989) was used to measure social discourse. The students with LLD were also found to be less social overall as well as demonstrating more problem behaviors. The researchers hypothesized that the language problems may interfere with a student's language, cognitive, and social processes, thus increasing in the display of behavior problems including internalizing disorders. Language disorders also appear to manifest in higher levels of anxiety as well. In a fourteen-year longitudinal study conducted by Beitchman and colleagues (2001), students who had both speech and language impairments (S/L) were found to have a higher prevalence of anxiety disorders (most of which were social phobic disorder) later in life than the control group or those with only a speech impairment or language impairment group. Early onset of S/L impairments was found to be associated with a higher likelihotxi of developing an anxiety disorder later in adolescence. These findings point to the accumulation of risk factors leading to poorer adaptive outcomes.
Specific Speech Disorders Specific speech disorders are also associated with internalizing behaviors. Selective mutism (SM), for example, is highly corre-lated with symptoms of anxiety. Ford, Sladeczek, Carlson, and Kratochwill (1998) found that individuals with SM showed similar symptoms on the parent and self-report behavior rating scales as individuals with only anxiety disorders. Manassis and colleagues (2007) found that children with SM performed poorer on tasks involving verbal comprehension or visual mem-ory than normal controls. The children with SM also had a higher prevalence of social anxiety Craig, Hancock, Tran, and Craig (2003) examined the link between stuttering and anxiety in a sample cat adolesc.sents and adults. Individuals who stuttered had higher scores for anxiety than those who did not stutter. The researchers also found that cal the people in the group who stuttered, the ones who sot'ght treatment In their stuttering were more anxious, It was interred that these
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